BACKGROUND: Evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9, is safe and effective when dosed biweekly (Q2W) or monthly (QM) in patients with heterozygous familial hypercholesterolemia (HeFH) as demonstrated in two 12-week trials: Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD; phase 2) and RUTHERFORD-2 (phase 3). OBJECTIVE:The objective of the study was to evaluate long-term efficacy, safety, and tolerability of evolocumab during open-label extension trials. METHODS: Patients completing parent trials were re-randomized 2:1 to evolocumab plus standard of care (SOC) or SOC alone for 52 weeks (Open-Label Study of Long-term Evaluation Against LDL-C [OSLER-1]) or 48 weeks (OSLER-2). Evolocumab dosing was 420 mg QM (OSLER-1) and 140 mg Q2W or 420 mg QM (OSLER-2). A pooled analysis of OSLER data was performed from this subset of HeFH patients. RESULTS: Four hundred forty HeFH patients from RUTHERFORD (n = 147) and RUTHERFORD-2 (n = 293) (mean [standard deviation] age 51 [12] years, 58% male, 90% White) were randomized to evolocumab plus SOC (n = 289) or SOC (n = 151). The 48-week period was completed by 425 patients (96.6%). Eight patients discontinued evolocumab plus SOC (2.8%) and 7 discontinued SOC (4.6%). Compared to parent study baseline, patients receiving evolocumab plus SOC experienced a mean 53.6% reduction in low-density lipoprotein cholesterol after 48 weeks. No patient experienced an adverse event leading to permanent evolocumab discontinuation during the 1-year SOC-controlled period. Serious adverse event rates were similar between groups (evolocumab plus SOC, 7.3%; SOC, 8.6%). CONCLUSION: Continued use of evolocumab added to SOC in patients with HeFH yields persistent and marked low-density lipoprotein cholesterol reductions during 48 weeks of follow-up. Long-term dosing of evolocumab with SOC was safe and well tolerated.
Long-term safety, tolerability, and efficacy of evolocumab in patients with heterozygous familial hypercholesterolaemia / Kees Hovingh, G.; Raal, Frederick J.; Dent, Ricardo; Stefanutti, Claudia; Descamps, Olivier; Lira, Armando; Bridges, Ian; Somaratne, Ransi; Sullivan, David. - In: EUROPEAN HEART JOURNAL. - ISSN 0195-668X. - ELETTRONICO. - 37:1 P1709(2016), pp. 343-343. [10.1016/j.jacl.2017.09.003]
Long-term safety, tolerability, and efficacy of evolocumab in patients with heterozygous familial hypercholesterolaemia
STEFANUTTI, Claudia;
2016
Abstract
BACKGROUND: Evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9, is safe and effective when dosed biweekly (Q2W) or monthly (QM) in patients with heterozygous familial hypercholesterolemia (HeFH) as demonstrated in two 12-week trials: Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD; phase 2) and RUTHERFORD-2 (phase 3). OBJECTIVE:The objective of the study was to evaluate long-term efficacy, safety, and tolerability of evolocumab during open-label extension trials. METHODS: Patients completing parent trials were re-randomized 2:1 to evolocumab plus standard of care (SOC) or SOC alone for 52 weeks (Open-Label Study of Long-term Evaluation Against LDL-C [OSLER-1]) or 48 weeks (OSLER-2). Evolocumab dosing was 420 mg QM (OSLER-1) and 140 mg Q2W or 420 mg QM (OSLER-2). A pooled analysis of OSLER data was performed from this subset of HeFH patients. RESULTS: Four hundred forty HeFH patients from RUTHERFORD (n = 147) and RUTHERFORD-2 (n = 293) (mean [standard deviation] age 51 [12] years, 58% male, 90% White) were randomized to evolocumab plus SOC (n = 289) or SOC (n = 151). The 48-week period was completed by 425 patients (96.6%). Eight patients discontinued evolocumab plus SOC (2.8%) and 7 discontinued SOC (4.6%). Compared to parent study baseline, patients receiving evolocumab plus SOC experienced a mean 53.6% reduction in low-density lipoprotein cholesterol after 48 weeks. No patient experienced an adverse event leading to permanent evolocumab discontinuation during the 1-year SOC-controlled period. Serious adverse event rates were similar between groups (evolocumab plus SOC, 7.3%; SOC, 8.6%). CONCLUSION: Continued use of evolocumab added to SOC in patients with HeFH yields persistent and marked low-density lipoprotein cholesterol reductions during 48 weeks of follow-up. Long-term dosing of evolocumab with SOC was safe and well tolerated.File | Dimensione | Formato | |
---|---|---|---|
Hovingh_Long-term-safety_2016.pdf
accesso aperto
Tipologia:
Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza:
Tutti i diritti riservati (All rights reserved)
Dimensione
866.85 kB
Formato
Adobe PDF
|
866.85 kB | Adobe PDF |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.