Ixekizumab Linked With Improved Outcomes vs Adalimumab in PsA With Concomitant Psoriasis

A greater proportion of biologic-naive patients with psoriatic arthritis treated with ixekizumab vs adalimumab achieved the combined endpoint of 100% resolution in the Psoriasis Area Severity Index and 50% or greater improvement in the American College of Rheumatology criteria at week 24 and 52.

Ixekizumab may lead to consistent and improved skin outcomes vs adalimumab in biologic disease-modifying anti-rheumatic drug (DMARD)-naive patients with psoriatic arthritis (PsA), regardless of concomitant psoriasis severity. Results were published recently in Rheumatology and Therapy.

In treating the heterogeneous nature of PsA, current recommendations from the European League Against Rheumatism (EULAR) indicate that patients who do not respond to conventional DMARDs should be given biologic DMARDs, such as tumor necrosis factor (TNF)-α inhibitors or interleukin (IL) inhibitors.

Although recommendations no longer distinguish between TNF-α inhibitors and IL inhibitors, researchers note that preference of IL-17 or IL12/23 inhibitors for PsA and high levels of psoriasis involvement has caused effective therapies such as ixekizumab, a IL-17 inhibitor, to be more likely recommended in patients who present with moderate-to-severe skin involvement and less likely for mild skin involvement.

Seeking to establish whether the severity of concomitant psoriasis can affect the response to IL-17A inhibitor treatment, they conducted a post hoc analysis of the SPIRIT-H2H study, a 52-week, multicenter, randomized, open-label, rater-blinded, parallel-group study that compared ixekizumab with the TNF-α inhibitor adalimumab in biologic DMARD-naive patients (N = 566) with PsA and active psoriasis (≥ 3% body surface area involvement).

In the study, patients were randomized 1:1 to receive either ixekizumab or adalimumab with on-label dosing determined by psoriasis severity. Efficacy was assessed by the primary endpoint of the proportion of patients simultaneously achieving 50% or greater improvement in American College of Rheumatology criteria (ACR 50) and 100% improvement in Psoriasis Area Severity Index (PASI 100) at week 24.

Additional secondary endpoints included musculoskeletal, disease activity (defined by composite indices), skin and nail psoriasis, quality of life, and safety outcomes. “In this post hoc analysis, primary and secondary endpoints of SPIRIT-H2H were analyzed by baseline psoriasis severity,” added researchers.

Of the study cohort, 49 (17.3%) patients treated with ixekizumab and 51 patients treated with adalimumab had moderate-to-severe psoriasis at baseline. These patients with advanced disease were categorized as subgroup A, with those without moderate-to-severe psoriasis indicated as subgroup B.

In their findings, the efficacy of ixekizumab was shown to be consistent from week 24 to week 52 within the 2 subgroups.

For subgroup A, a significantly greater proportion of patients with moderate-to-severe psoriasis treated with ixekizumab achieved the primary endpoint of ACR 50  and  PASI 100 at week 24 (40.8% vs 17.6%; P = .015) and week 52 (38.8% vs 17.6%; P = .026), compared with adalimumab.

Conversely, patients of subgroup B treated with ixekizumab did not show significant differences in achieving ACR 50 and  PASI 100 at week 24 compared with adalimumab (35.0 vs 30.3%; P = .279), but significant differences were observed at week 52 (39.3 vs 28.1%; P = .014). ACR response rates and safety profiles of ixekizumab and adalimumab were similar across both patient subgroups, noted researchers.

Regarding the secondary endpoints, similar efficacy was shown for ixekizumab and adalimumab in addressing musculoskeletal outcomes, but ixekizumab was associated with greater responses for skin outcomes regardless of psoriasis severity.

Reference

Kristensen LE, Okada M, Tillett W, et al. Ixekizumab demonstrates consistent efficacy versus adalimumab in biologic disease-modifying anti-rheumatic drug-naïve psoriatic arthritis patients regardless of psoriasis severity: 52-Week post hoc results from SPIRIT-H2H. Rheumatol Ther. Published online October 28, 2021. doi:10.1007/s40744-021-00388-8