The live varicella-zoster vaccine may be effective in patients with RA who are starting treatment with tofacitinib.
Patients with rheumatoid arthritis face an increased risk of herpes zoster, but new research indicates that the live varicella-zoster vaccine can effectively prevent shingles in these patients before they start treatment with the drug tofacitinib.
Patients who live with rheumatoid arthritis are at increased risk for shingles compared with healthy adults, and disease-modifying antirheumatic drugs (DMARDs) used to treat rheumatoid arthritis are thought to increase this risk. Tofacitinib, a Janus kinase (JAK) inhibitor, is a targeted, synthetic DMARD approved for treatment of moderate to severely active rheumatoid arthritis in patients who have had an inadequate response to methotrexate.
A team of researchers led by Kevin Winthrop MD, MPH, of the Oregon Health and Science University conducted 2 studies to evaluate the effect of tofacitinib on the immune response and the safety of the live varicella-zoster vaccine. They found that the varicella-zoster vaccine elicits a robust immune response in patients when administered several weeks prior to the start of tofacitinib.
The researchers recently published their findings in Arthritis & Rheumatology.
The first study
This first study was a phase II trial of 112 patients older than 50 years with active rheumatoid arthritis receiving background methotrexate. All 112 patients were vaccinated with the live varicella-zoster vaccine; 2 to 3 weeks later, the participants were randomized to receive tofacitinib or placebo.
The start of tofacitinib after vaccination had no negative impact on the established immune response. Patients developed robust immune responses to the vaccine, and patients treated with tofacitinib had similar or even higher immune responses to the vaccine compared with placebo-treated patients. This result may have been the result of patients who received tofacitinib having better control of their rheumatoid arthritis than patients treated with placebo.
“We showed that the vaccine was adequately immunogenic in patients whether they were starting tofacitinib or placebo in a few weeks, and the immunogenicity and the response to the vaccine were similar to what we’ve seen outside the rheumatoid arthritis setting in general population studies,” said Dr Winthrop in a press release.
One patient experienced disseminated varicella infection after starting tofacitinib, but researchers discovered that this patient was the sole participant who had not had chicken pox in the past. Shingles arises when the chicken pox virus that remains dormant in the body is reactivated, so this finding emphasizes the importance of only giving the live varicella-zoster vaccine to patients who have had chickenpox.
The second study
This group’s second study was aimed to evaluate whether concomitant treatment with conventional synthetic DMARDs, such as methotrexate and chloroquine, or corticosteroids contributes to the increased risk of shingles linked to tofacitinib. The researchers analyzed 19 clinical trials that involved a total of 6192 patients who had rheumatoid arthritis. In this patient population, the rate of shingles was lowest for patients taking tofacitinib without conventional synthetic DMARDs or corticosteroids and highest for those taking tofacitinib with conventional synthetic DMARDs and corticosteroids.
Implications for physicians
These studies indicate that the live varicella-zoster vaccine can effectively prevent shingles in patients who have rheumatoid arthritis and are starting treatment with tofacitinib. The findings are encouraging in that the risk of shingles is higher in patients with rheumatoid arthritis than in healthy adults.
However, there appears to be a greater risk of shingles in patients receiving treatment with tofacitinib as well as conventional synthetic DMARDs and corticosteroids than in patients receiving tofacitinib monotherapy without additional medications. Thus, the use of tofacitinib alone should be considered to help reduce the risk of shingles in vaccinated patients, provided the patient’s rheumatoid arthritis remains controlled with the drug.
These studies were sponsored by Pfizer.
Winthrop KL, Wouters AG, Choy EH, et al. “The Safety and Immunogenicity of Live Zoster Vaccination in Patients With Rheumatoid Arthritis Before Starting Tofacitinib: A Randomized Phase II Trial.” Arthritis Rheumatol. 2017 Aug 28. doi: 10.1002/art.40187. [Epub ahead of print] 2017 Aug 28. doi: 10.1002/art.40187. [Epub ahead of print]
Winthrop KL, Curtis JR, Lindsey S, et al. “Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy.” Arthritis Rheumatol. 2017 Aug 28. doi: 10.1002/art.40189. [Epub ahead of print]
Peters D. “Studies Reveal How Shingles Vaccine Should Be Used in Arthritis Patients.” Wiley Newsroom. Published online August 28, 2017.