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Solitano V, Yuan Y, Singh S, Ma C, Nardone OM, Fiorino G, Acosta Felquer ML, Barra L, D'Agostino MA, Pope J, Peyrin-Biroulet L, Danese S, Jairath V. Efficacy and safety of Advanced Combination Treatment in immune-mediated inflammatory disease: A systematic review and meta-analysis of randomized controlled trials. J Autoimmun 2024; 149:103331. [PMID: 39509741 DOI: 10.1016/j.jaut.2024.103331] [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: 06/24/2024] [Revised: 09/30/2024] [Accepted: 10/27/2024] [Indexed: 11/15/2024]
Abstract
OBJECTIVES Advanced combination treatment (ACT), defined as a combination of at least 2 biologic agents, a biologic agent and an oral small molecule, 2 oral small molecules drug with different mechanisms of action is a proposed strategy to improve outcomes in patients with immune-mediated inflammatory disease (IMID). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing ACT with monotherapy in patients with select IMIDs. METHODS Through a systematic literature search, we identified 10 RCTs (n = 1154) comparing ACT with single agent therapy (monotherapy). The primary outcome was induction of clinical remission. Secondary outcomes were adverse events, serious adverse events, infections, and serious infections. We performed random-effects meta-analysis and used GRADE to appraise certainty of evidence. RESULTS Eight out of 10 trials investigated an anti-TNF-α drug (e.g., etanercept, infliximab, golimumab, certolizumab) combined with another biologic (e.g anti-IL-23, anti-integrin, anti-IL-1) or an oral small molecule. There was no significant difference in the likelihood of achieving clinical remission with ACT vs. monotherapy in patients with rheumatoid arthritis (n = 7 RCTs) (RR, 1.75 [95 % CI 0.60-5.13]; moderate heterogeneity (I2 = 33 %)] and systemic lupus erythematosus (n = 1) (RR, 1.20 [0.53-2.72]) (GRADE; low certainty evidence). Patients with rheumatoid arthritis in the ACT arm were more likely to experience adverse events (RR, 1.07 [1.01-1.12]) compared to monotherapy. ACT led to higher rates of induction of clinical remission in patients with IBD (n = 2 RCTs) (RR, 1.68 [1.15-2.46]) with minimal heterogeneity (I2 = 15 %) (GRADE; low certainty evidence), and no differences in the likelihood of adverse events (RR 0.92 [0.80-1.05]). There were no differences in the risk of infections or serious infections in patients treated with ACT or monotherapy with rheumatological disease or IBD. CONCLUSIONS ACT did not offer clinical benefit in patients with rheumatological IMIDs and resulted in higher rate adverse events in rheumatoid arthritis. ACT may offer clinical benefit without a clear safety signal in patients with IBD, but further trials are warranted. The variability in ACT regimens across studies limits the generalizability of these findings.
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Affiliation(s)
- Virginia Solitano
- Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada; Gastroenterology and Endoscopy, IRCCS Hospital San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Yuhong Yuan
- Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada; Lawson Health Research Institute, London Health Science Center, London, Ontario, Canada
| | - Siddharth Singh
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA
| | - Christopher Ma
- Division of Gastroenterology & Hepatology, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Olga Maria Nardone
- Gastroenterology, Department of Public Health, University Federico II of Naples, Naples, Italy
| | - Gionata Fiorino
- Gastroenterology and Endoscopy, IRCCS Hospital San Raffaele and University Vita-Salute San Raffaele, Milan, Italy; IBD Unit, Department of Gastroenterology & Digestive Endoscopy, San Camillo-Forlanini Hospital, 00152, Rome, Italy
| | - Maria Laura Acosta Felquer
- Rheumatology Unit, Internal Medical Services, Hospital Italiano de Buenos Aires, Argentina and Instituto Universitario, Peron 4190 (C1199ABB), CABA, Argentina
| | - Lillian Barra
- Schulich School of Medicine, University of Western Ontario, London, Ontario, Canada; Department of Medicine, Division of Rheumatology, Western University, London, ON, Canada
| | - Maria-Antonietta D'Agostino
- Department of Rheumatology, Fondazione Policlinico Universitario A. Gemelli, IRCSS, Catholic University of Sacred Heart, Rome, Italy
| | - Janet Pope
- Department of Medicine, Division of Rheumatology, Western University, London, ON, Canada
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, F-54500, Vandœuvre-lès-Nancy, France; INFINY Institute, Nancy University Hospital, F-54500, Vandœuvre-lès-Nancy, France; Groupe Hospitalier Privé Ambroise Paré - Hartmann Paris IBD Center, 92200, Neuilly sur Seine, France
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Hospital San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Vipul Jairath
- Department of Medicine, Division of Gastroenterology, Western University, London, Ontario, Canada; Department of Epidemiology & Biostatistics, Western University, London, Ontario, Canada.
