Do biologics increase the risk of infection?

This review explored the risk of infection in rheumatoid arthritis patients treated with biologics.

Biologics are a popular treatment choice for rheumatoid arthritis, particularly in patients who have not responded to disease-modifying antirheumatic drugs, such as methotrexate (Trexall). Biologics suppress or modulate inflammation, an important part of the immune response (which is overactive in rheumatoid arthritis).  However, suppressing the immune system in any way can leave patients vulnerable to serious infection.

In rheumatoid arthritis patients, this infection risk is heightened to begin with, as patients with mild disease activity have a 2.7-fold increase in the risk of infections such as septic arthritis and skin infections. For patients with more severe rheumatoid arthritis, that risk increases 4.8-fold. These risks are important to take into consideration when choosing a treatment course. The current review examined the specific infection risks raised by biologic drug treatment in rheumatoid arthritis. 

Rheumatoid arthritis patients today receive more aggressive therapy than did patients in the past which, while decreasing the rates of certain infections, has increased the rates of others. In particular, rates of Clostridium difficile, a serious gastrointestinal illness, have increased in frequency.

Tumor-necrosis factor-inhibitors are used to inhibit the inflammatory response. Different tumor-necrosis factor-inhibitors have different infection risk rates. For instance, a trend towards more serious infections was found more often in patients treated with infliximab (Remicade) and adalimumab (Humira) compared to patients treated with etanercept (Enbrel). Tumor-necrosis factor-inhibitors also increased the risk of shingles to 1.6 per 100 patient years (a measure used in clinical trials that takes into account the number of people in the study, the amount of time spent in the study, and the number of times a specific complication occurred) compared to 0.8 per 100 patient years for patients treated with disease-modifying anti-rheumatic drugs.

Tocilizumab (Actemra) is a drug that inhibits C-reactive protein, another factor in the immune response. Evaluation of tocilizumab in 6 early clinical trial involving 601 patients showed that tocilizumab led to a serious infection rate of 6.22 per 100 patient years, though lowering the dose from 8 mg/kg to 4 mg/kg reduced that risk. One study comparing different administrations of tocilizumab (intravenous versus injection) noted serious infections in 1.4% of 1,262 patients.

While many newer biologics, including some still under investigation, have been associated with serious infections, such as anakinra (Kineret), secukinumab, and sarilumab, not all have clearly shown an increased infection rate. Abatacept (Orencia), for instance, did not raise infection rates in the short-term compared to a placebo (a substance with no effect on the body often used as a control in clinical trials).

This review suggested that biologics vary in their risk of serious infection, and the general health of the patient should be considered when choosing a treatment method.