Two double-blinded, placebo-controlled, prospective phase 2 trials have been conducted in patients with progressive forms of fibrotic interstitial lung disease, on pirfenidone. The primary endpoint was an absolute change in % predicted FVC from baseline, until week 48 or 24, respectively. The RELIEF study (n=127) was terminated due to low recruitment. In the second study (n=253), the planned statistical model could not be applied to the primary endpoint analysis due to high intra-individual variability in home spirometry. In spite of this, both studies concluded that pirfenidone was generally well-tolerated, that its addition to a conventional therapy reduced disease progression (RELIEF), and that key secondary endpoint results suggest the benefit of pirfenidone in this population.
Two studies have been conducted in patients with non-IPF chronic fibrosing ILDs with progressive phenotype, treated with Nintedanib. In the INBUILD study (n=663) patients received nintedanib or placebo. The primary endpoint was the annual rate of decline in FVC (mL/yr) assessed over 52 weeks. The study provided insights into the natural history and role of nintedanib in treating patients with various progressive fibrosing ILDs. The SENSCIS study assessed the cumulative distribution of subjects by a change in FVC% predicted at week 52. Absolute declines in FVC >5% predicted were significantly higher in the placebo group and higher but not significant in FVC >10%.
A phase 3 randomised, placebo-controlled, double-blind study in systemic sclerosis (SSc) with subcutaneous tocilizumab (TCZ). The primary endpoint was the difference in modified Rodnan skin score (mRSS) change from baseline (∆BL) between TCZ and placebo (n=210). The primary mRSS endpoint was not met. A clinically relevant difference in FVC was seen for TCZ, with preservation of lung function.
In a proof-of-concept multicentre, double-blind, randomised controlled trial, the safety and efficacy of B-cell depletion with rituximab was studied in patients with systemic sclerosis-associated pulmonary arterial hypertension. The primary endpoint was a change in the 6-minute walk distance (6MWD) at 24 weeks. Rituximab was well tolerated with a non-significant trend towards improvement in the primary endpoint.
The RACE study compared the balloon pulmonary angioplasty with riociguat, in the treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH). This randomised controlled study (n=105) will provide important information on the effect of riociguat compared to that of balloon pulmonary angioplasty (BPA) as first-line therapy in treatment-naïve patients with inoperable CTEPH.
A multicentre study (COLDICE) comparing transbronchial lung cryobiopsy (TBLC) and surgical lung biopsy (SLB) (n=65). There was a strong comparison between TBLC and SLB supporting the clinical utility of TBLC in ILD diagnostic algorithms.