Ixekizumab Leads to Consistent Efficacy for Psoriatic Arthritis, Despite Psoriasis Severity

Ixekizumab leads to rapid and consistent efficacy among individuals with psoriatic arthritis psoriatic arthritis (PsA) and psoriasis with skin, joint, and nail involvement, according to recent findings, regardless of level of baseline psoriasis severity.¹

These results were the findings of a post-hoc analysis of the SPIRIT-P1 and SPIRIT-P2 studies. The research was led by April W. Armstrong, MD, of University of California Los Angeles’s (UCLA) department of dermatology.

There had been a comparison after these 2 studies titled SPIRIT-H2H which compared the results of ixekizumab versus the tumor necrosis factor (TNF) alpha inhibitor adalimumab through 52 weeks in active PsA and active plaque psoriasis patients who were biologic-naïve. A later subgroup analysis of that study had indicated that ixekizumab was consistent in its efficacy versus adalimumab in patients with PsA both with and without moderate-to-severe psoriasis.^2,3

“The objective of this post hoc analysis was to evaluate joint, skin, and nail efficacy outcomes for IXE through 24 weeks in patients with mild, moderate, or severe psoriasis at baseline, integrated from SPIRIT-P1 and SPIRIT-P2,” Armstrong and colleagues wrote.¹

Trial Design

The research team explained the design of the SPIRIT-P1 and SPIRIT-P2 studies, which they noted were phase 3, double-blinded, multicenter, randomized trials that lasted 24 weeks and compared the safety and effectiveness of ixekizumab versus placebo among adult patients with both active PsA and either current plaque psoriasis or a history of the condition. They explained that SPIRIT-P1 used biologic-naïve participants and SPIRIT-P2 used subjects with experience treating their condition with TNF inhibitors.

Both of these 2 studies continued to assess subjects’ results in terms of long-term efficacy and safety of the drug for up to 156 weeks following the initial 24-week period. The research team pointed to recent research further highlighting elements of the study design and participant eligibility criteria from SPIRIT-P1 and SPIRIT-P2.

In their post hoc analysis, the team combined data from both studies’ intent-to-treat populations, with a focus on individuals who had been placed in either the placebo or treatment arm. They were given 80 mg every 4 weeks or every 2 weeks.

Study participants who did not respond or have an adequate response by the 16-week mark were given a course of rescue therapy. Subjects initially placed in the placebo arm were re-randomized 1:1 to be given ixekizumab, beginning with a dose of 160 mg at the 16-week mark followed then by 80 mg either provided every 4 weeks or every 2 weeks.

Up to week 24 the investigators’ efficacy outcomes were looked into, specifically categorized by baseline psoriasis severity. Severity measurement was based upon participants’ body surface area (BSA) impacted by disease, with ratings being labeled as mild (BSA < 3%), as moderate (3% ≤ BSA ≤ 10%), and as severe (BSA > 10%).

The research team’s primary outcomes were determined to be the proportions of subjects showing American College of Rheumatology (ACR)20, ACR50, and ACR70 responses. The team’s secondary outcomes evaluated in the study included musculoskeletal disease activity measures, as well as measures of nail and skin health and health-related quality of life.

New Findings

The investigators found that comparable proportions of the trial participants were able to reach ACR20, ACR50, and ACR70 over the course of time across each of the pre-determined severity subgroups and treatment cohorts. They reported that over a third of subjects treated with the drug were at ACR20 by the 4-week mark or ACR50 by 24 weeks, adding that no major distinctions had been based on baseline psoriasis severity.

Outcomes related to severity remained consistent through to the 24-week mark, with the research team reporting both IXEQ4W and IXEQ2W, regardless of participants’ initial severity of psoriasis. Over 24 weeks, the team identified no substantial distinctions in proportions of ixekizumab-treated individuals with either mild, moderate, or severe levels of baseline psoriasis achieving Minimal Disease Activity (MDA).

Those treated with ixekizumab were shown by the team to have achieved PASI100 responses as early as the fourth week over each of the subgroups. The investigators expressed that about a third of drug-treated individuals had reached a level of complete clearance of their skin by the 24-week mark.

“This analysis demonstrated that IXEQ4W and IXEQ2W provided rapid and consistent therapeutic benefit with respect to musculoskeletal outcomes for patients with (psoriatic arthritis) and plaque psoriasis, irrespective of the baseline percent BSA affected,” they wrote. “Both (ixekizumab) dosing regimens also showed rapid and consistent efficacy across multiple disease activity measures, regardless of psoriasis severity at baseline.”

References

1. ^{Armstrong AW, Jaleel T, Merola JF, Gottlieb AB, Khattri S, Helt CC, Malatestinic WN, Ross SE, Ngantcha ME, de Vlam K. Ixekizumab Demonstrates Rapid and Consistent Efficacy for Patients with Psoriatic Arthritis, Regardless of Psoriasis Severity. Dermatol Ther (Heidelb). 2024 Jun;14(6):1615-1631. doi: 10.1007/s13555-024-01188-y. Epub 2024 May 30. PMID: 38814433; PMCID: PMC11169211.}
2. ^{Mease PJ, Smolen JS, Behrens F, et al. A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naive patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial. Ann Rheum Dis. 2020;79(1):123–131. doi: 10.1136/annrheumdis-2019-215386.}
3. ^{Kristensen LE, Okada M, Tillett W, et al. Ixekizumab demonstrates consistent efficacy versus adalimumab in biologic disease-modifying anti-rheumatic drug-naive psoriatic arthritis patients regardless of psoriasis severity: 52-week post hoc results from SPIRIT-H2H. Rheumatol Ther. 2022;9(1):109–125. doi: 10.1007/s40744-021-00388-8.}