Pirfenidone and Nintedanib for Treatment of Idiopathic Pulmonary Fibrosis

Gayathri Sathiyamoorthy, MD; Sameep Sehgal, MD; Rendell W. Ashton, MD


South Med J. 2017;110(6):393-398. 

In This Article


Pirfenidone and nintedanib are the only two drugs that have been approved by the FDA for the treatment of IPF.[20] Based on the data, treatment can be initiated in patients with mild to moderate disease. Such treatment usually is started and monitored by a pulmonary specialist who has experience with the management of ILD. These drugs slow disease progression, and pirfenidone has shown to increase PFS in some studies. Despite their different mechanisms of action, the two drugs are considered to have similar efficacy. Neither drug shows significant improvement in respiratory symptoms or survival (Table 2). The different adverse effect profiles and tolerance of individual patients may be important criteria for choosing between the agents.

Treatment should be individualized after careful discussion with the patient regarding the outcome of therapy and potential adverse effects of the drugs. Both medications can lead to significant gastrointestinal symptoms. Diarrhea is a common adverse effect of nintedanib, whereas nausea, dyspepsia, and vomiting were observed more commonly in pirfenidone. Pirfenidone also may cause photosensitivity and rash. Both drugs require monthly LFTs for 3 months and then every 3 months thereafter. The choice of medication may be affected by the fact that pirfenidone has a higher pill burden, requiring three pills to be taken three times daily, compared with nintedanib, which requires one pill to be taken twice daily.

The cost of treatment with either medication can be prohibitive for many patients. Both medications cost nearly $100,000/year in the United States. Insurance companies may cover all or part of the cost of the drugs if the patient meets the appropriate clinical criteria for the prescription.

Conceptually, the combination of the two agents seems an appealing option. The two agents have different mechanisms of action and have been shown to be individually efficacious; however, combination therapy has not yet been shown to be safe or effective. Multiple trials evaluating the safety and tolerability of combined treatment with nintedanib and pirfenidone (clinicaltrials.gov identifiers NCT02579603 and NCT02598193) are under way. Based on the findings of these studies, treatment recommendations may change.

Finally, we emphasize that the treatments for IPF are not curative. Treatment with pirfenidone or nintedanib may reduce progression in some patients with moderate disease. The effect of these drugs beyond the first year of therapy also is ambiguous. There is no clear standard of care for gauging the response to therapy. Patient expectations must be addressed early, and there should be ongoing discussion of the appropriate goals of care, including the role of palliative care and lung transplantation options if ILD progresses. Although many unanswered questions remain, including long-term outcomes and the effects of combination therapy, pirfenidone and nintedanib have shown promising results in an otherwise untreatable and ultimately fatal disease and offer a beacon of hope to patients with IPF and the providers who care for them.