Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib

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,

Systematic review with meta‐analysis: efficacy and safety of oral Janus kinase inhibitors for inflammatory bowel disease

“…Although most cases of HZ cases occurred in patients exposed to JAK inhibitors compared to placebo in our review, it should be acknowledged that our study was underpowered to accurately determine the risk of HZ because open‐label maintenance and extension phases were excluded. Using individual patient data from phase II, III, open‐label, long‐term extension, and ongoing tofacitinib for UC trials, Winthrop et al identified 65 patients (5.6%) who developed HZ, with 11 patients developing severe multi‐dermatomal involvement . Importantly, the incidence of HZ was highest in patients ≥65 years, Asians, those receiving tofacitinib 10 mg BID, and patients previously failing a TNF antagonist.…”

Efficacy and safety of tofacitinib dose de‐escalation and dose escalation for patients with ulcerative colitis: results from OCTAVE Open

“…6 The safety profile of tofacitinib in the UC clinical programme appeared similar to that reported in patients with rheumatoid arthritis and-with the exception of higher rates of herpes zoster infectionsimilar to biologic therapies for the treatment of UC. 7 Dose-related increases in the rate of herpes zoster infections observed during OCTAVE Sustain 5,7,8 and an increased incidence of venous thromboembolic events manifested as pulmonary embolism events observed in patients treated with tofacitinib 10 mg twice daily (b.d.) compared to tofacitinib 5 mg b.d.…”

The Who and Why of Herpes Zoster Vaccination in Patients With Inflammatory Bowel Diseases

“…11 In the OCTAVE trials, the HZ incidence was 4.07 per 100 patients and was reported to be mild and involved fewer than 2 dermatomes in the majority of cases. 12 The risk of HZ with tofacitinib appears to be dose-dependent, with a numerically higher risk of HZ associated with tofacitinib 10 mg twice daily (10 cases) compared with 5 mg twice daily (3 cases), with only 1 case in a placebo patient. Collectively, a total of 69 HZ events occurred in 65 patients enrolled in the OCTAVE induction, maintenance, and open-label trials.…”

“…Collectively, a total of 69 HZ events occurred in 65 patients enrolled in the OCTAVE induction, maintenance, and open-label trials. 12,13 Overall, 5.6% of 1157 patients developed HZ for an incidence ratio of 4.07 (95% CI, 3.14-5.19). Although most events (n ¼ 51; 74%) involved 1 or 2 adjacent dermatomes, there were 18 multidermatomal or disseminated HZ events.…”

“…Asian patients had a higher risk for HZ (hazard ratio, 1.76; 95% CI, 0.97-3.19) compared with those of non-Asian race. 12 It is worth noting that tofacitinib mainly blocks JAK1 and JAK3, and to a lesser extent JAK-2, whereas filgotinib, an oral JAK inhibitor, selectively blocks JAK1 over JAK 2 and JAK 3. Filgotinib was not associated with an increased risk of HZ in a phase II study evaluating the efficacy of treating patients with CD.…”