Inhaled colistimethate sodium reduces bronchiectasis exacerbations
The use of colistimethate sodium (CMS), delivered via the I-neb, reduces pulmonary exacerbations among patients with bronchiectasis and chronic Pseudomonas aeruginosa (P. aeruginosa) infection, according to the PROMIS-1* study presented at ERS 2021.
This phase III, multinational, double-blind, placebo-controlled trial evaluated 377 patients (mean age 64.2 years, ≥64 percent female) with bronchiectasis who had a history of chronic P. aeruginosa infection. Participants were randomized in a 1:1 ratio to receive either CMS (0.3 mL of 1 MIU in 1 mL of 0.45% saline; n=177) or placebo (consisting of 0.3 mL of 0.45% saline; n=200), both delivered via the I-neb device twice daily for 12 months. [ERS 2021, abstract 4267]
Patients treated with CMS experienced a significantly lower annual rate of exacerbations compared with placebo (mean 0.580 vs 0.948; rate ratio [RR], 0.61, 95 percent confidence interval [CI], 0.46–0.82; p=0.00101).
A significantly lower rate of severe exacerbations, defined as the need for intravenous antibiotics or hospitalization or presence of radiographically-confirmed pneumonia, was also observed among patients on CMS than those on placebo (mean 0.116 vs 0.283; RR, 0.41, 95 percent CI, 0.23–0.74; p=0.003).
Finally, there was a prolonged time to first exacerbation in the active therapy group, with a hazard ratio 0.59 (95 percent CI, 0.43–0.81, p=0.00074).
Treatment with CMS resulted in a significant improvement in quality of life (QoL), based on change in the St. George’s Respiratory Questionnaire (SGRQ) total score, with a least squares mean difference of -4.6 between the two groups (95 percent CI, -7.8 to -1.3; p=0.00550), which exceeded the minimally important difference.
In addition, after 28 days of treatment, there was a significant reduction in P. aeruginosa sputum density in the active therapy group vs the control group (LS mean difference, -1.62 log10 CFY/mL, 95 percent CI, -1.99 to -1.25; p<0.00001). No significant increase in resistance to P. aeruginosa was identified in sputum samples submitted at the end of the study or upon leaving the study.
After 28 days of treatment, CMS-treated patients demonstrated a statistically significant decrease in P. aeruginosa density from baseline compared with placebo-treated patients (LS mean difference, -1.62 log10 CFY/mL, 95 percent CI, -1.99 to -1.25; p<0.00001).
Treatment-emergent adverse events (TEAEs) occurred at a similar rate between CMS and placebo treatment groups (80.7 percent for both), but serious TEAEs occurred at a lower rate in the CMS than the placebo group (17.6 percent vs 23.4 percent).
There are currently no FDA-approved treatments for patients with bronchiectasis, said lead author Dr Charles Haworth from Cambridge Centre for Lung Infection at Royal Papworth Hospital in Cambridge, UK.
“[Our findings suggest that treatment with] CMS via I-neb significantly reduced the annual rate of exacerbations and severe exacerbations … [CMS also] prolonged time to first exacerbation … [with] an improvement in QoL,” he said.
“[Moreover,] there was no significant increase in P. aeruginosa resistance to CMS, … [and CMS delivered via the I-neb] was safe and well tolerated,” he added.
*PROMIS-1: Long-term efficacy and safety of inhaled colistimethate sodium in bronchiectasis subjects with chronic pseudomonas aeruginosa infection