Continuous indices of core data set measures in rheumatoid arthritis clinical trials: Lower responses to placebo than seen with categorical responses with the American College of Rheumatology 20% criteria

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.

Download Full-text

Composite Indices Using 3 or 4 Components of the Core Data Set Have Similar Predictive Ability to Measure Disease Activity in RA: Evidence from the DANCER and REFLEX Studies

Autoimmune Diseases ◽

10.1155/2013/367190 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Martin J. Bergman ◽

William Reiss ◽

Carol Chung ◽

Pamela Wong ◽

Adam Turpcu

Keyword(s):

Clinical Trials ◽

Assessment Tool ◽

Predictive Ability ◽

Disease Assessment ◽

Control Treatment ◽

Routine Practice ◽

Data Set ◽

Study Objective ◽

Core Data ◽

Composite Indices

Background. Understanding how disease-assessment indices perform in rheumatoid arthritis (RA) clinical trials can inform their use in routine practice. The study objective was to assess the capacity of combinations of RA Core Data Set measures to distinguish rituximab from control treatment.Methods. Post hoc analysis of two randomised clinical trials was used. Composite Efficacy Indices were derived by combining three or four RA Core Data Set measures from three possible sources: physician, patient, and laboratory.Results. All 105 Composite Efficacy Indices evaluated significantly distinguished rituximab from control treatment (P<10−7). Generally, indices containing measures from three different sources had a greater capacity to distinguish rituximab from control treatment than indices containing three measures from one source. Composite Efficacy Indices performed as well as validated indices such as DAS28, RAPID3, and CDAI.Conclusions. All indices composed of three or four RA Core Data Set measures have a similar capacity to detect treatment differences. These results suggest that the precise measurement used is less important than whether any measurement is performed, although selection should be consistent for each patient. Therefore, the choice of assessment tool should not be limited to a prescribed list and should instead be left to the clinician’s discretion.

Download Full-text

PMS52 Validation of Remission of Rheumatoid Arthritis by Traditional Disease Activity Score and Provisional Criteria by American College of Rheumatology and European League Agaisnt Rheumatism: Analysis Based on Patient Reported Outcomes from 3 Phase III Clinical Trials of Golimumab

Value in Health ◽

10.1016/j.jval.2012.03.241 ◽

2012 ◽

Vol 15 (4) ◽

pp. A43

Author(s):

C. Han ◽

E. Keystone ◽

R. Fleischmann ◽

J.S. Smolen ◽

P. Emery ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Trials ◽

Disease Activity ◽

Patient Reported Outcomes ◽

Disease Activity Score ◽

Phase Iii ◽

Phase Iii Clinical Trials ◽

American College Of Rheumatology ◽

Patient Reported ◽

European League

Download Full-text

Clinical contrasts with the American College of Rheumatology/European League Against Rheumatism provisional definitions of remission in rheumatoid arthritis for clinical trials: Comment on the article by Felson et al

Arthritis & Rheumatism ◽

10.1002/art.30552 ◽

2011 ◽

Vol 63 (11) ◽

pp. 3642-3643 ◽

Cited By ~ 3

Author(s):

Žiga Rotar ◽

Sonja Praprotnik ◽

Matija Tomšič

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Trials ◽

American College Of Rheumatology ◽

European League Against Rheumatism ◽

European League

Download Full-text

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

Annals of Pharmacotherapy ◽

10.1345/aph.1l268 ◽

2008 ◽

Vol 42 (11) ◽

pp. 1660-1668 ◽

Cited By ~ 16

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.

Download Full-text