Abstract and Introduction
Background: Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A, a cornerstone cytokine in psoriasis, has shown long-lasting efficacy and safety in the complete spectrum of psoriasis manifestations.
Objectives; To report the long-term (2·5-year) efficacy and safety of secukinumab in nail psoriasis.
Methods: TRANSFIGURE, a double-blind, randomized, placebo-controlled, parallel-group, multicentre phase IIIb study in 198 patients, investigated secukinumab 150 mg and 300 mg in patients with moderate-to-severe nail psoriasis.
Results: At week 16, the primary endpoint Nail Psoriasis Severity Index (NAPSI) was met, demonstrating superiority of secukinumab to placebo. The effect was sustained over 2·5 years with a large benefit for nail clearance, with mean NAPSI improvement of −73·3% and −63·6% with secukinumab 300 mg and 150 mg, respectively. At 2·5 years, secukinumab demonstrated sustained clinically significant reductions in total mean Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) quality-of-life (QoL) scores of −52·4% and −18·1%, and 70% and 71% of patients achieved a weighted NAPPA Patient Benefit Index global score of ≥ 2 with secukinumab 300 mg and 150 mg, respectively. Patients showed considerable improvements in the EuroQol 5-Dimension health status questionnaire at 2·5 years, reporting a decrease in pain and discomfort. No new safety findings were observed.
Conclusions: Secukinumab demonstrated strong and clinically meaningful efficacy for up to 2·5 years in nail psoriasis, with significant sustained QoL improvements and a favourable safety profile.
Psoriasis is a chronic immune-mediated disease that affects around 3% of the population worldwide. Nail involvement is common in patients with psoriasis and the estimated lifetime incidence is as high as 90%. The prevalence of nail symptoms in psoriasis ranges from ≤ 40% in patients with mild psoriasis to 50–70% in those with severe forms, and ≥ 80% in patients with concomitant psoriatic arthritis (PsA).[3,4] The association of nail psoriasis and PsA can be explained by the fact that the nail matrix is made of different structures and is associated with entheses of the underlying distal interphalangeal joint. Furthermore, nail and joint inflammation in plaque psoriasis (PsO) seem to be mediated predominantly by innate immune cells, suggesting a common pathogenetic background. Nail psoriasis exhibits a heterogeneous clinical spectrum depending on which areas of the nail are involved, and includes pitting, discoloration, leuconychia, and onychodystrophy ranging to onycholysis.[2,7]
Nail psoriasis is associated with significant pain, impaired finger mobility and function, and loss of manual dexterity. This very visible and exposed disease feature may cause a significant negative impact on health-related quality of life (HRQoL), and if left untreated, can eventually progress to a debilitating stage that significantly impairs patients' daily activties. Nail psoriasis is often difficult to treat, as nails are slow to heal and conventional treatments such as topical and intralesional therapies are generally difficult to administer and are frequently ineffective. Given the anatomical structure of the nail unit, sufficient concentrations of active topical drugs are difficult to achieve in the involved nail, nailbed or matrix.[9,10]
Currently, not only is there no standardized treatment regimen, but there is also a lack of clinical evidence for patients with nail psoriasis. However, studies have shown that the use of biological agents provides significant benefit.[12,13] An improvement in the nail manifestations of psoriasis, based on Nail Psoriasis Severity Index (NAPSI) scores, has been reported with infliximab, adalimumab, etanercept, ustekinumab, guselkumab and ixekizumab treatments.[13–19]
Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, the cornerstone cytokine involved in the development of psoriasis. Secukinumab has shown long-lasting efficacy and safety in the various domains of psoriasis, including nails, scalp, palms/soles and joints.[20–24] The TRANSFIGURE study (NCT01807520) was conducted to evaluate the long-term efficacy and safety of secukinumab for the treatment of patients with moderate-to-severe psoriasis that includes significant nail involvement. This is the first study specifically designed to evaluate nail psoriasis rather than a retrospective study subgroup analysis of patients with psoriasis who had nail disease of varying severity at baseline (BL). This difference is important, as patients with severe nail disease, such as those enrolled in this study, are more likely to represent a distinct patient population. In addition, most recent studies[13–17] on nail psoriasis used NAPSI to evaluate the degree of psoriatic progression but have failed to address the patient-relevant aspects of nail psoriasis, such as pain and functional deficit. This gap has been addressed in the current study by using validated tools including the Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) - Quality of Life (NAPPA-QoL), which assesses patients' quality-of-life (QoL) conditions involving nail changes, emotions and daily activities, and the NAPPA - Patient Benefit Index (NAPPA-PBI), which assesses the defined needs of patients before treatment and patient-rated benefits after treatment.
Here we report the efficacy, QoL and safety results from the 2·5-year follow-up of the TRANSFIGURE study, the first robust long-term study reported in patients with nail psoriasis.
The British Journal of Dermatology. 2021;184(3):425-436. © 2021 Blackwell Publishing