So this is new and fancy. Just when I thought I had the whole “shingles vaccine thing” covered, along come the JAK inhibitors to throw a monkey wrench into the whole shebang.
Let’s start with what I thought I knew: Shingles are bad, patients with autoimmune inflammatory diseases are at higher risk for shingles, there’s a vaccine available (Zostavax®), and the timing of the vaccine can get tricky in patients being treated with high-dose prednisone and/or biologics because, you know, it’s a live vaccine. Grossly oversimplified, sure, but that’s the crux of the matter.
Then tofacitinib came along and made my brain hurt.
Tofacitinib is a JAK inhibitor approved for use in patients with moderate-to-severe rheumatoid arthritis (RA) who have an inadequate response or intolerance to methotrexate.1 The one glaring safety signal that came out of the tofacitinib clinical trials and subsequent real-world studies involved shingles. A study by Dr. Jeff Curtis and colleagues found that the risk of shingles in patients on tofacitinib is approximately double compared to the rates seen in patients on biologics.2 The same seems to be true for baricitinib, another JAK inhibitor that is not yet approved in the United States.3
So then what’s the logical next step for providers when we find out that a medication puts patients at higher risk for shingles? More vaccine please.
But wait! Safety first! Remember, we are super-duper careful about giving the shingles vaccine to patients on biologics. But wait! Are the JAK inhibitors biologics? No, they are not. They are “targeted synthetic disease modifying antirheumatic drugs,” aka tsDMARDs (thank you ever so much, that’s just what I needed—another acronym to remember). So we should theoretically be able to give patients on JAK inhibitors the shingles vaccine, right?
But wait! Dr. Kevin Winthrop at Oregon Health & Sciences University says it’s not that easy. Dr. Winthrop is ūber smart—he gets studies conceived, approved, enrolled, completed, and published while I’m still rolling out of bed and lamenting the fact that I’m not allowed to wear my pajamas to work.
In 2015, Dr. Winthrop presented a late-breaking abstract at the annual American College of Rheumatology meeting entitled “Assessment of immunogenicity of live zoster vaccination (Zostavax®) in rheumatoid arthritis patients on background methotrexate before and after initiating tofacitinib or placebo” (apparently, being ūber smart doesn’t always equate to an ability to write a catchy abstract title).4
The major point of the study was to show that patients given the live zoster vaccine and then started on tofacitinib were able to mount an adequate immune response (i.e., the vaccine “took”). But what Dr. Winthrop and his co-authors also found was that one patient developed disseminated shingles from the vaccine. When they went back and looked, they realized that that particular patient did not have varicella antibodies before being vaccinated.
Let that sink in a moment. Perhaps reread those sentences again. Don’t worry, it took me a while to get it, too.
What the study findings mean from a clinical perspective—and this is giving me palpitations as I write it because the LAST thing a Vaccine Queen like me wants to do is complicate the vaccination process—is that we should probably check varicella zoster virus immunoglobulin G levels (VZV IgG) on all of our patients before they start a JAK inhibitor. If they don’t have evidence of previous infection, they need VARICELLA vaccination, not ZOSTER vaccination.
The live zoster vaccine is 14x stronger than the varicella vaccine,5 which is why, in an immunocompromised person, the zoster vaccine can cause disseminated illness. Like the zoster vaccine, the varicella vaccine is live, so the same precautions apply. Unlike the zoster vaccine, the varicella vaccine requires two doses, given at least 28 days apart.
I suspect a good many of you are now thinking to yourself, “Holy Moly! What are we going to do about our patients born after 1980 who should therefore have received the varicella vaccine series, but VZV IgG won’t show up because the commercially‑available tests don’t pick up IgG from vaccine, only from actual chicken pox disease?”
Right? Am I right? Amiright? Of course I am. You’re smart, almost as smart as Dr. Kevin Winthrop.
Bad news: I don’t really have an answer for you here. This would be an excellent time to consult with your good friends over in Infectious Disease.
Good news: This whole headache will theoretically go away once the new subunit shingles vaccine is approved (which will hopefully happen later this year or maybe in 2018). It’s not live, so we won’t have to perform all these mental acrobatics just to protect our patients. Stay tuned for more on that, because when that vaccine comes out, I can assure you that I will be waiting with baited breath for Dr. Kevin Winthrop to tell us all about it!
(With apologies to Dr. Kevin Winthrop, who really doesn’t deserve this kind of abuse.)
Elizabeth Kirchner, CNP, RN-BC Elizabeth Kirchner, CNP, RN-BC, is a nurse practictioner at the Cleveland Clinic in Cleveland, Ohio, and the Education and Curriculum Chair of the Rheumatology Nurses Society.
1. U.S. Food and Drug Administration. XELJANZ ® (tofacitinib): Highlights of Prescribing Information. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203214s010lbl.pdf. Accessed May 18, 2017. 2. Curtis JR, Xie F, Yun H, et al. Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis. Ann Rheum Dis. 2016;75:1843-1847. 3. Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374:1243-52. 4. Winthrop K, Wouters A, Choy EH. Assessment of immunogenicity of live zoster vaccination (Zostavax®) in rheumatoid arthritis patients on background methotrexate before and after initiating tofacitinib or placebo. Available at http://acrabstracts.org/abstract/assessment-of-immunogenicity-of-live-zoster-vaccination-zostavax-in-rheumatoid-arthritis-patients-on-background-methotrexate-before-and-after-initiating-tofacitinib-or-placebo/. Accessed May 18, 2017. 5. Centers for Disease Control and Prevention. Varicella (Chickenpox) and Herpes Zoster (Shingles): Overview of VZV Disease and Vaccination for Healthcare Professionals. Available at https://www.cdc.gov/vaccines/vpd-vac/shingles/downloads/vzv_clinical_slideset_jul2010.pdf. Accessed May 18, 2017.