Nail Involvement May Reduce Efficacy of Ustekinumab For Psoriasis

Secukinumab provided overall higher efficacy than ustekinumab and similar response rates regardless of nail involvement in the treatment of moderate to severe psoriasis. Findings were published in Dermatology and Therapy.

Affecting up to 50% of patients with psoriasis and 70% to 80% of those with psoriatic arthritis, nail psoriasis was noted by researchers to be more common in patients negative for the human leukocyte antigen (HLA)-C*0602 allele. Moreover, the allele has been shown to affect disease course, phenotypic features, disease severity, associated comorbidities, and treatment response, with previous studies demonstrating that HLA-C*0602–negative patients are less responsive to methotrexate and ustekinumab.

With contrasting findings in a previous phase 3 study indicating similar response rates for secukinumab in both HLA-C*0602–positive and HLA-C*0602–negative patients with psoriasis, the study authors sought to further investigate the impact of nail involvement, and its negative association with the HLA-C*0602 allele, as a predictive indicator of secukinumab and ustekinumab response.

They conducted a post hoc analysis of the CLEAR and CLARITY studies, 2 phase 3b trials designed as 52-week, randomized, double-blind, active-controlled, parallel-group, superiority studies where patients were randomized 1:1 to receive secukinumab at baseline and at weeks 1, 2, and 3, then every 4 weeks from weeks 4 to 48 or ustekinumab at baseline and week 4 and then every 12 weeks from weeks 16 to 40.

The studies were stratified by nail involvement status at baseline for the post hoc analysis, with Psoriasis Area and Severity Index (PASI) 75 and 90 responses assessed over 52 weeks, as well as absolute PASI less than or equal to 3 (≤ 3), less than or equal to 1 (≤ 1), and 0 values at weeks 16 and 52.

Of the 886 and 891 patients who received secukinumab and ustekinumab in the studies, respectively, 30.4% and 29.7% reported history of nail involvement. Patients with nail involvement were shown to have had a longer disease duration (secukinumab, 20.5 years; ustekinumab, 17.3 years) than those without nail involvement (16.6 years in both arms) at baseline.

For those treated with secukinumab, nail involvement exhibited little to no impact on efficacy of treatment, as comparable responses were achieved at weeks 16 and 52 for patients with and without nail involvement for PASI 75/90, PASI ≤ 3, and 0 responses. A slightly lower PASI ≤ 1 score was achieved in patients with nail involvement.

Conversely, a higher PASI ≤ 3 response was observed in patients treated with ustekinumab who did not have nail involvement (week 16: 71.3%; week 52: 75.8%) vs those with nail involvement (week 16: 64.6%; week 52: 68.7%). A higher proportion of ustekinumab-treated patients without nail involvement were shown to achieve PASI 75 and 90 scores than patients with nail involvement over 52 weeks.

Overall, a higher percentage of secukinumab-treated vs ustekinumab-treated patients attained PASI 75 and 90 responses over 52 weeks. Differential efficacy was shown at weeks 16 and 52 for PASI ≤ 1 response in both treatment arms, but the difference between the groups with and without nail involvement was less pronounced in the secukinumab arm.

“These findings indicate that nail involvement can serve as an observable prognostic factor for efficacy in skin psoriasis treatment and guide the choice between secukinumab and ustekinumab,” concluded the study authors.

Reference

Conrad C, Ortmann C-E, Vandemeulebroecke M, Kasparek T, Reich K. Nail Involvement as a predictor of differential treatment effects of secukinumab versus ustekinumab in patients with moderate to severe psoriasis. Dermatol Ther (Heidelb). Published online December 6, 2021. doi:10.1007/s13555-021-00654-1