The Effectiveness of Zoster Vaccine in Patients Subsequently Treated with Tofacitinib

Introduction: Tofacitinib is an oral, small molecule JAK inhibitor approved for the treatment of rheumatoid arthritis (RA) currently being investigated for several immune-mediated inflammatory diseases incl. ulcerative colitis. Patients (pts) with these conditions can be at increased risk for herpes zoster (HZ). Live zoster vaccine (LZV) has shown 70% and 51% efficacy in immunocompetent adults aged 50-59 and ≥60 years, respectively.1 LZV is recommended to be used in pts over 50 years old prior to starting immunosuppression with biologic disease-modifying antirheumatic drugs.2,3 We recently documented this vaccine to provide adequate immune responses in RA pts receiving methotrexate prior to starting tofacitinib.4 Here, we report long-term follow-up data of this cohort evaluating the effectiveness of LZV. Methods: The initial study involved 112 RA pts given LZV and randomized 2-3 weeks (wks) later to tofacitinib 5 mg twice daily (BID) or placebo for 12 wks (NCT02147587). At 14 wks, pts were offered inclusion in the long-term extension study ORAL Sequel (NCT00413699) at doses of either 5 or 10 mg BID. From this cohort, we calculated incidence of HZ after tofacitinib start, up to 27 months after. Among HZ cases, we analyzed varicella zoster virus (VZV)-specific immunity with average immunity after LZV. Results: Of 112 randomized pts (placebo, n=57; 5 mg BID, n=55), 100 continued to receive tofacitinib in ORAL Sequel. Five cases (not adjudicated) of HZ occurred at 202, 267, 702, 699, 446 days after initiation of tofacitinib in Cases 1-5, respectively. Cases #1-4 were monodermatomal; #5 involved 5 dermatomes; all resolved with treatment. Cases #1, #4, and #5 had undetectable VZV cell-mediated immunity (measured by ELISPOT) at baseline (BL) and Wk 6 post-vaccination, indicating a lack of VZV-specific immunity. Cases #2 and #3 responded adequately to vaccination by both immunoglobulin G (IgG) and ELISPOT measures, but had lower than average VZV IgG levels at BL and Wk 6. Conclusion: LZV prior to treatment with tofacitinib is effective at boosting IgG levels and cell-mediated immunity towards VZV. Of the 5 pts who developed HZ, 3 did not have any cell-mediated response and 2 had a low humoral response. Funded by Pfizer Inc.Table: Table. VZV ELISPOT and IgG levels