Update on Herpes Zoster Studies Presented at ACR 2015

Herpes zoster was a hot topic at this year’s American College of Rheumatology Annual Meeting with no less than 13 abstracts that addressed this important opportunistic infection.

I previously commented on our work that demonstrated herpes zoster (HZ) is associated with an about 30% increased risk of stroke in the month after infection. For patients afflicted with HZ of the trigeminal nerve (i.e., herpes zoster ophthalmicus), this increase may exceed 300% for the first several months. We also demonstrated that prompt treatment may mitigate these risks. In light of these data, we were interested in what was presented in terms of understanding pathogenesis and what can be done to prevent HZ.

Tofacitinib is kinase inhibitor well known to be associated with a high rate of HZ exceeding that observed for patients on traditional biologics. Data have suggested the risk is genetically enhanced for patients of Asian extraction. Nan Bing, MD, and colleagues performed a genome-wide association study of 5,246 tofacitinib-treated patients and examined more than 8 million genetic variants with a case-control methodology to exam genetic associations with HZ. Several associations were identified, including several involved with iNKT cells, which may be important in viral surveillance. The risk allele of one polymorphism also was noted to be over-expressed in a Japanese population giving some credence to the clinical risk of race.

In another important study, Kevin L. Winthrop, MD, MPH, and colleagues clearly demonstrated that concomitant use of disease-modifying antirheumatic drugs and glucocorticoids dramatically increase the risk of HZ. They also demonstrated that tofactinib monotherapy had a more benign risk profile.

In terms of vaccine prevention, several important studies were presented. Jeffrey R. Curtis, MD, MS, MPH, and colleagues provided an update on the preliminary findings from VERVE, a study designed to primarily explore the safety of live HZ vaccine in 1,000 patients on tumor necrosis factor inhibitors. While their study is far from over, preliminary results are encouraging with no obvious safety signals.

Stephen Lindsey, MD, also continued to document the safety of live HZ vaccine in patients on biologics in his own open “drug pause” protocol. Alternatively, Winthrop reported a small trial of live HZ vaccination in tofacitinib-treated patients who demonstrated similar boosting of cell-mediated and humoral immunity compared with a placebo-exposed population. Unfortunately in this very small study of roughly 100 patients, one patient developed cutaneous dissemination of the vaccine strain of HZ that occurred 2 days after starting tofacitinib and 16 days after vaccination. Of note in the pivotal trial of this vaccine in healthy adults was that no case of dissemination was observed within 30 days in more than 18,000 subjects. I believe this single case speaks strongly to a highly specific breach of varicella immune surveillance associated with the tofacitinib mechanism of action. Further work is need.

Lastly, the group from the Geisinger Clinic reminded us that exposure to the HZ vaccine is poor in patients with immune suppressive illnesses as it is in the general population. New strategies that involve patients directly and, in particular, advanced practitioners are sorely needed.

Leonard H. Calabrese, DO, is the Chief Medical Editor, Healio Rheumatology and Professor of Medicine, Cleveland Clinic Lerner, College of Medicine of Case Western Reserve University, RJ Fasenmyer Chair of Clinical Immunology, Theodore F. Classen, DO Chair of Osteopathic Research and Education, Vice Chairman, Department of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland. He can be reached on Twitter at @LcalabreseDO.

References:

http://consultqd.clevelandclinic.org/2015/11/herpes-zoster-raises-near-term-stroke-risk-in-patients-with-autoimmune-diseases/

Bing N, et al. Abstract #566.

Curtis JR, et al. Abstract #1520.

Lindsey S, et al. Abstract #1836.

Meadows A, et al. Abstract #2504.

Winthrop KL, et al. Abstract #12L.

Winthrop KL, et al. Abstract #559.

All presented at the American College of Rheumatology Annual Meeting; Nov. 7-11, 2015; San Francisco.

Disclosure: Calabrese reports he is a consultant for Genentech, Pfizer, Bristol-Myers Squibb, GlaxoSmithKline, Sanofi, Jansen and Abbvie; and is on the speakers bureau for Genentech, Abbvie and Bristol-Myers Squibb and Crescendo Bioscience.