Characterizing unmet medical need and the potential role of new biologic treatment options in patients with ulcerative colitis and Crohn's disease: a systematic review and clinician surveys

Jason P Gordon, Phil C McEwan, Andy Maguire, Daniel M Sugrue, Jorge Puelles, Jason P Gordon, Phil C McEwan, Andy Maguire, Daniel M Sugrue, Jorge Puelles

Abstract

Objectives: Comparative outcomes of patients with ulcerative colitis (UC) and Crohn's disease (CD) prescribed a biologic therapy are inconclusive. The aim of this research was to characterize the degree of unmet medical need in patients with UC or CD and to identify the potential role for new therapies.

Methods: A systematic literature review was undertaken of studies reporting outcomes associated with the use of existing biologic therapies in patients with UC or CD, focusing on the nature and rate of treatment failure. To complement the systematic review, contemporaneous data were obtained from a survey of practising gastroenterologists in the UK and France. Data were qualitatively combined in a narrative framework to evaluate the degree of unmet medical need among patients with UC or CD.

Results: Studies identified in the systematic review (n = 120) were heterogeneous, particularly with respect to the definitions of treatment failure; estimates of treatment failure were high but uncertain. On the basis of standardized definitions, estimates of treatment failure provided by clinicians (n = 102) were high, and they were higher for second-line treatment failure (primary: ≤ 37%; secondary: ≤ 41%) compared with first-line treatment failure (primary: ≤ 26%; secondary: ≤ 28%). The majority of the systematic review and survey data were reflective of outcomes with infliximab and adalimumab.

Conclusion: High treatment failure rates associated with existing biologics, identified by the review and clinician surveys, indicate a need for other biologic treatment options to improve the management and outcomes for people with UC and CD. Outcomes associated with existing and new biologic treatments should be investigated in head-to-head randomized trials in the context of their likely uses in clinical practice.

Figures

Fig. 1
Fig. 1
The trial flow of the review process (per PRISMA statement 32). NHS EED, NHS Economic Evaluation Database.
Fig. 2
Fig. 2
Treatment failure during anti-TNFα therapy as estimated by UK clinicians. Estimates of treatment failure are consistently lower for first-line biologic therapy (black boxes) compared with second-line biologic therapy (grey boxes) in (a) UC and (b) CD, on the basis of the experience of UK gastroenterologists. Median line with box of 25th/75th percentiles and upper/lower adjacent values; while reading the figure, please observe that each category on the x-axis is assigned two boxes. ADA, adalimumab; anti-TNFα, anti-tumour necrosis factor-α; CD, Crohn’s disease; IFX, infliximab; PF, primary failure; SF, secondary failure; UC, ulcerative colitis.
Fig. 3
Fig. 3
Treatment failure during anti-TNFα therapy as estimated by French clinicians. Estimates of treatment failure are consistently lower for first-line biologic therapy (black boxes) compared with second-line biologic therapy (grey boxes) in (a) UC and (b) CD, on the basis of the experience of French gastroenterologists. Median line with box of 25th/75th percentiles and upper/lower adjacent values; while reading the figure please observe that each category on the x-axis is assigned two boxes. ADA, adalimumab; anti-TNFα, anti-tumour necrosis factor-α; CD, Crohn’s disease; IFX, infliximab; PF, primary failure; SF, secondary failure; UC, ulcerative colitis.

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