Herpes Zoster in Tofacitinib Users with and without Concomitant Methotrexate and Glucocorticoids

Jeffrey R. Curtis¹, Fenglong Xie¹, Sasha Bernatsky², Shuo Yang¹, Lang Chen¹, Huifeng Yun¹ and Kevin Winthrop³, ¹University of Alabama at Birmingham, Birmingham, AL, ²Division of Rheumatology, The Research Institute of the McGill University Health Centre, Montreal, QC, Canada, ³Oregon Health and Science University, Portland, OR

Meeting: ACR/ARHP Annual Meeting 2018

Keywords: glucocorticoids, Medicare, Methotrexate (MTX) and tofacitinib

Session Information

Date: Sunday, October 21, 2018

Title: 3S086 ACR Abstract: RA–DX, Manifestations, & Outcomes I: Other Co-Morbidities (880–885)

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: An increased incidence of herpes zoster (HZ) has been observed with Janus kinase inhibitors such as tofacitinib (TOF). However, among TOF users, a potentially additive or multiplicative risk of HZ associated with concomitant methotrexate (MTX) and glucocorticoid (GC) use is not clear. We evaluated HZ risk in TOF users with and without MTX and GC, to evaluate potential interactions.

Methods: MarketScan and Medicare data (2011-2016) was used to identify all rheumatologist-diagnosed RA patients initiating TOF (index date); demographics and covariates were evaluated in the 12 prior months (baseline); pts with HIV, malignancy or prior HZ (or anti-viral commonly used for HZ) in baseline were excluded. All 3 main drug exposures were time-varying with a 30 day extension. HZ was ascertained using ICD9/10 codes with anti-viral drug use (+-7 days). Multivariable (MV) Cox regression was used to evaluate hazard ratios (HRs) for HZ in TOF users with and without MTX and GC, controlling for baseline covariates.

Results: A total of 8,030 new TOF users met eligibility criteria for analysis. Mean (SD) age was 60.3 (12.6) years, 83.3% women. The crude HZ incidence with TOF use was numerically lowest in the absence of GC (e.g. 3.4/100py with MTX and 3.7/100py without MTX, Table). An approximately two-fold increased crude incidence of HZ was observed for TOF users receiving either GCs alone (6.0/100 py) or both MTX and GCs (6.5/100py). After MV adjustment, the HR for HZ associated with TOF was unchanged when given with MTX but approximately double when TOF was given with GC. Based on the non-significant interaction p value, there was no indication of an interaction between MTX and GC. Among various covariates, older age was a significant albeit weak risk factor for HZ (adjusted HR = 1.05, 95% CI 1.03-1.18, per 5 year increment).

Conclusion: These analyses suggest that HZ risk in TOF users is doubled with GC exposure. Concomitant MTX did not confer increased risk.

Table: Herpes Zoster Risk Associated with Tofacitinib
according to Concomitant Use of Methotrexate and Glucocorticoids

Concomitant Medications with TOF	Events	Incidence Rate per 100PY	Adjusted Hazard Ratio
No MTX; no GC	73/1986	3.7 (2.9-4.6)	1.0 (ref)
With MTX; no GC	27/791	3.4 (2.3-5.0)	1.00 (0.64, 1.55)
No MTX; with GC	82/1356	6.0 (4.9-7.5)	2.03 (1.42, 2.91)
With MTX; with GC	40/617	6.5 (4.8-8.8)	2.24 (1.47, 3.43)
PY = Patient-years; MTX = methotrexate; GC = glucocorticoid

Disclosure: J. R. Curtis, AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Radius, Roche/Genentech, UCB, 2,AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Radius, Roche/Genentech, UCB, 5; F. Xie, None; S. Bernatsky, None; S. Yang, None; L. Chen, None; H. Yun, Bristol Myers Squibb, 2; K. Winthrop, Pfizer, Inc., 5,Lilly, 5,AbbVie Inc., 5,Galapagos, 5.

To cite this abstract in AMA style:

Curtis JR, Xie F, Bernatsky S, Yang S, Chen L, Yun H, Winthrop K. Herpes Zoster in Tofacitinib Users with and without Concomitant Methotrexate and Glucocorticoids [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/herpes-zoster-in-tofacitinib-users-with-and-without-concomitant-methotrexate-and-glucocorticoids/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/herpes-zoster-in-tofacitinib-users-with-and-without-concomitant-methotrexate-and-glucocorticoids/