Autoimmunity reviews
June 1, 2026 · via Europe PMC
Comparison of treatment effects between ACR response criteria and target-based outcomes for contemporary rheumatoid arthritis drug approval trials: A meta-epidemiological study.
Dong W, Wang G, Hu X, +5 more, Guan X.
AI summary — for doctors, generated from the abstract only
Across 53 rheumatoid arthritis trials, ACR20 produced larger apparent treatment effects than remission or low disease activity endpoints, while ACR50 and ACR70 aligned better with target-based outcomes.
What was studied
A meta-epidemiological analysis of 53 randomized placebo-controlled trials (392 arms, 30,778 patients) of approved biologic and targeted synthetic DMARDs, comparing odds ratios for ACR responses versus target-based outcomes via ratios of odds ratios.
Key findings
- ACR20 showed greater treatment effects than remission (ROR 0.65, 0.52-0.81) and low disease activity (ROR 0.78, 0.69-0.89)
- ACR70 aligned with remission (ROR 0.88, 0.76-1.01)
- ACR50 aligned with low disease activity (ROR 0.95, 0.81-1.11)
- Discordance between ACR20 and target-based outcomes persisted across drugs, comparison types, and prior treatments
Clinical relevance
The findings suggest endpoint choice materially affects how effective a drug appears, supporting use of stricter or co-primary endpoints in trial design rather than changing patient care directly.
Who should care
Limitations
Trial-level meta-epidemiological analysis across heterogeneous study populations and designs, not patient-level data.
How RA trial success is measured shapes how large a drug's benefit looks.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Objective
Regulatory priorities diverge between agencies - the FDA maintained ACR20 response as primary endpoint in rheumatoid arthritis (RA) trials, whereas the EMA emphasized target-based outcomes. We aim to systematically compare treatment effect estimates between American College of Rheumatology (ACR) response criteria (ACR20/50/70) and target-based outcomes in placebo-controlled trials of approved RA therapies.
Methods
A meta-epidemiological study was performed on randomized placebo-controlled trials investigating approved biological and targeted DMARDs (bioDMARDs and tsDMARDs) in patients with RA. Trials reporting at least one ACR response criterion and one target-based outcome were included. Odds ratios (ORs) for each outcome were computed, followed by calculation of a risk of odds ratio (ROR) to quantify differences in treatment effects between ACR and target-based outcomes. The primary outcome was the treatment effect differences between ACR20 and target-based efficacy estimates, and the second outcome was to explore which alternative ACR response criteria were concordant with target-based outcomes.
Results
A total of 53 RCTs (392 study arms) involving 30,778 RA patients were analyzed. Trials using ACR20 demonstrated significantly greater treatment effect estimates compared to those using remission outcomes (ROR = 0.65, 95% CI 0.52-0.81) and LDA outcomes (ROR = 0.78, 95% CI 0.69-0.89). Higher ACR thresholds (ACR50 and ACR70) showed better consistency with target-based outcomes, with ACR70 aligning with remission (ROR = 0.88, 95% CI 0.76-1.01) and ACR50 aligning with LDA (ROR = 0.95, 95% CI 0.81-1.11). Subgroup analyses indicated that the discordance between ACR20 and target-based outcomes persisted across different intervention drugs, comparison types, and previous treatments.
Conclusion
ACR20 overestimates treatment effects relative to target-based outcomes, while ACR50/70 demonstrate better concordance. Harmonizing endpoints by integrating more stringent ACR response or co-primary endpoints (ACR response criteria + target-based outcomes) could bridge regulatory discrepancies and enhance clinical relevance in RA drug development.
DOI
10.1016/j.autrev.2026.104099
PMID
42229607
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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