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Suggested edit to Nintedanib Article
I would like to propose the following updates to the Nintedanib Wikipedia entry (http://en.wikipedia.org/wiki/Nintedanib) to ensure the content is up-to-date and reflects the current regulatory status of nintedanib. As currently noted, nintedanib is approved by the FDA for the treatment of idiopathic pulmonary fibrosis under the trade name Ofev®. Also, the CHMP provided a positive opinion for the approval of nintedanib in IPF in the European Union. (www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm418994.htm; http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003821/smops/Positive/human_smop_000760.jsp&mid=WC0b01ac058001d127 ). Regulations dictate that the Ofev® brand name – which also relates to the particular dosage of nintedanib for use in IPF – only be linked with this disease. In November Vargatef® received approval from the European Commission for the treatment of non-small cell lung cancer (NSCLC) (www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002569/smops/Positive/human_smop_000727.jsp&mid=WC0b01ac058001d127). The brand name Vargatef® is only associated with NSCLC. I have provided some suggested wording amendments to the entry for nintedanib to make this important distinction clear to readers. As noted, the recent FDA approval of nintedanib (Ofev®), and positive opinion from the CHMP, for the treatment IPF would suggest the need for further details on the disease and relevant clinical trials. I have provided suggested wording to provide a brief overview of these points following a similar format to the existing content. I would be grateful for any further guidance you may be able to offer to bring the nintedanib entry up-to-date and to clarify any perceived inaccuracies.
Nintedanib From Wikipedia, the free encyclopedia
Nintedanib (trade name, Vargatef® in NSCLC, Ofev® in IPF) is a small molecule tyrosine kinase inhibitor (TKI) developed by Boehringer Ingelheim for the treatment of lung cancer patients with advanced adenocarcinoma and patients with idiopathic pulmonary fibrosis (IPF). Nintedanib inhibits the receptors for vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and platelet derived growth factor (PDGF) which are involved in the formation and maintenance of new blood vessels (angiogenesis) and signalling pathways of fibrotic processes. Nintedanib is approved in the EU under the brand name Vargatef® for use in combination with docetaxel in adult patients with locally advanced, metastatic or locally recurrent NSCLC of adenocarcinoma tumour histology after first-line chemotherapy. It is also approved for the treatment of idiopathic pulmonary fibrosis (IPF) in the USA under the trade name Ofev®. Ofev® received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) on 20 November 2014.
Nintedanib is also under investigation in a number of other solid cancers including hepatic cell carcinoma, mesothelioma and colorectal cancer.
Contents 1. Nintedanib in oncology 1.1 Mechanism of action 1.2 Clinical studies 1.3 Adverse events
2. Nintedanib in IPF 2.1 Mechanism of action 2.2 Clinical studies 2.3 Adverse events
2. Nintedanib in IPF 2.1 Mechanism of action
Nintedanib targets growth factor receptors, which have been shown to be involved in the mechanisms by which pulmonary fibrosis occurs. Most importantly, nintedanib inhibits receptors for platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF).   By blocking these signaling pathways involved in fibrotic processes, it is believed that nintedanib reduces disease progression in IPF by slowing the decline of lung function.   
1.3 Clinical studies The clinical efficacy and safety of nintedanib in IPF has been established in 1,231 patients with IPF in one Phase II clinical trial (TOMORROW) and two replicate Phase III clinical trials, INPULSIS®-1 and -2. These were double blind, randomised and placebo-controlled trialscomparing treatment with nintedanib 150 mg twice daily to placebo for 52 weeks. The INPULSIS® trials were identical in design and patients were randomised with a 3:2 ratio to nintedanib and placebo, the TOMORROW trial was similar in design but also included other treatment arms (dose finding study) in addition to treatment with 150 mg twice daily. Results from INPULSIS®-1 –and -2 show nintedanib slows disease progression by reducing the annual rate of decline in lung function by approximately 50%. The treatment effect on FVC was consistent across all 3 studies. The TOMORROW and INPULSIS®-2 trials also met both secondary endpoints – results demonstrate there was significantly less deterioration in quality of life (measured by the St. George’s Respiratory Questionnaire - SGRQ), and a reduced risk of a first acute exacerbation in patients taking nintedanib versus placebo. In the INPULSIS®-1 trial there was no difference between the treatment groups for these key secondary endpoints. . 2.2 Adverse events In INPULSIS®, the most common adverse events with nintedanib* were gastrointestinal, generally manageable and of mild to moderate intensity, rarely leading to treatment discontinuation. • Diarrhoea was the most common adverse event experienced in 62% of patients treated with nintedanib versus 18% in patients in the placebo groups • Less than 5% of patients discontinued treatment due to diarrhoea events • In those patients who experienced diarrhoea, 95% of events were mild to moderate in intensity The proportion of patients with serious adverse events was similar in both treatment groups.  More than 90% of eligible patients who participated in the INPULSIS® trials opted to continue with nintedanib treatment as part of an open-label extension trial.
