Nintedanib and pirfenidone use has grown substantially since their 2017 PBS listing, a sign that more idiopathic pulmonary fibrosis (IPF) patients are getting diagnosed and accessing treatment, an Australian respiratory specialist says.
A study of PBS Item Reports for 2017 to 2020 found nintedanib and pirfenidone prescriptions grew 72% in their first two years on the PBS, from 8,999 per year to 15,512 per year and another 26% to 19,499 per year in year three.
In total, 44,010 prescriptions were issued for the drugs over the study period, worth $131,377,951, Respiratory Staff Specialist Associate Professor Tamera Corte and her colleagues wrote in Australian Health Review.
Associate Professor Corte told the limbic the “impressive” figures were the result of sudden access to antifibrotic drugs and increasing IPF diagnoses.
“We didn’t have access to [any IPF treatments] before [nintedanib and pirfendione] and there was a whole bunch of people on nothing; so that’s why the figures look so impressive, because they’ve got all these untreated people suddenly treated”, she said.
Clinicians were also identifying the disease more often and earlier via high-resolution CT scans, she said, noting that IPF prevalence appeared to be increasing globally.
Her study showed nintedanib to be the (slightly) preferred drug, accounting for 54% of prescriptions overall, and the Australian Capital Territory, the biggest users, making up 24% of prescriptions when adjusting for population size.
The study provides “valuable insights” into Australian IPF antifibrotic prescription practices that could be “useful for economic evaluation and modelling future health expenditure”, she and her colleagues wrote.
PBS access and the multidisciplinary team
The IPF-slowing drugs were PBS listed for patients over 40 years of age, who were diagnosed by a multidisciplinary team and met certain clinical and treatment criteria.
While there may have been some concerns about rural Australians’ accessing multidisciplinary teams and the drugs earlier on, Associate Professor Corte said clinicians quickly mitigated the problem, with respiratory physicians, radiologists, histopathologists and rheumatologists conducting video calls with patients well before COVID.
“Essentially, we already had hybrid meetings [before COVID, where a patient may see a clinician face-to-face] with other physicians dialling in from different centres.”
“But when we went fully virtual with COVID, we were able to use what we had already set up and the networks were ready to go that extra step.”
“We’ve since got 15 to 20 different sites dialling in to our weekly meeting in New South Wales. We’ve got eight patients discussed each week; so, [it’s] really allowing that expertise to be available beyond the specialist centres and get patients on treatment quicker.”
As restrictions dwindle, Associate Professor Corte said expects to see more hybrid meetings again. The multidisciplinary meetings were important for ensuring patients get a correct diagnosis and treatment, particularly as IPF was “only one of about 200 types of pulmonary fibrosis” and early recognition could help extend patients’ life expectancy, she said.
Antifibrotic adherence, efficacy and side effects
Nintedanib and pirfenidone were “definitely not cures, but if you diagnose IPF really early, then you can help keep those patients as stable as possible, for as long as possible and make a real difference to those patients”, with the drugs able to slow disease progression by about 50% at 12 months, she said.
“The drugs they’re both associated with significant side effects, and they don’t completely stop the decline, but they’re in the first step in the right direction,” she added.
Initially, pirfenidone 267 mg capsule was the preferred medication formulation, but was surpassed by the nintedanib 150 mg capsule in most jurisdictions during 2018.
With no consensus guidelines on first-line treatments, drug preference may have been influenced by the order of availability on PBS, said researchers, noting that nintedanib was introduced a few months before pirfenidone. Pill burden may also have been a factor, with the initial formulations requiring patients to take two nintedanib capsules per day versus nine pirfenidone tablets.
The 2018 introduction of an 801 mg pirfenidone tablet did reduce pill burden from nine to three, though nintedanib won out despite this addition.
Side effects may also affect choice, the researchers said, with the drugs having different side effects despite comparative effectiveness and tolerability. Nearly two thirds (62%) of nintedanib may develop diarrhoea, while patients on pirfenidone were more likely to develop a photosensitive rash, which, with Australia’s high UV light index might be of particular concern.
Given these factors and others such as drug interactions and concomitant comorbidities, it may be worth exploring how prescribing practices and physician preferences affect treatment decisions in Australia, they suggested.
Meanwhile, a new systematic review and meta-analysis has provided evidence of the impact of nintedanib and pirfenidone on both death and acute exacerbation in IPF.
The drugs appear to have similar efficacy in slowing lung function decline and were more recently associated with a decreased risk of all cause mortality (relative risk [RR]: 0.55, 95% CI: 0.45–0.66) and acute exacerbation (RR: 0.63, 95% CI: 0.53–0.76) according to the meta-analysis of 26 randomised controlled trials and real-world studies, featuring 12,956 patients.
The study “clarifies our understanding of the role of antifibrotic therapy in IPF, providing real-world evidence on which to base discussions with patients”, and could help “improve physicians’ confidence” when treating the disease with nintedanib and pirfenidone, Austin Health Respiratory and Sleep Medicine Physician Dr Yet Khor wrote in an accompanying editorial.