Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis

Abstract

Background Serious infections are a major concern for patients considering treatmentsfor rheumatoid arthritis (RA). Evidence is inconsistent on whether biologicsare associated with an increased risk of serious infection compared to traditional disease-modifying anti-rheumatic drugs (DMARDs). Methods A systematic literature search was undertaken using MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and www.clinicaltrials.gov from inception through February 11, 2014. Search terms included biologics, rheumatoid arthritis and their synonyms. Trials were eligible for inclusion if they included any of the biologics and reported serious infections. The risk of bias was assessed using the Cochrane Risk of Bias Tool. We conducted a Bayesian network meta-analysis,using a binomial likelihood model, of published trials to assess the risk of serious infections of biologics in RA patients, compared to traditional DMARDs. Findings The systematic review identified 106 trials that included RA patients on biologic and reported on serious infections. Compared to traditional DMARDs, standard-dose biologic (odds ratio [OR],1.31; 95% credible interval [CrI], 1.09 to 1.58) andhigh-dose biologic (OR, 1.90; 95% Crl, 1.50 to 2.39) were associated with an increased risk of serious infections, while low-dose biologics (OR, 0.93; 95% CrI, 0.65 to 1.33) were not. The risk was lower in patients who are methotrexate naïve compared withtraditional DMARD- or anti-TNF-biologic-experienced. The absolute increase in the number of serious infectionsper 1000 patients treated each year compared to traditional DMARDs ranged from 6 for standard-dose biologic to 55 for combination biologic therapy. Interpretation Standard-dose and high-dose biologics (with/without traditional DMARDs) are associated with an increase in serious infections compared to traditional DMARDs in RA, while low-dose biologics are not.Clinicians should discuss the balance between benefit and harm with the individual RA patient before initiating biologic therapy. Funding Rheumatology division at the University of Alabama at Birmingham.