Disease activity 4.5 years after starting cladribine: experience in 264 patients with multiple sclerosis

Abstract

Background: Cladribine is an effective immunotherapy for people with multiple sclerosis (pwMS). Whilst most pwMS do not require re-treatment following standard dosing (two treatment courses), disease activity re-emerges in others. The characteristics of pwMS developing re-emerging disease activity remain incompletely understood. Objectives: To explore whether clinical and/or paraclinical baseline characteristics, including the degree of lymphocyte reduction, drug dose and lesions on magnetic resonance imaging (MRI) are associated with re-emerging disease activity. Design: Service evaluation in pwMS undergoing subcutaneous cladribine (SClad) treatment. Methods: Demographics, clinical, laboratory and MRI data of pwMS receiving two courses of SClad were extracted from health records. To assess associations of predictor variables with re-emerging disease activity, a series of Cox proportional hazards models was fitted (one for each predictor variable). Results: Of n = 264 pwMS 236 received two courses of SClad and were included in the analysis. Median follow-up was 4.5 years (3.9, 5.3) from the first, and 3.5 years (2.9, 4.3) from the last SClad administration. Re-emerging disease activity occurred in 57/236 pwMS (24%); 22/236 received further cladribine doses (SClad or cladribine tablets) at 36.7 months [median; interquartile range (IQR): 31.7, 42.1], and 22/236 other immunotherapies 18.9 months (13.0, 30.2) after their second course of SClad, respectively. Eligibility was based on MRI activity in 29, relapse in 5, both in 13, elevated cerebrospinal fluid neurofilament light chain level in 3, deterioration unrelated to relapse in 4 and other in 3. Only 36/57 of those eligible for additional immunotherapy had received a reduced dose of SClad for their second treatment course. Association was detected between re-emerging disease activity and (i) high baseline MRI activity and (ii) low second dose of SClad. Conclusion: Re-emerging disease activity was associated with baseline MRI activity and low dose second course of SClad.

Holistic, Long-Term Management of People with Relapsing Multiple Sclerosis with Cladribine Tablets: Expert Opinion from France

“…Long-term suppression of MS disease activity beyond the 4-year period studied in the CLARITY trial and its extension is therefore clearly possible. One real-world study showed that 26% of people with MS treated with CladT demonstrated recurrent MS disease activity during a median follow-up period of 4.5 years and that this was associated with higher MRI activity at baseline and receipt of a lower than indicated dose for the second course of CladT [ 79 ]. Another registry-based study found that 74% of a Clad-T-treated population achieved NEDA-2 during year 4 of treatment of a population with highly active MS [ 80 ].…”