Randomized double-blind comparison of cognitive and EEG effects of lacosamide and carbamazepine

Differential effectiveness of antiepileptic drugs (AEDs) is more commonly determined by tolerability than efficacy. Cognitive effects of AEDs can adversely affect tolerability and quality of life. This study evaluated cognitive and EEG effects of lacosamide (LCM) compared with carbamazepine immediate-release (CBZ-IR). A randomized, double-blind, double-dummy, two-period crossover, fixed-dose study in healthy subjects compared neuropsychological and EEG effects of LCM (150mg, b.i.d.) and CBZ-IR (200mg, t.i.d.). Testing was conducted at screening, predrug baseline, the end of each treatment period (3-week titration; 3-week maintenance), and the end of each washout period (4weeks after treatment). A composite Z-score was derived for the primary outcome variable (computerized cognitive tests and traditional neuropsychological measures) and separately for the EEG measures. Other variables included individual computer, neuropsychological, and EEG scores and adverse events (AEs). Subjects included 60 healthy adults (57% female; mean age: 34.4years [SD: 10.5]); 44 completed both treatments; 41 were per protocol subjects. Carbamazepine immediate-release had worse scores compared with LCM for the primary composite neuropsychological outcome (mean difference=0.33 [SD: 1.36], p=0.011) and for the composite EEG score (mean difference=0.92 [SD: 1.77], p=0.003). Secondary analyses across the individual variables revealed that CBZ-IR was statistically worse than LCM on 36% (4/11) of the neuropsychological tests (computerized and noncomputerized) and 0% of the four EEG measures; none favored CBZ-IR. Drug-related AEs occurred more with CBZ-IR (49%) than LCM (22%). Lacosamide had fewer untoward neuropsychological and EEG effects and fewer AEs and AE-related discontinuations than CBZ-IR in healthy subjects. Lacosamide exhibits a favorable cognitive profile. •A randomized, double-blind, crossover study in healthy subjects.•Compared neuropsychological and EEG effects of lacosamide and carbamazepine.•Carbamazepine also worse for composite EEG score and drug-related adverse events.•Lacosamide exhibits a favorable cognitive profile compared to carbamazepine

Safety of upadacitinib in moderate-to-severe atopic dermatitis: An integrated analysis of phase 3 studies

BACKGROUND: Upadacitinib is a selective, reversible, Janus kinase (JAK) inhibitor with established efficacy in moderate-to-severe atopic dermatitis (AD). OBJECTIVE: Evaluate the safety of upadacitinib in patients with moderate-to-severe AD. METHODS: Integrated safety data from the 16-week placebo-controlled periods of 1 phase 2b and 3 ongoing phase 3 studies (16-Week) and longer-term safety data from patients receiving upadacitinib during the blinded extension periods of the 3 phase 3 studies were analyzed (All Upadacitinib Exposure). Treatment-emergent adverse events (TEAEs) were presented as exposure-adjusted rates per 100 patient years (PY). RESULTS: Safety results were similar between the 16-week and All Upadacitinib Exposure groups. The All Upadacitinib Exposure group included 2485 patients (333 adolescents), receiving upadacitinib 15 mg (n=1239) or 30 mg (n=1246) for a mean duration of approximately 1 year. Upadacitinib was well tolerated in both adults and adolescents. TEAEs and discontinuation due to AEs were reported more frequently in patients receiving 30-mg upadacitinib (311.9 and 5.7 events per 100 PY) versus 15 mg (274.6 and 4.4 events per 100 PY). Serious AE rates (15/30 mg, 7.1/7.7 per 100 PY) were similar in both groups. Acne was the most frequently reported AE (15/30 mg, 13.3/20.2 per 100 PY). Serious infection rates were similar across treatment groups. Adjudicated major adverse cardiovascular event and venous thromboembolic event rates were ≤0.1 per 100 PY. Rates of malignant neoplasms were within the expected range for the general population. CONCLUSION: Upadacitinib was well tolerated, and no new important safety risks were observed among adults and adolescents with moderate-to-severe AD treated for approximately 1 year compared with the known safety profile of upadacitinib. CLINICAL IMPLICATIONS: Integrated safety data support the use of both upadacitinib 15-mg and 30-mg doses in patients with moderate-to-severe atopic dermatitis who are candidates for longer-term systemic therapy