Background/Purpose: Interleukin (IL) inhibitors are increasingly being used for rheumatologic diseases. There are many controlled clinical trials assessing the efficacy of IL inhibitors, but there are few meta-analyses which have examined the pooled risk of infection with these drugs. Our objective was to assess the risk of serious infection and opportunistic infections in patients with rheumatologic diseases treated with IL inhibitor therapy (anakinra, brodalumab, canakinumab, secukinumab, tocilizumab, olokizumab, ixekizumab, ustekinumab, clazakizumab, and rilanocept).

Methods: Medline via Pubmed, Embase, conference proceedings from ASCO, AACR and ACR and reference lists from published systematic reviews related to rheumatologic diseases and interleukin inhibitors for were searched for RCTs using PICOS strategy. We extracted the incident data for serious infections and opportunistic infections. We conducted a fixed-effect meta-analysis via calculating a pooled odds ratio (Mantel-Haenszel methods with a continuity correction designed for sparse data) using STATA software version 14 (Stata Corp., College Station, Texas, USA). Heterogeneity was assessed using Q-statistic and quantified using I² statistic.

Results: The initial search of PubMed and Embase yielded 881 citations. We included 38 eligible RCTs that included 16,841 patients. We extracted data on serious infections (death or hospitalization), candidiasis, herpes zoster, and Pneumocystis carinii Pneumonia (PCP) as the main outcomes of interest. Serious infections were significantly more common with patients who received IL inhibitors compared to standard of care (OR 1.97, 95% CI 1.48-2.62) and the heterogeneity was minimal (I² = 0%, P = 0.99). Moreover, we found that candidiasis also was significantly more common with patients who received IL inhibitors than standard of care (OR 5.41, 95% CI 2.04-14.33; I² = 0%, P = 0.99). However, we found no significant difference between patients who received IL inhibitors or standard of care in terms of the risk of herpes zoster or PCP (OR 1.23, 95% CI 0.39-3.84; I² = 0%, p = 0.97 and OR 0.99, 95% CI 0.10-9.65; I² = 0%, p = 0.70, respectively). There was no increased incidence of secondary assessed opportunistic infections such as TB, non-TB mycobacterium, coccidiodomycosis, histoplasmosis, asperillosis, cryptococcus, etc.

Conclusion: We found an increased risk of serious infections, and a significantly increased risk of candidiasis with the use of IL inhibitors, but there was no appreciable increase in the risk of herpes zoster or PCP. Other opportunistic infections were also found to have no appreciable increased risk. Patients and providers need to remain vigilant in recognizing the risk of serious and opportunistic infections with the use of IL inhibitors, and proper care must be taken to quickly identify and treat any infections as a result of IL inhibitor therapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-risk-of-serious-and-opportunistic-infections-in-rheumatologic-patients-on-interleukin-inhibitors-a-systematic-review-and-meta-analysis/