Background: Patients with lichen planus (LP) refractory to available therapies often experience a high disease burden, representing a population with a clear unmet need for new treatments.
Objectives: To evaluate the efficacy and safety of secukinumab 300 mg over 32 weeks in adult patients with biopsy-proven cutaneous LP (CLP), mucosal LP (MLP) or lichen planopilaris (LPP) that is inadequately controlled by topical corticosteroids.
Methods: PRELUDE was a randomized double-blind placebo-controlled phase II proof-of-concept study that enrolled patients with CLP, MLP or LPP. Eligible patients were randomized to either secukinumab 300 mg every 4 weeks for 32 weeks (SECQ4W) or placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (SECQ2W) for 16 weeks. The primary endpoint was achievement of the newly designed Investigator's Global Assessment (IGA) score ≤ 2 at week 16.
Results: Overall, 111 patients were randomized (n = 37 each) to CLP, MLP and LPP cohorts. As the proof-of-concept criteria were not met for any of the three cohorts, the primary objective was not met. A numerically higher proportion of patients achieved IGA ≤ 2 response at week 16 with SECQ4W vs. placebo in the MLP {37.5% [95% credibility interval (Crl) 20.3-57.2] vs. 23.1% (95% Crl 6.5-49.2)} and LPP cohorts [37.5% (95% Crl 20.2-57.3) vs. 30.8% (95% Crl 10.8-57.6)]. In the LPP cohort, a sustained response for IGA ≤ 2 from week 16 to week 32 was achieved with SECQ4W (week 16, 37.5%; week 32, 45.8%), and a substantial improvement was observed in IGA ≤ 2 response in patients from this cohort who switched from placebo (week 16, 30.8%) to SECQ2W after week 16 (week 32, 63.6%). The safety profile was consistent with the known profile of secukinumab and showed no new or unexpected signals.
Conclusions: PRELUDE is the first randomized controlled basket trial evaluating interleukin (IL)-17A inhibition with secukinumab across three subtypes of LP. Secukinumab was well tolerated and safe, showing different response rates across the three subtypes, with numerical IGA improvements in MLP and LPP, and no response in CLP. The study raises the question of a differential role of IL-17A across LP subtypes. The novel IGA score showed significant correlation with both patient- and physician-reported outcome measurements.
Lichen planus (LP) is a skin disease that causes itchy, reddish-purple bumps on the skin. LP can affect different parts of the body, including the skin, mouth, genitals and nails. People with LP often experience intense itch, pain and discomfort, which can affect their daily lives. Secukinumab is a drug specifically designed to target and block a protein called ‘interleukin-17A’, which is found in high amounts in the lesions of LP. We carried out a clinical study to look at the effect of secukinumab separately in three different types of LP: cutaneous LP (CLP), mucosal LP (MLP) and lichen planopilaris (LPP). The study was conducted in the USA, France and Germany. A total of 111 adults who had not responded to topical treatment (treatment applied directly on the skin) took part in the study. Patients were divided into two groups. In one group, patients were treated with secukinumab 300 mg every 4 weeks for 16 weeks and continued with the treatment for another 16 weeks. In the other group, patients received placebo for 16 weeks and then received secukinumab 300 mg every 2 weeks for the next 16 weeks. All the patients were followed up for 8 weeks after stopping treatment. We measured whether secukinumab could reduce symptoms associated with LP using both doctor- and patient-assessed severity and quality-of-life measures. We also measured the side-effects related to the drug. We found that secukinumab was safe for people with LP, but it did not substantially reduce symptoms in people with CLP and only showed a tendency for improvement in people with MLP and LPP.
© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.