Long-term safety study of colistimethate sodium (Colobreathe®): Findings from the UK Cystic Fibrosis Registry.

Abstract

BACKGROUND:

As part of the risk management plan in Europe, a long-term observational study was conducted to monitor the safety of colistimethate sodium dry powder for inhalation (CMS-DPI) compared to other inhaled antibiotics.

METHODS:

A cohort of CMS-DPI patients and a matched cohort were identified from the UK Cystic Fibrosis Registry (UKCFR) from 2014-2018. The primary outcome was a composite endpoint, defined as adverse events (AEs) or new cystic fibrosis (CF) complications. Other outcomes included pulmonary exacerbations and treatment discontinuations.

RESULTS:

Of 1466 and 3503 patients in the CMS-DPI and comparator cohorts, respectively, 82.7% and 79.4% had AEs. Among the most common new CF complications were osteopenia, CF-related diabetes, and increased liver enzymes. The adjusted event rate ratio (ERR) for the primary outcome was 1.25 (95% confidence interval [CI]: 1.18-1.33, p<0.001). After excluding new CF complications, there was no difference between cohorts (ERR=1.04, 95% CI: 0.79-1.38, p=0.785). Pulmonary exacerbations were common in CMS-DPI and comparator cohorts (78.0% and 79.9% of patients, respectively), with adjusted ERR of 1.02 (95% CI: 0.95-1.10, p=0.523). Rates of discontinuation were similar in the CMS-DPI and Tobramycin inhalation powder comparator cohorts (37.8% and 39.8% of patients, respectively).

CONCLUSIONS:

There was no difference in the rate of adverse events between CMS-DPI and comparator cohorts. The safety profile of CMS-DPI is similar to those of other inhaled antibiotics, supporting its long-term safety in people with CF. The UKCFR has developed a successful model for partnership with industry to conduct long-term studies aimed at assessing drug safety.

• Authors: Sigal Kaplan, Andrew Lee, Noreen Caine, Susan C Charman, Diana Bilton
• Journal: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society (J Cyst Fibros) Vol. 20 Issue 2 Pg. 324-329 (03 2021) ISSN: 1873-5010 [Electronic] Netherlands
• PMID: 32807645 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020. Published by Elsevier B.V.

Chemical References

• Anti-Bacterial Agents
• colistinmethanesulfonic acid
• Colistin

Topics

• Administration, Inhalation
• Adolescent
• Adult
• Aged
• Anti-Bacterial Agents (administration & dosage, therapeutic use)
• Child
• Colistin (administration & dosage, analogs & derivatives, therapeutic use)
• Cystic Fibrosis (complications)
• Female
• Humans
• Male
• Middle Aged
• Pseudomonas Infections (drug therapy)
• Registries
• Respiratory Tract Infections (drug therapy, microbiology)
• Symptom Flare Up
• United Kingdom