Cladribine for People with Progressive MS.There are options available

Today we provide further evidence that people with Progressive MS can respond to DMT

MS is neurodegenerative from day one to the last day and is also inflammatory from day one to the last day.

Why don't we do something about the inflammation in MS in every one?. 
The simple answer is due to cost-effectiveness. 

The powers that be have decided that it is not cost-effective to use high cost treatments in people with progressive/Advanced MS.

Will this change with the demonstration that orelizumab is useful in PPMS.

We have been using generic cladribine, which is a potent DMT at a fraction of the cost of other MS drugs. 

Disease activity can be seen on MRI scans.

In this study we have used neurofilaments, as a biomarker of ongoing nerve damage, to help inform on people who may respond to DMT treatment. People treated have shown a marked decrease in neurofilament loss, so the treatment is blocking the processes that lead to nerve damage.

Disease activity in progressive multiple sclerosis can be effectively reduced by cladribine

O. Yildiz, Z. Mao, A. Adams, N. Dubuisson, K. Allen-Philbey, G. Giovannoni, A. Malaspina, D. Baker, S. Gnanapavan, K. Schmierer


  • People with advanced (“progressive”) MS (pwPMS) currently have only one licensed disease modifying treatment (DMT) option (ocrelizumab), and this option is highly restricted to a specific MS subpopulation living in high cost economies
  • The cerebro-spinal fluid (CSF) neurofilament light chain (NfL) level is a sensitive index of ongoing neuro-axonal damage
  • pwPMS who had significantly elevated NfL levels alongside MRI detectable disease activity, were treated using off-label injectable cladribine
  • Cladribine was well tolerated without any side effects and led to reduction of disease activity as indicated by a substantial drop in CSF NfL concentration alongside reduction in active MRI lesions, whilst total lymphocyte counts remained within the normal reference range.



Evidence suggests people with non-relapsing deteriorating (“progressive”) multiple sclerosis (pwPMS) may benefit from disease-modifying immune therapy (DMT). However, only one such treatment (ocrelizumab) has been licensed and is highly restricted to pwPMS suffering from the primary progressive phenotype. The difficulties assessing treatment outcome in pwPMS is one important reason for the lack of respective DMT. The concentration of neurofilaments in the cerebrospinal fluid (CSF) provides a biomarker of neuro-axonal damage, and both neurofilament light (NfL) and heavy chain (NfH) levels have been used as outcome indices and to guide treatment choices.


We report on two pwPMS, who were treated with off-label subcutaneous cladribine undergoing CSF NfL testing, alongside MRI and clinical follow-up, before and after treatment.


Cladribine treatment was well tolerated without any side effects. CSF NfL after treatment revealed significant reduction (by 73% and 80%, respectively) corroborating the MRI detectable drop in disease activity. Disability mildly progressed in one, and remained stable in the other pwPMS.


pwPMS with detectable disease activity (MRI, elevated NfL) should be considered for DMT. NfL appears to be a sensitive index of treatment effect in pwPMS, and may be a useful outcome in clinical trials targeting this patient group. Over and above its licensed indication (relapsing MS), cladribine may be an effective treatment option for pwPMS.

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CoI This is work by DrK and other members of the Team