Retroperitoneal fibrosis and β-blocking agents: Is there an association?

Aims: Retroperitoneal fibrosis (RPF) is a rare chronic fibro-inflammatory disorder that may be secondary to certain drugs, including beta-blocking agents (BBAs). However, their causative role is unclear. We aimed to investigate this association. Methods: Disproportionality analysis was carried out on cases from 1985 to 4 October 2020 in VigiBase, the World Health Organization pharmacovigilance database. The Bayesian-based IC025 metric and reporting odds ratio were used in order to assess the adverse event signal. We also analysed all published case reports from the literature regarding BBA-associated RPF to assess the value of suggested supportive clinical evidence. Results: In total, 1599 individual case safety reports of RPF were reported to VigiBase, of which 132 (32%) concerned 16 different single BBA. For 12 of these agents (75%), reporting of RPF was disproportionate, indicating a potential safety signal. Line listing analysis of individual case safety reports showed no consistent time interval from start of BBA to RPF diagnosis (range 0.7-264 mo). Dechallenge was negative or unknown in the majority of cases (74%). In 18 published cases from the literature, time from start of BBA to RPF diagnosis varied widely (range 3-156 mo). BBA were discontinued 6 months before (n = 1) or at the time of RPF diagnosis (n = 17). Most patients (84%) also received RPF specific treatment. Follow-up duration was short (median 5 mo [range 1-24 mo]) and in most cases (83%) relevant follow-up data were lacking. Conclusion: Although disproportionality analysis indicated a potential safety signal for RPF associated with BBAs, clinical evidence did not support a cause-and-effect relationship.

Automated summary

Disproportionality analysis of cases in VigiBase showed a potential safety signal for RPF associated with BBAs, but clinical evidence did not support a cause-and-effect relationship. Most cases did not show consistent dechallenge results after discontinuation of BBAs, indicating the need for further research and validation.