Exploring the Humanistic and Economic Burden of Crohnʼs Disease: Considerations for Novel Compounds

Abstract

BACKGROUND: Crohn's disease (CD), an inflammatory bowel disease (IBD), affects approximately 1.4 million people in the United States (US). With the increasing focus on patient-centred outcomes, novel CD treatments must demonstrate efficacy and tolerability with added value for patients, carers, healthcare systems and society. Therefore, it is important to focus on patient-reported outcomes (PRO) such as health-related quality of life (HRQoL) along with the economic costs when evaluating novel CD treatments. We reviewed the patient-reported and economic burden of CD and documented, for the first time, CD symptoms and impact of symptoms in an all-encompassing conceptual model. PRO measures currently used to assess these concepts were identified and critically reviewed. METHODS: Articles were identified in MEDLINE, EMBASE, EconLit, HEED, CRD databases and PSYCINFO using pre-defined search terms/limits. The literature search revealed 561 abstracts of which 31 articles met full review criteria. Concepts were extracted to form a conceptual model and identify patient-relevant concepts that may be valuable to measure when assessing new treatments. PRO measures were identified via the PRO and Quality of Life Database (PROQOLID) and were reviewed according to the US FDA PRO Guidance for industry. Data on direct and indirect costs of CD were also extracted. RESULTS: CD symptoms manifest primarily as gastrointestinal disturbances including abdominal pain/cramping and diarrhoea. Fever, fatigue and weight loss are also prominent symptoms. These symptoms impact patients' physical functioning, daily activities, emotional well-being, and ability to work. CD is also associated with substantial direct costs (e.g. hospitalisations), estimated at $18-$19,000 perpatient per-year in the US, and indirect costs (e.g. work absenteeism), estimated at $7,260 per-patient per-year. Costs are especially high in specific sub-groups (e.g. presence of fistulas). Seven disease-specific and generic PRO instruments and one composite measure were reviewed in-depth; measures of HRQoL (IBDQ, SF-36 and IBDQOL), occupational functioning (CPWDQ and WPAI-CD) and disease activity/symptoms (CDAI, CDAI-short and GSRS). The CDAI is the current standard measure of CD severity and serves as a key indicator of treatment efficacy. While there is evidence as to the quantitative measurement properties for the CDAI there are limitations regarding symptom coverage and validity in certain subpopulations. Instruments to assess HRQoL and occupational functioning used concurrently with the CDAI may demonstrate the wider influence of treatment on other symptoms and patients' lives. CONCLUSION(S): The disease course of CD is characterised by remissions and relapses, thus the lifetime human and economic burden of CD is substantial. PRO measures can be important complementary measures to demonstrate the efficacy, tolerability and value of a treatment in clinical trials and clinical practice. This review highlights the need for disease-specific PRO measures that provide comprehensive assessment of relevant domains of disease activity/symptoms, HRQoL and occupational functioning. Qualitative research to identify the salient symptoms for patients and their effect on HRQoL would be useful to ensure comprehensive measurement of patient burden in future clinical trials. Further patient and cost-of-illness research into the drivers of direct and indirect costs of CD is necessary in light of increasing requirements for cost-effectiveness data to support reimbursement.