Immune Response to an Adjuvanted Recombinant Zoster Vaccine in Japanese Patients with Rheumatoid Arthritis Receiving Upadacitinib (End Zoster-J Study): Study Protocol for an Exploratory Parallel Triple-Arm Prospective Trial

Abstract

Background: Janus kinase (JAK) inhibitors have emerged as a new class of disease-modifying anti-rheumatic drugs in the treatment of rheumatoid arthritis (RA). However, herpes zoster is one of the common adverse events of JAK inhibitors, including upadacitinib, which is especially high in Japanese patients with RA compared to those from Western countries. Recombinant zoster vaccine (Shingrix®) is an adjuvanted subunit vaccine containing varicella-zoster virus (VZV) glycoprotein E (gE) that is effective in adults over 50 years of age. Despite this, no studies have examined its immunogenicity in Japanese patients receiving upadacitinib. Therefore, this study aims to examine the effectiveness of the recombinant zoster vaccine in Japanese patients with RA receiving upadacitinib. Methods: This is a single-center, exploratory, interventional, open-label, parallel triple-arm, prospective study. A total of 69 patients (23 in each group) aged 50 years or over and treated with a stable dose of methotrexate (MTX) monotherapy (6–12 mg/week), upadacitinib monotherapy (15 mg/day), or MTX (6–12 mg/week) + upadacitinib 15 mg/day (combination) for at least 1 month prior to study entry will be included. Moreover, all three groups will receive two intramuscular injections of the recombinant zoster vaccine at 8-week intervals. The primary endpoint is the proportion of positive anti-gE antibodies 4 weeks after the second injection. Secondary endpoints include RA disease activity, positive gE-specific CD4+ T-cells, and VZV-specific antibodies at indicated time points. Data on outcome measures will be collected at baseline and at 4, 8, 12, and 20 weeks. Endpoints will be summarized using descriptive statistics from baseline therapy, and results will be compared in an exploratory manner. Discussion: Despite the limited generalizability due to its design as a single-center, single-ethnic study, small sample size, and short observation period, this study provides evidence on the effectiveness and tolerability of recombinant zoster vaccine in Japanese patients with RA receiving upadacitinib.