Real-world experience with CLAIRYG® 50 mg/mL (intravenous immunoglobulin) in children under 12 years with primary immunodeficiency or immmune thrombocytopenia: a post-approval safety study.

Introduction: This study presents the results of a real-life, multicenter, prospective, post-approval safety evaluation of Clairyg® 50 mg/mL, a 5% intravenous immunoglobulin (IVIg) liquid, in 59 children (aged < 12 years) with primary immunodeficiency diseases (PID) (n = 32) or immune thrombocytopenia (ITP) (n = 27) in France. Methods: The primary objective of the study was to assess the safety and tolerability of Clairyg®, recording all serious and non-serious adverse events (AEs), whether related (rAEs) or not related to the product. Secondary objectives aimed at evaluating the administration of Clairyg® under routine conditions and the available efficacy data to better document the benefit/risk ratio in this pediatric population. An exploratory objective was added to evaluate the potential factors associated with the occurrence of rAEs. Patients received Clairyg® according to the approved dosage under normal conditions of prescriptions over a median follow-up period of 11.8 months. Results: A total of 549 infusions (PID: n = 464 and ITP: n = 85), were administered, of which 58.8% were preceded by premedication. The most frequent rAEs were headache, vomiting, and pyrexia in both indications. Most of them were considered non-serious and mild or moderate in intensity. A severe single rAE was observed (aseptic meningitis) in a 4-year-old girl presenting with chronic ITP. The exploratory multivariate analysis of potential co-factors showed that the occurrence of rAEs is significantly linked to high IVIg doses and possibly to female gender. The annualized rate of serious bacterial infections was 0.11 for patients with PID. For patients with ITP, 74.1% experienced at least one bleeding episode during the follow-up, mostly a cutaneous one, and none had gastrointestinal, genitourinary, or central nervous system bleeding. Conclusion: Clairyg® was well tolerated and allowed for control of serious bacterial infection in PID and serious bleeding in ITP, which are the main complications in these respective pediatric disorders. No new safety signal was detected in children less than 12 years-old in real-life conditions of use.

A post-approval observational study to evaluate the safety and tolerability of perampanel as an add-on therapy in adolescent, adult, and elderly patients with epilepsy.

OBJECTIVE: Perampanel is a once-daily oral anti-seizure medication for focal-onset seizures, with or without focal to bilateral tonic-clonic seizures (FBTCS), and generalized tonic-clonic seizures. Study 402 (NCT02033902) collected safety information on clinically important treatment-emergent adverse events (TEAEs) from real-world clinical practice in patients aged ≥12 years with refractory epilepsy who were receiving perampanel as an add-on therapy. METHODS: Study 402 was a multicenter, observational, 52-week cohort study conducted in Austria, Belgium, Czech Republic, Denmark, France, Israel, Sweden, and the United Kingdom. Safety data were gathered prospectively from patients at clinic visits. The primary endpoint was the incidence of clinically important TEAEs defined as dizziness; blurred vision; somnolence; aggression; balance disorders (including ataxia and falls); weight gain; suicidality; drug abuse, misuse, dependence, and withdrawal; skin photosensitivity; and unintended pregnancy while taking levonorgestrel-containing contraceptives. Off-label use of perampanel and outcomes associated with any suspected drug-drug interaction were also monitored and recorded. Secondary endpoints included the Hospital Anxiety and Depression Scale (HADS) and Clinical Global Impression of Change. RESULTS: Of 483 patients in the Safety Analysis Set, mean (standard deviation [SD]) age was 38.3 (15.1) years, 48.4% were female, mean (SD) time since diagnosis was 23 (14.8) years, 56.5% had focal impaired awareness seizures, and 48.7% had FBTCS. Overall, 243 (49.3%) patients treated with perampanel completed the study and 227 (46.0%) patients discontinued. The most common primary reason for discontinuation was adverse events (n = 130 [26.4%]). A total of 301 (62.3%) patients reported at least one TEAE, of which 45 (15.0%) patients had severe TEAEs and 256 (85.0%) patients had TEAEs judged as mild to moderate in severity. Overall, 51 (10.6%) patients had serious TEAEs, including two deaths that were judged as not related to perampanel, and 136 (28.2%) patients experienced a TEAE that led to treatment discontinuation. Clinically important TEAEs were reported by 153 (31.7%) patients, with the most common being dizziness (13.9%), balance disorders (5.6%), aggression (5.4%), and weight gain (5.4%). In general, the frequencies of clinically important TEAEs were lower in this study compared with previous interventional clinical studies, except for the incidence of suicidality (2.1% vs 1.0%) and aggression (5.4% vs 5.1%). Mean total HADS scores were similar at the end of the study compared with baseline; at the end of treatment, most (>60%) patients had no shift in HADS score category; ∼15% of patients moved to a worse category vs baseline and ∼20% of patients moved to an improved category vs baseline for both anxiety and depression. Based on investigator assessment, disease severity was improved in 185/415 (44.6%) patients. A subanalysis in elderly patients aged ≥65 years showed similar results to the overall population. CONCLUSIONS: The data from this observational study are consistent with the known safety profile of perampanel derived from previous interventional phase II and III clinical studies. No unusual or unexpected TEAEs were observed in this real-world clinical practice setting.