Safety of Anti-fibrotics Ofev, Esbriet Supported by Real-world Data

Rare serious cardiac events seen with Ofev in study of patient records in France

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Real-world data support the safety profile of the anti-fibrotic medications Esbriet (pirfenidone) and Ofev (nintedanib) in people with idiopathic pulmonary fibrosis (IPF), according to a new study.

More than half of patients experienced treatment-related adverse events, the majority being non-severe gastrointestinal symptoms. Rare cases of serious heart-related adverse events were reported for Ofev and included two cases of reduced blood flow to the heart and one heart attack.

These results highlight the importance of assessing the “potential risk of arterial and venous thromboembolism with nintedanib [Ofev], taking into account the cardiovascular risk of each patient,” researchers wrote.

The study, “Real-world safety profiles of pirfenidone and nintedanib in idiopathic pulmonary fibrosis patients,” was published in the journal Pulmonary Pharmacology & Therapeutics.

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Ofev and Esbriet can be associated with adverse side effects

Ofev (marketed by Boehringer Ingelheim) and Esbriet (marketed by Genentech) are two medications approved for IPF. Data from clinical trials demonstrated the benefits of these medications in reducing disease progression and respiratory-related hospitalizations, and in increasing patient survival. However, their use can be associated with adverse side effects, including gastrointestinal, metabolic, and skin issues. Ofev can also potentially affect heart function.

To date, however, few real-world studies have reported the safety of these medications, with a lack of information on rare and/or delayed adverse reactions.

“Post-marketing drug safety surveillance is an essential component of overall drug safety profiling as it can signal safety problems (especially serious events), [and] provide information on rare and/or delayed [adverse drug reactions],” the researchers wrote.

Now, a team of researchers in France conducted a pharmacovigilance (also known as drug safety) study, called SAfety of PIrfenidone and Nintedanib, or SAPIN, in which they analyzed the medical records of a group of IPF patients followed at the Rennes University Hospital, in France, from January 2011 to May 2020.

Among the 176 patients selected, 115 (65%) began treatment with Esbriet and the remaining 61 (35%) received Ofev. Patients were followed for a median of 15.3 months.

The criteria for patient inclusion in the study “were less restrictive than those of trials and registries and the patient cohort was more representative of the target population,” the researchers wrote.

One or more adverse reactions were registered for 90 patients taking Esbriet (78.3%) and 43 patients given Ofev (70.5%).

Serious reactions in both groups led to treatment change or discontinuation. For non-serious events, treatment was continued in 45%–62% of the cases.

Post-marketing drug safety surveillance is an essential component of overall drug safety profiling as it can signal safety problems (especially serious events)

Majority of treatment-related adverse events were considered non-serious

In the Esbriet group, the majority of treatment-related adverse events were non-serious (75.6% or 68 cases). These included gastrointestinal and skin-related adverse events (resulting in photosensitivity and isolated rashes), as well as metabolic and nutritional disorders (most common being loss of appetite and weight).

The 22 reported serious adverse events to Esbriet included one fatal pulmonary embolism. Unexpected serious adverse reactions included tooth loss, burning sensation, tachycardia (fast heart rate) and palpitations, hypertension (high blood pressure), erectile dysfunction, depression, loss of treatment efficacy, and IPF worsening.

In patients taking Ofev, the majority of adverse reactions reported were also non-serious (79% or 34 cases), and included gastrointestinal symptoms, such as nausea/vomiting, diarrhea, and abdominal pain. None of these adverse reactions were fatal.

Unexpected serious adverse reactions included fainting, retinal artery occlusion (blockage of the retinal artery that carries oxygen to the nerve cells in the retina), and loss of therapeutic efficacy.

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Overall, the incidence of treatment-related adverse reactions for both medications was about 33 reactions per 100 person-years. In the case of Ofev, non-serious treatment-related adverse reactions could reach 130 per 100 person-years.

Person-years is a composite measure that reflects both the number of people and the amount of time each person was followed. For example, 100 person-years pertains to data gathered by following 100 people for one year.

Cardiovascular adverse events occurred in about 10 cases per 100 person-years with either Ofev or Esbriet.

Serious cardiovascular adverse reactions in the Ofev group included two cases of acute coronary syndrome, a condition where there is a sudden decrease in blood reaching the heart, and myocardial infarction (heart attack). For Esbriet, cardiovascular complications included a case of pulmonary embolism (blockage in the lung arteries) and ischemic heart disease (poor blood supply to the heart muscle).

Overall, “most ADRs [adverse drug reactions] were consistent with the expected antifibrotic safety profiles, including data from international registries, which can be reassuring,” the researchers wrote.

“The safety signal of arterial and venous thromboembolic events with nintedanib [Ofev] should be evaluated in a dedicated pharmacoepidemiological study, because they are so rare,” the team added.

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