• efficacy
• methotrexate
• model‐based meta‐analysis
• rheumatoid arthritis

• JAK inhibitors
• TB infection
• ankylosing spondylitis
• biologic DMARDs
• preventive therapy
• psoriatic arthritis
• rheumatoid arthritis
• tuberculosis disease

• Humans
• Tuberculosis/prevention & control
• Tuberculosis/diagnosis
• Tuberculosis/epidemiology
• Tuberculosis/etiology
• Tuberculosis/immunology
• Immunosuppressive Agents/therapeutic use
• Immunosuppressive Agents/adverse effects
• Autoimmune Diseases/drug therapy
• Autoimmune Diseases/immunology
• Mycobacterium tuberculosis
• Arthritis, Rheumatoid/drug therapy
• Arthritis, Rheumatoid/immunology
• Antirheumatic Agents/therapeutic use
• Antirheumatic Agents/adverse effects
• Arthritis, Psoriatic/drug therapy
• Chronic Disease
• Spondylitis, Ankylosing/drug therapy
• Risk Factors

• Ministero della Salute

• Cognition
• Depression
• Inflammation
• Infliximab
• Neuropsychiatric disorders

• Humans
• Infliximab/therapeutic use
• Infliximab/pharmacology
• Animals
• Mental Disorders/drug therapy
• Tumor Necrosis Factor-alpha/antagonists & inhibitors

• Drug Discovery
• Monkey Pox infection
• Protein Network
• Repurposing

• Drug Repositioning
• Humans
• Antiviral Agents/pharmacology
• Antiviral Agents/chemistry
• Monkeypox virus/drug effects
• Monkeypox virus/genetics
• Genomics
• Phylogeny
• Mpox (monkeypox)

• PSAU/2024/R/1445 Prince Sattam bin Abdulaziz University

• antibodies
• antirheumatic agents
• arthritis, rheumatoid
• methotrexate
• tumor necrosis factor inhibitors

• Adult
• Aged
• Female
• Humans
• Male
• Middle Aged
• Antibodies, Monoclonal, Humanized/therapeutic use
• Antibodies, Monoclonal, Humanized/adverse effects
• Antibodies, Monoclonal, Humanized/administration & dosage
• Antirheumatic Agents/therapeutic use
• Antirheumatic Agents/adverse effects
• Antirheumatic Agents/administration & dosage
• Arthritis, Rheumatoid/drug therapy
• Drug Therapy, Combination
• Methotrexate/therapeutic use
• Methotrexate/administration & dosage
• Methotrexate/adverse effects
• Treatment Outcome
• Tumor Necrosis Factor-alpha/antagonists & inhibitors

• Taisho Pharmaceutical Co., Ltd.

• Rheumatoid arthritis
• biological treatment
• dosage reduction
• tumor necrosis factor-alpha inhibitors
• withdrawal

• Humans
• Arthritis, Rheumatoid/drug therapy
• Arthritis, Rheumatoid/immunology
• Antirheumatic Agents/therapeutic use
• Antirheumatic Agents/adverse effects
• Antirheumatic Agents/administration & dosage
• Tumor Necrosis Factor-alpha/antagonists & inhibitors
• Tumor Necrosis Factor-alpha/immunology
• Quality of Life

• RA
• administrative health data
• interrupted time-series
• severe infection

• Humans
• Retrospective Studies
• Arthritis, Rheumatoid/drug therapy
• Arthritis, Rheumatoid/epidemiology
• Arthritis, Rheumatoid/diagnosis
• Antirheumatic Agents/therapeutic use
• Biological Products/therapeutic use
• British Columbia/epidemiology

• Canadian Institute of Health Research
• THC-135235 CIHR
• RGPIN-2018-04313 Natural Sciences and Engineering Research Council

• Biosimilar
• Meta-analysis
• Rheumatoid arthritis
• TNFI

• Humans
• Methotrexate/therapeutic use
• Biosimilar Pharmaceuticals/therapeutic use
• Infliximab/adverse effects
• Adalimumab/adverse effects
• Etanercept/therapeutic use
• Tumor Necrosis Factor Inhibitors/therapeutic use
• Arthritis, Rheumatoid/drug therapy
• Antirheumatic Agents/therapeutic use
• Treatment Outcome
• Tumor Necrosis Factor-alpha
• Randomized Controlled Trials as Topic

