Impact of previous disease-modifying treatment on effectiveness and safety outcomes, among patients with multiple sclerosis treated with alemtuzumab

ObjectivesAlemtuzumab is effective in patients with active multiple sclerosis but has a complex safety profile, including the development of secondary autoimmunity. Most of patients enrolled in randomised clinical trials with alemtuzumab were either treatment naïve or pretreated with injectable substances. Other previous disease-modifying treatments (DMTs) were not used in the study cohorts, and therefore, associated risks might yet remain unidentified.MethodsWe retrospectively evaluated a prospective dual-centre alemtuzumab cohort of 170 patients. We examined the baseline characteristics as well as safety and effectiveness outcomes, including the time to first relapse, the time to 3 months confirmed disability worsening and the time to secondary autoimmunity.ResultsThe regression analysis showed that, among all previously used DMTs, the pretreatment with fingolimod (n=33 HRs for the time to first relapse (HR 5.420, 95% CI 2.520 to 11.660; p<0.001)) and for the time to worsening of disability (HR 7.676, 95% CI 2.870 to 20.534; p<0.001). Additionally, patients pretreated with fingolimod were more likely to experience spinal relapses (55% vs 10% among previously naïve patients; p<0.001) and had an increased risk of secondary autoimmunity (HR 5.875, 95% CI 2.126 to 16.27; p<0.001).ConclusionIn the real-world setting, we demonstrated suboptimal disease control and increased risk of secondary autoimmunity following alemtuzumab, among patients previously treated with fingolimod. These data can provide guidance for improving MS therapeutic management.

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EARLY RELAPSES IN PATIENTS WITH HIGHLY ACTIVE MULTIPLE SCLEROSIS COMMENCED ON FINGOLIMOD; THE LEEDS TEACHING HOSPITAL EXPERIENCE

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2015-312379.123 ◽

2015 ◽

Vol 86 (11) ◽

pp. e4.28-e4

Author(s):

Kalani Chisha Weerasinghe ◽

Priya Shanmugarajah ◽

Melanie Russell ◽

Helen Ford

Keyword(s):

Multiple Sclerosis ◽

Patient Choice ◽

Oral Disease ◽

Highly Active ◽

Previously Treated ◽

Disease Modifying ◽

Disease Modifying Treatment ◽

Highly Active Multiple Sclerosis ◽

Active Disease ◽

Active Multiple Sclerosis

Fingolimod is the much anticipated oral disease modifying treatment for patients with highly active Multiple sclerosis. A total of 42 patients were commenced on Fingolimod from December 2012 to June 2014 in Leeds Hospitals NHS Trust.Four patients discontinued treatment due to patient choice, consecutive severe relapses and hepatotoxicity. No other severe side effects were noted in these 42 patients. A total of ten relapses were seen in nine patients. Of which eight out of ten relapses occurred within the first two months. Of the nine patients who experienced relapses, five (55%) were previously treated with Natalizumab, as opposed to four on injectable Disease Modifying Treatments (45%).The five patients previously treated with Natalizumab all underwent a three month wash out period prior to commencing Fingolimod. The relapses all took place within the first two months following initiation of Fingolimod.Early relapses in a patient group with highly active disease would suggest that a period of three months without disease modifying treatment could be too long. Currently this period has been shortened to four weeks and it remains to be seen if this will result in fewer early relapses in patients commencing Fingolimod.

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