The Safety and Immunogenicity of Live Zoster Vaccination in Patients With Rheumatoid Arthritis Before Starting Tofacitinib: A Randomized Phase II Trial

Kevin Winthrop, Ann G. Wouters, Ernest H. Choy, Koshika Soma, Jennifer A. Hodge, Chudy I. Nduaka, Pinaki Biswas, Elie Needle, Sherry Passador, Christopher F. Mojcik, William F. Rigby

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Objective: Patients with rheumatoid arthritis (RA) are at increased risk of herpes zoster, and vaccination is recommended for patients ages 50 years and older, prior to starting treatment with biologic agents or tofacitinib. Tofacitinib is an oral JAK inhibitor for the treatment of RA. We evaluated its effect on the immune response and safety of live zoster vaccine (LZV). Methods: In this phase II, 14-week, placebo-controlled trial, patients ages 50 years and older who had active RA and were receiving background methotrexate were given LZV and randomized to receive tofacitinib 5 mg twice daily or placebo 2-3 weeks postvaccination. We measured humoral responses (varicella zoster virus [VZV]-specific IgG level as determined by glycoprotein enzyme-linked immunosorbent assay) and cell-mediated responses (VZV-specific T cell enumeration, as determined by enzyme-linked immunospot assay) at baseline and 2 weeks, 6 weeks, and 14 weeks postvaccination. End points included the geometric mean fold rise (GMFR) in VZV-specific IgG levels (primary end point) and T cells (number of spot-forming cells/106 peripheral blood mononuclear cells) at 6 weeks postvaccination. Results: One hundred twelve patients were randomized to receive tofacitinib (n=55) or placebo (n=57). Six weeks postvaccination, the GMFR in VZV-specific IgG levels was 2.11 in the tofacitinib group and 1.74 in the placebo group, and the VZV-specific T cell GMFR was similar in the tofacitinib group and the placebo group (1.50 and 1.29, respectively). Serious adverse events occurred in 3 patients in the tofacitinib group (5.5%) and 0 patients (0.0%) in the placebo group. One patient, who lacked preexisting VZV immunity, developed cutaneous vaccine dissemination 2 days after starting tofacitinib (16 days postvaccination). This resolved after tofacitinib was discontinued and the patient received antiviral treatment. Conclusion: Patients who began treatment with tofacitinib 2-3 weeks after receiving LZV had VZV-specific humoral and cell-mediated immune responses to LZV similar to those in placebo-treated patients. Vaccination appeared to be safe in all of the patients except 1 patient who lacked preexisting VZV immunity.

Original languageEnglish (US)
JournalArthritis and Rheumatology
DOIs
StateAccepted/In press - 2017

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Fingerprint Dive into the research topics of 'The Safety and Immunogenicity of Live Zoster Vaccination in Patients With Rheumatoid Arthritis Before Starting Tofacitinib: A Randomized Phase II Trial'. Together they form a unique fingerprint.

  • Cite this

    Winthrop, K., Wouters, A. G., Choy, E. H., Soma, K., Hodge, J. A., Nduaka, C. I., Biswas, P., Needle, E., Passador, S., Mojcik, C. F., & Rigby, W. F. (Accepted/In press). The Safety and Immunogenicity of Live Zoster Vaccination in Patients With Rheumatoid Arthritis Before Starting Tofacitinib: A Randomized Phase II Trial. Arthritis and Rheumatology. https://doi.org/10.1002/art.40187