HONOLULU – Patients taking natalizumab showed similar or only slightly delayed humoral immune responses following vaccinations, compared with patients not taking the drug for relapsing-remitting multiple sclerosis in a multicenter, randomized, open-label study.
Natalizumab (Tysabri) acts as an immunomodulator, which raised questions about its potential effects on patients’ responses to neoantigens and recall antigens. Previous studies have shown that some other biologic immunomodulatory drugs reduce antibody responses in patients, said Dr. Gabriel Pardo, director of the Oklahoma Medical Research Foundation’s Multiple Sclerosis Center of Excellence, Oklahoma City.
Dr. Gabriel Pardo
Dr. Pardo and his associates studied 30 patients who had been taking natalizumab (Tysabri) for 6 months to treat their multiple sclerosis and 30 others with the disease who had never taken the drug. All 60 patients received a single tetanus toxoid vaccination in order to assess memory antibody responses to a recall antigen. At least 2 weeks later, they also received three keyhole limpet hemocyanin (KLH) vaccinations in order to assess de novo antibody responses.
Overall, 27 patients in the control group and 24 in the natalizumab group completed the study. None stopped the drug or dropped out of the study because of drug-related side effects.
A similar proportion of both groups responded to the tetanus immunization within 28 days – 15 of 16 patients in the natalizumab group (94%) and all of 24 control patients. The difference between groups was not statistically significant, Dr. Pardo and his associates reported at the annual meeting of the American Academy of Neurology.
The one patient in the natalizumab group who did not respond within 28 days had a clinical response at 56 days after immunization.
Responses were defined as at least a twofold increase in specific serum immunoglobulin G (IgG) by 28 days after immunization, compared with baseline levels.
Median antitetanus toxoid antibody levels measured before and after immunization were similar between groups.
Antibody responses to the KLH vaccines also were similar between groups at 14, 28, and 56 days after immunizations. Anti-KLH antibody levels were similar between groups at all time points.
In the natalizumab group, the numbers of various lymphocytes increased over time, including CD3-positive, CD4-positive, and CD8-positive lymphocytes and B cells and natural killer (NK) cells.
The study did not analyze humoral responses to live vaccines.
Adverse events were seen in 26 of 30 patients on natalizumab, which were most commonly disease relapse (5 patients) and influenza, paresthesia, or injection site reaction, each of which occurred in 4 patients.
Biogen Idec and Elan Pharmaceuticals, which comarket Tysabri, funded the study. Dr. Pardo disclosed financial relationships with Biogen Idec, Acorda Therapeutics, Bayer, EMD Serono, Novartis, Pfizer, and Teva Neuroscience. A coinvestigator disclosed relationships with these and other companies, and two other co-investigators were employees of Biogen Idec.