Under starting orders, Rebound of Fingolimod Withdrawal

ProfG recently posted on rebound disease activity after fingolimod 
based on the this paper

Rebound Syndrome in Patients With Multiple Sclerosis After Cessation of Fingolimod Treatment. Hatcher SE, Waubant E, Nourbakhsh B, Crabtree-Hartman E, Graves JS. JAMA Neurol. 2016 May 2. doi: 10.1001/jamaneurol.2016.0826. [Epub ahead of print]

So hot on its heels comes this one

Davion JB, Cambron M, Duhin E, Chouraki A, Lacour A, Labauge P, Carra C, Ayrignac X, Vermersch P. Two cases of relapses in primary progressive multiple sclerosis after fingolimod withdrawal.J Neurol. 2016 May 9. [Epub ahead of print]

We report two cases of primary progressive multiple sclerosis (PPMS) included in the INFORMS cohort, experiencing a relapse related to a single MRI gadolinium-enhancing lesion 3 months after fingolimod withdrawal. These two patients share similarities with relapsing-remitting multiple sclerosis cases described in the same situation, suggesting that the initiating process of the active demyelinating plaques is also present in PPMS, even without relapses, but may be triggered as fingolimod is withdrawn. Although the results of the INFORMS study suggest that fingolimod may not slow down the progression, some PPMS patients might still benefit from a disease-modifying treatment.

Rebound disease activity happens with natalizumab. Here immune cells are trapped in the blood and once natalizumab treatment is stopped they are all lined up ready to go back in the brain. In contrast a depleting treatment may be associated with reactivation of disease but as cells come back slowly then reactivation does not come back with a bang. Fingolimod works effectively like natalizumab and trapps cells in the lymph glands. Stop treatment and they are ready to flow back into the blood and then the brain. So it would be surprising if rebound didn't occur.

In this study rebound relapse occurred in people with progressive MS. This occurred following the end of the trial. Will this figure be higher. About 15% of people with PPMS have active lesions, which should be suppressed by fingolimod so they rebound when fingolimod is stopped.

 I think Novartis want to tell us what the real story is.