A multinational international research team concluded that rheumatoid arthritis (RA) patients treated with Xeljanz, the trade name of tofactinib citrate, have a diminished response to pneumococcal but not influenza vaccines. Discontinuation among patients undergoing tofactinib treatment, however, did not affect response to vaccines. The study entitled “The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis” was published on line 20 March, 2015 in Annals of the Rheumatic Diseases, the journal of the European league against rheumatism (EULAR).
Influenza and pneumococcal infections have been associated with high morbidity in patients with RA due to both underlying autoimmune mechanisms of the disease and to disease-modifying anti-rheumatic drug (DMARD) therapies. These infections can be prevented, with vaccinations being important to evaluate whether drug treatments can affect the immunogenicity of the vaccines such as antibody production in RA patients.
Tofactinib was developed by Pfizer and is currently approved for RA treatment in the United States. In this study, researchers designed two different approaches to evaluate tofactinib’s effect on the immune response of patients to pneumococcal and influenza vaccines. In one of the studies, 200 patients were randomized to receive placebo or 10 mg tofacitinib twice daily. Antibody titers against pneumococcal and influenza were analyzed after 4 weeks of tofacitinib therapy, which was followed by administration of influenza and 23-serotype pneumococcal polysaccharide vaccine (PPSV-23). Antibody titers reanalyzed 35 days after vaccination showed that only 46 patients undergoing tofactinib treatment (45.1%) developed an adequate response compared with 67 (68.4%) of patients treated with placebo. The response was even lower in patients taking tofactinib in combination with another DMARD, methotrexate. Therapy with tofacitinib did not significantly affect the response to influenza vaccine.
In the second study, researchers tested whether discontinuation of the therapy could improve the response to the vaccines. Patients who received 10 mg tofacitinib twice daily for at least 3 months were randomly assigned to withdraw from treatment 1 week prior to vaccination. Antibody titers analyzed 1 week after vaccination showed that temporary drug discontinuation had limited effect upon pneumococcal and influenza vaccine responses.
This study may help to prevent infections in RA patients. “Consequently, clinicians should consider offering PPSV-23 prior to starting either of these therapies. Once patients are already using tofacitinib, our results suggest that temporary discontinuation of tofacitinib has little effect upon responses to either vaccine, and that the majority of patients will mount satisfactory responses to either vaccine,” noted the authors of the publication.