G McCormack1, D O'Donoghue, A Baird. 1. Department of Gastroenterology and Liver Unit, St Vincent's University Hospital, Dublin, Ireland.
Abstract
BACKGROUND: The efficacy of cyclosporin in the management of ulcerative colitis is recognized. Not all patients respond to this treatment. Existing clinical and laboratory parameters are of little use in identifying those most likely to respond. AIMS: To determine whether in-vitro sensitivity to cyclosporin as measured by a lymphocyte proliferation assay is predictive of in-vivo response to therapy. METHODS: The study comprised seven responders with ulcerative colitis, seven non-responders, and 14 healthy matched controls. A lymphocyte proliferation assay was carried out in the presence of a range of concentrations of cyclosporin and a dose-response curve constructed for each subject. The IC(50) value, the concentration of cyclosporin that resulted in 50% inhibition of proliferation, was calculated for each subject. IC(50) values for responders, non-responders and controls were compared using a Mann-Whitney test. RESULTS: There was a wide range of values obtained for the study group as a whole. IC(50) values for non-responders were significantly higher than those of responders (P < 0.05). CONCLUSIONS: There is a population-wide variation of in-vitro sensitivity to cyclosporin. This is reflected in in-vivo sensitivity as measured by clinical response to cyclosporin treatment. Future therapeutic strategies need to address this inherent variability of individual response to therapy.
BACKGROUND: The efficacy of cyclosporin in the management of ulcerative colitis is recognized. Not all patients respond to this treatment. Existing clinical and laboratory parameters are of little use in identifying those most likely to respond. AIMS: To determine whether in-vitro sensitivity to cyclosporin as measured by a lymphocyte proliferation assay is predictive of in-vivo response to therapy. METHODS: The study comprised seven responders with ulcerative colitis, seven non-responders, and 14 healthy matched controls. A lymphocyte proliferation assay was carried out in the presence of a range of concentrations of cyclosporin and a dose-response curve constructed for each subject. The IC(50) value, the concentration of cyclosporin that resulted in 50% inhibition of proliferation, was calculated for each subject. IC(50) values for responders, non-responders and controls were compared using a Mann-Whitney test. RESULTS: There was a wide range of values obtained for the study group as a whole. IC(50) values for non-responders were significantly higher than those of responders (P < 0.05). CONCLUSIONS: There is a population-wide variation of in-vitro sensitivity to cyclosporin. This is reflected in in-vivo sensitivity as measured by clinical response to cyclosporin treatment. Future therapeutic strategies need to address this inherent variability of individual response to therapy.