[Antifibrotic therapy - new approvals for non-IPF interstitial lung diseases].

Interstitial lung diseases (ILD) encompass more than 200 disorders of known and unknow etiology. Until recently, the antifibrotic drugs nintedanib and pirfenidone had only been approved for the treatment of idiopathic pulmonary fibrosis (IPF), but not for other ILD. In the randomized, double-blind, placebo-controlled SENSCIS trial, the efficacy and safety of nintedanib was investigated in patients with ILD associated with systemic sclerosis (SSc-ILD). Nintedanib significantly reduced the annual rate of decline in FVC compared with placebo leading to the approval of nintedanib for the treatment of SSc-ILD. Very recently, nintedanib has got approval for chronic fibrosing ILD with a progressive phenotype based on the data from the INBUILD trial. In this randomized, double-blind, placebo-controlled, phase III trial, patients with chronic hypersensitivity pneumonitis, idiopathic non-specific interstitial pneumonia, unclassifiable ILD, autoimmune ILD, sarcoidosis, and others were included, and nintedanib slowed the annual decline of pulmonary function by 57 % in these patients. Promising data are also available for pirfenidone in the treatment of patients with progressive, non-IPF lung fibrosis and unclassifiable progressive fibrosing ILD. In this article, we summarize the new approvals of antifibrotic drugs in non-IPF ILD, the results from the underlying clinical trials and the clinical implications.

Markart P ，Drakopanagiotakis F ，Wygrecka M 《-》

Nintedanib in patients with progressive fibrosing interstitial lung diseases-subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial.

The INBUILD trial investigated the efficacy and safety of nintedanib versus placebo in patients with progressive fibrosing interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF). We aimed to establish the effects of nintedanib in subgroups based on ILD diagnosis. The INBUILD trial was a randomised, double-blind, placebo-controlled, parallel group trial done at 153 sites in 15 countries. Participants had an investigator-diagnosed fibrosing ILD other than IPF, with chest imaging features of fibrosis of more than 10% extent on high resolution CT (HRCT), forced vital capacity (FVC) of 45% or more predicted, and diffusing capacity of the lung for carbon monoxide (DLco) of at least 30% and less than 80% predicted. Participants fulfilled protocol-defined criteria for ILD progression in the 24 months before screening, despite management considered appropriate in clinical practice for the individual ILD. Participants were randomly assigned 1:1 by means of a pseudo-random number generator to receive nintedanib 150 mg twice daily or placebo for at least 52 weeks. Participants, investigators, and other personnel involved in the trial and analysis were masked to treatment assignment until after database lock. In this subgroup analysis, we assessed the rate of decline in FVC (mL/year) over 52 weeks in patients who received at least one dose of nintedanib or placebo in five prespecified subgroups based on the ILD diagnoses documented by the investigators: hypersensitivity pneumonitis, autoimmune ILDs, idiopathic non-specific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, and other ILDs. The trial has been completed and is registered with ClinicalTrials.gov, number NCT02999178. Participants were recruited between Feb 23, 2017, and April 27, 2018. Of 663 participants who received at least one dose of nintedanib or placebo, 173 (26%) had chronic hypersensitivity pneumonitis, 170 (26%) an autoimmune ILD, 125 (19%) idiopathic non-specific interstitial pneumonia, 114 (17%) unclassifiable idiopathic interstitial pneumonia, and 81 (12%) other ILDs. The effect of nintedanib versus placebo on reducing the rate of FVC decline (mL/year) was consistent across the five subgroups by ILD diagnosis in the overall population (hypersensitivity pneumonitis 73·1 [95% CI -8·6 to 154·8]; autoimmune ILDs 104·0 [21·1 to 186·9]; idiopathic non-specific interstitial pneumonia 141·6 [46·0 to 237·2]; unclassifiable idiopathic interstitial pneumonia 68·3 [-31·4 to 168·1]; and other ILDs 197·1 [77·6 to 316·7]; p=0·41 for treatment by subgroup by time interaction). Adverse events reported in the subgroups were consistent with those reported in the overall population. The INBUILD trial was not designed or powered to provide evidence for a benefit of nintedanib in specific diagnostic subgroups. However, its results suggest that nintedanib reduces the rate of ILD progression, as measured by FVC decline, in patients who have a chronic fibrosing ILD and progressive phenotype, irrespective of the underlying ILD diagnosis. Boehringer Ingelheim.

Wells AU ，Flaherty KR ，Brown KK ，Inoue Y ，Devaraj A ，Richeldi L ，Moua T ，Crestani B ，Wuyts WA ，Stowasser S ，Quaresma M ，Goeldner RG ，Schlenker-Herceg R ，Kolb M ，INBUILD trial investigators ... -  《-》

Nintedanib: A Review in Fibrotic Interstitial Lung Diseases.

Lamb YN 《-》

Possible value of antifibrotic drugs in patients with progressive fibrosing non-IPF interstitial lung diseases.

Torrisi SE ，Kahn N ，Wälscher J ，Sarmand N ，Polke M ，Lars K ，Eichinger M ，Heussel CP ，Palmucci S ，Sambataro FM ，Sambataro G ，Sambataro D ，Vancheri C ，Kreuter M ... -  《BMC Pulmonary Medicine》

Progressive fibrosing interstitial lung diseases: A new concept and indication of nintedanib.

Makino S 《-》