When to start and when to stop antifibrotic therapies

Abstract

Idiopathic pulmonary fibrosis (IPF) is characterised by progressive changes of the lung architecture causing cough and dyspnoea and ultimately leading to lung failure and death. Today, for the first time, two drugs that may reduce the inexorable progression of the disease are available, suggesting that treatment with specific drugs for IPF should be started as soon as diagnosis is made. This applies to any disease and particularly to IPF, which is marked by a 5-year survival comparable or even worse than many cancers. However, despite common sense and even worse, in spite of scientific data coming from clinical trials, post hoc analysis, long-term safety studies and real-life experiences, the question of when to start and when to stop treatment with antifibrotics is still debated. In IPF, particularly when the disease is diagnosed at an early stage, "wait and watch" behaviour is not rare to observe. This is largely due to the lack of awareness of both patients and clinicians regarding the progression of the disease and its prognosis. Another important issue is when treatment should be stopped. In general, there are two main reasons to stop a therapy: unbearable side-effects and/or lack of efficacy. According to current (although preliminary) evidence, antifibrotic drugs should not be discontinued except for safety issues.

Possible value of antifibrotic drugs in patients with progressive fibrosing non-IPF interstitial lung diseases

“…Interestingly, as some patients may also be classified as IPAF, antifibrotics could represent a valid therapeutic option also for this specific group [22][23][24]. Furthermore, as documented in IPF patients, both pirfenidone and nintedanib were generally well tolerated, with the need of a dose reduction only in a few cases [12][13][14][15][16][17]. The one-year survival of PF-ILDs looks incredibly similar to IPF making the two diseases very similar (Fig.…”

“…In recent years, undeniable progress has been achieved in understanding the pathogenic mechanisms of IPF. This has progressively led to the advent of pirfenidone and nintedanib, the first two drugs able to reduce lung function decline [12][13][14][15][16][17]. Comparable to IPF, some PF-ILDs are triggered by repetitive lung parenchymal injuries and demonstrate TGFβ-mediated fibroblast activation and myofibroblast accumulation that may lead to a progressive phenotype [18][19][20][21].…”

“…Antifibrotic therapy, either pirfenidone or nintedanib, was introduced after a proven progression of the disease and lack of response to corticosteroids and/or immunomodulators, after approval of the respective health insurance company and according to German laws for off-label use and after consent by the patient. As in IPF patients, pirfenidone was given as continuous oral treatment at a dose of 2403 mg·day − 1 (3 capsules three times·day − 1 ) and nintedanib 300 mg·day − 1 (1 capsule twice·day − 1 ) [12][13][14][15][16][17]. Patients under antifibrotic therapy were reevaluated every 6-12 weeks after initiation according to the standard of care in our department.…”

“…However, response to these therapies is highly variable, sometimes without meaningful improvement [11]. In recent years two antifibrotic drugs, pirfenidone and nintedanib, have been developed and approved for the treatment of IPF [12][13][14][15][16][17]. Their impact on the course of other fibrosing ILDs is unknown.…”

Rare pulmonary diseases: a common fight

“…MILANI et al [5] tackle the subject of a little known but clinically relevant condition, lung involvement in amyloidosis, with regards to the possible clinical consequences for the affected patients. TORRISI et al [6] take on the difficult task of exploring the indications and contraindications of antifibrotic therapies in IPF, a topical issue of great relevance, while CAMINATI et al [7] discuss how to deal with the most advanced phases of this disease. Finally, RAGHU [8], a worldwide expert on IPF and other interstitial lung diseases, discusses the future landscapes for the treatment of IPF and analyses the most important and promising trials in the pharmacological therapy of this disease.…”