Starting Tofacitinib After First Shingles Vaccine Dose May Preserve Antibody Response in RA patients: Study
Japan: In an exploratory randomized trial from Japan, patients with rheumatoid arthritis who started the JAK inhibitor tofacitinib after the first dose of a two-dose shingles vaccine achieved similar varicella-zoster virus antibody levels at 12 weeks compared with patients who waited until after the second dose.
Although arthritis activity improved earlier in the group starting tofacitinib after the first vaccine dose, Clinical Disease Activity Index scores were comparable between the groups by week 12, suggesting that delaying JAK inhibitor therapy until completion of the vaccine series may not be necessary in all patients.
Patients with rheumatoid arthritis receiving Janus kinase (JAK) inhibitors are at increased risk of herpes zoster. Although the recombinant zoster vaccine can be administered during immunosuppressive therapy, the optimal timing of vaccination relative to JAK inhibitor initiation remains uncertain for balancing vaccine response and disease control.
To explore this question, Satoshi Takanashi, MD, PhD, from the Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, and colleagues conducted the multicenter, open-label, randomized STOP-HZ (Effectiveness and SafeTy Of Prophylactic Recombinant Herpes Zoster Virus Vaccination for Rheumatoid Arthritis Patients with Tofacitinib Treatment) trial.
The study, published in Annals of Internal Medicine, included patients aged 50 years or older with rheumatoid arthritis who were initiating tofacitinib therapy. All participants received the two-dose recombinant zoster vaccine on day 1 and at week 8. Twenty-nine patients started tofacitinib on day 1, while 30 began treatment after the second vaccine dose at week 8. Researchers evaluated VZV-specific antibody responses at 12 weeks, along with disease activity and safety outcomes.
Key findings from the study include:
- Patients who started tofacitinib after the first vaccine dose achieved similar VZV antibody responses at 12 weeks as those who initiated treatment after the second vaccine dose.
- The geometric mean fold rise in antibody levels at week 12 was 2.66 in the day-1 group and 2.91 in the week-8 group, indicating comparable immune responses.
- Patients beginning tofacitinib immediately experienced earlier improvement in rheumatoid arthritis activity at weeks 4 and 8.
- By week 12, Clinical Disease Activity Index (CDAI) scores were similar between the two treatment strategies.
- A smaller proportion of patients who started tofacitinib on day 1 achieved an early antibody response at week 4, but this difference was no longer evident by week 12.
- Varicella-zoster virus-specific T-cell responses remained largely unchanged in both groups.
- Delaying tofacitinib initiation was associated with more arthritis flares, whereas adverse events, including infections, occurred less frequently in this group.
The findings suggest that initiating a JAK inhibitor after the first shingles vaccine dose may delay, but not compromise, vaccine-induced immunity while allowing earlier rheumatoid arthritis control. By 12 weeks, antibody responses were similar regardless of when tofacitinib was started.
The study was limited by its small sample size, short follow-up, absence of clinical herpes zoster cases, and limited power to detect between-group differences.
Overall, the findings indicate that delaying JAK inhibitor therapy until completion of the two-dose shingles vaccine series may not be necessary for all patients. The authors emphasized balancing prompt disease control with optimal vaccine response and called for larger studies to confirm these results.
Reference:
Takanashi S, et al "Timing of recombinant herpes zoster virus vaccination administration and JAK inhibitor initiation in rheumatoid arthritis: a multicenter, open-label, randomized comparative study" Ann Intern Med 2026; DOI: 10.7326/ANNALS-25-05493.
Next Story