Background/Purpose: Tofacitinib is a novel, oral Janus kinase inhibitor being investigated as a targeted immunomodulator and disease-modifying therapy for RA. Clinical guidelines recommend the use of influenza and pneumococcal vaccines in patients with RA; however, the effect of tofacitinib on vaccine immunogenicity is unknown.

Methods: Patients with RA taking tofacitinib 10 mg twice daily (BID) were recruited from an open-label, long-term extension trial (NCT00413699). In this vaccine substudy, participants were randomized into 2 groups and stratified by methotrexate (MTX) use: 1) those who continued tofacitinib 10 mg BID during and after randomization (“continuous”); or 2) those who interrupted tofacitinib use for 1 week prior to and 1 week after vaccination (“withdrawn”). Vaccination baseline serum pneumococcal and influenza antibody titers were measured and all patients were vaccinated with the 2011-2012 influenza vaccine and PNEUMOVAX^® 23 (PCV23, Merck & Co., Inc) at 1 week post-randomization; antibody titers were measured at 35 days post-vaccination. The primary endpoint was the proportion of continuous and withdrawn patients who achieved a satisfactory humoral response to (a) pneumococcal vaccine (≥2-fold increase in antibody concentrations against ≥6 of 12 pneumococcal antigens [serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 19A, 19F, 23F, 18C]) and (b) influenza vaccine (≥4-fold increase in antibody titers against at least 2 of 3 influenza antigens). Secondary endpoints included comparison of pre- and post-vaccine hemaglutination titers (HI), and influenza and pneumococcal serotype-specific Geometric Mean Fold Rise (GMFR) between groups.

Results: Of 199 patients enrolled, 183 (continuous, N=92; withdrawn, N=91) completed vaccination and antibody titer evaluations and were included in the analysis. The proportion of patients achieving a satisfactory humoral response to pneumococcal and influenza vaccines was similar between patients who continued tofacitinib and those who were temporarily withdrawn (Table). Post-vaccination pneumococcal antigen GMFRs trended higher in patients withdrawn from tofacitinib, while GMFRs were similar between groups for influenza (Table). Protective influenza HI titers (≥1:40 influenza antibody titer in ≥2 of three antigens) were similar for continuous (75%) and withdrawn patients (82%) at 35 days post-vaccination.

Conclusion: Among patients with RA, continuous tofacitinib use did not significantly impair overall responsiveness to pneumococcal and influenza vaccines, although the pneumococcal antigen GMFRs trended higher in patients who discontinued tofacitinib. A study limitation is the absence of a MTX-only control group or group lacking tofacitinib exposure. These data suggest that it is not necessary to discontinue tofacitinib in order to attain meaningful responses to pneumococcal and influenza vaccines.