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Zyryanov SK, Baybulatova EA. [Current challenges for therapy of comorbid patients: a new look at celecoxib. A review]. TERAPEVT ARKH 2024; 96:531-542. [PMID: 38829816 DOI: 10.26442/00403660.2024.05.202769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 05/29/2024] [Indexed: 06/05/2024]
Abstract
The use of non-steroidal anti-inflammatory drugs (NSAIDs) for a wide range of diseases is increasing, in part due to an increasing elderly population. Elderly patients are more vulnerable to adverse drug reactions, including side effects and adverse effects of drug-drug interactions, often occurring in this category of patients due to multimorbidity and polypharmacy. One of the most popular NSAIDs in the world is celecoxib. It is a selective cyclooxygenase (COX)-2 inhibitor with 375 times more COX-2 inhibitory activity than COX-1. As a result, celecoxib has a better gastrointestinal tract safety profile than non-selective NSAIDs. Gastrointestinal tolerance is an essential factor that physicians should consider when selecting NSAIDs for elderly patients. Celecoxib can be used in a wide range of diseases of the musculoskeletal system and rheumatological diseases, for the treatment of acute pain in women with primary dysmenorrhea, etc. It is also increasingly used as part of a multimodal perioperative analgesia regimen. There is strong evidence that COX-2 is actively involved in the pathogenesis of ischemic brain damage, as well as in the development and progression of neurodegenerative diseases, such as Alzheimer's disease. NSAIDs are first-line therapy in the treatment of acute migraine attacks. Celecoxib is well tolerated in patients with risk factors for NSAID-associated nephropathy. It does not decrease the glomerular filtration rate in elderly patients and patients with chronic renal failure. Many meta-analyses and epidemiological studies have not confirmed the increased risk of cardiovascular events reported in previous clinical studies and have not shown an increased risk of cardiovascular events with celecoxib, irrespective of dose. COX-2 activation is one of the key factors contributing to obesity-related inflammation. Specific inhibition of COX-2 by celecoxib increases insulin sensitivity in overweight or obese patients. Combination therapies may be a promising new area of treatment for obesity and diabetes.
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Affiliation(s)
- S K Zyryanov
- Peoples' Friendship University of Russia named after Patrice Lumumba
| | - E A Baybulatova
- Peoples' Friendship University of Russia named after Patrice Lumumba
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Sheoran S, Arora S, Velingkar A, Pawar SC, Vuree S. Empowering treatment strategies for pancreatic cancer by employing lipid nanoparticle-driven drug delivery. RECENT ADVANCES IN NANOCARRIERS FOR PANCREATIC CANCER THERAPY 2024:239-266. [DOI: 10.1016/b978-0-443-19142-8.00016-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Sarayani A, Brown JD, Hampp C, Donahoo WT, Winterstein AG. Adaptability of High Dimensional Propensity Score Procedure in the Transition from ICD-9 to ICD-10 in the US Healthcare System. Clin Epidemiol 2023; 15:645-660. [PMID: 37274833 PMCID: PMC10237200 DOI: 10.2147/clep.s405165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 04/20/2023] [Indexed: 06/07/2023] Open
Abstract
Background High-Dimensional Propensity Score procedure (HDPS) is a data-driven approach to assist control for confounding in pharmacoepidemiologic research. The transition to the International Classification of Disease (ICD-9/10) in the US health system may pose uncertainty in applying the HDPS procedure. Methods We assembled a base cohort of patients in MarketScan® Commercial Claims Database who had newly initiated celecoxib or traditional NSAIDs to compare gastrointestinal bleeding risk. We then created bootstrapped hypothetical cohorts from the base cohort with predefined patient selection patterns from the ICD eras. Three strategies for HDPS deployment were tested: 1) split the cohort by ICD era, deploy HDPS twice, and pool the relative risks (pooled RR), 2) consider codes from each ICD era as a separate data dimension and deploy HDPS in the entire cohort (data dimensions) and 3) map ICD codes from both eras to Clinical Classifications Software (CCS) concepts before deploying HDPS in the entire cohort (CCS mapping). We calculated percent bias and root-mean-squared error to compare the strategies. Results A similar bias reduction was observed in cohorts where patient selection pattern from each ICD era was comparable between the exposure groups. In the presence of considerable disparity in patient selection, we observed a bimodal distribution of propensity scores in the data dimensions strategy, indicating instrument-like covariates. Moreover, the CCS mapping strategy resulted in at least 30% less bias than pooled RR and data dimensions strategies (RMSE: 0.14, 0.19, 0.21, respectively) in this scenario. Conclusion Mapping ICD codes to a stable terminology like CCS serves as a helpful strategy to reduce residual bias when deploying HDPS in pharmacoepidemiologic studies spanning both ICD eras.
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Affiliation(s)
- Amir Sarayani
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA
- Center for Drug Safety and Evaluation, University of Florida, Gainesville, FL, USA
| | - Joshua D Brown
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA
- Center for Drug Safety and Evaluation, University of Florida, Gainesville, FL, USA
| | - Christian Hampp
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA
- Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA
| | - William T Donahoo
- Division of Endocrinology, Diabetes, & Metabolism, College of Medicine, University of Florida, Gainesville, FL, USA
- Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Almut G Winterstein
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA
- Center for Drug Safety and Evaluation, University of Florida, Gainesville, FL, USA
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Zhu JY, Yan J, Xiao J, Jia HG, Liang HJ, Xing GY. Effects of individual shock wave therapy vs celecoxib on hip pain caused by femoral head necrosis. World J Clin Cases 2023; 11:1974-1984. [PMID: 36998970 PMCID: PMC10044968 DOI: 10.12998/wjcc.v11.i9.1974] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 02/07/2023] [Accepted: 03/03/2023] [Indexed: 03/16/2023] Open
Abstract
BACKGROUND Celecoxib has been used to treat hip discomfort and functional difficulties associated with osteonecrosis of the femoral head (ONFH), although significant adverse reactions often follow long-term use. Extracorporeal shock wave therapy (ESWT) can delay the progression of ONFH, alleviate the pain and functional limitations it causes, and avoid the adverse effects of celecoxib.
AIM To investigate the effects of individual ESWT, a treatment alternative to the use of celecoxib, in alleviating pain and dysfunction caused by ONFH.
METHODS This was a randomized, controlled, double-blinded, non-inferiority trial. We examined 80 patients for eligibility in this study; 8 patients were excluded based on inclusion and exclusion criteria. A total of 72 subjects with ONFH were randomly assigned to group A (n = 36; celecoxib + alendronate + sham-placebo shock wave) or group B (n = 36; individual focused shock wave [ESWT based on magnetic resonance imaging three-dimensional (MRI-3D) reconstruction] + alendronate). The outcomes were assessed at baseline, at the end of treatment, and at an 8-wk follow-up. The primary outcome measure was treatment efficiency after 2 wk of intervention using the Harris hip score (HHS) (improvement of 10 points or more from the baseline was deemed sufficient). Secondary outcome measures were post-treatment HHS, visual analog scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores.
RESULTS After treatment, the pain treatment efficiency of group B was greater than that of group A (69% vs 51%; 95%CI: 4.56% to 40.56%), with non-inferiority thresholds of -4.56% and -10%, respectively. Furthermore, the HHS, WOMAC, and VAS scores in group B dramatically improved during the follow-up period as compared to those in group A (P < 0.001). After therapy, the VAS and WOMAC in group A were significantly improved from the 2nd to 8th wk (P < 0.001), although HHS was only significantly altered at the 2 wk point (P < 0.001). On the 1st d and 2nd wk after treatment, HHS and VAS scores were different between groups, with the difference in HHS lasting until week 4. Neither group had severe complications such as skin ulcer infection or lower limb motor-sensory disturbance.
CONCLUSION Individual shock wave therapy (ESWT) based on MRI-3D reconstruction was not inferior to celecoxib in managing hip pain and restrictions associated with ONFH.
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Affiliation(s)
- Jun-Yu Zhu
- Orthopedic Department, The Third Medical Center of Chinese People’s Liberation Army General Hospital, The Armed Police Clinical College, Anhui Medical University, Hefei 230022, Anhui Province, China
- Orthopedic Department, The Third Medical Center of Chinese People’s Liberation Army General Hospital, Beijing 100039, China
| | - Jun Yan
- Orthopedic Department, The Third Medical Center of Chinese People’s Liberation Army General Hospital, Beijing 100039, China
| | - Jian Xiao
- Orthopedic Department, The Third Medical Center of Chinese People’s Liberation Army General Hospital, Beijing 100039, China
| | - Hai-Guang Jia
- Orthopedic Department, The Third Medical Center of Chinese People’s Liberation Army General Hospital, Beijing 100039, China
| | - Hao-Jun Liang
- Orthopedic Department, The Third Medical Center of Chinese People’s Liberation Army General Hospital, Beijing 100039, China
| | - Geng-Yan Xing
- Orthopedic Department, The Third Medical Center of Chinese People’s Liberation Army General Hospital, The Armed Police Clinical College, Anhui Medical University, Hefei 230022, Anhui Province, China
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Fu JL, Perloff MD. Pharmacotherapy for Spine-Related Pain in Older Adults. Drugs Aging 2022; 39:523-550. [PMID: 35754070 DOI: 10.1007/s40266-022-00946-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/05/2022] [Indexed: 12/12/2022]
Abstract
As the population ages, spine-related pain is increasingly common in older adults. While medications play an important role in pain management, their use has limitations in geriatric patients due to reduced liver and renal function, comorbid medical problems, and polypharmacy. This review will assess the evidence basis for medications used for spine-related pain in older adults, with a focus on drug metabolism and adverse drug reactions. A PubMed/OVID search crossing common spine, neck, and back pain terms with key words for older adults and geriatrics was combined with common drug classes and common drug names and limited to clinical trials and age over 65 years. The results were then reviewed with identification of commonly used drugs and drug categories: nonsteroidal anti-inflammatories (NSAIDs), acetaminophen, corticosteroids, gabapentin and pregabalin, antispastic and antispasmodic muscle relaxants, tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tramadol, and opioids. Collectively, 138 double-blind, placebo-controlled trials were the focus of the review. The review found a variable contribution of high-quality studies examining the efficacy of medications for spine pain primarily in the geriatric population. There was strong evidence for NSAID use with adjustments for gastrointestinal and renal risk factors. Gabapentin and pregabalin had mixed evidence for neuropathic pain. SNRIs had good evidence for neuropathic pain and a more favorable safety profile than TCAs. Tramadol had some evidence in older patients, but more so in persons aged < 65 years. Rational therapeutic choices based on geriatric spine pain diagnosis are helpful, such as NSAIDs and acetaminophen for arthritic and myofascial-based pain, gabapentinoids or duloxetine for neuropathic and radicular pain, antispastic agents for myofascial-based pain, and combination therapy for mixed etiologies. Tramadol can be well tolerated in older patients, but has risks of cognitive and classic opioid side effects. Otherwise, opioids are typically avoided in the treatment of spine-related pain in older adults due to their morbidity and mortality risk and are reserved for refractory severe pain. Whenever possible, beneficial geriatric spine pain pharmacotherapy should employ the lowest therapeutic doses with consideration of polypharmacy, potentially decreased renal and hepatic metabolism, and co-morbid medical disorders.
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Affiliation(s)
- Jonathan L Fu
- Department of Neurology, Boston University School of Medicine, Boston Medical Center, 85 E. Concord St, 1122, Boston, MA, 02118, USA
| | - Michael D Perloff
- Department of Neurology, Boston University School of Medicine, Boston Medical Center, 85 E. Concord St, 1122, Boston, MA, 02118, USA.
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Safety of Non-Steroidal Anti-Inflammatory Drugs in the Elderly: An Analysis of Published Literature and Reports Sent to the Portuguese Pharmacovigilance System. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19063541. [PMID: 35329224 PMCID: PMC8949212 DOI: 10.3390/ijerph19063541] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 03/11/2022] [Accepted: 03/14/2022] [Indexed: 11/28/2022]
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently used agents to treat musculoskeletal disorders (principally by the elderly), thus raising the risk of adverse drug reactions (ADRs). This work aims to monitor NSAIDs safety profile in older people by using literature and pharmacovigilance data. Published clinical studies reporting the NSAIDs safety in elderly patients (age ≥ 65) were identified by a literature search and were then deeply analyzed. In addition, suspected ADRs reports submitted to the Portuguese Pharmacovigilance System (PPS) involving patients aged ≥65 with at least one NSAID as suspected drug were explored in detail. Most studies concluded that the risk of gastrointestinal, cardiovascular, and renal ADRs was significantly lower with cyclooxygenase-2 (COX-2)-selective NSAIDs use than with nonselective NSAIDs. The PPS data analysis showed that serious gastrointestinal ADRs occurred mostly in patients taking more than one NSAID and/or another concomitant drug that increases the incidence of these events, in the absence of gastroprotection. The results suggest that while NSAID toxicity is well understood, their safe use needs to be monitored in clinical practice. Furthermore, the pharmacovigilance data analyzed also showed that monitoring NSAIDs use in elderly remains essential to mitigate the associated risks, especially in those with comorbidities and under polytherapy.
