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      Real World Experiences: Pirfenidone and Nintedanib are Effective and Well Tolerated Treatments for Idiopathic Pulmonary Fibrosis

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          Abstract

          Idiopathic Pulmonary Fibrosis (IPF) now has two licensed treatments available. Pirfenidone was the first drug to be licensed and approved for use, followed by nintedanib. We set out our real world experience with these agents in terms of their adverse events profile outside the restrictions of a clinical trial. We have demonstrated in the real world setting, that side effects are common and predominantly gastrointestinal with both therapies. Our study shows that the side effects can be effectively managed in the majority of patients with an acceptable discontinuation rate similar to that seen in the clinical trials. These findings are compelling despite the fact that the patients in our study are older, have severer disease as depicted by baseline lung function and more co-morbidities. Our data provides ongoing evidence of the safety and tolerability of both pirfenidone and nintedanib in patients who would not have met the rigorous criteria to be included in a clinical trial. Both these agents are effective in the management of IPF and slow the progression of this debilitating life limiting condition.

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          Most cited references13

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          Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis.

          Idiopathic pulmonary fibrosis is a progressive lung disease with a high mortality rate. Because the signaling pathways activated by several tyrosine kinase receptors have been shown to be involved in lung fibrosis, it has been suggested that the inhibition of these receptors may slow the progression of idiopathic pulmonary fibrosis. In a 12-month, phase 2 trial, we assessed the efficacy and safety of four different oral doses of the tyrosine kinase inhibitor BIBF 1120 as compared with placebo in patients with idiopathic pulmonary fibrosis. The primary end point was the annual rate of decline in forced vital capacity (FVC). Secondary end points included acute exacerbations, quality of life (measured with the St. George's Respiratory Questionnaire [SGRQ]), and total lung capacity. A total of 432 patients underwent randomization to receive one of four doses of BIBF 1120 (50 mg once a day, 50 mg twice a day, 100 mg twice a day, or 150 mg twice a day) or placebo. In the group receiving 150 mg of BIBF 1120 twice a day, FVC declined by 0.06 liters per year, as compared with 0.19 liters per year in the placebo group, a 68.4% reduction in the rate of loss with BIBF 1120 (P = 0.06 with the closed testing procedure for multiplicity correction; P = 0.01 with the hierarchical testing procedure). This dose also resulted in a lower incidence of acute exacerbations, as compared with placebo (2.4 vs. 15.7 per 100 patient-years, P = 0.02) and a small decrease in the SGRQ score (assessed on a scale of 0 to 100, with lower scores indicating better quality of life) as compared with an increase with placebo (-0.66 vs. 5.46, P = 0.007). Gastrointestinal symptoms (which led to more discontinuations in the group receiving 150 mg twice a day than in the placebo group) and increases in levels of liver aminotransferases were more frequent in the group receiving 150 mg of BIBF 1120 twice daily than in the placebo group. In patients with idiopathic pulmonary fibrosis, BIBF 1120 at a dose of 150 mg twice daily, as compared with placebo, was associated with a trend toward a reduction in the decline in lung function, with fewer acute exacerbations and preserved quality of life. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT00514683 .).
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            Pirfenidone in Idiopathic Pulmonary Fibrosis: Expert Panel Discussion on the Management of Drug-Related Adverse Events

            Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose. Electronic supplementary material The online version of this article (doi:10.1007/s12325-014-0112-1) contains supplementary material, which is available to authorized users.
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              Drug-induced photosensitivity: culprit drugs, management and prevention.

              Photo-induced drug eruptions are cutaneous adverse events due to exposure to a drug and either ultraviolet or visible radiation. Based on their pathogenesis, they can be classified as phototoxic or photoallergic drug eruptions, although in many cases it is not possible to determine whether a particular eruption is due to a phototoxic or photoallergic mechanism. In this review, the diagnosis, prevention and management of drug-induced photosensitivity are discussed. Diagnosis is based primarily on the history of drug intake and the clinical appearance of the eruption, primarily affecting sun-exposed areas of the skin. Phototesting and photopatch testing can be useful adjuncts in making a diagnosis. The mainstay of management is prevention, including informing patients of the possibility of increased sun sensitivity and the use of sun protective measures. However, once the eruption has occurred, it may be necessary to discontinue the culprit medication and treat the eruption with a potent topical corticosteroid. Drugs that have been implicated in causing photosensitive eruptions are reviewed. Tetracycline, doxycycline, nalidixic acid, voriconazole, amiodarone, hydrochlorothiazide, naproxen, piroxicam, chlorpromazine and thioridazine are among the most commonly implicated medications. We review the medical literature regarding evidence for the culpability of each drug, including the results of phototesting, photopatch testing and rechallenge testing.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                02 September 2016
                September 2016
                : 5
                : 9
                : 78
                Affiliations
                [1 ]North West Interstitial Lung Disease Unit, University Hospital of South Manchester, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M29 9LT, UK; gareth.e.hughes@ 123456doctors.org.uk (G.H.); helen.morris4@ 123456nhs.net (H.M.); Colm.Leonard@ 123456UHSM.NHS.UK (C.L.)
                [2 ]Manchester Academic Health Science Centre, The University of Manchester, Oxford Road, Manchester M13 9PL, UK
                [3 ]Manchester Medical School, The University of Manchester, Oxford Road, Manchester M13 9PL, UK; hannah.toellner@ 123456student.manchester.ac.uk
                Author notes
                [* ]Correspondence: Nazia.Chaudhuri@ 123456uhsm.nhs.uk ; Tel.: +44-161-291-5234
                Article
                jcm-05-00078
                10.3390/jcm5090078
                5039481
                27598213
                dbbc173a-ae45-44d9-9123-885b7c327b8b
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 24 July 2016
                : 30 August 2016
                Categories
                Review

                pirfenidone,nintedanib,ipf,idiopathic pulmonary fibrosis

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