Background/Purpose: The risk of serious infection when using disease-modifying antirheumatic drugs (DMARDs), including biologic drugs is one of the major concerns for psoriasis/psoriatic arthritis (PsO/PsA) patients. Limited evidence exists on the comparative risk of infection among newer medications including ustekinumab (anti-IL-12/23), secukinumab and ixekizumab (anti IL-17), and a phosphodiesterase-4 inhibitor apremilast compared with TNF inhibitors (TNFi) in patients with PsO or PsA.

Methods: We conducted a cohort study using two large US claims databases, MarketScan (9/25/2009–12/31/2017) and Optum (9/25/2009–12/31/2018). We identified the initiators of one of the following biologic DMARDS: ustekinumab, secukinumab, ixekizumab, or TNFi, (i.e., adalimumab, etanercept, infliximab, certolizumab, golimumab). Apremilast, albeit not a biologic DMARDs (bDMARDs), was also included since it is a relatively new medication used to treat PsO and PsA. The index date was the date of the 1^st dispensing for a given drug. We required a 6-month washout period to define new users of each study drug. Patients were required to have at least two PsO or two PsA diagnosis during the 6-month baseline period. We excluded patients with a recent serious infection, rheumatoid arthritis, inflammatory bowel disease, malignancy, HIV, or organ transplant at baseline. Our primary outcome was a composite endpoint of hospitalized serious infection including bacterial, viral, or opportunistic infection. Follow-up time started from the day after the index date to the earliest date of the outcome, disenrollment, death, end of database, discontinuation, or switching to other study drugs. Propensity score (PS) was estimated as the predicted probability of receiving ustekinumab versus each of the aforementioned study drugs conditioning on >50 baseline characteristics. Cox proportional hazards regression estimated hazard ratios (HR) for serious infection associated with each study drug versus ustekinumab after controlling for confounding using PS-based fine stratification weights. Database-specific HRs were combined using a random-effects meta-analysis.

Results: We identified 123,383 PsO/PsA patients who initiated one of the study drugs. Among these, 61% had PsO, 22% had PsA, and 17% had both PsO and PsA. The mean (SD) age of the total cohort was 48.2 (12.8) years, and 50.6% were female (see Figure 1). The crude incidence rate per 100 person-years was highest in Infliximab (2.47 in MarketScan and 3.17 in Optum) and the lowest ixekizumab (0.69 in MarketScan) and ustekinumab (1.03 in Optum). After the PS stratification, ustekinumab had lower risk of hospitalized serious infection compared to other bDMARDs or apremilast (Figure 2). However, our estimates comparing certolizumab and golimumab versus ustekinumab were imprecise due to a limited sample size even after combining results from the two databases.

Conclusion: In this multi-database cohort of 123,383 PsO or PsA patients, ustekinumab initiators had a generally lower risk of hospitalized serious infection compared to TNFi, IL-17 therapy, and apremilast initiators.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparative-risk-of-hospitalized-serious-infection-in-patients-with-psoriasis-and-psoriatic-arthritis-a-population-based-multi-database-study/