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Roflumilast increases PDE4B2 production, resulting in COPD patients developing a drug tolerance

The use of roflumilast in patients with COPD increases the production of a protein called PDE4B2, which may result in patients developing a tolerance to the drug after repeated use, according to study results published in the Proceedings of the National Academy of Sciences USA.

“There is clinical evidence showing that patients could develop a tolerance if they keep taking repeated dosing of this drug, but why or how has been unknown,” study researcher Jian-Dong Li, MD, PhD, of Georgia State University, said in a press release. “If we can figure out why people have a tolerance, we can probably improve the therapeutics.”

Researchers indicated that — even in high concentrations — roflumilast (Daliresp, Forest Pharmaceuticals) cannot fully suppress the inflammatory response caused by the increase in PDE4B2 because it is independent of enzymatic activity.

“We found there is some inflammatory response which cannot be suppressed by the drug because it has little to do with the enzyme activity,” Li said in the release. “The patient keeps taking the drug and over time, you give more drug and you produce more target protein, which is even more counterproductive for suppressing inflammation. Over time, we develop a tolerance.”

Disclosure: The researchers report no relevant financial disclosures.