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Magni A, Agostoni P, Bonezzi C, Massazza G, Menè P, Savarino V, Fornasari D. Management of Osteoarthritis: Expert Opinion on NSAIDs. Pain Ther 2021; 10:783-808. [PMID: 33876393 PMCID: PMC8586433 DOI: 10.1007/s40122-021-00260-1] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 03/27/2021] [Indexed: 12/13/2022] Open
Abstract
Osteoarthritis (OA) is a leading cause of disability among older adults worldwide. Treatment aims are to alleviate inflammatory pain and improve physical function through non-pharmacological and pharmacological interventions. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line therapy. However, selection is challenged by patient age, comorbidities and polypharmacy, and by the drug's benefit/risk balance, all of which together influence the risk of cardiovascular (CV), gastrointestinal (GI) and renal adverse events (AEs). While the efficacy profile of the various NSAIDs is delineated, the differences in their safety profile are not straightforward. This narrative review provides practical indications by a multidisciplinary Italian expert panel for general practitioners and specialists managing OA patients with chronic inflammatory pain; the goal is to maximize therapy efficacy while reducing untoward effects caused by inappropriate NSAID use. The discussion on the best approach to NSAIDs spanned the following topics: (1) patient evaluation: investigate pain origin, duration and components together with possible risk factors for CV, GI and renal AEs; (2) non-pharmacological interventions: the physiatrist provides a person-centered, holistic approach accounting for all patient aspects; (3) pharmacological interventions: patient profile and drugs' pharmacological properties affect NSAID selection, which drugs to be used in combination or to be avoided, formulation and therapy duration; (4) the pharmacologist's, general practitioner's and pain therapist's points of view; (5) NSAID safety: the individual baseline risk and the drug's safety profile are major determinants of CV, GI and renal risk; consider possible drug-drug interactions; (6) periodical re-evaluation of treatment response and adherence, using scales to assess pain and function.
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Affiliation(s)
- Alberto Magni
- Italian College of General Practitioners and Primary Care, Via Del Sansovino 179, Florence, Italy
| | - Piergiuseppe Agostoni
- Centro Cardiologico Monzino, IRCCS, Via Carlo Parea, 4, Milan, Italy ,Dipartimento di scienze cliniche e di comunità, Università degli Studi di Milano, Via Carlo Parea 4, Milan, Italy
| | - Cesare Bonezzi
- Unità di Terapia del dolore, Istituti Clinici Scientifici Maugeri, Via Salvatore Maugeri 10, Pavia, Italy
| | - Giuseppe Massazza
- Division of Physical Medicine and Rehabilitation, Department of Surgical Sciences, University of Turin, Via Zuretti 29, Turin, Italy ,“Città della Salute e della Scienza” University Hospital, Corso Bramante, 88, Turin, Italy
| | - Paolo Menè
- Division of Nephrology and Dialysis, Sant’Andrea University Hospital, “Sapienza” University of Rome, Via di Grottarossa, 1035/1039, Rome, Italy
| | - Vincenzo Savarino
- Department of Internal Medicine, University of Genoa, Viale Benedetto XV, 6, Genoa, Italy
| | - Diego Fornasari
- Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Via Vanvitelli, 32, 20133, Milan, Italy.
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Cosgrove KT, Kuplicki R, Savitz J, Burrows K, Simmons WK, Khalsa SS, Teague TK, Aupperle RL, Paulus MP. Impact of ibuprofen and peroxisome proliferator-activated receptor gamma on emotion-related neural activation: A randomized, placebo-controlled trial. Brain Behav Immun 2021; 96:135-142. [PMID: 34052365 PMCID: PMC8319138 DOI: 10.1016/j.bbi.2021.05.023] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 05/08/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen have shown initial promise in producing antidepressant effects. This is perhaps due to these drugs being peroxisome proliferator-activated receptor gamma (PPARγ) agonists, in addition to their inhibition of cyclooxygenase enzymes. Some, albeit mixed, evidence suggests that PPARγ agonists have antidepressant effects in humans and animals. This double-blind, placebo-controlled, pharmacologic functional magnetic resonance imaging (ph-fMRI) study aimed to elucidate the impact of ibuprofen on emotion-related neural activity and determine whether observed effects were due to changes in PPARγ gene expression. Twenty healthy volunteers completed an emotional face matching task during three fMRI sessions, conducted one week apart. Placebo, 200 mg, or 600 mg ibuprofen was administered 1 h prior to each scan in a pseudo-randomized order. Peripheral blood mononuclear cells were collected at each session to isolate RNA for PPARγ gene expression. At the doses used, ibuprofen did not significantly change PPARγ gene expression. Ibuprofen dose was associated with decreased blood oxygen level-dependent (BOLD) activation in the dorsolateral prefrontal cortex and fusiform gyrus during emotional face processing (faces-shapes). Additionally, PPARγ gene expression was associated with increased BOLD activation in the insula and transverse and superior temporal gyri (faces-shapes). No interaction effects between ibuprofen dose and PPARγ gene expression on BOLD activation were observed. Thus, results suggest that ibuprofen and PPARγ may have independent effects on emotional neurocircuitry. Future studies are needed to further delineate the roles of ibuprofen and PPARγ in exerting antidepressant effects in healthy as well as clinical populations.
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Affiliation(s)
- Kelly T. Cosgrove
- Laureate Institute for Brain Research, 6655 S. Yale Ave., Tulsa, OK, 74136,Department of Psychology, University of Tulsa, 800 S. Tucker Dr., Tulsa, OK, 74104
| | - Rayus Kuplicki
- Laureate Institute for Brain Research, 6655 S. Yale Ave., Tulsa, OK 74136 USA.
| | - Jonathan Savitz
- Laureate Institute for Brain Research, 6655 S. Yale Ave., Tulsa, OK 74136 USA.
| | - Kaiping Burrows
- Laureate Institute for Brain Research, 6655 S. Yale Ave., Tulsa, OK 74136 USA.
| | - W. Kyle Simmons
- Center for Health Sciences, Oklahoma State University, 1013 E 66th Pl, Tulsa, OK 74136
| | - Sahib S. Khalsa
- Laureate Institute for Brain Research, 6655 S. Yale Ave., Tulsa, OK, 74136,School of Community Medicine, University of Tulsa, 800 S. Tucker Dr., Tulsa, OK, 74104
| | - T. Kent Teague
- School of Community Medicine, University of Oklahoma, 4502 E. 41st St., Tulsa, OK, 74135
| | - Robin L. Aupperle
- Laureate Institute for Brain Research, 6655 S. Yale Ave., Tulsa, OK, 74136,School of Community Medicine, University of Tulsa, 800 S. Tucker Dr., Tulsa, OK, 74104
| | - Martin P. Paulus
- Laureate Institute for Brain Research, 6655 S. Yale Ave., Tulsa, OK, 74136,School of Community Medicine, University of Tulsa, 800 S. Tucker Dr., Tulsa, OK, 74104
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Cadet C, Maheu E. Non-steroidal anti-inflammatory drugs in the pharmacological management of osteoarthritis in the very old: prescribe or proscribe? Ther Adv Musculoskelet Dis 2021; 13:1759720X211022149. [PMID: 34211591 PMCID: PMC8216401 DOI: 10.1177/1759720x211022149] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Accepted: 05/15/2021] [Indexed: 11/20/2022] Open
Abstract
Osteoarthritis (OA) is the most common form of arthritis worldwide, and ranges in the top 5–10 most disabling diseases. Contrary to common opinion, this disease is severe, often symptomatic, and may lead to loss of mobility and independence, as well as being responsible for increased frailty and excess mortality [standardized ratio: 1.55 (95% confidence interval, CI: 1.41–1.70)]. The incidence of OA increases dramatically with age in an increasingly ageing world. Therefore, practitioners involved in the management of OA often have to manage very old patients, aged 75–80 years and above, as part of their daily practice. Treatment options are limited. In addition to education and physical treatments, which are at the forefront of all treatment recommendations but require a low level of symptoms to be implemented, many pharmacological options are proposed. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be used as a second-line treatment but with great caution. However, the precise incidence of cardiovascular, renal, and gastrointestinal adverse events in very elderly patients is unclear. All of these risks are increased in the elderly. The relative risks can be extrapolated from various studies. However, what is the absolute risk according to age categorization? The answer to this question is important because NSAIDs should be used in very elderly patients with OA only if full information has been provided and the decision to prescribe this treatment is shared between the patient and their doctor. This article reviews the risks and currently available recommendations, and proposes practical options and warnings to allow for a responsible and limited use of NSAIDs in the very old.
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Affiliation(s)
- Christian Cadet
- Medical Practice, 4, Place Martin Nadaud, PARIS, 75020, France
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Clinical Efficacy and Safety of Thai Herbal Formulation-6 in the Treatment of Symptomatic Osteoarthritis of the Knee: A Randomized-Controlled Trial. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2020:8817374. [PMID: 33381209 PMCID: PMC7749772 DOI: 10.1155/2020/8817374] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 10/24/2020] [Accepted: 11/03/2020] [Indexed: 01/22/2023]
Abstract
Background Osteoarthritis of the knee is the most common form of arthritis. Identifying effective and safe herbal formulations that are locally available is viewed as a priority for sustainable development in a region. This study aimed to evaluate the efficacy and safety of Thai herbal formulation-6 (THF-6) in comparison with oral diclofenac in patients with moderate-to-severe osteoarthritis of the knee. Methods This randomized, double-blind, active-controlled, noninferiority trial randomly assigned patients with osteoarthritis of the knee to receive either THF-6 or diclofenac for four weeks. The primary outcome measure was the change from baseline in knee pain as measured by a 100 mm visual analog scale (VAS). Secondary outcome measures included knee stiffness, a stair climb test, the Knee Injury and Osteoarthritis Outcome Score, and safety parameters. Outcomes were assessed on a biweekly basis. Modified intention-to-treat (MITT) and perprotocol (PP) analyses were applied. Results A total of 200 patients were enrolled of whom 175 (87.5%) were included in the MITT analysis and 153 (76.5%) in the PP analysis. The mean change in VAS pain did not differ between the two groups, and the upper limit of the two-sided 95% confidence interval (CI) for comparison between the two groups was within the prespecified margin of 10 mm for noninferiority (MITT analysis: mean difference = 0.86, 95% CI = -4.39 to 6.10, p=0.748; PP analysis: mean difference = 1.98, 95% CI = -3.61 to 7.56, p=0.486). Significant improvement was observed in all the efficacy parameters in both groups. Dyspepsia was the most common adverse event: 23 patients in the THF-6 group and 28 in the diclofenac group (p=0.417). Conclusions THF-6 offers an alternative to oral diclofenac for the short-term treatment of osteoarthritis of the knee. It was shown to be noninferior to oral diclofenac in relieving knee pain. This trial is registered with ChiCTR-IPR-15007213.
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Ho KY, Cardosa MS, Chaiamnuay S, Hidayat R, Ho HQT, Kamil O, Mokhtar SA, Nakata K, Navarra SV, Nguyen VH, Pinzon R, Tsuruoka S, Yim HB, Choy E. Practice Advisory on the Appropriate Use of NSAIDs in Primary Care. J Pain Res 2020; 13:1925-1939. [PMID: 32821151 PMCID: PMC7422842 DOI: 10.2147/jpr.s247781] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 06/24/2020] [Indexed: 12/14/2022] Open
Abstract
Cyclo-oxygenase (COX)-2 selective and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are important in managing acute and chronic pain secondary to inflammation. As a greater understanding of the risks of gastrointestinal (GI), cardiovascular (CV) and renal events with NSAIDs use has emerged, guidelines have evolved to reflect differences in risks among NSAIDs. Updated guidelines have yet to reflect new evidence from recent trials which showed similar CV event rates with celecoxib compared to naproxen and ibuprofen, and significantly better GI tolerability for celecoxib. This practice advisory paper aims to present consensus statements and associated guidance regarding appropriate NSAID use based on a review of current evidence by a multidisciplinary group of expert clinicians. This paper is especially intended to guide primary care practitioners within Asia in the appropriate use of NSAIDs in primary care. Following a literature review, group members used a modified Delphi consensus process to determine agreement with selected recommendations. Agreement with a statement by 75% of total voting members was defined a priori as consensus. For low GI risk patients, any nonselective NSAID plus proton pump inhibitor (PPI) or celecoxib alone is acceptable treatment when CV risk is low; for high CV risk patients, low-dose celecoxib or naproxen plus PPI is appropriate. For high GI risk patients, celecoxib plus PPI is acceptable for low CV risk patients; low-dose celecoxib plus PPI is appropriate for high CV risk patients, with the alternative to avoid NSAIDs and consider opioids instead. Appropriate NSAID prescription assumes that the patient has normal renal function at commencement, with ongoing monitoring recommended. In conclusion, appropriate NSAID use requires consideration of all risks.
