Therapeutic approaches for difficult-to-treat rheumatoid arthritis: a systematic literature review of current evidence
Authors' conclusion
This SLR summarised evidence supporting DMARD efficacy/safety across multiple comorbidities. In patients with active RA with ≥2 prior bDMARDs, JAKi offer substantial clinical benefits but require careful risk stratification given cardiovascular and malignancy risks.
Study context
- Population
- Patients with D2T RA: active disease and limited treatment options; active disease with ≥2 prior b/tsDMARDs; poor health-related quality of life and low objective disease activity131 studies
- Comparison
- Treatments in difficult-to-treat RA
Methodological detailsMEDLINE, Embase and Cochrane Library searched until July 2025; 8589 records screened
- MEDLINE, Embase and Cochrane Library searched until July 2025; 8589 records screened
Pooled result
As reported in the abstract
- RQ2: all b/tsDMARDs except otilimab showed better efficacy than placebo (mostly high risk of bias)
- Meta-regression: Janus kinase inhibitors (JAKi) efficacy maintained despite increasing number of prior bDMARD failures (1 to ≥3)
- RQ1: DMARD efficacy and safety evidence synthesised across comorbidities incl. obesity, CVD, history of malignancy, respiratory comorbidities
- RQ3: limited evidence suggested orthopaedic surgical intervention as potential non-pharmacological option
Safety
- Increased occurrence of infection and malignancy with JAKi confirmed
Original publication
Therapeutic approaches for difficult-to-treat rheumatoid arthritis: a systematic literature review of current evidence. RMD Open. Published 4 August 2026. doi:10.
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