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Vincenzo Papa, Paolo Rama, Federica Ferrario, Andrea Ramoni, Stanislav Matuska, Cherry Radford, John Kenneth George Dart; Orphan Drug for Acanthamoeba Keratitis (ODAK) project: results of a 10-Year retrospective study in Italy and in the United Kingdom. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5520.
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A 10-year retrospective study has been conducted to evaluate the clinical outcome of patients affected by Acanthamoeba keratitis (AK). AK is a rare but severe infectious disease which may result in loss of sight in the affected eye. The most used compound for the treatment of AK is polyhexamethylene biguanide (PHMB), an unlicensed drug which has received the orphan drug designation by the European Union (EU). ODAK is a project funded by the EU under the Seventh Framework Programme (GA N 305661) with the aim to develop PHMB as the first approved drug medicinal product for the treatment of AK.
Records from patients affected by AK treated from 1997 to 2007 at Moorfields and San Raffaele hospitals were selected. The primary end point of the study was the clinical resolution rate (CRR) defined as percentage of patients cured 1 month after discontinuing all therapies. A descriptive statistic was performed.
100 patients were evaluated. Ninety six were contact lens wearers. In 84 cases diagnosis was based on either culture or histology. 83 patients were treated with multiple agents. PHMB was the most used drug whereas PHMB and a diamidine (hexamidine or propamidine) were prevalently used as combination therapy. The median duration of treatment was 139 days (interquartile range =108-239 days). The overall CRR was 86%. Patients treated with monotherapy (PHMB or Chlorhexidine) had a higher CRR (96-100%) than patients treated with combination therapy (80-83%); these differences were not statistically significant. The 14 patients not cured medically had penetrating keratoplasty. The most common adverse event reported was ocular toxicity; 5 cases were related to the use of diamidines and 3 cases to that of biguanides.
PHMB was the most used medication for patients with AK in this study. Data suggest that PHMB used as monotherapy has a good risk to benefit ratio and is a good candidate for a new drug licensing application. The next clinical step in the ODAK project, after the completion of preclinical studies (toxicity, pharmacokinetic and pharmacodynamics) is a prospective randomized clinical trial comparing PHMB as monotherapy with a combination therapy including PHMB and propamidine.
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