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P136. Induction and maintenance of clinical remission by adalimumab in patients with moderate-to-severe ulcerative colitis

W.J. Sandborn1, G. Van Assche2, W. Reinisch3, J. Colombel4, G. D'Haens5, D.C. Wolf6, M. Kron7, M. Tighe8, A. Lazar7, R.B. Thakkar8

1University of California, San Diego, La Jolla, CA, United States; 2University Hospital of Gasthuisberg, Leuven, Belgium; 3Medical University Vienna, Vienna, Austria; 4Centre Hospitalier Universitaire de Lille, Lille, France; 5Imelda GI Clinical Research Center, Bonheiden, Belgium; 6Atlanta Gastroenterology Associates, Atlanta, GA, United States; 7Abbott GmbH & Co. KG, Ludwigshafen, Germany; 8Abbott, Abbott Park, IL, United States

Aim: Assess efficacy and safety of adalimumab for induction and maintenance of clinical remission in patients with moderate-to-severe ulcerative colitis (UC).

Materials and Methods: Adult patients with UC (Mayo score: 6–12 points; endoscopy subscore: 2–3 points despite concurrent treatment with oral corticosteroids/immunosuppressants) were randomized 1:1 to placebo or adalimumab (160 mg, Week 0; 80 mg, Week 2; 40 mg every other week [eow] starting Week 4). Patients were allowed previous anti-TNF agent use. Co-primary endpoints were proportion of patients with (1) clinical remission at Week 8; (2) clinical remission at Week 52. Major secondary endpoints included sustained clinical remission at both Week 8 and 52, clinical response and mucosal healing at Week 8, Week 52, and both Week 8 and 52. At/after Week 8 patients were permitted corticosteroid tapering. Patients demonstrating inadequate response1 could switch to open-label (OL) 40 mg eow at Week 12. Dose escalation to 40 mg weekly was permitted for patients demonstrating inadequate response on OL administration. Efficacy analyses were conducted on the ITT population; using NRI for missing/incomplete data. Safety analyses were conducted on the safety population

Results: 248 (of 494) ITT patients received adalimumab. Significantly more adalimumab-treated patients achieved clinical remission, clinical response, and mucosal healing at Week 8, Week 52, and both Week 8 and 52, compared with placebo. Among patients with corticosteroid use at baseline, significantly more adalimumab-treated patients discontinued corticosteroids before Week 52 and achieved clinical remission at Week 52, compared with placebo (13.3% vs. 5.7%, P = 0.035). Among patients with prior anti-TNF agent use (40.3% of ITT patients), significantly more adalimumab-treated patients achieved clinical remission at Week 52, clinical response at Week 52, and sustained clinical response at both Week 8 and 52, compared with placebo. No deaths, tuberculosis or lymphomas were reported. Incidence rates of serious and infectious AEs were similar between placebo and adalimumab groups.

Table. Clinical Remission and Major Secondary Endpoints at Week 8 and 52a
 Week 8Week 52Week 8 and 52
 Placebo (N = 246)ADA (N = 248)P valuebPlacebo (N = 246)ADA (N = 248)P valuebPlacebo (N = 246)ADA (N = 248)P valueb
All Patients
Clinical remissionc n (%)23
(9.3)
41
(16.5)
0.0221
(8.5)
42
(17.3)
<0.0110
(4.1)
21
(8.5)
<0.05
Clinical responsed n (%)85
(34.6)
125
(50.4)
<0.00145
(18.3)
75
(30.2)
<0.0130
(12.2)
59
(23.8)
<0.001
Mucosal healinge n (%)78
(31.7)
102
(41.1)
0.0338
(15.4)
62
(25.0)
<0.0126
(10.6)
46
(18.5)
0.01
Patients with No Prior Anti-TNF
Clinical remissionc n (%)16
(11.0)
32
(21.3)
0.0218
(12.4)
33
(22.0)
0.039
(6.2)
16
(10.7)
0.17
Clinical responsed n (%)56
(38.6)
89
(59.3)
<0.00135
(24.1)
55
(36.7)
0.0224
(16.6)
44
(29.3)
<0.01
Patients with Prior Anti-TNF
Clinical remissionc n (%)7
(6.9)
9
(9.2)
0.563
(3.0)
10
(10.2)
0.041
(1.0)
5
(5.1)
0.12
Clinical responsed n (%)29
(28.7)
36
(36.7)
0.2310
(9.9)
20
(20.4)
0.046
(5.9)
15
(15.3)
0.03
aIntent-to-treat (ITT) population; non-responder imputation (NRI). bP values to compare treatment groups were based on Cochran-Mantel-Haenszel test (for all patients) or chi-square test (for patients with/without prior anti-TNF, respectively). cMayo score ≤2 with no individual subscore >1. dDecrease from baseline in Mayo score ≥3 points and ≥30%, rectal bleeding subscore 0 or 1 or decrease from baseline ≥1 point. eEndoscopy subscore ≤1.
Abbreviations: ADA = adalimumab; TNF = tumor necrosis factor.

Conclusion: Adalimumab was efficacious in inducing and maintaining clinical remission in patients with moderate-to-severe UC who did not adequately respond to conventional therapy with oral corticosteroids/immunosuppressants. The safety profile in UC was consistent with the known safety profile of adalimumab.

1Partial Mayo score (PMS) ≥ Baseline on 2 consecutive visits at least 14 days apart (for patients with Baseline PMS of 4–7); PMS ≥ 7 on 2 consecutive visits at least 14 days apart (for patients with Baseline PMS of 8 or 9).