TY - JOUR
T1 - Evolving spectrum of drug-induced uveitis at the era of immune checkpoint inhibitors results from the WHO's pharmacovigilance database
AU - Anquetil, Céline
AU - Salem, Joe Elie
AU - Lebrun-Vignes, Bénédicte
AU - Touhami, Sara
AU - Desbois, Anne Claire
AU - Maalouf, Georgina
AU - Domont, Fanny
AU - Allenbach, Yves
AU - Cacoub, Patrice
AU - Bodaghi, Bahram
AU - Saadoun, David
N1 - Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Purpose: Drug-induced uveitis is a rare but sight-threatening condition. We seek to determine the spectrum of drug-induced uveitis at the era of immune checkpoint inhibitors (ICI). Methods: Retrospective pharmacovigilance study based on adverse drug reactions reported within VigiBase, the WHO international pharmacovigilance database. We included deduplicated individual case safety reports (ICSRs) reported as ‘uveitis’ at Preferred Term level according to the Medical Dictionary for Drug Regulatory Activities between 1967 and 04/28/2019. We performed a case/non-case analysis to study if suspected drug-induced uveitis were differentially reported for each suspected treatment compared to the full database. We excluded drugs with potential indication bias. Results: 1404 ICSRs corresponding to 37 drugs had a significant over-reporting signal with a median age of 57 [42–68] years and 45.7% of males. We identified five major groups of treatments: bisphosphonates (26.9%), non-antiviral anti-infectious drugs (25.4%), protein kinase inhibitors (15.5%), ICI (15.0%), and antiviral drugs (11.1%). Severe visual loss was reported in 12.1% of cases. ICI and protein kinase inhibitors were the most recently emerging signals. The time to onset between first infusion and uveitis was significantly different between groups ranging from 5 days [2–19] in the bisphosphonate group to 138.5 [47.25–263.75] in protein kinase inhibitors group (p < 0.0001). Anti-Programmed Cell death 1 represented more than 70% of ICI-induced uveitis. We identified Vogt-Koyanagi-Harada (VKH)-like syndrome as being associated with ICI use. Conclusions: The spectrum of drug-induced uveitis has changed with the evolution of pharmacopeia and the recent emergence of ICIs. VKH-like syndrome has been reported with ICI and protein kinase inhibitors therapy.
AB - Purpose: Drug-induced uveitis is a rare but sight-threatening condition. We seek to determine the spectrum of drug-induced uveitis at the era of immune checkpoint inhibitors (ICI). Methods: Retrospective pharmacovigilance study based on adverse drug reactions reported within VigiBase, the WHO international pharmacovigilance database. We included deduplicated individual case safety reports (ICSRs) reported as ‘uveitis’ at Preferred Term level according to the Medical Dictionary for Drug Regulatory Activities between 1967 and 04/28/2019. We performed a case/non-case analysis to study if suspected drug-induced uveitis were differentially reported for each suspected treatment compared to the full database. We excluded drugs with potential indication bias. Results: 1404 ICSRs corresponding to 37 drugs had a significant over-reporting signal with a median age of 57 [42–68] years and 45.7% of males. We identified five major groups of treatments: bisphosphonates (26.9%), non-antiviral anti-infectious drugs (25.4%), protein kinase inhibitors (15.5%), ICI (15.0%), and antiviral drugs (11.1%). Severe visual loss was reported in 12.1% of cases. ICI and protein kinase inhibitors were the most recently emerging signals. The time to onset between first infusion and uveitis was significantly different between groups ranging from 5 days [2–19] in the bisphosphonate group to 138.5 [47.25–263.75] in protein kinase inhibitors group (p < 0.0001). Anti-Programmed Cell death 1 represented more than 70% of ICI-induced uveitis. We identified Vogt-Koyanagi-Harada (VKH)-like syndrome as being associated with ICI use. Conclusions: The spectrum of drug-induced uveitis has changed with the evolution of pharmacopeia and the recent emergence of ICIs. VKH-like syndrome has been reported with ICI and protein kinase inhibitors therapy.
KW - Drug induced-adverse event
KW - Immune checkpoint inhibitors
KW - Protein kinase inhibitors
KW - Uveitis
KW - Visual loss
UR - http://www.scopus.com/inward/record.url?scp=85083113226&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2020.102454
DO - 10.1016/j.jaut.2020.102454
M3 - Article
C2 - 32303423
AN - SCOPUS:85083113226
SN - 0896-8411
VL - 111
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
M1 - 102454
ER -