Efficacy and Safety of Nail Psoriasis Targeted Therapies: A Systematic Review

Nail changes are frequent clinical findings in patients with cutaneous psoriasis and psoriatic arthritis, often causing significant impairments in quality of life. Numerous targeted therapies have been previously studied for treatment of nail psoriasis, however, newer agents have not been captured in prior systematic reviews. With over 25 new studies published since 2020, the landscape of nail psoriasis systemic treatments is rapidly evolving, warranting analysis of recently approved therapies.

An updated systematic review of all PubMed and OVID database studies assessing efficacy and safety of targeted therapies for nail psoriasis was performed, with the goal of incorporating clinical data of recent trials and newer agents, namely brodalumab, risankizumab, and tildrakizumab. Eligibility criteria included clinical human studies reporting at least one of the nail psoriasis clinical appearance outcomes (Nail Psoriasis Severity Index, modified Nail Psoriasis Severity Index).

A total of 68 studies on 15 nail psoriasis targeted therapeutic agents were included. Biological agents and small molecule inhibitors included TNF-alpha inhibitors (adalimumab, infliximab, etanercept, certolizumab, golimumab), IL-17 inhibitors (ixekizumab, brodalumab, secukinumab), IL-12/23 inhibitors (ustekinumab), IL-23 inhibitors (guselkumab, risankizumab, tildrakizumab), PDE-4 inhibitors (apremilast), and JAK inhibitors (tofacitinib). These agents all demonstrated statistically significant improvements in nail outcome scores, compared with placebo or with baseline values, at weeks 10-16 and weeks 20-26, with some studies assessing efficacy up to week 60. Safety data for these agents were acceptable and consistent with known safety profiles within these timepoints, with nasopharyngitis, upper respiratory tract infections, injection site reactions, headache, and diarrhea being the most reported adverse events. Specifically, the newer agents, brodalumab, risankizumab, and tildrakizumab, showed promising outcomes for treatment of nail psoriasis on the basis of current data.

Numerous targeted therapies have shown significant efficacy in improving nail findings in patients with psoriasis and psoriatic arthritis. Data from head-to-head trials have shown greater efficacy of ixekizumab over adalimumab and ustekinumab, as well as brodalumab over ustekinumab, while prior meta-analyses have demonstrated superiority of ixekizumab and tofacitinib to other included agents at various assessed timepoints. Further studies on the long-term efficacy and safety of these agents, as well as randomized controlled trials involving comparison with placebo arms, are needed to fully analyze differences in efficacy of newer agents compared with previously established therapies.