Cladribine, which was represented in the highest proportion of patients developing protective SARS-CoV-2 antibody response among other DMTs, had humoral response findings independent of lymphocyte count.
Anat Achiron, MD, PhD
Research published in Therapeutic Advances in Neurological Disorders characterized humoral immunity in patients with multiple sclerosis (MS) who have received mRNA-COVID-19 vaccines and were treated with high-efficacy disease-modifying therapies (DMT) and found that cladribine (Mavenclad; EMD Serono) was the only DMT observed to not impair humoral response.1
Lead author Anat Achiron, MD, PhD, professor of neurology, Sackler School of Medicine, Tel-Aviv University, and colleagues evaluated the BNT162b2-COVID-19 (Pfizer-BioNTech) vaccine in 125 adults with multiple sclerosis (MS) to provide evidence-based guidelines to the MS community regarding the magnitude of protective humoral immunity in patients treated with high-efficacy DMTs.
Protective humoral immunity was demonstrated in 46 of 47 (97.9%) of healthy subjects (n = 47) and untreated patients with MS (n = 32). All patients (100%) treated with cladribine (n = 23) developed a high level of antibodies post-COVID-19 vaccination (P <.0001). Notably, cladribine was the only DMT with a 100% protective humoral immunity rate.
"Bringing Mavenclad-treated patients into a state where they can live their lives as normally as possible during a global pandemic is of utmost importance to us.” Danny Bar-Zohar, MD, Global Head, Development, Merck KGaA, said in a statement.2 “Beyond the convenient oral dosing schedule, proven efficacy, and well-characterized safety profile of MAVENCLAD, newly generated data now show encouraging initial evidence for these patients’ ability to generate adequate antibody response to COVID-19 vaccination, which is so important for patients.”
The same was not observed for the other DMTs evaluated in the study. Patients treated with fingolimod (n = 26; Gilenya; Novartis) showed no development of a post-vaccination humoral response. Only 1 of 26 patients (3.8%) had an antibody response that, although attenuated, was above the cut-off value for a positive response (P <.0001).
The study authors noted that the failure to develop antibody response in patients treated with fingolimod could be related to the low lymphocyte count in the majority of patients. In total, 38.5% (10 of 26) had a lymphocyte count below 500 cells/mm3, and an additional 50% (13 of 26) had lymphocyte count between 500 and 1000 cells/mm3.
Among 44 patients treated with ocrelizumab (Ocrevus; Genentech), 10 (22.7%) demonstrated a protective antibody titer (P <.0001). Additionally, 42 of 44 (95.5%) patients had lymphocyte counts above 1000 cells/mm3, indicating that the failure to develop humoral response was not related to absolute lymphocyte count.
Achiron et al wrote, “For ocrelizumab-treated patients, the failure to mount appropriate [immunoglobulin G] immune response was regardless of the absolute lymphocyte counts that were in the normal range, or to the time-interval from the last ocrelizumab treatment dose that was from 3.1 to 8.9 months, suggesting the need to postpone the next dosing to enable an effective post-vaccination humoral response.”
After the last treatment DMT dose, development of a protective SARS-CoV-2 antibody titer was as early as 4.4 months in the cladribine group. In comparison, the majority (34 of 44; 77.3%) of patients treated with ocrelizumab did not develop a protective SARS-CoV-2 antibody titer when vaccinated up to 8.9 months after the last treatment dose. Notably, those that did develop protective antibody response were vaccinated between 3.7 and 6.4 months after the last treatment dose.
Of 125 COVID-19 MS vaccinees, 76 (60.8%) were relapsing-remitting, 24 (19.2%) primary-progressive, 18 (14.4%) secondary progressive, 4 (3.2%) clinically isolated syndrome, and 3 (2.4%) patients with radiologically isolated syndrome.