Optimal timing of recombinant herpes zoster virus vaccination for a JAK inhibitor treatment in rheumatoid arthritis: a multicentre, open-label, randomised comparative study (STOP-HZ study): study protocol.

Introduction: Janus kinase (JAK) inhibitors are an important therapeutic option in the treatment of rheumatoid arthritis, but increase the risk of developing herpes zoster. Although a dry recombinant zoster vaccine (RZV) that can be used under immunosuppressive conditions has recently been developed, its optimal use and appropriate timing in patients scheduled to start JAK inhibitors is still unclear. The present study is designed to clarify the appropriate timing of JAK inhibitor initiation to measure varicella zoster virus (VZV)-specific IgG titers and VZV-specific T cell response in patients with rheumatoid arthritis who start tofacitinib at the first RZV vaccination or at the second one.
Methods and Analysis: STOP HZ (Effectiveness and S afe T y O f P rophylactic Recombinant H erpes Z oster Virus Vaccination for Rheumatoid Arthritis Patients with Tofacitinib Treatment) study is a multicentre, open-label, randomised, comparative study in patients with rheumatoid arthritis who are scheduled to start tofacitinib. This study enrols 60 study subjects in 12 sites. Enrolled subjects receive RZV two times on day 1 and week 8 and initiate tofacitinib 5 mg two times a day at the time of their first RZV (day 1, group A) or second RZV (week 8, group B) based on randomisation. The random assignment is performed centrally in a 1:1 ratio. Patients in Group B continue the same treatment until the start of tofacitinib treatment. Primary endpoint is VZV-specific IgG antibody titers at week 12 compared with those at baseline in each group. Secondary endpoints include comparison of VZV-specific IgG antibody between the groups, changes in disease activity of rheumatoid arthritis, VZV-specific T cell response and adverse events.
Ethics and Dissemination: The study has been approved by the Certified Review Board of Keio (No. 2022008), and conforms to the Declaration of Helsinki and good clinical practice guidelines. Written informed consent is obtained from participants prior to enrolment. The results of this study are planned to be submitted for publishment in relevant peer-review journals.
Trial Registration Number: jRCTs031230329.
Competing Interests: Competing interests: STa has received honoraria from Abbvie, Astellas, Eisai, Eli Lilly and Pfizer. KO has received honoraria and research support from Eisai, Gilead and AstraZeneca. KM has received honoraria and research support from AbbVie, Eli Lilly and Company, Eisai and Ono Pharmaceutical Co. Ltd. AI received research grant and speaker fees from AbbVie, Asahikasei, AstraZeneca, Boehringer Ingelheim, Chugai, Eli Lilly, Ono, Pfizer, Tanabe and Taisho pharmaceutical. TMatsui has received honoraria and research support from Pfizer, Chugai Pharmaceutical Co. Ltd and AsahiKASEI Co. Ltd. STo has received honoraria and research support from Pfizer Japan, Abbvie Japan Co. Ltd, Chugai pharmaceutical Co. Ltd, AsahiKASEI Co. Ltd, Mitsubishi-Tanabe Pharm Co, Eisai Co. Ltd. Janssen pharmaceutical K.K. SS has received honoraria, research support from Eisai Pharma and received honoraria from Abbvie, GlaxoSmithKline, Eli lilly, Pfizer, Astellas Pharma. TMatsub has received research support and/or speaker honoraria from Astellas Pharma, Bristol-Myers Squibb., AbbVie GK, Eli Lilly Japan K.K., Pfizer Japan, Gilead Sciences K.K. and AYUMI Pharmaceutical Corporation. KY has received honoraria, consultant fees and research support from Pfizer, Abbvie, GlaxoSmithkline, Eli lilly, Astellas Pharma, Gilead G.K., Eisai Pharma. KA has received honoraria from Pfizer Japan and GlaxoSmithKline. YK has received research grants and speaking fees from AbbVie, Astellas, Eisai, Eli Lilly, Pfizer and Gilead Sciences. JS, TMi and YM have no conflict of interest.
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