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Affiliation(s)
- Kok Yuen Ho
- The Pain Clinic, Mt Alvernia Hospital, Singapore
| | | | - Sumapa Chaiamnuay
- Rheumatic Disease Unit, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand
| | - Rudy Hidayat
- Rheumatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusomo Hospital, Jakarta, Indonesia
| | | | - Ozlan Kamil
- Gleneagles Hospital, Kuala Lumpur, Malaysia.,Prince Court Medical Center, Kuala Lumpur, Malaysia
| | - Sabarul A Mokhtar
- Department of Orthopaedics and Traumatology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Ken Nakata
- Department of Health and Sport Sciences, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Sandra V Navarra
- Section of Rheumatology, Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Van Hung Nguyen
- Department of Rheumatology, Bach Mai Hospital, Hanoi, Vietnam
| | - Rizaldy Pinzon
- Department of Neurology, Faculty of Medicine, Kristen Duta Wacana University, Bethesda Hospital, Yogyakarta, Indonesia
| | | | - Heng Boon Yim
- Mount Elizabeth Novena Hospital, Singapore.,Faculty of Medicine, National University of Singapore, Singapore
| | - Ernest Choy
- Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK
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12
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Wang H, Wang L, Xie Z, Zhou S, Li Y, Zhou Y, Sun M. Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer. Cancers (Basel) 2020; 12:E1881. [PMID: 32668616 PMCID: PMC7408898 DOI: 10.3390/cancers12071881] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Revised: 07/10/2020] [Accepted: 07/10/2020] [Indexed: 12/13/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most lethal malignancies worldwide and CRC therapy remains unsatisfactory. In recent decades, nitric oxide (NO)-a free-radical gas-plus its endogenous producer NO synthases (NOS), have attracted considerable attention. NO exerts dual effects (pro- and anti-tumor) in cancers. Endogenous levels of NO promote colon neoplasms, whereas exogenously sustained doses lead to cytotoxic functions. Importantly, NO has been implicated as an essential mediator in many signaling pathways in CRC, such as the Wnt/β-catenin and extracellular-signal-regulated kinase (ERK) pathways, which are closely associated with cancer initiation, metastasis, inflammation, and chemo-/radio-resistance. Therefore, NO/NOS have been proposed as promising targets in the regulation of CRC carcinogenesis. Clinically relevant NO-donating agents have been developed for CRC therapy to deliver a high level of NO to tumor sites. Notably, inducible NOS (iNOS) is ubiquitously over-expressed in inflammatory-associated colon cancer. The development of iNOS inhibitors contributes to targeted therapies for CRC with clinical benefits. In this review, we summarize the multifaceted mechanisms of NO-mediated networks in several hallmarks of CRC. We review the clinical manifestation and limitations of NO donors and NOS inhibitors in clinical trials. We also discuss the possible directions of NO/NOS therapies in the immediate future.
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Affiliation(s)
- Hao Wang
- College of Laboratory Medicine, Jilin Medical University, Jilin 132013, China;
| | - Liye Wang
- Department of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, TX, 77204, USA; (L.W.); (Z.X.); (S.Z.); (Y.L.)
| | - Zuoxu Xie
- Department of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, TX, 77204, USA; (L.W.); (Z.X.); (S.Z.); (Y.L.)
| | - Shuang Zhou
- Department of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, TX, 77204, USA; (L.W.); (Z.X.); (S.Z.); (Y.L.)
| | - Yan Li
- Department of Pharmacological and Pharmaceutical Science, College of Pharmacy, University of Houston, Houston, TX, 77204, USA; (L.W.); (Z.X.); (S.Z.); (Y.L.)
| | - Yue Zhou
- Department of Statistics, North Dakota University, Fargo, ND 58105, USA;
| | - Meiyan Sun
- College of Laboratory Medicine, Jilin Medical University, Jilin 132013, China;
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13
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Role of proteinase-activated receptors 1 and 2 in nonsteroidal anti-inflammatory drug enteropathy. Pharmacol Rep 2020; 72:1347-1357. [DOI: 10.1007/s43440-020-00119-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 06/16/2020] [Accepted: 06/17/2020] [Indexed: 12/12/2022]
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14
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Bruyère O, Honvo G, Veronese N, Arden NK, Branco J, Curtis EM, Al-Daghri NM, Herrero-Beaumont G, Martel-Pelletier J, Pelletier JP, Rannou F, Rizzoli R, Roth R, Uebelhart D, Cooper C, Reginster JY. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum 2019; 49:337-350. [PMID: 31126594 DOI: 10.1016/j.semarthrit.2019.04.008] [Citation(s) in RCA: 315] [Impact Index Per Article: 52.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 03/31/2019] [Accepted: 04/25/2019] [Indexed: 12/27/2022]
Abstract
OBJECTIVES The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) sought to revisit the 2014 algorithm recommendations for knee osteoarthritis (OA), in light of recent efficacy and safety evidence, in order to develop an updated stepwise algorithm that provides practical guidance for the prescribing physician that is applicable in Europe and internationally. METHODS Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process, a summary of evidence document for each intervention in OA was provided to all members of an ESCEO working group, who were required to evaluate and vote on the strength of recommendation for each intervention. Based on the evidence collected, and on the strength of recommendations afforded by consensus of the working group, the final algorithm was constructed. RESULTS An algorithm for management of knee OA comprising a stepwise approach and incorporating consensus on 15 treatment recommendations was prepared by the ESCEO working group. Both "strong" and "weak" recommendations were afforded to different interventions. The algorithm highlights the continued importance of non-pharmacological interventions throughout the management of OA. Benefits and limitations of different pharmacological treatments are explored in this article, with particular emphasis on safety issues highlighted by recent literature analyses. CONCLUSIONS The updated ESCEO stepwise algorithm, developed by consensus from clinical experts in OA and informed by available evidence for the benefits and harms of various treatments, provides practical, current guidance that will enable clinicians to deliver patient-centric care in OA practice.
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Affiliation(s)
- Olivier Bruyère
- Division of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart Tilman, 4000, Liège, Belgium; WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium.
| | - Germain Honvo
- Division of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart Tilman, 4000, Liège, Belgium; WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium
| | - Nicola Veronese
- Nicola Veronese: National Research Council, Neuroscience Institute, Aging Branch, Padova, Italy
| | - Nigel K Arden
- Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, University of Oxford, Oxford, UK; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK
| | - Jaime Branco
- CEDOC, NOVA Medical School, Universidade Nova de Lisboa, Department of Rheumatology, CHLO, Hospital Egas Moniz, Lisbon, Portugal
| | - Elizabeth M Curtis
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK
| | - Nasser M Al-Daghri
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Gabriel Herrero-Beaumont
- Department of Rheumatology, Bone and Joint Research Unit, Fundación Jiménez Diaz, Universidad Autonoma, Madrid, Spain
| | - Johanne Martel-Pelletier
- Division of Rheumatology, University of Montreal Hospital Centre (CHUM), Osteoarthritis Research Unit, CHUM Research Centre (CRCHUM), Montreal, Quebec, Canada
| | - Jean-Pierre Pelletier
- Division of Rheumatology, University of Montreal Hospital Centre (CHUM), Osteoarthritis Research Unit, CHUM Research Centre (CRCHUM), Montreal, Quebec, Canada
| | - François Rannou
- Division of Physical Medicine and Rehabilitation, Department of Rheumatology, AP-HP Cochin Hospital, Université Paris Descartes Sorbonne Paris Cité, and INSERM U1124, France
| | - René Rizzoli
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium; Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - Roland Roth
- Max-Reger-Strasse 17-19, 45128, Essen-Suedviertel, Germany
| | - Daniel Uebelhart
- Division of Musculoskeletal, Internal Medicine and Oncological Rehabilitation, Department of Orthopaedics and Traumatology, Hôpital du Valais (HVS), Centre Hospitalier du Valais Romand (CHVR), CVP, 3963, Crans-Montana, Switzerland
| | - Cyrus Cooper
- WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK; NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK
| | - Jean-Yves Reginster
- Division of Public Health, Epidemiology and Health Economics, University of Liège, CHU Sart Tilman, 4000, Liège, Belgium; WHO Collaborating Centre for Public Health Aspects of Musculoskeletal Health and Aging, Liège, Belgium; Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
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15
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Curtis E, Fuggle N, Shaw S, Spooner L, Ntani G, Parsons C, Corp N, Honvo G, Baird J, Maggi S, Dennison E, Bruyère O, Reginster JY, Cooper C. Safety of Cyclooxygenase-2 Inhibitors in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis. Drugs Aging 2019; 36:25-44. [PMID: 31073922 PMCID: PMC6509094 DOI: 10.1007/s40266-019-00664-x] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Objective Our aim was to assess the safety of cyclooxygenase-2 (COX-2) inhibitors in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials. Methods A comprehensive literature search was undertaken in the databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with COX-2 inhibitors in patients with OA were eligible for inclusion. Two authors appraised titles, abstracts and full-text papers for suitability and then assessed the studies for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcomes reporting. The primary outcomes of interest were gastrointestinal disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatobiliary disorders, renal and urinary disorders, as well as overall severe and serious AEs, drug-related AEs and mortality. Secondary outcomes were withdrawals due to AEs (i.e. the number of participants who stopped the treatment due to an AE) and total number of AEs (i.e. the number of patients who experienced any AE at least once). Results Database searches identified 2149 records from which, after exclusions, 40 trials were included in the meta-analysis. The use of COX-2 inhibitors in OA was associated with a significant increased risk of drug-related AEs compared with placebo (relative risk (RR) 1.26, 95% CI 1.09–1.46; I2 = 24%). The risk of upper gastrointestinal complications (including dyspepsia, gastritis and heartburn) was significantly increased with COX-2 inhibitors versus placebo (RR 1.19, 95% CI 1.03–1.38; I2 = 0%), particularly for abdominal pain, which increased by 40% with COX-2 inhibitors (RR 1.40, 95% CI 1.08–1.80; I2 = 0%). The risk of hypertension increased by 45% overall (RR 1.45, 95% CI 1.01–2.10; I2 = 25%); however, when rofecoxib was removed from the analysis the risk of hypertension in the COX-2 inhibitor group was no longer significant (RR 1.21, 95% CI 0.80–1.83; I2 = 20%). The overall risk of heart failure and edema was increased by nearly 70% with COX-2 inhibitors versus placebo (RR 1.68, 95% CI 1.22–2.31; 0%) and this level of risk did not change appreciably when rofecoxib was excluded (RR 1.67, 95% CI 1.21–2.29; 0%). Conclusions In our analysis, COX-2 inhibitors were associated with an increased risk of upper gastrointestinal AEs, especially abdominal pain. We also found an increased risk of cardiovascular AEs with COX-2 inhibitors, namely hypertension, heart failure and edema. Electronic supplementary material The online version of this article (10.1007/s40266-019-00664-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Elizabeth Curtis
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK
| | - Nicholas Fuggle
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK
| | - Sarah Shaw
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK
| | | | - Georgia Ntani
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK
| | - Camille Parsons
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK
| | - Nadia Corp
- Arthritis Research UK Primary Care Centre, Institute for Primary Care and Health Sciences, Keele University, Keele, UK
| | - Germain Honvo
- Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.,WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liège, Belgium
| | - Janis Baird
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK
| | - Stefania Maggi
- Aging Program, National Research Council, Neuroscience Institute, Padua, Italy
| | - Elaine Dennison
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK
| | - Olivier Bruyère
- Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.,WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liège, Belgium
| | - Jean-Yves Reginster
- Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.,WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liège, Belgium.,Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Cyrus Cooper
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. .,WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liège, Belgium. .,National Institute for Health Research (NIHR) Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK.
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16
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Nekrasov AA, Timoshchenko ES, Erofeeva SG, Karpukhina EV. [Predictors for development of major cardiovascular events in elderly patients with severe and extremely severe chronic obstructive pulmonary disease in combination with early stages of chronic kidney disease]. ACTA ACUST UNITED AC 2019; 59:43-51. [PMID: 30990152 DOI: 10.18087/cardio.2536] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2019] [Accepted: 04/13/2019] [Indexed: 11/18/2022]
Abstract
The aim of the study was to evaluate efficacy, safety and treatment compliance for different ASA forms (Aspirin Cardio, Cardiomagnyl and Trombo Ass) in a 6-month study. MATERIALS AND METHODS A prospective 6-month open, comparative study originally included 600 patients with IHD and stable angina who received chronic therapy with different forms of aspirin. In the prospective part of the study, these patients were subdivided into four groups: group 1 consisted of 200 patients switched to Aspirin Cardio; group 2 - 200 pa - tients receiving chronic therapy with this drug; group 3 - 100 patients continuing on the Trombo Ass treatment; and group 4 - 100 pa - tients who had been treated with Cardiomagnyl for a long time. Efficacy, safety and compliance to the treatment were evaluated using standard tests and analogue scales; symptoms of dyspepsia were evaluated with a study-specific questionnaire. Switching to Aspirin Cardio (group 1) was on discretion of the physician in charge based on the history of gastrointestinal (GI) complications or significant manifestations of dyspepsia. RESULTS The efficacy in prevention of cardiovascular events was similar in all groups. No "major" or "minor, clinically significant" bleeding (ISTH) were observed. Proportions of patients with "minor" bleeding were similar in all groups with a tendency towards their decrease under the Aspirin Cardio treatment. After switching to Aspirin Cardio, positive changes in severity of GI symptoms by results of the questionnaire: a significant improvement of compliance by the treatment satisfaction index in group 1 and 2; and a 1.7 time decrease in the proportion of ASA-noncompliant patients were observed. According to the results of ROC analysis an average GI symptom score ≥3 predicted an improvement of compliance in case of switching to Aspirin Cardio with a diagnostic sensitivity of 72.3% and specificity of 51.1% (р=0.012) as well as alleviation of GI symptoms (sensitivity, 74.5%; specificity, 63.8%, р=0.001). CONCLUSIONS Different dosage forms of ASA are characterized with similar efficacy in prevention of cardiovascular events and effects on the risk of bleeding. Aspirin Cardio showed a better tolerability due to a less effect on GI symptoms. It provided a better compliance to chronic treatment. This study confirmed advisability of using the proposed questionnaire to evaluate GI symptoms for specification of prediction and modification of therapy.
