TY - JOUR
T1 - Improvements in Disease Activity Partially Mediate the Effect of Tofacitinib Treatment on Generic and Disease-Specific Health-Related Quality of Life in Patients with Ulcerative Colitis
T2 - Data from the OCTAVE Program
AU - Dubinsky, Marla C.
AU - Armuzzi, Alessandro
AU - Gecse, Krisztina B.
AU - Ullman, Thomas
AU - Bushmakin, Andrew G.
AU - Dibonaventura, Marco
AU - Cappelleri, Joseph C.
AU - Connelly, Susan B.
AU - Woolcott, John C.
AU - Salese, Leonardo
N1 - Funding Information: This study was sponsored by Pfizer. Medical writing support, under the direction of the authors, was provided by Eleanor Finn, PhD, on behalf of CMC Connect, a division of IPG Health Medical Communications, and Eric Comeau, CMC Connect, and was funded by Pfizer, New York, NY, USA in accordance with Good Publication Practice (GPP 2022) guidelines (Ann Intern Med 2022; 175: 1298–1304). Publisher Copyright: © 2023 S. Karger AG, Basel. All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
PY - 2023/7/1
Y1 - 2023/7/1
N2 - Background: Patients with ulcerative colitis (UC) often report impaired health-related quality of life (HRQoL). Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of UC. In addition to previous demonstrations of improved clinical measures (e.g., Mayo score), tofacitinib has been shown to improve HRQoL in patients with UC. This analysis explored the interrelationships among tofacitinib treatment, HRQoL, and disease activity (measured using Mayo subscores) using mediation modeling. Methods: Data were collected from two 8-week induction studies (OCTAVE Induction 1 and 2) in patients with moderate to severe UC treated with tofacitinib or placebo. Two mediation models were specified. First, Mayo subscores were mediators between the binary treatment variable (tofacitinib vs. placebo) and the eight Short Form-36 Health Survey (SF-36) domain scores as outcomes. Second, the four Inflammatory Bowel Disease Questionnaire (IBDQ) domain scores served as outcomes. Both models used data collected at week 8. Results: Overall, 1,073 and 1,079 patients were included in the SF-36- and IBDQ-based models, respectively. For all SF-36 domains, improvements in Mayo subscores were estimated to explain 65.6% (bodily pain) to 92.9% (mental health) of the total treatment effect on SF-36 domain scores (all p < 0.05). For all IBDQ domains, improvements in Mayo subscores explained 71.6% (systemic symptoms) to 84.7% (emotional function) of the total treatment effect (all p < 0.05). Conclusion: Mayo scores and Mayo subscores are significant but incomplete contributors to tofacitinib's effect on HRQoL in patients with moderate to severe UC. ClinicalTrials.gov: NCT01465763; NCT01458951.
AB - Background: Patients with ulcerative colitis (UC) often report impaired health-related quality of life (HRQoL). Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of UC. In addition to previous demonstrations of improved clinical measures (e.g., Mayo score), tofacitinib has been shown to improve HRQoL in patients with UC. This analysis explored the interrelationships among tofacitinib treatment, HRQoL, and disease activity (measured using Mayo subscores) using mediation modeling. Methods: Data were collected from two 8-week induction studies (OCTAVE Induction 1 and 2) in patients with moderate to severe UC treated with tofacitinib or placebo. Two mediation models were specified. First, Mayo subscores were mediators between the binary treatment variable (tofacitinib vs. placebo) and the eight Short Form-36 Health Survey (SF-36) domain scores as outcomes. Second, the four Inflammatory Bowel Disease Questionnaire (IBDQ) domain scores served as outcomes. Both models used data collected at week 8. Results: Overall, 1,073 and 1,079 patients were included in the SF-36- and IBDQ-based models, respectively. For all SF-36 domains, improvements in Mayo subscores were estimated to explain 65.6% (bodily pain) to 92.9% (mental health) of the total treatment effect on SF-36 domain scores (all p < 0.05). For all IBDQ domains, improvements in Mayo subscores explained 71.6% (systemic symptoms) to 84.7% (emotional function) of the total treatment effect (all p < 0.05). Conclusion: Mayo scores and Mayo subscores are significant but incomplete contributors to tofacitinib's effect on HRQoL in patients with moderate to severe UC. ClinicalTrials.gov: NCT01465763; NCT01458951.
KW - Gastroenterology
KW - Health-related quality of life
KW - Inflammatory bowel disease
KW - Patient-reported outcomes
KW - Statistical modeling
KW - Ulcerative colitis
UR - http://www.scopus.com/inward/record.url?scp=85164234699&partnerID=8YFLogxK
U2 - https://doi.org/10.1159/000528788
DO - https://doi.org/10.1159/000528788
M3 - Article
C2 - 36603566
SN - 0257-2753
VL - 41
SP - 604
EP - 614
JO - Digestive diseases (Basel, Switzerland)
JF - Digestive diseases (Basel, Switzerland)
IS - 4
ER -