Safety and Efficacy of Cladribine in Patients Discontinuing Fingolimod Due to Elevated Transaminase Levels: The FinClad Study

Abstract

Background: Elevated liver enzymes pose a significant challenge for patients with multiple sclerosis (pwMS) undergoing treatment with fingolimod. Cladribine has demonstrated comparable efficacy with a more favorable safety profile in terms of hepatotoxicity risk. However, there is still limited data regarding the transition from fingolimod to cladribine for patients with elevated transaminase levels.

Objective: The objective of this study is to evaluate the safety and short-term efficacy of cladribine in pwMS who are discontinuing fingolimod due to elevated liver enzyme levels.

Methods: This retrospective, multicenter study included 45 pwMS who transitioned from fingolimod to cladribine because their AST/ALT levels were greater than three times the upper limit of normal. Clinical data, liver function tests, and disease activity parameters were collected at predefined time points. Disease activity was assessed based on relapse rates and radiological findings, which included new or enlarging T2 lesions and gadolinium-enhancing lesions.

Results: Both AST and ALT levels normalized and remained within the normal range after transition to cladribine (p < 0.001) with no reports of liver-related adverse events. During three months of follow-up, 86.7 % of patients maintained effective disease control, five patients had relapses, and one showed signs of radiological activity. A longer washout period was significantly associated with the presence of disease activity (p = 0.011).

Conclusion: Cladribine emerges as a safe and effective option for pwMS discontinuing fingolimod due to hepatotoxicity concerns. To optimize treatment outcomes, implementing shorter washout periods alongside close monitoring is essential to prevent disease reactivation.

Keywords: Cladribine; Disease-modifying therapies (DMTs); Expanded disability status scale (EDSS); Fingolimod; Hepatotoxicity; Liver function tests (LFTs); Relapsing-remitting multiple sclerosis (RRMS); Transaminases; Treatment transition; Washout period.