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Affiliation(s)
- A A Nekrasov
- Privolzhsky Research Medical University, Minin and Pozharsky square 10/1, Nizhny Novgorod 603950
| | - E S Timoshchenko
- Municipal Clinical Hospital #5, Nesterova 34, Nizhny Novgorod 603005
| | - S G Erofeeva
- Municipal Clinical Hospital #5, Nesterova 34, Nizhny Novgorod 603005
| | - E V Karpukhina
- Privolzhsky Research Medical University, Minin and Pozharsky square 10/1, Nizhny Novgorod 603950
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17
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Cooper C, Chapurlat R, Al-Daghri N, Herrero-Beaumont G, Bruyère O, Rannou F, Roth R, Uebelhart D, Reginster JY. Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say? Drugs Aging 2019; 36:15-24. [PMID: 31073921 PMCID: PMC6509083 DOI: 10.1007/s40266-019-00660-1] [Citation(s) in RCA: 128] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely recommended and prescribed to treat pain in osteoarthritis. While measured to have a moderate effect on pain in osteoarthritis, NSAIDs have been associated with wide-ranging adverse events affecting the gastrointestinal, cardiovascular, and renal systems. Gastrointestinal toxicity is found with all NSAIDs, which may be of particular concern when treating older patients with osteoarthritis, and gastric adverse events may be reduced by taking a concomitant gastroprotective agent, although intestinal adverse events are not ameliorated. Cardiovascular toxicity is associated with all NSAIDs to some extent and the degree of risk appears to be pharmacotherapy specific. An increased risk of acute myocardial infarction and heart failure is observed with all NSAIDs, while an elevated risk of hemorrhagic stroke appears to be restricted to the use of diclofenac and meloxicam. All NSAIDs have the potential to induce acute kidney injury, and patients with osteoarthritis with co-morbid conditions including hypertension, heart failure, and diabetes mellitus are at increased risk. Osteoarthritis is associated with excess mortality, which may be explained by reduced levels of physical activity owing to lower limb pain, presence of comorbid conditions, and the adverse effects of anti-osteoarthritis medications especially NSAIDs. This narrative review of recent literature identifies data on the safety of non-selective NSAIDs to better understand the risk:benefit of using NSAIDs to manage pain in osteoarthritis.
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Affiliation(s)
- Cyrus Cooper
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD UK
- National Institute for Health Research Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK
- WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liège, Belgium
| | - Roland Chapurlat
- INSERM, UMR 1033, Université de Lyon, Hôpital E Herriot, Lyon, France
| | - Nasser Al-Daghri
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
| | - Gabriel Herrero-Beaumont
- Rheumatology Service, Joint and Bone Research Unit, Autonomous University of Madrid, Fundación Jiménez Díaz, Madrid, Spain
| | - Olivier Bruyère
- WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liège, Belgium
- Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
| | - François Rannou
- Division of Physical Medicine and Rehabilitation, Department of Rheumatology, AP-HP Cochin Hospital, INSERM U1124, Université Paris Descartes Sorbonne Paris Cité, Paris, France
| | - Roland Roth
- Max-Reger-Strasse 17-19, Essen-Suedviertel, Germany
| | - Daniel Uebelhart
- Division of Musculoskeletal, Internal Medicine and Oncological Rehabilitation, Department of Orthopaedics and Traumatology, Hôpital du Valais, Centre Hospitalier du Valais Romand, CVP, Crans-Montana, Switzerland
| | - Jean-Yves Reginster
- WHO Collaborating Centre for Public Heath Aspects of Musculoskeletal Health and Aging, Liège, Belgium
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
- Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
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18
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Moilanen E, Vuolteenaho K. Nonsteroidal Anti-inflammatory Drugs. NIJKAMP AND PARNHAM'S PRINCIPLES OF IMMUNOPHARMACOLOGY 2019:689-707. [DOI: 10.1007/978-3-030-10811-3_33] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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19
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Are All Oral COX-2 Selective Inhibitors the Same? A Consideration of Celecoxib, Etoricoxib, and Diclofenac. Int J Rheumatol 2018; 2018:1302835. [PMID: 30631366 PMCID: PMC6304524 DOI: 10.1155/2018/1302835] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 10/31/2018] [Indexed: 12/15/2022] Open
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used for the treatment of arthritic conditions. Drugs in this heterogeneous class alleviate pain and inflammation by inhibiting cyclooxygenase-2 (COX-2). Cyclooxygenase-1 (COX-1) inhibition has traditionally been associated with increased gastrointestinal (GI) harm, whereas increased COX-2 selectivity has more recently become associated with greater risk of cardiovascular (CV) harm. When the entirety of data is considered, NSAIDs can be seen to exhibit a range of COX isoform selectivity, with all oral NSAIDs appearing to be associated with an increase in CV events. This review focuses on a comparison of the efficacy and the GI and CV safety profiles of three commonly used NSAIDs-celecoxib, etoricoxib, and diclofenac-using direct comparisons where available. While all three treatments are shown to have comparable efficacy, there are differences in their safety profiles. Both celecoxib and etoricoxib are associated with less GI harm than diclofenac despite the similarity of its COX-2 selectivity to celecoxib. Each of the three medicines under consideration is associated with a similar overall risk of CV events (fatal and nonfatal heart attacks and strokes). However, there are consistent differences in effects on blood pressure (BP), reported both from trials using ambulatory techniques and from meta-analyses of randomized trials, reporting investigator determined effects, with etoricoxib being associated with a greater propensity to destabilize BP control than either diclofenac or celecoxib.
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20
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Lai ECC, Shin JY, Kubota K, Man KKC, Park BJ, Pratt N, Roughead EE, Wong ICK, Kao Yang YH, Setoguchi S. Comparative safety of NSAIDs for gastrointestinal events in Asia-Pacific populations: A multi-database, international cohort study. Pharmacoepidemiol Drug Saf 2018; 27:1223-1230. [PMID: 30232832 DOI: 10.1002/pds.4663] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Revised: 08/06/2018] [Accepted: 08/16/2018] [Indexed: 02/03/2023]
Abstract
PURPOSE The safety of nonsteroidal anti-inflammatory drugs (NSAIDs) commonly used in Asia-Pacific countries has had limited study. We assessed the risk of hospitalization for gastrointestinal events with loxoprofen and mefenamic acid compared with other NSAIDs in Asia-Pacific populations. METHODS We conducted a cohort study using a distributed network with a common data model in Australia, Hong Kong, Japan, Korea, and Taiwan. We included patients who initiated diclofenac, loxoprofen, mefenamic acid, or celecoxib and followed them until their first gastrointestinal hospitalization, switch or discontinuation of medication, disenrollment, or end of database coverage. We used Cox proportional hazards models to assess hospitalization risk. RESULTS We identified 9879 patients in Japan, 70 492 in Taiwan, 263 741 in Korea, and 246 in Hong Kong who initiated an NSAID, and 44 013 patients in Australia, a predominantly Caucasian population. The incidence of gastrointestinal hospitalization was 25.6 per 1000 person-years in Japan, 32.8 in Taiwan, 11.5 in Korea, 484.5 in Hong Kong, and 35.6 in Australia. Compared with diclofenac, the risk of gastrointestinal events with loxoprofen was significantly lower in Korea (hazards ratio, 0.37; 95% CI, 0.25-0.54) but not in Japan (1.65; 95% CI, 0.47-5.78). The risk of gastrointestinal events with mefenamic acid was significantly lower in Taiwan (0.45; 95% CI, 0.26-0.78) and Korea (0.11; 95% CI, 0.05-0.27) but not Hong Kong (2.16; 95% CI, 0.28-16.87), compared with diclofenac. CONCLUSIONS Compared with diclofenac, loxoprofen was associated with a lower risk of gastrointestinal hospitalizations in Korea and mefenamic acid with a lower risk in Taiwan and Korea.
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Affiliation(s)
- Edward Chia-Cheng Lai
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University, Tainan, Taiwan.,Department of Pharmacy, National Cheng Kung University Hospital, Tainan, Taiwan.,Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA
| | - Ju-Young Shin
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Kiyoshi Kubota
- Department of Pharmacoepidemiology, University of Tokyo, Tokyo, Japan
| | - Kenneth K C Man
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong
| | - Byung Joo Park
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea.,Office of Drug Utilization Review, Korea Institute of Drug Safety and Risk Management, Seoul, South Korea
| | - Nicole Pratt
- Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute for Health Research, University of South Australia, Adelaide, Australia
| | - Elizabeth E Roughead
- Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute for Health Research, University of South Australia, Adelaide, Australia
| | - Ian C K Wong
- Health Outcome Research Center, National Cheng-Kung University, Tainan, Taiwan
| | - Yea-Huei Kao Yang
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University, Tainan, Taiwan.,Health Outcome Research Center, National Cheng-Kung University, Tainan, Taiwan
| | - Soko Setoguchi
- Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.,Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.,Rutgers Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Rutgers University, New Brunswick, NJ, USA
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21
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Martín Arias LH, Martín González A, Sanz Fadrique R, Vazquez ES. Cardiovascular Risk of Nonsteroidal Anti-inflammatory Drugs and Classical and Selective Cyclooxygenase-2 Inhibitors: A Meta-analysis of Observational Studies. J Clin Pharmacol 2018; 59:55-73. [PMID: 30204233 DOI: 10.1002/jcph.1302] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Accepted: 07/23/2018] [Indexed: 01/09/2023]
Abstract
The purpose of this study was to review the published evidence on the clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) and to assess the cardiovascular risk (CVR) of cyclooxygenase-2 inhibitors (coxibs), excluding aspirin, by means of a meta-analytic procedure. A search was conducted on MEDLINE and EMBASE databases between October 1999 and June 2018. Cohort and case-control studies showing CVR as relative risk (RR), odds ratio, hazard ratio, or incidence rate ratio associated with NSAIDs versus no treatment were selected. We estimated the pooled RR and the 95% confidence interval (CI) for all NSAIDs as a whole and individually. Eighty-seven studies met the inclusion criteria. Overall, NSAIDs were found to be associated with a statistically significantly increased CVR (RR, 1.24 [95%CI, 1.19-1.28]). The risk was slightly higher for coxibs (RR, 1.22 [95%CI, 1.17-1.28]) as compared with nonselective NSAIDs (RR, 1.18 [95%CI, 1.12-1.24]). Data analysis by drug disclosed that rofecoxib (RR, 1.39 [95%CI, 1.31-1.47]), followed by diclofenac (RR, 1.34 [95%CI, 1.26-1.42]) and etoricoxib (RR, 1.27 [95%CI, 1.12-1.43]) were the NSAIDs associated with the highest CVR. Analysis by type of event showed that the highest risk corresponded to vascular events for both coxibs (RR, 2.18 [95%CI, 1.72-2.78]) and nonselective NSAIDs (RR, 2.46 [95%CI, 2.00-3.02]). The meta-analysis results suggest that the use of the marketed coxibs celecoxib and etoricoxib would be related to a statistically significant CVR increase. Etoricoxib CVR could be higher than that for celecoxib. This increment would be similar to classical NSAID CVR.
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Affiliation(s)
| | | | - Rosario Sanz Fadrique
- Centre for Drug Surveillance (CESME), School of Medicine, Valladolid University, Valladolid, Spain
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Martin Arias LH, Martin Gonzalez A, Sanz Fadrique R, Salgueiro E, Sainz M. Cardiovascular and gastrointestinal safety of selective cyclooxygenase-2 inhibitors: a case/non-case study. Int J Clin Pharm 2018; 40:928-935. [PMID: 30066292 DOI: 10.1007/s11096-018-0705-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2018] [Accepted: 07/24/2018] [Indexed: 10/28/2022]
Abstract
Background Coxibs cardiovascular (CV) safety continues being a current issue after rofecoxib worldwide withdrawal in 2004. Objective To evaluate the cardiovascular and gastrointestinal (GI) risk of coxibs through case/non-case study. Setting The Spanish Pharmacovigilance System for Human Use Drugs (FEDRA) and the Uppsala Monitoring Centre (VigiBase) databases. Method We identified adverse drug reactions (ADRs) cases reported under the MedDRA system organ classes of "cardiac disorders", "vascular disorders", "nervous system disorder" and "gastrointestinal disorders". Disproportionality was considered when the following criteria were met simultaneously: proportional reporting ratio (PRR) ≥ 2, 95% confidence interval lower limit of reporting odds ratio (ROR) > 1, Chi square test (χ2) ≥ 4; and number of ADR reports (n rep.) > 3. Main outcome measure Potential disproportionality between cardiovascular and GI ADRs as reported to FEDRA and VigiBase and the use of coxibs. Results We found association between coxibs and CV-ADRs in FEDRA [PRR 2.11 (95% CI 1.97-2.27); ROR 2.53 (95% CI 2.29-2.89); χ2 367.81; n rep., 561] and VigiBase [PRR 2.67 (95% CI 2.64-2.71); ROR 3.26 (95% CI 3.20-3.31); χ2 23,950.93; n rep., 21,047]; and between coxibs and GI-ADRs in VigiBase [PRR 2.91 (95% CI 2.84-2.97); ROR 3.08 (95% CI 3.01-3.16); χ2 8762.82; n rep. 6954]. No association was found between coxibs and GI-ADRs in FEDRA. Conclusion The association found support a potential coxibs class effect in terms of cardiovascular safety. Classical NSAIDs GI risk may be higher than that for coxibs.