• Biosimilar
• Infliximab
• Network meta-analysis
• Rheumatoid arthritis

• Humans
• Antirheumatic Agents/adverse effects
• Arthritis, Rheumatoid/diagnosis
• Arthritis, Rheumatoid/drug therapy
• Biosimilar Pharmaceuticals/adverse effects
• Drug Therapy, Combination
• Infliximab/adverse effects
• Methotrexate
• Treatment Outcome

• AIA rats
• chronic disease
• inflammtion
• molecular docking

• dmards
• mortality
• rheumatoid arthritis

• Antirheumatic Agents/adverse effects
• Arthritis, Rheumatoid/complications
• Biological Products/adverse effects
• Databases, Factual
• Humans

• certolizumab pegol
• effectiveness
• post-marketing surveillance
• rheumatoid arthritis
• safety

To evaluate the safety of each anti-TNF therapy for patients with rheumatoid arthritis (RA) and then make the best choice in clinical practice.

We searched PUBMED, EMBASE, and the Cochrane Library. The deadline for retrieval is August 2021. The ORs, Confidence Intervals (CIs), and p values were calculated by STATA.16.0 software for assessment.

72 RCTs involving 28332 subjects were included. AEs were more common with adalimumab combined disease-modifying anti-rheumatic drugs (DMARDs) compared with placebo (OR = 1.60, 95% CI: 1.06, 2.42), DMARDs (1.28, 95% CI: 1.08, 1.52), etanercept combined DMARDs (1.32, 95% CI: 1.03, 1.67); certolizumab combined DMARDs compared with placebo (1.63, 95% CI: 1.07, 2.46), DMARDs (1.30, 95% CI: 1.10, 1.54), etanercept combined DMARDs (1.34, 95% CI: 1.05, 1.70). In SAEs, comparisons between treatments showed adalimumab (0.20, 95% CI: 0.07, 0.59), etanercept combined DMARDs (0.39, 95% CI: 0.15, 0.96), golimumab (0.19, 95% CI: 0.05, 0.77), infliximab (0.15, 95% CI: 0.03,0.71) decreased the risk of SAEs compared with golimumab combined DMARDs. In infections, comparisons between treatments showed adalimumab combined DMARDs (0.59, 95% CI: 0.37, 0.95), etanercept (0.49, 95% CI: 0.28, 0.88), etanercept combined DMARDs (0.56, 95% CI: 0.35, 0.91), golimumab combined DMARDs (0.51, 95% CI: 0.31, 0.83) decreased the risk of infections compared with infliximab combined DMARDs. No evidence indicated that the use of TNF-α inhibitors influenced the risk of serious infections, malignant tumors.

In conclusion, we regard etanercept monotherapy as the optimal choice for RA patients in clinical practice when the efficacy is similar. Conversely, certolizumab + DMARDs therapy is not recommended.

identifier PROSPERO CRD42021276176.

• TNF-α inhibitors
• adverse effects
• network meta-analysis
• rheumatoid arthritis
• serious adverse events

Despite improved care for rheumatoid arthritis (RA) patients, many still experience treatment failure with biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs [tsDMARDs; typically Janus kinase inhibitors (JAKi)], and eventually switch to other agents. We compared the efficacy of a second tumor necrosis factor inhibitor (TNFi) and non-TNF-targeted treatment as the second-line treatment in patients showing an insufficient response to the first TNFi.

Patients were included if they had received at least one prescription for a TNFi, and at least one follow-up prescription for a second TNFi or non-TNF-targeted treatment after discontinuation of the first drug. In total, 209 patients were analyzed, including 69 with a second TNFi and 140 with a non-TNF-targeted treatment (106 non-TNFi biologics and 34 JAKi). Cox regression was used to estimate the hazard ratio (HR) for discontinuation.

