Kalydeco Enhances Bicarbonate Secretion, Improving Outcomes in Some CF Patients

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by Patricia Inacio PhD |

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Bicarbonate secretion and MS

Kalydeco (ivacaftor, VX-770) improves bicarbonate secretion in cystic fibrosis (CF) patients with a certain gene mutation, according to a study.

Bicarbonate is essential to digestion and the flow of several secretions in the body, including those of the intestine and pancreas.

The report, “Impact of CFTR Modulation on Intestinal pH, Motility, and Clinical Outcomes in Patients With Cystic Fibrosis and the G551D Mutation,” was published in the journal Clinical and Translational Gastroenterology.

Previous studies suggested that the release of bicarbonate from the intestine, particularly from the duodenum, occurs by way of the cystic fibrosis transmembrane conductance regulator (CFTR). This ion channel is defective in CF patients, suggesting bicarbonate secretion may be important in the disease. In fact, lack of bicarbonate leads to intestinal mucus becoming excessively adhesive.

In addition, in parts of the intestine, bicarbonate secretion is required to rapidly neutralize the acidic gastric, or stomach acid, pH level of 1–3 to the level of 5.5–7 the body needs.

Kalydeco is an oral CFTR potentiator that improves CF patients’ outcomes, particularly those with a gene mutation known as the CFTR G551D gating mutation.

Researchers hypothesized that these benefits could be the result of increased bicarbonate secretion. They decided to measure pH levels in the intestine to see whether CFTR mediates bicarbonate secretion. They correlated the measurements with disease parameters in patients with the G551D mutation before and after treatment with Kalydeco.

The team analyzed data from two longitudinal observational cohort studies assessing Kalydeco’s effectiveness. The studies were performed at tertiary, or specialized, care settings at CF centers in the United States and Canada.

Researchers assessed patients’ pH level before Kalydeco treatment and a month after. They also evaluated patients’s intestinal motility and abdominal pain, and registered their body weight before and after treatment. Motility disorders are characterized by abnormal intestinal contractions, such as spasms.

“One month after administering ivacaftor, a significant increase in mean pH was observed after gastric emptying,” researchers wrote. The Kalydeco-related improvement in G551D CFTR mutation patients’ intestinal pH levels was a result of increased levels of bicarbonate, they said.

The results could prove significant in managing CF in clinics, the team said.

“We have demonstrated that CFTR modulation improves the proximal small intestinal pH profile in patients with the G551D CFTR mutation, and we observed clinically relevant, contemporaneous weight gain, although it did not reach statistical significance. These data provide in vivo evidence that CFTR is an important regulator of bicarbonate secretion, which may be a translational link between CFTR function and clinical improvement.” the researchers concluded.


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