Unclear benefit of Zostavax in people starting on tofacitinib

Zostavax may not provide adequate long-term protection in people taking tofacitinib for their rheumatoid arthritis.

Introduction
Rheumatoid arthritis is a chronic inflammatory disease that can affect a person’s joints, and may cause pain and disability. Rheumatoid arthritis affects people of all ages, and is more common in women than men. People with rheumatoid arthritis naturally have an increased risk of developing infections due to the underlying disease, as well as some of the medicines that are used to treat it. In particular, Herpes zoster, which causes shingles, is more common in people with rheumatoid arthritis.

Vaccinations can prevent infections. Vaccines may be live or non-live. Live vaccines are made from living organisms or viruses that have been altered so they are unlikely to cause illness, but they can still replicate in order to produce a protective immune response. Non-live vaccines use killed organisms or viruses, or certain parts of their structure. Some vaccines are fine to take if you have rheumatoid arthritis. However, some medicines used to treat rheumatoid arthritis may affect how a person’s immune system responds to vaccination (their immune response), and may mean that people are not properly protected by the vaccine.

Current guidelines from the American College of Rheumatology conditionally recommend that people aged 50 or over with rheumatoid arthritis receive herpes zoster vaccination before they start taking tofacitinib or biologic medicines. These drugs work by targeting specific molecules that cause inflammation. By doing so, they reduce inflammation in the joints and decrease pain and disease worsening in rheumatoid arthritis. Tofacitinib is one of a group of medicines called the JAK inhibitors. Like biologics, it helps reduce inflammation, but it works in a different way inside cells to block a molecule called a Janus kinase (JAK).

What did the authors hope to find?
The authors hoped to find out how well people did after having the live Herpes zoster vaccine, and then starting treatment with tofacitinib.

Who was studied?
The study looked at 100 people with rheumatoid arthritis who were using tofacitinib, and who had been vaccinated with the live shingles vaccine (Zostavax). These people were all taking part in a long-term clinical trial called the ORAL Sequel study which was looking at tofacitinib.

How was the study conducted?
This was a longitudinal follow-up of people vaccinated in a prior study which had looked at the safety of the vaccine in people treated with tofacitinib. The authors went back to see how many of the people developed shingles.

What were the main findings of the study?
The authors found 5 people had developed shingles despite being vaccinated. This rate was about the same as would have been expected for unvaccinated people taking tofacitinib.

These results suggest that Zostavax might not provide adequate long-term protection against shingles in people with rheumatoid arthritis taking tofacitinib. This is in contrast to previous results in people over the age of 60 without rheumatoid arthritis, whose risk of getting shingles is halved even 3 years after vaccination.

Are these findings new?
Yes, there is not much known about how shingles happens after taking this vaccine in people with rheumatic disease, particularly those using the new JAK inhibitor medicines like tofacitinib.

What are the limitations of the study?
The major limitation is that this was a small study, and it did not have an unvaccinated group to compare against.

What do the authors plan on doing with this information?
More studies are needed to look into this. The authors think that it is possible that having another shot of the vaccine (a booster) could improve the efficacy, but there is not yet much information to support this, and no recommendations on Zostavax booster vaccinations currently exist. It will be important to test the newly approved non-live vaccine (Shingrix) in people with  rheumatoidarthritis who are receiving tofacitinib to see if this works better. It is more effective in people without rheumatoid arthritis, so it might also be more effective in people with the disease.

What does this mean for me?
If you have rheumatoid arthritis, it is important that you stay up to date with the recommended vaccines to help protect you against infections. At the moment, if you are 50 or over, talk with your doctor about shingles prevention.

If you have any concerns about your disease or its treatment, you should talk to your doctor. It is important that you do not stop taking any medicine you have been prescribed without getting proper medical advice.

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Date prepared: March 2020
Summary based on research article published on: 11 March 2020
From: Winthrop K, et al. Long-term effectiveness of live herpes zoster vaccine in patients with rheumatoid arthritis subsequently treated with tofacitinib. Ann Rheum Dis 2020;79:669–671. doi:10.1136/annrheumdis-2019-216566

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