(Y) Use of Valganciclovir/Ganciclovir [(v)GCV] for Treatment of Congenital Cytomegalovirus (cCMV) Infection in the United States: Evidence from The Sentinel Distributed Database, 2008-2020

Sunday, August 28, 2022

8:00 AM – 6:00 PM CEST

Location: Hall E South

Publication Number: 1023

Presenting Author(s)

Ashish Rai, MBBS, PhD, MSPH
– Harvard Pilgrim Health Care Institute, Boston, Massachusetts, United States

Co-Author(s)

Emmanuel Ojo, MPH
– Research Analyst, Harvard Pilgrim Health Care Institute, Harvard Medical School Department of Population Medicine, United States
Takashi Komatsu
– U.S. Food and Drug Administration, Silver Spring, MD, United States
Mayura Shinde, DrPH
– Harvard Medical School, Boston, Massachusetts, United States
Danijela Stojanovic, PharmD, PhD
– U.S. Food and Drug Administration, Silver Spring, MD, United States
Adebola Ajao
– Epidemiologist, US Food and Drug Administration, Food and Drug Administration, Silver Spring, Maryland, United States
Hengrui Sun
– U.S. Food and Drug Administration, United States
Amy Bishara
– U.S. Food and Drug Administration, United States
Joy Kolonoski
– Harvard Pilgrim Healthcare Institute, United States
Ann McMahon, MD, MS, FISPE
– Team Leader, Science and Innovation Team, U.S. Food and Drug Administration, Silver Spring, United States
Prabha Viswanathan
– U.S. Food and Drug Administration, Silver Spring, MD, United States

Background: Congenital cytomegalovirus (cCMV) infection can cause serious audiologic and neurodevelopmental impairment. Although no therapies have been approved specifically to prevent or treat cCMV, six months of (v)GCV initiated within the 1st month of life is recommended for newborns with moderate to severe disease to improve outcomes.

Objectives: To describe (v)GCV use for treatment of cCMV in the United States.

Methods: We used the FDA Sentinel System’s Distributed Database (1/2008-3/2021) to identify infants with cCMV, defined as any diagnosis code for cCMV or CMV in the first 45 days of life (G1). The date of earliest observed diagnosis code during the study period served as the index date. Additionally, we identified two subsets: cCMV treated with (v)GCV within 45 days of the index diagnosis (G2), and cCMV treated with (v)GCV within 180 days of the index diagnosis (G3). We assessed hearing loss and common cCMV-related clinical characteristics at baseline, and periodically assessed hearing loss and hematological outcomes, associated with both cCMV and (v)GCV, in the 365 days following the cCMV diagnosis.

Results: We identified 1,500 infants with cCMV (G1), of which 15% were treated with (v)GCV within 45 days (G2) and 20% within 180 days (G3). Among all G1-G3 infants, mean age at diagnosis was 8-9 days (SD 11.5-12.3 days) and 53-54% were male. Among G1 infants, 70% had at least one cCMV-related clinical characteristic with or without hearing loss at baseline, of whom 23% received (v)GCV. Among the G1 infants treated with (v)GCV, 17% had no cCMV-related clinical characteristics documented at baseline. The most common clinical characteristics in all groups were jaundice (48-49%), thrombocytopenia (36-47%), and brain abnormalities (19-34%). Hearing loss was diagnosed in 9% of G1 and 19-22% of G2/3 infants at baseline; at 365 days, 21% of G1 and 58-62% of G2/3 infants had hearing loss. Neutropenia and treatment with granulocyte colony-stimulating factor (G-CSF), respectively, were more frequent at 180 days in G2/3 (26-28%, 3%) vs. G1 (16%, 1%). The need for blood or platelet transfusion was low in all groups.

Conclusions: Our preliminary results suggest that (v)GCV treatment in the US may not fully align with current recommendations, as demonstrated by inadequate evidence of moderate to severe illness at baseline and initiation of (v)GCV beyond the neonatal period in many patients. Regardless of treatment, the proportion of infants with hearing loss increased over time. This study is limited by lack of validation of the cCMV diagnoses. Additional work assessing patient-level data is ongoing.