From Injectable to Oral: Optimal Durable Clearance Across the IL-23 Class

Two-year data from the phase 3 ICONIC-TOTAL trial show icotrokinra (Icotyde; Johnson & Johnson), the first oral interleukin-23 (IL-23) receptor antagonist, sustained or improved clearance of scalp, genital, and hand and foot psoriasis (PsO) through week 112, with no new safety signals, according to Linda Stein Gold, MD, director of dermatology clinical research at Henry Ford Health, and Andrew Blauvelt, MD, MBA, chair of the National Psoriasis Foundation Medical Board. The data are from a late-breaking abstract at the 2026 European Academy of Dermatology and Venereology (EADV) Congress in Vienna, Austria, held September 30-October 3, during which Stein Gold and Blauvelt sat down to discuss the new findings with HCPLive.¹

ICONIC-TOTAL enrolled adults and adolescents aged 12 years and older with body surface area involvement of at least 1% and at least moderate scalp, genital, or hand and foot PsO. Of 311 randomized patients, 208 received once-daily icotrokinra 200 mg and 103 received placebo before transitioning to icotrokinra at week 16, and 254 (82%) completed treatment through week 112.¹ Among icotrokinra-randomized patients, the proportion with clear or almost clear skin (Investigator's Global Assessment 0/1) rose from 57% at week 16 to 70% at week 112.¹

"We had maintained efficacy over time in the scalp and the genital area. We had improved efficacy over time in the palms and soles," Stein Gold said.

By site, scalp clear or almost clear rates were 66% at week 16, 78% at week 24, and 74% at week 112, with 60% completely clear at week 112.¹ Genital rates were 77%, 90%, and 89%, respectively.¹ Hand and foot disease, which missed statistical significance at week 16, reached 42% at week 16, 62% at week 52, and 68% at week 112, while mean nail severity improvement rose from 33% to 62% to 71%.¹ Blauvelt said the pattern tracks plaque thickness: genital lesions are thinnest and respond best, followed by scalp, then palms and soles, which are thickest. He said the steady gains fit IL-23 biology, which typically improves slowly over time, and that efficacy waning would have been a concern. For quality of life, about 59% of patients reported a Dermatology Life Quality Index score of 0 or 1 at 1 year; Blauvelt said efficacy remains his first consideration over quality-of-life measures when choosing a drug.

Exposure-adjusted rates of patients with at least 1 adverse event (AE) did not increase, at 160 per 100 patient-years (95% CI, 138-182) through week 52 and 122 per 100 patient-years (95% CI, 106-137) through week 112, and serious AE rates held at 2.7 per 100 patient-years, with no deaths.¹

"I tend to be a very conservative dermatologist, and safety is paramount in my mind," Stein Gold said, adding that the lack of new signals from year 1 to year 2 reassured her.

On positioning, Stein Gold described icotrokinra as the next step after topicals for patients who need systemic therapy. Blauvelt said the choice depends on the patient: he ranked its efficacy above at least half of available biologics but below the best ones, favored it where a patient wants a pill, and would steer patients prioritizing maximum efficacy to a top biologic and those with psoriatic arthritis toward IL-17 inhibition.

Reported disclosures for Stein Gold include AbbVie, Amgen, Arcutis, Bristol Myers Squibb, Organon Health, Eli Lilly, Johnson & Johnson, Novartis, Pfizer, and UCB. Blauvelt’s disclosures include Abbvie, Almirall, Alumis, Amgen, AnaptysBio, Apogee Therapeutics, Arcutis Biotherapeutics, Eli Lilly, Incyte, Janssen, LEO Pharma, Lipidio Pharma, Novartis, Oruka Therapeutics, Pfizer, Regeneron Pharmaceuticals, Sanofi, Sun Pharma, Takeda, and UCB.

References

1. Warren RB, Song EJ, Lain T, et al. Long-term durability and safety of the targeted oral peptide icotrokinra for high-impact site psoriasis: 2-year findings from the ICONIC-TOTAL randomized controlled trial. Abstract 245. Presented at: European Academy of Dermatology and Venereology (EADV) Congress 2026; September 30-October 3, 2026; Vienna, Austria.

2. Johnson & Johnson. FDA approval of ICOTYDE (icotrokinra) ushers in new era for first-line systemic treatment of plaque psoriasis with a targeted oral peptide. News release. March 18, 2026.