Herpes zoster infection in patients with ulcerative colitis receiving tofacitinib

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

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).

Original languageEnglish (US)
Pages (from-to)2258-2265
Number of pages8
JournalInflammatory Bowel Diseases
Volume24
Issue number10
DOIs
StatePublished - Oct 1 2018

Fingerprint

Herpes Zoster
Ulcerative Colitis
Infection
Tumor Necrosis Factor-alpha
Incidence
Maintenance
tofacitinib
Confidence Intervals
Janus Kinases
Psoriatic Arthritis
Encephalitis
Proportional Hazards Models
Rheumatoid Arthritis
Cohort Studies
Multivariate Analysis
Demography

Keywords

  • Herpes zoster
  • Janus kinase
  • Safety
  • Shingles
  • Tofacitinib
  • Ulcerative colitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

Cite this

Winthrop, K., Melmed, G. Y., Vermeire, S., Long, M. D., Chan, G., Pedersen, R. D., ... Su, C. (2018). Herpes zoster infection in patients with ulcerative colitis receiving tofacitinib. Inflammatory Bowel Diseases, 24(10), 2258-2265. https://doi.org/10.1093/ibd/izy131

Herpes zoster infection in patients with ulcerative colitis receiving tofacitinib. / Winthrop, Kevin; Melmed, Gil Y.; Vermeire, Séverine; Long, Millie D.; Chan, Gary; Pedersen, Ronald D.; Lawendy, Nervin; Thorpe, Andrew J.; Nduaka, Chudy I.; Su, Chinyu.

In: Inflammatory Bowel Diseases, Vol. 24, No. 10, 01.10.2018, p. 2258-2265.

Research output: Contribution to journalArticle

Winthrop, K, Melmed, GY, Vermeire, S, Long, MD, Chan, G, Pedersen, RD, Lawendy, N, Thorpe, AJ, Nduaka, CI & Su, C 2018, 'Herpes zoster infection in patients with ulcerative colitis receiving tofacitinib', Inflammatory Bowel Diseases, vol. 24, no. 10, pp. 2258-2265. https://doi.org/10.1093/ibd/izy131
Winthrop, Kevin ; Melmed, Gil Y. ; Vermeire, Séverine ; Long, Millie D. ; Chan, Gary ; Pedersen, Ronald D. ; Lawendy, Nervin ; Thorpe, Andrew J. ; Nduaka, Chudy I. ; Su, Chinyu. / Herpes zoster infection in patients with ulcerative colitis receiving tofacitinib. In: Inflammatory Bowel Diseases. 2018 ; Vol. 24, No. 10. pp. 2258-2265.
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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).",
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T1 - Herpes zoster infection in patients with ulcerative colitis receiving tofacitinib

AU - Winthrop, Kevin

AU - Melmed, Gil Y.

AU - Vermeire, Séverine

AU - Long, Millie D.

AU - Chan, Gary

AU - Pedersen, Ronald D.

AU - Lawendy, Nervin

AU - Thorpe, Andrew J.

AU - Nduaka, Chudy I.

AU - Su, Chinyu

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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).

AB - 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).

KW - Herpes zoster

KW - Janus kinase

KW - Safety

KW - Shingles

KW - Tofacitinib

KW - Ulcerative colitis

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