P395 Etrolizumab demonstrated no difference among doses in symptomatic and endoscopic-based evaluation of remission in anti-TNF-α-naïve patients in a post-hoc analysis of the phase 2 ulcerative colitis trial (EUCALYPTUS)
Sandborn W.J.1, Schreiber S.2, Tang M.T.3, Tatro A.R.3, Oh Y.S.*3, Maciuca R.3
1University of California, San Diego, La Jolla, United States 2Kiel University, Kiel, Germany 3Genentech, South San Francisco, United States
The use of the Physician Global Assessment (PGA) subscore, a component of the full Mayo Clinic Score (MCS), has been discouraged as a primary endpoint by the US Food and Drug Administration (FDA) and the European Medicines Agency in 2016 draft guidance. Instead, a composite, clinical remission primary endpoint based on stool frequency (SF), rectal bleeding (RB), and endoscopic subscores (ES) (i.e. MCS w/o PGA) is recommended by the FDA. Etrolizumab, a humanized anti-β7 mAb, showed greater clinical remission at week (wk) 10 based on the full MCS (w/PGA) compared with placebo (PBO) in the phase 2 EUCALYPTUS trial (Vermeire et al.
EUCALYPTUS was an international, multicentre, double-blind, PBO-controlled, randomised, phase 2 study (NCT01336465) in 124 pts with moderate-to-severe UC who had not responded to conventional therapy. Eligible pts were randomly assigned (1:1:1) to subcutaneous etrolizumab (100 mg at wks 0, 4 and 8, with PBO at wk 2; or 420-mg loading dose at wk 0, followed by 300 mg at wks 2, 4 and 8), or matching PBO. The primary endpoint was clinical remission (full MCS ≤2, with no individual subscore >1 at wk 10). Post-hoc analyses assessed SF remission (SF ≤1 and ≥1-point decrease from baseline), RB remission (RB =0), symptomatic remission (SF and RB remission — SFRB), endoscopic remission (ES ≤1), and a composite of both SFRB and ES remission in aTNF-naive pts at wk 10.
PBO-adjusted treatment differences observed with symptomatic and endoscopic remission assessments were similar (30–37%) to those of the primary full MCS remission endpoint (36%), except for RB remission, which had the highest PBO rate and the smallest treatment effect size (24%). Remission rates based on symptomatic remission (SF, SFRB), endoscopic remission (ES) or ES + SFRB were similar between the 100 and 300 mg etrolizumab arms.
When PGA is removed from the MCS-defined remission assessment, aTNF-naive pts experienced similar rates of remission whether treated with low- or high-dose etrolizumab. Treatment effects observed with SFRB remission and ES + SFRB remission were of similar magnitude to that observed for the primary MCS remission endpoint.