Both tobramycin nebuliser solution (Tobi, Pathogenesis) and inhaled colistin (Colomycin, Pharmax) decrease bacterial density in sputum but only tobramycin increases lung function, said Professor Margaret Hodson (Royal Brompton hospital, London) on March 2. Professor Hodson was presenting the results of a UK trial comparing the two drugs, which are used for the management of Pseudomonas aeruginosa in cystic fibrosis, at a Pathogenesis-sponsored meeting in London.
The results have been disputed by Pharmax, which claims that the trial was biased.
Professor Hodson said that tobramycin and colistin gave statistically significant reductions in Pseudomonas aeruginosa colony counts, while the mean relative change in FEV1 (forced expiratory volume in one second) was 6.7 per cent for the tobramycin group and 0.37 per cent for the colistin group. There were no significant differences in adverse events.
The open label, parallel group trial compared twice daily dosing of Tobi nebuliser solution (300mg/5ml) and colistin solution (80mg/3ml, 1MU). The trial lasted for one month and was completed by 108 patients over six years of age.
Dr Martin Goldman (senior medical advisor, Pharmax) told The Journal on March 7 that, in his opinion, the trial was biased in favour of tobramycin. The dose of colistin used was sub-optimal - 1MU rather than the company's recommended 2MU dose. Dr Goldman also questioned the value of the trial because of its short duration. Final measurements were taken after 28 days' treatment but, during the subsequent "off" phase of tobramycin, the pseudomonal load was likely to increase, he said. Outcome measures should be viewed long-term and the trial was just a "snapshot". The cost of Tobi compared with Colomycin should also be considered, he said. In response to a question about cost at the meeting, Professor Hodson said: "It has to be remembered that [cystic fibrosis] is a life-threatening disease in children and if something stabilises the patient then clinicians should fight for it."
Although lower than recommended by Pharmax, the colistin trial dose was the same as recommended in the British National Formulary. Mr Michael Vasiljev (director of clinical development, Pathogenesis) said that the dose of colistin was chosen because 83 per cent of trial patients had previously used a dose of 1MU twice daily.
Mr Andrew Whitehead (senior pharmacist, regional adult cystic fibrosis unit, Seacroft hospital, Leeds) told The Journal that the dose of colistin used varied between hospitals. At Leeds, 2MU twice daily was the normal dose but other centres used 1MU. Mr Whitehead said that he also had reservations about the duration of the trial. The results reported efficacy after four weeks but there had been some suggestion by cystic fibrosis experts that during Tobi's "off" period, respiratory function decreased.