Low Rate of Opportunistic Infection Reported in Patients with PsA Treated with DMARDs

The overall incidence of opportunistic infections (OIs) in patients with psoriatic arthritis (PsA) treated with either biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) is low. However, monitoring for herpes zoster infection following treatment with Janus kinase inhibitors (JAKi), Mycobacterium tuberculosis infection following anti-tumor necrosis factor (anti-TNF) treatment, and mucocutaneous candidiasis following anti-interleukin-17 (anti-IL-17) treatment is recommended, according to a study published in Frontiers in Pharmacology.¹

“bDMARDs and tsDMARDs have broadened the treatment options and are increasingly used for patients with PsA,” investigators explained. “These agents block different pro-inflammatory cytokines or specific intracellular signaling pathways that promote inflammation and can place patients at risk of serious infections. We aimed to review the incidence of OIs in patients with PsA who were treated with these agents.”

Investigators searched PubMed and EMBASE for randomized clinical trials (RCTs) that analyzed the effect of bDMARD or tsDMARD treatment in patients with PsA. Eligible trials were those that compared treatment with placebo and included safety data. Investigators utilized the Revised Cochrane risk-of-bias tool. The primary outcome was the incidence of all OIs stratified by mechanism of action (MOA). Agents of interest included anti-TNFs (infliximab, golimumab, etanercept, adalimumab, and certolizumab), anti-IL-17 (ixekizumab, brodalumab, secukinumab, and bimekizumab), anti-IL-12/23 (ustekinumab), anti-IL-23 (risankizumab and guselkumab), T-cell co-stimulation modulators (alefacept and abatacept), a PDE4 inhibitor (apremilast), and JAKi (upadacitinib, deucravacitinib, filgotinib, and tofacitinib).

Of the 1066 studies published between 2000 and 2022, 47 RCTs (and 26 studies reporting extension follow-up data) were included in the analysis, using information from 17,197 patients who had received 1 or more doses of a bDMARD or tsDMARD. Cumulative incidence of OIs by MOA was 2.72% (95% CI: 1.05%–5.04%) among 2740 patients receiving JAK inhibitors. The most common OI was herpes zoster infection (89%, n = 130/146). Of those receiving anti-IL-17 drugs, OIs were reported in 1.18% (95% CI: 0.60%–1.9%), with 87% (n = 58/67) reporting candidiasis. In patients treated with anti-IL-23 drugs, only 8 patients reported OIs (0.24%, 95% CI: 0.04%–0.54%). Among the 3425 patients treated with an anti-TNF, 0.01% (95% CI: 0.00%–0.21%) of patients experienced an OI.

The cumulative incidence of herpes zoster infection following treatment with JAKi was 2.53% (95% CI: 1.03%–4.57%) and the cumulative incidence of opportunistic candidiasis infections after anti-IL-17 treatment was 0.97% (95% CI: 0.51%–1.56%).

The specific timeframe when OIs developed could not be determined, consequently limiting the study. Further, the trials did not follow a universal definition of OIs and risk of OIs could not be evaluated in comparison to other treatment options, thus warranting future studies. Other studies may also be beneficial in determining the risk of more uncommon OIs, including those with prolonged latent periods.

“Data from our meta-analysis indicate that both biologic and targeted synthetic DMARDs are safe agents concerning OIs for the treatment of PsA, since the incidence of OIs was found to be low across various different agents,” investigators concluded. “However, due to the increasing use of these biologic agents in clinical settings, it is important to continue thorough monitoring of patients with PsA who are treated with biologic and targeted synthetic DMARDs.”

Reference:

Vassilopoulos A, Shehadeh F, Benitez G, et al. The incidence of opportunistic infections in patients with psoriatic arthritis treated with biologic and targeted synthetic agents: A systematic review and meta-analysis. Front Pharmacol. 2022;13:992713. Published 2022 Oct 5. doi:10.3389/fphar.2022.992713