Critically Ill IPF Patients May Benefit From Autoimmune Disease Therapies

A study recently published in the journal PloS One revealed that patients with acute exacerbations of idiopathic pulmonary fibrosis (IPF) may benefit from treatments similar to the ones employed in autoimmune diseases. The study is entitled “Autoantibody-Targeted Tratments for Acute Exacerbations of Idiopathic Pulmonary Fibrosis” and was conducted by researchers at the University of Alabama at Birmingham (UAB), the University of Pittsburgh, the University of Texas Medical Branch at Galveston and the University of North Carolina at Chapel Hill.

IPF is a progressive fatal lung disease of unknown origin in which the alveoli and the lung tissue are damaged, becoming thick and scarred (fibrosis), leading to severe breathing difficulties and compromising oxygen transfer between the lungs and the bloodstream. The disorder is characterized by a shortness of breath that gradually worsens, with respiratory failure being the main cause of death. There is no cure for IPF and it is estimated that almost 130,000 individuals in the United States and 5 million worldwide suffer from the disease. IPF has a poor prognosis and around two-thirds of the patients die within five years after being diagnosed.

Recent studies have suggested that autoantibodies may play a role in IPF progression. Autoantibodies are antibodies produced due to an overreaction of the body’s immune system, leading to the attack of the person’s own healthy tissues and organs causing inflammation, pain, disability and often tissue destruction. Autoantibodies and this dysfunctional immune response are intrinsically linked to autoimmune diseases.

In the study, researchers conducted a pilot trial (NCT01266317) to test the hypothesis that therapies targeting autoantibodies may have a beneficial impact on the exacerbations of IPF patients. “Severe acute exacerbations of IPF are medically untreatable and often fatal within days,” explained the study’s senior author Dr. Steve Duncan from the UAB in a news release. “We wanted to test the hypothesis that autoantibody-targeted therapies used to treat autoimmune disease also may benefit IPF patients with acute exacerbations.”

In total, 11 critically ill IPF patients with acute exacerbations were treated with up to nine therapeutic plasma exchanges (TPE, a method that allows the removal of harmful autoantibodies from the patient’s blood) and the drug rituximab (which targets immune B cells which are responsible for the production of autoantibodies). Four of the patients also received intravenous immunoglobulin to help suppress B cells.

Researchers found that 9 patients (82%) had an improved lung function after treatment in comparison to the control IPF patients treated with conventional glucocorticoid therapy. The response was sustained without relapses after 96 to 237 days. Autoantibody levels were found to be reduced in patients who responded positively to the treatment. No serious adverse events were reported.

In addition, “One-year survival of trial subjects was nearly 50 percent, which is remarkable,” noted Dr. Duncan. “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.”

The research team concluded that specific therapies to reduce autoantibody levels can benefit critically ill IPF patients with acute exacerbations. The team believes that trials on autoantibody-targeted therapies should be conducted in these patients.

“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,” said Dr. Duncan.

“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,” concluded the UAB Director of the Division of Pulmonary, Allergy and Critical Care Medicine Dr. Victor Thannickal. “It is now time for a randomized controlled trial of this treatment approach in IPF patients.”