Arundathi Jayatilleke, MD
Herpes zoster infection is another well-known complication of RA and its treatment, including glucocorticoid therapy. An increased incidence has recently been noted in people who use JAK inhibitors, though other bDMARDs including TNF inhibitors are also known to increase risk. Redeker et al. compare the incidence of herpes zoster in people with RA using csDMARDs, bDMARDs, and tsDMARDs using a German prospective RA registry. In nearly 14,000 patients, 559 cases of herpes zoster were documented; after adjusting for age, sex, and glucocorticoid use, an increased risk was noted for treatment with monoclonal anti-TNF therapy, B-cell directed therapy, and JAK inhibitors compared to csDMARDs, whereas soluble TNF receptor fusion protein, T cell costimulation modulators and IL-6 inhibitors were not associated with a higher risk of herpes zoster compared with csDMARDs. Unfortunately, zoster vaccination status was not extracted for all patients. The study confirms what we already know with direct risk comparison between different agents and underscores the importance of vaccination in RA patients, especially those being treated with glucocorticoids and tsDMARDs.
Finally, another important consideration in the use of bDMARDs is the increase in cancer risk due to a potential reduction in immunosurveillance. Initial meta-analyses of clinical trials of anti-TNF agents highlighted an early increase in cancer risk, though later studies including meta-analyses and registry studies with longer follow-up durations have been equivocal. Huss et al. examine a Swedish registry of people with RA and no prior history of cancer and found a small increase in cancer-risk in patients with RA compared to the general population (HR 1.2). However, there was no increase in overall cancer incidence in patients treated with TNF inhibitors, rituximab, abatacept, or JAK inhibitors compared to RA patients naïve to bDMARDs and tsDMARDs. Interestingly, urinary tract cancer risk was slightly increased in several treatment groups, though the effect size was small. Considering the generally long duration of follow-up (with the exception of JAK inhibitors), this study is very reassuring regarding long-term risk of cancer of bDMARD use and useful in counseling people with RA on therapeutic risks.