P257. Importance of deep remission compared with mucosal healing only: Results from EXTEND
W. Sandborn1, J.‑F. Colombel2, R. Panaccione3, E. Louis4, M. Yang5, P. Pollack5, R. Thakkar5, A. Camez5, P. Mulani5, J. Chao5
1University of California, San Diego, La Jolla, United States; 2Centre Hospitalier Universitaire de Lille, Hôpital Claude Huriez, Lille, France; 3University of Calgary, Director, Inflammatory Bowel Disease Clinic, Calgary, Canada; 4University of Liège and CHU Liège, Department of Gastroenterology, Liège, Belgium; 5Abbott Laboratories, Illinois, United States
Background: Adalimumab (ADA) is effective for inducing and maintaining clinical remission and mucosal healing in Crohn's disease (CD). We explored the concept of deep remission, a novel composite measure of clinical remission (CDAI <150) plus complete mucosal healing.
Methods: EXTEND was a randomized, placebo (PBO)-controlled study in patients with moderate to severe ileocolonic CD (CDAI 220450) and baseline mucosal ulceration (score of 2 or 3 for ≥1 colon segments in Ulcerated Surface subscore of the Simple Endoscopic Score-CD). All patients (N = 135) received open-label ADA 160-/80-mg induction therapy at Weeks 0/2 and 129 were randomized at Week 4 to ADA maintenance therapy (40 mg every other week [eow]) or PBO. From Week 8, patients with flares or nonresponse could receive open-label eow then weekly ADA. In a prespecified analysis, the percentage of patients achieving deep remission was assessed at Weeks 12 and 52. The current analysis included only ADA-treated patients and compared Week-52 outcomes for patients who achieved early deep remission at Week 12 vs. those who achieved only mucosal healing.
Results: Of the 64 ADA-treated patients, 11 achieved deep remission; 8, mucosal healing only; and 19, clinical remission only at Week 12. Patients with early deep remission achieved better Week-52 outcomes compared with patients who achieved mucosal healing only (table).
|Deep Remission (N = 11)||Mucosal Healing (N = 8)|
|IBDQ remission (IBDQ score >170), n (%)||7 (64)*||1 (13)|
|Normal SF-36 PCS (SF-36 PCS >50), n (%)||6 (55)*|
|CD-related hospitalization, n (%)||2 (25)|
|CD flare (switch to open-label eow), n (%)||1 (9)*||5 (63)|
|Dosage increase (switch to open-label weekly), n (%)||0*||3 (38)|
|WPAI total work productivity impairment, %||25||53|
|WPAI total activity impairment, %||17||39|
Conclusions: Early deep remission, a composite endpoint combining clinical remission and mucosal healing, was associated with better long-term disease-specific quality of life and physical function, fewer flares and CD-related hospitalizations, greater work productivity, and lesser activity impairment compared with mucosal healing only. Although the concept of deep remission has yet to be validated, it represents a potentially important new treatment goal in CD.