scholarly journals Non-overlapping American College of Rheumatology response rates: A better way to report response in rheumatoid arthritis Clinical Trials

2010 ◽  
Vol 62 (12) ◽  
pp. 3524-3527 ◽  
Author(s):  
Maarten Boers ◽  
Piet J. Kostense
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Response Rates ◽  
American College Of Rheumatology

scholarly journals Incorporating adjustments for variability in control group response rates in network meta-analysis: a case study of biologics for rheumatoid arthritis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chris Cameron ◽  
Abhishek Varu ◽  
Arthur Lau ◽  
Mahdi Gharaibeh ◽  
Marcelo Paulino ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Meta Analysis ◽  
Response Rates ◽  
Control Group ◽  
Severe Rheumatoid Arthritis ◽  
American College Of Rheumatology ◽  
Group Response ◽  
Study Heterogeneity ◽  
Treatment Comparisons

Abstract Background The importance of adjusting for cross-study heterogeneity in control group response rates when conducting network meta-analyses (NMA) was demonstrated using a case study involving a comparison of biologics for the treatment of moderate-to-severe rheumatoid arthritis. Methods Bayesian NMAs were conducted for American College of Rheumatology (ACR) 50 treatment response based upon a set of randomized controlled trials (RCTs) identified by a recently completed systematic review of the literature. In addition to the performance of an unadjusted NMA, a model adjusting for cross-study heterogeneity of control group response rates using meta-regression was fit to the data. Model fit was evaluated, and findings from both analyses were compared with regard to clinical interpretations. Results ACR 50 response data from a total of 51 RCTs and 16,223 patients were analyzed. Inspection of cross-study variability in control group response rates identified considerable differences between studies. NMA incorporating adjustment for this variability was associated with an average change of 38.1% in the magnitude of the ORs between treatment comparisons, and over 64% of the odds ratio changed by 15% or more. Important changes in the clinical interpretations drawn from treatment comparisons were identified with this improved modeling approach. Conclusions In comparing biologics for moderate to severe rheumatoid arthritis, failure to adjust for cross-trial differences in the control arm response rates in NMA can lead to biased estimates of comparative efficacy between treatments.

scholarly journals Placebo Response in Rheumatoid Arthritis Clinical Trials

2019 ◽  
Vol 47 (1) ◽  
pp. 28-34 ◽  
Author(s):  
Katie Bechman ◽  
Mark Yates ◽  
Sam Norton ◽  
Andrew P. Cope ◽  
James B. Galloway
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Kinase Inhibitors ◽  
Placebo Response ◽  
Janus Kinase ◽  
Controlled Trials ◽  
American College Of Rheumatology ◽  
Factor Therapy ◽  
Expectation Bias ◽  
Over Time

Objective.Understanding the placebo response is critical to interpreting treatment efficacy, particularly for agents with a ceiling to their therapeutic effect, where an increasing placebo response makes it harder to detect potential benefit. The objective of this study is to assess the change in placebo responses over time in rheumatoid arthritis (RA) randomized placebo-controlled trials (RCT) for drug licensing authorization.Methods.The Cochrane Controlled Trials Register database was searched to identify RCT of biological or targeted synthetic disease-modifying antirheumatic drugs (DMARD) in RA. Studies were excluded if patients were conventional synthetic DMARD (csDMARD)–naive, not receiving background csDMARD therapy, or were biologic experienced. Metaregression model was used to evaluate changes in American College of Rheumatology (ACR) 20, ACR50, and ACR70 treatment response over time.Results.There were 32 trials in total: anti–tumor necrosis factor therapy (n = 15), tocilizumab (n = 4), abatacept (n = 2), rituximab (n = 2), and Janus kinase inhibitors (n = 9). From 1999 to 2018, there was no significant trend in the age or sex of patients in the placebo arm. Disease duration, swollen joint count, and 28-joint count Disease Activity Score using erythrocyte sedimentation rate at baseline all significantly declined over time. There was a statistically significant increase in placebo ACR50 and ACR70 responses (ACR50 β = 0.41, 95% CI 0.09–0.74, p = 0.01; ACR70 β = 0.18, 95% CI 0.04–0.31, p = 0.01) that remained significant after controlling for potential confounders.Conclusion.There has been a rise in the placebo response in RA clinical trials over the last 2 decades. Shifting RA phenotype, changes in trial design, and expectation bias are possible explanations for this phenomenon. This observation has important implications when evaluating newer novel agents against established therapies.

Tocilizumab: An lnterleukin-6 Receptor Inhibitor for the Treatment of Rheumatoid Arthritis

2008 ◽  
Vol 42 (11) ◽  
pp. 1660-1668 ◽  
Author(s):  
Susyn L Plushner
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Adverse Effects ◽  
English Language ◽  
Data Extraction ◽  
Joint Damage ◽  
Clinical Trial Data ◽  
Liver Function Tests ◽  
Biologic Agent ◽  
American College Of Rheumatology

Objective: To review the pharmacology, pharmacokinetics, clinical trial data, and safety profile of tocilizumab, a new biologic agent targeting the lnterleukin-6 cytokine receptor. Data Sources: A systematic search of MEDLINE (1998–June 2008) and International Pharmaceutical Abstracts (1970–June 2008) was performed to identify published clinical trials and review articles. Key search terms were tocilizumab, MRA, interleukin-6/receptors, interleukln-6/immunology, and rheumatoid arthritis. The search was limited to studies in humans that were published in the English language. References from articles located during this search were evaluated for other relevant citations. Abstracts from national and international rheumatology meetings (American College of Rheumatology and European League Against Rheumatism) and from unpublished Phase 3 clinical trials in progress (using www.clinicaltrials.gov ) were also reviewed. Study Selection and Data Extraction: All available human studies describing the pharmacology, pharmacokinetics, efficacy, safety, and adverse effects of tocilizumab were included. Data Synthesis: At doses greater than 4 mg/kg, tocilizumab use has resulted In significant improvement in clinical outcomes, including the American College of Rheumatology parameters indicating a patient's level of improvements and disease remission. Improvements were noted when tocilizumab was used as monotherapy or in combination with methotrexate or other disease-modifying antirheumatic drugs. The most effective dose of tocilizumab appears to be 8 mg/kg, which has shown significant improvements in radiographic measures of joint damage. The most common adverse effects have included abnormal results of liver function tests, hyperlipidemia, neutropenia, infections, nasopharyngitis, gastrointestinal complaints, musculoskeletal disorders, headache, rash, and pruritus. Conclusions: Tocilizumab represents a promising new treatment for rheumatoid arthritis. Additional research is warranted to confirm its radiographic benefits, clarify its safely profile, and identify its place in rheumatoid arthritis treatment relative to current biologic agents.

Sign in / Sign up

Export Citation Format

Share Document