Icotrokinra, a recently approved oral peptide targeting the interleukin (IL)-23 receptor, showed strong and sustained activity through 2 years in psoriasis affecting high-impact areas, defined as hands and feet, genitals, scalp, and nails, in a newly completed phase 3 trial.

Presenting 2-year follow-up data from the ICONIC-TOTAL trial, Richard B. Warren, MBChB, PhD, professor of dermatology and therapeutics at the University of Manchester, UK, described the efficacy in these areas as “durable.” 

The benefit was demonstrated by relatively rigorous scores of 0 or 1, meaning clear or almost clear on measures such as the Investigator's Global Assessment (IGA) and Physician's Global Assessment (PGA). For example, for the scalp-specific IGA (ss-IGA) of 0 or 1, 75% of patients had sustained responses at 112 weeks. 

The data were presented as a late-breaker at the European Academy of Dermatology and Venereology (EADV) 2026 Congress.

Icotrokinra Approved in Europe Just Weeks Earlier

ICONIC-TOTAL is the most recent of the phase 3 trials of icotrokinra (Icotyde), which was approved by the FDA in March and by the European Medicines Agency in September for the treatment of psoriasis in patients aged ≥ 12 years, based primarily on the previously reported ICONIC-ADVANCE 1 and 2 trials. 

In ICONIC-TOTAL, 311 patients aged ≥ 12 who had moderate to severe psoriasis with significant involvement of at least one high-impact area were randomized (2:1) to 200 mg once-daily icotrokinra or placebo for the initial blinded 16-week part of the trial. At the end of 16 weeks, those taking placebo switched to icotrokinra.

Significant involvement of high-impact areas was defined by IGA or PGA scores at baseline: an ss-IGA score ≥ 3 for the scalp, a static PGA of genitalia (sPGA-G) score ≥ 3, and a PGA of hands and/or feet (hf-PGA) score ≥ 3. Baseline score on the modified Nail Psoriasis Severity Index (mNAPSI) had to be > 0.

At the end of the 16-week blinded period, the proportion of patients achieving an overall IGA score of 0 or 1 was 57% and 6% (P < .001) for the icotrokinra and placebo groups respectively. 

After patients in the placebo group were switched to icotrokinra, response rates climbed rapidly, Warren said. At 112 weeks, an IGA score of 0 or 1 was achieved by 70% of those initially randomized to icotrokinra and 64% of those who switched to icotrokinra. An IGA score of 0 (complete clearance) was achieved by 48% in both groups at 112 weeks.

The proportion of patients with an ss-IGA scalp score of 0 or 1 climbed from 66% at 16 weeks to 74% at week 112 in the group initiated on icotrokinra, and increased from 11% to 77% among those switched from placebo. An ss-IGA of 0 was achieved at week 112 in 60% of those initiated on icotrokinra and 69% of those who switched.

Among those with genital psoriasis, the sPGA-G score of 0 or 1 climbed from 77% at week 16 to 89% at week 112 in the group initiated on icotrokinra and from 21% to 93% among those switched from placebo. An sPGA-G score of 0 was reached at week 112 by 89% of those initiated on icotrokinra and 92% of those who switched. 

Among those with hands and feet involvement, the hf-PGA score of 0 or 1 climbed from 42% at week 16 to 68% at week 112 in the group initiated on icotrokinra and from 26% to 66% among those who switched. An hf-PGA score of 0 was achieved at week 112 in 63% of those initiated on icotrokinra and 66% of those who switched.

Slower But Sustained Nail Improvement Reported

The average percentage improvements in mNAPSI scores at week 16 were 33% and 9% in the icotrokinra and placebo groups, respectively. By week 112, the percentages had climbed to 71% in the icotrokinra group and 74% in those who switched, and complete clearance of nail psoriasis was achieved in 42% and 54%. 

In addition to the high proportions of patients achieving clearing or near clearing of psoriasis in high-impact areas, the sustained benefit is noteworthy, according to Warren. For the scalp and genital areas, peak response rates were achieved by about 24 weeks and sustained without decline to week 112. 

The peak hand/foot response was not achieved until week 52, but again, the peak response, once achieved, was sustained to week 112. 

Not surprisingly, nail improvement was slower. Although most of the response had been gained by week 52, there was still additional gain between weeks 52 and 112, Warren reported.

As seen with injectable IL-23 inhibitors, rates of adverse events were similar between the icotrokinra and placebo groups during the blinded period and remained low over the 112-week follow-up, he said. Serious adverse events during the blinded period were numerically lower in the icotrokinra than placebo group (< 1% vs 2%, respectively). In subsequent follow-up, no differences were seen in rates of overall adverse events or adverse events of interest, including immune function-related events, such as infection. 

No trials have directly compared the safety or efficacy of icotrokinra and an injectable anti-IL-23 therapy. However, a network meta-analysis suggests similar clinical activity, according to results of another study presented at the congress. 

The network analysis included 21 phase 2 or 3 randomized, placebo-controlled trials conducted in patients aged ≥ 12 years with moderate to severe psoriasis. The studies evaluated oral icotrokinra or injectable IL-23 inhibitors including guselkumab (100 mg every 8 weeks), risankizumab (150 mg every 12 weeks), and tildrakizumab (100 mg every 12 weeks).

Expressed in odds ratios (OR) at week 12 or 16, the data indicated the drugs were not interchangeable, according to Sana Gupta, a medical student at the University of Ottawa, Ontario, Canada. She conducted the study in collaboration with her advisor and coauthor, Mohannad Abu-Hilal, MD, director of the Division of Dermatology at McMaster University, Hamilton, Ontario, Canada.

Comparison of ORs for Treatment Responses

For the endpoint of a ≥ 75% reduction in the Psoriasis Area and Severity Index (PASI 75) score, the OR of a response was 22 times higher with icotrokinra and tildrakizumab than with placebo, but it was approximately 90 times higher with risankizumab and guselkumab.

However, differences diminished with more rigorous endpoints, such as PASI 90 and PASI 100. Gupta reported that patients taking icotrokinra had an OR of achieving PASI 100 that was about 38 times higher than placebo, the second-highest relative to risankizumab (OR, 41.5). The OR for guselkumab was slightly lower (36.1) but was much lower for tildrakizumab (16.2).

“None of these differences reached statistical significance,” said Gupta, suggesting that these data are exploratory, with limitations that include the low number of icotrokinra trials and potential for methodological heterogeneity. Head-to-head studies are needed, and comparative safety needs to be investigated, but she said that the efficacy of icotrokinra, even if lower than the most potent injectable agents, will make it a valuable option for selected patients, “potentially addressing potential barriers for injectable IL-23 inhibitors.”

ICONIC-TOTAL was sponsored by Johnson & Johnson. Warren has reported financial relationships with AbbVie, Almirall, Alumis, Amgen, Apogee, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dice, Eli Lilly, Galderma, GlaxoSmithKline, Johnson & Johnson, LEO Pharma, Meiji, Nektar, Novartis, Pfizer, RAPT, Sanofi, Sitryx, Sun, UCB, and Union. Gupta and Abu-Hilal have reported no relevant relationships. 

Ted Bosworth, a career medical writer based in New York City, has been covering advances in clinical medicine, including dermatology and oncology, for several decades.