Observational Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2022; 28(34): 5058-5075
Published online Sep 14, 2022. doi: 10.3748/wjg.v28.i34.5058
Impact of adalimumab on disease burden in moderate-to-severe ulcerative colitis patients: The one-year, real-world UCanADA study
Talat Bessissow, Geoffrey C Nguyen, Osman Tarabain, Laurent Peyrin-Biroulet, Nathalie Foucault, Kevin McHugh, Joannie Ruel
Talat Bessissow, Department of Medicine, McGill University Health Center, Montreal H3G 1A4, Quebec, Canada
Geoffrey C Nguyen, Mount Sinai Hospital Inflammatory Bowel Disease Centre, Toronto M5T 3L9, Ontario, Canada
Osman Tarabain, Dr. O. Tarabain Clinic, Windsor N8W 1E6, Ontario, Canada
Laurent Peyrin-Biroulet, Department of Gastroenterology, University of Lorraine, CHRU-Nancy, Nancy F-54000, France
Nathalie Foucault, Kevin McHugh, AbbVie Corporation, Saint-Laurent H4S 1Z1, Quebec, Canada
Joannie Ruel, Department of Medicine, Sherbrooke University Hospital Center, Sherbrooke J1H 5N4, Quebec, Canada
Author contributions: Bessissow T was involved in study design, coordinating the data collection, interpretation of the results, and review and revision of the manuscript; Ruel J, Nguyen GC, and Tarabain O were involved in coordinating the data collection, interpretation of the results, and review and revision of the manuscript; Foucault N and McHugh K were involved in study design, interpretation of the results, and review and revision of the manuscript.
Institutional review board statement: All sites had the study reviewed and approved by an ethics committee. While CEC Advarra IRB Services (Aurora, Ontario, Canada) reviewed and approved for some sites, other sites were approved through local/multi centres ethics committees (Dr. Everett Chalmers Regional Hospital, MUHC-Royal Victoria Hospital, CHUM-Hôpital Maisonneuve-Rosemont, CHAU-Hôpital Hôtel-Dieu de Levis, Royal University Hospital, Centre Hospitalier de l'Université de Sherbrooke, CHUM-Hôpital St-Luc, Zeidler Ledcor Centre, Ottawa Hospital-General Campus, Mount Sinai Hospital, London Health Sciences Centre, Centre Hospitalier de l'Université Laval (CHUL), University of Calgary Gastrointestinal Research Group).
Informed consent statement: All patients were required to sign a patient authorization form (or written informed consent) to participate in the study, and to disclose personal health information.
Conflict-of-interest statement: The authors have either received research support from, served as consultant, speakers bureau, scientific officer, participants of steering committees and advisory boards, and/or received honoraria from the following sponsors: T.B.: AbbVie, Janssen, Takeda, Merck, Pfizer, Roche, Bristol Myers Squibb, Gilead, Sandoz, Ferring, Alimentiv Inc. (formerly Robarts Clinical Trials); J.R.: AbbVie, Janssen, Takeda, Pfizer, Sandoz, Ferring, Alimentiv Inc. (formerly Robarts Clinical Trials); G.N.: AbbVie and Takeda; O.T.: AbbVie; N.F. and K.M.: are employees of AbbVie and may own AbbVie stock; L.P.B.: Dr. Peyrin-Biroulet reports personal fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Inotrem, Allergan, MSD, Roche, Arena, Gilead, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, OSE Immunotherapeutics, Enthera, Theravance, Pandion Therapeutics, Gossamer Bio, Viatris, Thermo Fisher. Grants from AbbVie, MSD, Takeda, Fresenius Kabi. Stock options: CTMA.
Data sharing statement: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and Clinical Study Reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. This clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). Data requests can be submitted at any time and the data will be accessible for 12 mo, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Talat Bessissow, FRCP (C), MD, MSc, Associate Professor, Department of Medicine, McGill University Health Center, 1650 Avenue Cedar, Montreal H3G 1A4, Quebec, Canada. talat.bessissow@mcgill.ca
Received: March 30, 2022
Peer-review started: March 30, 2022
First decision: June 10, 2022
Revised: July 27, 2022
Accepted: August 17, 2022
Article in press: August 17, 2022
Published online: September 14, 2022
Research background

The efficacy and safety of adalimumab have been demonstrated in pivotal trials, but there remained a need to assess more holistically how the clinical results translate into concrete improvements in key aspects of the daily lives of ulcerative colitis (UC) patients, such as symptoms, health-related quality of life (HRQoL), and disability.

Research motivation

Although some patient-reported outcomes (PROs) from existing studies may have items capturing some of these aspects, limited data was available for adalimumab in UC, specifically on psychological distress/depression, disability, fatigue, and pain or sleep quality in real-life setting.

Research objectives

The overarching goal for the UCanADA study was to assess the real-life effectiveness of adalimumab on PRO measures, while taking the opportunity to use the inflammatory bowel disease disability index to assess the impact of adalimumab on key components of patients’ functioning when affected with moderate-to-severe UC.

Research methods

UCanADA was a single arm, prospective, 1-year multicenter Canadian post-marketing observational study in which multiple PRO questionnaires were completed—with psychologic distress/depression symptoms as the primary endpoint—by patients with moderate-to-severe UC. Assessments were performed during patients’ routine care visit schedule, which was at the initiation of adalimumab (baseline), after induction (approximately 8 wk), and 52 wk after baseline. Additional optional assessments between weeks 8 and 52 were collected at least once but no more than two times during this period. Serious safety events and per-protocol adverse events were collected.

Research results

One hundred patients were included in this final analysis, with 94 (94%) patients included in the efficacy population (identified as the intent-to-treat (ITT) population), 48 (48%) patients included in the completers’ population, and 98 (98%) patients included in the safety population. The primary endpoint–the proportion of patients who achieved a change from baseline, defined as an improvement in total severity score relative to baseline, in the Patient Health Questionnaire–9 items (PHQ-9) measure at week 52–was 61.5% [40/65 patients; 95% confidence interval (CI): 49.7%-73.4%] for the ITT population and 65.9% (29/44 patients; 95%CI: 51.9%-79.9%) for completers. The safety profile was consistent with the known safety profile of adalimumab, and no new signal or unexpected trend was identified for the patient population.

Research conclusions

At week 52, adalimumab, used in a real-life study, was effective in reducing depressive symptoms in patients with UC, with more than 60% of the patients achieving an improvement the PHQ-9 with a mean improvement of 2.4 points. Thus, the treatment with adalimumab contributed to reducing the depressive symptoms frequently experienced in patients with UC as well as improving a broad range of PROs such as HRQoL and work productivity, as assessed with PRO instruments. The safety profile was consistent with the known safety profile of adalimumab, and no new signal or unexpected trend was identified for the patient population.

Research perspectives

Improvements in PHQ-9 were associated with clinical remission. Beyond the PHQ-9, significant improvements in several PROs were observed suggesting an improvement in HRQoL and work productivity as well. The population in the study, as well as the inclusion and exclusion criteria, was representative of the target population. In addition, coinciding the study visits with the patient’s routine care visit schedule helped increase generalizability of the PRO instruments by decreasing the impact on real life.