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

Kimberley Allen-Philbey; Stefania De Trane; Amy MacDougall; Ashok Adams; Lucia Bianchi; Thomas Campion; Gavin Giovannoni; Sharmilee Gnanapavan; David W Holden; Monica Marta; Joela Mathews; Benjamin P Turner; David Baker; Klaus Schmierer

doi:10.1177/17562864231200627

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

Ther Adv Neurol Disord. 2023 Nov 10:16:17562864231200627. doi: 10.1177/17562864231200627. eCollection 2023.

Authors

Kimberley Allen-Philbey^{1

2}, Stefania De Trane^{1

2

3}, Amy MacDougall⁴, Ashok Adams⁵, Lucia Bianchi^{1

2}, Thomas Campion⁵, Gavin Giovannoni^{1

2

6}, Sharmilee Gnanapavan^{1

2}, David W Holden^{1

2}, Monica Marta^{1

2}, Joela Mathews¹, Benjamin P Turner^{1

2}, David Baker², Klaus Schmierer⁷

Affiliations

¹ Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, UK.
² Centre for Neuroscience, Surgery and Trauma, Faculty of Medicine and Dentistry, The Blizard Institute, Queen Mary University of London, London, UK.
³ Neurological Rehabilitation and Spinal Unit, Istituti Clinici Scientifici Maugeri, IRCCS Bari, Italy.
⁴ Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
⁵ Department of Neuroradiology, The Royal London Hospital, Barts Health NHS Trust, London, UK.
⁶ Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁷ The Blizard Institute, 4 Newark Street, London E1 2AT, UK.

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.

Keywords: cladribine; disease activity; disease breakthrough; multiple sclerosis; re-treatment; treatment switch.