Contributions
Abstract: EP1366
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - MS and gender
Introduction: Rebound of disease activity beyond pretreatment levels has been associated with discontinuation of highly-effective multiple sclerosis (MS) therapies, especially natalizumab, but also after stopping fingolimod. This fact is important especially for pregnancy planning due to that most MS therapies must be discontinued to avoid potential fetal risks.
Objectives: To (1) describe the frequency of rebound activity, clinical features and outcome, after cessation of fingolimod for childbearing desire, and (2) analyze the contributor factors associated with early activity reappearance.
Methods: Clinical and radiological data of 7 MS women from our center who discontinued fingolimod from May 2012 to March 2018 for pregnancy planning.
Results: Three of the 7 (42.8%) patients had a rebound of the disease after stopping fingolimod, and all of them became pregnant. The median time to pregnancy was 76 days (range, 0-263). Before pregnancy only one patient had a relapse (214 days after discontinuation). During pregnancy, the 3 patients had a mean (standard deviation, SD) of 5.3 (1.3) relapses, and 13 of the 16 relapses were treated with intravenous steroids and/or immunoglobulins. They had a median increase of the Expanded Disability Status Scale of 3 points (range, 2-4), and a median increase of 27 (range, 9-40) new gadolinium-enhancing lesions and 38 (range, 21-70) of new T2 lesions seen on a magnetic resonance imaging performed within the first three weeks after delivery. The 3 pregnancies resulted in delivery of healthy babies with low birth weight in two of them. A strong correlation was found between the lymphocyte count at fingolimod onset and the annualized relapse rate in the period without therapy (r= -0.84, p=0.005). The time to first relapse was shorter in those patients who had < 300/µl lymphocytes in the 3 first months of fingolimod onset (median time 46 vs 426 days, p=0.010).
Conclusions: Fingolimod rebound represents a severe long-lasting inflammatory syndrome that may affect up to 40% of the MS women who discontinuing fingolimod to attempt pregnancy. Lymphopenia < 300/µl within the first 3 months from fingolimod onset may predispose to suffer early and higher MS activity after cessation. It takes priority to determine the best discontinuing fingolimod strategy in MS women with childbearing potential to diminish the risk for this syndrome.
Disclosure: MS received speaker honoraria from Sanofi, Novartis and Biogen, and funding from the Generalitat de Catalunya (SLT002/16/00354); YB received speaking honoraria from Biogen, Novartis and Genzyme; CM, HA, E M-H, FG: declare nothing to disclose; N S-V: receives funding from the Spanish Government (Instituto de Salud Carlos III, Spain, and Fondo Europeo de Desarrollo Regional [FEDER, FI16/00251], and the Predoctoral Grant for Health Research) and compensation for consulting services and speaker honoraria from Sanofi, Bayer-Schering, Novartis and Biogen-Idec; IZ travel reimbursement from Genzyme and Biogen; I P-V travel reimbursement from Roche and Genzyme, and she holds stock in Aura Innovative Robotics; E M-L researcher in the OCTIMS study, an observational study (that involves no specific drugs) to validate SD-OCT as a biomarker for MS, sponsored by Novartis. She has received honoraria from Biogen, Roche, Novartis and Sanofi for speaking, and a travel reimbursement from Roche, Biogen, Novartis and Sanofi; SL received speaker honoraria from Biogen Idec, Novartis, Teva, Genzyme and Merck, and research support from the Spanish Government (PI15/00587); AS received compensation for consulting services and speaker honoraria from Bayer-Schering, Merck-Serono, Biogen-Idec, Sanofi-Aventis, TEVA and Novartis.
Abstract: EP1366
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - MS and gender
Introduction: Rebound of disease activity beyond pretreatment levels has been associated with discontinuation of highly-effective multiple sclerosis (MS) therapies, especially natalizumab, but also after stopping fingolimod. This fact is important especially for pregnancy planning due to that most MS therapies must be discontinued to avoid potential fetal risks.
Objectives: To (1) describe the frequency of rebound activity, clinical features and outcome, after cessation of fingolimod for childbearing desire, and (2) analyze the contributor factors associated with early activity reappearance.
Methods: Clinical and radiological data of 7 MS women from our center who discontinued fingolimod from May 2012 to March 2018 for pregnancy planning.
Results: Three of the 7 (42.8%) patients had a rebound of the disease after stopping fingolimod, and all of them became pregnant. The median time to pregnancy was 76 days (range, 0-263). Before pregnancy only one patient had a relapse (214 days after discontinuation). During pregnancy, the 3 patients had a mean (standard deviation, SD) of 5.3 (1.3) relapses, and 13 of the 16 relapses were treated with intravenous steroids and/or immunoglobulins. They had a median increase of the Expanded Disability Status Scale of 3 points (range, 2-4), and a median increase of 27 (range, 9-40) new gadolinium-enhancing lesions and 38 (range, 21-70) of new T2 lesions seen on a magnetic resonance imaging performed within the first three weeks after delivery. The 3 pregnancies resulted in delivery of healthy babies with low birth weight in two of them. A strong correlation was found between the lymphocyte count at fingolimod onset and the annualized relapse rate in the period without therapy (r= -0.84, p=0.005). The time to first relapse was shorter in those patients who had < 300/µl lymphocytes in the 3 first months of fingolimod onset (median time 46 vs 426 days, p=0.010).
Conclusions: Fingolimod rebound represents a severe long-lasting inflammatory syndrome that may affect up to 40% of the MS women who discontinuing fingolimod to attempt pregnancy. Lymphopenia < 300/µl within the first 3 months from fingolimod onset may predispose to suffer early and higher MS activity after cessation. It takes priority to determine the best discontinuing fingolimod strategy in MS women with childbearing potential to diminish the risk for this syndrome.
Disclosure: MS received speaker honoraria from Sanofi, Novartis and Biogen, and funding from the Generalitat de Catalunya (SLT002/16/00354); YB received speaking honoraria from Biogen, Novartis and Genzyme; CM, HA, E M-H, FG: declare nothing to disclose; N S-V: receives funding from the Spanish Government (Instituto de Salud Carlos III, Spain, and Fondo Europeo de Desarrollo Regional [FEDER, FI16/00251], and the Predoctoral Grant for Health Research) and compensation for consulting services and speaker honoraria from Sanofi, Bayer-Schering, Novartis and Biogen-Idec; IZ travel reimbursement from Genzyme and Biogen; I P-V travel reimbursement from Roche and Genzyme, and she holds stock in Aura Innovative Robotics; E M-L researcher in the OCTIMS study, an observational study (that involves no specific drugs) to validate SD-OCT as a biomarker for MS, sponsored by Novartis. She has received honoraria from Biogen, Roche, Novartis and Sanofi for speaking, and a travel reimbursement from Roche, Biogen, Novartis and Sanofi; SL received speaker honoraria from Biogen Idec, Novartis, Teva, Genzyme and Merck, and research support from the Spanish Government (PI15/00587); AS received compensation for consulting services and speaker honoraria from Bayer-Schering, Merck-Serono, Biogen-Idec, Sanofi-Aventis, TEVA and Novartis.