medwireNews: Two studies published in Arthritis & Rheumatology explore strategies for reducing herpes zoster risk among patients with rheumatoid arthritis (RA) treated with the Janus kinase inhibitor tofacitinib.
Kevin Winthrop (Oregon Health and Science University, Portland, USA), lead author of both studies, and co-authors explain that patients with RA “are at 1.5- to 2-fold higher risk of [herpes zoster] compared with similarly aged individuals in the general population,” and note that this risk can be further increased by RA treatments, including conventional disease-modifying antirheumatic drugs (DMARDs) and biologic therapies.
In the first study, Winthrop and colleagues carried out a phase II trial to assess whether tofacitinib affected the safety and immunogenicity of live zoster vaccine among patients with active RA who were receiving background methotrexate therapy.
The team found comparable varicella-zoster virus (VZV)-specific humoral and cell-mediated immune responses among the 55 patients who were randomly assigned to receive live zoster vaccine followed by tofacitinib 5 mg twice daily 2–3 weeks after vaccination and the 57 patients who were given live zoster vaccine followed by placebo.
Six weeks after vaccination, mean VZV-specific immunoglobulin (Ig)G levels were 403.42 U/mL for patients in the tofacitinib group and 322.49 U/mL for those receiving placebo, and the geometric mean fold rise (GMFR) from baseline was 2.11 U/mL and 1.74 U/mL, respectively. The VZV-specific T-cell GMFR measurements were a corresponding 1.50 U/mL and 1.29 U/mL.
Although GMFR measurements were numerically higher among tofacitinib-treated patients, the researchers note that these differences were “small and not statistically significant,” and conclude that tofacitinib-treated patients “are capable of mounting adequate immune responses to this vaccine.”
In all, three patients in the tofacitinib group and none in the placebo group experienced serious adverse events, including one case of disseminated primary varicella infection. Subsequent blood evaluation revealed that this patient was the sole study participant with no prior exposure to VZV.
These findings “indicate the potential need to either screen for prior exposure before giving this vaccine or waiting longer than 2–3 weeks before starting immunosuppression with tofacitinib,” emphasize the researchers.
In the second study, Winthrop and team analyzed data from 19 clinical trials and long-term extension studies to determine whether treatment with DMARDs or glucocorticoids in addition to tofacitinib increases the risk for herpes zoster infection.
They found that 10.3% of 6192 tofacitinib-treated patients experienced herpes zoster over a median follow-up of 3.0 years, and the majority (92.8%) of cases were non-serious.
When the incidence of herpes zoster was compared in groups of patients treated with tofacitinib at different doses with and without concomitant therapies, the highest rates were observed in patients receiving tofacitinib 10 mg twice daily together with conventional DMARDs and glucocorticoids, while the lowest rates were seen among those receiving tofacitinib monotherapy 5 mg twice daily without glucocorticoids (incidence rate=5.44 and 0.56 patients with events per 100 patient–years, respectively).
After adjustment for factors including gender, disease duration, background therapy, and comorbidities, patients taking glucocorticoids were 49% more likely to experience herpes zoster infection than those who were not taking glucocorticoids. Older age, smoking, enrolment in Asia, and tofacitinib dose were also identified as independent predictors of herpes zoster.
These findings “suggest that the use of the FDA approved 5 mg [twice daily] dose, and elimination of concomitant therapies, may represent potential risk-reduction strategies for physicians and patients, provided disease activity remains controlled,” write the study authors.
And summarizing the results from both studies, Winthrop told the press: “If you want to lower shingles risk for rheumatoid arthritis patients, there are two strategies: one is vaccinating them and the other is getting them off steroids and methotrexate if you can.”
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