Effect of Ocrelizumab on Vaccine Responses in Patients With Multiple Sclerosis (S36.002)

Objective: VELOCE (NCT02545868) is a randomized, open-label, Phase IIIb study to assess if ocrelizumab recipients with relapsing multiple sclerosis (RMS) raise adequate humoral responses to selected vaccines. Background: Ocrelizumab selectively depletes CD20 + B cells while preserving the capacity for pre-existing humoral immunity. Vaccinations against infections are an important part of the management of patients with MS. Design/Methods: Patients (N=102) were randomized 2:1 into Group A (n=68), receiving a single dose of ocrelizumab 600 mg; or Control Group B (n=34), on no disease-modifying therapy or interferon-beta. All patients received a tetanus toxoid-containing vaccine, keyhole limpet hemocyanin (KLH), and a 23-valent pneumococcal polysaccharide vaccine (23-PPV). At randomization, Group A was subdivided into Groups A1 (n=33), receiving pneumococcal booster vaccine (13-PCV) 4 weeks after 23-PPV, and A2 (n=35), receiving seasonal influenza vaccine. Group B was treated the same as Group A2. Vaccinations in Group A started 12 weeks after ocrelizumab treatment start, and in Group B on Day 1 Results: Positive response (% of patients; definition of response included in poster) to tetanus vaccine at 8 weeks was 23.9% in Group A (ocrelizumab) versus 54.5% in Group B (control). Positive response to ≥5 serotypes in 23-PPV at 4 weeks was 71.6% in Group A (ocrelizumab) and 100% in Group B (control). In Group A1 (ocrelizumab), booster vaccine (13-PCV) did not enhance the response to 12 serotypes in common with 23-PPV. The humoral response to the neoantigen KLH was decreased in Group A (ocrelizumab) versus Group B (control) at all time points measured. Seroprotective titers at 4 weeks against five influenza strains (season 2015/2016 and 2016/2017) ranged from 55.6% to 80.0% in Group A2 (ocrelizumab) and 75.0% to 97.0% in Group B (control). Conclusions: As expected, ocrelizumab attenuated the humoral response to the studied vaccines. Study Supported by: Sponsored by F. Hoffmann-La Roche Ltd; writing and editorial assistance was provided by Health Interactions, USA, and Articulate Science, UK. Disclosure: Dr. Stokmaier has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of F. Hoffman-La Roche Ltd. Dr. Winthrop has nothing to disclose. Dr. Chognot has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd. Dr. Evershed has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Yes - employment at Roche Products Ltd and shareholder of F. Hoffman-La Roche Ltd. Dr. Manfrini has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of F. Hoffman-La Roche Ltd. Dr. McNamara has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche LtdYES (I am a contract statistician, and have provided my services to Roche during the past year). Dr. McNamara has received compensation for serving on the Board of Directors of YES (I run my own very small freelance contract statistician business, John McNamara Consulting Limited, and I am a director of this business. My wife is a director also. There are no other directors or employees). Dr. Bar-Or has nothing to disclose.