Background/Purpose: Rheumatoid arthritis (RA) patients are at increased risk for herpes zoster (HZ), and vaccination is recommended in patients over the age of 50 years, prior to starting biologics or tofacitinib, an oral Janus kinase inhibitor for the treatment of RA. In immunocompetent adults aged ≥50 years zoster vaccine has shown 70% efficacy (in 50–59 year-olds over 1.3 years) to 51% efficacy (in ≥60-year-olds over 4.9 years) for the prevention of HZ.¹ We previously reported the safety and immunogenicity of live zoster vaccine in RA patients on background methotrexate (MTX) before initiating tofacitinib or placebo.² Briefly, patients with RA who started 3 months of treatment with tofacitinib after zoster vaccination generated immunity to varicella zoster virus (VZV) similar to placebo-treated recipients. Furthermore their VZV immunity at Week 6 post-vaccination was comparable with immunity in healthy people aged 50 years and older.² However, the long-term effectiveness of the vaccine in this setting is unknown.

Methods: From a prior cohort of patients (n=100) given zoster vaccine and then randomized 2 to 3 weeks later to tofacitinib 5 mg BID, or placebo, for 12 weeks (A3921237 [NCT02147587]), we evaluated the incidence of HZ post-vaccination during long-term tofacitinib use. At 14 weeks post-vaccination, patients joining the long-term extension (LTE) study (ORAL Sequel; [NCT00413699]) initiated open-label treatment with tofacitinib 5 mg or 10 mg BID at the discretion of the investigator. HZ cases after tofacitinib exposure up to 19 months were evaluated. Among HZ cases, we described and compared measures of VZV-specific immunity with average immunity after live zoster vaccination.

Results: 112 pts were randomized to placebo (n=57) or tofacitinib 5 mg BID (n=55), and 100 of these patients continued to receive tofacitinib in the ORAL Sequel study. The overall exposure to tofacitinib ranged from 9 to 19 months. Two HZ cases occurred, one at 202 days (219 days from vaccination) and another at 267 days (281 days from vaccination) after tofacitinib start. Both were monodermatomal and resolved with antiviral therapy. Review of immunogenicity data at 6 weeks post-vaccination revealed that Case #1 had undetectable ELISPOT measures at baseline and at Week 6 post-vaccination. Case #2 responded adequately to vaccination by both IgG and ELISPOT measures, but had much lower than average post-vaccination IgG levels (Table 1).

Conclusion: The observed HZ incidence rate after vaccination was low among this cohort of tofacitinib-treated patients. Zoster vaccination prior to tofacitinib start is effective at boosting IgG levels and cell-mediated immunity towards VZV, although individuals with poor vaccine response may be more likely to develop HZ. Reference: 1. Hales CM et al. MMWR Morb Motal Wkly Rep 2014; 63:729-31. 2. Winthrop K et al. Arthritis Rheumatol 2015; 67 (suppl 10): Abstract 12L.