Sunday, 2 October 2016

NeuroSpeak & #ThinkHand: Lublin Poland

Will cladribine work in progressive MS? Only way to find-out is to do a study. #NeuroSpeak #ThinkHand #MSBlog

As promised my slides from my presentation at the Neuro Forum meeting in Lublin, Poland. I feel very much at home here amongst a friends of cladribine. The MS clinic in Lublin has the most experience in the use of off-label cladribine, having treated ~400 patients with the drug. There results are very promising and my friend, and colleague, Professor Konrad Rejdak, who is now the head of department in Lublin, is studying the long-term impact of the cladribine on the disease. He presented a poster at ECTRIMS on the safety of using the drug in SPMS. 

We are convinced that cladribine may have an impact on the pathology of MS within the CNS and are hoping to get a trial funded to test cladribine in more advanced MS, including pwMS in wheelchairs. This is one of our motivations for running the #ThinkHand campaign. I have urged Professor Rejdak and his colleagues to study the impact of cladribine on the intrathecal (within the CNS) immune response. If we can show that cladribine impacts on MS pathology within the CNS then we will have a much stronger case for doing a trial in progressive MS. DrK is leading on this study and is quite advanced stage in its design. Over the next few months Barts-MS will be making a strong case for getting this trial funded and started. 





P1146: Rejdak et al. Induction therapy of relapsing secondary progressive multiple sclerosis using generic cladribine. ECTRIMS 2016.

Background: Evidence suggests Cladribine is an effective, safe and convenient disease modifying induction therapy for people with multiple sclerosis.

Objective: To report our experience using subcutaneous Cladribine as a treatment for people with relapsing secondary progressive MS (SPMS).

Methods: Study was performed at the Department of Neurology,Medical University of Lublin and received local ethics approval.Cladribine (Biodribine) was offered to 45 patients with SPMS (30 women and 15 men; aged 42 years [25-56]; EDSS = 6 [2-7], disease duration= 10 years [5-15]; median, range). Cladribine was given subcutaneously at a dose of 0.07 mg/kg/day for 4-6 days.
Treatment courses were given every 5 weeks for a total of five courses (total dose: 1.4 - 2.1 mg/kg). Blood samples were collected before treatment initiation, before each subsequent treatment course, and three months after the last dose. Patients were followed-up for initial 28 weeks of treatment course, and there was extended follow up of up to 5 years to record relapses, disability progression and adverse events.

Results: All patients completed the follow-up period. Cladribine induced a gradual decline in the total lymphocyte count from 1.8±0.5 (x10*9/L; mean±SD) at baseline to 1.5±0.5 after the 1st, 1.3±0.5 after the 2nd; 1.0±0.4 after the 3rd; 1.0±0.4 after the 4th, and 0.9±0.3 after the 5th doses, respectively. Lymphocyte count then remained stable for 3 months after follow up (0.9±0.4). The total white cell count was also reduced however remained within the normal range throughout the observation period (6.4±1.6 x10*9/L at baseline, and 5.5±2.7 at last follow up). Other blood counts remained unaffected. In seven cases mild infections occurred during the follow-up period. No serious adverse events, relapses or disability progression were observed.

Conclusion: Cladribine induction therapy was safe and well tolerated in people with SPMS followed up for 28 weeks. Extended follow-up is underway to collect further data on safety and efficacy.

CoI: multiple

5 comments:

  1. Prof G do you have a home life? I have been following your travelling in the last few weeks and you don't seem to spend much time at home; MS Life, MS Ireland and now Neuro Forum in Poland on consecutive weekends. You need to take some time off!

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    1. Just back from Lublin, and yes, I agree I am travelling too much and doing too much MS. Your comment could have been made by my wife, one of my daughters or even my dog Cody if he could talk. Believe, it or not, he misses his walks with me on the weekend as much as I do. I need time and out and I am very tired, but have 'many meetings to go' before I sleep.

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  2. A fascinating post, Prof G. A few points (and from someone who is on Cladribine therapy...)

    1. Rice et al. in 2000 published a report that found no impact of Cladribine versus placebo on progression rates over a 12 month period (https://www.ncbi.nlm.nih.gov/pubmed/10720289).
    Are you suggesting that Rice (and other trials with other drugs on PPMS / SPMS) were just too short? That you might see a divergence of progression both over time and also over function (i.e. focusing too much on legs might be too late and that hands should be the thing looked at)? Could you not just go back to Rice and ask him to contact the patients treated in both groups and see how they were faring 16 years later?

    2. Have you considered - too - trying to do a progressive trial with combination therapies? Cladribine and Alpha Lipoic Acid (ECTRIMS saw a presentation that showed significant differences in brain volume size between those who took ALA and placebo)? Or Cladribine and Inteferon? Or Cladribine and something else?

    3. Finally, in an age of effective RRMS DMTs, and induction therapies, etc,. how can you begin to separate the wheat from the chaff when it comes to new drug impact on progression? If you argue a lag period and then test Cladribine on SPMS patients, how can you prove that the Cladribine was working and not a prior drug's delayed effect at work? For instance, Terry Wahls talks about how eating a mountain of kale etc. every day stopped her progressive MS. But she mentions in casual passing that prior to her Paleo-style diet she also had chemotherapy for her progression. What was working? The drugs or the greens? Or - as I think - both? If MS is a disease caused by a cumulation of factors, perhaps you need a cumulation of treatments (neuroprotection, diet, anti-inflammatory, mitochondrial stimulation etc.) to get the body back to some normalcy. If this is true, then no single drug / intervention will stop progression - you need a holistic treatment approach.

    Good luck in Poland. I wonder if Brexit will impact such important sharing of information...

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  3. 1. Rice a trial of 12months is too short maybe DrK will do a post on this trial
    2. Have had thoughts

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  4. Why are the nurses at Barts only allowed to give two courses of Cladribine a year, if this study is suggesting that five are safe? What if two is too few?

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