TSANZ has updated its position on the management of idiopathic pulmonary fibrosis (IPF) and, for the first time, included the treatment of non-IPF progressive pulmonary fibrosis (PPF).

The position statement, published in Respirology [link here], recognises the important role of anti-fibrotic therapy in both conditions and non-pharmacological therapies, including oxygen and pulmonary rehabilitation.

Regarding anti-fibrotic therapy for IPF, the position paper said both nintedanib and pirfenidone have been shown to be effective in slowing the rate of decline in lung function.

It also said that several national IPF registries, including Australia’s, reported a survival benefit with anti-fibrotic therapies compared to untreated cohorts.

“Given that both anti-fibrotics demonstrate efficacy in early/mild disease, all patients should be considered for anti-fibrotic therapy at IPF diagnosis,” it said.

However, there was no evidence of a superior benefit from the combination of pirfenidone and nintedanib; therefore, combination anti-fibrotic therapy is not currently recommended outside clinical trials.

The position statement provides tips for the management of adverse events with anti-fibrotic therapy, noting that disease progression and treatment toxicity are the most common reasons for discontinuing treatment.

It said that PBS funding allows for switching between the two drugs for toxicity, but switching may also lead to time off therapy and potentially expose patients to new intolerances.

“There is no evidence that switching to an alternative anti-fibrotic favourably impacts disease progression,” it said.

The position statement noted that nintedanib should be considered in patients with PPF “with evidence for treatment benefit across a range of ILD subgroups. ”

“Despite demonstrating progressive disease behaviour, certain ILDs may still be best treated with immunosuppression such as CTD-ILD, or antigen avoidance in fibrotic hypersensitivity pneumonitis, potentially alongside the addition of nintedanib,…” it said.

The position paper said all patients with IPF and PPF should be presented with the option to participate in clinical trials of novel agents such as fibulin-1c inhibitors, checkpoint inhibitors, inhibitors of profibrotic macrophages, and modulators of cellular senescence.

Unmet areas of clinical need

The position paper said there were no proven therapies for acute exacerbations of IPF.

Non-invasive ventilation and high-flow oxygen were often initiated, as were high-dose corticosteroids, but without any data to support these approaches.

Mechanical ventilation was discouraged except in limited situations such as bridge to transplant.

“Management consists of supportive care with a focus on palliation of symptoms, supplemental oxygen to correct hypoxaemia and consideration of broad-spectrum antibiotics and antiviral agents to cover possible infection,” it said.

Regarding timely access to palliative care, the position paper said the pervasive misconception that palliative care is solely for end-of-life care continued to be a barrier to best practice.

It referenced 2023 ERS guidelines [link here] which call for palliative care initiation “when there are unmet physical, psychological, social or spiritual/existential unmet needs.”

“This is particularly pertinent to IPF and PPF, where patients are faced with a significantly shortened survival, inevitable disease progression in an unpredictable fashion, and worsening symptoms despite anti-fibrotic therapy.”

Genetic risk

The position paper said telomere shortening, secondary to mutations in telomere-related genes, was the most common genetic association in families with pulmonary fibrosis.

“Additionally, telomere shortening is identified in up to 25% of sporadic IPF cases and associates with worse prognosis.”

As well as the more aggressive disease trajectory, patients with telomere shortening appeared to be particularly susceptible to the harmful effects of immunosuppression.

“Such patients may experience rapid deterioration, and early referral to a lung transplant unit should be considered,” the position paper said.

The position statement’s authors, led by Dr John Mackintosh from The Prince Charles Hospital in Brisbane, said the future of IPF and PPF management was likely to be increasingly complex and individualised.

“Despite current limitations in the management of IPF and PPF, through a global collaborative effort and clinical trial endeavours, the future for this patient cohort looks promising,” they concluded.