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Abstract
The disease course of autoimmune diseases such as rheumatoid arthritis is altered during pregnancy, and a similar modulatory role of pregnancy on inflammatory bowel disease (IBD) has been proposed. Hormonal, immunological, and microbial changes occurring during normal pregnancy may interact with the pathophysiology of IBD. IBD consists of Crohn's disease and ulcerative colitis, and because of genetic, immunological, and microbial differences between these disease entities, they may react differently during pregnancy and should be described separately. This review will address the pregnancy-induced physiological changes and their potential effect on the disease course of ulcerative colitis and Crohn's disease, with emphasis on the modulation of epithelial barrier function and immune profiles by pregnancy hormones, microbial changes, and microchimerism.
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Warren LR, Clarke JM, Arora S, Barahona M, Arebi N, Darzi A. Transitions of care across hospital settings in patients with inflammatory bowel disease. World J Gastroenterol 2019; 25:2122-2132. [PMID: 31114138 PMCID: PMC6506584 DOI: 10.3748/wjg.v25.i17.2122] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 02/05/2019] [Accepted: 02/23/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic, inflammatory disorder characterised by both intestinal and extra-intestinal pathology. Patients may receive both emergency and elective care from several providers, often in different hospital settings. Poorly managed transitions of care between providers can lead to inefficiencies in care and patient safety issues. To ensure that the sharing of patient information between providers is appropriate, timely, accurate and secure, effective data-sharing infrastructure needs to be developed. To optimise inter-hospital data-sharing for IBD patients, we need to better understand patterns of hospital encounters in this group.
AIM To determine the type and location of hospital services accessed by IBD patients in England.
METHODS This was a retrospective observational study using Hospital Episode Statistics, a large administrative patient data set from the National Health Service in England. Adult patients with a diagnosis of IBD following admission to hospital were followed over a 2-year period to determine the proportion of care accessed at the same hospital providing their outpatient IBD care, defined as their ‘home provider’. Secondary outcome measures included the geographic distribution of patient-sharing, regional and age-related differences in accessing services, and type and frequency of outpatient encounters.
RESULTS 95055 patients accessed hospital services on 1760156 occasions over a 2-year follow-up period. The proportion of these encounters with their identified IBD ‘home provider’ was 73.3%, 87.8% and 83.1% for accident and emergency, inpatient and outpatient encounters respectively. Patients living in metropolitan centres and younger patients were less likely to attend their ‘home provider’ for hospital services. The most commonly attended specialty services were gastroenterology, general surgery and ophthalmology.
CONCLUSION Transitions of care between secondary care settings are common for patients with IBD. Effective systems of data-sharing and care integration are essential to providing safe and effective care for patients. Geographic and age-related patterns of care transitions identified in this study may be used to guide interventions aimed at improving continuity of care.
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Affiliation(s)
- Leigh R Warren
- Patient Safety Translational Research Centre, Imperial College London, London W2 1NY, United Kingdom
- Department of Surgery and Cancer, Imperial College London, London W2 1NY, United Kingdom
| | - Jonathan M Clarke
- Centre for Health Policy, Imperial College London Centre for Mathematics of Precision Healthcare, Imperial College London, London SW7 2BX, United Kingdom
- Department of Biostatistics, Harvard University, Boston, MA 02115, United States
- Department of Surgery and Cancer, Imperial College London, London W2 1NY, United Kingdom
| | - Sonal Arora
- Patient Safety Translational Research Centre, Imperial College London, London W2 1NY, United Kingdom
- Department of Surgery and Cancer, Imperial College London, London W2 1NY, United Kingdom
| | - Mauricio Barahona
- Centre for Health Policy, Imperial College London Centre for Mathematics of Precision Healthcare, Imperial College London, London SW7 2BX, United Kingdom
- Department of Mathematics, Imperial College London, London SW7 2BX, United Kingdom
| | - Naila Arebi
- Department of Gastroenterology, St. Marks Academic Institute, Harrow HA1 3UJ, United Kingdom
| | - Ara Darzi
- Patient Safety Translational Research Centre, Imperial College London, London W2 1NY, United Kingdom
- Department of Surgery and Cancer, Imperial College London, London W2 1NY, United Kingdom
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Extraintestinal manifestations of Crohn's disease. GASTROENTEROLOGY REVIEW 2016; 11:218-221. [PMID: 27713787 PMCID: PMC5047972 DOI: 10.5114/pg.2016.61439] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Accepted: 09/21/2015] [Indexed: 12/11/2022]
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Váradi C, Holló Z, Póliska S, Nagy L, Szekanecz Z, Váncsa A, Palatka K, Guttman A. Combination of IgG N-glycomics and corresponding transcriptomics data to identify anti-TNF-α treatment responders in inflammatory diseases. Electrophoresis 2015; 36:1330-5. [PMID: 25639738 DOI: 10.1002/elps.201400575] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2014] [Revised: 01/06/2015] [Accepted: 01/06/2015] [Indexed: 12/14/2022]
Abstract
Prediction of responsiveness in biological therapies is an important and challenging issue in different diseases. Analyzing glycosylation pattern changes of key serum glycoproteins is one of the possible avenues to follow disease remission. The aim of this study was to investigate the changes of serum IgG glycoforms in Crohn's disease (CD) and rheumatoid arthritis patients in response to antitumor necrosis factor alpha (anti-TNF-α) treatment. IgG was isolated from patient serum samples using Protein A affinity pull-down, followed by the release of N-glycans with peptide-N-glycosidase F. The released glycans were fluorescently tagged with 8-aminopyrene-1,3,6-trisulfonate and analyzed by CGE with laser-induced fluorescent detection. Significant alterations were detected between responders and nonresponders in both disease groups. In CD patients, disease-specific alteration was found in response to anti-TNF-α therapy, which was also confirmed by transcriptomics data analysis of the corresponding glycosyltransferases and glycosidases.