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Affiliation(s)
| | | | - Rosario Sanz Fadrique
- Centre for Drug Surveillance (CESME), School of Medicine, Valladolid University, Valladolid, Spain
| | - Esther Salgueiro
- Department of Pharmacology, School of Medicine, Oviedo University, Valladolid, Spain
| | - Maria Sainz
- Centre for Drug Surveillance (CESME), School of Medicine, Valladolid University, Valladolid, Spain
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Ho KY, Gwee KA, Cheng YK, Yoon KH, Hee HT, Omar AR. Nonsteroidal anti-inflammatory drugs in chronic pain: implications of new data for clinical practice. J Pain Res 2018; 11:1937-1948. [PMID: 30288088 PMCID: PMC6160277 DOI: 10.2147/jpr.s168188] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
COX2-selective and nonselective (ns) nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for chronic pain management. There are marked differences in the risk of adverse gastrointestinal (GI) and cardiovascular (CV) events among different NSAIDs. In 2017, publication of two randomized controlled trials and an individual patient-data meta-analysis provided robust data on the relative GI and CV tolerability profiles of currently available NSAIDs. The PRECISION study showed similar CV-event rates with celecoxib vs naproxen and ibuprofen, but GI tolerability was better for celecoxib. In the CONCERN study of high-GI-risk patients, celecoxib was associated with fewer adverse GI-tract events than naproxen. The meta-analysis showed no significant difference between celecoxib and ns-NSAIDs in the rate of acute myocardial infarction, and celecoxib was the only COX2-selective NSAID with a lower risk of adverse CV and GI events vs ns-NSAIDs. These data add to the body of knowledge about the relative tolerability of different NSAIDs and were used to propose an updated treatment algorithm. The decision about whether to use an NSAID and which one should be based on a patient's risk of developing adverse GI and CV events. Lower- and upper-GI-tract events need to be considered. Celecoxib has a better lower-GI-tract tolerability profile than ns-NSAIDs plus a proton-pump inhibitor. In addition, the latest data suggest that long-term use of celecoxib 200 mg/day may be appropriate for patients at increased CV risk.
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Affiliation(s)
| | - Kok Ann Gwee
- Stomach, Liver, and Bowel Centre, Gleneagles Hospital
| | - Yew Kuang Cheng
- Farrer Park Hospital
- Yong Loo Lin School of Medicine, National University of Singapore
| | - Kam Hon Yoon
- El Shaddai Arthritis and Rheumatism Specialist Medical Centre
| | - Hwan Tak Hee
- Pinnacle Spine and Scoliosis Centre, Mt Elizabeth Medical Centre
| | - Abdul Razakjr Omar
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
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Katchamart W, Narongroeknawin P, Chevaisrakul P, Dechanuwong P, Mahakkanukrauh A, Kasitanon N, Pakchotanon R, Sumethkul K, Ueareewongsa P, Ukritchon S, Bhurihirun T, Duangkum K, Intapiboon P, Intongkam S, Jangsombatsiri W, Jatuworapruk K, Kositpesat N, Leungroongroj P, Lomarat W, Petcharat C, Sittivutworapant S, Suebmee P, Tantayakom P, Tipsing W, Asavatanabodee P, Chiowchanwisawakit P, Foocharoen C, Koolvisoot A, Louthrenoo W, Siripaitoon B, Totemchokchyakarn K, Kitumnuaypong T. Evidence-based recommendations for the diagnosis and management of rheumatoid arthritis for non-rheumatologists: Integrating systematic literature research and expert opinion of the Thai Rheumatism Association. Int J Rheum Dis 2017; 20:1142-1165. [PMID: 27452207 DOI: 10.1111/1756-185x.12905] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
AIM Rheumatoid arthritis (RA) is a chronic inflammatory joint disease leading to joint damage, functional disability, poor quality of life and shortened life expectancy. Early diagnosis and aggressive treatment are a principal strategy to improve outcomes. To provide best practices in the diagnosis and management of patients with RA, the Thai Rheumatism Association (TRA) developed scientifically sound and clinically relevant evidence-based recommendations for general practitioners, internists, orthopedists, and physiatrists. METHODS Thirty-seven rheumatologists from across Thailand formulated 18 clinically relevant questions: three for diagnosis, 10 for treatments, four for monitoring, and one for referral. A bibliographic team systematically reviewed the relevant literature on these topics up to December 2013. A set of recommendations was proposed based on the results of systematic reviews combined with expert opinions. Group consensus was achieved for all statements and recommendations using the nominal group technique. RESULTS A set of recommendations was proposed. For diagnosis, either American College of Rheumatology (ACR) 1987 or ACR/European League Against Rheumatism 2010 classification criteria can be applied. For treatment, nonsteroidal anti-inflammatory drugs, glucocorticoid, and disease-modifying antirheumatic drugs, including antimalarials, methotrexate and sulfasalazine are recommended. Physiotherapy should be suggested to all patients. Tight control strategy and monitoring for efficacy and side effects of treatments, as well as indications for referral to a rheumatologist are provided. CONCLUSIONS These evidence-based recommendations provide practical guidance for diagnosis, fundamental management and referral of patients with RA for non-rheumatologists. However, it should be incorporated with clinical judgments and decisions about care for each individual patient.
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Affiliation(s)
- Wanruchada Katchamart
- Division of Rheumatology, Department of Medicine, Faculty of Medicine, Siriraj hospital, Mahidol University, Bangkok, Thailand
| | - Pongthorn Narongroeknawin
- Division of Rheumatology, Department of Medicine, Pramongkutklao and College of Medicine, Bangkok, Thailand
| | - Parawee Chevaisrakul
- Division of Allergy, Immunology and Rheumatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol, Bangkok, Thailand
| | - Pornchai Dechanuwong
- Division of Rheumatology, Department of Medicine, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
| | - Ajanee Mahakkanukrauh
- Division of Allergy, Immunology and Rheumatology, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Nuntana Kasitanon
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Rattapol Pakchotanon
- Division of Rheumatology, Department of Medicine, Pramongkutklao and College of Medicine, Bangkok, Thailand
| | - Kittiwan Sumethkul
- Rheumatology Unit, Department of Internal Medicine, Rajavithi Hospital, Bangkok, Thailand
| | - Parichat Ueareewongsa
- Division of Rheumatology, Department of Medicine, Faculty of Medicine, Prince of Songkla University, Songkla, Thailand
| | - Sittichai Ukritchon
- Division of Rheumatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Thitirat Bhurihirun
- Division of Rheumatology, Department of Medicine, Faculty of Medicine, Siriraj hospital, Mahidol University, Bangkok, Thailand
| | - Kittikorn Duangkum
- Division of Allergy, Immunology and Rheumatology, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Porntip Intapiboon
- Division of Rheumatology, Department of Medicine, Faculty of Medicine, Prince of Songkla University, Songkla, Thailand
| | - Samanan Intongkam
- Division of Rheumatology, Department of Medicine, Pramongkutklao and College of Medicine, Bangkok, Thailand
| | - Wimol Jangsombatsiri
- Division of Allergy, Immunology and Rheumatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol, Bangkok, Thailand
| | - Kanon Jatuworapruk
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Naravadee Kositpesat
- Division of Rheumatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Pawinee Leungroongroj
- Division of Allergy, Immunology and Rheumatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol, Bangkok, Thailand
| | - Wiyanoot Lomarat
- Division of Rheumatology, Department of Medicine, Pramongkutklao and College of Medicine, Bangkok, Thailand
| | - Chonachan Petcharat
- Division of Rheumatology, Department of Medicine, Faculty of Medicine, Siriraj hospital, Mahidol University, Bangkok, Thailand
| | | | - Patcharawan Suebmee
- Division of Allergy, Immunology and Rheumatology, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Pongchirat Tantayakom
- Division of Rheumatology, Department of Medicine, Faculty of Medicine, Siriraj hospital, Mahidol University, Bangkok, Thailand
| | - Worakan Tipsing
- Division of Rheumatology, Department of Medicine, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
| | - Paijit Asavatanabodee
- Division of Rheumatology, Department of Medicine, Pramongkutklao and College of Medicine, Bangkok, Thailand
| | - Praveena Chiowchanwisawakit
- Division of Rheumatology, Department of Medicine, Faculty of Medicine, Siriraj hospital, Mahidol University, Bangkok, Thailand
| | - Chingching Foocharoen
- Division of Allergy, Immunology and Rheumatology, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Ajchara Koolvisoot
- Division of Rheumatology, Department of Medicine, Faculty of Medicine, Siriraj hospital, Mahidol University, Bangkok, Thailand
| | - Worawit Louthrenoo
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Boonjing Siripaitoon
- Division of Rheumatology, Department of Medicine, Faculty of Medicine, Prince of Songkla University, Songkla, Thailand
| | - Kitti Totemchokchyakarn
- Division of Allergy, Immunology and Rheumatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol, Bangkok, Thailand
| | - Tasanee Kitumnuaypong
- Rheumatology Unit, Department of Internal Medicine, Rajavithi Hospital, Bangkok, Thailand
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Bakhriansyah M, Souverein PC, de Boer A, Klungel OH. Gastrointestinal toxicity among patients taking selective COX-2 inhibitors or conventional NSAIDs, alone or combined with proton pump inhibitors: a case-control study. Pharmacoepidemiol Drug Saf 2017; 26:1141-1148. [PMID: 28370857 PMCID: PMC5655916 DOI: 10.1002/pds.4183] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2016] [Revised: 01/12/2017] [Accepted: 01/22/2017] [Indexed: 02/02/2023]
Abstract
PURPOSE To assess the risk of gastrointestinal perforation, ulcers, or bleeding (PUB) associated with the use of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) with proton pump inhibitors (PPIs) and selective COX-2 inhibitors, with or without PPIs compared with conventional NSAIDs. METHODS A case-control study was performed within conventional NSAIDs and/or selective COX-2 inhibitors users identified from the Dutch PHARMO Record Linkage System in the period 1998-2012. Cases were patients aged ≥18 years with a first hospital admission for PUB. For each case, up to four controls were matched for age and sex at the date a case was hospitalized (index date). Logistic regression analysis was used to calculate odds ratios (ORs). RESULTS At the index date, 2634 cases and 5074 controls were current users of conventional NSAIDs or selective COX-2 inhibitors. Compared with conventional NSAIDs, selective COX-2 inhibitors with PPIs had the lowest risk of PUB (adjusted OR 0.51, 95% confidence interval [CI]: 0.35-0.73) followed by selective COX-2 inhibitors (adjusted OR 0.66, 95%CI: 0.48-0.89) and conventional NSAIDs with PPIs (adjusted OR 0.79, 95%CI: 0.68-0.92). Compared with conventional NSAIDs, the risk of PUB was lower for those aged ≥75 years taking conventional NSAIDs with PPIs compared with younger patients (adjusted interaction OR 0.79, 95%CI: 0.64-0.99). However, those aged ≥75 years taking selective COX-2 inhibitors, the risk was higher compared with younger patients (adjusted interaction OR 1.22, 95%CI: 1.01-1.47). CONCLUSIONS Selective COX-2 inhibitors with PPIs, selective COX-2 inhibitors, and conventional NSAIDs with PPIs were associated with lower risks of PUB compared with conventional NSAIDs. These effects were modified by age. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.
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Affiliation(s)
- Mohammad Bakhriansyah
- Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, The Netherlands.,Department of Pharmacology, Medical Faculty, Lambung Mangkurat University, Banjarmasin, Indonesia
| | - Patrick C Souverein
- Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, The Netherlands
| | - Anthonius de Boer
- Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, The Netherlands
| | - Olaf H Klungel
- Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, The Netherlands
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Olson JM, Haas AW, Lor J, McKee HS, Cook ME. A Comparison of the Anti-Inflammatory Effects of Cis-9, Trans-11 Conjugated Linoleic Acid to Celecoxib in the Collagen-Induced Arthritis Model. Lipids 2017; 52:151-159. [PMID: 28078603 DOI: 10.1007/s11745-016-4228-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2016] [Accepted: 12/13/2016] [Indexed: 01/07/2023]
Abstract
Cyclooxygenase (COX)-2 inhibitors, such as celecoxib, for chronic inflammatory disease are associated with adverse health events, while cis-9, trans-11 (c9t11) conjugated linoleic acid (CLA) is anti-inflammatory without adverse events attributed to pure intake. Mechanistically, celecoxib and c9t11 disrupt the arachidonic acid cascade; however, the equivalency of anti-inflammatory effects between these compounds is unknown. Therefore, to test the hypothesis that 0.5% dietary c9t11 reduces inflammation equivalently to a celecoxib dose intended to treat rheumatoid arthritis (RA; 5 mg/kg bw), arthritic mice received diets containing one of the following supplements: 1% corn oil (CO, w/w), 0.5% c9t11 (>91% purity) +0.5% CO, or 1% CO + 0.5, 5, or 50 mg/kg bw celecoxib, and were assessed for changes in arthritic severity over 6 weeks. Overall, arthritic severity in mice fed c9t11 was reduced (34%, P < 0.01) while celecoxib doses (0.5, 5, 50 mg/kg) reduced arthritic severity (16, 56, 48%, respectively) compared to CO-fed arthritic mice. Linear regression of the celecoxib dose-response showed 0.5% c9t11 (570 mg/kg bw) reduced arthritic severity equivalently to 1.5 mg/kg celecoxib. Interleukin-6 (IL-6) was increased in paws of arthritic mice fed CO compared to shams, but was decreased in arthritic groups fed 0.5% c9t11 and 5 mg/kg celecoxib, compared to arthritic mice fed CO (Ps ≤ 0.05). Additionally, paw and plasma IL-10 levels in arthritic mice were decreased by 5 mg/kg celecoxib, but were unaffected by c9t11 compared to CO. Results suggest dietary c9t11 may be an effective adjunct to COX-2 inhibition for treating chronic inflammation.