11.^ "Boehringer Ingelheim - AGO-OVAR 12 / LUME-Ovar 1 Trial Information". 2011. 12.^ "Boehringer Ingelheim - LUME-Lung 2 Trial Information". 2011. 13.^ "Boehringer Ingelheim - LUME-Lung 1 Trial Information". 2011. 14.^ http://clinicaltrials.gov/ct2/results?term=++%09+BIBF+1120&phase=1 18. L. Richeldi, U. Costabel, M. Selman, D.S. Kim, D.M. Hansell, A.G. Nicholson, K.K. Brown, K.R. Flaherty, P.W. Noble, G. Raghu, M. Brun, A. Gupta, N. Juhel, M. Klüglich, R.M. du Bois (2011). “Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis”. N Engl J Med. 365:1079-1087; doi: 10.1056/NEJMoa1103690 19. M. Selman, T.E. King, A. Pardo (2001) “Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy”. Ann Intern Med 134(2):136-51; doi:10.7326/0003-4819-134-2-200101160-00015 20. L. Wollin, I. Maillet, V. Quesniaux, A. Holweg, B. Ryffel (2014) “Antifibrotic and Anti-inflammatory Activity of the Tyrosine Kinase Inhibitor Nintedanib in Experimental Models of Lung Fibrosis”. J Pharmacol Exp Ther 349(2):209–220; doi: 10.1124/jpet.113.208223 21. L. Richeldi, V. Cottin, K.R. Flaherty, M. Kolb, Y. Inoue, G. Raghu, H. Taniguchi, D.M. Hansell, A.G. Nicholson, F. Le Maulf, S. Stowasser, H.R. Collard (2014). “Design of the INPULSIS trials: Two phase 3 trials of nintedanib in patients with idiopathic pulmonary fibrosis”. Respir Med 108(7); 1023-1030; doi: 10.1016/j.rmed.2014.04.011. Epub 2014 Apr 29 22. L. Richeldi, R.M. du Bois, G. Raghu, A. Azuma, K.K. Brown, U. Costabel, V. Cottin, K.R. Flaherty, D.M. Hansell, Y. Inoue, D.S. Kim, M. Kolb, A.G. Nicholson, P.W. Noble, M. Selman, H. Taniguchi, H. Brun, F. Le Maulf, M. Girard, S. Stowasser, R. Schlenker-Herceg, B. Disse, H.R. Collard (2014). “Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis”. N Engl J Med 2014; 370:2071-2082;doi: 10.1056/NEJMoa1402584. 23. www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf Ovef® highlights of prescribing information. Boehringer Ingelheim. Revised 2014. 24. Boehringer Ingelheim. Data on file.
- @Lismmq:, thank you for being upfront and restrained about your COI, it is very helpful to do so. It is very productive when citing a source to provide some form of link to it. Most often the preferred way here is to simply furnish the PubMed identifier, such as PMID 21992121 for Richeldi et al. (2011). The Wikimedia software automatically links that to the PubMed record, making it much easier for others to find and read the reference. If you have the doi, it can be linked too as doi:10.1056/NEJMoa1103690. In that particular example, the paper is a primary source, which we avoid in favour of reviews (particularly systematic reviews) and other secondary sources as described at wp:MEDRS. We might, for instance, use PMID 25410822 instead of PMID 21992121. While an unfamiliar practice in the research community, it is necessary here in order to avoid a number of problems inherent to an open wiki. LeadSongDog come howl! 19:18, 22 October 2015 (UTC)