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Affiliation(s)
- Csaba Váradi
- Horváth Laboratory of Bioseparation Sciences, School of Medicine, MMKK, University of Debrecen, Debrecen, Hungary
| | | | - Szilárd Póliska
- Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary
| | - László Nagy
- Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary
| | - Zoltán Szekanecz
- Department of Rheumatology, School of Medicine, University of Debrecen, Debrecen, Hungary
| | - Andrea Váncsa
- Department of Rheumatology, School of Medicine, University of Debrecen, Debrecen, Hungary
| | - Károly Palatka
- Department of Internal Medicine, University of Debrecen, Debrecen, Hungary
| | - András Guttman
- Horváth Laboratory of Bioseparation Sciences, School of Medicine, MMKK, University of Debrecen, Debrecen, Hungary.,MTA-PE Translational Glycomics Research Group, MUKKI, University of Pannonia, Veszprém, Hungary
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Curtis JR, Chen SY, Werther W, John A, Johnson DA. Validation of ICD-9-CM codes to identify gastrointestinal perforation events in administrative claims data among hospitalized rheumatoid arthritis patients. Pharmacoepidemiol Drug Saf 2011; 20:1150-8. [PMID: 22020901 DOI: 10.1002/pds.2215] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2010] [Revised: 06/02/2011] [Accepted: 06/22/2011] [Indexed: 11/12/2022]
Abstract
PURPOSE To validate, using physician review of abstracted medical chart data as a gold standard, a claims-based algorithm developed to identify gastrointestinal (GI) perforation cases among rheumatoid arthritis (RA) patients. METHODS Patients with established RA, aged 18 years or older with hospital admissions between January 2004 and September 2009, were selected from a large US-hospital-based database. An algorithm with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes for GI perforation and combinations of GI-related diagnosis codes and Current Procedural Terminology (CPT-4) procedure codes for relevant GI surgeries was used to identify potential GI perforation cases. Two senior experienced specialist physicians independently reviewed abstracted chart data and classified cases as confirmed or unconfirmed GI perforations. Positive predictive values (PPVs) to identify confirmed GI perforation were calculated and stratified by upper versus lower GI tract. RESULTS Overall, 86 of 92 GI perforation cases were confirmed, yielding an overall PPV of 94% (95%confidence interval [CI] = 86%-98%). PPV was 100% (95%CI = 100%-100%) for upper GI perforation (esophagus, stomach) and 91% (95%CI = 90%-97%) for lower GI perforation (small intestine, PPV = 100%; large intestine, PPV = 94%; unspecified lower GI, PPV = 89%). CONCLUSIONS This algorithm, consisting of a combination of ICD-9-CM diagnosis and CPT-4 codes, could be used in future safety studies to evaluate GI perforation risk factors in RA patients.
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Affiliation(s)
- Jeffrey R Curtis
- Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, FOT 805D, 510 20th Street South, Birmingham, AL 35294, USA.
