Faculty Bibliography

GOALS/OBJECTIVE:Our aim was to identify and compare the effectiveness of antitumor necrosis factor biologics when used as initial agents and when used in succession for the treatment of moderate to severe Crohn's disease (CD). BACKGROUND:Studies directly comparing the efficacy of biologics are lacking. When one biologic loses efficacy, patients are often treated with an alternate biologic. The effectiveness of this strategy has not been thoroughly investigated. STUDY/METHODS:This is a retrospective cohort study from a database of 153 patients with CD treated with infliximab, adalimumab, or certolizumab pegol. Response rates determined by physician global assessment were compared between biologics when given as initial agents and after failure of 1 or 2 prior biologics. RESULTS:There were no significant differences in response between infliximab (64.5%), adalimumab (60.0%), and certolizumab pegol (66.7%) when given as initial biologics. As second-line or third-line agents after prior biologic failure, there was a trend toward increased response with infliximab (83.3%) versus adalimumab (52.7%) and certolizumab pegol (59.4%); however, this did not meet statistical significance. After failure or loss of response of 2 previous biologics, use of a third biologic was still effective with a response rate of 54.2%. CONCLUSIONS:All 3 biologics have similar efficacy in the treatment of CD when given as initial agents. Infliximab has a trend toward increased response after prior biologic failure; however, this did not meet statistical significance. Even after loss of response or failure of 2 previous biologics, trial of a third alternate biologic is an effective strategy.

It is well established that mast cells occur within the brain of many species, and that the brain mast cell population is not static, but changes with the behavioral and physiological state of the animal. In this study, we tested whether exposure to conspecifics alters the number of brain mast cells in male rats, and then investigated the nature of stimuli influencing the changes observed in the number and localization of brain mast cells. Five days of cohabitation with an ovariectomized, estrogen-progesterone (OVX + EP)-treated female resulted in the largest number of thalamic mast cells, while pairing with such a female physically separated by a wire mesh or with a novel male produced a smaller, but significant increase over other pairings (OVX females for 5 days, OVX and OVX + EP females for 1 day, familiar or isolated males for 5 days). In all groups, mast cells were localized within specific dorsal thalamic nuclei, including the paraventricular nucleus, anterior nuclear group, or mediodorsal, ventroposterior, or medial geniculate nuclei. The results suggest that the behavioral and/or endocrine factors associated with cohabitation with conspecifics are sufficient to alter the number of brain mast cell-specific nuclei in the thalami of male rats and thus can provide targeted delivery of neuromodulators to specific regions of the brain that process information concerning the normal physiological state of the animal.