Abstract

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.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study did not receive any funding.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study used only data made previously publicly-available and/or was was gained using institutional-access. Databases searched were AMED, MEDLINE, CINAHL Plus, SPORTDiscus, EMBASE, Google Scholar and Web of Science. A manual search of reference lists of included studies and NICE evidence reviews for DMARDs and analgesics was also performed to identify potentially-relevant articles.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Abbreviations1RM1 Repetition Maximum (1 Rep Max);95% CIs95% Confidence Intervals;ACRAmerican College of Rheumatology;ATAerobic Training;BDSTwice-Daily (x2/day);CGControl Group;cmcentimetres;DMARDDisease-Modifying Anti-Rheumatic Drug;EULAREuropean Alliance of Associations for Rheumatology;GRADEGrading of Recommendations Assessment, Development and Evaluation (GRADE);HIITHigh-intensity Interval Training;IGIntervention Group;IL-1/6/10/11Interleukin-1/6/10/11;JAK/STATJanus Kinase/Signal Transducers and Activators of Transcription;MCIDMinimally Clinically Important Difference;MDMean Difference;MeSHMedical Subject Headings;microRNAmicro ribonucleic acid;mmmillimetres;MPAModerate-Intensity Physical Activity;N/ANot Available/Assessed;NICENational Institute of Health and Care Excellence;NSAIDNon-Steroidal Anti-Inflammatory Drug;ODOnce-Daily (x1/day);PAPhysical Activity;PICOSPopulation, Intervention, Comparator, Outcome, Study Design;PRESSPeer Review of Electronic Search Strategies;PRISMAPreferred Reporting Items for Systematic Review and Meta-Analysis;QDSx4/day;RARheumatoid Arthritis;RCTRandomised Controlled Trial;ROB2Risk of Bias 2;ROMRange of Motion;RPERating of Perceived Exertion;RTResistance Training;UKUnited Kingdom;VASVisual Analogue Scale;VPAVigorous-Intensity Physical Activity.