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Affiliation(s)
- Jake M Olson
- Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, WI, 53706, USA
| | - Alexander W Haas
- Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA
| | - Jennifer Lor
- Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA
| | - Holly S McKee
- Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA
| | - Mark E Cook
- Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, WI, 53706, USA.
- Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA.
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27
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Parada L, Marstein JP, Danilov A. Tolerability of the COX-1/COX-2 inhibitor lornoxicam in the treatment of acute and rheumatic pain. Pain Manag 2016; 6:445-54. [DOI: 10.2217/pmt.16.7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: To assess the safety of lornoxicam with particular focus on gastrointestinal (GI) events. Methods: Data on adverse drug reactions (ADRs) were pooled from 60 comparative studies of lornoxicam. Results: A total of 6420 patients received lornoxicam, 1192 received placebo and 3770 received a comparator analgesic. ADRs were reported by 21% of lornoxicam-treated patients, with GI events the most frequent (14 vs 8% with placebo). Across 15 studies that compared lornoxicam (n = 1287) with another NSAID (n = 1010), there was a reduced risk of a GI ADR with lornoxicam (0.78 [95% CI: 0.64–0.96]; p = 0.017). Conclusion: Lornoxicam was well tolerated with the type of GI events observed consistent with the known safety profile of NSAIDs.
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Affiliation(s)
- Luis Parada
- Central University of Venezuela, Caracas, Venezuela
| | | | - Andrey Danilov
- IM Sechenov First Moscow State Medical University, Moscow, Russia
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28
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Goswami SK, Wan D, Yang J, Trindade da Silva CA, Morisseau C, Kodani SD, Yang GY, Inceoglu B, Hammock BD. Anti-Ulcer Efficacy of Soluble Epoxide Hydrolase Inhibitor TPPU on Diclofenac-Induced Intestinal Ulcers. J Pharmacol Exp Ther 2016; 357:529-36. [PMID: 26989141 PMCID: PMC4885505 DOI: 10.1124/jpet.116.232108] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2016] [Accepted: 03/16/2016] [Indexed: 12/18/2022] Open
Abstract
Proton pump inhibitors such as omeprazole (OME) reduce the severity of gastrointestinal (GI) ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs) but can also increase the chance of dysbiosis. The aim of this study was to test the hypothesis that preventive use of a soluble epoxide hydrolase inhibitor (sEHI) such as TPPU can decrease NSAID-induced ulcers by increasing anti-inflammatory epoxyeicosatrienoic acids (EETs). Dose- [10, 30, and 100 mg/kg, by mouth (PO)] and time-dependent (6 and 18 hours) ulcerative effects of diclofenac sodium (DCF, an NSAID) were studied in the small intestine of Swiss Webster mice. Dose-dependent effects of TPPU (0.001-0.1 mg/kg per day for 7 days, in drinking water) were evaluated in DCF-induced intestinal toxicity and compared with OME (20 mg/kg, PO). In addition, the effect of treatment was studied on levels of Hb in blood, EETs in plasma, inflammatory markers such as myeloperoxidase (MPO) in intestinal tissue homogenates, and tissue necrosis factor-α (TNF-α) in serum. DCF dose dependently induced ulcers that were associated with both a significant (P < 0.05) loss of Hb and an increase in the level of MPO and TNF-α, with severity of ulceration highest at 18 hours. Pretreatment with TPPU dose dependently prevented ulcer formation by DCF, increased the levels of epoxy fatty acids, including EETs, and TPPU's efficacy was comparable to OME. TPPU significantly (P < 0.05) reversed the effect of DCF on the level of Hb, MPO, and TNF-α Thus sEHI might be useful in the management of NSAID-induced ulcers.
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Affiliation(s)
- Sumanta Kumar Goswami
- Department of Entomology and Nematology, and Comprehensive Cancer Center (S.K.G., D.W., J.Y., C.A.T.S., C.M., S.D.K., B.I., B.D.H.), University of California-Davis, Davis, California; Department of Genetics and Biochemistry (C.A.T.S.), Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil; Department of Pathology (G.-Y.Y.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Debin Wan
- Department of Entomology and Nematology, and Comprehensive Cancer Center (S.K.G., D.W., J.Y., C.A.T.S., C.M., S.D.K., B.I., B.D.H.), University of California-Davis, Davis, California; Department of Genetics and Biochemistry (C.A.T.S.), Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil; Department of Pathology (G.-Y.Y.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Jun Yang
- Department of Entomology and Nematology, and Comprehensive Cancer Center (S.K.G., D.W., J.Y., C.A.T.S., C.M., S.D.K., B.I., B.D.H.), University of California-Davis, Davis, California; Department of Genetics and Biochemistry (C.A.T.S.), Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil; Department of Pathology (G.-Y.Y.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Carlos A Trindade da Silva
- Department of Entomology and Nematology, and Comprehensive Cancer Center (S.K.G., D.W., J.Y., C.A.T.S., C.M., S.D.K., B.I., B.D.H.), University of California-Davis, Davis, California; Department of Genetics and Biochemistry (C.A.T.S.), Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil; Department of Pathology (G.-Y.Y.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Christophe Morisseau
- Department of Entomology and Nematology, and Comprehensive Cancer Center (S.K.G., D.W., J.Y., C.A.T.S., C.M., S.D.K., B.I., B.D.H.), University of California-Davis, Davis, California; Department of Genetics and Biochemistry (C.A.T.S.), Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil; Department of Pathology (G.-Y.Y.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Sean D Kodani
- Department of Entomology and Nematology, and Comprehensive Cancer Center (S.K.G., D.W., J.Y., C.A.T.S., C.M., S.D.K., B.I., B.D.H.), University of California-Davis, Davis, California; Department of Genetics and Biochemistry (C.A.T.S.), Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil; Department of Pathology (G.-Y.Y.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Guang-Yu Yang
- Department of Entomology and Nematology, and Comprehensive Cancer Center (S.K.G., D.W., J.Y., C.A.T.S., C.M., S.D.K., B.I., B.D.H.), University of California-Davis, Davis, California; Department of Genetics and Biochemistry (C.A.T.S.), Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil; Department of Pathology (G.-Y.Y.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Bora Inceoglu
- Department of Entomology and Nematology, and Comprehensive Cancer Center (S.K.G., D.W., J.Y., C.A.T.S., C.M., S.D.K., B.I., B.D.H.), University of California-Davis, Davis, California; Department of Genetics and Biochemistry (C.A.T.S.), Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil; Department of Pathology (G.-Y.Y.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Bruce D Hammock
- Department of Entomology and Nematology, and Comprehensive Cancer Center (S.K.G., D.W., J.Y., C.A.T.S., C.M., S.D.K., B.I., B.D.H.), University of California-Davis, Davis, California; Department of Genetics and Biochemistry (C.A.T.S.), Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil; Department of Pathology (G.-Y.Y.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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Abrahamowicz M, Bjerre LM, Beauchamp ME, LeLorier J, Burne R. The missing cause approach to unmeasured confounding in pharmacoepidemiology. Stat Med 2016; 35:1001-16. [PMID: 26932124 DOI: 10.1002/sim.6818] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2014] [Revised: 10/15/2015] [Accepted: 11/02/2015] [Indexed: 11/10/2022]
Abstract
Unmeasured confounding is a major threat to the validity of pharmacoepidemiological studies of medication safety and effectiveness. We propose a new method for detecting and reducing the impact of unobserved confounding in large observational database studies. The method uses assumptions similar to the prescribing preference-based instrumental variable (IV) approach. Our method relies on the new 'missing cause' principle, according to which the impact of unmeasured confounding by (contra-)indication may be detected by assessing discrepancies between the following: (i) treatment actually received by individual patients and (ii) treatment that they would be expected to receive based on the observed data. Specifically, we use the treatment-by-discrepancy interaction to test for the presence of unmeasured confounding and correct the treatment effect estimate for the resulting bias. Under standard IV assumptions, we first proved that unmeasured confounding induces a spurious treatment-by-discrepancy interaction in risk difference models for binary outcomes and then simulated large pharmacoepidemiological studies with unmeasured confounding. In simulations, our estimates had four to six times smaller bias than conventional treatment effect estimates, adjusted only for measured confounders, and much smaller variance inflation than unbiased but very unstable IV estimates, resulting in uniformly lowest root mean square errors. The much lower variance of our estimates, relative to IV estimates, was also observed in an application comparing gastrointestinal safety of two classes of anti-inflammatory drugs. In conclusion, our missing cause-based method may complement other methods and enhance accuracy of analyses of large pharmacoepidemiological studies.
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Affiliation(s)
- Michal Abrahamowicz
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada.,Division of Clinical Epidemiology, McGill University Health Centre, Montreal, QC, Canada
| | - Lise M Bjerre
- Department of Family Medicine, University of Ottawa, Ottawa, ON, Canada.,School of Epidemiology, Public Health, and Preventive Medicine, University of Ottawa, Ottawa, ON, Canada.,Bruyère Research Institute, Ottawa, ON, Canada
| | - Marie-Eve Beauchamp
- Division of Clinical Epidemiology, McGill University Health Centre, Montreal, QC, Canada
| | - Jacques LeLorier
- Departments of Medicine and Pharmacology, University of Montreal, Montreal, QC, Canada.,Pharmacoepidemiology and Pharmacoeconomics, University of Montreal Hospital Research Center, Montreal, QC, Canada
| | - Rebecca Burne
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada
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Masoumi SJ, Mehrabani D, Moradi F, Zare N, Saberi-Firouzi M, Mazloom Z. The prevalence of dyspepsia symptoms and its correlation with the quality of life among Qashqai Turkish migrating nomads in Fars Province, Southern Iran. Pak J Med Sci 2015; 31:325-30. [PMID: 26101484 PMCID: PMC4476335 DOI: 10.12669/pjms.312.6956] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Accepted: 01/08/2015] [Indexed: 12/31/2022] Open
Abstract
Objectives: To determine the prevalence of dyspepsia and its correlation with quality of life in Fars Qashqai Turkish migrating nomads from Southern Iran. Methods: During 2010 we enrolled 397 Qashqai migrating nomads from Southern Iran who were 25 years of age or older. Participants completed a questionnaire that consisted of demographic factors, lifestyle data, gastrointestinal symptoms, and the Short-Form 36 Health Survey (SF-36) questionnaire. Results: There was a 48% prevalence of dyspepsia symptoms among participants. The prevalence was higher among females, those less than 35 years of age, married participants, and those with a low body mass index (BMI). The correlation between dyspepsia and quality of life was significant. Dyspeptic patients were classified into ulcer-like (27.9%), dysmotility-like (26.2%), and unspecified (45.9%) groups. A significant correlation existed between dyspepsia symptoms and consumption of dairy products, drinking water and tea before and after meals, smoking, dysphagia, reflux, heartburn, and use of non-steroid anti-inflammatory drugs and acetaminophen. Conclusion: The high prevalence of dyspepsia in Qashqai nomads necessitates educational health programs for the migrating tribes in order to decrease prevalence of this disease.
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Affiliation(s)
- Seyed Jalil Masoumi
- Seyed Jalil Masoumi, Nutrition and Food Sciences Research Center, School of Nutrition and Food Sciences, Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Davood Mehrabani
- Davood Mehrabani, Department of Pathology, Stem Cell and Transgenic Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fariba Moradi
- Fariba Moradi, Shiraz Geriatric Research Center, Office of Vice Chancellor for Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Najaf Zare
- Najaf Zare, Department of Biostatistics, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mehdi Saberi-Firouzi
- Mehdi Saberi-Firouzi, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Zohreh Mazloom
- Zohreh Mazloom, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
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Gaydukova IZ, Rebrov AP. [Efficiency and safety of different etoricoxib regimens in patients with axial spondyloarthritis, including ankylosing spondylitis]. TERAPEVT ARKH 2015; 87:77-82. [PMID: 26027245 DOI: 10.17116/terarkh201587377-82] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
AIM To study the clinical and laboratory efficiency and safety of different etoricoxib (ET) regimens in patients with axial spondyloarthritis (axSpA), including ankylosing spondylitis. SUBJECTS AND METHODS Forty patients with high axSpA activity (Bath Ankylosing Disease Activity Index (BASDAI 4) were examined and randomized to 2 groups: 1) 30 patients who received ET 90 mg continuously every day; 2) 10 patients who took the drug in the same dose intermittently 1-3 times weekly. The activity of axSpA (BASDAI, Ankylosing Spondylitis Disease Activity Score (ASDAS), erythrocyte sedimentation rate (ESR), and high-sensitivity C-reactive protein (hs-CRP)) was evaluated at baseline, 2 and 12 weeks; adverse events were recorded at baseline, 2, 6, and 12 weeks. The number of patients who had achieved an ASAS40 response at 2 and 12 weeks were taken into consideration. RESULTS At 12 weeks, the continuous administration group displayed decreases in BASDAI from 8 to 4, in ASDAS from 3.8 to 2.6, and in hs-CRP levels from 9.5 to 3.9 mg/l; the intermittent administration group exhibited decreases in BASDAI from 7.6 to 6.0, in ASDAS from 3.5 to 3.1, and hs-CRP from 8.8 to 4.5 mg/l (p<0.05). At this time, an AS40 response was achieved by 22 (73.3%) and 2 (20%) patients in Groups 1 and 2, respectively (p<0.05 for all). No serious adverse events were recorded. CONCLUSION The efficacy of ET given in a daily dose of 90 mg was much higher than that of the drug used thrice or less weekly in the patients with axSpA.
