TGF-𝛃; Transforming Growth Factor-beta, CTGF inhibitor; Connective Tissue Growth Factor inhibitor, GPR40; G-protein-coupled receptor 40, GPR84; G-protein-coupled receptor 84, LPA1 antagonists; Lysophosphatidic Acid 1 Antagonists.
Symptomatic treatment of IPF
There aren’t many well-powered trials that have been done, hence managing an IPF exacerbation is not yet reported. Most respiratory doctors test pulsing of methylprednisolone (0.5 - 1 g a day over three days), while anecdotal reports have also mentioned the use of cyclophosphamide and rituximab[66]. Although often used, intravenous steroids have not been the subject of a randomized, placebo-controlled trial. The responsiveness to corticosteroids based on accumulating dose in IPF acute phases was examined in a retrospective trial. Higher doses of steroids were favorable in ILDs except in IPF, according to the authors [67]. However, in a different investigation, steroid treatment in the acute phase of IPF was linked to greater death rate[68]. One more retrospective study demonstrated that early reduction of steroids after pulses provided superior results [69]. Corticosteroid therapy had a negative influence on IPF patients, especially on diabetes and osteoporosis [70], as well as in randomized, double-blind, placebo-controlled trials that have clarified that adding prednisone to azathioprine and N-acetylcysteine (NAC) increases mortality rate [71], so corticosteroids aren’t recommended to patients with IPF, as it is known that the corticosteroids have anti-inflammatory effect and recent studies have shown IPF’s  secondary role of inflammation in addition to the primary role of fibrosis in the pathogenesis of IPF [71], so we recommended in using antifibrotic agents instead of anti-inflammatory agents in IPF. Regardless of the paucity of high-quality proofs, the most recent updates of IPF management guidelines continue to recommend using steroids in the treatment of acute phases[72]. Prospective randomized trials are therefore required. Other immunosuppressive medications are frequently used in some nations [71].
The Role of Sotatercept in the Treatment of Pulmonary Hypertension in IPF
There is an urgent need for better treatments of pulmonary hypertension (PH) in the context of IPF since patients with advanced ILDs who also have coexisting pulmonary vascular disease have worse outcomes than they would have with either diagnosis alone [72].
A newly developing fusion-protein, named sotatercept, attempts to balance pro- and anti-proliferative (BMPR-II- and ActRIIA-mediated) signals by binding to and sequestering a subset of TGF superfamily ligands (figure 2). Sotatercept has been demonstrated to stop right ventricular remodeling and pulmonary arterial wall remodeling in PH preclinical models [73]. Sotatercept largely reduced vascular resistance in the lungs in patients with PH on background therapy in a phase 2 trial (NCT03496207), and for now, sotatercept is the subject of operating clinical studies (NCT03738150, NCT04576988, NCT04811092, NCT04896008).