Oral Icotrokinra Meets Primary End Point in Phase 3 Psoriatic Arthritis Trial

IL-23 inhibitors used in psoriatic arthritis (PsA), including the recently approved tildrakizumab, are all given by injection. New phase 3 data evaluate whether a once-daily oral peptide that blocks the IL-23 receptor can improve joint and skin disease in patients who have not received biologic therapy.

In the ICONIC-PsA 1 trial, icotrokinra (Icotyde; Johnson & Johnson) 200 mg met its primary end point, with 58% of patients achieving an ACR20 response at week 16 vs 41% with placebo (P = .002).^1,2 The findings were presented as a late-breaking poster at ACR Convergence 2026, held November 6-11 in Orlando, Florida.

“Effective management of psoriatic arthritis requires addressing both joint and skin disease,” said Joseph F. Merola, MD, MMSc, a rheumatologist, dermatologist and study coauthor.¹

ICONIC-PsA 1 Trial Design and Week 16 ACR Response Results

ICONIC-PsA 1 is a randomized, double-blind, placebo-controlled trial. It enrolled biologic-naïve adults whose PsA remained active despite conventional synthetic disease-modifying antirheumatic drugs and/or apremilast. Of 552 participants, 153 were randomized to icotrokinra 200 mg, 154 to icotrokinra 400 mg and 154 to placebo. Another 91 received ustekinumab as a safety reference arm.2 Patients receiving placebo crossed over to icotrokinra at week 16.¹

The 400-mg dose did not reach statistical significance on the primary end point, with an ACR20 response rate of 52% (P = .052).2 Higher response thresholds also favored the 200-mg dose, although those comparisons were reported with nominal P values. ACR50 response was 29% vs 16% with placebo (nominal P = .004), and ACR70 response was 13% vs 5% (nominal P = .015). Corresponding rates with 400 mg were 23% and 10%. The investigators concluded that 400 mg provided no additional benefit over 200 mg.2

Skin Clearance and Week 24 Responses With Icotrokinra in PsA

The analysis of skin outcomes included patients with psoriasis covering at least 3% of body surface area and an Investigator’s Global Assessment (IGA) score of at least 2 at baseline. In that group, 57% of patients receiving either icotrokinra dose achieved an IGA score of 0 or 1 at week 16, vs 14% with placebo (nominal P < .001).2 A Psoriasis Area and Severity Index (PASI) 90 response was reached by 37% of patients receiving 200 mg vs 6% with placebo (nominal P < .001).¹

Responses with 200 mg increased through week 24. By then, 69% of patients had an ACR20 response, 40% had ACR50 and 18% had ACR70. Among patients with qualifying baseline skin involvement, 64% achieved IGA 0/1 and 56% achieved PASI 90.¹ Because patients receiving placebo switched to active treatment at week 16, the week 24 results include no placebo comparison.

Icotrokinra Safety Findings and IL-23 Receptor Mechanism

Through week 16, adverse events occurred in 44% of patients receiving icotrokinra 200 mg, 52% receiving 400 mg, 41% receiving placebo and 51% receiving ustekinumab. Investigators reported no new safety signals through week 24.2 Rates of serious adverse events and infections were not included in the press release.¹

Icotrokinra binds the IL-23 receptor and inhibits IL-23 pathway signaling.1 In March 2026, the US Food and Drug Administration (FDA) approved it for moderate to severe plaque psoriasis in adults and in patients aged 12 years and older who weigh at least 40 kg and are candidates for systemic therapy or phototherapy. That approval made it the first targeted oral peptide to block the IL-23 receptor.3 Icotrokinra is not approved for PsA.¹

Limitations of the ICONIC-PsA 1 Data and Next Steps

The results come from a congress presentation and have not been published in a peer-reviewed journal. The trial enrolled only biologic-naïve patients, most of them from Europe and Asia, and almost no Black participants. This may limit how well the results apply to US practice.² Because ustekinumab served as a safety reference rather than an efficacy comparator, the data do not show how icotrokinra compares with injectable biologics.

The parallel phase 3 ICONIC-PsA 2 trial is evaluating icotrokinra in biologic-experienced and biologic-naïve patients with active PsA.4 Johnson & Johnson has not announced a timeline for a PsA regulatory filing.¹

References

1. Johnson & Johnson announces ICOTYDE (icotrokinra) delivers significant improvement in psoriatic arthritis disease activity among biologic-naïve patients with once-daily targeted oral peptide. News release. Johnson & Johnson. November 7, 2026. Accessed November 10, 2026. https://www.jnj.com/media-center/press-releases/johnson-johnson-announces-icotyde-icotrokinra-delivers-significant-improvement-in-psoriatic-arthritis-disease-activity-among-biologic-naive-patients-with-once-daily-targeted-oral-peptide

2. Kishimoto M, Nash P, Mease P, et al. Icotrokinra, an IL-23 receptor targeted oral peptide, in biologic-naïve participants with active psoriatic arthritis: results through week 24 of a phase 3, randomized, double-blind, placebo-controlled study. Abstract LB12. Presented at: ACR Convergence 2026; November 6-11, 2026; Orlando, FL. https://acrabstracts.org/abstract/icotrokinra-an-il-23-receptor-targeted-oral-peptide-in-biologic-naive-participants-with-active-psoriatic-arthritis-results-through-week-24-of-a-phase-3-randomized-double-blind-placebo-controlled/

3. FDA approval of ICOTYDE (icotrokinra) ushers in new era for first-line systemic treatment of plaque psoriasis with a targeted oral peptide. News release. Johnson & Johnson. March 18, 2026. Accessed November 10, 2026. https://www.jnj.com/media-center/press-releases/fda-approval-of-icotyde-icotrokinra-ushers-in-new-era-for-first-line-systemic-treatment-of-plaque-psoriasis-with-a-targeted-oral-peptide

4. A study to evaluate the efficacy and safety of icotrokinra (JNJ-77242113) in biologic-experienced and biologic-naive participants with active psoriatic arthritis (ICONIC-PsA 2). ClinicalTrials.gov identifier: NCT06807424. Accessed November 10, 2026. https://clinicaltrials.gov/study/NCT06807424