Contributions
Abstract: P1215
Type: Poster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Fingolimod is an oral sphingosine-1 receptor antagonist licensed as a second line treatment for relapsing remitting multiple sclerosis. Recent data and real world experience has suggested that discontinuation can be associated with severe rebound refractory to standard corticosteroid therapy.
Methods: 128 patients commenced FIngolimod in a tertiary referral centre between January 2011 and January 2017. 14 (9%) were identified who discontinued Fingolimod during this period. Clinical and demographic data were extracted from paper medical records. Magnetic resonance images were reviewed with an MS neurologist (LC). Rebound syndrome was defined as severe clinical and radiological evidence of new disease activity occurring within 16 weeks of discontinuing Fingolimod.
Results: 3 (21%) patients experienced an unexpectedly severe clinical relapse with significantly increased number of T2 and enhancing lesions on MRI. All had a normal lymphocyte count at time of relapse (range 1.08 - 2.31). Enhancing lesions continued to accumulate despite treatment with intravenous and oral corticosteroids (n=3). Patients were treated with Alemtuzumab (n=2) and Natalizumab (n=1) with subsequent radiological evidence of stability (n=2). Mean(SD) EDSS prior to discontinuation was 2.1(2) and following rebound was 3.8(2.3). 2 discontinued due to planning pregnancy, 1 patient discontinued due to progression of disease.
Discussion: Due to efficacy, ease of administration and tolerability, Fingolimod is a frequently used treatment for relapsing remitting MS. Discontinuation rates are low, as is evidenced in our cohort. A washout period of two months is recommended prior to attempting pregnancy and prior to treatment with another immunosuppressive agent. Our data matches that of previous studies suggesting that there is a significant risk of severe rebound during this washout period. Standard therapy with corticosteroids may not be sufficient to manage clinical relapse in the context of Fingolimod withdrawal. Patients with more active disease may be more vulnerable to rebound and should be counselled appropriately. Treatment with Alemtuzumab and Natalizumab stabilised the aggressive clinical course in our cohort. There are currently no clear guidelines on prevention of this phenomenon.
Disclosure: Maria Gaughan: Nothing to Disclose
Lisa Costelloe has received travel grants and honoraria from Novartis, Biogen-IDEC, Merck-Serono, Sanofi and TEVA.
Abstract: P1215
Type: Poster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Fingolimod is an oral sphingosine-1 receptor antagonist licensed as a second line treatment for relapsing remitting multiple sclerosis. Recent data and real world experience has suggested that discontinuation can be associated with severe rebound refractory to standard corticosteroid therapy.
Methods: 128 patients commenced FIngolimod in a tertiary referral centre between January 2011 and January 2017. 14 (9%) were identified who discontinued Fingolimod during this period. Clinical and demographic data were extracted from paper medical records. Magnetic resonance images were reviewed with an MS neurologist (LC). Rebound syndrome was defined as severe clinical and radiological evidence of new disease activity occurring within 16 weeks of discontinuing Fingolimod.
Results: 3 (21%) patients experienced an unexpectedly severe clinical relapse with significantly increased number of T2 and enhancing lesions on MRI. All had a normal lymphocyte count at time of relapse (range 1.08 - 2.31). Enhancing lesions continued to accumulate despite treatment with intravenous and oral corticosteroids (n=3). Patients were treated with Alemtuzumab (n=2) and Natalizumab (n=1) with subsequent radiological evidence of stability (n=2). Mean(SD) EDSS prior to discontinuation was 2.1(2) and following rebound was 3.8(2.3). 2 discontinued due to planning pregnancy, 1 patient discontinued due to progression of disease.
Discussion: Due to efficacy, ease of administration and tolerability, Fingolimod is a frequently used treatment for relapsing remitting MS. Discontinuation rates are low, as is evidenced in our cohort. A washout period of two months is recommended prior to attempting pregnancy and prior to treatment with another immunosuppressive agent. Our data matches that of previous studies suggesting that there is a significant risk of severe rebound during this washout period. Standard therapy with corticosteroids may not be sufficient to manage clinical relapse in the context of Fingolimod withdrawal. Patients with more active disease may be more vulnerable to rebound and should be counselled appropriately. Treatment with Alemtuzumab and Natalizumab stabilised the aggressive clinical course in our cohort. There are currently no clear guidelines on prevention of this phenomenon.
Disclosure: Maria Gaughan: Nothing to Disclose
Lisa Costelloe has received travel grants and honoraria from Novartis, Biogen-IDEC, Merck-Serono, Sanofi and TEVA.