Despite Benefits, Many IPF Patients Switching from Esbriet to Ofev Stop Treatment, Possibly Due to Low BMI

Apr 23, 2019

Many patients with idiopathic pulmonary fibrosis (IPF) who switch from taking Esbriet (pirfenidone) to taking Ofev (nintedanib) discontinue treatment soon after the switch, especially if they became underweight or had a loss of appetite while being treated with Esbriet, a Japanese study suggests.

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. Anorexia as used in this article means loss of appetite; it does not refer to the eating disorder anorexia nervosa, a mental health condition. 

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 slow disease progression in patients with IPF. These recommendations were created based on promising findings from multiple clinical trials assessing the safety and effectiveness of both therapies in IPF patients. Both medications have been shown to slow the decline in forced vital capacity (FVC), a measure of lung function, when compared with placebo.

There may be other benefits to the medications. According to the research team, results from the INPULSIS-1 (NCT01335464) and INPULSIS-2 (NCT01335477) clinical trials suggested that Ofev reduced the risk of acute disease exacerbations. A pooled analysis of data from the CAPACITY I (NCT00287729), CAPACITY II (NCT00287716), and ASCEND (NCT01366209) clinical trials suggested that Esbriet reduced patients’ risk of mortality.

“Because treatment options for IPF are limited, these two anti-fibrotic drugs should be maximally utilized. 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 enrolled 30 IPF patients with a median age of 72 years who had previously taken Esbriet and had discontinued treatment. The median length of time these patients had taken Esbriet was about 8 months. This group was called the “switch group”.

Of these 30 patients, 15 patients had discontinued treatment with Esbriet due to intolerable adverse events (side effects) and 15 patients discontinued due to a severe decline in lung function (measured by FVC). All of the patients had switched to Ofev (150 mg, twice-a-day) sometime between September 2015 and August 2017. The switch happened quickly for most patients. Of the 30 patients who switched, 23 patients (76.6%) had less than 1 month between stopping Esbriet and starting Ofev.

The study enrolled a second group of 64 IPF patients who also started treatment with Ofev between September 2015 and August 2017. These patients had never been treated with Esbriet (the “naïve” group). 

Patients’ characteristics, treatment status, and adverse events were recorded and compared between the switch group and the naïve group.

When the switch group had been on Esbriet, the most common adverse events were loss of appetite/anorexia (63.3%) and excessive weight loss (56.7%). 

After they switched to Ofev, treatment successfully prevented respiratory decline in 70% of the patients who had been treated previously with Esbriet.

However, during Ofev treatment, the most common adverse events 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 loss of appetite/anorexia (46.7%), and diarrhea (46.7%).

Sixteen of the 30 switch patients (53.3%) had to stop treatment with Ofev within the first six months of therapy (early termination) because of intolerable adverse events (side effects). In comparison, only 21 of the 64 naïve patients (32.8%) had to stop treatment with Ofev within the first six months. 

To understand the difference, the team compared adverse event data between the groups. Loss of appetite/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 types of adverse events were found between the two patient groups. 

The team also found a strong correlation between low body mass index (BMI) at the beginning of Ofev treatment and risk of early Ofev termination in the switch group.

Before starting treatment with Ofev, the switch group had significantly lower average body weight (54.9 kg, or 121 lbs) than the naïve group did (63.2 kg, or 139 lbs.), The average BMI in the switch group at the start of Ofev treatment was 21.0 kg/m2, versus 23.9 kg/m2 in the naïve group.

“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.

They added, “when clinicians consider switching from pirfenidone to nintedanib due to gastrointestinal adverse events, it would probably be better to have a certain washout period.”

“Further investigation is required to establish an optimal treatment strategy,” the team concluded.

Adapted from