Gonçalo Boleto1, Lukshe Kanagaratnam2, Moustapha Dramé2, Jean-Hugues Salmon3. 1. Rheumatology Department, Maison Blanche Hospital, Reims University Hospitals, 45 Rue Cognacq-Jay, Reims 51092, France. 2. Department of Research and Innovation, Robert Debré Hospital, Reims University Hospitals, 51092 Reims, France; Faculty of Medicine, EA 3797, University of Reims Champagne-Ardenne, 51095 Reims, France. 3. Rheumatology Department, Maison Blanche Hospital, Reims University Hospitals, 45 Rue Cognacq-Jay, Reims 51092, France; Faculty of Medicine, EA 3797, University of Reims Champagne-Ardenne, 51095 Reims, France. Electronic address: jhsalmon@chu-reims.fr.
Abstract
OBJECTIVES: 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). METHODS: 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). RESULTS: 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%). CONCLUSION: 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.
OBJECTIVES: 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). METHODS: 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). RESULTS: 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%). CONCLUSION: 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.
Authors: Quazim A Alayo; Marc Fenster; Osama Altayar; Kerri L Glassner; Ernesto Llano; Kindra Clark-Snustad; Anish Patel; Lukasz Kwapisz; Andres J Yarur; Benjamin L Cohen; Matthew A Ciorba; Deborah Thomas; Scott D Lee; Edward V Loftus; David I Fudman; Bincy P Abraham; Jean-Frederic Colombel; Parakkal Deepak Journal: Crohns Colitis 360 Date: 2022-02-10