The mean follow-up period after switching was 28.0 (range: 0–80) months and 24.4% of the 209 patients switched or discontinued the second drug. In multivariate Cox proportional hazard analysis, the non-TNF-targeted treatment group had a lower likelihood of discontinuing their treatment than the second TNFi group [HR = 0.326, 95% confidence interval (CI): 0.170–0.626, p = 0.001]. When analyzed separately, the risk of discontinuation was significantly lower in both the non-TNFi biologic (HR = 0.318, 95% CI: 0.160–0.633, p = 0.001) and JAKi (HR = 0.356, 95% CI: 0.129–0.980, p = 0.046) groups than in the second TNFi group.

Our study supported switching to a non-TNF-targeted treatment instead of TNF cycling in patients with RA showing an inadequate response to initial TNFi.

Background: Adalimumab, golimumab, infliximab, certolizumab, and etanercept are five anti-tumor necrosis factor (anti-TNF) medicines that have been approved for use in rheumatology. Apart from their well-established therapeutic usefulness, -it is unclear to what extent -they are linked to an increased risk of various side effects. The present meta-analysis was carried out to assess the risk of infection and other side effects after anti-TNF- α for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

Methods: We searched PubMed, Cinahl (via Ebsco), Scopus, and Web of Sciences databases for trials comparing anti-TNF medications to placebo or no therapy in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis from August 2006 to August 2020. A total of 23 articles were used for meta-analysis. The Cochrane Collaboration’s risk of bias tool was used to assess the methodological quality of the included studies. In addition, a random-effects model was used to calculate the pooled odds ratio, and Forest plots were constructed to determine the risk of infections and cancer following the use of anti-TNF treatment.

Results: Treatment with anti-TNFα agents resulted in an increase in the risk of serious infections (OR: 1.72, 95% CI: 1.56–1.90, p < 0.00001) and an increase in cancer risk (OR: 1.36, 95% CI: 1.20–1.53, p < 0.00001) whereas the risk of developing tuberculosis was not significantly different with anti-TNFα agents versus those without treatment with anti-TNFα agents (OR: 2.55, 95% CI: 0.40–16.23, p = 0.32) although the number of studies is limited to make a definitive conclusion. The risk of bias of the included studies was unclear to high across most domains, and there was evidence of publication bias for most outcomes.

Conclusion: The present meta-analysis suggests an increased risk of infectious adverse events, including overall adverse events and cancer following anti-TNFα treatment, whereas the risk of tuberculosis was not significantly different. Although anti-TNF agents have shown promise to treat inflammatory conditions, their use should be balanced by the risk-benefit ratio as suggested by the meta-analysis.

• ankylosing spondylitis
• anti TNF therapy
• malignancy
• psoriatic arthritis (artritis psoriatica)
• rheumatoid arthritis
• risk of infections

Coronavirus disease 2019 (COVID-19) has caused significant devastation globally. Despite the development of several vaccines, with uncertainty around global uptake and vaccine efficacy, the need for effective therapeutic agents remains. Increased levels of cytokines including tumour necrosis factor are significant in the pathogenesis of COVID-19 and associated with poor outcomes including ventilator requirement and mortality. Repurposing tumour necrosis factor blocker therapy used in conditions such as rheumatoid arthritis and inflammatory bowel disease seems promising, with early feasibility data showing a reduction in circulation of pro-inflammatory cytokines and encouraging the evaluation of such interventions in preventing disease progression and clinical deterioration in patients with COVID-19. Here, we examine the biological activities of tumour necrosis factor inhibitors indicative of their potential in COVID-19 and briefly outline the randomised control trials assessing their benefit-risk profile in COVID-19 therapy.

• COVID-19
• Clinical trials
• Cytokines
• International standards
• SARS-COV-2
• Therapy
• Tumour necrosis factor (TNF)

• Axis
• Biologic agents
• Cervical spine
• Computer-assisted navigation system
• Pedicle screw
• Rheumatoid arthritis
• Vertebral artery injury

Our objective was to evaluate the long-term efficacy, safety, and immunogenicity of the infliximab biosimilar, PF-06438179/GP1111 (PF-SZ-IFX), in patients with rheumatoid arthritis (RA) who continued biosimilar treatment throughout 78 weeks or who switched from reference infliximab (Remicade^®) sourced from the EU (IFX-EU) at week 30 or week 54 in the REFLECTIONS B537-02 study.

