PF-ILD

Pharmacologic treatment³

Patients with PF-ILD have generally been treated with either antifibrotic therapy for idiopathic pulmonary fibrosis (IPF) or immunosuppressive therapy for non-IPF ILD. The distinction between IPF and non-IPF ILD is particularly important because immunosuppressive therapy is harmful for patients with IPF, but potentially beneficial for patients with non-IPF ILD.³

Nintedanib^2,4

Nintedanib is an intracellular inhibitor of tyrosine kinases which has shown antifibrotic, anti- inflammatory and vascular remodeling effects in several non-clinical models of fibrosis.² Nintedanib competitively binds to the adenosine triphosphate binding pocket of these receptors inhibiting the activation of the platelet-derived growth factor receptor, vascular endothelial growth factor receptor and fibroblast growth factor receptors signaling cascades, which are critically involved in the proliferation, migration and differentiation of lung fibroblasts/myofibroblasts, the hallmark cells in the pathology of IPF.⁴ It has demonstrated efficacy in IPF and could be effective to slow down progressive fibrosis in PF-ILDs irrespective of the trigger for the injury.² In addition, nintedanib has also been shown to inhibit nonreceptor tyrosine kinases of the Src family including Src, Lck and Lyn. Lck inhibition may reduce downstream signaling of human T-cell receptors to reduce the release of immune-stimulating and profibrotic mediators such as interferon-γ and several other interleukins. This inhibition may be particularly important in the treatment of connective tissue disease-associated ILDs (CTD-ILDs).⁴

Approval of nintedanib^{1, 4, 5}

Nintedanib 150 mg twice daily consistently slowed disease progression and was also associated with a reduction in the risk of acute IPF exacerbations, maintenance of health-related QoL and reduction in the risk of all-cause mortality.⁴ Diarrhea was the most commonly reported adverse effect in nintedanib treatment.^{4, 5} Based on the outcomes of these clinical studies, the recommended daily dose of nintedanib for patients with IPF is 150 mg twice daily, administered every 12 h, with the option to reduce the dose to 100 mg twice daily to manage side-effects.⁴ On the other hand, the INBUILD trial recently demonstrated the efficacy of nintedanib to slow down disease progression in PF-ILD.¹ Nintedanib has since been approved in the US, and in 45 other countries, including Japan, Canada and the European Union for treatment of chronic fibrosing ILDs with a progressive phenotype.¹ In Taiwan, Ofev® Soft Capsules 100 mg and Ofev® Soft Capsules 150 mg were approved for the treatments of IPF, systemic sclerosis interstitial lung disease (Ssc-ILD) and PF-ILD.⁵

Pirfenidone^{1, 2, 4}

Pirfenidone is a small molecule with antifibrotic, anti- inflammatory and anti-oxidative effects, suppresses the production of transforming growth factor-β, the proliferation and differentiation of myofibroblasts, and the deposition of collagen, and has favorable effects in non-clinical models of lung fibrosis.² However, how pirfenidone exerts its antifibrotic and anti-inflammatory properties has not yet been fully established.⁴ Pirfenidone was investigated in patients with progressive unclassifiable ILD.¹ It also has demonstrated efficacy in IPF and could be effective to slow down progressive fibrosis in PF-ILDs irrespective of the trigger for the injury.²
Pirfenidone was generally well-tolerated, and no significant treatment group differences were reported in either study in terms of acute exacerbations (worsening IPF).⁴ Gastrointestinal and skin-related events were more common in the pirfenidone group than the placebo group.⁴