Adverse events with IL-17 and IL-23 inhibitors for psoriasis and psoriatic arthritis: a systematic review and meta-analysis of phase III studies.

Biologics targeting interleukin (IL)-17 and IL-23 are generally well-tolerated and considered safe, though adverse events are seen more often compared with placebo. The objectives of this systematic review and meta-analysis were to assess the prevalence of adverse events in patients with psoriasis or psoriatic arthritis with any adverse events after 12, 16, 24 and 52 weeks of treatment with IL-17 or IL-23 inhibitors. Two independent authors searched the databases PubMed and EMBASE for studies reporting on adverse events in phase 3 trials of IL-17 and IL-23 inhibitors for patients with psoriasis and psoriatic arthritis. The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data synthesis was performed using a random-effects model. In total, 44 publications (43 studies) were included in the analyses. The proportion of patients with any adverse events for all treatments pooled were 0.57 [95% confidence interval (CI): 0.55-0.59] after 12 weeks, 0.52 (95% CI: 0.49-0.55) after 16 weeks, 0.72 (95% CI: 0.66-0.78) after 24 weeks and 0.81 (95% CI: 0.76-0.86) after 52 weeks. Across therapies, the most prevalent AEs were infections, nasopharyngitis and headache. For ixekizumab one of the most prevalent AEs was injection site reactions, reported in 15.7% of the patients after 52 weeks. Overall, IL-17 and IL-23 inhibitors appear to be well-tolerated with good safety profiles. Our findings may aid the clinical decision making when choosing the most appropriate therapy for patients with moderate-to-severe psoriasis.

Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis.

Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment. Associations between genetic variants and treatment outcomes (drug survival and Psoriasis Area Severity Index reduction) were assessed using logistic regression analyses (crude and adjusted for gender, age, psoriatic arthritis and previous treatment). After correction for multiple testing controlling the false discovery rate, six SNPs (IL1B (rs1143623, rs1143627), LY96 (rs11465996), TLR2 (rs11938228, rs4696480) and TLR9 (rs352139)) were associated with response to anti-TNF treatment and 4 SNPs (IL1B (rs1143623, rs1143627), TIRAP (rs8177374) and TLR5 (rs5744174)) were associated with response to ustekinumab treatment (q<0.20). The results suggest that genetic variants related to increased IL-1ß levels may be unfavorable when treating psoriasis with either anti-TNF or ustekinumab, whereas genetic variants related to high interferon-γ levels may be favorable when treating psoriasis with ustekinumab.