CF Patients Can Safely Stop Inhaled Corticosteroids

LONDON, June 15 - Patients with cystic fibrosis (CF) can safely stop using inhaled corticosteroids, according to researchers here.

In a six-month randomized trial, there was no apparent impact, adverse or beneficial, for cystic fibrosis patients when the use of Flovent (fluticasone) was halted, Ian Balfour-Lynn, M.D., of Royal Brompton Hospital here in the American Journal of Respiratory and Critical Care Medicine.

Dr. Balfour-Lynn and colleagues concluded that it is safe to stop using inhaled corticosteroids in order to lower their drug burden, to reduce adverse side effects, and to save money.

But "it must be stressed that we are not advocating stopping inhaled corticosteroids in all patients, but urging clinicians to assess the need in each individual," the researchers added. "If there is objective evidence that a patient benefited when inhaled corticosteroids were first started, then it is likely they should be continued on inhaled corticosteroids."

While it is known that oral corticosteroids slow the progression of CF lung disease, Dr. Balfour-Lynn said, a systematic review concluded there was no evidence to support prescribing inhaled corticosteroids for CF patients. Despite the lack of evidence, he and colleagues noted, there has been a sharp increase in inhaled corticosteroids prescriptions for CF patients, both in the United Kingdom and the U.S., between the mid-1990s and 2001.

For instance, in 1995 only 26% of American CF patients were using ICS, but by 2001, 41% of children and 48% of adults were using the medications.

"The concern over this increased prescribing is that inhaled corticosteroids are not necessarily free of adverse effects," the researchers said.

Because the drugs are widely used, the researchers noted, a prospective trial was difficult. Instead, they chose to initiate a withdrawal trial, in which all patients would begin as inhaled corticosteroids users, but some would be randomly assigned to an inhaler containing a placebo.

They enrolled 171 patients from 18 British pediatric and adult centers; patients had to be over the age of six, have a one-second forced expiratory volume (FEV₁) of at least 40% of the predicted value, and have used inhaled corticosteroids for more than three months.

During a two-month run-in period, all patients used Flovent, switching to it if they had been using another medication. After the run-in, they were randomly assigned to either continue with Flovent or a placebo in an identical inhaler.

Analysis of the results found that:

• The time to first exacerbation, which was the primary outcome, did not differ between the groups; the hazard ratio was 1.07, with a 95% confidence interval from 0.68 to 1.70, for Flovent versus placebo.
• Neither age, atopy, corticosteroid dose, FEV₁, nor Pseudomonas aeruginosa status made a difference.
• There was no change in lung function or differences in antibiotic or rescue bronchodilator use.
• Fewer patients in the Flovent group withdrew from the study because of lung-related adverse events - 9% versus 15% -- but the difference was non-significant. The relative risk was 0.59, with a 95% confidence interval from 0.23 to 1.48, for Flovent versus placebo.

The conclusion, the researchers said, is that "it is likely that the majority of patients taking inhaled corticosteroids no longer need to do so." They suggested that "the prescribing practice of inhaled corticosteroids in a CF patient become more like that for an asthmatic. Justification is needed to start them, reassessment is necessary to see whether they are having an effect (particularly on any tight cough or wheeze), and consideration is always given to reducing the dose or stopping them altogether."