Efficacy and safety of oral JAK, TYK2 and PDE4 inhibitors in the treatment of chronic plaque psoriasis'A network meta-analysis.

Abstract

Purpose: This systematic review and network meta-analysis (SR-NMA) aimed to evaluate and compare the efficacy of novel oral treatments for psoriasis, specifically Janus kinase (JAK) inhibitors, phosphodiesterase-4 (PDE-4) inhibitors, and tyrosine kinase 2 (TYK2) inhibitors, to determine the most effective therapeutic option. Method(s): A comprehensive search of randomised control trials was performed in Embase, MEDLINE, and Cochrane databases from inception to November 2024, employing search terms such as "TYK2," "PDE-4," "JAK," and "psoriasis," along with their relevant synonyms. The included studies were evaluated for risk of bias and assessed for their efficacy in achieving a 50%, 75%, 90% and 100% reduction in Psoriasis Area and Severity Index (PASI 50, PASI 75, PASI 90 and PASI 100 respectively). Data were analysed using a random-effects network meta-analysis approach. Result(s): Initial search yielded 8795 results. 23 studies assessing 11 novel oral agents were included for analysis after title/abstract and full-text screening performed independently by four investigators. Outcomes were measured over a range of 4-52 weeks. After 16-24 weeks of treatment, tofacitinib and deucravacitinib had the highest efficacy, followed by apremilast, orismilast, upadacitinib and brepocitinib. Zasocitinib, a new highly selective allosteric TYK2 inhibitor, has recently demonstrated promising efficacy in the treatment of psoriasis, with 33% of patients achieving PASI 100 (complete clearance of psoriasis lesions) after just 12 weeks of treatment. Conclusion(s): Oral TYK2 inhibitors have shown efficacy in the treatment of chronic plaque psoriasis comparable to adalimumab, with newer agents demonstrating enhanced effectiveness and surpassing PDE4 inhibitors in therapeutic outcomes. JAK inhibitors, particularly tofacitinib, exhibit comparable efficacy to some TYK2 and PDE4 inhibitors.