Idiopathic Pulmonary Fibrosis: A Specialty "Specialty"

Patients treated for idiopathic pulmonary fibrosis (IPF) respond well to the high-touch specialty pharmaceutical service model. The IPF treatment paradigm is better than ever, and guidelines now reflect updated recommendations, as well as what not to prescribe. Despite the growing number of clinical trials, specialty pharmacists need to know the limitations of these data when it comes to treating patients in the real world, which was the focus of a session at the Asembia Specialty Pharmacy Summit 2019.

Speakers Lisa Lancaster, MD, and Geoffrey Wall, PharmD, BCPS, FCCP, helped attendees understand this complicated disease and evaluate various treatment options.

Lancaster discussed interstitial lung disease, an umbrella term that covers more than 200 diseases possessing similar clinical, radiographic, physiologic, or pathophysiologic features. IPF is the most common of the idiopathic interstitial pneumonias. Ultimately, IPF leads to fibrotic abnormalities.

“Because this disease tends to occur in older adults, the likelihood of comorbidities is high,” Lancaster said. “Many patients may have associated diseases or comorbidities, such as diabetes, obstructive sleep apnea, gastroesophageal reflux disease [GERD], and pulmonary arterial hypertension. Depression affects approximately a quarter of patients with IPF.”

Lancaster discussed the importance of treating GERD, which is comorbid in approximately 90% of patients, just half of whom will be symptomatic. She next discussed obstructive sleep apnea, its risk factors, and the high likelihood that patients who have IPF will also have sleep apnea.

When clinicians cannot diagnose IPF using radiology, biopsy may be needed, although it should be avoided in patients with significant physiologic impairment and comorbidities. Clinicians need to be active team players, collaborating with radiologists, pathologists, and rheumatologists.

Since median survival is just 2 to 4 years, treatment must be aggressive. Patients ultimately need oxygen for progressive respiratory failure, and clinicians should keep vaccinations updated. Pulmonary rehabilitation can help improve the shortness of breath and deconditioning that accompanies IPF.

Lancaster also discussed lung transplant and stem cell therapy (SCT). Researchers have many unanswered questions regarding commercial SCT. Currently, only phase 1 trials of SCT have been done, with remaining questions regarding safety and efficacy. The Pulmonary Fibrosis Foundation has issued a letter of caution that addresses commercial SCTs.

Wall continued the session by discussing basic treatment principles, emphasizing that IPF is incurable but manageable.

Currently, the FDA has approved some therapies, notably pirfenidone (Esbriet) and nintedanib, but they are expensive and can cause adverse effects. Overall, both therapies reduce the rate of decline of forced vital capacity by approximately 50%.

“The decision to start medications for IPF is based on the provider’s and the patient’s assessment of the risks and benefits,” Wall said. “Both need to realize that pharmacologic treatment has its limitations.”

He covered pirfenidone, indicating that it reduces fibroblast growth and collagen synthesis; it can also inhibit cytokine production, but its precise mechanism of action is unknown. Important counseling points include taking it with food to avoid an upset stomach, the potential for photosensitivity requiring daily use of a sunscreen with a sunscreen protection factor of at least 50, and patients who take certain cytochrome P450 (CYP) inhibitors needing close monitoring if they decide to start pirfenidone.

There have been some data to show pirfenidone may reduce the incidence of multiple disease progression events and decrease the risk of both first and second disease progression events compared with placebo.

Wall next discussed nintedanib, a triple kinase inhibitor that acts on tyrosine kinase receptors for platelet-derived growth factor, vascular endothelial growth factor, and fibroblast growth factor. It inhibits fibroblast migration, proliferation, and myofibroblast transformation. Key counseling points include management of adverse effects such as diarrhea and nausea and vomiting, monitoring for hepatotoxicity, being aware of drug interactions with P-glycoprotein and CYP3A4 inducers, and how concurrent anticoagulant use can increase bleeding risk.

Wall indicated that several new therapies are in clinical trials and seem to be progressing. Unfortunately, few studies have discussed the pharmacoeconomics associated with IPF treatment, so more research is needed.

Certain drugs, including azathioprine, prednisone, ambrisentan, bosentan, and macitentan, are considered of no use in IPF and can be harmful, according to Wall. “Patients who have IPF should not be treated for pulmonary hypertension routinely,” he added. “This is a strong recommendation from the American Board of Internal Medicine and actually noted on their Choosing Wisely site.”

Wall’s final message was that specialty pharmacists need to help patients obtain their medication and educate them about IPF, how it is treated, and the importance of close monitoring. He also discussed all categories of insurance and reminded audience members, “When you’re dealing with these patients, discourage ‘guesstimates’ when they are discussing their income and preparing to ask for financial assistance. Urge them to have their tax returns in hand.”

The combination of serious disease and prognosis, the need for specialty drugs, and access issues makes IPF a high-touch specialty pharmacy concern.