In this phase III, double-blind, active-controlled study, patients with moderate-to-severe active RA were initially randomized to PF-SZ-IFX or IFX-EU, each with methotrexate (treatment period [TP] 1; N = 650). At week 30, patients receiving PF-SZ-IFX continued PF-SZ-IFX; patients receiving IFX-EU were re-randomized to continue IFX-EU or switch to PF-SZ-IFX (TP2; n = 566). From weeks 54 to 78, all patients received open-label treatment with PF-SZ-IFX (TP3; n = 505). Efficacy, safety, and immunogenicity data were analyzed during TP3.

Efficacy was sustained and comparable across groups at week 78, with American College of Rheumatology criteria for ≥ 20% clinical improvement response rates of 75.9% (biosimilar group), 77.8% (week 30 switch group), and 68.3% (week 54 switch group). The incidence of treatment-emergent adverse events was 28.9%, 29.4%, and 30.2%, respectively. The proportion of patients who were antidrug antibody (ADA) positive and neutralizing antibody positive (as a percentage of ADA-positive patients) was stable and comparable between groups.

Results to week 78 continue to support the efficacy, safety, and immunogenicity of PF-SZ-IFX in patients with moderate-to-severe active RA. There were no clinically meaningful differences between groups, independent of a single treatment transition from IFX-EU to PF-SZ-IFX at week 30 or week 54.

NCT02222493.

The online version of this article (10.1007/s40259-019-00403-z) contains supplementary material, which is available to authorized users.

• Biological therapy
• Refractory disease
• Rheumatoid arthritis

Adherence is a key factor for therapeutic success in patients with rheumatoid arthritis (RA). The aim of this study was to determine whether results from the 5-item Compliance Questionnaire for Rheumatology (CQR5) can predict future poor adherence to biological disease-modifying anti-rheumatic drugs (bDMARDs) in patients with RA, using medication possession ratio (MPR) as the gold standard comparator.

RA patients starting a bDMARD were prospectively followed for 12 months. At baseline, CQR5 was collected in relation to the prescribed bDMARD. Patients were dichotomised into good adherers and poor adherers, categories that were then used as the variable in a predictive function analysis of the CQR5 in order to determine the accuracy of the classification at the end of the study period in comparison with the MPR. The sensitivity, specificity, and likelihood ratio of detecting poor adherers were also determined because this is the clinically important purpose of the questionnaire. Satisfactory adherence was defined as > 80% compliance with the prescribed dose regimen.

Of the 210 RA patients enrolled (147 women and 63 men; mean age 58.6 ± 12.8 years; mean disease duration 7.4 ± 2.5 years), at the end of the 12-month follow-up, 152 patients (72.4%) were good adherers and 58 (27.6%) were poor adherers according to MPR. Predictive analyses showed that the sensitivity and specificity of the CQR5 in detecting poor adherence were respectively 89.9% (95% CI 84.07–94.10%) and 80.8% (95% CI 67.46–90.37%). The accuracy of the CQR5 was 83.04% (95% CI 77.27–87.85%), the positive likelihood ratio (i.e. detecting ≤ 80% adherence) 4.67 (95% CI 2.58–8.18), and the area under curve 0.85 (95% CI 0.79–0.89).

Higher baseline CQR5 scores significantly predict the treatment adherence of RA patients. This suggests that this instrument could be used for screening purposes in order to identify patients who are poorly adherent to bDMARDs.

