Standard- and high-dose biologics for RA associated with increased risk of serious infections compared to DMARDs alone

Standard-dose and high-dose biological drugs with or without disease-modifying antirheumatic drugs (DMARDs) were associated with an increase in serious infections compared to DMARDs alone, a meta-analysis found.

Researchers did a systematic review and meta-analysis of 106 trials published between 1992 and 2014 (totaling 42,330 patients with rheumatoid arthritis) that reported serious infections in patients treated with biological drugs compared with those treated with DMARDs. Any of the 9 approved biological drugs were compared to placebo, DMARDs, or another biological drug.

Results appeared online May 11 at the Lancet.

Compared with DMARDs, risk of serious infection was higher with standard-dose biological drugs (odds ratio [OR], 1.31; 95% credible interval [CrI], 1.09 to 1.58) and high-dose biological drugs (OR, 1.90; 95% CrI, 1.50 to 2.39), but not with low-dose biological drugs (OR, 0.93; 95% CrI, 0.65 to 1.33).

The risk was lower in patients who were methotrexate-naive compared with those exposed to DMARDs or anti-tumor necrosis factor biological drugs. The absolute increase in the number of serious infections compared with DMARDs ranged from 6 per 1,000 patients for standard-dose biological drugs to 55 per 1,000 patients for combination biological therapy.

Clinicians should discuss the balance between benefit and harm with patients before starting biological treatment for rheumatoid arthritis, the authors wrote.

“The benefits of biological therapy for patients with rheumatoid arthritis are well known, and now these patients can think about these benefits alongside the absolute risk increase of serious infections (6 per 1,000 per year for standard-dose biological drugs and 17 per 1,000 per year for high-dose biological therapy) at the time when decisions about treatment with biological drugs are made,” the study said. “Clinical guidelines should also incorporate the fact that this risk varies with several characteristics of patients, such as previous DMARD exposure, concurrent use of traditional DMARD or not, and established versus early rheumatoid arthritis.”