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P419 Rapid Changes in Laboratory Parameters and Early Response to Adalimumab: Pooled Analysis from ULTRA 1 and ULTRA 2

S. Hanauer*1, W.J. Sandborn2, J.-F. Colombel3, W. Reinisch4, 5, S. Vermeire6, J. Petersson7, B. Pappalardo7, A.M. Robinson7, A. Lazar8, Q. Zhou7, R.B. Thakkar7

1Northwestern University Feinberg School of Medicine, Digestive Health Centre, Chicago, United States, 2University of California San Diego, Division of Gastroenterology , La Jolla, United States, 3Icahn School of Medicine at Mount Sinai, Gastroenterology, New York City, United States, 4McMaster University, Gastroenterology, Hamilton, Canada, 5Medical University of Vienna, Dept. for Gastroenterology and Hepatology, Vienna, Austria, 6University Hospital Leuven, Gastroenterology, Leuven, Belgium, 7AbbVie Inc., Global Pharmaceutical Research & Development, North Chicago, United States, 8AbbVie Deutschland GmbH & Co, KG, GPRD, Ludwigshafen, Germany

Background

The efficacy and safety of adalimumab (ADA) for induction and maintenance of clinical remission in patients with moderately to severely active ulcerative colitis (UC) was demonstrated in ULTRA 11 and ULTRA 2.2 Early changes in laboratory parameters, Mayo subscores and health-related quality of life (QoL) were assessed in a pooled analysis of patients from both studies.

Methods

ULTRA 1 patients were randomized to placebo (PBO) or ADA [80/40 or 160/80 mg at weeks (wks) 0/2, 40 mg every other wk (eow) from wk 4] in the 8 to 12 wk double-blind (DB) phase. ULTRA 2 was a 52-wk DB trial in which patients were randomized to PBO or ADA (160/80 mg at wks 0/2, 40 mg eow from wk 4). Pooled data from patients who received 160/80 mg ADA or PBO in both studies were evaluated in post-hoc analyses. Mean changes from baseline (BL) at wks 4 and 8 in albumin, high-sensitivity (hs)-CRP, total protein, hematocrit, hemoglobin, and red blood cell count (RBC) were evaluated. Mean changes from BL at wks 2, 4, 6, and 8 in Mayo subscores [rectal bleeding subscores (RBS) and stool frequency subscores (SFS)] were evaluated, and QoL (Inflammatory Bowel Disease Questionnaire, IBDQ scores) were evaluated at wks 4 and 8. results were compared for ADA- v. PBO-treated patients using the ANCOVA model. Last observation carried forward (LOCF) was used for missing data.

Mean changes from baseline in laboratory parameters

Baseline MeanBaseline MeanWeek 4Week 4Week 8Week 8
PBO (N=468)160/80 ADA (N=470)PBO160/80 ADAPBO160/80 ADA
Albumin (g/L)41.641.9-0.1 (N=457)0.7*** (N=455)0.4 (N=422)1.2*** (N=434)
hs-CRP (mg/L)12.8 (N=461)12.7 (N=464)-2.5 (N=448)-4.7* (N=443)-0.4 (N=412)-5.0*** (N=425)
Total protein (g/L)69.669.9-0.1 (N=456)0.2 (N=454)0.4 (N=423)1.1** (N=434)
Hematocrit (fraction)0.4030.400-0.002 (N=451)0.005** (N=449)0.002 (N=423)0.012*** (N=433)
Hemoglobin (g/L)130.3129.6-1.5 (N=454)0.9*** (N=451)-0.4 (N=424)3.0*** (N=433)
Red blood cell count (x1012/L)4.424.39-0.02 (N=450)0.04** (N=449)0.04 (N=423)0.14*** (N=433)

Results

ADA treatment significantly improved albumin, hematocrit, hemoglobin, and RBC compared to PBO at wks 4 and 8 (Table), and greater reductions in hs-CRP were observed in ADA-treated patients v. PBO at wks 4 and 8. Significant reductions in mean RBS (-0.6 v. -0.3) and mean SFS (-0.5 v. -0.2) were observed in ADA- v. PBO-treated patients, respectively, as early as wk 2 (all p<0.001), and were sustained up to wks 4, 6, and 8. Mean IBDQ scores were significantly improved in ADA- v. PBO-treated patients at wk 4 (29.2 v. 19.4) and wk 8 (31.4 v. 22.8), respectively (all p<0.001).

Conclusion

ADA treatment resulted in early, rapid improvements in laboratory values, including reductions in hs-CRP levels, in patients with moderately to severely active UC. Clinically meaningful early reductions in RBS and SFS, and early improvements in IBDQ scores were also observed following ADA treatment.

Reference:

1. Reinisch W. et al Gut, 2011;60:780. 2. Sandborn W.J. et al Gastroenterol, 2012;142:257