High-Dose Acetylcysteine in Idiopathic Pulmonary Fibrosis
Maurits Demedts, M.D., Juergen Behr, M.D., Roland Buhl, M.D., Ulrich Costabel, M.D., P.N., Richard Dekhuijzen, M.D., Henk M. Jansen, M.D., William MacNee, M.D., Michiel Thomeer, M.D., Benoit Wallaert, M.D., François Laurent, M.D., Andrew G. Nicholson, M.D., Eric K. Verbeken, M.D., Johny Verschakelen, M.D., Christopher D.R. Flower, M.D., Frédérique Capron, M.D., Stefano Petruzzelli, M.D., Paul De Vuyst, M.D., Jules M.M. van den Bosch, M.D., Eulogio Rodriguez-Becerra, M.D., Giuseppina Corvasce, Ph.D., Ida Lankhorst, M.D., Marco Sardina, M.D., Mauro Montanari, Ph.D., for the IFIGENIA Study Group
Background Idiopathic pulmonary fibrosis is a chronic progressivedisorder with a poor prognosis.
Methods We conducted a double-blind, randomized, placebo-controlledmulticenter study that assessed the effectiveness over one yearof a high oral dose of acetylcysteine (600 mg three times daily)added to standard therapy with prednisone plus azathioprine.The primary end points were changes between baseline and month12 in vital capacity and in single-breath carbon monoxide diffusingcapacity (DLCO).
Results A total of 182 patients were randomly assigned to treatment(92 to acetylcysteine and 90 to placebo). Of these patients,155 (80 assigned to acetylcysteine and 75 to placebo) had usualinterstitial pneumonia, as confirmed by high-resolution computedtomography and histologic findings reviewed by expert committees,and did not withdraw consent before the start of treatment.Fifty-seven of the 80 patients taking acetylcysteine (71 percent)and 51 of the 75 patients taking placebo (68 percent) completedone year of treatment. Acetylcysteine slowed the deteriorationof vital capacity and DLCO: at 12 months, the absolute differencesin the change from baseline between patients taking acetylcysteineand those taking placebo were 0.18 liter (95 percent confidenceinterval, 0.03 to 0.32), or a relative difference of 9 percent,for vital capacity (P=0.02), and 0.75 mmol per minute per kilopascal(95 percent confidence interval, 0.27 to 1.23), or 24 percent,for DLCO (P=0.003). Mortality during the study was 9 percentamong patients taking acetylcysteine and 11 percent among thosetaking placebo (P=0.69). There were no significant differencesin the type or severity of adverse events between patients takingacetylcysteine and those taking placebo, except for a significantlylower rate of myelotoxic effects in the group taking acetylcysteine(P=0.03).
Conclusions Therapy with acetylcysteine at a dose of 600 mgthree times daily, added to prednisone and azathioprine, preservesvital capacity and DLCO in patients with idiopathic pulmonaryfibrosis better than does standard therapy alone.
Source Information
From University Hospital, Katholieke Universiteit Leuven, Leuven, Belgium (M.D., M.T., E.K.V., J.V.); Medizinische Klinik I, Klinikum Grosshadern der Ludwig-Maximilians-Universität, Munich, Germany (J.B.); Medizinische Klinik III, Klinikum der Johannes-Gutenberg-Universität, Mainz, Germany (R.B.); Medical Faculty Essen, Ruhrlandklinik, Essen-Heidhausen, Germany (U.C.); Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands (P.N.R.D.); Academic Medical Center, Amsterdam (H.M.J.); University of Edinburgh Medical School, Edinburgh (W.M.); Centre Hospitalier Régional Universitaire de Lille, Hôpital Calmette, Lille, France (B.W.); Hôpital Cardiologique, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France (F.L.); Royal Brompton Hospital, London (A.G.N.); Evelyn Hospital, Cambridge, United Kingdom (C.D.R.F.); Hôpital Antoine-Béclère, Clamart, France (F.C.); Dipartimento Cardio-Toracico, Università degli Studi di Pisa, Pisa, Italy (S.P.); Université Libre de Bruxelles, Erasmus Hospital, Brussels (P.V.); Heart Lung Center Utrecht, St. Antonius Ziekenhuis, Nieuwegein, the Netherlands (J.M.M.B.); Hospital Universitario Virgen del Rocio, Seville, Spain (E.R.-B.); Zambon Group, Bresso, Milan (G.C., I.L., M.S.); and Innopharma, Varedo, Milan (M.M.).
Address reprint requests to Dr. Demedts at the Division of Pneumology, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium, or at maurits.demedts{at}uz.kuleuven.ac.be.
Acetylcysteine in Pulmonary Fibrosis
Hull J. H.K., Toma T. P., Bhowmik A., Rajakulasingam R., Demedts M., Buhl R., Costabel U., the IFIGENIA Study Group
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N Engl J Med 2006;
354:1089-1091, Mar 9, 2006.
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