TGF-đ; 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 arenât 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 arenât recommended
to patients with IPF, as it is known that the corticosteroids have
anti-inflammatory effect and recent studies have shown IPFâs  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).