Mucosal Healing With Adalimumab in Crohn's Disease
Background & Aims We investigated the efficacy of adalimumab for inducing and maintaining mucosal healing in patients with Crohn's disease (CD).
Methods A randomized, double-blind, placebo-controlled trial (extend the safety and efficacy of adalimumab through endoscopic healing [EXTEND]) evaluated adalimumab for induction and maintenance of mucosal healing in 135 adults with moderate to severe ileocolonic CD. The baseline degree of mucosal ulceration was documented by ileocolonoscopy. All patients received induction therapy (subcutaneous adalimumab 160/80 mg at weeks 0/2). At week 4, patients were randomly assigned to groups given 40 mg adalimumab or placebo every other week through week 52. Open-label adalimumab was given to patients with flares or no response, starting at week 8. Mucosal healing was reassessed by ileocolonoscopy at weeks 12 and 52.
Results Twenty-seven percent of patients receiving adalimumab had mucosal healing at week 12 (the primary end point) versus 13% given placebo (P = .056). At week 52, rates of mucosal healing were 24% and 0, respectively (P < .001). Remission rates, based on the Crohn's Disease Endoscopic Index of Severity, were 52% for adalimumab and 28% for placebo at week 12 (P = .006) and 28% and 3%, respectively, at week 52 (P < .001). Rates of clinical remission based on the Crohn's Disease Activity Index were greater among patients given continuous adalimumab therapy versus placebo at weeks 12 (47% vs 28%; P = .021) and 52 (33% vs 9%; P = .001). Five serious (1 during induction and 4 during open-label therapy) and 3 opportunistic infections (1 in each group during double-blind therapy and 1 during open-label therapy) were reported (n = 135).
Conclusions Following induction therapy with adalimumab, patients with moderately to severely active CD who continue to receive adalimumab are more likely to achieve mucosal healing than those given placebo.
Crohn's disease (CD) is a chronic condition characterized by transmural intestinal inflammation, often with ulceration, involving any part of the gastrointestinal tract but most frequently localized in the colon and/or terminal ileum. Because the clinical signs and symptoms of CD are not necessarily predictive of the severity of mucosal ulceration, quantifying the extent of mucosal inflammation via endoscopy is the gold standard for assessing the severity of luminal disease activity. Preliminary data suggest that mucosal healing in patients with active mucosal inflammation is associated with prolonged clinical remission and longer time to relapse, as well as with reductions in hospitalizations and surgeries. Thus, mucosal healing is an increasingly important therapeutic goal in the treatment of patients with CD.
Adalimumab, a human immunoglobulin G1 antibody to tumor necrosis factor (TNF), is effective for induction and maintenance of clinical remission in both infliximab-naïve and infliximab-experienced adults and children with moderately to severely active CD. Our study, called EXTEND (Extend the Safety and Efficacy of Adalimumab through Endoscopic Healing), was a randomized, double-blind, placebo-controlled maintenance/withdrawal trial of adalimumab in patients with moderate to severe ileocolonic CD and mucosal ulcers documented at ileocolonoscopy who had received open-label induction therapy with adalimumab. EXTEND is the first endoscopic study of adalimumab and the first randomized placebo-controlled trial in CD with mucosal healing as the primary end point.
Abstract and Introduction
Abstract
Background & Aims We investigated the efficacy of adalimumab for inducing and maintaining mucosal healing in patients with Crohn's disease (CD).
Methods A randomized, double-blind, placebo-controlled trial (extend the safety and efficacy of adalimumab through endoscopic healing [EXTEND]) evaluated adalimumab for induction and maintenance of mucosal healing in 135 adults with moderate to severe ileocolonic CD. The baseline degree of mucosal ulceration was documented by ileocolonoscopy. All patients received induction therapy (subcutaneous adalimumab 160/80 mg at weeks 0/2). At week 4, patients were randomly assigned to groups given 40 mg adalimumab or placebo every other week through week 52. Open-label adalimumab was given to patients with flares or no response, starting at week 8. Mucosal healing was reassessed by ileocolonoscopy at weeks 12 and 52.
Results Twenty-seven percent of patients receiving adalimumab had mucosal healing at week 12 (the primary end point) versus 13% given placebo (P = .056). At week 52, rates of mucosal healing were 24% and 0, respectively (P < .001). Remission rates, based on the Crohn's Disease Endoscopic Index of Severity, were 52% for adalimumab and 28% for placebo at week 12 (P = .006) and 28% and 3%, respectively, at week 52 (P < .001). Rates of clinical remission based on the Crohn's Disease Activity Index were greater among patients given continuous adalimumab therapy versus placebo at weeks 12 (47% vs 28%; P = .021) and 52 (33% vs 9%; P = .001). Five serious (1 during induction and 4 during open-label therapy) and 3 opportunistic infections (1 in each group during double-blind therapy and 1 during open-label therapy) were reported (n = 135).
Conclusions Following induction therapy with adalimumab, patients with moderately to severely active CD who continue to receive adalimumab are more likely to achieve mucosal healing than those given placebo.
Introduction
Crohn's disease (CD) is a chronic condition characterized by transmural intestinal inflammation, often with ulceration, involving any part of the gastrointestinal tract but most frequently localized in the colon and/or terminal ileum. Because the clinical signs and symptoms of CD are not necessarily predictive of the severity of mucosal ulceration, quantifying the extent of mucosal inflammation via endoscopy is the gold standard for assessing the severity of luminal disease activity. Preliminary data suggest that mucosal healing in patients with active mucosal inflammation is associated with prolonged clinical remission and longer time to relapse, as well as with reductions in hospitalizations and surgeries. Thus, mucosal healing is an increasingly important therapeutic goal in the treatment of patients with CD.
Adalimumab, a human immunoglobulin G1 antibody to tumor necrosis factor (TNF), is effective for induction and maintenance of clinical remission in both infliximab-naïve and infliximab-experienced adults and children with moderately to severely active CD. Our study, called EXTEND (Extend the Safety and Efficacy of Adalimumab through Endoscopic Healing), was a randomized, double-blind, placebo-controlled maintenance/withdrawal trial of adalimumab in patients with moderate to severe ileocolonic CD and mucosal ulcers documented at ileocolonoscopy who had received open-label induction therapy with adalimumab. EXTEND is the first endoscopic study of adalimumab and the first randomized placebo-controlled trial in CD with mucosal healing as the primary end point.
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