A double-blind clinical trial for treatment of Crohn's disease by oral administration of Alequel, a mixture of autologous colon-extracted proteins: a patient-tailored approach.
OBJECTIVE
In this study, we evaluated the safety and efficacy of a personalized mode of treatment for Crohn's disease (CD) by oral administration of Alequel an extract of autologous colonic proteins.


METHODS
Thirty-one patients with moderate to severe CD were enrolled in a 27-wk randomized, double-blind, placebo-controlled trial. Patients were randomized to receive either a placebo or the study drug prepared from autologous colonic extract.


RESULTS
Oral administration of autologous colonic proteins resulted in clinical remission (58% vs 29%; 46.6% vs 26.6%, using an intention to treat analysis, p= NS), clinical response (67% vs 43%; 53.3% vs 40%, using an intention to treat analysis, p= NS) and improved quality of life (Inflammatory Bowel Disease Questionnaire score improvement 43%vs 12%) in the drug study group, compared to placebo group. No treatment-related adverse events were noted. Only in the study-drug-treated cohort who achieved clinical remission (DR), there was a decreased number of subject-specific, antigen-directed, IFNgamma spot-forming colonies. DR subjects had a lower initial C-reactive protein level than DNOR or placebo subjects, an increased percentage of peripheral blood nature killer T cells, and an increased CD4+/CD8+ T-cell ratio throughout the period of drug administration.


CONCLUSIONS
Oral administration of Alequel is a safe method for treatment of patients with moderate to severe CD, and its efficacy needs to be proven. Several markers may be applicable as surrogate markers for the clinical effect.
Margalit
Maya
M
Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel IL-91120.
Israeli
Eran
E
Shibolet
Oren
O
Zigmond
Ehud
E
Klein
Athalia
A
Hemed
Nilla
N
Donegan
James J
JJ
Rabbani
Elazar
E
Goldin
Eran
E
Ilan
Yaron
Y
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001324:Autoantigens / Q000276:immunology / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000097:blood; D016516:CD4-CD8 Ratio; D016827:CD8 Antigens / Q000097:blood; D015331:Cohort Studies; D003106:Colon / Q000276:immunology* / Q000473:pathology; D003113:Colonoscopy; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000523:psychology; D004311:Double-Blind Method; D000939:Epitopes / Q000276:immunology / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011788:Quality of Life / Q000523:psychology; D018434:Sickness Impact Profile; D016896:Treatment Outcome
D001324:Autoantigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D000939:Epitopes; D007166:Immunosuppressive Agents; D011241:Prednisone