Study Explores Why COPD Drug May Lose Efficacy Over Time

Roflumilast may become less effective in treating chronic obstructive pulmonary disease (COPD) over time due to an increased production of a protein that causes inflammation, which may result in the patient possibly developing tolerance, new research has shown. The study is published in the Proceedings of the National Academy of Sciences USA.

Researchers at Georgia State University, Kumamoto University, and the University of Rochester Medical Center set out to possibly improve the drug’s therapeutic efficacy by understanding why patients develop tolerance. Roflumilast works by inhibiting the phosphodiesterase 4 (PDE4) enzyme but the team found that it also increases the production of PDE4B2, which increases inflammation.

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The team reported that even at high concentrations, roflumilast can’t fully suppress inflammation because of the inflammatory response that is independent of enzymatic activity. Another protein called PKA-Cβ, appears to be a new target in reducing the PDE4B2 production.

Roflumilast was approved in 2011 to reduce the risk of COPD exacerbations in severe COPD patients with chronic bronchitis and a history of exacerbations.

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