Impact of Concomitant Corticosteroids on Tofacitinib Induction Efficacy and Infection Rates in Ulcerative Colitis.

Abstract

BACKGROUND:

Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis.

AIM:

To report efficacy and infection rates in patients receiving tofacitinib induction treatment, by baseline corticosteroid status.

METHODS:

We evaluated efficacy and safety data from OCTAVE Induction 1&2 in patients with moderately-to-severely active ulcerative colitis who received tofacitinib 10 mg twice daily or placebo for 8 weeks, based on induction baseline oral corticosteroid use (Corticosteroid-Yes/No) and dose (< 20/ ≥ 20 mg/day). Infections of interest included serious infections, herpes zoster (HZ), and adjudicated opportunistic infections (OIs).

RESULTS:

At OCTAVE Induction 1&2 baseline, 478/1092 (43.8%) patients were receiving corticosteroids. Tofacitinib demonstrated significant induction efficacy versus placebo for both Corticosteroid-Yes and Corticosteroid-No. With adjustment for prior tumor necrosis factor inhibitor and immunosuppressant failure, there were no statistically significant differences in remission and clinical response rates for Corticosteroid-Yes versus Corticosteroid-No. Among tofacitinib-treated patients, HZ and OIs occurred more frequently in Corticosteroid-Yes versus Corticosteroid-No, regardless of dose (< 20 mg vs. ≥ 20 mg). Infection incidence rates (regardless of severity/seriousness) during tofacitinib induction were generally similar regardless of baseline corticosteroid use. The proportion of tofacitinib-treated patients with HZ was 0.2% for Corticosteroid-No versus 1.1% for Corticosteroid-Yes < 20 mg and 1.0% for Corticosteroid-Yes ≥ 20 mg. Two out of three patients had HZ OIs.

CONCLUSIONS:

Tofacitinib induction efficacy (clinical response and remission) was similar in baseline corticosteroid subgroups. Infections of interest were rare; HZ and OIs occurred more frequently among those receiving tofacitinib and corticosteroids versus those receiving tofacitinib without corticosteroids.

TRIAL REGISTRATION:

http://www.

CLINICALTRIALS:

gov (NCT01465763[21/10/2011]; NCT01458951[21/10/2011]).

• Authors: Gary R Lichtenstein, Benjamin L Cohen, Leonardo Salese, Irene Modesto, Wenjin Wang, Gary Chan, Haytham Mohamed Ahmed, Chinyu Su, Laurent Peyrin-Biroulet
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 68 Issue 6 Pg. 2624-2634 (06 2023) ISSN: 1573-2568 [Electronic] United States
• PMID: 36739367 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s).

Chemical References

• tofacitinib
• Protein Kinase Inhibitors
• Pyrroles
• Adrenal Cortex Hormones

Topics

• Humans
• Colitis, Ulcerative (diagnosis, drug therapy, chemically induced)
• Protein Kinase Inhibitors (adverse effects)
• Pyrroles (adverse effects)
• Herpes Zoster (chemically induced, epidemiology)
• Adrenal Cortex Hormones (adverse effects)
• Treatment Outcome
• Remission Induction