Difficult-to-treat rheumatoid arthritis: systematic review and meta-analysis on global prevalence
Authors' conclusion
Based on available global data, approximately 12% of patients with RA meet standard D2T-RA criteria, with nearly half exhibiting persistent inflammatory disease.
Study context
- Population
- Patients with rheumatoid arthritis (RA) in observational studies reporting difficult-to-treat rheumatoid arthritis (D2T-RA) prevalence per the European League Against Rheumatism (EULAR) definition; PubMed, EMBASE, Cochrane Library up to April 2025
- Participants
- 27,987 patients23 studies13 countries
- Outcome
- Global prevalence of D2T-RA (EULAR definition)
Methodological detailsrandom-effects meta-analysis of proportions, generalised linear mixed models, subgroup analyses
- Random-effects meta-analysis of proportions
- Generalised linear mixed models
- Subgroup analyses
Pooled result
As reported in the abstract
Global pooled prevalence of D2T-RA
Global pooled prevalence of D2T-RA
11.7%
95% CI 9.5%–14.3%
Further pooled results
| Outcome | P value |
|---|---|
| D2T-RA prevalence by enrolled periodpre-2020 vs post-2020 | P = 0.08 |
- D2T-RA prevalence by enrolled period: pre-2020 9.86% (95% CI: 7.6%-12.7%) vs post-2020 14.3% (95% CI: 10.3%-19.6%)
Pooled D2T-RA prevalence by cohort type
- Overall RA cohorts
- 10.9% (95% CI: 8.2%-14.2%)
- b/tsDMARD-treated populations
- 13.2% (95% CI: 9.1%-18.8%)
D2T-RA prevalence by enrolled period
- Stable by region, RA criteria and study setting
Proportion of D2T-RA with persistent inflammatory refractory RA
- Pooled proportion
- 47.1% (95% CI: 33.3%-61.4%)
Prevalence with stricter definitions
- D2T(3)-RA (≥3 b/tsDMARD failures) (2.7%-6.7%)
- 4.3%
- D2T(4)-RA (≥4 failures) (0.6%-4.3%)
- 1.6%
Original publication
Difficult-to-treat rheumatoid arthritis: systematic review and meta-analysis on global prevalence. Ann Rheum Dis. Published 3 November 2025. doi:10.
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