Long term safety of subcutaneous cladribine

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Cladribine as an immune reconstituion therapy that is given over 4 courses over a year and a bit and then that is it for 4 years. But what happens next? If we look at alemtuzumab about 50% fail after their two courses and are given more antibody and about 50% fail who are given three courses, but it is an effective drug. So if you fail cladribine should you get another course of switch treatment? That is for the neuros to decide but you can look to the cladribine pioneers who used subcutaneous cladribine to get clues and a number have been followed for a number of years without switch but additional doses were given. Prof K has a cohort of people with some dating back to 2014 and the results of follow-up were recently reported at ECTRIMS. Here is some real world data from Poland and ProfR where additional doses were given.

Long-Term Safety and Efficacy of Subcutaneous Cladribine Used in Increased Dosage in Patients with Relapsing Multiple Sclerosis: 20-Year Observational Study.Rejdak K, Zasybska A, Pietruczuk A, Baranowski D, Szklener S, Kaczmarek M, Stelmasiak Z.J Clin Med. 2021;10(21):5207. doi: 10.3390/jcm10215207

Cladribine is currently registered as a 10-milligram tablet formulation with a fixed cumulative dosage of 3.5 mg/kg over 2 years. It is important to investigate if an increased dosage may lead to further clinical stability with preserved safety. This study used an off-label subcutaneous (s.c.) formulation of cladribine and compared outcomes (Expanded Disability Status Scale (EDSS) scores and disease progression) between 52 relapsing multiple sclerosis (RMS) patients receiving different s.c. dosing regimens with up to 20 years of follow-up. The study group received induction therapy with s.c. cladribine (1.8 mg/kg cumulative dose; consistent with 3.5 mg/kg of cladribine tablets). Patients were subsequently offered maintenance therapy (repeated courses of 0.3 mg/kg s.c. cladribine during 5-20-year follow-up). Forty-one patients received an increased cumulative dose (higher than the induction dose of 1.8 mg/kg); 11 received the standard induction dose. Risk of progression on the EDSS correlated with lower cumulative dose (p < 0.05) and more advanced disability at treatment initiation (p < 0.05) as assessed by EDSS change between year 1 and years 5 and 10 as the last follow-up. Maintenance treatment was safe and well-tolerated, based on limited source data. Subcutaneous cladribine with increased cumulative maintenance dosage was associated with disease stability and favorable safety over a prolonged period of follow-up (up to 20 years) in RMS patients.

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