The benefits of Daliresp (roflumilast), an approved chronic obstructive pulmonary disease therapy, may include an anti-inflammatory effect, with the treatment seen in a Phase 3 clinical trial to lower the number of eosinophils — a type of immune cell linked to inflammation — in the lungs of patients with moderate to severe COPD.
The study reporting this finding, “Anti-inflammatory effects of roflumilast in chronic obstructive pulmonary disease (ROBERT): a 16-week, randomised, placebo-controlled trial,” was published in the journal The Lancet – Respiratory Medicine.
Daliresp, by AstraZeneca, is approved as an add-on oral therapy for reducing the number of exacerbations in patients with severe COPD. It works by selectively inhibiting phosphodiesterase 4 (PDE4), an enzyme previously linked to COPD progression.
While animal studies suggest that Daliresp may also reduce inflammation in the lungs, few studies have investigated its anti-inflammatory potential in humans.
The Roflumilast Biopsy European Research Trial (ROBERT) (NCT01509677), a Phase 3 study performed in five European countries. It randomized 158 moderate-to-severe COPD patients (ages 40 to 80) with chronic productive cough to treatment with 500 micrograms of Daliresp, or a placebo tablet, once daily as an add-on therapy — meaning the 79 patients in each group continued with standard bronchodilator therapy — for 16 weeks.
Before randomization, all patients completed a six-week single-blind phase were they received a placebo daily to assess compliance.
The study’s main (primary) goal was to assess the differences in the number of inflammatory cells at the end of the treatment. Specifically, researchers collect a piece of lung tissue, and sputum and blood samples to determine the number of CD8 T-cells and other inflammatory markers, including neutrophils and eosinophils, both types of immune cells.
At excessive levels, eosinophils can cause inflammation in the lungs, leading to excess sputum production and contributing to the worsening of respiratory symptoms in COPD patients. Those with high eosinophil levels are known to be at greater risk of exacerbations.
Following the treatment’s conclusion (week 16), researchers also evaluated biopsy samples from 148 patients — 76 from the Daliresp group and 72 from the placebo group.
Results showed that the number of CD8 T-cells was similar between those given Daliresp or placebo at week 16 – a mean of 442.4 cells per square millimeter (mm2) versus 427.1, respectively.
However, compared with placebo, treatment with Daliresp was associated with a significant reduction in eosinophils in lung tissue at week 16. This decrease was also detected in the sputum samples. Blood samples showed no differences between the two groups.
No differences between groups were found for other inflammatory markers, including other classes of T-cells (called CD4 or CD45 T-cells) and for neutrophils.
The safety and tolerability profile of Daliresp was in line with that previously reported, and no new additional safety issues found. In total, serious adverse events (including COPD worsening) occurred in eight (10%) of the Daliresp-treated patients, and in five (16%) in the placebo group.
While Daliresp had no effect on the number of CD8 T-cells, results showed the therapy reduced the number of eosinophils in airway mucosa and sputum samples compared to placebo.
These results suggest that “the anti-inflammatory effect of roflumilast in COPD could be mediated by an effect on lung eosinophils,” the researchers wrote. They recommended further studies “to specifically investigate the precise mechanism responsible for the reduction in airway eosinophil counts with roflumilast.”