Authors: Maha Mohammed Alkharisi , Yara Ayman Zein , Fares Fahad Alammari , Nawaf Abdullah Alzahrani , Noufa Afri Alonazi , Raghad H Albalawi , Shada Khalid Alanazi , Taif Abdullah A Alqahtani , Mohammad Alrashed , Abeer Abdulkarim Aloraini , Rahaf H Albalawi , Mohamed Ali , Haifa Alfalah

Abstract

Icotrokinra (JNJ-2113) is a first-in-class targeted oral peptide that selectively binds to the interleukin-23 (IL-23) receptor and blocks IL-23 signaling. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) of Icotrokinra to assess its efficacy and safety versus control in moderate-to-severe plaque psoriasis. We performed a PRISMA-adherent systematic literature search across Scopus, PubMed, and Web of Science from their inception up to January 2026. Screening, data extraction, and risk of bias assessment were made by two independent authors. A meta-analysis was conducted in R with sensitivity and subgroup analyses. We included four studies comprising five RCTs. Oral icotrokinra significantly improved physician-assessed and psoriasis area and severity index (PASI) responses compared with control in RCTs. For Investigator’s Global Assessment (IGA) 0/1, benefit was evident by week 2 (risk ratios (RR) = 3.24%, 95% confidence interval (CI) 1.01–10.46) and remained consistent through week 16 (RR = 7.35%, 95% CI 5.67–9.54), with an overall pooled effect RR = 7.31 (95% CI 6.25–8.55). Complete clearance (IGA 0) emerged from week 8 (RR = 23.65%, 95% CI 6.74–82.95), overall RR = 12.44 (95% CI 6.88–22.51). PASI 75 overall RR = 6.74 (95% CI 5.75–7.91); PASI 90 RR = 14.38; PASI 100 RR = 11.17. PSSD symptom 0 at week 16: 256/1226 vs 9/551 (RR=9.62%, 95% CI 5.14–18.01). Icotrokinra offers rapid and clinically significant improvements in plaque psoriasis, particularly on IGA and PASI, and these responses continue to improve over time; by week 8, complete clearance became significantly more frequent with icotrokinra. Safety outcomes were comparable between icotrokinra and placebo, and there was no meaningful increase in serious adverse events.

Keywords: Interleukin-23 receptor, icotrokinra, plaque psoriasis, psoriasis area and severity index.