Cladribine…Should this not be on the WHO essential drug list

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Efficacy and Safety of Intravenous Cladribine in Patients with Rapidly Evolving or Early Secondary Progressive Multiple Sclerosis. Alshamrani F, Alnajashi H, Almuaigel MF. Cureus. 2020;12:e6995. doi: 10.7759/cureus.6995

Background Multiple sclerosis (MS) is an autoimmune and demyelinating inflammatory disease that affects the central nervous system (CNS). The etiology of the disease remains unknown. Multiple theories highlight genetic, environmental, and infectious factors that may a role. MS is considered as the main cause of disability in young people. Cladribine, known chemically as (2-Chloro-2′-deoxyadenosine), is a purine analog chemotherapy used for hairy cell leukemia and other B-cell lymphomas. The goal of this study was to evaluate the safety and efficacy of cladribine in patients with rapidly evolving or early secondary progressive MS.

Methods This observational, single-center, retrospective chart review at the MS Clinic in the Ottawa General Hospital, Ottawa, Canada. A total of 24 patients (median Expanded Disability Status Scale (EDSS) of 4.5) received cladribine (0.07 mg/kg/day) for four consecutive days every six months for ≥ 2 cycles (0.56mg/kg per year which is abit lower that the oral variant equivalent) with further cycles depending on lymphocyte recovery or disease activity to a maximum of eight cycles from 2005 until 2016 were included. Four patients who were already diagnosed with rapidly evolving or early secondary progressive multiple sclerosis (SPMS) were induced with cladribine. We evaluated relapse, EDSS, and magnetic resonance imaging (MRI) results. Results Out of 24 patients (ages ranging from 30 – 60), 80% were female. Median follow-up time was seven years. The mean relapse rate in the two years before patients were given cladribine was 1.25. Twenty patients had previously received multiple disease-modifying therapies (DMTs) (≥ 2) prior to receiving cladribine. Following cladribine, eight patients suffered 10 relapses (33.3% of the cohort. This would be lower than alemtuzumab). Annualized relapse rates (ARRs) were reduced from 1.25 to 0.42, which was statistically significant (p-value = 0.002). There was no mean difference in EDSS (p-value = 0.06): 16% deteriorated, 62% did not change, and 12.5% improved. New MRI activity (new T2 or Gad+ lesions) was noted in only seven of 24 patients.  Conclusion Parenteral cladribine reduced the relapse rate from 1.25 to 0.42, which was statistically significant (p-value = 0.002). MRI activity in patients with rapidly evolving or early secondary progressive multiple sclerosis had a reasonable safety profile.

CoI: Multiple.

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7 comments

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  • I don’t get why all hospitals doesn’t use the intraveneous version. Here in Norway it is the hospitals who take the bill. I’m sure they are capable of using it in liquid form.

      • Sorry, I just used the article’s wording; what I meant was that I don’t get it why the norwegian hospitals by Mavenclad (cladribine tablets) for millions of NOKs, when cladribine is available in liquid form. If it could be taken as a subcutaneous injection instead of as an infusion, that is even better.

        Actually, the norwegian government is refusing to make an agreement with Roche on Ocrevus because they don’t see any added value over Rituximab/ MabThere, so I am surprised they are not taking the same route for Cladribine.

        But a quick question; when the article states “33.3% of the cohort. This would be lower than alemtuzumab” can you elaborate on what this means?

        Thank you for keeping the blog great, I truly appreciate it.

        • Yes but it is not a trial and the demographics of the trial are different. However the NEDA rate for cladribine in the pivotal trial was lower than that found with alemtuzumab. 33% says few people showed disease activity. We had planned on doing a head to head trial against alemtuzumab to show there was no difference by not putting 600 people on alemtuzuab we would have saved the NHS over £32,000,000 but we could not get it funded, we tried to do it in Mexico and had lots of centres signed up, but we could not get that funded from the USA or the UK. We will now never now if they are the same in terms of efficacy, side-effect wise cladribine appears to be lower

          Cladribine is essentially a chemical CD19 plus abit more, as it depletes abit more than CD20. The Scandi’s (no disrespect intended..i’m fan of our Nordic friends) should do a trial of rituximab verses cladribine. You could treat 5-6 people for every one on rituximab I bet there would be not much difference. If they follwo their own logic biosimilars could be used

          As for ocrelizumab, I think COVID is going to make a dint in its sales,once ofatumumab comes in as it has more rapid reversibility

          • There is actually an ongoing trial comparing cladribine tablets with rituximab. I just wrote the lead investigator and asked them why they did not include off-label cladribine (Litak) instead of tablets. I am afraid that if the results come out in favour of rituximab measured in annulized relapse rate, the government will exclude Mavenclad from the list of available DMTs. Although I am a fan of Rituximab, I do recognize that each drug has their benefits and would like to keep both on the list.

            If they had compared with off label cladribine, this fear would be less real.

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