Comment
FREEDOMS II will probably not change the status of fingolimod from a second-line to a first-line treatment for relapsing-remitting multiple sclerosis. Only postmarketing experience in large cohorts of patients will make it possible to weigh the benefits against risks and provide the evidence needed to justify changes in the labelling of fingolimod for treatment of relapsingremitting multiple sclerosis. In the European Union, the European Medicines Agency has given fingolimod the same labeling as natalizumab and it would be preferred to natalizumab in patients with antibodies against John Cunningham (JC) virus in the blood, which indicates that they have been infected with a virus that might cause progressive multifocal encephalomyelitis if treated with natalizumab.8 Dimethyl fumarate, which seems to have comparable efficacy to fingolimod, was approved this year in the European Union as an oral first-line treatment for relapsing-remitting multiple sclerosis and could even be an alternative to fingolimod in patients with breakthrough disease activity on other first-line treatments. Hence, a head-to-head trial of fingolimod and dimethyl fumarate is warranted. Fingolimod crosses the blood–brain barrier to cells in the CNS that express sphingosine-1-phosphate receptors (neurons, astrocytes, oligodendrocytes, and microglia) in sufficient quantities that might have an effect on CNS
inflammation and neurodegeneration. The results of the fingolimod trial in primary progressive multiple sclerosis (INFORMS [NCT00731692]) are also awaited with great interest. Per Soelberg Sorensen Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, DK2100 Copenhagen, Denmark [email protected] I have served on scientific advisory boards for Merck Serono, Teva, Novartis, Sanofi-Aventis, and Biogen Idec; I have received research support from Biogen Idec, Novartis, and Sanofi-Aventis; and I have received speaker honoraria from Merck Serono, Novartis, Teva, Sanofi-Aventis, Biogen Idec, and Genzyme. 1
2 3
4 5 6
7
8
Kappos L, Radue EW, O’Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010; 362: 387–401. Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010; 362: 402–15. Calabresi PA, Radue E-W, Goodin D, et al. Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Neurology 2014; published online March 28. http://dx.doi. org/10.1016/S1474-4422(14)70049-3. Gold R, Kappos L, Arnold DL, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med 2012; 367: 1098–107. Fox RJ, Miller DH, Phillips JT, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 2012; 367: 1087–97. Cohen JA, Coles AJ, Arnold DL, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet 2012; 380: 1819–28. Uitdehaag BM, Barkhof F, Coyle PK, Gardner JD, Jeffery DR, Mikol DD. The changing face of multiple sclerosis clinical trial populations. Curr Med Res Opin 2011; 27: 1529–37. Sorensen PS, Bertolotto A, Edan G, et al. Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab. Mult Scler 2012; 18: 143–52.
Occupational therapy for Parkinson’s disease: increasing awareness Despite progress in the medical and surgical treatments of Parkinson’s disease, patients still develop difficulties with gait, balance, and activities of daily living, which affect their quality of life and ability for self-care. Rehabilitation specialists, in physical therapy, occupational therapy, and speech therapy, play an important part in delivery of care. There is a growing body of evidence for the role of physical therapy to reduce disability and optimise quality of life in Parkinson’s disease,1 and well-designed studies in occupational therapy are needed. In The Lancet Neurology, Ingrid Sturkenboom and colleagues2 now provide evidence that occupational therapy is beneficial in Parkinson’s disease. www.thelancet.com/neurology Vol 13 June 2014
Sturkenboom and colleagues did a multicentre, randomised controlled trial in 191 patients: 124 in the intervention group and 67 in the control group. The intervention took place at home over a period of 10 weeks, and participants were assessed at baseline and at 3 months and 6 months after the intervention by a masked assessor. The occupational therapy intervention was tailored to each patient’s particular needs, concerns, and social situation; the control group did not receive any occupational therapy. The efficacy of the intervention was primarily assessed by the change in score on the Canadian Occupational Performance Measure (COPM),3 which rates a patient’s self-perceived performance in
Published Online April 9, 2014 http://dx.doi.org/10.1016/ S1474-4422(14)70074-2 See Articles page 557
527
Comment
three to five areas of difficulties with activities of daily living identified at baseline, and measures both patients’ perceived performance (COPM-P) and satisfaction (COPM-S). Caregivers’ quality of life and perceived burden were also assessed in both groups. At the assessments at 3 months and 6 months, the intervention group showed a significantly better score relative to the control group on the COPM-P and COPM-S (all p
