How do you treat a patient who doesn’t quite fit the criteria for any ILD diagnostic group? With difficulty.
Professor Toby Maher, head of the Fibrosis Research Group at the National Heart and Lung Institute at London’s Imperial College, told the ERS Congress that as many as 10-15% of ILD patients were unclassifiable and there were currently no approved drugs for this group of patients.
A fantastic ALERT session at #ERSCongress2019 with great audience engagement. We now have high quality trial data to guide treatment of progressive fibrosis. A real breakthrough for preserving lung health for patients and preventing deaths from respiratory failure. pic.twitter.com/rER4LN8s0c
— Toby Maher (@TobyMMaher) September 30, 2019
However a phase 2 international trial conducted at 70 sites, including in Australia, has provided some evidence that patients with progressive fibrosing unclassifiable ILD may benefit from pirfenidone.
The study, concurrently published in The Lancet Respiratory Medicine, randomised 253 patients with a mean age of 70 years to either pirfenidone or placebo for 24 weeks.
Patients had a predicted forced vital capacity (FVC) of ≥ 45%, a diffusing capacity for carbon monoxide (DLco) of ≥30%, and more than 10% fibrosis on high-resolution CT.
A planned primary end point using daily home spirometry measurements was unable to be assessed due to technical and analytical difficulties.
However on the basis of hospital-based spirometry, the decline in FVC from baseline was lower in treated patients than controls.
Secondary end points were mixed with 6MWD favouring pirfenidone treatment but DLco showing no significant difference between the patient groups.
There were no differences in progression-free survival between the pirfenidone and placebo groups and no difference in patient reported outcomes.
The safety outcomes in the study were consistent with the established safety profile of pirfenidone in patients with IPF.
Nintedinib in non-IPF
Speaking in the same session highlighting selected abstracts leading to an evolution in ILD, Professor Kevin Flaherty presented the results the INBUILD trial of nintedinib in patients with a broad range of fibrosing ILD.
The phase 3 study randomised 663 patients, with a mean age of 65 years from 153 sites in 15 countries, to 52 weeks of treatment or placebo.
Because the efficacy of nintedinib has already been shown in IPF, the cohort was deliberately enriched with patients with other progressive fibrosing phenotypes.
The most frequent diagnoses were chronic hypersensitivity pneumonitis and autoimmune ILD.
Professor Flaherty, director of the Michigan Medicine Interstitial Lung Disease program, said the study found the annual rate of decline in FVC was significantly lower in treated patients – both in the overall population (57% relative reduction) and in a sub-group of patients with a UIP-like fibrotic pattern (61% relative reduction).
YES!!! Amazing results in @NEJM from the INBUILD trial!
Nintedanib reduces lung function decline across progressive fibrosing interstitial lung diseases!
Major step to antifibrotic use in #pulmonaryfibrosis beyond #IPF@PFFORG @UChicagoPCCM #ERSCongress https://t.co/IbT5Fe5X56 pic.twitter.com/SG495lhuQ6
— Deji Adegunsoye (@drdayjee) September 30, 2019
Despite a numerically reduced risk of ILD exacerbation or death with nintedinib, there was no difference between groups on time to first ILD exacerbation or death and very little change in quality of life measures.
Consistent with the evidence in IPF patients, the most common adverse effect of treatment was diarrhoea.
The study and an accompanying editorial were concurrently published in NEJM.