• Adherence
• Biological disease-modifying anti-rheumatic drugs
• CQR5
• Rheumatoid arthritis

• Biologic disease-modifying antirheumatic drugs
• Cycling
• Rheumatoid arthritis
• Switching
• Tumor necrosis factor inhibitors

• Sanofi
• Regeneron Pharmaceuticals

• TNF antagonists
• TNF inhibitors
• anti-TNF therapy
• herpes zoster
• vaccination
• varicella zoster virus

On August 24, 1998, Remicade^® (infliximab), the first tumor necrosis factor-α (TNF) inhibitor, received its initial marketing approval from the US Food and Drug Administration for the treatment of Crohn’s disease. Subsequently, Remicade was approved in another five adult and two pediatric indications both in the USA and across the globe. In the 20 years since this first approval, Remicade has made several important contributions to the advancement of science and medicine: 1) clinical trials with Remicade established the proof of concept that targeted therapy can be effective in immune-mediated inflammatory diseases; 2) as the first monoclonal antibody approved for use in a chronic condition, Remicade helped in identifying methods of administering large, foreign proteins repeatedly while limiting the body’s immune response to them; 3) the need to establish Remicade’s safety profile required developing new methods and setting new standards for postmarketing safety studies, specifically in the real-world setting, in terms of approach, size, and duration of follow-up; 4) the study of Remicade has improved our understanding of TNF’s role in the immune system, as well as our understanding of the pathophysiology of a range of diseases characterized by chronic inflammation; and 5) Remicade and other TNF inhibitors have transformed treatment practices in these chronic inflammatory diseases: remission has become a realistic goal of therapy and long-term disability resulting from structural damage can be prevented. This paper reviews how, over the course of its development and 20 years of use in clinical practice, Remicade was able to make these contributions.

• Crohn’s disease
• Remicade
• TNF inhibition
• immune-mediated inflammatory disease
• infliximab
• monoclonal antibody
• rheumatoid arthritis

We evaluated the clinical responses and radiographic outcomes of 90 patients with rheumatoid arthritis (RA) undergoing continuous or dose-adjusted infliximab treatment over 104 weeks.

Patients received 3 mg/kg infliximab continuously (the contin group; n=50), or the dose escalation and de-escalation of infliximab (3, 6, and 10 mg/kg) from week 14 (the adjusted group; n=40) based on the patient’s Disease Activity Score in 28 joints (DAS28). The retention rate, clinical response, and radiographic assessment were determined at week 104.

The contin and adjusted groups’ retention rates at week 104 were 56.8 and 66.7%, and the groups’ low disease activity in the DAS28 was 39.1 and 66.7%, respectively. Remission based on the DAS28 and the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) Boolean-based criteria was significantly increased in the adjusted group. In the radiographic assessment, there was also a significant reduction in the mean changes in total Sharp score. The cumulative rates of any adverse effects showed no significant difference between the groups.

In an assessment of adequate DAS28 results, the RA patients who did not respond to the initial dose of infliximab showed improved clinical responses and radiographic assessment after a dose adjustment of infliximab, without an increased risk of serious adverse events.

• DAS28
• REVIVE
• dose adjustment
• infliximab
• mTSS
• rheumatoid arthritis

• Certolizumab
• Clinical trial
• Methotrexate
• Rheumatoid arthritis
• Tumor necrosis factor inhibitor

• Adolescent
• Adult
• Aged
• Antirheumatic Agents/adverse effects
• Antirheumatic Agents/therapeutic use
• Arthritis, Rheumatoid/diagnosis
• Arthritis, Rheumatoid/drug therapy
• Certolizumab Pegol/adverse effects
• Certolizumab Pegol/therapeutic use
• Disability Evaluation
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Male
• Methotrexate/adverse effects
• Methotrexate/therapeutic use
• Middle Aged
• Recovery of Function
• Remission Induction
• Republic of Korea
• Time Factors
• Treatment Outcome
• Young Adult

• F. Hoffmann‐La Roche Ltd./Genentech, Inc.

