One-year maintenance outcomes among patients with moderately-to-severely active ulcerative colitis who responded to induction therapy with adalimumab: subgroup analyses from ULTRA 2.

BACKGROUND: Patients with moderately-to-severely active ulcerative colitis (UC) are unlikely to continue anti-TNF therapy in the absence of early therapeutic response. AIM: To assess week 52 efficacy, safety and benefit/risk balance of adalimumab treatment in patients with moderately-to-severely active UC failing conventional therapy who achieved clinical response at week 8 in the 52-week ULTRA 2 trial. METHODS: Patients randomised to adalimumab (160/80 mg, week 0/2; 40 mg, every other week thereafter) in ULTRA 2 who achieved clinical response at week 8 per partial Mayo score (Mayo score without endoscopy subscore) were assessed for week 52 clinical remission, clinical response, mucosal healing, steroid-free remission and steroid discontinuation rates, overall and by prior anti-TNF use. Benefit/risk balance for the overall ITT population (regardless of week 8 responder status) was assessed using 'net efficacy adjusted for risk' (NEAR) odds ratios. Safety was assessed using adverse event rates. RESULTS: Of 248 adalimumab-treated patients, 123 (49.6%) achieved clinical response at week 8. Of these, 30.9%, 49.6%, and 43.1% achieved clinical remission, clinical response, and mucosal healing, respectively, at week 52. Of the week 8 responders using corticosteroids at baseline (N = 90), 21.1% achieved steroid-free remission and 37.8% were steroid-free at week 52. NEAR odds ratios indicated a positive benefit/risk balance for achievement of week 8 and week 52 response or remission without serious adverse events or serious infections. No safety concerns were identified. CONCLUSIONS: Adalimumab treatment was associated with a positive benefit/risk balance in the overall population of patients with moderately-to-severely active ulcerative colitis in ULTRA 2; early response was predictive of a positive outcome at 1 year (NCT00408629).

Wound epithelialization deficits in the transforming growth factor-alpha knockout mouse.

In vitro, transforming growth factor-alpha is an important factor controlling epithelial cell proliferation and migration. However, the transforming growth factor-alpha knockout mouse has shown no wound epithelialization defect in tail amputation and full-thickness back wounds. To resolve this disparity, we combined a full-thickness head wound and a partial-thickness ear wound on the transforming growth factor-alpha knockout mouse for analysis of wound epithelialization with or without granulation tissue formation. Three-millimeter ear wounds were made on the transforming growth factor-alpha knockout and heterozygous control mice. Full-thickness head wounds were made using a 6-mm trephine on the crown of the skull. In the ear model, transforming growth factor-alpha knockout mice had significantly larger epithelial gaps versus control at post-operative day 3 and 5. Epithelial thickness at the wound edge of transforming growth factor-alpha deficient mice was also depressed at post-operative day 3 and post-operative day 5 compared to control mice. On post-operative day 8, most wounds of both groups were epithelialized. In contrast, no difference in epithelial gap or new granulation tissue was found in the head model. The data support the concept that transforming growth factor-alpha plays a significant early role in wound epithelialization in vivo but its deficit is compensated if accompanied by granulation tissue formation. The data further show the importance of appropriate wound models to address the role of vulnerary factors.