TY - JOUR
T1 - Assessment of Safety and Efficacy of Tofacitinib, Stratified by Age, in Patients from the Ulcerative Colitis Clinical Program
AU - Lichtenstein, Gary R.
AU - Bressler, Brian
AU - Francisconi, Carlos
AU - Vermeire, Severine
AU - Lawendy, Nervin
AU - Salese, Leonardo
AU - Sawyerr, Gosford
AU - Shi, Hongjiong
AU - Su, Chinyu
AU - Judd, Donna T.
AU - Jones, Thomas
AU - Loftus, Edward V.
N1 - Publisher Copyright:
© 2022 Crohn's & Colitis Foundation. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - Background: In patients with ulcerative colitis (UC), risks of infection and malignancies increase with age. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. This analysis assessed age as a risk factor for adverse events of special interest (AESI) in the tofacitinib UC clinical program. Methods: Data were from phase 2 and 3 induction studies, a phase 3 maintenance study, and an open-label, long-term extension study. Efficacy and/or safety outcomes were analyzed in the Induction, Maintenance, and Overall Cohorts (patients who received≥1 dose of tofacitinib), stratified by age. The effects of baseline demographic and disease-related factors on AESI incidence were assessed by Cox proportional-hazards regression analysis. Results: In the Overall Cohort (1157 patients with≤6.8 years' tofacitinib treatment), age was a statistically significant predictor of herpes zoster (HZ), malignancies excluding nonmelanoma skin cancer (NMSC), and NMSC. Other statistically significant predictors included prior tumor necrosis factor inhibitor failure for HZ, NMSC, and opportunistic infection events, and prior duration of UC for malignancies excluding NMSC. In the Induction and Maintenance Cohorts, a higher proportion of tofacitinib-treated than placebo-treated patients (numerical difference) achieved the efficacy endpoints (endoscopic improvement, clinical remission, clinical response) across all age groups. Conclusions: Older individuals receiving tofacitinib as induction and maintenance therapy to treat UC may have an increased risk of HZ, malignancies (excluding NMSC), and NMSC versus similarly treated younger patients, consistent with findings from the general population. Across all age groups, tofacitinib demonstrated greater efficacy than placebo as an induction and maintenance therapy. ClinicalTrials.gov Registration Numbers: NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612.
AB - Background: In patients with ulcerative colitis (UC), risks of infection and malignancies increase with age. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. This analysis assessed age as a risk factor for adverse events of special interest (AESI) in the tofacitinib UC clinical program. Methods: Data were from phase 2 and 3 induction studies, a phase 3 maintenance study, and an open-label, long-term extension study. Efficacy and/or safety outcomes were analyzed in the Induction, Maintenance, and Overall Cohorts (patients who received≥1 dose of tofacitinib), stratified by age. The effects of baseline demographic and disease-related factors on AESI incidence were assessed by Cox proportional-hazards regression analysis. Results: In the Overall Cohort (1157 patients with≤6.8 years' tofacitinib treatment), age was a statistically significant predictor of herpes zoster (HZ), malignancies excluding nonmelanoma skin cancer (NMSC), and NMSC. Other statistically significant predictors included prior tumor necrosis factor inhibitor failure for HZ, NMSC, and opportunistic infection events, and prior duration of UC for malignancies excluding NMSC. In the Induction and Maintenance Cohorts, a higher proportion of tofacitinib-treated than placebo-treated patients (numerical difference) achieved the efficacy endpoints (endoscopic improvement, clinical remission, clinical response) across all age groups. Conclusions: Older individuals receiving tofacitinib as induction and maintenance therapy to treat UC may have an increased risk of HZ, malignancies (excluding NMSC), and NMSC versus similarly treated younger patients, consistent with findings from the general population. Across all age groups, tofacitinib demonstrated greater efficacy than placebo as an induction and maintenance therapy. ClinicalTrials.gov Registration Numbers: NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612.
KW - age
KW - clinical response
KW - safety
KW - tofacitinib
KW - ulcerative colitis
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U2 - 10.1093/ibd/izac084
DO - 10.1093/ibd/izac084
M3 - Article
C2 - 36342120
AN - SCOPUS:85145955477
SN - 1078-0998
VL - 29
SP - 27
EP - 41
JO - Inflammatory bowel diseases
JF - Inflammatory bowel diseases
IS - 1
ER -