Long-Term Treatment With Evolocumab Among Japanese Patients　- Final Report of the OSLER Open-Label Extension Studies.

Abstract

BACKGROUND:

Treatment with evolocumab reduces mean low-density lipoprotein cholesterol (LDL-C) up to 75% and cardiovascular events by 16% in the first year and 25% thereafter. Methods and Results: Japanese patients with hypercholesterolemia enrolled in the parent YUKAWA-1-2 studies could enroll, once eligible, in the OSLER studies (n=556). OSLER re-randomized patients 2:1 to evolocumab plus standard of care (SOC; evolocumab+SOC) or SOC alone for 1 year; after year 1, patients could enter the all-evolocumab+SOC open-label extension of OSLER. Patients received evolocumab+SOC from the 2nd year through up to 5 years. Long-term efficacy and safety, including antidrug antibodies, were evaluated. Of 556 patients, 532 continued to the all-evolocumab+SOC extension: mean (standard deviation [SD]) age 61 (10) years, 39% female. A total of 91% of 532 patients completed the studies. Mean (SD) LDL-C change from parent-study baseline with evolocumab from a mean (SD) baseline of 142.3 (21.3) and 105.0 (31.1) mg/dL in OSLER-1 and OSLER-2, respectively, was maintained through the end of the study: -58.0% (19.1%) at year 5 in OSLER-1, -62.7% (25.6%) at year 3 in OSLER-2. The overall safety profile of the evolocumab+SOC periods was similar to that of the year-1 controlled period. Antidrug antibodies were detected transiently in 3 patients. No neutralizing antibodies were detected.

CONCLUSIONS:

Japanese patients who continued evolocumab+SOC for up to 5 years experienced sustained high LDL-C level reduction. Long-term evolocumab+SOC exposure showed no new safety signals.

• Authors: Atsushi Hirayama, Shizuya Yamashita, Andrea Ruzza, Hyoe Inomata, Marcoli Cyrille, Chen Lu, Andrew W Hamer, Masayuki Yoshida, Arihiro Kiyosue, Tamio Teramoto
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 83 Issue 5 Pg. 971-977 (04 25 2019) ISSN: 1347-4820 [Electronic] Japan
• PMID: 30930429 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Antibodies, Monoclonal, Humanized
• Cholesterol, LDL
• evolocumab

Topics

• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Asian People
• Cholesterol, LDL (blood)
• Female
• Follow-Up Studies
• Humans
• Hypercholesterolemia (blood, drug therapy)
• Japan
• Male
• Middle Aged
• Time Factors