Market share and costs of biologic therapies for inflammatory bowel disease in the USA.

BACKGROUND: Real-world data quantifying the costs of increasing use of biologics in inflammatory bowel disease (IBD) are unknown. AIM: To determine the outpatient IBD drug utilization trends, relative market share, and costs in the USA during a 9-year period. METHODS: The Truven MarketScan® Database was analysed for patients with Crohn's disease (CD) and ulcerative colitis (UC) during 2007-2015. National drug codes were used to identify prescription drugs; Healthcare Common Procedure Coding System J-codes were used to capture biologic out-patient infusions. Proportion of drug usage, relative market share and per-member per-year (PMPY) costs were analysed for biologics, immunomodulators, 5-ASAs and corticosteroids. RESULTS: In 415 405 patients (188 842 CD; 195 183 UC; 31 380 indeterminate colitis; 54.67% female), utilization trends show a consistent rise in the market share of biologics during the 9-year study period. The proportion of patients using biologics increased from 21.8% to 43.8% for CD and 5.1%-16.2% for UC. This contrasts a small decrease in immunomodulator and 5-ASA use for CD and relative constancy of other classes including corticosteroids-only use as primary IBD medication from 2007 to 2015. The average biologic-taking patient accounted for $25 275 PMPY in 2007 and $36 051 PMPY in 2015. The average paediatric biologic-taking patient accounted for $23 616 PMPY in 2007 and $41 109 PMPY in 2015. In all patients, the share of costs for biologics increased from 72.9% in 2007 to 85.7% in 2015 (81.7% in 2007 to 94.9% in 2015 in paediatrics). CONCLUSION: The vast majority of costs allocated to out-patient IBD medications in the USA is attributed to increasing use of biologic therapies despite the relative minority of biologic-taking patients.

A role for guanylate cyclase C in acid-stimulated duodenal mucosal bicarbonate secretion.

Luminal acidification provides the strongest physiological stimulus for duodenal HCO3- secretion. Various neurohumoral mechanisms are believed to play a role in acid-stimulated HCO3- secretion. Previous studies in the rat and human duodenum have shown that guanylin and Escherichia coli heat-stable toxin, both ligands of the transmembrane guanylyl cyclase receptor [guanylate cyclase C (GC-C)], are potent stimulators for duodenal HCO3- secretion. We postulated that the GC-C receptor plays an important role in acid-stimulated HCO3- secretion. In vivo perfusion studies performed in wild-type (WT) and GC-C knockout (KO) mice indicated that acid-stimulated duodenal HCO3- secretion was significantly decreased in the GC-C KO animals compared with the WT counterparts. Pretreatment with PD-98059, an MEK inhibitor, resulted in attenuation of duodenal HCO3- secretion in response to acid stimulation in the WT mice with no further effect in the KO mice. In vitro cGMP generation studies demonstrated a significant and comparable increase in cGMP levels on acid exposure in the duodenum of both WT and KO mice. In addition, a rapid, time-dependent phosphorylation of ERK was observed with acid exposure in the duodenum of WT mice, whereas a marked attenuation in ERK phosphorylation was observed in the KO animals despite equivalent levels of ERK in both groups of animals. On the basis of these studies, we conclude that transmembrane GC-C is a key mediator of acid-stimulated duodenal HCO3- secretion. Furthermore, ERK phosphorylation may be an important intracellular mediator of duodenal HCO3- secretion.