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Affiliation(s)
- I Z Gaydukova
- Department of Hospital Therapy, Faculty of Therapeutics, V.I. Razumovsky Saratov State Medical University, Ministry of Health of Russia, Saratov, Russia
| | - A P Rebrov
- Department of Hospital Therapy, Faculty of Therapeutics, V.I. Razumovsky Saratov State Medical University, Ministry of Health of Russia, Saratov, Russia
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THAKKAR ARVIND, CHENREDDY SUSHMA, WANG JEFFREY, PRABHU SUNIL. Evaluation of ibuprofen loaded solid lipid nanoparticles and its combination regimens for pancreatic cancer chemoprevention. Int J Oncol 2015; 46:1827-34. [DOI: 10.3892/ijo.2015.2879] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Accepted: 01/05/2015] [Indexed: 11/06/2022] Open
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Clinical guidelines «Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) in clinical practice». Part I. Zh Nevrol Psikhiatr Im S S Korsakova 2015; 115:70-82. [DOI: 10.17116/jnevro20151154170-82] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Nalamachu S, Pergolizzi JV, Raffa RB, Lakkireddy DR, Taylor R. Drug-drug interaction between NSAIDS and low-dose aspirin: a focus on cardiovascular and GI toxicity. Expert Opin Drug Saf 2014; 13:903-17. [PMID: 24905189 DOI: 10.1517/14740338.2014.924924] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
INTRODUCTION The aging of the population in the US and other countries means that a large number of people will likely take NSAIDs for the relief of pain and low-dose aspirin (LD-ASA) for cardioprotection. However, the cardioprotective value of LD-ASA can be compromised in patients who take NSAIDs concomitantly, because some NSAIDs competitively bind to critical amino-acid residues on cyclooxygenase (COX) enzymes and interfere with the mechanism of antiplatelet activity of LD-ASA. AREAS COVERED A review of the literature was conducted to provide an overview of current issues surrounding the concomitant use of NSAIDs and LD-ASA, to explore potential mechanisms for this drug-drug interaction and to consider current and future treatment options that may mitigate the risk associated with their concomitant use. EXPERT OPINION NSAIDs offer effective pain relief for the most common forms of pain, such as low back pain, musculoskeletal pain associated with arthritis, postsurgical pain, headache, acute pain syndromes, menstrual pain and dental pain. The development of NSAID formulations that offer effective pain control with fewer or less serious adverse effects due to interference with ASA would be a valuable medical advance. Several promising treatment options and regimens may be available in the future.
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van de Glind EMM, Rhodius-Meester HFM, Reitsma JB, Hooft L, van Munster BC. Reviews of individual patient data (IPD) are useful for geriatrics: an overview of available IPD reviews. J Am Geriatr Soc 2014; 62:1133-8. [PMID: 24802290 DOI: 10.1111/jgs.12830] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVES To determine how many individual patient data (IPD) reviews that included older people were available in MEDLINE and whether the effectiveness of treatments differed between older and younger individuals. DESIGN Overview of IPD reviews. SETTING A MEDLINE search was conducted for IPD reviews of randomized controlled trials published before July 2012. PARTICIPANTS IPD reviews that presented a regression model that included age as a factor or a subgroup analysis of individuals aged 70 and older or in which all participants were aged 70 and older. MEASUREMENTS Whether the IPD reviews reported similar conclusions for the younger and older populations was evaluated. RESULTS Twenty-six IPD reviews with a subgroup of older individuals and eight reviews with only older individuals were included (median N = 3,351). The most important reason for choosing an IPD review was the ability to perform a subgroup analysis in the older population. Fourteen IPD reviews suggested that older people should receive different treatments from younger people because of differences in effectiveness, six of which indicated that the investigated treatment(s) should be avoided in older adults. CONCLUSION IPD review is a valuable approach for generating evidence in older adults. Treatment effects frequently differed between older and younger individuals. Still, IPD results should be applied to older adults cautiously, because they are often excluded from primary trials. The collaborative sharing of raw data should be promoted to improve evidence-based decisions for this group.
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Affiliation(s)
- Esther M M van de Glind
- Section of Geriatrics, Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands; Dutch Cochrane Centre, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
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Du Y, Shi A, Han B, Li S, Wu D, Jia H, Zheng C, Ren L, Fan Z. COX-2 silencing enhances tamoxifen antitumor activity in breast cancer in vivo and in vitro. Int J Oncol 2014; 44:1385-93. [PMID: 24535190 DOI: 10.3892/ijo.2014.2299] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Accepted: 01/16/2014] [Indexed: 11/06/2022] Open
Abstract
Tamoxifen (Tam), a selective estrogen receptor modulator, is in wide clinical use for the treatment and prevention of breast cancer. However, extended TAM administration for breast cancer induces increased VEGF levels in patients, promoting new blood vessel formation and thereby limiting its efficacy and highlighting the need for improved therapeutic strategies. Cyclooxygenase-2 (COX-2) silencing via a replication-incompetent lentivirus (LV-COX-2) induce cancer apoptosis and suppresses VEGF gene expression. In this study, the effect of LV-COX-2 infection, either alone or in combination with TAM, was analyzed in a breast cell lines for suppressing VEGF expression and simultaneously reducing doses of TAM. Cell proliferation, apoptosis, angiogenesis, metastasis, cell cycle distribution, an receptor signaling were determined after LV-COX-2 combination with TAM treatment. In addition, tumor growth ability in nude mice was detected to define the combination treatment effect in tumorigenesis in vivo. It is found that LV-COX-2 combination with TAM treatment in breast cancer cell significantly suppressed the proliferation and metastasis, and induced tumor apoptosis in vitro, and tumor growth also was suppressed in vivo. In addition, we also found that LV-COX-2 combination with TAM treatment could inhibit angiogenesis and VEGF expression. Taken together, our experimental results indicate that LV-COX-2 combination with TAM has promising outcome in anti-metastatic and apoptotic studies. Furthermore, these results showed that LV-COX-2 combination with TAM is a potential drug candidate for treatment of breast tumors expressing high levels of VEGF.
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Affiliation(s)
- Ye Du
- Department of Breast Surgery, The First Hospital, Jilin University, Changchun 130021, Jilin, P.R. China
| | - Aiping Shi
- Department of Breast Surgery, The First Hospital, Jilin University, Changchun 130021, Jilin, P.R. China
| | - Bing Han
- Department of Breast Surgery, The First Hospital, Jilin University, Changchun 130021, Jilin, P.R. China
| | - Sijie Li
- Department of Breast Surgery, The First Hospital, Jilin University, Changchun 130021, Jilin, P.R. China
| | - Di Wu
- Department of Breast Surgery, The First Hospital, Jilin University, Changchun 130021, Jilin, P.R. China
| | - Hongyao Jia
- Department of Breast Surgery, The First Hospital, Jilin University, Changchun 130021, Jilin, P.R. China
| | - Chao Zheng
- Department of Breast Surgery, The First Hospital, Jilin University, Changchun 130021, Jilin, P.R. China
| | - Liqun Ren
- Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun 130021, Jilin, P.R. China
| | - Zhimin Fan
- Department of Breast Surgery, The First Hospital, Jilin University, Changchun 130021, Jilin, P.R. China
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Abstract
The discovery of ibuprofen's anti-inflammatory activity by Dr (now Professor) Stewart Adams and colleagues (Boots Pure Chemical Company Ltd, Nottingham, UK) 50 years ago represented a milestone in the development of anti-inflammatory analgesics. Subsequent clinical studies were the basis for ibuprofen being widely accepted for treating painful conditions at high anti-rheumatic doses (≤ 2400 mg/d), with lower doses (≤ 1200 mg/d for ≤ 10 days) for mild-moderate acute pain (e.g. dental pain, headache, dysmenorrhoea, respiratory symptoms and acute injury). The early observations have since been verified in studies comparing ibuprofen with newer cyclo-oxygenase-2 selective inhibitors ('coxibs'), paracetamol and other non-steroidal anti-inflammatory drugs (NSAIDs). The use of the low-dose, non-prescription, over-the-counter (OTC) drug was based on marketing approval in 1983 (UK) and 1984 (USA); and it is now available in over 80 countries. The relative safety of OTC ibuprofen has been supported by large-scale controlled studies. It has the same low gastro-intestinal (GI) effects as paracetamol (acetaminophen) and fewer GI effects than aspirin. Ibuprofen is a racemate. Its physicochemical properties and the short plasma-elimination half-life of the R(-) isomer, together with its limited ability to inhibit cyclo-oxygenase-1 (COX-1) and thus prostaglandin (PG) synthesis, compared with that of S(+)-ibuprofen, are responsible for the relatively low GI toxicity. The R(-) isomer is then converted in the body to the S(+) isomer after absorption in the GI tract. Ex vivo inhibition of COX-1 (thromboxane A(2)) and COX-2 (PGE(2)) at the plasma concentrations of S(+)-ibuprofen corresponding to those found in the plasma following ingestion of 400 mg ibuprofen in dental and other inflammatory pain models provides evidence of the anti-inflammatory mechanism at OTC dosages. R(-)-ibuprofen has effects on leucocytes, suggesting that ibuprofen has anti-leucocyte effects, which underlie its anti-inflammatory actions. Future developments include novel gastro-tolerant forms for 'at risk' patients, and uses in the prevention of neuro-inflammatory states and cancers.
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Affiliation(s)
- K D Rainsford
- Biomedical Research Centre, Sheffield Hallam University, Sheffield, UK.
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Sun YH, Dong YL, Wang YT, Zhao GL, Lu GJ, Yang J, Wu SX, Gu ZX, Wang W. Synergistic analgesia of duloxetine and celecoxib in the mouse formalin test: a combination analysis. PLoS One 2013; 8:e76603. [PMID: 24116126 PMCID: PMC3792058 DOI: 10.1371/journal.pone.0076603] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2013] [Accepted: 08/25/2013] [Indexed: 11/18/2022] Open
Abstract
Duloxetine, a serotonin and noradrenaline reuptake inhibitor, and celecoxib, a non-steroidal anti-inflammatory drug, are commonly used analgesics for persistent pain, however with moderate gastrointestinal side effects or analgesia tolerance. One promising analgesic strategy is to give a combined prescription, allowing the maximal or equal efficacy with fewer side effects. In the current study, the efficacy and side effects of combined administration of duloxetine and celecoxib were tested in the mouse formalin pain model. The subcutaneous (s.c.) injection of formalin into the left hindpaw induced significant somatic and emotional pain evaluated by the biphasic spontaneous flinching of the injected hindpaw and interphase ultrasonic vocalizations (USVs) during the 1 h after formalin injection, respectively. Pretreatment with intraperitoneal (i.p.) injection of duloxetine or celecoxib at 1 h before formalin injection induced the dose-dependent inhibition on the second but not first phase pain responses. Combined administration of duloxetine and celecoxib showed significant analgesia for the second phase pain responses. Combination analgesia on the first phase was observed only with higher dose combination. A statistical difference between the theoretical and experimental ED50 for the second phase pain responses was observed, which indicated synergistic interaction of the two drugs. Concerning the emotional pain responses revealed with USVs, we assumed that the antinociceptive effects were almost completely derived from duloxetine, since celecoxib was ineffective when administered alone or reduced the dosage of duloxetine when given in combination. Based on the above findings, acute concomitant administration of duloxetine and celecoxib showed synergism on the somatic pain behavior but not emotional pain behaviors.
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Affiliation(s)
- Yong-Hai Sun
- Anesthesia and Operation Center, Department of Anesthesiology, Chinese PLA General Hospital, Beijing, P. R. China
| | - Yu-Lin Dong
- Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, Xi’an, P. R. China
| | - Yu-Tong Wang
- Department of Emergency, Xi’jing Hospital, Fourth Military Medical University, Xi’an, P. R. China
| | - Guo-Li Zhao
- Anesthesia and Operation Center, Department of Anesthesiology, Chinese PLA General Hospital, Beijing, P. R. China
| | - Gui-Jun Lu
- Anesthesia and Operation Center, Department of Anesthesiology, Chinese PLA General Hospital, Beijing, P. R. China
| | - Jing Yang
- Anesthesia and Operation Center, Department of Anesthesiology, Chinese PLA General Hospital, Beijing, P. R. China
| | - Sheng-Xi Wu
- Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, Xi’an, P. R. China
| | - Ze-Xu Gu
- Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi’an, P. R. China
- * E-mail: (WW); (ZXG)
| | - Wen Wang
- Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, Xi’an, P. R. China
- * E-mail: (WW); (ZXG)
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Essex MN, O'Connell M, Bhadra Brown P. Response to nonsteroidal anti-inflammatory drugs in African Americans with osteoarthritis of the knee. J Int Med Res 2013; 40:2251-66. [PMID: 23321182 DOI: 10.1177/030006051204000623] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVE This 6-week, randomized, double-blind, parallel-group study compared the analgesic efficacy, tolerability and safety of celecoxib, naproxen and placebo in African Americans with osteoarthritis (OA) of the knee. METHODS A total of 322 patients aged ≥ 45 years with OA of the knee in a flare state received 200 mg celecoxib orally once daily, 500 mg naproxen orally twice daily or placebo for 6 weeks. The primary endpoint was change from baseline in the Patient's Assessment of Arthritis Pain. RESULTS Celecoxib was as effective as naproxen in reducing OA pain. Similar efficacy was observed in many of the secondary outcome measures. Celecoxib was well tolerated and demonstrated favorable upper gastro-intestinal tolerability. Improvements in outcome measures were numerically greater in the active treatment groups compared with the placebo group, but did not reach statistical significance. CONCLUSIONS Celecoxib was as effective as naproxen in relieving OA pain in African Americans and was well tolerated. Few significant differences were observed between active treatments and placebo, possibly because of a strong placebo effect.
