Background/Purpose: The real-world risk of serious infections associated with interleukin (IL) and tumor necrosis factor-alpha (TNF-α) inhibitors for patients with psoriasis (PsO) and psoriatic arthritis (PsA) is unclear. The objective of this study was to examine whether initiation of IL-17, IL-12/23, or TNF-α, was associated with increased risk of serious infection among PsO and PsA patients.

Methods: We built a cohort of commercially insured adults diagnosed with PsO or PsA between 2015–2018 using data from the OptumLabs^® Data Warehouse. Exposure was new use of IL-17 (ixekizumab or secukinumab), IL-12/23 (ustekinumab), or TNF-α (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab). The main outcome was hospitalized infection after date of biologic initiation. Incidence rates (IR) per 100 person-years were computed, and hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazards regression models, adjusted for inverse probability of treatment weighted propensity scores to control for confounding. In sensitivity analyses, we varied the permissible gap between prescriptions, and to restrict to infection listed as the first diagnosis code position.

Results: A total of 11,560 new treatment episodes were included (19% IL-17, 25% IL-12/23, 56% TNF-α inhibitors). Overall, 190 serious infections (2% of treatment episodes) were identified in 9,264 person-years of follow-up (Table). Class-specific IR were similar among IL-17 and TNF- α, and significantly lower for IL-12/23. After adjustment for propensity scores, there was no evidence of an increased risk of serious infections with IL-17, as compared to either TNF-α (HR=0.89, 95% CI 0.48-1.66) or IL-12/23 (HR=1.12, 95% CI 0.62-2.03). By contrast, IL-23/23 were associated with a lower risk of infections than TNF-α (HR=0.59, 95% CI 0.39-0.90). In the subgroup of patients with PsA, we observed a similar risk of serious infections between the three biologics exposure groups. Indeed, compared to the PsA cohort, the PsO cohort patients were younger, more likely to be male, had fewer comorbidities, fewer physician office visits, lower proportions of DMARD use, and less glucocorticoid exposure during baseline. Nevertheless, we note that the effect estimate even in the PsA patients for IL-12/23 exposure was numerically lower (0.74 , 95% CI 0.40 – 1.36) and compatible with the significantly protective association observed in the psoriasis patients (0.59, 95% CI 0.38 – 0.92).

Conclusion: We did not find empirical evidence of an increased risk of serious infection with the IL-17 inhibitors, and observed a significantly lower infection risk with IL-12/23 biologics, compared to TNF- α therapy. Given the relatively small magnitude of absolute effect (difference less than 1 per 100 person-years) yet strong relative risk reduction compared to TNF-a, these results may inform clinical decision-making regarding the safety of the available choices.

ACR abstract Table

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/no-evidence-of-an-increased-risk-of-serious-infections-among-3-classes-of-biologics-for-psoriasis-or-psoriatic-arthritis-a-retrospective-real-world-cohort-study/