Introduction
IPF is a deadly interstitial lung disease (ILD) that progresses over time and is identified by radiologic and histopathologic signs of typical interstitial pneumonia. IPF has a terrible prognosis, with an average life expectancy of only three to four years in patients who are not taking antifibrotic medication. Lung function falls along with severe dyspnea, functional ability, and a decline in quality of life as the disease advances. At any point during the progression of the disease, individuals with idiopathic pulmonary fibrosis (IPF) may experience sudden worsening of respiratory function characterized by the emergence of new bilateral ground-glass opacification or consolidation on computed tomography (CT). These acute exacerbations are often accompanied by alarmingly high mortality rates. The majority of IPF patients succumb to respiratory failure or an abrupt deterioration of their condition.
Despite this, a large number of IPF patients do not receive treatment. This frequently occurs because the doctor believes the disease is stable and does not thus require treatment or because the doctor is worried about possible adverse effects of antifibrotic medications. It is still necessary to inform pulmonologists that IPF is a deadly, progressive condition and that quick diagnosis and treatment are essential to maintaining patients' lung function and enhancing outcomes. The majority of patients can tolerate antifibrotic medication, and studies have shown that dose optimization can reduce adverse effects without sacrificing efficacy. Individuals diagnosed with IPF derive advantages from a comprehensive approach to their healthcare, encompassing symptom control, personalized supportive care, and the administration of anti-fibrotic medications.
What Is the Clinical Course of Antifibrotic Therapy?
Although the rates of illness development vary from person to person, all IPF patients eventually experience a reduction in lung function. According to data from a single-center study using daily hand-held spirometry, only eight percent of patients with IPF exhibit stable forced vital capacity (FVC) over the course of a year. The majority of IPF patients exhibit a reduction in FVC. Clinical studies involving IPF patients with varying degrees of lung function impairment have indicated that those receiving a placebo experience an average annual decline in forced vital capacity (FVC) of approximately 150 to 200 mL. However, it is important to note that even if the baseline FVC is relatively preserved, it does not guarantee future stability in lung function.
What Are the Benefits of Antifibrotic Therapies?
Two medications, Nintedanib and Pirfenidone, have IPF therapy approval in the US, Europe, and many other nations. According to in vitro research, Nintedanib prevents the recruitment and proliferation of fibroblasts as well as the deposition of extracellular matrix by blocking the signaling mediated by tyrosine kinases. According to data from fibrosis-related animal models, Nintedanib may also function to restore the lungs' deformed microvascular architecture. Pirfenidone's mechanism of action is less clear because it has not been identified as a target. Still, non-clinical research indicates that it inhibits pro-fibrotic actions in fibroblasts and fibrocytes.
According to clinical trials, Nintedanib and Pirfenidone exhibit consistent effects across the range of baseline FVC investigated (FVC > 50 % anticipated), across subgroups by age, race, gender, and concurrent drug use, and they also slow the loss in lung function in patients with IPF. In participants with mild or moderate FVC impairment at baseline, Phase III demonstrated that Nintedanib and Pirfenidone significantly slowed the rate of FVC decline over the course of a year of treatment. Data from the open-label extension of the studies also support the idea that Nintedanib has a long-lasting impact on slowing the loss of lung function over the course of more than four years of treatment. Current trial data suggests that Nintedanib affects FVC decrease similarly in persons with significant baseline gas exchange impairment as well as in subjects with less advanced illness. A growing body of research indicates that Nintedanib and Pirfenidone reduce the risk of acute deterioration in lung function and increase life expectancy by slowing the progression of IPF, even though individual clinical trials have not been powered to demonstrate significant effects on acute exacerbations and mortality.
Large clinical trials have not demonstrated that Nintedanib or Pirfenidone significantly improves dyspnea, cough, or quality of life issues related to IPF. It is unclear if this is due to the fact that antifibrotic medications have no appreciable impact on symptoms or that these trials, which lasted only a year, involved patients with mild baseline lung function impairment. Clinical observational data imply that antifibrotic therapy may help to some extent with symptom reduction. Greater deterioration in FVC is thought to be linked to greater deterioration in health-related quality of life as measured by patient-reported outcomes, according to data from clinical studies and patient registries. A decrease in the ability of patients to exercise is also linked to worsening of FVC. This shows that antifibrotic medicines may be able to slow down the rate at which FVC drops over time, hence slowing the rate at which symptoms, functional ability, and quality of life deteriorate in patients.
How to Manage Side-Effects of Antifibrotic Therapies?
Gastrointestinal side effects are linked to antifibrotic therapy. In clinical trials, diarrhea was reported by 62.4 % of patients receiving Nintedanib compared to 18.4 % of subjects receiving a placebo. However, only 4.4 % of the group permanently discontinued therapy as a result. Pirfenidone is advised to be taken after or after a meal to reduce gastrointestinal troubles because these side effects are more frequently linked to it than diarrhea. Patients should be encouraged to wear high-factor sunscreen and limit their exposure to the sun because Pirfenidone is also linked to rash and photosensitivity. Elevations in liver enzymes have been linked to both Nintedanib and Pirfenidone.
Limited information is available regarding the tolerability of combining Nintedanib and Pirfenidone in the treatment of fibrotic conditions. However, it appears that the adverse event profile of the combination therapy aligns with that of the individual medications. To ensure the uninterrupted administration of antifibrotic treatment, it is crucial to effectively manage any potential side effects that may arise. To control side effects, it is advised to adjust dosage through treatment interruption and dose reduction, as well as to treat symptoms of gastrointestinal adverse events with Loperamide and appropriate hydration. Interestingly, dose modifications made during clinical trials to address adverse effects did not diminish the advantages of the medication in slowing the loss of lung function. Most patients can tolerate antifibrotic medication, and the number of patients who stop using it because of side effects goes down over time.
Conclusion
Nintedanib and Pirfenidone are two antifibrotic treatments that have been authorized for the treatment of IPF. These medications lessen the likelihood of acute respiratory deteriorations, which are linked to extremely high morbidity and death, and they decrease the loss of lung function.
