Background Rheumatoid arthritis (RA) patients (pts) are at increased risk of herpes zoster (HZ). The most recent ACR guidelines of 2015 recommend vaccination in pts aged ≥50 years prior to starting biologic DMARDs or tofacitinib,1 an oral Janus kinase inhibitor for the treatment of RA. Live zoster vaccine (LZV) has shown 70% efficacy in immunocompetent adults aged 50–59 years and 51% efficacy in those aged ≥60 years.2 We previously reported that pts with RA on background methotrexate who started 3 months of treatment with tofacitinib after LZV had similar varicella zoster virus (VZV)-specific immunity to placebo (PBO) pts, and their VZV immunity at Week 6 post-vaccination was comparable with healthy individuals aged ≥50 years.3
Objectives To evaluate the long-term effectiveness of LZV in pts with RA via the incidence of HZ after treatment with tofacitinib for up to 27 months.
Methods Data were analysed from a prior cohort of pts (n=100) given LZV and then randomised 2–3 weeks later to tofacitinib 5 mg twice daily (BID) or PBO for 12 weeks (A3921237 [NCT02147587]). At 14 weeks post-vaccination, pts joining the long-term extension (LTE) study ORAL Sequel (NCT00413699; study ongoing; database not locked) initiated open-label treatment with tofacitinib 5 or 10 mg BID. The incidence of HZ post-vaccination after tofacitinib exposure up to 27 months (based on an extended follow-up beyond January 2016 data snapshot) was evaluated. Among HZ cases, we analysed measures of VZV-specific immunity with average immunity after LZV.
Results 112 pts were randomised to PBO (n=57) or tofacitinib 5 mg BID (n=55). 100 pts continued to receive tofacitinib in ORAL Sequel. Five cases (not adjudicated) of HZ occurred (#1: 202 days [219 days post-LZV], #2: 267 days [281 days post-LZV], #3: 702 days [748 days post-LZV], #4: 699 days [741 days post-LZV], #5: 446 days [544 days post-LZV] after initiation of tofacitinib. Cases #1, #2, #3 and #4 were monodermatomal; #5 involved 5 dermatomes. All cases resolved with treatment. Cases #1, #4 and #5 had undetectable ELISPOT measures at baseline and Week 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, both at baseline and at Week 6. (Table).
Conclusions LZV prior to treatment with tofacitinib is effective at boosting IgG levels and cell-mediated immunity towards VZV. No pts who developed both strong cell-mediated and humoral immunity against VZV developed HZ. Of the 5 pts who developed HZ, 3 did not have any cell-mediated response and 2 had a low humoral response.
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Acknowledgements This study was sponsored by Pfizer Inc. The authors would like to acknowledge Lisa McNeil. Editorial support was provided by K Haines and C Evans of CMC and was funded by Pfizer Inc.
Disclosure of Interest K. Winthrop Grant/research support from: Bristol-Myers Squibb, Pfizer Inc, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Pfizer Inc, UCB, A. Wouters Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, E. Choy Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, C. Nduaka Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, P. Biswas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Hodge Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, I. Lazariciu Consultant for: Pfizer Inc, Employee of: Quintiles, K. Soma Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Mojcik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, W. F. Rigby Grant/research support from: Amgen, Pfizer Inc, Roche, Consultant for: Bristol-Myers Squibb, Eli Lilly, Pfizer Inc, Roche