Many patients with idiopathic pulmonary fibrosis (IPF) who are switching from Esbriet (pirfenidone) to Ofev (nintedanib) discontinue treatment, especially if they are underweight or have anorexia while being treated with Esbriet, a Japanese study says.
The findings, “Negative impact of anorexia and weight loss during prior pirfenidone administration on subsequent nintedanib treatment in patients with idiopathic pulmonary fibrosis,” were published in the journal BMC Pulmonary Medicine.
Current guidelines in clinical practice recommend the use of Ofev (marketed by Boehringer Ingelheim) or Esbriet (marketed by Genentech), two approved anti-fibrotic therapies, to manage the symptoms of IPF and slow disease progression. These recommendations were created based on promising findings from multiple clinical trials assessing the safety and effectiveness of both therapies in IPF patients.
According to the team, results from INPULSIS-1 (NCT01335464) and INPULSIS-2 (NCT01335477) clinical trials showed that Ofev reduced the risk of acute disease exacerbations, and slowed disease progression compared to a placebo; while a pooled analysis from the CAPACITY I (NCT00287729), CAPACITY II (NCT00287716), and ASCEND (NCT01366209) trials showed that Esbriet reduced patients’ mortality.
“However, an optimal treatment sequence has not yet been established,” the researchers wrote.
The team set out to examine the safety and effectiveness profile of Ofev in IPF patients who had been treated previously with Esbriet.
The retrospective study analyzed 30 IPF patients, with a median age of 72 years, who discontinued treatment with Esbriet due to adverse events (side effects), or due to a severe decline in lung function (measured by forced vital capacity, FVC), and switched to Ofev (150 mg, twice-a-day) from September 2015 to August 2017.
Patients’ characteristics, treatment status, and adverse events were recorded for all participants in the switch-group, and compared to data from a subset of 64 IPF patients who had started treatment with Ofev during the same time period, but who had never been treated with Esbriet (the “naïve” group).
Results showed the most common adverse events associated with Ofev treatment in patients from the switch-group were abnormally high levels (63.3%) of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) — liver enzymes that, when elevated, may indicate liver inflammation or damage — followed by anorexia (46.7%), and diarrhea (46.7%).
Conversely, the most common adverse events associated with Esbriet treatment in patients from the switch-group were anorexia (63.3%) and excessive weight loss (56.7%).
Ofev treatment successfully prevented respiratory decline in 70% of the patients who had been treated previously with Esbriet.
However, 16 patients (53.3%) had to stop treatment with Ofev within the first six months of therapy (early termination). Data analysis found a strong correlation between low body mass index (BMI) and early Ofev termination in patients from the switch-group.
Data comparison also revealed that a higher percentage of patients from the switch-group stopped treatment with Ofev within the first six months compared to those from the Esbriet-naïve group (53.3% vs 32.8%).
In addition, those who had been treated previously with Esbriet (before starting treatment with Ofev) had significantly lower body weight (54.9 kg, or 121 lbs) vs 63.2 kg, 139 lbs.), BMI (21.0 kg/m2 vs 23.9 kg/m2), and %FVC (52.9% vs 67.7%), compared to those who had never been treated with Esbriet.
Although anorexia associated with Ofev treatment was more frequent among patients from the switch-group, compared to those from the naïve group, no significant differences in the prevalence of other adverse events were found between the two patient groups.
“Anorexia and weight loss during prior pirfenidone [Esbriet] treatment may increase the rate of early termination of subsequent nintedanib [Ofev] treatment. Thus, careful monitoring of body weight and the maintenance of nutritional status is mandatory in patients receiving anti-fibrotic therapies,” the researchers wrote.
“Further investigation is required to establish an optimal treatment strategy,” the team concluded.