DX38
Life-Threatening Tumefactive Rebound of Multiple Sclerosis Following Fingolimod Discontinuation
Fingolimod is an oral disease modifying agent, FDA-approved for multiple sclerosis (MS) that acts by selectively retaining T-lymphocytes in secondary lymphoid organs. It has been shown to reduce annualized relapse rate, MRI activity and brain volume loss in patients with relapsing remitting multiple sclerosis (RRMS). However, aggressive rebound activity after withdrawal of fingolimod, especially after 2-4 months following discontinuation has been reported.
Objectives:
We report a case of severe MS relapse after cessation of fingolimod in a patient with previously good baseline function.
Methods:
Case history and literature review
Results:
A 40-year-old woman with a 10-year history of RRMS who was started on Fingolimod in January 2014, presented to the emergency room in August 2017. She was previously on Natalizumab from February 2012 to October 2013 which was discontinued due to very high levels of serum antibodies to JCV. She did very well on fingolimod for two and half years after which she had a relapse, so it was discontinued. Her last dose was in June 2017. After doing well for 6 weeks, she started to have a clinical relapse with gait instability which was treated with high dose steroids with partial improvement initially, followed by worsening lower extremity weakness for which she received steroids again with poor response. Subsequently, she received 5 sessions of plasmapheresis which did not help her much. She was then transferred to the rehabilitation unit where she now developed severe worsening weakness to a point that she was now unable to even move her legs. Magnetic resonance imaging showed numerous coalescing new enhancing lesions throughout the brain and spinal cord along with a large enhancing lesion in the brainstem. Previously independent with ambulation, she now became severely disabled (Expanded Disability Status Score 9.5). Soon she went into respiratory distress and had to be intubated. Multiple laboratory tests in cerebrospinal fluid and serum were sent including aquaporin antibody, JCV PCR which came back negative. She had a prolonged hospital course, complicated by pneumonia and pulmonary embolism. She eventually stabilized with steroids and another 5 sessions of plasmapheresis with moderate improvement. She was then started on rituximab and sent to rehabilitation.
Conclusions:
There have been a number of reports emerging about severe relapses of MS following discontinuation of fingolimod. Even though this type of rebound phenomenon is well known with discontinuation of natalizumab, it is yet to be characterized well with fingolimod withdrawal. Predisposing factors, timeline for discontinuation are yet to be elucidated in addition to preventive measures and timely treatment strategies as this population seem to respond poorly to steroids.