FC12 A systematic review and network meta-analysis on serious infection risk associated with biologics and systemic nonbiologics in patients with psoriasis
Journal: British Journal of Dermatology (2024)

Abstract Psoriasis is a chronic inflammatory skin disorder. Biologics have excellent efficacy against moderate-to-severe psoriasis, but serious infection is a concern. The aim is to systematically search and collate evidence to evaluate the serious infection risk associated with biologics in people with psoriasis. Medline, Embase, CINAHL, Cochrane Register, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) comparing biologics and systemic nonbiologics including novel targeted therapies licensed for psoriasis treatment in adults and children with psoriasis. Infections leading to hospitalization, intravenous antibiotics or death were considered serious. Number of patients with the outcome, sample size and person-time from RCTs and adjusted effect estimates from NRSIs were used to compute relative effects using the random-effects model. NRSIs with a critical risk of bias were excluded from the analysis. We conducted a frequentist network meta-analysis (NMA) using netmeta package in R. Three separate networks were fitted (RCT only; NRSI only; Combined RCTs and NRSIs). SIDE method was used to assess network coherence and P-scores for treatment ranking. Of 103 eligible RCTs, 71 with at least one serious infection event (n = 37 348; I2 ≤ 40%) and from 33 eligible NRSIs, seven without critical risk of bias (n = 308 901; I2 ≤ 71%) were included in the analysis. Patients were predominantly male (≤85%); mean age ranged from 13 to 52 years. Statistical incoherence was observed for three comparisons in the Combined network but not in the other two networks. The RCT-network found a higher risk with ustekinumab than IL-23 inhibitors (IRR 2.23; 95% CI 1.05–4.77). The NRSI-network found higher risk with infliximab and adalimumab [e.g. infliximab vs. methotrexate (IRR 2.85; 95% CI 1.48–5.46), infliximab vs. ustekinumab (IRR 2.73; 95% CI 1.94–3.84) and adalimumab vs. ustekinumab (IRR 1.51; 95% CI 1.25–1.83)]. In the Combined network, infliximab and adalimumab had a higher risk than bimekizumab, risankizumab, and secukinumab in addition to NRSI-network; IL-23 inhibitors had a lower risk than TNF-α inhibitors (IRR 0.53; 95% CI, 0.28–1.0). Sensitivity analysis with coherence achieved by removing two studies in the Combined network additionally found higher risk with certolizumab, etanercept, and secukinumab than risankizumab. In the treatment rankings, risankizumab had the highest probability of having the lowest risk of serious infection (P-score 0.87) followed by deucravacitinib, bimekizumab and tildrakizumab. Newer biologics, IL-23 inhibitors in particular, showed a lower risk of serious infection. However, these results should be interpreted with caution as there were no NRSIs for deucravacitinib and several newer biologics including bimekizumab, risankizumab and tildrakizumab. Large robust NRSIs are needed for these therapies for a reliable understanding of the relative risk of serious infection.