FDA Approves First Oral IL-23 Therapy for Psoriasis as Studies Show Site-Specific Responses

The FDA has approved icotrokinra (Icotyde, Johnson & Johnson), the first interleukin-23 (IL-23) oral targeted therapy for the treatment of moderate-to-severe plaque psoriasis. The approval is based on results from the phase 3 ICONIC clinical development program, which evaluated icotrokinra across multiple randomized trials in approximately 2500 patients, including studies in high-impact sites such as scalp and genital psoriasis.

Icotrokinra, the first oral peptide that blocks the IL-23 receptor, provides complete skin clearance and a favorable safety profile in a once-daily pill. The approved indication is for adults and children at least 12 years old who weigh at least 40 kg (88 pounds) and are candidates for systemic therapy or phototherapy. In head-to-head superiority studies, approximately 70% of patients experienced clear or almost clear skin and 55% of patients achieved a Psoriasis Area and Severity Index 90 response at week 16.

Meanwhile, a real-world study published in Dermatology and Therapy found that IL-23p19 inhibitors induced site-specific responses among patients with psoriasis in high-impact areas. The retrospective analysis of data from 37 sites in Italy evaluated 670 patients with psoriasis affecting high-impact areas who received guselkumab (177 patients), tildrakizumab 200 mg (239 patients), or risankizumab (254 patients) for at least 1 year.

Overall, the most affected high-impact area was the scalp (53.6%), followed by genitals (36.0%), palms or soles (25.2%), and nails (24.5%). The best early reduction in mean Psoriasis Area and Severity Index scores occurred with risankizumab at week 4, which was maintained through week 52. Mean scalp PGA scores were most significantly reduced at week 4 with risankizumab compared with tildrakizumab and guselkumab. At week 52, risankizumab and guselkumab were more effective than tildrakizumab for scalp involvement.

The three treatment strategies had distinct trajectories in nail psoriasis. Significant group differences in PGA were observed at week 6 and were maintained through week 52 with risankizumab, tildrakizumab, and guselkumab, respectively. The treatments had similar safety profiles, with an overall adverse event rate of 4.0% and no serious adverse events or discontinuations due to events reported.

In separate research, the phase 3b TOGETHER-PsO trial found that concomitant treatment with ixekizumab and tirzepatide met the primary endpoint of superiority vs ixekizumab monotherapy in achieving complete skin clearance and at least 10% weight reduction. At 36 weeks, 27% of patients receiving ixekizumab plus tirzepatide achieved both complete skin clearance and at least 10% weight loss compared with 6% receiving ixekizumab alone.

The TOGETHER-PsO trial enrolled 274 adult patients with moderate-to-severe plaque psoriasis and obesity, defined as a body mass index of at least 30 kg/m², or overweight with at least one weight-related comorbid condition. The study population reflected substantial disease burden, with a mean BMI greater than 39 kg/m² across both treatment arms, and 97% of patients had psoriasis involving high-impact areas, including the face, scalp, or genitals.

Rates of adverse reactions for patients treated with icotrokinra were within 1.1% of placebo through week 16, and no new safety signals were identified through week 52. The most common side effects of icotrokinra include headache, nausea, cough, fungal infection, and fatigue. Adverse events with concomitant ixekizumab and tirzepatide therapy were generally mild to moderate and consistent with the established safety profiles of each agent.

The real-world study investigators concluded that their results support a personalized approach to biologic therapy in psoriasis, where treatment selection is guided by factors such as anatomical involvement, baseline severity, prior treatment history, and individual therapeutic goals.