No sooner has the Polish bus rolled up, ProfK drives our team Bus and our work has been published relating to the longer term effects of cladribine treatment


Allen-Philby et al. Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients Therapeutic advaneces in Neurological disorders.


To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients.


Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3–4 days during week 1. Based on lymphocyte count at week 4, patients received another 0–3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts.


In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17–72) years and EDSS 0–8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data (n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data (n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months.


Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.

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  • Very good and interesting work and results look good indeed, I see hopes for the success of chariotMS to start changing the future of people with progressive forms.
    I wonder why there is difficulty to get data in homogenous way for many studies of this kind… it makes drawing conclusions difficult and decreases statistical power 🙁
    Other question is about CSF-NfL… did you do OCB test on people that underwent lumbar puncture for NfL?

  • MD 1 – thanks for this post.

    The results look interesting – particularly the results for progressive patients. What about OCBs – were these measured?

    Why is the dose given not linked to the patient’s weight?

    The real test will be how the patients are doing in 10, 15…. years time.

    • The dosing is related to size and lymphocyte number This is why ProfK got less lymphopenia than with the oral study

  • Can neurologists in the UK prescribe a third dose of cladrabine if they think it would be of benefit to patients?

    I started cladrabine around 3 months ago although I’ve not had my first blood tests yet. All in all I’m happy with the treatment, minimal side effects so far and I’m hoping it’s working.

    Just thinking down the road. Id be happy todo a third dose, as discussed before a third dose of Lemtrada can be highly effective in treating MS with arguably a worse safety profile

  • To receive this treatment did the patients regardless of disease severity have to have evidence of disease activity either on MRI or in NFL?

      • Would that not be unusual for edss 8.5?
        Unless of course that was 8.5 induced by a relapse destined to improve anyway!

        • One of the beauties of this effort was that it enabled us to shrug off preconceptions about age, degree of disability and disease activity. You find people aged >70 years, or people in their 30s with a fixed EDSS of 8.0, both with Gd+ lesions. However limited the phase III trial evidence may be at that age or level of disability, blood-brain-barrier breakdown and acute inflammation will never be beneficial in MS.

    • Numbers of people with complete datasets so far too small to test this formally. At next cut, we’ll have more, in part due to remote monitoring.

  • As always, many thanks to Prof K and the rest of the team for work on Cladribine.

    Many thanks to MD for sharing the information.

    • And thanks from me to both MD and Prof K.
      18 months post 2nd year of cladribine, still showing some improvements in fatigue and cognition, but would really like to know what happens after that if I need another course

  • We all know cladribine works. But no one knows how long it takes before its effect starts to wear off, and what should be done to prevent new brain damage.

    Research on IRTs should really start focusing on what to do next instead of «wait and watch» (which is the most ignorant treatment strategy ever).

    In Sweden and Norway they are pushing rituximab on everyone because it is cheap and off label. Why they don’t also offer subcutaneous cladribine, I dont know.

    • Retreatment will become a pressing issue similar to alemtuzumab. Currently, we’re relying on follow-up and EDA, some have received a 3rd course.

      • I know, this is what everyone keeps telling me, both you guys, ProfG did, and Merck does.

        However, knowing for sure that cladribine does not prevent disease activity forever (for the large majority of people), starting this medication is the same as being doomed to have more brain damage. And if there is one thing I have learned from Dr. Boster’s youtube channel and this Blog (MS Blog), with the medication we have today, this should not be necessary.

        So why are no one looking into the strategies put forward by ProfG in his “Cladribine re-treatment” post?

        1. What is the expected efficacy duration of Cladribine, for most people? (I guess now it is stated to be 4 years, based on previous trials)
        2. What are the best options following the defined duration to maintain NEDA` (plus all the other acronyms being used to describe disease progression, absence etc.)?

        Please, if someone could just say something about how this is being worked on/ researched?

        • Does not prevent disease activity forever (for the large majority of people)….is this true?
          Alemtuzumab may not need to be given for ever….The key is when you start these treatments again we heard this week of the London experience of HSCT and again is frank progression is established it is not stopped by HSCT

          Cladribine + BTK inhibitor?. Icompanies told what they were planning they would all do the same thing.

        • In the CLASSIC-MS study of pwMS participating in CLARITY (n=93) and CLARITY Ext (n=79), 69% did not receive any further DMT for a median of >10 years after their last dose; 24% received a platform injectable.

  • Encouraging paper thank you 🙂

    Re progressive MS NEPAD 62% and NEPAD* 56% over a year, how does this compare to what might be expected from untreated progressive MS?
    Anecdotally noticing getting worse over a year is the norm?

    So for NEPAD data I guess can look at the placebo arms of previous trials eg EXPAND (siponimod)? But for hand function… CHARIOT will be the first?

    • In ORATORIO (ocrelizumab in PPMS) the proportion of patients with NEPAD from baseline to week 120 was 30% in people on OCR compared to 9.4% in those on placebo. Please note that was a controlled trial with n= 234 people in the placebo and n=465 in the OCR arm, so a far more robust result. Ours are preliminary data.

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