Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib

Kevin L Winthrop, Gil Y Melmed, Séverine Vermeire, Millie D Long, Gary Chan, Ronald D Pedersen, Nervin Lawendy, Andrew J Thorpe, Chudy I Nduaka, Chinyu Su, Kevin L Winthrop, Gil Y Melmed, Séverine Vermeire, Millie D Long, Gary Chan, Ronald D Pedersen, Nervin Lawendy, Andrew J Thorpe, Chudy I Nduaka, Chinyu Su

Abstract

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for ulcerative colitis (UC). Tofacitinib is approved for rheumatoid arthritis and psoriatic arthritis, where it has been shown to increase herpes zoster (HZ) risk. We evaluated HZ risk among UC patients using tofacitinib.

Methods: HZ cases were identified in tofacitinib phase II/III/ongoing, open-label, long-term extension (OLE) UC trials. We calculated HZ incidence rates (IRs) per 100 patient-years of tofacitinib exposure within phase III maintenance (Maintenance Cohort) and phase II/III/OLE (Overall Cohort) studies, stratified by baseline demographics and other factors. HZ risk factors were evaluated in the Overall Cohort using Cox proportional hazard models.

Results: Overall, 65 (5.6%) patients developed HZ. Eleven patients had multidermatomal involvement (2 nonadjacent or 3-6 adjacent dermatomes), and 1 developed encephalitis (resolved upon standard treatment). Five (7.7%) events led to treatment discontinuation. HZ IR (95% confidence interval [CI]) in the Overall Cohort was 4.07 (3.14-5.19) over a mean (range) of 509.1 (1-1606) days, with no increased risk observed with increasing tofacitinib exposure. IRs (95% CI) were highest in patients age ≥65 years, 9.55 (4.77-17.08); Asian patients, 6.49 (3.55-10.89); patients with prior tumor necrosis factor inhibitor (TNFi) failure, 5.38 (3.86-7.29); and patients using tofacitinib 10 mg twice daily, 4.25 (3.18-5.56). Multivariate analysis identified older age and prior TNFi failure as independent risk factors.

Conclusions: In tofacitinib-treated UC patients, there was an elevated risk of HZ, although complicated HZ was infrequent. Increased HZ rates occurred in patients who were older, Asian, or had prior TNFi failure (NCT00787202, NCT01465763, NCT01458951, NCT01458574, NCT01470612).

Figures

FIGURE 1.
FIGURE 1.
Overview of the tofacitinib development program for moderate to severe UC and the cohorts investigated. Patients meeting positive response criteria at the end of the 8-week OCTAVE Induction 1 and 2 studies were re-randomized to receive either tofacitinib 5-mg BID or tofacitinib 10-mg BID doses during the 52-week maintenance (OCTAVE Sustain) study. Nonresponders from the induction studies were eligible for inclusion within the OLE study, as were those completing the maintenance study. Abbreviations: N, number of patients treated; P, Phase.
FIGURE 2.
FIGURE 2.
IRs of HZ by time interval in Overall Cohort (phase II/phase III/OLE). Abbreviations: N, number of evaluable patients; n, number of unique patients with HZ infection.
FIGURE 3.
FIGURE 3.
Cox proportional hazards model of risk factors predicting HZ among UC patients using tofacitinib.

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Source: PubMed

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