Outcomes after fingolimod to alemtuzumab treatment shift in relapsing–remitting MS patients: a multicentre cohort study

• Published in: Journal of neurology Vol. 266; no. 10; pp. 2440 - 2446
• Main Authors: Frau, Jessica, Saccà, Francesco, Signori, Alessio, Baroncini, Damiano, Fenu, Giuseppe, Annovazzi, Pietro, Capobianco, Marco, Signoriello, Elisabetta, Laroni, Alice, La Gioia, Sara, Sartori, Arianna, Maniscalco, Giorgia Teresa, Bonavita, Simona, Clerico, Marinella, Russo, Cinzia Valeria, Gallo, Antonio, Lapucci, Caterina, Carotenuto, Antonio, Sormani, Maria Pia, Cocco, Eleonora
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2019; Springer Nature B.V
• Subjects: Adult; Alemtuzumab - administration & dosage; Alemtuzumab - adverse effects; Alemtuzumab - pharmacology; Cell number; Cohort analysis; Female; Fingolimod Hydrochloride - administration & dosage; Fingolimod Hydrochloride - adverse effects; Fingolimod Hydrochloride - pharmacology; Gadolinium; Humans; Immunologic Factors - administration & dosage; Immunologic Factors - adverse effects; Immunologic Factors - pharmacology; Immunotherapy; Lymphocytes; Magnetic Resonance Imaging; Male; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - diagnostic imaging; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - physiopathology; Neurology; Neuroradiology; Neurosciences; NMR; Nuclear magnetic resonance; Original Communication; Outcome Assessment, Health Care; Retrospective Studies; Risk factors; Severity of Illness Index; NEDA; Real life; Alemtuzumab; Fingolimod
• ISSN: 0340-5354; 1432-1459; 1432-1459
• DOI: 10.1007/s00415-019-09424-8

Background A high reactivation of multiple sclerosis (MS) was reported in patients treated with alemtuzumab after fingolimod. We aimed to understand whether this shift enhanced the risk for reactivation in a real-life cohort. Methods Subjects with relapsing MS, shifting from fingolimod to alemtuzumab were enrolled. We collected the following data: age, sex, disease duration, relapses after fingolimod withdrawal, new T2/gadolinium (Gd)-enhancing lesions in the last magnetic resonance imaging (MRI) during fingolimod and in the first, while on alemtuzumab, lymphocyte counts at alemtuzumab start, and Expanded Disability Status Scale (EDSS) before and after alemtuzumab. Results We enrolled 77 patients (women 61 (79%); mean age 36.2 years (SD 9.6), and disease duration 12.3 years (SD 6.8) at fingolimod discontinuation; median washout 1.8 months). The annualised relapse rate was 0.89 during fingolimod, 1.32 during washout, and 0.15 after alemtuzumab ( p  = 0.001). The EDSS changed from a median of 3 (IQR 2–4) at the end of fingolimod to 2.5 after alemtuzumab (IQR 1.5–4) ( p  = 0.013). The washout length and the lymphocyte count before alemtuzumab were not associated with EDSS change after alemtuzumab ( p  = 0.59 and p  = 0.33, respectively). MRI activity decreased after alemtuzumab compared to that during fingolimod ( p  = 0.001). At alemtuzumab start, lymphocyte counts were < 0.8 × 10 3 /mL in 21 patients. Conclusions In our cohort, alemtuzumab reduced relapse, new T2/Gd-enhancing lesions, and EDSS score, as compared to the previous periods (fingolimod/washout). These results were not related to washout length or lymphocyte counts. Therefore, a rapid initiation of alemtuzumab after fingolimod does not seem to be a risk factor for MS reactivation.