FREEDOMS II will probably not change the status of fingolimod from a second-line to a first-line treatment for relapsing-remitting multiple sclerosis. Only postmarketing experience in large cohorts of patients will make it possible to weigh the benefits against risks and provide the evidence needed to justify changes in the labelling of fingolimod for treatment of relapsingremitting multiple sclerosis. In the European Union, the European Medicines Agency has given fingolimod the same labeling as natalizumab and it would be preferred to natalizumab in patients with antibodies against John Cunningham (JC) virus in the blood, which indicates that they have been infected with a virus that might cause progressive multifocal encephalomyelitis if treated with natalizumab.8 Dimethyl fumarate, which seems to have comparable efficacy to fingolimod, was approved this year in the European Union as an oral first-line treatment for relapsing-remitting multiple sclerosis and could even be an alternative to fingolimod in patients with breakthrough disease activity on other first-line treatments. Hence, a head-to-head trial of fingolimod and dimethyl fumarate is warranted. Fingolimod crosses the blood–brain barrier to cells in the CNS that express sphingosine-1-phosphate receptors (neurons, astrocytes, oligodendrocytes, and microglia) in sufficient quantities that might have an effect on CNS
inflammation and neurodegeneration. The results of the fingolimod trial in primary progressive multiple sclerosis (INFORMS [NCT00731692]) are also awaited with great interest. Per Soelberg Sorensen Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, DK2100 Copenhagen, Denmark [email protected] I have served on scientific advisory boards for Merck Serono, Teva, Novartis, Sanofi-Aventis, and Biogen Idec; I have received research support from Biogen Idec, Novartis, and Sanofi-Aventis; and I have received speaker honoraria from Merck Serono, Novartis, Teva, Sanofi-Aventis, Biogen Idec, and Genzyme. 1
2 3
4 5 6
7
8
Kappos L, Radue EW, O’Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010; 362: 387–401. Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010; 362: 402–15. Calabresi PA, Radue E-W, Goodin D, et al. Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Neurology 2014; published online March 28. http://dx.doi. org/10.1016/S1474-4422(14)70049-3. Gold R, Kappos L, Arnold DL, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med 2012; 367: 1098–107. Fox RJ, Miller DH, Phillips JT, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 2012; 367: 1087–97. Cohen JA, Coles AJ, Arnold DL, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet 2012; 380: 1819–28. Uitdehaag BM, Barkhof F, Coyle PK, Gardner JD, Jeffery DR, Mikol DD. The changing face of multiple sclerosis clinical trial populations. Curr Med Res Opin 2011; 27: 1529–37. Sorensen PS, Bertolotto A, Edan G, et al. Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab. Mult Scler 2012; 18: 143–52.
Occupational therapy for Parkinson’s disease: increasing awareness Despite progress in the medical and surgical treatments of Parkinson’s disease, patients still develop difficulties with gait, balance, and activities of daily living, which affect their quality of life and ability for self-care. Rehabilitation specialists, in physical therapy, occupational therapy, and speech therapy, play an important part in delivery of care. There is a growing body of evidence for the role of physical therapy to reduce disability and optimise quality of life in Parkinson’s disease,1 and well-designed studies in occupational therapy are needed. In The Lancet Neurology, Ingrid Sturkenboom and colleagues2 now provide evidence that occupational therapy is beneficial in Parkinson’s disease. www.thelancet.com/neurology Vol 13 June 2014
Sturkenboom and colleagues did a multicentre, randomised controlled trial in 191 patients: 124 in the intervention group and 67 in the control group. The intervention took place at home over a period of 10 weeks, and participants were assessed at baseline and at 3 months and 6 months after the intervention by a masked assessor. The occupational therapy intervention was tailored to each patient’s particular needs, concerns, and social situation; the control group did not receive any occupational therapy. The efficacy of the intervention was primarily assessed by the change in score on the Canadian Occupational Performance Measure (COPM),3 which rates a patient’s self-perceived performance in
Published Online April 9, 2014 http://dx.doi.org/10.1016/ S1474-4422(14)70074-2 See Articles page 557
527
Comment
three to five areas of difficulties with activities of daily living identified at baseline, and measures both patients’ perceived performance (COPM-P) and satisfaction (COPM-S). Caregivers’ quality of life and perceived burden were also assessed in both groups. At the assessments at 3 months and 6 months, the intervention group showed a significantly better score relative to the control group on the COPM-P and COPM-S (all p
