Friday, 18 August 2017

Quality of life is better on effective DMT

Positive impact of cladribine on quality of life in people with relapsing multiple sclerosis.
Dayo Afolabi, Christo Albor, Lukasz Zalewski, Dan R Altmann, David Baker
and Klaus Schmierer. Mult Scler J, August 17, 2017

Abstract
Background: A number of elements of the pivotal ‘cladribine tablets treating multiple sclerosis orally’ (CLARITY) trial have remained unpublished.
Objective: To report the impact of cladribine on health-related quality of life (QoL) in people with relapsing multiple sclerosis (pwRMS).
Methods: QoL data from the phase III trial of two different doses (3.5 and 5.25 mg/kg) of oral cladribine in pwRMS were acquired from the European Medicines Agency through Freedom of Information. Spearman’s rank correlation was used to analyse the relationship between baseline QoL scores and baseline
Expanded Disability Status Scale (EDSS) scores. Responses of the Euro Quality of Life 5 Dimensions (EQ-5D) and Multiple Sclerosis Quality of Life-54 (MSQOL-54) questionnaires were compared between treatment and control groups using univariate analyses of covariance.
Results: In total, n = 5148 EQ-5D responses and n = 894 MSQOL-54 physical, mental health and dimension scores were extracted. Baseline EQ-5D indices correlated with EDSS scores. After 2 years, pwRMS taking 3.5 (p = .001) and 5.25 mg/kg (p = .022) reported significantly improved EQ-5D index scores compared with placebo. Positive, yet non-significant, differences were detected in MSQOL-54 scores between cladribine and placebo.
Conclusion: Analysis of the CLARITY dataset suggests that, over and above its established clinical efficacy, cladribine leads to improved QoL over 96 weeks. ClinicalTrials.gov identifier: NCT00213135.

We maintained our interest in cladribine even after it had been rejected by the EMA in 2011, because its efficacy was impressive, and its adverse effects comparatively minor. We revealed important pathophysiological insights from the cell count data collected during CLARITY, confirmed that the cancer risk of cladribine in pwMS is no different when compared to licensed DMT, and subsequently started using the drug in a select group of pwMS.

Here's further output from our work on cladribine, an analysis of the quality of life data collected during the largest ever trial of the compound in pwMS. Though the data was available since 2010 nobody cared to analyse and publish them, so we did it after receiving the CLARITY dataset from the EMA through freedom of information, and with zero industry support.

Congratulations to Dayo Afolabi BSc, medical student at Cambridge University and Christo Albor PhD, epidemiologist and currently junior doctor at Barts Health NHS Trust for their excellent work, supported by QMUL IT (Lukasz Zalewski) and Dan Altmann, statistician at QMUL, UCL and The London School for Hygiene & Tropical Medicine.

The abstract summarises the results well, however reading the paper you will learn more about various aspects of this project and the potential of the drug. 

Open access.


CoI: Multiple, however none related to this paper.

14 comments:

  1. Thanks again for your cladribine work! The more we learn, the better this drug looks.

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  2. Thanks for persistent work with c amazing what a talented team can do with a stack of data from a foi request! Look forward to reading the paper :)

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  3. Cladribine was conceived as a “magic bullet” drug and first used to treat cancers of lymphoid tissue, with great benefit for hairy cell leukemia. Not MS .

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    1. Yes cladribine was designed to kill white blood cells by virtue of their expression of DCK which phoprylates adenosine to a toxic product. It is funny that mice white cells do not express much DCK and so it does not work in mice...We found this out the hard way many many years ago.

      Furthermore hairy cell leukemia is a bit like a B memory cell and so they get hit by cladribine as cladribine targets B cells more than T cells by virutue of their DCK expression.

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  4. MD and Dr. Klaus What are the tests needed to know if I can use Cladribine or not?

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    1. We have made our checklist publicly available on slideshare: https://www.slideshare.net/mobile/KlausSchmierer/bartsms-informationpackcladribine Currently under revision following approval (well, almost) of Mavenclad.

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  5. Don't forget that using Gilenya before Cladribine may cause the Cladribine to be ineffective.

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    1. I am not sure why, cladribine can access the bone marrow and lymph glands so cells can't hide from it. However with greater use we may find d out

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    2. Certainly seemed to work in patient with progressive MS who came off fingolimod: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5497536/

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  6. "Over the course of INFORMS, a total duration of 3 years and 7 months including the extension phase, her EDSS deteriorated from 5.5 to 6.5"

    "...fingolimod effectively suppressed disease activity over the course of the study..."

    Clearly, a contradiction.

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    1. Relapses were suppressed there was some progression

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    2. Therefore suppressing disease activity is different than suppressing the disease. People should be aware that you make such a distinction.

      "Six months after taking the last capsule of fingolimod, [] Her EDSS was 8"

      "On follow‐up 3 months after treatment initiation her EDSS had improved to 7"

      Taking out the transient deterioration due to inflammation (rebound), the background disability kept a steady climb (5.5 - 6.5 - 7)

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