Contributions
Abstract: 203
Type: Oral
Alemtuzumab is a recently licensed treatment for active relapsing-remitting multiple sclerosis. Prospective head-to-head comparisons are lacking, but a large retrospective cohort study suggested alemtuzumab and natalizumab are broadly comparable in relapse-suppressing impact: treatment decisions between these agents ´might therefore be primarily governed by their safety profiles´ [1]. These are quite different.
The side effects of alemtuzumab might be divided into preventable and non-preventable. The commonest potentially serious effect is non-preventable: autoimmunity occurs in 22-50% of patients, arising a median of 32 months after first treatment and unassociated with the number of treatment cycles [2,3]. Thyroid disease and immune thrombocytopoenia are the commonest manifestations. While neither disease is preventable, currently, their adverse clinical consequences can be very effectively prevented by careful blood monitoring.
Infectious complications proved perhaps less common in the principal trials than the extent and duration of alemtuzumab-induced peripheral lymphocyte depletion might have suggested, though a propensity towards herpes infections was seen - affecting some 16% of patients, a mean interval of 12 months from most recent treatment [4,5]. Aciclovir is routinely prescribed with each course of alemtuzumab to help prevent this complication.
One case of Listeria infection was reported in the phase II trial [6], but none in the phase III studies [4,5]. Post-marketing surveillance has, however, suggested Listeria meningitis may be a specific if uncommon complication. It is likely to arise from Listeria already colonising the bowel at the time of alemtuzumab treatment. One fatal case has occurred in the UK, and published case reports describe other, non-fatal incidences. Since marketing authorisation, GenzymeSanofi pharmacovigilance has been informed of 32 cases of Listeria meningitis/septicaemia - allowing a very crude estimate of the frequency of 0.25% in the first month after each cycle of alemtuzumab treatment. Many had occurred despite the recommendation since 2016 of dietary advice to reduce Listeria risk. As a consequence, in the UK, the ABN now recommends prophylaxis with co-trimoxazole as the safest approach [7].
Disclosure:
Acknowledgements: We are grateful to Genzyme Sanofi for their support and assistance and for freely providing access to their pharmacovigilance data.
References:
1 Kalincik, T. et al. Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting MS: a cohort study. The Lancet. Neurology 16, 271-281, doi:10.1016/S1474-4422(17)30007-8 (2017).
2 Cossburn, M. et al. Autoimmune disease after alemtuzumab treatment for multiple sclerosis in a multicenter cohort. Neurology 77, 573-579 (2011).
3 Tuohy, O. et al. Alemtuzumab treatment of multiple sclerosis: long-term safety and efficacy. Journal of neurology, neurosurgery, and psychiatry 86, 208-215, doi:10.1136/jnnp-2014-307721 (2015).
4 Coles, A. J. et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet (London, England) 380, 1829-1839 (2012).
5 Cohen, J. A. et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet380, 1819-1828, doi:10.1016/s0140-6736(12)61769-3 (2012).
6 Coles, A. J. et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. The New England journal of medicine 359, 1786-1801 (2008).
7 Coles, A. and the ABN MS Advisory Group. Guidance on the prevention of Listeria infection after alemtuzumab treatment of multiple sclerosis. www.theabn.org/media/Guidance%20on%20the%20prevention%20of%20Listeria%20infection%20after%20alemtuzumab%20treatment%20of%20multiple%20sclerosis.pdf?ct=t(May_20175_19_2017)&mc_cid=6f2e247b73&mc_eid=92ba418a45 (2017).
Abstract: 203
Type: Oral
Alemtuzumab is a recently licensed treatment for active relapsing-remitting multiple sclerosis. Prospective head-to-head comparisons are lacking, but a large retrospective cohort study suggested alemtuzumab and natalizumab are broadly comparable in relapse-suppressing impact: treatment decisions between these agents ´might therefore be primarily governed by their safety profiles´ [1]. These are quite different.
The side effects of alemtuzumab might be divided into preventable and non-preventable. The commonest potentially serious effect is non-preventable: autoimmunity occurs in 22-50% of patients, arising a median of 32 months after first treatment and unassociated with the number of treatment cycles [2,3]. Thyroid disease and immune thrombocytopoenia are the commonest manifestations. While neither disease is preventable, currently, their adverse clinical consequences can be very effectively prevented by careful blood monitoring.
Infectious complications proved perhaps less common in the principal trials than the extent and duration of alemtuzumab-induced peripheral lymphocyte depletion might have suggested, though a propensity towards herpes infections was seen - affecting some 16% of patients, a mean interval of 12 months from most recent treatment [4,5]. Aciclovir is routinely prescribed with each course of alemtuzumab to help prevent this complication.
One case of Listeria infection was reported in the phase II trial [6], but none in the phase III studies [4,5]. Post-marketing surveillance has, however, suggested Listeria meningitis may be a specific if uncommon complication. It is likely to arise from Listeria already colonising the bowel at the time of alemtuzumab treatment. One fatal case has occurred in the UK, and published case reports describe other, non-fatal incidences. Since marketing authorisation, GenzymeSanofi pharmacovigilance has been informed of 32 cases of Listeria meningitis/septicaemia - allowing a very crude estimate of the frequency of 0.25% in the first month after each cycle of alemtuzumab treatment. Many had occurred despite the recommendation since 2016 of dietary advice to reduce Listeria risk. As a consequence, in the UK, the ABN now recommends prophylaxis with co-trimoxazole as the safest approach [7].
Disclosure:
Acknowledgements: We are grateful to Genzyme Sanofi for their support and assistance and for freely providing access to their pharmacovigilance data.
References:
1 Kalincik, T. et al. Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting MS: a cohort study. The Lancet. Neurology 16, 271-281, doi:10.1016/S1474-4422(17)30007-8 (2017).
2 Cossburn, M. et al. Autoimmune disease after alemtuzumab treatment for multiple sclerosis in a multicenter cohort. Neurology 77, 573-579 (2011).
3 Tuohy, O. et al. Alemtuzumab treatment of multiple sclerosis: long-term safety and efficacy. Journal of neurology, neurosurgery, and psychiatry 86, 208-215, doi:10.1136/jnnp-2014-307721 (2015).
4 Coles, A. J. et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet (London, England) 380, 1829-1839 (2012).
5 Cohen, J. A. et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet380, 1819-1828, doi:10.1016/s0140-6736(12)61769-3 (2012).
6 Coles, A. J. et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. The New England journal of medicine 359, 1786-1801 (2008).
7 Coles, A. and the ABN MS Advisory Group. Guidance on the prevention of Listeria infection after alemtuzumab treatment of multiple sclerosis. www.theabn.org/media/Guidance%20on%20the%20prevention%20of%20Listeria%20infection%20after%20alemtuzumab%20treatment%20of%20multiple%20sclerosis.pdf?ct=t(May_20175_19_2017)&mc_cid=6f2e247b73&mc_eid=92ba418a45 (2017).