Cladribine Personalized Dosing Well Tolerated and Efficacious in Multiple Sclerosis

March 1, 2021
Victoria Johnson
Victoria Johnson

Victoria Johnson, Assistant Editor for NeurologyLive, joined the MJH Life Sciences team in October 2020. Follow her on Twitter @VictoriaJNeuro or email her at vjohnson@neurologylive.com

Researchers found that 22 of 23 patients with elevated CSF NfL at baseline had normal levels at 2-year follow-up.

Data from a recent study suggest that subcutaneous cladribine personalized dosing (CPD) was well-tolerated in patients with relapsing multiple sclerosis (RMS), with efficacy in line with oral cladribine (Mavenclad; EMD Serono) trial data.

These findings were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2021, February 25-27, 2021, by Kimberley Allen-Philbey, PhD candidate, Neuroscience and Trauma, The Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London. 

“Oral cladribine is a licensed disease-modifying treatment (DMT) for [RMS]. We have experience treating a large cohort with this compound, ranging from early to advanced MS, using off-label subcutaneous cladribine personalized dosing since 2014,” Allen-Philbey and colleagues wrote.

The researchers offered CPD to people with MS regardless of disease course. Treatment schedule consisted of 10 mg on 3 consecutive days in week 1 (4 days in people over 90 kg), another 0-3 doses in week 5 based on total lymphocyte count in week 4. A second cycle of CPD was administered 11 months later. 

Follow-up recorded adverse events (AEs), relapses, annual Expanded Disability Status Scale (EDSS) scores, 9-Hole Peg Test scores, Timed 25-Foot Walking Test scores, and Symbol Digit Modalities Test scores. Magnetic resonance imaging (MRI) with gadolinium to enhance T1 and T2 lesions was performed, and cerebrospinal fluid (CSF) neurofilament light chain (NfL) measurements and full blood counts were obtained.

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Allen-Philbey and colleagues analyzed data from 250 patients with MS that received CPD in order to assess its safety and efficacy as an immunotherapy, 113 with RMS and 137 with progressive MS. Out of these patients, 211 completed a second cycle. The mean age of patients at baseline was 45 years (range, 17-72) and EDSS score ranged from 0 to 8.5.

CPD was generally well-tolerated. Over the follow-up period, 1 myocardial infarction, 1 breast cancer, 1 pulmonary embolism, and 3 severe allergic skin reactions without long-term sequelae occurred. Death occurred in 2 severely disabled patients with MS, 1 from influenza and 1 from encephalitis. Lymphopenia of at least grade 3 occurred in 7%.

EDSS remained stable or improved in 99 (82%) patients with MS with baseline and 2-year follow-up data. Of the 23 patients with MS that had elevated baseline CSF-NfL (median, 652 pg/mL; interquartile range [IQR], 458-1063), 22 had normal levels at follow-up (median, 344 pg/mL; IQR, 186-505).

“Our uncontrolled real-world data suggests CPD may be an effective alternative for patients with active MS irrespective of disability level. ChariotMS (a UK multi-center trial of cladribine tablets) will establish whether there is efficacy in advanced MS (EDSS 6.5-8.5),” Allen-Philbey and colleagues concluded.

For more coverage of ACTRIMS Forum 2021, click here.

REFERENCE
Allen-Philbey K, De Trane S, Stennett A, et al. Cladribine personalised dosing to treat active multiple sclerosis - follow-up in 250 patients. Presented at ACTRIMS Annual Forum; February 25-27, 2021. Abstract P160.