Contributions
Abstract: EP1668
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Many reports of MS rebound syndrome after cessation of fingolimod have emerged over the last 6 years. This complication, defined as a severe clinical and radiographic reactivation of inflammatory activity exceeding that at baseline, is yet poorly understood.
Aims: To report a case of MS rebound syndrome after fingolimod cessation and review the key features and outcomes of previously reported cases.
Methods: Case report. Systematic review in PubMed using the search terms "fingolimod" + either "rebound", “withdrawal” or “cessation”.
Results: A woman whose first MS symptoms date back to age 30 was initially diagnosed with relapsing-remitting MS and treated with interferon β-1a. At age 49, she was escalated to fingolimod due to breakthrough disease, and remained clinically and radiographically stable for 5 years. The emergence of basal cell carcinoma and coincident onset of secondary progressive MS prompted discontinuation of fingolimod at age 54. Five months later, she presented subacute, severe deterioration of cognitive, cranial nerve, motor, sensory and sphincteric function with >15 gadolinium-enhancing lesions on MRI. High dose IV steroids led to nearly complete recovery. A comprehensive literature review identified a total of 45 cases (87% women) across the spectrum of disease (RRMS [80%], SPMS [13%], PPMS [7%]). At time of rebound, the median age was 36 years (range 19-60) with median duration of disease being 11 years (range 2-42). Median fingolimod treatment duration was 2.5 years (range 0.1-10) and reasons for stopping included adverse events (41%), patient decision (33%), onset of SPMS (9%) and lack of efficacy (9%). Median latency from cessation to rebound was 9 weeks (range 2-39). Lymphocyte count was back to normal in 75%. On MRI, 75% had >10 gadolinium-enhancing lesions. 30% required further-line acute treatment after high dose steroids. Recovery was partial or complete in 85%. 15% had life-threatening complications and 1 patient died.
Conclusions: MS rebound after cessation of fingolimod can occur regardless of age, whether relapsing or progressive, even after short treatment periods. It mostly follows discontinuation for reasons other than lack of efficacy. The fulminant enhancement pattern across all stages and duration of disease suggests widespread blood-brain-barrier dysfunction, which may provide key insights into MS pathophysiology. Our analysis may inform patient counselling and strategies to manage this syndrome.
Disclosure: G. dos Passos has received scholarships from the ECTRIMS, the World Federation of Neurology, and Novartis; funding for research from Biogen, Novartis and Roche; travel grants from Roche, Sanofi-Genzyme and Teva; and fees for editorial content from Bayer, Merck Serono and Roche. R. Geraldes has received support for scientific meetings and courses and honoraria for advisory work from Bayer, Biogen, Merck, Novartis. C. Rigozzi declares no competing interests. P. Monaghan declares no competing interests. G. C. DeLuca is supported by the NIHR Biomedical Research Centre (BRC), Oxford and has research funding from the Oxford BRC, MRC (UK), and Merck-Serono. G. C. DeLuca has received travel expenses from Bay Schering, Biogen Idec, Genzyme, Merck Serono, and Novartis, and honoraria as an invited speaker for Bayer Schering and Novartis.
Abstract: EP1668
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Many reports of MS rebound syndrome after cessation of fingolimod have emerged over the last 6 years. This complication, defined as a severe clinical and radiographic reactivation of inflammatory activity exceeding that at baseline, is yet poorly understood.
Aims: To report a case of MS rebound syndrome after fingolimod cessation and review the key features and outcomes of previously reported cases.
Methods: Case report. Systematic review in PubMed using the search terms "fingolimod" + either "rebound", “withdrawal” or “cessation”.
Results: A woman whose first MS symptoms date back to age 30 was initially diagnosed with relapsing-remitting MS and treated with interferon β-1a. At age 49, she was escalated to fingolimod due to breakthrough disease, and remained clinically and radiographically stable for 5 years. The emergence of basal cell carcinoma and coincident onset of secondary progressive MS prompted discontinuation of fingolimod at age 54. Five months later, she presented subacute, severe deterioration of cognitive, cranial nerve, motor, sensory and sphincteric function with >15 gadolinium-enhancing lesions on MRI. High dose IV steroids led to nearly complete recovery. A comprehensive literature review identified a total of 45 cases (87% women) across the spectrum of disease (RRMS [80%], SPMS [13%], PPMS [7%]). At time of rebound, the median age was 36 years (range 19-60) with median duration of disease being 11 years (range 2-42). Median fingolimod treatment duration was 2.5 years (range 0.1-10) and reasons for stopping included adverse events (41%), patient decision (33%), onset of SPMS (9%) and lack of efficacy (9%). Median latency from cessation to rebound was 9 weeks (range 2-39). Lymphocyte count was back to normal in 75%. On MRI, 75% had >10 gadolinium-enhancing lesions. 30% required further-line acute treatment after high dose steroids. Recovery was partial or complete in 85%. 15% had life-threatening complications and 1 patient died.
Conclusions: MS rebound after cessation of fingolimod can occur regardless of age, whether relapsing or progressive, even after short treatment periods. It mostly follows discontinuation for reasons other than lack of efficacy. The fulminant enhancement pattern across all stages and duration of disease suggests widespread blood-brain-barrier dysfunction, which may provide key insights into MS pathophysiology. Our analysis may inform patient counselling and strategies to manage this syndrome.
Disclosure: G. dos Passos has received scholarships from the ECTRIMS, the World Federation of Neurology, and Novartis; funding for research from Biogen, Novartis and Roche; travel grants from Roche, Sanofi-Genzyme and Teva; and fees for editorial content from Bayer, Merck Serono and Roche. R. Geraldes has received support for scientific meetings and courses and honoraria for advisory work from Bayer, Biogen, Merck, Novartis. C. Rigozzi declares no competing interests. P. Monaghan declares no competing interests. G. C. DeLuca is supported by the NIHR Biomedical Research Centre (BRC), Oxford and has research funding from the Oxford BRC, MRC (UK), and Merck-Serono. G. C. DeLuca has received travel expenses from Bay Schering, Biogen Idec, Genzyme, Merck Serono, and Novartis, and honoraria as an invited speaker for Bayer Schering and Novartis.