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OP011 Etrolizumab treatment leads to early improvement in symptoms and inflammatory biomarkers in anti-TNF-refractory patients in the open-label induction cohort of the phase 3 HICKORY study

Peyrin-Biroulet L.*1, Feagan B.G.2, Mansfield J.3, Rubin D.T.4, Arulmani U.5, Maciuca R.5, Tyrrell H.6, Thommes J.5, Tole S.6

1Université de Lorraine, Vandœuvre-lès-Nancy, France 2University of Western Ontario, London, Canada 3Newcastle University, Newcastle upon Tyne, United Kingdom 4University of Chicago Medicine, Chicago, United States 5Genentech, South San Francisco, United States 6Roche, Welwyn Garden City, United Kingdom

Background

Etrolizumab, an anti-β7 mAb targeting integrins α4β7 and αEβ7, showed significantly greater clinical remission at wk 10 vs placebo (PBO) in the phase 2 EUCALYPTUS trial. We assessed changes in symptoms and inflammatory biomarkers in aTNF refractory or intolerant (aTNF-IR) pts treated in a non-pivotal open-label induction (OLI) cohort of a phase 3 study.

Methods

HICKORY is a multicentre, randomised, double-blind, PBO-controlled phase 3 study (NCT02100696) evaluating the safety and efficacy of etrolizumab during induction and maintenance in aTNF-IR pts with moderate-to-severe UC. The study includes a non-pivotal OLI cohort that treated 130 pts with etrolizumab 105 mg every 4 wk for 14 wk. Symptomatic improvement in this cohort was assessed based on the change in weekly mean rectal bleeding (RB) and stool frequency (SF) scores (each scored on a scale of 0–3), derived from pts' daily eDiary entries. SF remission was defined as a weekly mean score of ≤1 (rounded to the nearest integer) with ≥1 point reduction from baseline (BL). RB remission was defined as a weekly mean score of 0 (rounded to the nearest integer) with ≥0.5 point reduction from BL. Faecal calprotectin (FC) and C-reactive protein (CRP) were measured at BL and wk 14 or early termination. Changes in SF, RB, PRO score (SF + RB), FC and CRP were assessed descriptively.

Results

Of 130 treated pts, 97% received all induction doses, 80% had a BL Mayo Clinic endoscopic score of 3, and 45% had received ≥2 prior aTNFs. RB remission rates improved from BL to wk 4 (∼30%) and 14 (∼50%). SF remission rates improved from BL to wk 4 (∼10%) and 14 (∼25%). PRO scores improved regardless of disease severity and irrespective of prior treatment with 1 or ≥2 aTNFs. The mean (± SE) decrease in PRO was 22% (±3%) at wk 4 and 36% (±3%) at wk 14; this decrease mirrored mean reductions in FC and CRP. Overall, FC and CRP levels decreased at wk 14 by a mean (95% CI) of 57% (42 to 69) and 33% (15 to 47), respectively. Mean decrease in CRP in pts with CRP levels >2.87 mg/L (ULN) at BL was 47%. Mean decreases in FC and CRP levels at wk 14 were greater in pts in SF remission (FC, 83%; CRP, 54%) and in pts in RB remission (FC, 69%; CRP, 49%). Etrolizumab demonstrated favourable safety and tolerability.

Figure 1

Conclusion

aTNF-IR pts with moderate-to-severe UC reported symptom improvement as early as wk 4 during OLI treatment with etrolizumab. Clinically meaningful improvement in disease activity was observed in pt-reported SF and RB scores, serum CRP and FC by wk 14.