Beating the drum for drug C yet again...

Alvarez-Gonzalez CAdams A, Mathews J, Turner BP, Giovannoni G, Baker D, Schmierer K. 
Cladribine to treat disease exacerbation after fingolimod discontinuation in progressive multiple sclerosis.
Ann Clin Transl Neurol 17 May 2017


Rebound disease following cessation of disease modifying treatment (DMT) has been reported in people with both relapsing and progressive multiple sclerosis (pwRMS, pwPMS) questioning strict separation between these two phenotypes. While licensed DMT is available for pwRMS to counter rebound disease, no such option exists for pwPMS. We report on a pwPMS who developed rebound disease, with 45 Gadolinium-enhancing lesions on T1 weighted MRI brain, within 6 months after fingolimod 0.5 mg/day was stopped. Treatment with a short course of subcutaneous cladribine 60 mg led to effective suppression of inflammatory activity and partial recovery with no short-term safety issues or adverse events.

We have been accused of beating the drum for cladribine a little too often. However, please read this case of one of my patients, consider the alternatives, and you may agree there aren't many with a comparable risk:benefit profile. The arguments are detailed in the discussion.

There are a few lessons beyond the effect of the drug used such as:

(i) Even in somebody with the clinical phenotype "primary progressive" MS, the principal mode of disability accrual may be through inflammatory lesions that look no different on MRI from relapsing MS.

(ii) Based on this and previous reports one should be very careful stopping a DMT known to be effective in relapsing MS, even when efficacy in the trial (INFORMS) was not significant *on the cohort level*. In our case, my impression would certainly be that fingolimod did work.

Unfortunately, our acknowledgement appears to have been lost in the course of proof editing the paper: We would like to thank Novartis for letting us use the clinical data of this participant, and for providing the lymphocyte counts, acquired during INFORMS.

CoI: multiple