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.
COI Multiple
Hi,
This is an interesting article. I wish Merck would come up with recommendations for re-treatment or maintenance treatment following the first 4 years on cladribine.
BTW I can see that you have taken down the article written by Prof G about cladribine re-treatment. What is the reason for this? It was a very interesting article indeed.
You obviously have missed events of the past week. For reasons best known to him, all Prof G’s were taken down by himself and can now be found on his MS Selfie site. Hopefully the article you were referring to will be available there.
I’m aware that Prof G has left the blog, but I was not aware that his posts also has been removed. Well, that is a pity.
Thanks for replying!
yes – but he has moved rather than removed, if that makes any sense?
https://ms-selfie.blog/2019/08/29/cladribine-retreatment/
Thanks!!
No it doesn’t make sense, he removed the posts here period 🙂
Nice post
Very interesting data
Thanks
For Cladribine, theoretically subcutaneous or infusion would be better routes than oral? As it would affect fewer organs?