Long-term evolocumab effective, safe for hypercholesterolemia
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Evolocumab in addition to standard of care for the treatment of hypercholesterolemia was shown to have consistent, significant LDL-lowering ability after 5 years of treatment, according to final data from the OSLER-1 trial.
Patients who received the PCSK9 inhibitor evolocumab (Repatha, Amgen) plus standard of care experienced LDL lowering of 56% at 2 years, 57% at 3 years, 56% at 4 years and 56% at 5 years from randomization, according to results published in the Journal of the American College of Cardiology, a preliminary version of which were presented at the American Heart Association Scientific Sessions in November 2018 and reported on by Healio.
In the evolocumab plus standard of care group, mean LDL decreased from 140 mg/dL to 61 mg/dL and 5.7% of these patients discontinued evolocumab due to adverse events.
Valuable information
“The final report of the OSLER-1 study adds valuable information about treating patients with hypercholesterolemia using evolocumab over an extended timeframe,” Michael J. Koren, MD, CEO and director at the Jacksonville Center for Clinical Research, and colleagues wrote. “During this extended exposure, LDL reduction persisted without attenuation. ... This consistent efficacy over time provides reassurance, especially given the expressed concerns about overcoming possible tendencies for less aggressive background pharmacotherapy and diet following the initiation of anti-PCSK9 therapy.”
Moreover, researchers observed that the proportion of patients receiving standard of care plus evolocumab who experienced adverse events (range of annual rates, 6.9% to 7.9%) was comparable to that of the patients who received standard of care alone at 1 year (6.8%).
“The yearly incidence of adverse events during extended exposure to evolocumab compared similarly to patients randomized to standard of care alone for year 1,” the researchers wrote. “Adverse event rates did not increase over time and decreased for injection-site reactions.”
In other findings, two patients in the evolocumab plus standard of care group and two in the standard of care-only group developed new, transient, binding antidrug antibodies. However, no neutralizing antidrug antibodies were detected for any patients during 5 years, according to the study.
“Transient antidrug antibodies occurred rarely, with none detected after the first year of exposure,” the researchers wrote. “Collectively, these data provide reassurance about the long-term safety of evolocumab.”
Researcher randomly assigned 1,255 patients to evolocumab plus standard or care or standard or care alone. After the first year, 1,151 patients (mean age, 57 years; mean BMI, 29 kg/m2; 52% women; 73% white; 14.4% with type 2 diabetes) progressed to the all-evolocumab phase, in which they received 420 mg evolocumab administered subcutaneously every 4 weeks and were scheduled for study visits every 12 weeks.
Encouraging findings
“Overall, these findings augur well for the use of PCSK9 inhibitors in the chronic treatment of high and very high-risk hypercholesterolemic patients, and particularly in those with residual cardiovascular risk whose LDL level on treatment with either a statin or statin-ezetimibe combination is not at the guideline-recommended goal of < 70 mg/dL,” M. John Chapman, BSc (Hons), PhD, DSc, of the endocrinology-metabolism division, Pitié-Salpetriere Hospital, Sorbonne University and National Institute for Health and Medical Research, Paris, and Henry N. Ginsberg, MD, Irving professor of medicine at the Vagelos College of Physicians and Surgeons at Columbia University, wrote in a related editorial. “It is noteworthy that the 2019 European Society of Cardiology/European Atherosclerosis Society guidelines for the management of dyslipidemias recommend a new goal of < 55 mg/dL for LDL in very high-risk patients and of < 70 mg/dL in those at high risk.” – by Scott Buzby
Disclosures: Koren reports he is employed by the Jacksonville Center for Clinical Research, a company that has received research funds and consultant fees from Amgen, Pzer, Regeneron, Sano and The Medicines Company. Please see the study for all other authors’ relevant financial disclosures. Chapman reports he has received research grants from CSL, Kowa, MSD, Pzer and Randox; and has received honoraria for advisory boards, consultancy or speaker activities from Alexion, Amarin, Amgen, CSL, Daiichi-Sankyo, Kowa, Merck, Pzer, Regeneron, Sano, Servier and Unilever. Ginsberg reports he has received research grants from Amgen and Sano-Regeneron; and has consulted for Amgen, Kowa, Merck, Pzer, Regeneron, Resverlogix and Sano.
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