TY - JOUR
T1 - Transaminase Levels and Hepatic Events During Tocilizumab Treatment
T2 - Pooled Analysis of Long-Term Clinical Trial Safety Data in Rheumatoid Arthritis
AU - Genovese, Mark C.
AU - Kremer, Joel M.
AU - van Vollenhoven, Ronald F.
AU - Alten, Rieke
AU - Scali, Juan Jose
AU - Kelman, Ariella
AU - Dimonaco, Sophie
AU - Brockwell, Laura
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Objective: To investigate liver enzyme abnormalities and hepatic adverse events (AEs) during long-term tocilizumab treatment for rheumatoid arthritis in clinical trials. Methods: Data were pooled from patients who received intravenous tocilizumab (4, 8, or 10 mg/kg with or without disease-modifying antirheumatic drugs [DMARDs]) in phase III or IV clinical trials, long-term extensions, and a pharmacology study. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured routinely in these trials. AE rates were measured per 100 patient-years of tocilizumab exposure for this pooled analysis. Results: Overall, 16,204.8 patient-years of tocilizumab exposure (mean ± SD duration of exposure 3.9 ± 2.0 years) were evaluated for 4,171 patients. ALT and AST elevations greater than the upper limit of normal (ULN) occurred in 70.6% and 59.4% of patients, respectively. ALT/AST elevations were >1–3× ULN in 59%/55% of patients, >3–5× ULN in 8.9%/3.3% of patients, and >5× ULN in 2.9%/0.9% of patients. Most elevations occurred during the first year of treatment. Single ALT/AST elevations >3× ULN occurred in 7.7%/3.6% of patients, and ≥2 consecutive elevations >3× ULN occurred in 1.9%/0.4% of patients. Elevations >3× ULN returned to normal in 80% of patients (median of 5.6 weeks to normalization). A total of 2.5% of patients withdrew from tocilizumab treatment following ALT/AST elevations. A total of 7 hepatic serious AEs (SAEs) (0.04 per 100 patient-years [95% confidence interval 0.02–0.09]) occurred in the tocilizumab studies. Conclusion: Transaminase elevations with tocilizumab were frequent, but rates of hepatic SAEs were low in this clinical trial data set. Regular monitoring, with dose adjustment of tocilizumab/DMARDs for persistent elevations, is recommended.
AB - Objective: To investigate liver enzyme abnormalities and hepatic adverse events (AEs) during long-term tocilizumab treatment for rheumatoid arthritis in clinical trials. Methods: Data were pooled from patients who received intravenous tocilizumab (4, 8, or 10 mg/kg with or without disease-modifying antirheumatic drugs [DMARDs]) in phase III or IV clinical trials, long-term extensions, and a pharmacology study. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured routinely in these trials. AE rates were measured per 100 patient-years of tocilizumab exposure for this pooled analysis. Results: Overall, 16,204.8 patient-years of tocilizumab exposure (mean ± SD duration of exposure 3.9 ± 2.0 years) were evaluated for 4,171 patients. ALT and AST elevations greater than the upper limit of normal (ULN) occurred in 70.6% and 59.4% of patients, respectively. ALT/AST elevations were >1–3× ULN in 59%/55% of patients, >3–5× ULN in 8.9%/3.3% of patients, and >5× ULN in 2.9%/0.9% of patients. Most elevations occurred during the first year of treatment. Single ALT/AST elevations >3× ULN occurred in 7.7%/3.6% of patients, and ≥2 consecutive elevations >3× ULN occurred in 1.9%/0.4% of patients. Elevations >3× ULN returned to normal in 80% of patients (median of 5.6 weeks to normalization). A total of 2.5% of patients withdrew from tocilizumab treatment following ALT/AST elevations. A total of 7 hepatic serious AEs (SAEs) (0.04 per 100 patient-years [95% confidence interval 0.02–0.09]) occurred in the tocilizumab studies. Conclusion: Transaminase elevations with tocilizumab were frequent, but rates of hepatic SAEs were low in this clinical trial data set. Regular monitoring, with dose adjustment of tocilizumab/DMARDs for persistent elevations, is recommended.
UR - http://www.scopus.com/inward/record.url?scp=85026542481&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/art.40176
DO - https://doi.org/10.1002/art.40176
M3 - Article
C2 - 28597609
SN - 2326-5191
VL - 69
SP - 1751
EP - 1761
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 9
ER -