Biologic combination therapy for RA may increase risk for side effects
medwireNews: Findings from a systematic review and meta-analysis suggest that rheumatoid arthritis (RA) patients who receive combination therapy with two biologic DMARDs are more likely to experience adverse events (AEs) than those given one biologic.
The meta-analysis included six studies – five randomized controlled trials and one retrospective cohort study – with a total of 623 participants, of whom 410 were treated with two biologic agents and 213 were treated with one. The combination of a tumor necrosis factor (TNF) inhibitor plus abatacept was investigated in two studies, as was the TNF inhibitor plus rituximab regimen, while the combinations of a TNF inhibitor plus anakinra, abatacept plus anakinra, and rituximab plus tocilizumab were each assessed in one study.
As reported in Seminars in Arthritis and Rheumatism, patients receiving two biologics had significantly higher rates of AEs and serious AEs over a median follow-up of 9.5 months than those given a single agent, at 94.6% versus 89.1% (odds ratio [OR]=2.07) and 14.9% versus 6.0% (OR=2.51), respectively.
Dual biologic treatment was not associated with a significantly elevated risk for infection or serious infection overall. However, in the subgroup of patients who received only full doses of their biologics, those in the combination therapy group were significantly more likely to experience serious infections than those given single agents, with rates of 6.7% versus 0.6% (OR=5.58).
The risk for serious adverse events was also significantly elevated among patients given dual- versus single-agent therapy in the subgroup receiving full doses, but neither this nor the risk for serious infections was significantly increased among patients receiving dual therapy when the analysis was restricted to those who received tapered doses of at least one of the combination agents.
These results suggest that “using higher doses [of two biologic agents] may be associated with higher [risk for] AEs in particular serious infections,” say Jean-Hugues Salmon (Hôpital Maison Blanche, Reims, France) and fellow researchers.
They add that “[u]sing tapered doses of [biologic] DMARDs seems to be a safer approach,” but caution that the findings in the subgroup of patients given tapered doses were based on a “low number of events with wide confidence intervals,” and “further studies are warranted to confirm this signal.”
And the team concludes that “clinicians should assess the risk/benefit ratio before considering a combination therapy in the management of patients with RA.”
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