Safety of combination therapy with two bDMARDs in patients with rheumatoid arthritis: A systematic review and meta-analysis

• Published in: Seminars in arthritis and rheumatism Vol. 49; no. 1; pp. 35 - 42
• Main Authors: Boleto, Gonçalo, Kanagaratnam, Lukshe, Dramé, Moustapha, Salmon, Jean-Hugues
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2019; WB Saunders
• Subjects: Antirheumatic Agents - adverse effects; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Biological Products - adverse effects; Biological Products - therapeutic use; Drug therapy, Combination; Drug Therapy, Combination - adverse effects; Drug tolerance; Humans; Life Sciences; Meta-analysis as topic; Rheumatoid arthritis-drug therapy; Treatment Outcome; Rheumatoid arthritis-drug therapy; Meta-analysis as topic; Drug therapy, Combination; Drug tolerance
• ISSN: 0049-0172; 1532-866X; 1532-866X
• DOI: 10.1016/j.semarthrit.2018.12.003

We performed a systematic review and meta-analysis of the current literature to assess the safety of combining two biologic disease-modifying antirheumatic drugs (bDMARDs) in the treatment of rheumatoid arthritis (RA). We systematically searched for controlled studies evaluating safety in patients with RA treated with two bDMARDs independently of dose-regimen. Databases used were MEDLINE (via Pubmed), EMBase, Cochrane Library, Scopus, ClinicalTrials.gov, and the WHO International Clinical Trials Registry platform. A meta-analysis was performed between groups on combination therapy and patients on single therapy using random effects model calculating odds ratio (OR) as well as 95% confidence interval (CI). The primary outcome was the rate of serious adverse events (SAEs). Six studies with a total of 623 patients (410 on combination therapy and 213 on single therapy) were included. Median follow-up was 9.5 months (range 6–12 months). There was a significant increase in SAEs in the combination group (14.9 vs 6.0%, OR 2.51, 95% CI 1.29–4.89, I2 0%) as well as in total adverse events (94.6 vs 89.1%, OR 2.07, 95% CI 1.11–3.86, I2 0%). When performing subgroup analysis in patients receiving only full-dose of both bDMARDs there was a significant increase in serious infections (6.7 vs 0.6%, OR 5.58, 95% CI 1.25–24.90, I2 0%) and the risk of SAEs remained significantly higher (17.1 vs 6.2%, OR 2.72, 95% CI 1.30–5.69, I2 0%). Our findings suggest that combination therapy with two bDMARDs in RA appears to increase the risk of SAEs during the first twelve months of treatment.