In people with rheumatoid arthritis, some doses of biologic drugs increase serious infection

Singh JA, Cameron C, Noorbaloochi S, et al. Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis. Lancet. 2015;386:258-65.

Review question

In people with rheumatoid arthritis, do biologic disease-modifying antirheumatic drugs (biologics) increase serious infections compared with traditional disease-modifying antirheumatic drugs (DMARDs)?

Background

Rheumatoid arthritis is a chronic condition that causes inflammation of the small joints, usually in the hands and feet. Treatment focuses on controlling symptoms (pain and swelling) and preventing joint damage. Doctors will usually start by prescribing drugs that have the fewest side-effects; if they don’t work well, they move onto different types of drugs or combinations of drugs. Biologics are a fairly new type of drug that is prescribed for people who do not respond to DMARDs or who have had side-effects from DMARDs.

How the review was done

The researchers did a systematic review, including studies up to February 2014. They found 106 randomized controlled trials that included 42,330 adults with rheumatoid arthritis.

Any dose or combination of a variety of biologics (e.g., etanercept, adalimumab, infliximab, golimumab, certolizumab pegol, anakinra, tocilizumab, abatacept, or rituximab) was compared with a traditional DMARD (including methotrexate).

Trials were combined using a type of analysis that lets you compare treatments even if they were not compared directly in the individual trials.

The main results were for standard-, high-, and low-doses of biologics or a combination of biologics (given with or without DMARDs) compared with treatment with one DMARD.

What the researchers found

45 trials had low risk for bias.

Compared with treatment with one DMARD:

• treatment with a standard or high dose of biologics increased the risk of serious infections;
• treatment with a combination of biologics increased the risk of serious infections; and
• treatment with a low dose of biologics did not differ for serious infections.

Conclusion

In people with rheumatoid arthritis, standard- and high-dose, but not low-dose, biologic drugs increase the risk of serious infection compared with treatment with one traditional disease-modifying antirheumatic drug.

Biologic treatment (with or without a DMARD*) vs single DMARD treatment in people with rheumatoid arthritis

*DMARD = disease-modifying antirheumatic drug.

†Absolute risk of serious infection per year with a single DMARD was 20 infections for every 1000 patients.