Evaluation of long-term effectiveness of the use of carglumic acid in patients with propionic acidemia (PA) or methylmalonic acidemia (MMA): study protocol for a randomized controlled trial.

INTRODUCTION: Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare autosomal recessive inborn errors of metabolism characterized by hyperammonemia due to N-acetylglutamate synthase (NAGS) dysfunction. Carglumic acid (Carbaglu®; Orphan Europe Ltd.) is approved by the US Food and Drug Administration (USFDA) for the treatment of hyperammonemia due hepatic NAGS deficiency. Here we report the rationale and design of a phase IIIb trial that is aimed at determining the long-term efficacy and safety of carglumic acid in the management of PA and MMA. METHODS: This prospective, multicenter, open-label, randomized, parallel group phase IIIb study will be conducted in Saudi Arabia. Patients with PA or MMA (≤15 years of age) will be randomized 1:1 to receive twice daily carglumic acid (50 mg/kg/day) plus standard therapy (protein-restricted diet, L-carnitine, and metronidazole) or standard therapy alone for a 2-year treatment period. The primary efficacy outcome is the number of emergency room visits due to hyperammonemia. Safety will be assessed throughout the study and during the 1 month follow-up period after the study. DISCUSSION: Current guidelines recommend conservative medical treatment as the main strategy for the management of PA and MMA. Although retrospective studies have suggested that long-term carglumic acid may be beneficial in the management of PA and MMA, current literature lacks evidence for this indication. This clinical trial will determine the long-term safety and efficacy of carglumic acid in the management of PA and MMA. TRIAL REGISTRATION: King Abdullah International Medical Research Center ( KAIMRC ): (RC13/116) 09/1/2014. Saudi Food and Drug Authority (SFDA) (33066) 08/14/2014. ClinicalTrials.gov (identifier: NCT02426775) 04/22/2015.

The Influence of the COVID-19 Pandemic on Seasonal Influenza Vaccine Uptake Among Patients Visiting a University Hospital in Saudi Arabia.

INTRODUCTION: Influenza vaccination is a subject of importance in Saudi Arabia. The study measured the uptake of annual influenza vaccination from 2019 to 2021 among patients attending outpatient clinic of a University Hospital.  Materials and methods: A cross-sectional study design was used, and the questionnaire was administered by trained interviewers. Descriptive and inferential statistics were done using the Statistical Package for the Social Sciences (SPSS) version 21 (IBM, Armonk, New York).  Results: The three-year annual influenza vaccine uptake for 2019-2021 was 19.7%, 11.4%, and 14.2%, respectively. In the year 2022, only 28.2% of the patients were offered influenza vaccines by their physicians, and among those offered, 49.6% showed vaccine acceptance. Higher vaccine acceptance was significantly associated with past episodes of influenza infection (p<0.001) and vaccination history before the COVID-19 pandemic (p<0.001). Lower acceptance of the influenza vaccine was observed during the pandemic (p<0.001) and lower uptake among those who were not offered influenza vaccines (p=0.02). No association was found between influenza vaccine acceptance and smoking status, chronic illness, history of COVID-19 infection, or living with those susceptible to influenza. Reasons for vaccine denial include an assumption of not being at risk, a lack of information about the vaccine, and a fear of side effects. CONCLUSION: The COVID-19 pandemic has had a detrimental effect on annual influenza vaccination. Efforts must be taken to increase influenza vaccination among vulnerable groups.

Long-term effectiveness of carglumic acid in patients with propionic acidemia (PA) and methylmalonic acidemia (MMA): a randomized clinical trial.

BACKGROUND: Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare, autosomal recessive inborn errors of metabolism that require life-long medical treatment. The trial aimed to evaluate the effectiveness of the administration of carglumic acid with the standard treatment compared to the standard treatment alone in the management of these organic acidemias. METHODS: The study was a prospective, multicenter, randomized, parallel-group, open-label, controlled clinical trial. Patients aged ≤ 15 years with confirmed PA and MMA were included in the study. Patients were followed up for two years. The primary outcome was the number of emergency room (ER) admissions because of hyperammonemia. Secondary outcomes included plasma ammonia levels over time, time to the first episode of hyperammonemia, biomarkers, and differences in the duration of hospital stay. RESULTS: Thirty-eight patients were included in the study. On the primary efficacy endpoint, a mean of 6.31 ER admissions was observed for the carglumic acid arm, compared with 12.76 for standard treatment, with a significant difference between the groups (p = 0.0095). Of the secondary outcomes, the only significant differences were in glycine and free carnitine levels. CONCLUSION: Using carglumic acid in addition to standard treatment over the long term significantly reduces the number of ER admissions because of hyperammonemia in patients with PA and MMA.