Long-term Risk of Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib

Inflamm Bowel Dis. 2023 Jan 5;29(1):85-96. doi: 10.1093/ibd/izac063.

Abstract

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We report herpes zoster (HZ) incidence and risk factors in the tofacitinib UC clinical program (up to 7.8 years).

Methods: Proportions and incidence rates (IRs; unique patients with events/100 patient-years) of HZ were evaluated in 4 cohorts: Induction (phase 2 and 3 induction study data), Maintenance (phase 3 maintenance study data), Overall (data from all phase 2, 3, and open-label, long-term extension studies), and Overall plus interim 6-month phase 3b and 4 data. Herpes zoster risk factors were assessed by Cox regression analysis.

Results: In the Induction and Maintenance Cohorts, IRs for HZ (nonserious and serious) were numerically higher with tofacitinib 10 mg twice daily (BID) vs placebo and tofacitinib 10 vs 5 mg BID, respectively. With all tofacitinib doses (5 or 10 mg BID), IRs (95% confidence intervals) for HZ in the Overall and Overall plus phase 3b/4 Cohorts (total exposure, 2814.4 and 2999.7 patient-years, respectively) were 3.38 (2.73-4.15) and 3.30 (2.67-4.04), respectively. In the Overall plus phase 3b/4 Cohort, >90% of HZ were nonserious; >90% were mild/moderate; >90% resolved without discontinuing tofacitinib; 0.6% of patients had multiple HZ events. Herpes zoster IRs were stable when analyzed by 6-month intervals up to >30 months. Herpes zoster risk factors included older age, lower weight, geographic region, and prior tumor necrosis factor inhibitor (TNFi) failure.

Conclusions: Most HZ events were mild/moderate. Herpes zoster IRs remained stable over 7.8 years of exposure. Older age, lower weight, geographic region, and prior TNFi failure were associated with increased HZ risk.

Clinicaltrials.gov: NCT00787202;NCT01465763;NCT01458951;NCT01458574;NCT01470612;NCT03281304.

Keywords: herpes zoster; tofacitinib; ulcerative colitis.

Plain language summary

Incidence rates for herpes zoster in patients with ulcerative colitis have remained stable over 7.8 years of tofacitinib exposure. Older age, lower weight, geographic region, and prior tumor necrosis factor inhibitor failure were identified as significant herpes zoster risk factors.

Publication types

  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colitis, Ulcerative* / chemically induced
  • Colitis, Ulcerative* / drug therapy
  • Herpes Zoster* / chemically induced
  • Herpes Zoster* / epidemiology
  • Herpesvirus 3, Human
  • Humans
  • Piperidines / therapeutic use
  • Pyrimidines / therapeutic use

Substances

  • tofacitinib
  • Piperidines
  • Pyrimidines

Associated data

  • ClinicalTrials.gov/NCT00787202
  • ClinicalTrials.gov/NCT01465763
  • ClinicalTrials.gov/NCT01458951
  • ClinicalTrials.gov/NCT01458574
  • ClinicalTrials.gov/NCT01470612
  • ClinicalTrials.gov/NCT03281304