Using data from 2 large pharmacovigilance databases, investigators confirmed that proton pump inhibitors (PPIs) were associated with pharmacovigilance signals for the manifestation of drug-induced lupus erythematosus (DILE), according to a research letter published in JAMA Dermatology.
"The role of PPIs in the occurrence of DILE has been suggested for both drug-induced systemic lupus erythematosus (DI-SLE) and drug-induced cutaneous lupus erythematosus (DI-CLE) but remains poorly characterized,” investigators explained.
A disproportionality study was performed using data from VigiBase, the World Health Organization’s global pharmacovigilance database. Case-non-case studies were performed for all PPIs and each molecule to evaluate potential pharmacovigilance signals in computing the information components (ICs) and reporting odds ratios (RORs). Sensitivity analyses were performed for cases published after January 1, 2002, that were reported by physicians. Clinical, immunological, and therapeutic management of potential PPI-associated DILE from the French pharmacovigilance database was accounted for. Investigators aimed to better characterize the spectrum of PPI-associated DILE by using both the type of DILE and therapeutic management.
Between January 1985 and December 2019, 21,104,559 cases were reported in the VigiBase, of which 625 were DILE associated with a PPI. The median age at onset of DILE was 59 years and 78.2% (n = 489) of cases included female patients. In approximately half (49.1%, n = 307) of these cases, a PPI was the only suspected drug, with omeprazole reported as the most frequent PPI (30.4%, n = 190). Pharmacovigilance signals were noted for esomeprazole (IC 0.67; ROR, 1.84; 95% CI, 1.60-2.13), lansoprazole (IC 0.72; ROR, 1.97; 95% CI, 1.65-2.36), and omeprazole (IC 0.70; ROR, 1.87; 95% CI, 1.63-2.13).
In the French pharmacovigilance database, 791,922 cases were reported between January 1985 and December 2019, of which 60 were DILE associated with a PPI, and 49 were ultimately included. The median age was 68 years and 65.3% (n = 32) were female patients. In this database, Esomeprazole was the most frequently involved PPI (46.9%, n = 23). An isolated DI-CLE was observed in most (79.6%, 39 patients), including subacute DI-CLE (48.7%, n = 19), discoid DI-CLE (5.1%, n = 2), tumidus DI-CLE (2.6%, n = 1), and unspecified DI-CLE (43.6%, n = 17). Additionally, 7 patients (14.3%) reported DI-SLE with cutaneous involvement, with most specified cases being of the subacute type (42.9%, n = 3). PPI was stopped in 71.5% of patients (n = 35/41) and remission occurred in 51.4% (n = 18/35) without specific treatment.
The heterogeneity of the data available regarding adverse events limits the study. Further, there is a possibility that SLE and CLE may have been confused with other diseases in certain instances. To minimize this risk, investigators only included cases with validated classification criteria and performed sensitivity analyses.
“This descriptive case series highlights that PPIs may be associated with not only isolated DI-CLE, but also DI-SLE with or without cutaneous involvement,” investigators concluded.