Ocrelizumab in MS patients with persistence of disease activity after alemtuzumab: A multi-center Italian study.

Background: The reason why some multiple sclerosis (MS) patients show disease activity after alemtuzumab (ALM) is still unclear, but ocrelizumab (OCR) could represent an interesting sequential therapeutic approach.
Objectives: To investigate safety and efficacy of OCR in MS patients with disease activity after two ALM courses.
Methods: Observational retrospective multi-centers Italian cohort study.
Results: Seventy-two subjects were included. Mean follow-up (FU) was 2.4 (±1) years. Forty-five patients (62.5%) experienced at least one adverse event (AE), with infections accounting for 96.7% of cases. A reduction in total lymphocytes was observed between OCR start and 6 months FU, driven by BCD19+ lymphocytes depletion ( p < 0.001). Immunoglobulin M (IgM) levels decreased between OCR start and 6 months FU ( p < 0.001). At 2-year FU, relapse, magnetic resonance imaging (MRI) activity and disability worsening-free survival were 92.1%, 90.8%, and 89.2%. The evidence of inflammatory activity between the two ALM courses was associated with higher risk of relapse, MRI activity, and NEDA-3 status loss in relapsing-remitting multiple sclerosis (RRMS; p = 0.02, p = 0.05, p = 0.01, respectively).
Conclusions: OCR after two ALM courses seemed to be safe and effective. Early IgM hypogammaglobulinemia occurred in a high proportion of patients. The evidence of inflammatory activity between ALM courses seemed to increase the risk of MS re-activation on OCR treatment.
Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: C. Lapucci has received honoraria for speaking, travel grants, and for participating in the advisory board from Merck, Sanofi, Novartis, Roche, Alexion. J. Frau served on scientific advisory boards for Biogen and Genzyme, and has received honoraria as a speaker from Merck Serono, Genzyme, Biogen, and Teva. E. Cocco reported grants, personal fees, and non-financial support from Biogen and Merck; personal fees and non-financial support from Novartis; grants from Roche; and personal fees from Genzyme. G. Coghe received honoraria for consultancy or speaking from Biogen, Novartis, Sanofi, Genzyme, Serono, Teva, and Almirall. M. Petracca has received travel/meeting expenses from Novartis, Janssen, Roche, and Merck; speaking honoraria from HEALTH&LIFE S.r.l., AIM Education S.r.l., Biogen, Novartis, and FARECOMUNICAZIONE E20; honoraria for consulting services and advisory board participation from Biogen; research grants from Baroni Foundation and the Italian Ministry of University and Research. R. Lanzillo has received honoraria from Biogen, Merck, Novartis, Roche, and Teva. V. Brescia Morra has received research grants from the Italian MS Society and Roche, and honoraria from Bayer, Biogen, Merck, Mylan, Novartis, Roche, Sanofi-Genzyme, and Teva. C.G. Nicoletti received travel funding from Biogen, Merck Serono, Sanofi-Genzyme, Roche, Teva, Novartis, Bristol Mayer Squibb, Janssen, Almirall and consultation fees from Sanofi, Almirall, Merck- Serono, Roche, Novartis, and Biogen. She is a sub-investigator in clinical trials being conducted for Biogen, Merck Serono, Roche, Biogen, Sanofi, Novartis, Teva, Bristol Mayer Squibb. D. Landi has received travel funding from Biogen, Merck Serono, Sanofi, Teva, Bristol Myers Squibb, Mylan; speaking or consultations fees from Sanofi, Merck Serono, Teva, Biogen, Roche, Novartis, Bristol Myers Squibb, BayerSchering. G. Marfia has received travel funding, speaking or consultation fees from Almirall, Bayer-Schering, Biogen, Sanofi, Merck Serono, Novartis, Teva, Mylan, Bristol Mayers Squibb and research grants from Roche and Biogen. M. Vercellino has received congress grants, speaker fees and advisory board fees from Merck-Serono, Novartis, Roche, Biogen, Sanofi Genzyme. P. Cavalla has received honoraria as speaker or travel grants to attend national and international conferences or consultation for advisory boards from Alexion, Almirall, Bayer Schering, Biogen, Cellgene-BMS, Merck-Serono, Teva, Roche, Novartis, Sanof-Genzyme, and Janssen. A. Bianco has received honoraria for speaking, advisory board/consulting from Biogen, Novartis, Merck Serono, Roche, Sanofi Genzyme. M. Mirabella has received honoraria for speaking, advisory board/consulting from Biogen, Novartis, Merck Serono, Roche, Almirall, Sanofi Genzyme, Janssen, Bristol-Myers Squibb, Viatris, Alexion. He is principal investigator in clinical trials for Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, CSL Behring, Ultragenix, Argenx. V. Torri Clerici acted as an Advisory Board member of Biogen Idec, Novartis, Merck Serono, Roche, Sanofi Genzyme, Almirall, Lundbeck and Bristol Myers Squibb; she received funding for traveling and honoraria for speaking or writing from Novartis, Sanofi Genzyme, Horizon, Merck Serono, Roche, Bristol Myers Squibb, Janssen and Almirall. She received support for research project by Almirall. E. Tomas received funding for work contract from Roche. M.T. Ferrò has received consultancy fees or speaker compensation from Sanofi, Bristol, Biogen Idec, and Novartis. L. Moiola has received honoraria for speaking and for participating in advisory board from Merck, Celgene, Biogen, Sanofi, Novartis, Roche, Alexion. M. Zaffaroni has received advisory board membership, speakers honoraria, travel support, research grants, consulting fees or clinical trial support from Actelion, Almirall, Bayer Schering, Biogen, Celgene, Excemed, Genzyme, Merck, Novartis, Sanofi, Roche, Teva. M. Ronzoni has received travel grants for congresses participation from Biogen, Genzyme, Novartis e Merck. G. Novi has received speaker honoraria from Merck, Novartis, Roche, Alexion. M. Cellerino has received consulting fees from Novartis, Genzyme, Teva and Zambon. A. Uccelli has received grants (to his institution) from FISM, Biogen, Roche, Alexion, and Merck Serono and has participated on a data safety monitoring board or advisory board (to his institution) for BD, Biogen, Iqvia, Sanofi, Roche, Alexion, and Bristol Myers Squibb. M. Inglese received grants from NIH, NMSS, and FISM; received fees for consultation from BMS, Janssen, Roche, Genzyme, Merck, Biogen and Novartis. P. Grossi, A. Nozzolillo, and F. Pinardi have nothing to disclose.