Background: Increased activity of intestinal alkaline phosphatase (AP) occurs locally in patients with ulcerative colitis (UC), aimed at repairing inflammatory tissue damage. We evaluated the safety and preliminary efficacy of exogenous AP administered to patients with UC in an open-label, first-in-patient exploratory trial, conducted in the Internal Medicine and Gastroenterology hospital departments in the Czech Republic and Italy.
Methods: Twenty-one patients were enrolled (13 females), age 23-54 years, with steroid- and/or immunosuppressant-refractory, moderate/severe UC (Mayo score 6-11). Oral AP enzyme 30,000 U was administered daily for 7 days, intraduodenally. Efficacy outcomes were changes in Mayo score at Day 21 posttreatment; changes in Modified Truelove-Witts Severity index (MTWSI) at Days 21, 63; C-reactive protein and stool calprotectin levels at Days 7, 21, 63. Safety evaluations were adverse events and laboratory abnormalities reported up to Day 63 posttreatment.
Results: No clinically relevant adverse events causing withdrawal or considered serious, or laboratory abnormalities or antibody formation against AP were observed. Mayo scores were significantly decreased at Day 21, and MTWSI at Days 21 and 63. C-reactive protein and stool calprotectin levels were decreased at Days 21 and 63. Clinical response on the Mayo score after a single 7-day AP course was 48% at Day 21.
Conclusions: In this uncontrolled trial, administration of exogenous AP enzyme daily over a 7-day course to patients with UC was associated with short-term improvement in disease activity scores, with clinical effects being observed within 21 days and associated with reductions in C-reactive protein and stool calprotectin. AP enzyme treatment was well tolerated and nonimmunogenic.