216

ADALIMUMAB RAPIDLY INDUCES CLINICAL REMISSION AND RESPONSE IN PATIENTS WITH MODERATE TO SEVERE CROHN'S DISEASE WHO HAD SECONDARY FAILURE TO INFLIXIMAB THERAPY: RESULTS OF THE GAIN STUDY

RA Enns¹, R Panaccione², WJ Sandborn³, SB Hanauer⁴, JF Colombel⁵, PF Pollack⁶
¹University of British Columbia, Vancouver, British Columbia; ²University of Calgary, Calgary, Alberta; ³Mayo Clinic, Rochester, Minnesota; ⁴University of Chicago, Illinois, USA; ⁵CHU Lille, Lille, France; ⁶Abbott Laboratories, Parsippany, New Jersey, USA

AIM: To assess the safety and efficacy of adalimumab (ADA), a self-injectable, fully human anti-TNF monoclonal antibody, in the induction of clinical remission (CDAI<150) and response in patients with active Crohn's disease (CD) who had secondary failure to infliximab (IFX) therapy.
METHODS: Patients with moderate to severe CD (CDAI 220-450) and secondary failure to IFX therapy were enrolled in GAIN, a Phase III, double-blind, placebo-controlled study, and were randomized to receive ADA, 160 mg sc at Wk 0 (BL) and 80 mg sc at Wk 2, or placebo (PBO) at both time points. Primary endpoint was remission at Wk 4. Secondary endpoints were clinical response (CR) defined as a decrease from BL CDAI of =>70 or 100 (CR70/100) at Wk 4. Safety was assessed throughout the study.
RESULTS: Patients were randomized to receive ADA (N=159) or PBO (N=166). Baseline characteristics were similar between the two arms: mean age, 38 yrs; female, 65%; mean CDAI, 313; median CRP, 0.8 mg/dL; immunosuppressant use, 48%. Clinical remission and response rates observed in the ADA arm were significant vs PBO. Serious adverse events were observed in 4.8% of PBO patients (abscess, 3; sepsis, 1; CD flare, 2; abdominal pain, 2) and in 1.3% of ADA patients (dehydration, 2). No delayed hypersensitivity (serum sickness) reactions or deaths occurred. The overall safety profile of ADA was consistent with prior CD trials and the existing RA database.

Clinical Remission and Response in GAIN

Week PBO, N=166 ADA , N=159
CDAI<150 4 12 (7%) 34 (21%)*
CR-100 2 30 (18%) 58 (37%)*
4 41 (25%) 61 (38%)**
CR-70 2 55 (33%) 82 (52%)**
4 56 (34%) 82 (52%)*
*p<=0.001, **p<=0.01, both vs. PBO.

CONCLUSIONS: Adalimumab rapidly and significantly induced clinical remission and response in patients with moderate to severe CD who had secondary failure to IFX. Adalimumab was well-tolerated.
Funded by Abbott Laboratories

PREVIOUS NEXT

Clinical Remission and Response in GAIN
	Week	PBO, N=166	ADA , N=159
CDAI<150	4	12 (7%)	34 (21%)*
CR-100	2	30 (18%)	58 (37%)*
	4	41 (25%)	61 (38%)**
CR-70	2	55 (33%)	82 (52%)**
	4	56 (34%)	82 (52%)*
p<=0.001, *p<=0.01, both vs. PBO.