Behavioural and Pharmacological Interventions for the Management of Pain Perceptions in Rheumatoid Arthritis: A systematic-review and meta-analysis

Objectives

To evaluate and compare the individual therapeutic efficacy of NICE-recommended physical activity (PA) and pharmacological interventions on pain amongst adults with rheumatoid arthritis (RA).

Methods

A systematic-review and meta-analysis of studies published between March 1988 and April 2025 was conducted across seven databases; AMED, MEDLINE, CINAHL Plus, SPORTDiscus, EMBASE, Google Scholar, Web of Science, and reference lists. Included were monotherapeutic randomised controlled trials (RCTs) of DMARDs, NSAIDS, analgesics, aerobic and/or resistance training for managing pain perceptions; measured as change in pre-and-post-intervention scores using the visual analogue scale (VAS). Participants were aged ≥18 years whose condition met American College of Rheumatology (ACR; 1987/2010) RA-criteria. Pooled meta-analyses results were presented as mean differences (MDs) and 95% confidence-intervals (95% CIs). Risk of bias (ROB) and certainty of evidence were assessed with the ROB 2 tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Results

Searches identified 3286 articles. 25 trials were selected for inclusion (6468 participants); 14 RCTs of 11 aerobic-and/or-resistance-training programs (n=916), three yoga regimes, an individual joint-protection programme, a trial of Rocabado exercises, and 11 RCTs of 21 DMARD/NSAID monotherapies (n=5552); baricitinib, celecoxib, filgotinib, hydroxychloroquine, ketoprofen, leflunomide(n=2), methotrexate, naproxen (n=2), sarilumab, sulphasalazine, tofacitinib, and upadacitinib. Weighted mean differences in pain perceptions for behavioural and pharmacological interventions were −2.47mm (95% CI: −3.14 – −1.81, p<0.00001) and −11.20mm (95% CI: −11.35 – −11.05, p<0.00001) respectively.

Conclusion

Despite inconsistent control of medication histories and PA-prescription, adherence to behavioural and pharmacological interventions can successfully alleviate pain. First-line management using DMARDs or NSAIDs appears to be more effective than yoga, Rocabado exercises, or aerobic and/or resistance training alone.

Systematic review registration number

CRD420251069339

Key Messages

• Both pharmacological and physical activity interventions can successfully reduce pain perceptions amongst patients with RA.

• Independent use of DMARDs or NSAIDs appears to alleviate pain more than aerobic and/or resistance-training.