Combination treatment with adalimumab and partial enteral nutrition compared with adalimumab monotherapy in adults with active Crohn’s disease: The BIOPIC study

B. White, I. Campbell, C. Fandinga, C. Kerbiriou, J. Clowe, A. Jatkowska, E. Brownson, S. Milling, G.T. Ho, C. Mowat, E. Robertson, D. Gaya, A. Kefayat, S. Din, J.P. Seenan, J. Macdonald, K. Gerasimidis

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Slides compiled by Dr. Sally Lawrence 

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Introduction

Background & Objectives

• 50-60% of Crohn’s Disease (CD) patients achieve clinical remission with anti-TNF therapy.
• Exclusive enteral nutrition is an effective induction strategy for CD, but tolerability limits it’s use.
• Objective: Compare efficacy of adalimumab (ADA) + 50% partial enteral nutrition (PEN) vs ADA alone in biologic-naïve adults with active ileocolonic CD.

CD, Crohn’s Disease; PEN, partial enteral nutrition; ADA, adalimumab; CDAI, Crohn’s Disease Activity Index; RCT, randomized controlled trial.

White B et al. ECCO 26; (Abstract citation ID: jjaf231.137, DOP100).

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Methods

Primary Outcome:

W12 clinical response: CDAI decrease ≥70 points from baseline

W12 clinical remission: CDAI <150

RCT: 7 sites

Results: Flow Diagram

ADA, adalimumab; PEN, partial enteral nutrition; CDAI, Crohn’s Disease Activity Index.

White B et al. ECCO 26; (Abstract citation ID: jjaf231.137, DOP100).

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266 patients assessed for eligibility

3 withdrawn prior to active participation

• 2 withdrew consent in first 48 hours
• 1 found to be ineligible prior to commencing active participation

198 eligible patients approached by the research team

101 underwent randomisation

ADA + PEN

n = 51

48 commenced active participation

43 completed full study participation

ADA

n = 50

41 commenced active participation

37 completed full study participation

5 discontinued the study:

• 1 exited due to palatability issues
• 1 exited due to difficulties committing time to the study
• 3 exited due to symptom deterioration

3 excluded from primary outcome analysis due to protocol violations

9 withdrawn prior to active participation

• 5 withdrew consent in first 48 hours
• 4 found to be ineligible prior to commencing active participation

4 discontinued the study:

• 1 lost to follow-up
• 3 exited due to symptom deterioration

4 excluded from primary outcome analysis due to protocol violations

Results: Baseline characteristics

White B et al. ECCO 26; (Abstract citation ID: jjaf231.137, DOP100).

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Data presented as median (Q1, Q3) unless stated otherwise. ∞ CDAI data excluded from n = 3 ADA+PEN arm and n = 4 ADA arm due to presence of normal CDAI (<150) at baseline. × FC data missing for n = 1 ADA arm. * p ≤ 0.05 for comparisons between study arms.

Abbreviations: ADA+PEN, Adalimumab with 50% partial enteral nutrition; ADA, adalimumab; SIMD, Scottish Index of Multiple Deprivation; BMI, Body mass index; CDAI, Crohn’s Disease Activity Index; HBI, Harvey-Bradshaw Index; FC, Fecal calprotectin; CRP, C-reactive protein; ALB, Albumin.

Results: Primary outcome

ADA, adalimumab; PEN, partial enteral nutrition; CDAI, Crohn’s Disease Activity Index; ITT, intention-to-treat; FC, fecal calprotectin; CRP, C-reactive protein.

White B et al. ECCO 26; (Abstract citation ID: jjaf231.137, DOP100).

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• Similar reductions in FC and CRP between the cohorts over 12 weeks

Clinical response

Clinical remission

Results: subgroup analyses

ADA, adalimumab; PEN, partial enteral nutrition; CDAI, Crohn’s Disease Activity Index; CRP, C-reactive protein; FC, fecal calprotectin.

White B et al. ECCO 26; (Abstract citation ID: jjaf231.137, DOP100).

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Baseline CRP >5mg/L & FC >100ug/g Clinical Response

Clinical Response by Disease Location

Detectable anti-drug antibodies

Results: Endoscopic subgroup

ADA, adalimumab; PEN, partial enteral nutrition; SES-CD, Simple Endoscopic Score for Crohn’s Disease.

White B et al. ECCO 26; (Abstract citation ID: jjaf231.137, DOP100).

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n=7

n=9

SES-CD over time

>50% reduction in SES-CD at w 12

Conclusions

• The addition of 50% PEN to ADA was not associated with detectable differences in short-term clinical outcomes through week 12. However, signals of benefit were observed, including higher rates of mucosal endoscopic response and numerically lower frequency of anti-drug antibody formation (in a subset of patients).
• Exploratory analysis suggested that this combination strategy may have differential effects in subgroups with greater inflammatory burden and those with an ileal CD phenotype.

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Significance to clinical practice

• These findings should be considered hypothesis- generating and require confirmation in adequately powered prospective studies with robust objective endpoints.

White B et al. ECCO 26; (Abstract citation ID: jjaf231.137, DOP100).

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