Autoantibodies Targeted in New Strategy to Treat IPF

Novel research investigating the relationship between autoantibodies and idiopathic pulmonary fibrosis (IPF) may allow new therapies to be developed based on current treatments for autoimmune diseases. The laboratory of Steve Duncan, MD, at the University of Alabama at Birmingham Division of Pulmonary, Allergy, and Critical Care Medicine recently published a study in PLOS One that described how autoantibodies play an important role in IPF when patients are undergoing acute exacerbations.

“No one had ever really done this before,” said Dr. Duncan, in a news release from the university. “There is not widespread agreement that IPF is an autoimmune disease. Our findings indicate that specific treatments that reduce autoantibodies might benefit some severely ill IPF patients with acute exacerbations. Therapies that have been developed to treat autoimmune diseases may prove to be beneficial in the treatment of these IPF patients.”

The research began when Dr. Duncan was a faculty member at the University of Pittsburgh. In a clinical trial, “Combined PEX, Rituximab and Steroids in Acute IPF Exacerbations,” ten patients with acute IPF exacerbations were treated with plasma exchange, rituximab, and conventional corticosteroids. Plasma exchange involves removing autoantibodies from the blood of patients by pumping the patient’s blood through a machine and back into the patient once the blood is clean. Rituximab attacks and kills B-cells, which produce autoantibodies.

Levels of plasma autoantibodies and proteinases were measured and compared to those of IPF patients treated only with conventional glucocorticoid therapy prior to the study. The results appeared in “Autoantibody-Targeted Treatments for Acute Exacerbations of Idiopathic Pulmonary Fibrosis.” According to Dr. Duncan, “One-year survival of trial subjects was nearly 50 percent, which is remarkable. Acute exacerbations of IPF are almost always fatal in a very short period of time. None of the 20 historical controls survived for even a year.”

Nine out of ten experimental patients responded to treatment. When three patients relapsed after receiving five plasma exchanges, two responded to additional plasma exchange procedures. While the trial was ongoing, Dr. Duncan and the rest of the research team adapted the number of plasma exchange procedures from five to nine after seeing initial results. The last four patients were also treated with intravenous immunoglobulin.

Other researchers at Birmingham are taking note of this research. “Even though IPF is not considered a prototypical autoimmune disease, acute exacerbations may be driven by autoantibody production and the treatment strategy that Dr. Duncan advocates is highly innovative with the potential to reduce IPF mortality,” said Victor Thannickal, MD. “It is now time for a randomized controlled trial of this treatment approach in IPF patients.”

If this treatment moves past its current Phase 1/2 clinical trial into Phase 3 trials and eventual approval by the FDA, the treatment may help the 100,000 Americans living with IPF. Individuals who experience acute exacerbations may die after only a few days, demonstrating the need to develop a treatment for acute IPF exacerbations.