Corticosteroids May Worsen Gastroesophageal Reflux in Patients With Idiopathic Pulmonary Fibrosis: Response

Abstract

Indeed, it is well known to clinicians that patients treated with oral corticosteroids, regardless of the indication, manifest new and/or worsened symptoms suggestive of abnormal gastroesophageal reflux (GER). Thus, several patients receiving corticosteroids take over-the-counter remedies for such symptoms while taking corticosteroids, and several clinicians prescribe medications to suppress symptoms of GER for patients receiving corticosteroids. In the context of management of idiopathic pulmonary fibrosis (IPF), the longstanding and ongoing practice of using corticosteroids has evolved into a standard of care without evidence supported by well-designed, prospective clinical trials that compare the efficacy and safety of a treatment regimen with true-placebo control subjects. Thus, the comments and concerns raised by Fimognari and Pastorelli to our article1Raghu G Yang S Spada C et al.Sole treatment of acid gastroesophageal reflux in idiopathic pulmonary fibrosis: a case series.Chest. 2006; 129: 794-800Abstract Full Text Full Text PDF PubMed Scopus (168) Google Scholar are appropriate. Since it is unknown if any treatment regimen (including corticosteroids) that is being currently used for patients with IPF is effective when compared to no specific treatment, and since there is no evidence to support lone-corticosteroid treatment for IPF, it is hoped that the lingering standard of care using corticosteroids alone as a treatment will fade away soon while evidence that will determine an efficacious treatment regimen for IPF is being pursued.2Raghu G Idiopathic fibrosis treatment: options in pursuit of evidence-based approaches.Eur Respir J. 2006; 28: 463-465Crossref Scopus (19) Google Scholar Given the inevitable poor prognosis associated with the diagnosis of IPF and a safe and efficacious treatment regimen is yet to be determined, it is most appropriate to decrease and/or avoid further risks and minimize comorbid conditions for patients confronted with this fatal disease. Although the results of a recent clinical trial favors the use of combined prednisone with azathioprine and N-acetylcysteine (NAC) compared to prednisone plus azathioprine (the Idiopathic Pulmonary Fibrosis International Group Exploring N-Acetylcysteine I Annual [IFIGENIA] study conducted in Europe published by Demedts et al3Demedts M Behr J Buhl R et al.High-dose acetylcysteine in idiopathic pulmonary fibrosis.N Engl J Med. 2005; 353: 2229-2242Crossref PubMed Scopus (816) Google Scholar) and an earlier clinical trial4Raghu G Depaso WJ Cain K et al.Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial.Am Rev Respir Dis. 1991; 144: 291-296Crossref PubMed Scopus (377) Google Scholar suggested the potential benefits of combined prednisone plus azathioprine compared to prednisone alone, it is unknown if such regimens that include prednisone as a treatment agent improves the outcome of patients in IPF when compared to control subjects receiving absolutely no treatment at all (the “true-placebo” controls subjects). Despite the caution raised in interpreting results of clinical trials in IPF and plea that I have made to refrain the use of treatment regimen without firm evidence,2Raghu G Idiopathic fibrosis treatment: options in pursuit of evidence-based approaches.Eur Respir J. 2006; 28: 463-465Crossref Scopus (19) Google Scholar5Johnson WC Raghu G Clinical trials in idiopathic pulmonary fibrosis: a word of caution concerning choice of outcome measures.Eur Respir J. 2005; 26: 755-758Crossref PubMed Scopus (16) Google Scholar the concern raised by Fimognari and Pastorelli is appreciated since the current international consensus statement on the management guidelines for IPF6Idiopathic pulmonary fibrosis: diagnosis and treatment: international consensus statement.Am J Respir Crit Care Med. 2000; 161: 646-664Crossref PubMed Scopus (950) Google Scholar and the evidence provided by the IFIGENIA study will tempt clinicians to continue to try corticosteroids with or without combinations with agents such as azathioprine and NAC. Thus, the potential for enhanced risk for comorbid conditions and for possible progression of IPF if the hypothesis of abnormal GER contributing to IPF holds. While it is hoped that ongoing and future clinical trials will provide the needed evidence to recommend a specific treatment regimen for IPF, the Hippocratic oath and longstanding philosophy of “do no harm” must be respected in managing such medical problems.