Natalizumab Discontinuation and Treatment Strategies in Patients with Multiple Sclerosis (MS): A Retrospective Study from Two Italian MS Centers

被引:41
作者
Lo Re M. [1 ]
Capobianco M. [2 ]
Ragonese P. [1 ]
Realmuto S. [1 ]
Malucchi S. [2 ]
Berchialla P. [3 ]
Salemi G. [1 ]
Bertolotto A. [2 ]
机构
[1] Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo
[2] Regional Multiple Sclerosis Centre, San Luigi Gonzaga Hospital, Orbassano
[3] Department of Clinical and Biological Sciences, University of Turin, Torino
关键词
Disease reactivation; First-line therapies; Multiple sclerosis; Natalizumab discontinuation; Rebound; Second-line therapies;
D O I
10.1007/s40120-015-0038-9
中图分类号
学科分类号
摘要
Introduction: Natalizumab (NTZ) discontinuation can be followed by multiple sclerosis (MS) disease reactivation. Currently no disease-modifying drug (DMD) has been shown to be able to abolish disease reactivation. The aims of the current study were: (1) to determine the frequency of MS reactivation after NTZ discontinuation; (2) to evaluate predictors of reactivation risk, and (3) to compare the effect of different treatments in reducing this risk. Methods: Data from 132 patients with MS followed-up for 2 years before NTZ treatment and 1 year after interruption were collected from two Italian MS centers and retrospectively evaluated. Results: Overall, 72 of 132 patients (54.5%) had relapses after NTZ discontinuation and 60 of 125 patients (48%), who had magnetic resonance imaging, had radiological reactivation. Rebound was observed in 28 of 132 patients (21.2%). A higher number of relapses in the 2 years before NTZ treatment, a longer washout period, and a lower number NTZ infusions correlated with reactivation and rebound. Untreated patients (n = 37) had higher clinical and radiological activity and rebound in comparison to patients receiving DMDs. Moreover, a lower risk of relapses was found in patients treated with second-line therapies (NTZ and fingolimod) than in those treated with first-line therapies (interferon beta, glatiramer acetate, teriflunomide, azathioprine). Interestingly, no disease reactivation in off-label treatment (rituximab, autologous hematopoietic stem cell transplantation) was observed. Conclusion: NTZ discontinuation is a risk for MS reactivation and rebound. An alternative treatment should be promptly resumed mainly in patients with a previous very active disease course and with a shorter NTZ therapy. Second-line therapies demonstrate superiority in preventing relapses after NTZ discontinuation. © 2015, The Author(s).
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页码:147 / 157
页数:10
相关论文
共 37 条
[1]  
Polman C.H., O'Connor P.W., Havrdova E., Et al., A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis, N Engl J Med, 354, pp. 899-910, (2006)
[2]  
Rudick R.A., Stuart W.H., Calabresi P.A., Et al., Natalizumab plus interferon beta 1-a for relapsing multiple sclerosis, N Engl J Med, 354, pp. 911-923, (2006)
[3]  
Baldwin K.J., Hogg J.P., Progressive multifocal leukoencephalopathy in patients with multiple sclerosis, Curr Opin Neurol, 26, pp. 318-3223, (2013)
[4]  
Berger J.R., Aksamit A.J., Clifford D.B., Et al., PML diagnostic criteria, Neurology, 80, pp. 1430-1438, (2013)
[5]  
Sorensen S., Bertolotto A., Edan G., Et al., Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab, Mult Scler, 18, 2, pp. 143-152, (2012)
[6]  
Fox R.J., Cree B.A., De Seze J., Et al., MS disease activity in RESTORE: a randomized 24-week natalizumab treatment interruption study, Neurology, 82, pp. 1491-1498, (2014)
[7]  
O'Connor P.W., Goodman A., Kappos L., Et al., Disease activity return during natalizumab treatment interruption in patients with multiple sclerosis, Neurology, 76, pp. 1858-1865, (2011)
[8]  
Berger J.R., Centonze D., Comi G., Et al., Considerations on discontinuing natalizumab for the treatment of multiple sclerosis, Ann Neurol, 68, 3, pp. 409-410, (2010)
[9]  
Sangalli F., Moiola L., Ferre L., Et al., Long-term management of natalizumab discontinuation in a large monocentric cohort of multiple sclerosis patients, Mult Scler Relat Disord, 3, pp. 520-526, (2014)
[10]  
Killestein J., Vennegoor A., Strijbis E.M., Et al., Natalizumab drug holiday in multiple sclerosis: poorly tolerated, Ann Neurol, 68, pp. 392-395, (2010)