Effect of Ocrelizumab on Vaccine Responses in Patients with Multiple Sclerosis

Thursday, May 31, 2018
Exhibit Hall A (Nashville Music City Center)
Daniela Stokmaier, MSc Pharm PhD , F.Hoffmann-La Roche Ltd, Basel, Switzerland
Kevin Winthrop, MD MPH , Division of Infectious Diseases, OHSU, Portland, OR
Cathy Chognot, PhD , F. Hoffmann-La Roche Ltd, Basel, Switzerland
Joanna Evershed, BSc , Roche Products Ltd, Welwyn Garden City, United Kingdom
Marianna Manfrini, MD PhD , F. Hoffmann-La Roche Ltd, Basel, Switzerland
John McNamara, BSc MSc CStat , John McNamara Consulting Limited, Cambridge, United Kingdom
Amit Bar-Or, MD , University of Pennsylvania, Philadelphia, PA


Ocrelizumab (OCR) 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 multiple sclerosis (MS).


VELOCE (NCT02545868) is a randomized, open-label, Phase IIIb study to assess if OCR recipients with relapsing MS (RMS) raise adequate humoral responses to selected vaccines.


Patients (N=102) were randomized 2:1 into Group A (n=68), receiving a single dose of OCR 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 vaccinations were the same as Group A2. Vaccinations in Group A started 12 weeks after OCR treatment start, and in Group B on Day 1.


Positive response (% of patients; definition of response included in poster) to tetanus vaccine at 8 weeks was 23.9% in Group A (OCR) versus 54.5% in Group B (control). Positive response to ≥5 serotypes in 23-PPV at 4 weeks was 71.6% in Group A (OCR) and 100% in Group B (control). In Group A1 (OCR), 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 (OCR) 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 (OCR) and 75.0% to 97.0% in Group B (control).


As expected, ocrelizumab attenuated the humoral response to the studied vaccines.