ArticleRMD open2026
Impact of trial exclusion criteria on real-world comparative effectiveness of targeted therapies in rheumatoid arthritis: the FIRST Registry.
Article in RMD open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
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Authors and funding
11 authors.
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No grant is acknowledged in the PubMed record.
Abstract
objectivesRandomised controlled trials (RCTs) use restrictive eligibility criteria, raising concerns about external validity for heterogeneous routine-care populations. We aimed to characterise real-world patients with rheumatoid arthritis who would be ineligible for phase III RCTs, to evaluate their outcomes on biological/targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in routine care and to assess how eligibility status influences comparative effectiveness estimates.
methodsWe analysed 5462 patients who initiated b/tsDMARDs between 2003 and 2023. RCT ineligibility was defined using common phase III trial exclusions (eg, renal/hepatic impairment). Outcomes were treatment persistence and Clinical Disease Activity Index remission at 26 weeks. Comparative effectiveness across drug classes was estimated using propensity score weighting, stratified by RCT eligibility.
resultsOverall, 39.7% (2167/5462) met at least one RCT exclusion criterion and ineligible patients had higher baseline disease activity and worse functional status. However, after propensity score adjustment for clinical characteristics, remission rates did not differ between groups (24.0% vs 23.2%; OR 0.90; 95% CI 0.78 to 1.04). The proportion ineligible differed by b/tsDMARDs, highest with interleukin 6 inhibitors (47.4%) and CTLA4-Ig (45.1%) and lowest with Janus kinase (JAK) inhibitors (31.0%). In the RCT-eligible cohort, remission with JAK inhibitors exceeded that with tumour necrosis factor inhibitors (OR 1.39; 95% CI 1.09 to 1.76), consistent with head-to-head RCTs. In the RCT-ineligible cohort, this advantage was attenuated and no longer statistically significant (OR 1.24; 95% CI 0.81 to 1.91).
conclusionsApproximately 40% of routine-care patients would be RCT ineligible. Although these patients achieved comparable adjusted outcomes, between-drug differences were smaller than in trial-eligible populations. Real-world comparative analysis should therefore consider composition and calendar time when interpreting treatment effects.
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