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Live zoster vaccine confers limited protection during tofacitinib therapy

Key clinical point: Patients with RA given the live attenuated zoster vaccine (Zostavax) are still at risk for shingles during tofacitinib therapy.

Major finding: With 27-months’ follow-up, 5% of patients vaccinated before starting tofacitinib nonetheless developed herpes zoster.

Study details: An open-label, long-term extension study involving 100 patients with RA aged ≥50 years who were vaccinated before starting tofacitinib.

Disclosures: The study was sponsored by Pfizer. Dr. Winthrop disclosed consulting for AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, Pfizer, and UCB and receiving grant/research support from Bristol-Myers Squibb. Two coauthors disclosed financial relationships with Pfizer and other pharmaceutical companies, and the other seven coauthors were employees and shareholders of Pfizer.


"Patients with rheumatoid arthritis have an increased risk of developing herpes zoster, and tofacitinib and other JAK inhibitors are known to confer an additional risk on top of that. Because of this, the efficacy of herpes zoster vaccination is important to evaluate. The ORAL Sequel study looks at long-term followup of patients given a live attenuated varicella zoster vaccine after beginning tofacitinib therapy, in terms of varicella zoster virus (VZV) immunity and incidence of herpes zoster. Of the 100 enrolled patients, 5 developed herpes zoster despite live VZV vaccination; while numbers are small, this is similar to published results in non-vaccinated patients receiving tofacitinib. The study looks at humoral vs. cell-mediated immunity in these patients and patterns are hard to interpret due to small numbers of patients; however, there appears to be incomplete cell-mediate immunity in a 3 patients as measured by interferon-gamma enzyme-linked immunosorbent spot. A similar study looking at the efficacy of the non-live VZV vaccine would be helpful, as well as comparison of cell-mediated and humoral immunity in all 100 patients, not only those affected by herpes zoster, to determine whether more patients are at potential risk of herpes zoster based on lack of immunity."

Arundathi Jayatilleke, MD

Lewis Katz School of Medicine, Temple University


Winthrop KL et al. Ann Rheum Dis. 2020 Mar 11. doi: 10.1136/annrheumdis-2019-216566.