Importance: The US Food and Drug Administration (FDA) conducts ongoing public health safety surveillance for drug and therapeutic biologic products. Identifying cases of acute and subacute noninfectious pneumonia supports the public health mission of the FDA.
Objective: To identify and analyze postmarketing cases of noninfectious pneumonia associated with ustekinumab use.
Design, setting, and participants: This retrospective analysis of postmarketing (spontaneous) case reports reviewed the FDA Adverse Event Reporting System (FAERS) and the PubMed databases from September 25, 2009, through November 20, 2017. Twelve cases of new-onset acute and subacute noninfectious pneumonia were identified after general marketing of ustekinumab. Cases were excluded if the time to symptom onset was more than 2 years from ustekinumab initiation and if an alternative origin for the noninfectious pneumonia (other than drug-induced) was reported.
Main outcomes and measures: Cases of noninfectious pneumonia associated with ustekinumab use were analyzed for baseline and demographic information, reason for ustekinumab use, symptoms, time to onset, dose sequence, laboratory and diagnostic information, and clinical outcome.
Results: Of the 12 cases, 8 were identified from the FAERS database and 4 from PubMed. The 12 cases (7 men [58%] and 5 women [42%], with a median [range] age of 63 [27-80] years) included 7 interstitial pneumonia (58%), 3 eosinophilic pneumonia (25%), 1 organizing pneumonia (8%), and 1 hypersensitivity pneumonitis (8%) diagnoses. All 12 cases reported a serious outcome, including 7 hospitalizations (58%) and 1 respiratory failure requiring mechanical ventilation (8%). No outcome of death was reported. All 12 cases were supportive of a temporal association; specifically, in 9 cases (75%), the pulmonary symptoms appeared after 1 to 3 doses of ustekinumab. In addition, 7 cases (58%) of positive dechallenge were reported, including 1 case of a positive rechallenge.
Conclusions and relevance: The postmarketing cases suggest an association between noninfectious pneumonia and use of ustekinumab; these findings have led to the addition of a new warning for ustekinumab users regarding the risk of developing noninfectious pneumonia.