Filgotinib or lanraplenib in moderate to severe cutaneous lupus erythematosus: a phase 2, randomized, double-blind, placebo-controlled study.

OBJECTIVES: To explore the safety and efficacy of filgotinib (FIL), a Janus kinase 1 inhibitor, and lanraplenib (LANRA), a spleen kinase inhibitor, in cutaneous lupus erythematosus (CLE). METHODS: This was a phase 2, randomized, double-blind, placebo-controlled, exploratory, proof-of-concept study of LANRA (30 mg), FIL (200 mg) or placebo (PBO) once daily for 12 weeks in patients with active CLE. At week 12, PBO patients were rerandomized 1:1 to receive LANRA or FIL for up to 36 additional weeks. RESULTS: Of 47 randomized patients, 45 were treated (PBO, n = 9; LANRA, n = 19; FIL, n = 17). The primary endpoint [change from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score at week 12] was not met. The least squares mean CLASI-A score change from baseline was -5.5 (s.e. 2.56) with PBO, -4.5 (1.91) with LANRA and -8.7 (1.85) with FIL. Numerical differences between FIL and PBO were greater in select subgroups. A ≥5-point improvement in the CLASI-A score at week 12 was achieved by 50.0%, 56.3% and 68.8% in the PBO, LANRA and FIL arms, respectively. A numerically greater proportion of patients in the FIL arm (50%) also achieved ≥50% improvement in the CLASI-A score at week 12 (37.5% PBO, 31.3% LANRA). Most adverse events (AEs) were mild or moderate in severity. Two serious AEs were reported with LANRA and one with FIL. CONCLUSION: The primary endpoint was not met. Select subgroups displayed a numerically greater treatment response to FIL relative to PBO. LANRA and FIL were generally well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03134222.

Biologic therapy in psoriasis: perspectives on associated risks and patient management.

BACKGROUND: Previous publications have described practical considerations for initiating biologic therapy in psoriasis patients. However, most publications have focused on anti-tumor necrosis factor (TNF) therapy. OBJECTIVE: To create an evidence-based, practical tool that provides guidance on patient management for all biologics currently approved in Canada and the United States. METHODS: Psoriasis publications regarding safety issues in the initiation or monitoring of adalimumab, alefacept, etanercept, infliximab, or ustekinumab therapy were identified through a PubMed search. Phase III trials and open-label extensions (regardless of indication) and relevant guidelines from Health Canada were used to compile this review. RESULTS: Although these biologic agents have demonstrated efficacy in patients with psoriasis and are generally considered safe and well tolerated, rare but serious safety issues (ie, demyelination, infection, tuberculosis, malignancy, lymphoma, cardiovascular outcomes, hepatitis, pregnancy, surgery, and vaccination) have been observed. Attention to specific aspects of patient management (ie, prescreening requirements, symptoms to watch for, appropriate treatment, and referrals) is required to mitigate risk. CONCLUSION: Much of the evidence regarding the long-term safety of these agents has been based on experience in other patient populations. However, it does serve to guide us in understanding the risks that may impact the management of psoriasis patients.