Not only is herpes zoster (HZ) incidence higher in patients with rheumatoid arthritis (RA) compared with the general population, but past research has suggested risk could be further increased with disease-modifying antirheumatic drugs (DMARDs).
In fact, real-world data have indicated that HZ incidence is approximately twofold higher with tofacitinib, an oral Janus kinase inhibitor for the treatment of RA, compared with biological DMARDs (bDMARDs), according to a study in Annals of the Rheumatic Diseases.
Oregon Health & Science University–led researchers point out that current American College of Rheumatology guidelines conditionally recommend that patients with RA who are aged 50 years or older receive HZ vaccine prior to tofacitinib or bDMARDs.
The researchers explain that they previously evaluated the immunogenicity of a live attenuated zoster vaccine (LZV), administered 2 to 3 weeks prior to tofacitinib or placebo with background conventional synthetic DMARDs and found that both groups had similar varicella zoster virus (VZV)–specific immune responses. In addition, overall immune responses were determined to be comparable with those of healthy volunteers in previous studies.
Now, the study team has followed that patient cohort in an open-label, long-term extension (LTE) study of tofacitinib.
Patients enrolled in the index study could join ORAL Sequel 14 weeks postvaccination, where they received open label tofacitinib 5 mg or 10 mg two times per day, as well as any background RA therapy. With 27 months of follow-up, postvaccination, adverse events (AEs), including discontinuations due to AEs, were recorded during the study within 28 days of the last dose.
Researchers calculated incidence rates (IRs; patients with events/100 patient-years (PY)) and 95% CIs for HZ post-vaccination based on time to first event, with patients not reporting an event censored at last treatment dose. They also evaluated short-term VZV-specific immunity at baseline and Week 6 postvaccination during the index study.
Vaccine-related AEs in the index study included mild injection-site pain, swelling, redness, itching, and myalgia. Disseminated vaccine-strain varicella was also reported in a patient with no previous exposure to VZV.
With rollover into the ORAL Sequel, 100 patients received either an average tofacitinib dose of 5 mg (n = 46) or 10 mg (n = 54) two times per day. Mean (range) tofacitinib exposure was 489 (46-811) days and overall exposure was 139 PY, according to the study.
Results indicate that LZV did not provide adequate protection to all patients. Researchers report that five HZ cases (#1–5) occurred in the LTE study 218, 280, 748, 741, and 544 days postvaccination, respectively (IR = 3.60 (1.17, 8.39).
Cases #1 through #4 were monodermatomal, and case #5 involved five dermatomes, according to the report, which notes that all HZ events were mild/moderate in severity and resolved with antiviral treatment.
“These results suggest that LZV may not provide adequate long-term protection, as previously demonstrated in healthy individuals aged ≥60 years 3 years post-vaccination, in which HZ risk was reduced by 51%,” the authors write. “While it is possible that LZV booster vaccinations may improve vaccine efficacy, to date there is a lack of data on the use and timing of booster vaccinations, and no recommendations on the use of LZV booster vaccinations currently exist. This highlights the importance of evaluating the newly approved subunit non-live vaccine (Shingrix) in patients with RA receiving tofacitinib.”
The CDC recommends the recombinant zoster vaccine, Shingrix, as preferred over zoster vaccine live, marketed as Zostavax, for the prevention of HZ and related complications. The CDC recommends two doses of Shingrix separated by 2 to 6 months for immunocompetent adults aged 50 years and older, whether or not they report a prior episode of HZ or have received a prior dose of Zostavax.
The recombinant zoster vaccine also is urged for patients who have chronic medical conditions, including RA, as well as chronic renal failure, diabetes mellitus, and chronic pulmonary disease, unless a contraindication or precaution exists. Both vaccines also are considered safe for patients taking low-dose immunosuppressive therapy, who are anticipating immunosuppression or have recovered from an immunocompromising illness.
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