Niveles de transaminasas y Eventos Hepáticos Durante Tratamiento con Tocilizumab: Análisis Conjunta de Datos de Seguridad en Ensayos Clínicos de Largo Plazo en Artritis Reumatoide.
In this pooled analysis investigating liver enzyme abnormalities and hepatic adverse events (AEs) during long-term tocilizumab (TCZ) treatment for RA in clinical trials, although transaminase elevations were frequent, rates of hepatic serious AEs remained low.
Data were pooled from patients who received ≥1 dose of IV TCZ with or without DMARDs in Phase 3 or 4 clinical trials, long-term extensions, and a pharmacology study.
A total of 4171 patients were included in the all-exposure population with a total exposure to TCZ of 16 204.8 patient-years. ALT/AST elevations greater than the upper limit of normal (ULN) occurred in 70.6%/59.4% of patients. More than 2 consecutive elevations >3x ULN occurred in 1.9%/0.4% of patients, and elevations > 3x ULN returned to normal in 80% of patients studied. Patients with ALT/AST elevations >5x ULN or persistent elevations at least 3x ULN permanently discontinued TCZ, and patients with a history of or current hepatic disease were excluded from the study. A total of 7 hepatic SAEs (0.04 per 100 patient-years) occurred in the TCZ studies.
Rates of ALT/AST elevations were similar between MTX monotherapy and TCZ monotherapy. Higher rates of ALT/AST elevations were seen in patients treated with TCZ plus MTX/DMARDs than in those treated with MTX alone.
Based on these data, regular monitoring of transaminase levels and dose adjustments of TCZ and other DMARDs, when elevations are persistent, is recommended. Real-world data will also be needed to determine whether the elevation in ALT/AST levels could eventually lead to clinically significant disease.