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Affiliation(s)
- M N Essex
- US Medical Affairs, Pfizer Inc., New York, NY 10017, USA.
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Essex MN, Zhang RY, Berger MF, Upadhyay S, Park PW. Safety of celecoxib compared with placebo and non-selective NSAIDs: cumulative meta-analysis of 89 randomized controlled trials. Expert Opin Drug Saf 2013; 12:465-77. [DOI: 10.1517/14740338.2013.780595] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Datto C, Hellmund R, Siddiqui MK. Efficacy and tolerability of naproxen/esomeprazole magnesium tablets compared with non-specific NSAIDs and COX-2 inhibitors: a systematic review and network analyses. Open Access Rheumatol 2013; 5:1-19. [PMID: 27790020 PMCID: PMC5074787 DOI: 10.2147/oarrr.s41420] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs), such as non-selective NSAIDs (nsNSAIDs) or selective cyclooxygenase-2 (COX-2) inhibitors, are commonly prescribed for arthritic pain relief in patients with osteoarthritis (OA), rheumatoid arthritis (RA), or ankylosing spondylitis (AS). Treatment guidelines for chronic NSAID therapy include the consideration for gastroprotection for those at risk of gastric ulcers (GUs) associated with the chronic NSAID therapy. The United States Food and Drug Administration has approved naproxen/esomeprazole magnesium tablets for the relief of signs and symptoms of OA, RA, and AS, and to decrease the risk of developing GUs in patients at risk of developing NSAID-associated GUs. The European Medical Association has approved this therapy for the symptomatic treatment of OA, RA, and AS in patients who are at risk of developing NSAID-associated GUs and/or duodenal ulcers, for whom treatment with lower doses of naproxen or other NSAIDs is not considered sufficient. Naproxen/esomeprazole magnesium tablets have been compared with naproxen and celecoxib for these indications in head-to-head trials. This systematic literature review and network meta-analyses of data from randomized controlled trials was performed to compare naproxen/esomeprazole magnesium tablets with a number of additional relevant comparators. For this study, an original review examined MEDLINE®, Embase®, and the Cochrane Controlled Trials Register from database start to April 14, 2009. Using the same methodology, a review update was conducted to December 21, 2009. The systematic review and network analyses showed naproxen/esomeprazole magnesium tablets have an improved upper gastrointestinal tolerability profile (dyspepsia and gastric or gastroduodenal ulcers) over several active comparators (naproxen, ibuprofen, diclofenac, ketoprofen, etoricoxib, and fixed-dose diclofenac sodium plus misoprostol), and are equally effective as all active comparators in treating arthritic symptoms in patients with OA, RA, and AS. Naproxen/esomeprazole magnesium tablets are therefore a valuable option for treating arthritic symptoms in eligible patients with OA, RA, and AS.
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Essex MN, Bhadra P, Sands GH. Efficacy and tolerability of celecoxib versus naproxen in patients with osteoarthritis of the knee: a randomized, double-blind, double-dummy trial. J Int Med Res 2013; 40:1357-70. [PMID: 22971487 DOI: 10.1177/147323001204000414] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE To assess the efficacy and tolerability of celecoxib versus naproxen in patients with osteoarthritis (OA) of the knee. METHODS This 6-month, randomized, double-blind, double-dummy trial was conducted at 47 centres in the USA. Patients with OA of the knee were randomized to receive 200 mg celecoxib orally once daily or 500 mg naproxen orally twice daily. The primary endpoint was defined as a 20% improvement from baseline to 6 months in Western Ontario and McMaster Universities (WOMAC) OA total score. RESULTS A total of 586 out of 589 randomized patients received at least one dose of celecoxib (n=294) or naproxen (n=292). The primary endpoint (6-month response rate) was achieved by 52.7% and 49.7% of patients in the celecoxib and naproxen treatment groups, respectively. Significantly fewer discontinuations due to gastrointestinal adverse events occurred in patients receiving celecoxib than in those receiving naproxen (4.1% versus 15.1%, respectively). CONCLUSIONS Over the 6month study period, celecoxib provided similar improvements in OA symptoms to naproxen. In addition, celecoxib provided better upper gastrointestinal tolerability than naproxen.
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Affiliation(s)
- M N Essex
- Pfizer Inc., 235 East 42nd Street, New York, NY 10017, USA.
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Kellner HL, Li C, Essex MN. Efficacy and safety of celecoxib versus diclofenac and omeprazole in elderly arthritis patients: a subgroup analysis of the CONDOR trial. Curr Med Res Opin 2012; 28:1537-45. [PMID: 22852870 DOI: 10.1185/03007995.2012.717528] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE To compare the safety and efficacy of celecoxib versus diclofenac slow release (SR) plus omeprazole in elderly arthritis patients. RESEARCH DESIGN AND METHODS Patients aged≥65 years, with osteoarthritis and/or rheumatoid arthritis, at high gastrointestinal (GI) risk who participated in the CONDOR trial (Celecoxib vs. Omeprazole and Diclofenac in Patients With Osteoarthritis and Rheumatoid Arthritis) were included in this subanalysis. CONDOR was a 6-month prospective, double-blind, randomized, parallel-group, multicenter, international study comparing treatment with celecoxib 200 mg twice daily (BID) versus diclofenac SR 75 mg BID plus omeprazole 20 mg daily. MAIN OUTCOME MEASURES The primary end point was a composite of Clinically Significant Upper and Lower GI Events adjudicated by an independent blinded expert committee. Efficacy was determined by the Patient's Global Assessment of Arthritis. RESULTS A total of 2446 patients aged≥65 years were included in the intent-to-treat (ITT) population (n=1219 celecoxib; n=1227 diclofenac). Eight patients in the celecoxib group and 52 in the diclofenac group were adjudicated as having Clinically Significant Upper and Lower GI events (adjusted odds ratio: 6.27; p<0.0001). Clinically significant reductions in hemoglobin (≥2 g/dL) and/or hematocrit (≥10%) were observed in 23 patients in the celecoxib group and in 76 in the diclofenac group (relative risk: 3.22 [95% confidence interval: 2.04-5.07]; p<0.0001). Incidence of moderate-to-severe abdominal symptoms and discontinuation of treatment due to GI adverse events (AEs) were lower in the celecoxib group. The Patient's Global Assessment of Arthritis score least squares mean change from baseline to final visit and percentage of patients rating treatment efficacy as good/very good at baseline and final visit were similar in both groups. LIMITATIONS The dose of celecoxib used is consistent with the European label for the management of osteoarthritis and may not reflect what is commonly prescribed in current clinical practice in the United States. The data were obtained in a clinical trial setting where patients were enrolled based on specific inclusion and exclusion criteria; as such, the patients may not be broadly representative of the patient population in a general practice setting. CONCLUSIONS Efficacy was comparable in the two treatment groups. There were fewer endpoints as well as fewer GI AEs reported in patients treated with celecoxib compared with diclofenac. These data may help physicians in their treatment decisions for elderly patients with arthritis.
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Affiliation(s)
- Herbert L Kellner
- Division of Rheumatology, Center for Inflammatory Joint Diseases, Munich, Germany.
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Abstract
This retrospective, observational study was conducted to determine overlap of prevalence between atrial fibrillation (AF), an increasingly common condition that primarily affects the elderly population, and dyspepsia, which is also common. Because the overlap of these conditions could interfere with health care including medication selection, the effect on patient outcomes was also evaluated. A demographically representative population of adults in the United States self-administered an Internet-based questionnaire, and responses were evaluated to determine the presence of AF and measures of comorbidity, including CHADS2 score of stroke risk. Health-related quality of life, work productivity and activity impairment, and health care resource utilization were also assessed. The impact of dyspepsia on these patient outcomes was then examined with multiple regressions and generalized linear models. From the sample population, 1297 participants reported being diagnosed with AF, of whom 34% (449/1297) reported diagnosis of dyspepsia. Those with dyspepsia had a higher mean CHADS2 score than those without dyspepsia. Despite this higher risk, significantly fewer AF patients with dyspepsia than those without dyspepsia were taking either prescription medication to treat AF or anticoagulants for stroke prevention. Dyspepsia was associated with significantly lower levels of both mental and physical health-related quality of life. Work and activity impairment and health care resource utilization were also significantly higher among AF patients with dyspepsia than among those without. The burden of dyspepsia in AF patients should be considered during medication selection. Selection of agents associated with lower rates of dyspepsia may lead to greater patient acceptance of and adherence to therapy.
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Pavelka K. A comparison of the therapeutic efficacy of diclofenac in osteoarthritis: a systematic review of randomised controlled trials. Curr Med Res Opin 2012; 28:163-78. [PMID: 22168216 DOI: 10.1185/03007995.2011.649848] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVE Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) commonly prescribed for pain relief in osteoarthritis (OA). The relative efficacy of diclofenac compared to other pain relief medications used in OA (e.g., alternative NSAIDs, cyclooxygenase type 2 [COX-2] inhibitors) is uncertain. The objective of this systematic review is to compare the current evidence on efficacy of diclofenac versus other pain relief medications. RESEARCH DESIGN AND METHODS A systematic literature search was carried out for randomised, well controlled clinical trials comparing the efficacy of diclofenac with other pain relief medications in OA (reviews, meta-analyses and n = 1 trials were excluded). The databases searched were EMBASE, Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, and Ovid MEDLINE Daily Update. Articles were included from 1999 onwards. Retrieved articles were discussed by comparator medication. RESULTS Of the 263 articles identified in the literature search, 37 were eventually included in this review. These were comparisons with the selective COX-2 inhibitors etoricoxib, celecoxib, lumiracoxib and rofecoxib; comparisons with the NSAIDs aceclofenac, dexketoprofen, etodolac, lornoxicam, meloxicam, nabumetone and nimesulide; and comparisons to acetaminophen, tramadol, diacerein, oxaceprol, oral hydrolytic enzyme therapies, Chinese herbal remedies and castor oil supplementation. Overall, in the majority of the trials at therapeutic doses diclofenac provided similar efficacy to comparator treatments; and in general diclofenac was able to support its position as a reference medication of choice for OA trials. CONCLUSIONS The efficacy of diclofenac is largely unchallenged in that it remains as effective as newer pain relief medications employed in OA. A review of the available data demonstrates that diclofenac continues to provide physicians with a benchmark pharmacological treatment for OA.
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Affiliation(s)
- K Pavelka
- Institute of Rheumatology and Clinic of Rheumatology, Charles University, Prague, Czech Republic.
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The "MESACA" study: methylsulfonylmethane and boswellic acids in the treatment of gonarthrosis. Adv Ther 2011; 28:894-906. [PMID: 21986780 DOI: 10.1007/s12325-011-0068-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2011] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Osteoarthritis is a chronic rheumatoid disease mediated by metalloproteinases and inflammatory cytokines. Methylsulfonylmethane (MSM) and boswellic acids (BA) each show promise in the treatment of inflammatory processes, but the efficacy of combined treatment with these substances in the treatment of arthritis has not yet been studied. METHODS In this prospective randomized clinical trial, MESACA (for "methylsulfonylmethane and boswellic acids in the treatment of knee arthritis"), 60 subjects affected by arthritis of the knee were randomly assigned to an experimental group treated for 60 days with 5 g of MSM and 7.2 mg of BA daily, or a control group which was administered a placebo. At 2 and 6 months follow-up (FU), the efficacy of combined treatment with these two dietary supplements was assessed using the visual analog pain scale (VAS) and the Lequesne index (LI) for joint function, as well as monitoring the use of anti-inflammatory drugs (nonsteroidal anti-inflammatory drugs and anti-cyclooxygenase-2). RESULTS Pain, assessed with the VAS scale, was worse in the group treated with MSM and BA as compared with the placebo group at 2 months FU (3.8 vs. 2.7; P=0.04), whereas no difference between the two groups was observed at 6 months FU (2.7 vs. 3.6; P=0.2). No statistically significant differences were found in the LI between the two groups at either FU (2 months: 4.8 vs. 4.2; P=0.51; 6 months: 4.4 vs. 4.5; P=0.91). By contrast, a statistically significant difference in patients need for anti-inflammatory drugs was seen in the experimental as compared to the placebo group, even by 2 months FU (0.2 vs. 0.6 tablets/day; P<0.0001), that persisted up to the end of the study (0.1 vs. 0.6 tablets/day; P<0.0001). CONCLUSIONS Although the combined administration of MSM and BA in the treatment of gonarthrosis was not shown to be more efficacious than placebo in the management of the clinical and functional picture, it significantly reduced patients need for anti-inflammatory drugs.
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