Risankizumab Outperforms Deucravacitinib on Psoriasis Clearance Across Patient Subgroups in Phase 4 Head-to-Head Trial

Risankizumab (Skyrizi; AbbVie) demonstrated significantly greater skin clearance than deucravacitinib (Sotyktu; Bristol Myers Squibb) at week 16 across a broad range of patient subgroups in adults with biologic-naïve moderate plaque psoriasis, according to a subgroup analysis of the phase 4 IMMpactful trial presented at the 2026 American Academy of Dermatology (AAD) Annual Meeting held in Denver, Colorado, from March 27-31.¹

The results extend the primary efficacy findings of IMMpactful — first reported at the Fall Clinical Dermatology Conference in October 2025 — to subgroup populations defined by age, sex, race, smoking status, BMI, baseline disease severity, and presence of psoriatic arthritis.¹

Study Design

IMMpactful (NCT06333860) is an Abbvie-funded, ongoing phase 4, multicenter, randomized, open-label, efficacy assessor-blinded study comparing risankizumab with deucravacitinib in adults with moderate plaque psoriasis. Eligible patients had a body surface area involvement of 10–15%, a PASI score ≥12, and a static Physician Global Assessment (sPGA) score of 3, and had not previously received biologic therapy. Patients were randomized 1:2 to subcutaneous risankizumab 150 mg at baseline and week 4 (n = 131) or oral deucravacitinib 6 mg once daily (n = 262) for the initial 16-week period. Co-primary endpoints were PASI 90 and sPGA 0/1 at week 16. The study is ongoing, with 52-week data anticipated at a future congress.¹

Baseline demographics were comparable between arms. Mean age was 47.3 versus 44.8 years, mean PASI was 15.7 versus 15.3, and mean affected BSA was 13.2% versus 13.0% in the risankizumab and deucravacitinib groups, respectively.¹

Efficacy Across Subgroups

Investigator Nina Magnolo, MD, Professor of Dermatology and Neurodermatology at the University Hospital Münster, and colleagues found that in the overall population, risankizumab achieved significantly higher rates of PASI 90 (57.3% vs 22.9%), sPGA 0/1 (80.2% vs 39.7%), and PASI 100 (27.5% vs 6.5%) compared with deucravacitinib at week 16, all at P <.001.¹

The subgroup analysis at AAD 2026 examined whether this advantage was consistent across clinically relevant patient characteristics. Across nearly all subgroups examined, risankizumab maintained a statistically significant advantage on both PASI 90 and sPGA 0/1.¹

For PASI 90, differences favoring risankizumab reached statistical significance (P ≤.05) in patients under 40 years (77.8% vs 18.2%), those aged 40 to <65 years (54.5% vs 21.8%), White patients (58.1% vs 22.8%), non-White patients (50.0% vs 24.3%), male patients (60.0% vs 23.8%), female patients (53.8% vs 23.3%), current smokers (59.5% vs 22.1%), previous or never smokers (56.2% vs 23.2%), all three BMI categories, patients with baseline PASI above the median of 14.4 (52.8% vs 21.6%), patients with baseline PASI at or below the median (69.0% vs 23.3%), and patients without psoriatic arthritis (55.7% vs 23.3%).¹

The one subgroup where statistical significance was not reached was patients aged ≥65 years — though the proportion numerically favored risankizumab (77.8% vs 31.8%); the authors attributed this to the small sample size in that age stratum.¹ Similarly, in the small psoriatic arthritis subgroup (n = 9 risankizumab, n = 22 deucravacitinib), the PASI 90 difference was numerically but not statistically significant (47.1% vs 18.2%).¹

The sPGA 0/1 results followed a parallel pattern, with risankizumab achieving statistically significant superiority (P ≤.01) across all subgroups except patients aged ≥65 years.¹

Safety through week 16, previously reported at the Fall Clinical Dermatology Conference, was consistent with the established profiles of both agents.¹

Clinical and Competitive Context

IMMpactful is among the first prospective head-to-head randomized trials directly comparing an IL-23 inhibitor with a TYK2 inhibitor in psoriasis, addressing a gap that has previously required indirect methods. A 2024 matching-adjusted indirect comparison (MAIC) published in Dermatology and Therapy analyzed data from the UltIMMa-1 and UltIMMa-2 risankizumab trials and the POETYK PSO-1 and PSO-2 deucravacitinib trials, finding significantly higher rates of PASI 75, PASI 90, PASI 100, and DLQI 0/1 with risankizumab at both 16 and 52 weeks.² The IMMpactful direct comparison now provides prospective data in a moderate psoriasis population that MAICs cannot fully capture.

The mechanistic distinction between the 2 agents is relevant to interpreting the magnitude of the difference. Risankizumab selectively blocks the p19 subunit of IL-23, interrupting upstream cytokine signaling that drives Th17-mediated skin inflammation. Deucravacitinib allosterically inhibits TYK2, a kinase involved in signaling downstream of IL-12, IL-23, and type I interferon receptors — a broader mechanism that does not achieve the same degree of IL-23 pathway selectivity. Whether the differential PASI 90 and PASI 100 rates at week 16 are sustained or narrow over longer follow-up will be a key question when 52-week IMMpactful data are presented later this year.¹

References

1. Magnolo N, Soung J, Sivamani RK, et al. Risankizumab vs deucravacitinib in adults with moderate plaque psoriasis: week 16 subgroup results from the IMMpactful study. Poster presented at: 2026 American Academy of Dermatology Annual Meeting; March 27–31, 2026; Denver, CO. Poster DV-017716.

2. Armstrong AW, Soliman AM, Gisondi P, et al. Matching-adjusted indirect comparison of risankizumab versus deucravacitinib in patients with moderate to severe plaque psoriasis. Dermatol Ther (Heidelb). 2024;14(11):3071–3081. doi:10.1007/s13555-024-01293-y