Efficacy of pharmacological interventions and therapeutic exercises for rheumatoid arthritis: a systematic review and meta-analysis

Timothy Adeyemi^1,2*Vitalis Ikenna Chukwuike³Motunrayo Adebukunola Oladimeji⁴Ufuoma Shalom Ahwinahwi⁵Victor Ayodeji Ayeni⁶Aisha Adam Abdullahi⁷Abdulmuminu Isah⁸Love Bukola Ayamolowo⁹Oluchukwu Perpetual Okeke¹⁰Olunike Abodunrin¹¹Folahanmi Akinsolu^12,13Olajide Odunayo Sobande¹⁰

• ¹Department of Physiotherapy, Bowen University, Iwo, Nigeria
• ²Department of Physiotherapy, Bowen University Teaching Hospital, Ogbomosho, Oyo State, Nigeria
• ³Department of Industrial and Medicinal Chemistry, David Umahi Federal University of Health Sciences,, Uburu, Ebonyi State., Nigeria
• ⁴Department of Anaesthesia, Lagos University Teaching Hospital, Idi-Araba Lagos, Nigeria
• ⁵Department of Clinical Pharmacy and Pharmacy Administration, Delta State University, Abraka, Nigeria
• ⁶Department of Paediatrics, Babcock University, Ilishan-Remo, Nigeria
• ⁷Department of Epidemiology and Population Health, Kano Independent Research Centre Trust, Kano, Nigeria
• ⁸Department of Clinical Pharmacy and Pharmacy Management, University of Nigeria, Nsukka, Nigeria
• ⁹Department of Nursing Science, Obafemi Awolowo University, Ife, Nigeria
• ¹⁰Nigerian Institute of Medical Research Foundation, Yaba, Lagos State, Nigeria
• ¹¹Department of Epidemiology and Biostatistics, Nanjing Medical University, Nanjing, China
• ¹²Clinical Sciences Department, Lead City University, Ibadan, Nigeria
• ¹³Nigerian Institute of Medical Research, Yaba, Lagos State, Nigeria

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by persistent synovitis, systemic inflammation, and progressive joint damage. Medication and physical exercise are the most common interventions documented for the treatment of RA. The current systematic review examined the efficacy of pharmacological and physical exercise interventions for RA. Methods: A systematic literature search utilized databases (PubMed, Web of Science, Google Scholar, Scopus, and CINAHL) to identify relevant randomized controlled trials (RCTs). The search strategy included keywords related to rheumatoid arthritis, pharmacological interventions, exercise therapy, and clinical outcomes. The review was registered with PROSPERO (CRD42024587378). Two independent reviewers screened the identified articles, and relevant data were extracted for analysis. The quality of evidence for the outcomes of interest in this systematic review and meta-analysis was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. Meta-analysis was carried out using a random effects model. For the meta-analysis, we assessed heterogeneity using the I2 statistic and evaluated publication bias using funnel plots. Results: Eighteen RCTs with a total sample size of 7,062 were included. Of these, eleven studies (61.11%) investigated the efficacy of different pharmacological interventions, whereas seven (38.89%) assessed the effects of exercise interventions. Different exercise programmes showed improved functionality, reduced pain, and improved patient quality of life, while short-and medium-term sensorimotor training was reported. Pharmacological interventions also reported varying levels of reduction in disease activity and improved functionality. Pooled effects of four studies included in the meta-analysis revealed the different categories of incremental clinical outcomes (1.89, 2.46, and 2.63) after 24 months based on American College of Rheumatology (ACR) criteria-ACR 20, ACR 50, and ACR 70, respectively. Significant effect sizes (0.09 and −0.08) after 24 weeks were equally found in three studies, indicating the reduction of disease activity and an improvement of functionality, respectively. Conclusion: Pharmacological and physical exercise interventions are potentially synergistic, and benefit many patients with RA, particularly regarding clinical outcomes such as reduced disease activity and improved functional ability. However, more RCTs are required, especially in Sub-Saharan Africa, to buttress the evidence base for these interventions, and more studies on pharmacological intervention safety.