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On Gilenya? Important breaking research on rebound effect after halting drug

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  • On Gilenya? Important breaking research on rebound effect after halting drug

    Original Investigation | May 02, 2016

    Rebound Syndrome in Patients With Multiple Sclerosis After Cessation of Fingolimod Treatment

    Stacy Ellen Hatcher, BS1; Emmanuelle Waubant, MD, PhD1; Bardia Nourbakhsh, MD1; Elizabeth Crabtree-Hartman, MD1; Jennifer S. Graves, MD, PhD, MAS1

    JAMA Neurol. Published online May 02, 2016. doi:10.1001/jamaneurol.2016.0826


    Importance The appropriate sequencing of agents with strong immune system effects has become increasingly important. Transitions require careful balance between safety and protection against relapse. The cases presented herein highlight that rebound events after ceasing fingolimod treatment may happen even with short washout periods (4 weeks) and may perpetuate despite steroid treatment or the immediate use of fast-acting immune therapies, such as rituximab.

    Objective To describe rebound syndrome in patients with multiple sclerosis (MS) after cessation of fingolimod treatment.

    Design, Setting, and Participants Clinical and demographic data were extracted from electronic medical records from the University of California, San Francisco, Multiple Sclerosis Center from January 2014 to December 2015. Magnetic resonance images were reviewed by MS neurologists (J.S.G., E.W., B.N., and E.C.H.). Rebound syndrome was defined as new severe neurological symptoms after ceasing fingolimod treatment, with the development of multiple new or enhancing lesions exceeding baseline activity. We reviewed the PubMed database from January 2010 to December 2015 for similar cases of severe disease reactivation after ceasing fingolimod treatment using search terms fingolimod and either rebound or reactivation. Participants were included if they stopped receiving fingolimod between January 2014 and December 2015. Five patients were identified who experienced rebound after ceasing fingolimod treatment.

    Exposures Each patient received treatment with oral fingolimod for various durations.

    Main Outcomes and Measures Occurrence of rebound after ceasing fingolimod treatment.

    Results The mean (SD) age of the 5 female patients presented in this case series was 35.2 (6.4) years. Of the 46 patients that stopped fingolimod treatment within the 2-year period, 5 (10.9%) experienced severe relapse 4 to 16 weeks after ceasing fingolimod treatment. Despite varying prior severity of relapsing-remitting course, all participants experienced unexpectedly severe clinical relapses accompanied by drastic increases in new or enhancing lesions seen on magnetic resonance imaging evidenced by a median (range) increase of 9 (0->30) new gadolinium-enhancing lesions and a median (range) of 9 (0->30) new T2 lesions. New lesion development persisted for 3 to 6 months despite treatment with corticosteroids (n = 3) and initiation of B-cell depleting therapy (n = 2). In addition, 11 patients were identified through literature review reported as having severe relapses consistent with a rebound syndrome and similar features to our 5 cases.

    Conclusions and Relevance These cases provide evidence for a fingolimod rebound syndrome at a clinically relevant frequency, highlighting the need to determine the best methods for sequencing or discontinuing MS therapies. A large prospective registry or population-based study would be helpful to confirm this rebound phenomenon and to determine contributing factors, including immune biomarkers, that increase risk for this syndrome.

    Dave Bexfield

  • #2
    Prof Gavin Giavanonni blogged about his take on this study. Essentially, if you are doing well, think hard about stopping. And he has some thoughts on women who need to stop for pregnancy reasons.
    Dave Bexfield


    • #3
      I'm a recent addition to the forum. Found you by looking for cooling vests, which was very helpful!

      The following is my anecdotal personal experience. Take it for what it's worth...

      I was part of the clinical trial that brought the drug to market. I spent ~1-2 years on placebo and another ~2-3 on the actual medication, the .5mg being prescribed now (found out after the trial was over). I chose to discontinue the drug so my wife and I could start a family. This was early 2011.

      Within a few months of ending the drug, I only had one instance where I had any sort of trouble. It wasn't a relapse or progression, but I had a few hours at work where I couldn't get words out of my mouth. My thinking was fine, but when I went to talk, things just didn't work. I contacted the neurologist, but the symptoms subsided rather quickly.

      After we had our child (2012), I chose to not go back on a DMD, as I was doing well and was showing no signs of progression... until last January (2015). I had an episode where I lost feeling from my waist down and back spasms for several months. That kicked me in the rear to get back on a DMD. I started back on the gilenya mid 2015 and have been doing well since. Physical therapy is doing wonders for the back.
      Last edited by steedo; 05-25-2016, 11:56 PM.


      • #4
        Welcome steedo! Thanks for the comments. And good to hear you are back on drug. MS can be sneaky and silent in its work.
        Dave Bexfield