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D'Incà R, Podswiadek M, Ferronato A, Punzi L, Salvagnini M, Sturniolo GC. Articular manifestations in inflammatory bowel disease patients: a prospective study. Dig Liver Dis 2009; 41:565-9. [PMID: 19278908 DOI: 10.1016/j.dld.2009.01.013] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2008] [Revised: 12/17/2008] [Accepted: 01/27/2009] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Rheumatic manifestations are frequent in inflammatory bowel disease (IBD) and are associated with a wide range of clinical patterns. METHODS Articular symptoms and signs were investigated by questionnaire in a cohort of 651 pts, mean age 42+/-14 years, followed at two referral hospitals over a 12-month period. RESULTS 142 ulcerative colitis (UC) and 120 Crohn's disease (CD) patients referred articular pain during their IBD history: in 46% this was associated with active IBD, in 56% symptoms were intermittent and in 19% symptoms preceded IBD diagnosis. 62 pts (28 UC, 34 CD) complaining of articular symptoms at the time of the interview, were investigated by the rheumatologist: arthropathy was axial in 52%, oligoarticular in 16% and polyarticular in 23%. Oligoarthritis commonly involved the lower limbs and was more commonly associated with UC. The mean number of small joints involved was significantly higher in CD than in UC pts (9.9+/-8.2 vs. 5.6+/-4.3; p<0.01). Bone scintigraphy was abnormal in 70% of pts. CONCLUSIONS Prevalence of self-reported articular symptoms in IBD patients exceeds 40% with 9.5% incidence during 1-year follow up. Symptoms predict entheropatic involvement of the locomotor system.
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Affiliation(s)
- R D'Incà
- Department of Surgical and Gastroenterological Sciences, University of Padua, Italy.
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Bianchi Porro G, Cassinotti A, Ferrara E, Maconi G, Ardizzone S. Review article: the management of steroid dependency in ulcerative colitis. Aliment Pharmacol Ther 2007; 26:779-94. [PMID: 17767462 DOI: 10.1111/j.1365-2036.2007.03334.x] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Approximately 20% of patients with ulcerative colitis have a chronic active disease often requiring several courses of systemic steroids in order to achieve remission, but followed by relapse of symptoms during steroid tapering or soon after their discontinuation. Although short term control of symptoms can be achieved with steroid treatment, this pattern of drug response, known as steroid-dependency, leads to important complications of the treatment, while a significant proportion of patients requires colectomy. AIM To review the studies currently available specifically evaluating the management of steroid-dependent ulcerative colitis. RESULTS The clinical and biological mechanisms of steroid-dependency are not well understood compared with those determining steroid-refractoriness. Very few evidence-based data are available concerning the management of patients with steroid-dependent ulcerative colitis. The therapeutic role of aminosalicylates, thiopurines, methotrexate, infliximab, leukocyte apheresis and other drugs in the treatment of steroid-dependent ulcerative colitis are evaluated. CONCLUSIONS Outcomes of studies in steroid-refractory patients may not be applicable to steroid-dependency. Trials are needed to define the correct approaches and new strategies to ameliorate the therapy of steroid-dependent ulcerative colitis.
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Affiliation(s)
- G Bianchi Porro
- Department of Clinical Science, Chair of Gastroenterology, L Sacco University Hospital, Milan, Italy.
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Cholongitas E, Papatheodoridis GV, Zappoli P, Giannakopoulos A, Patch D, Marelli L, Shusang V, Kalambokis G, Shirling G, Rolando N, Burroughs AK. Combined HLA-DR and -DQ disparity is associated with a stable course of ulcerative colitis after liver transplantation for primary sclerosing cholangitis. Liver Transpl 2007; 13:552-7. [PMID: 17394153 DOI: 10.1002/lt.21077] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Combined disparity of human leukocyte antigen (HLA)-DR and -DQ between mother and fetus is associated with less severe ulcerative colitis (UC) during pregnancy. We evaluated whether donor-recipient HLA disparity after liver transplantation (LT) affects UC in patients with primary sclerosing cholangitis (PSC). Sixty-nine consecutive patients with PSC underwent LT; all underwent colonoscopy before LT; 48 had UC before and 3 had de novo UC after LT. Clinical and laboratory data, activity and treatment of UC, post-LT cytomegalovirus infection, and disparity of HLA-A, -B, -DR, and -DQ for each donor-recipient pair were evaluated. Pre-LT quiescent UC was present in 26 patients. Post-LT UC activity was evaluated in 36 of 51 patients with UC who had not undergone pre-LT colectomy and who had >12 months' post-LT survival. Of these, 16 were stable, 17 had worsened, and 3 had de novo UC. Seven required colectomy (4 for dysplasia or cancer) after LT. Post-LT cytomegalovirus viremia was neither associated with worse UC activity (P = 0.58) nor de novo UC. Disparity with respect to HLA-A, -B, -DR, and -DQ was found in 58%, 27%, 44%, and 39% donor-recipient pairs, respectively. Post-LT UC course was similar with respect to single HLA disparity. However, disparity in none or only one HLA-DR or -DQ was significantly associated with worse activity compared with patients with disparity at both (65% vs. 0%, P = 0.009). Logistic regression found that the disparity for both -DR and -DQ was the only factor statistically significantly associated with post-LT UC activity. We conclude that disparity in both HLA-DR and -DQ between donor and recipient is associated with stable UC activity after LT.
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Affiliation(s)
- Evangelos Cholongitas
- Liver Transplantation and Hepatobiliary Unit, Royal Free Hospital, Hampstead, London, UK
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