• dmards (biologic)
• rheumatoid arthritis
• treatment

• Antirheumatic Agents/therapeutic use
• Arthritis, Rheumatoid/classification
• Arthritis, Rheumatoid/drug therapy
• Arthritis, Rheumatoid/physiopathology
• Biological Products/therapeutic use
• Drug Resistance, Multiple
• Female
• Humans
• Male
• Needs Assessment
• Pain, Intractable/classification
• Pain, Intractable/drug therapy
• Pain, Intractable/physiopathology
• Prognosis
• Recurrence
• Severity of Illness Index
• Treatment Failure
• Treatment Outcome

• Department of Health

• Biological therapies
• Enfermedad tuberculosa
• Factor de necrosis tumoral alfa
• Infección tuberculosa latente
• Latent tuberculosis infection
• Terapias biológicas
• Tuberculosis
• Tumor necrosis factor-alpha

• Biological therapy
• Disease-modifying antirheumatic drugs
• Inflammation
• Ligands
• Rheumatoid arthritis

• biosimilar
• infliximab
• network meta-analysis
• rheumatoid arthritis

• Etanercept
• TNF-α gene polymorphisms
• TNF-α inhibitors
• psoriatic arthritis

• Antirheumatic Agents/pharmacology
• Antirheumatic Agents/therapeutic use
• Arthritis, Psoriatic/drug therapy
• Arthritis, Psoriatic/genetics
• Etanercept/pharmacology
• Etanercept/therapeutic use
• Humans
• Immunosuppressive Agents/pharmacology
• Immunosuppressive Agents/therapeutic use
• Pharmacogenetics
• Polymorphism, Single Nucleotide
• Psoriasis/drug therapy
• Psoriasis/genetics
• Research Design
• Treatment Outcome
• Tumor Necrosis Factor-alpha/antagonists & inhibitors
• Tumor Necrosis Factor-alpha/genetics

• Arthroplasty of hip
• Arthroplasty of knee
• Biologic therapy
• Pharmacoepidemiology
• Rheumatoid arthritis

• Adalimumab
• Biologic
• Corrona
• Real-world
• Rheumatoid arthritis
• Treat-to-target

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We compared patient‐reported outcomes (PROs) in patients with RA treated with tofacitinib or placebo in combination with conventional disease‐modifying antirheumatic drugs (DMARDs).

In a 12‐month, phase III randomized controlled trial (ORAL Sync), patients (n = 795) with active RA and previous inadequate response to therapy with ≥1 conventional or biologic DMARD were randomized 4:4:1:1 to tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID, placebo advanced to 5 mg BID, or placebo to 10 mg BID, in combination with stable background DMARD therapy. PROs included patient global assessment of arthritis (PtGA), patient assessment of arthritis pain (Pain), physical function (Health Assessment Questionnaire disability index [HAQ DI]), health‐related quality of life (Short Form 36 health survey [SF‐36]), fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue [FACIT‐F]), and sleep (Medical Outcomes Study Sleep [MOS Sleep]).

At month 3, statistically significant improvements from baseline versus placebo were reported in PtGA, Pain, HAQ DI, all 8 SF‐36 domains, FACIT‐F, and MOS Sleep with tofacitinib 10 mg BID, and in PtGA, Pain, HAQ DI, 7 SF‐36 domains, FACIT‐F, and MOS Sleep with tofacitinib 5 mg BID. Improvements were sustained to month 12. Significantly more tofacitinib‐treated patients reported improvements of greater than or equal to the minimum clinically important differences at month 3 versus placebo in all PROs, except the SF‐36 role‐emotional domain (significant for tofacitinib 10 mg BID).

Patients with active RA treated with tofacitinib combined with background conventional DMARD therapy reported sustained, significant, and clinically meaningful improvements in PROs versus placebo.

• adalimumab
• efficacy
• genetics
• rheumatoid arthritis

• Ankylosing Spondylitis
• Anti-TNF
• DMARDs (biologic)
• Treatment

• Adolescent
• Adult
• Aged
• Antibodies/immunology
• Antibodies, Monoclonal/immunology
• Antibodies, Monoclonal/therapeutic use
• Antirheumatic Agents/immunology
• Antirheumatic Agents/therapeutic use
• Biosimilar Pharmaceuticals
• Drug Resistance/immunology
• Drug Substitution
• Female
• Humans
• Infliximab/immunology
• Infliximab/therapeutic use
• Male
• Middle Aged
• Spondylitis, Ankylosing/drug therapy
• Treatment Outcome
• Young Adult