INTRODUCTION: Novel compounds targeting various aspects of fibrogenesis have 
been developed consequent to the increasing knowledge of the pathogenetic 
mechanisms of the interstitial lung diseases (ILDs). The authors review the 
evolution of treatment approaches in the ILDs, informed by recent 
placebo-controlled trials, and discuss current clinical trials in which emerging 
pathogenetic mechanisms are targeted as novel therapeutic agents.
AREAS COVERED: In idiopathic pulmonary fibrosis (IPF), recent randomised, 
placebo-controlled trials have tested the efficacy of new therapies, and 
although primary end points have not been met in most, treatment effects have 
been observed. The demonstration of harmful effects from widely used IPF 
therapies has been equally important. Pirfenidone and nintedanib are emerging 
agents that exert pleiotropic effects, reflective of the multiple mechanistic 
pathways of IPF. Treatment may necessitate a similarly multifaceted approach 
using combination regimens of antifibrotic and antioxidant agents in order to be 
effective. In other ILDs, including systemic sclerosis, other connective tissue 
diseases and pulmonary sarcoidosis, the inflammatory/fibrotic model remains 
appropriate. Studies in systemic sclerosis have provided 'proof of concept' data 
for immunosuppressive therapy in the prevention of disease progression but there 
is a continuing need for controlled clinical trials in the more prevalent ILDs.
EXPERT OPINION: In IPF, significant treatment effects have been reported with 
pirfenidone, nintedanib and N-acetylcysteine. Combinations of these pleiotropic 
agents, along with future monotherapies, in 'oncological regimens' may hold the 
key to more effective IPF treatment. In disorders other than IPF, there is an 
ongoing need for the controlled evaluation of traditional anti-inflammatory and 
immunosuppressive therapies. 'Cohort enrichment' (the selective recruitment of 
patients most likely to progress) holds the key to the identification of 
worthwhile treatment benefits.