Live Zoster Vaccine in Patients With Rheumatoid Arthritis Treated With Tofacitinib With or Without Methotrexate, or Adalimumab With Methotrexate: A Post Hoc Analysis of Data From a Phase IIIb/IV Randomized Study

Abstract

Objective To explore herpes zoster (HZ) rates and live zoster vaccine (LZV) safety in a subset of patients with rheumatoid arthritis who received LZV before tofacitinib ± methotrexate (MTX), or adalimumab (ADA) plus MTX in the ORAL Strategy. Methods ORAL Strategy was a 1‐year, phase IIIb/IV, randomized, triple‐dummy, active‐comparator–controlled study. MTX‐inadequate responder patients received tofacitinib 5 mg twice daily (BID), tofacitinib 5 mg BID plus MTX, or ADA 40 mg every other week plus MTX (1:1:1 randomization). Eligible patients age ≥50 years could opt to receive LZV 28 days before initiating study treatment. HZ incidence rates (IRs; patients with events per 100 patient‐years) were calculated. Opportunistic HZ infections (multidermatomal/disseminated), serious HZ events, and LZV‐related adverse events were monitored. Results In ORAL Strategy, 216 of 1,146 patients (18.8%) received LZV. Overall, 18 patients (1.6%) developed HZ (vaccinated: n = 3; nonvaccinated: n = 15). HZ IRs were 1.1 (95% confidence interval [95% CI] 0.3–2.9), 2.3 (95% CI 1.0–4.6), and 1.7 (95% CI 0.6–3.7) for tofacitinib monotherapy, tofacitinib plus MTX, and ADA plus MTX, respectively, and were generally similar between vaccinated and nonvaccinated patients. Three multidermatomal, 1 disseminated, and 2 serious HZ events occurred. No vaccinated patients had zoster‐like lesions within 42 days of vaccination; 1 patient had vaccination‐site erythema. Conclusion LZV was well tolerated, and HZ IRs were generally similar between treatment groups and vaccinated versus nonvaccinated patients. However, ORAL Strategy was not powered for comparisons between vaccinated and nonvaccinated patients because <20% of all patients were vaccinated. Furthermore, LZV has been shown to be effective only in ~50% of individuals.

Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a consensus statement

“…In a live zoster vaccination study, zoster IRs at follow-up were numerically similar in the tofacitinib 5 mg and adalimumab and MTX arms but higher rates were seen for the combination of tofacitinib 5 mg two times a day with MTX. 108 Notably, zoster rates at follow-up were generally similar in vaccinated versus non-vaccinated patients, but further studies are clearly needed. While the vaccination resulted in reasonable immune responses, 1 patient developed zoster infection having had no prior immunity.…”

JAK inhibitors and infections risk: focus on herpes zoster

“…A recent study indirectly estimated the effect of live zoster vaccination administered in a clinical trial cohort, before receiving tofacitinib monotherapy, tofacitinib plus MTX or adalimumab plus MTX, and calculated incidence rates of zoster infection in the non-vaccinated patients of 1.0, 2.2 and 2.1, respectively, compared with 1.5, 3.0 and 0, respectively, in the vaccinated RA patients. 109…”

“…It remains to be established whether the use of routine screening and vaccination reduces the risk of VZV infection, and is cost-effective, in patients receiving JAKinibs in real world settings. 109 There are no current treatment recommendations regarding the clinical approach in cases of reactivation during JAKinib treatment.…”

Translating JAKs to Jakinibs

“…Overall, the rate of zoster associated with tofacitinib is roughly the rate seen with biologics (88). Because of the increased risk, vaccination is recommended (88)(89)(90)(91). There has been one case of fatal John Cunningham virus infection with ruxolitinib (92).…”