Changes in health-related quality of life and work-related outcomes for patients with mild-to-moderate ulcerative colitis receiving short-term and long-term treatment with multimatrix mesalamine: a prospective, open-label study

Abstract

Background: Ulcerative colitis (UC) is associated with lower health-related quality of life (HRQoL), and with disease activity predicting lower HRQoL and worse work-related outcomes. The current study examined the burden of UC on patients' HRQoL, as well as changes in patients' HRQoL and work-related outcomes following short-term and long-term treatment with multimatrix mesalamine, and their correspondence with changes in disease activity.

Methods: Data were from an open-label, multinational, prospective trial (ClinicalTrials.gov identifier: NCT01124149) of 717 adults with active mild-to-moderate UC who were treated with 4.8 g/day multimatrix mesalamine tablets once daily for eight weeks (acute phase). Four-hundred sixty-one patients who achieved partial or complete clinical and endoscopic remission subsequently received treatment with daily 2.4 g/day multimatrix mesalamine for 12 months (maintenance phase). At baseline, Week 8, and Month 12, patients were administered patient-reported outcomes (PRO) measures of HRQoL (the SF-12v2® Health Survey [SF-12v2] and Short Inflammatory Bowel Disease Questionnaire) and work-related outcomes (Work Productivity and Activity Impairment questionnaire, UC-specific version). SF-12v2 scores were compared to the U.S. general population using Analysis of Variance models to assess burden of UC on HRQoL. Mixed-effects repeated-measures models compared PRO scores across visits to assess change in PRO scores over time. Correlations examined the correspondence of changes in PRO scores with changes on a modified UC disease activity index (UC-DAI).

Results: Baseline burden of disease observed on all SF-12v2 domains was partially eliminated at Week 8 and completely eliminated at Month 12. Statistically significant improvements from baseline were observed at both Week 8 and Month 12 for all PRO scores (all P < 0.001). Decreases in UC-DAI scores significantly predicted improvements in PRO scores during the acute treatment phase.

Conclusions: Patients with UC receiving daily multimatrix mesalamine treatment showed significant improvements in all measured domains of HRQoL and work-related outcomes. Patients who achieved partial or complete clinical and endoscopic remission maintained these improvements for most of these domains over 12 months with continued daily treatment. Changes in HRQoL and work-related outcomes were inversely related to changes in disease activity. Findings support the effectiveness of multimatrix mesalamine for improving, and sustaining improvements, in HRQoL and work-related outcomes.

Keywords: Absenteeism; Health-related quality of life; Inflammatory bowel disease; Multimatrix mesalamine; Presenteeism; Productivity; Ulcerative colitis; Work-related outcomes.

Conflict of interest statement

The study protocol, the final approved informed consent document, relevant supporting information, and all types of subject recruitment information were submitted to the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) for each site, and approval was gained from the IRB/IEC and regulatory agency (if appropriate) prior to study initiation. Drug supplies were not released and subject recruitment did not commence until this written approval was received by the CRO. Shire and the IRB/IEC approved any amendments to the protocol prior to implementing changes in the study. The investigator was responsible for keeping the IRB/IEC informed of study progress and of any changes made to the protocol as deemed appropriate, in addition to reporting any serious and significant adverse events. This study was conducted in accordance with current applicable regulations, International ICH Good Clinical Practice and local ethical and legal requirements, and with the principles of the 18th World Medical Assembly (Helsinki 1964) and amendments of the 29th (Tokyo 1975), 35th (Venice 1983), 41st (Hong Kong 1989) and 48th (South Africa 1996) World Medical Assemblies, Declaration of Helsinki. The subject’s informed consent was mandatory for study participation and was obtained in writing. The subject’s informed consent was documented (on an appropriate form approved by the Ethics Committee) by the dated signature of the subject and investigator (investigator signature as required by IRB/IEC). To guarantee subject confidentiality, personal details and consent documentation was kept by the investigator in the subject file.MKW and AVJ were employees of Shire at the time of the study and analysis and were holding stock and/or stock options at Shire. GD has received financial support for research from AbbVie, Janssen Biologics, Given Imaging, MSD, Dr. Falk Pharma, and Photopill; received lecture fees from AbbVie, Tillotts, Tramedico, Ferring, MSD, UCB, Norgine, and Shire; and consulted for AbbVie, Actogenix, Centocor, Cosmo, Engene, Ferring Pharmaceuticals, GlaxoSmithKline, Janssen Biologics, Millenium Pharmaceuticals, MSD, Novo Nordisk, PDL Biopharma, Pfizer, SetPoint, Shire, Takeda, Teva, and UCB. AY is an employee of Optum, which received funds from Shire Development LLC for data analyses and manuscript development.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

Flow chart for disposition of trial patients. aThe safety population within each phase was defined as all patients who took at least one dose of the investigational product during that phase. bThe efficacy population within each phase was defined as all patients who took at least one dose of the investigational product and had at least one post-dose efficacy assessment during that phase

Fig. 2

SF-12v2 score differences between trial patients and an age- and gender-matched US general population sample. PF: physical functioning; RP: role physical; BP: bodily pain; GH: general health; VT: vitality; SF: social functioning; RE: role emotional; MH: mental health; PCS: physical component summary; MCS: mental component summary. Error bars reflect 95% confidence intervals around mean differences. Significantly different from US general population sample based on P-values: * P < 0.05; † P < 0.01; ‡ P < 0.001