Evenity (Romosozumab) Cognitive Function Impact: What the Evidence Actually Shows

Does Evenity affect cognitive function?

The two major trials were designed around fractures. FRAME enrolled 7,180 postmenopausal women and compared romosozumab 210 mg monthly with placebo for 12 months, then denosumab in both groups; it reported new vertebral, clinical and nonvertebral fractures [1]. ARCH enrolled 4,093 postmenopausal women with a fragility fracture and compared romosozumab with alendronate; it reported new vertebral and clinical fractures, with serious cardiovascular events adjudicated [2]. Cognition was not among the endpoints described in these reports.

The Evenity label's adverse reactions table lists reactions seen in at least 2% of women in at least one trial. In FRAME, arthralgia occurred in 13.1% on Evenity vs 12.1% on placebo, headache in 6.6% vs 5.8%, and insomnia in 2.0% vs 1.9% [3]. Memory loss, confusion and dementia are not in that table [3].

What the label warns about

The boxed warning says Evenity may increase the risk of myocardial infarction, stroke and cardiovascular death. It says Evenity should not be initiated in patients who have had an MI or stroke within the preceding year, and should be discontinued if an MI or stroke occurs during therapy [3].

In ARCH, positively adjudicated major adverse cardiac events occurred in 2.0% (41 of 2,040) on Evenity vs 1.1% (22 of 2,014) on alendronate, hazard ratio 1.87 (95% CI 1.11 to 3.14) [3]. In FRAME, the rate was 0.8% in both groups, hazard ratio 1.03 (95% CI 0.62 to 1.72) [3].

Hypocalcemia is another label warning. The label says to correct hypocalcemia before starting, supplement calcium and vitamin D during treatment, and monitor patients; severe renal impairment (eGFR 15 to 29 mL/min/1.73 m2) or dialysis raises the risk [3]. In the trials, albumin-adjusted calcium fell below 8.3 mg/dL in 0.2% of both Evenity and control patients, and none fell below 7.5 mg/dL [3]. The label's hypocalcemia section does not name cognitive changes [3].

What the label says about how it works

The label describes romosozumab as a sclerostin inhibitor that increases bone formation and, to a lesser extent, decreases bone resorption [3]. Its mechanism section describes effects on bone and does not describe a cognitive mechanism [3].

Bottom line

For cognition, the evidence is a blank: the trials' endpoints were fractures and safety events, and the label's adverse reactions table does not list cognitive impairment [3][1][2]. The label's boxed warning concerns cardiovascular risk, and its other warnings include hypocalcemia, hypersensitivity, osteonecrosis of the jaw and atypical femoral fracture [3].