Shingles vaccine can be given before starting tofacitinib, industry-funded study says
The authors concluded that tofacitinib alone for the treatment of rheumatoid arthritis should be considered to help reduce the risk of shingles in vaccinated patients, provided that patients' arthritis remains controlled on the drug.
Live varicella-zoster vaccine elicits robust immune responses in patients when administered several weeks prior to the start of treatment with tofacitinib, a study found.
The research consisted of two studies sponsored by Pfizer Inc., with researchers reporting they were company employees or had received fees and other support. Results were published by Arthritis & Rheumatology on Aug. 28.
In the first study, 112 patients with active rheumatoid arthritis were vaccinated and then randomized to receive tofacitinib or placebo started two to three weeks after vaccination. In this phase II, 14-week, placebo-controlled trial, 112 patients older than age 50 years with active rheumatoid arthritis on background methotrexate were given live zoster vaccine (LZV) and then randomized to receive tofacitinib, 5 mg twice daily (n=55), or placebo (n=57).
Researchers measured humoral (varicella-zoster virus [VZV]-specific IgG via gpELISA) and cell-mediated responses (VZV-specific T-cell enumeration via ELISPOT) at baseline and at two, six, and 14 weeks postvaccination. Endpoints included the geometric mean fold rise (GMFR) in VZV-specific IgG levels (primary endpoint) and T-cells (spot-forming cells/106 PBMCs) at 6 weeks post-vaccination.
Six weeks postvaccination, VZV-specific IgG GMFR was 2.11 for tofacitinib and 1.74 for placebo, and VZV-specific T-cell GMFR increased similarly for tofacitinib (1.50) and placebo (1.29). Serious adverse events occurred in three (5.5%) patients receiving tofacitinib and 0 (0%) placebo patients.
One patient who had not had chicken pox developed cutaneous vaccine dissemination two days after starting tofacitinib (16 days postvaccination), which resolved after withdrawal of tofacitinib and antiviral therapy. The researchers wrote that the finding emphasizes the importance of only giving the vaccine to patients who have had chicken pox because shingles arises when the chicken pox virus that remains dormant in the body is reactivated. Arthritis drugs that suppress the immune system put patients at an elevated risk of disseminated varicella infection following vaccination, they noted.
The second study identified herpes zoster reports from 19 phase I-III and long-term extension tofacitinib studies in rheumatoid arthritis patients to see if concomitant use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs, such as methotrexate and chloroquine) or corticosteroids contribute to the increased risk of shingles linked to tofacitinib. The study involved an analysis of 19 clinical trials involving a total of 6,192 patients (16,839 patient-years) with rheumatoid arthritis.
Herpes zoster was reported in 636 tofacitinib-treated patients (incidence rate [IR], 4.0 [95% CI, 3.7 to 4.4]). Most cases were not serious (93%). Incident rates varied across regions, from 2.4 (95% CI, 2.0 to 2.9) in Eastern Europe to 8.0 (95% CI, 6.6 to 9.6) in Japan and 8.4 (95% CI, 6.4 to 10.9) in Korea. Within phase III studies, IRs varied by tofacitinib dose, background csDMARDs use, and baseline glucocorticoid use. IRs were numerically lowest for tofacitinib monotherapy, 5 mg twice daily, without glucocorticoids (IR, 0.56; 95% CI, 0.07 to 2.01) and highest for tofacitinib, 10 mg twice daily with csDMARDs, and glucocorticoids (IR, 5.44; 95% CI, 3.72 to 7.68). Age, glucocorticoids, tofacitinib dose, and enrollment within Asia were independent risk factors.
The investigators noted that similar efficacy has been observed with tofacitinib in phase III clinical studies regardless of whether it is administered as monotherapy or in combination with csDMARDs and/or corticosteroids. They concluded that tofacitinib alone for the treatment of rheumatoid arthritis should be considered to help reduce the risk of shingles in vaccinated patients, provided that patients' arthritis remains controlled on the drug.
An editorial outlined recommendations for vaccination and concluded, “Despite advances in our understanding, there remain some uncertainties regarding zoster vaccination especially in autoimmune patients or those patients receiving high risk drugs (high dose corticosteroids, biologics, and Jak inhibitors). For each of these uncertainties, there is a little to no evidence and thusly forms the basis for an ongoing research agenda in zoster vaccination.”