Assessment of Posaconazole Salvage Therapy in Chronic Pulmonary Aspergillosis by Using Predefined Response Criteria

Abstract

Objective: Chronic pulmonary aspergillosis (CPA) is a progressive infection that destroys lung tissue in immune competent patients. First-line therapies for CPA (itraconazole and/or voriconazole) are often curtailed due to toxicity or the development of drug resistance. Posaconazole is a potential alternative for these patients, but it is a high-cost medication. Methods: Use of posaconazole was funded by the NHS Highly Specialised National Commissioners on an individual basis for patients who failed or did not tolerate first line therapy; those who met predefined criteria for improvement at 4 and 6 months (weight gain and/or improvement in St George’s Respiratory Questionnaire) continued posaconazole long-term. We recorded response, failure, discontinuation rates and adverse events. Results: Seventy-eight patients received posaconazole as salvage therapy. Thirty-four (44%) achieved targets for continuation of therapy. Fourteen (18%) failed therapy; 5 (36%) patients did not achieve clinical targets at 4 or 6 months of assessment and 9 (64%) developed clinical and/or radiological failure. Twenty-eight (36%) discontinued their trial early; 8 (29%) died and 20 (71%) had significant side effects. One patient was non-compliant and another was lost to follow-up. Conclusions: Establishing criteria for therapeutic success offered a clear, safe and sustainable method of identifying patients who benefit from additional therapy and minimised continuation of ineffective therapy in those who did not.