Interstitial lung disease exacerbations following initiation of nerandomilast: A case series

Nerandomilast is a novel PDE4 inhibitor approved for the treatment of idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF). This case series reports 5 patients with an acute exacerbation of IPF or PPF within 2 weeks of administration of nerandomilast. One patient was on background nintedanib and none were on pirfenidone at the time of the exacerbation. All exacerbations were confirmed by a change in dyspnea and/or cough, worsening oxygen requirement, and new ground glass infiltrates on CT. All required hospitalization. A suggested mechanism for exacerbations on nerandomilast includes upregulation of cAMP by nerandomilast, which can drive IL-17 production. IL-17 has a known association with IPF exacerbations. The results of this case series need to be evaluated prospectively and ongoing pharmacovigilance is required.