Reassuring Evidence of Antibody Response During Treatment With Cladribine for Multiple Sclerosis
Individuals with relapsing multiple sclerosis (MS) who were vaccinated against varicella zoster virus (VZV; n=3) before, or seasonal influenza (n=12) after a first course of treatment with cladribine (MAVENCLAD; EMD Serono; Rockland, MA) retained effective antibody titers against those viruses. In 9 of 12 who received seasonal influenza vaccination, antibody titers even increased by a factor of 2 to 4, for at least 6 months. These increased antibody titers were observed during lymphocytopenia in some of the participants and were independent of lymphocyte counts and timing of vaccination across all participants. These data are from the MAGNIFY-MS (NCT03364036) study and were presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2021 being held online February 25-27, 2021.
Additionally, in a substudy of CLOCK-MS (NCT03963375), individuals who were vaccinated against seasonal influenza after having at least 1 dose of cladribine (n=3) also had protective antibody titers 4 weeks after vaccination. In this small substudy, 2 individuals had vaccination and antibody response even though they were experiencing lymphocytopenia and had a dose of cladribine 2 and 4 months before vaccination.
Although the cohorts are small, these studies provide preliminary evidence that treatment with cladribine does not affect antibody levels, and that people with relapsing MS receiving cladribine can mount a new antibody response despite (mild-moderate) lymphocytopenia.
Klaus Schmierer, Professor of Neurology at The Blizard Institute, Queen Mary University of London and The Royal London Hospital, Barts Health NHS Trust, UK said, “Even individuals who had grade 1 or 2 lymphopenia would have effective protection against viruses after vaccination. I expected this since cladribine resets only some immune cell populations, rather than depleting or eliminating all immune cells relevant for anti-viral responses. This is, of course, reassuring during a pandemic in which we are encouraging everyone to receive vaccination against severe acute respiratory coronavirus-2 (SARS-CoV-2) to prevent coronavirus disease 2019 (COVID19).”
Dr. Schmierer also noted that, “For people starting cladribine treatment, this suggests antiSARS-CoV-2 antibody levels are unlikely to be affected by the treatment, and they should safely receive the vaccination approximately 1 month before starting cladribine. For individuals already receiving cladribine treatment, the new data provide reassurance that they will be able to produce an effective immune response against SARS-CoV-2 following vaccination.” Dr Schmierer added, “In light of the new data, it appears justified to consider reducing the 3-month gap between completing a course of cladribine and vaccination to 4-6 weeks.”
In these studies, monthly blood tests provided 2 control blood samples 1 month apart before starting cladribine, the closest sample available just before vaccination, and two postvaccination samples.