Evenity (Romosozumab) Hair and Skin Changes: What Patients and Clinicians Need to Know

What skin reactions does the Evenity label describe?

Romosozumab is a sclerostin-inhibiting monoclonal antibody given as two 105 mg subcutaneous injections once a month for 12 doses, administered by a healthcare provider [1]. The skin findings in its labeling split into two separate groups: local injection-site reactions and systemic hypersensitivity reactions.

Injection-site reactions (pain, erythema) occurred in 4.9% of Evenity-treated patients versus 2.8% of controls across the two trials, and led to discontinuation in 0.1% [1].

Hypersensitivity reactions were reported in 6.5% (364 women) of the Evenity group and 6.5% (365) of controls across both trials [1]. The individual terms from the same labeling [1]:

• Rash: 1.1% versus 0.9%
• Dermatitis: 0.6% versus 0.8%
• Urticaria: 0.4% versus 0.5%
• Angioedema: fewer than 0.1% (3 women) in each group
• Erythema multiforme: 1 woman on Evenity, none on control

Rash and dermatitis were about as frequent in the control groups as in the romosozumab groups [1]. The two trials differ in what the control received: placebo in FRAME and alendronate in ARCH [1][2][3].

The label identifies arthralgia and headache as the most common adverse reactions, occurring in 5% or more of patients. In FRAME, arthralgia occurred in 13.1% versus 12.1% and headache in 6.6% versus 5.8%; in ARCH, arthralgia 8.1% versus 9.6% and headache 5.2% versus 5.5% [1]. Separately from those, the 6.5% hypersensitivity figure above groups together the skin and allergic terms [1].

Does romosozumab cause hair loss?

The label's table of adverse reactions occurring in at least 2% of Evenity-treated women lists arthralgia, headache, muscle spasms, peripheral edema, asthenia, neck pain, insomnia and paresthesia. Hair loss is not among them [1]. That is an evidence gap rather than a demonstration that hair is unaffected.

FRAME randomized 7,180 postmenopausal women to romosozumab 210 mg monthly or placebo for 12 months, and ARCH randomized 4,093 women with a fragility fracture to monthly romosozumab or weekly alendronate [2][3]. Their primary endpoints were fractures [2][3].

Timing makes attribution difficult. A review of estrogens and skin describes estrogen deficiency after menopause as causing atrophic skin changes, with thinner skin, less collagen, decreased elasticity, increased dryness and reduced vascularity, and lists hair loss among the changes associated with aging skin [4]. Romosozumab is labeled for postmenopausal women, the group in which those changes are already common [1][4].

What the label says about a reaction

The Evenity prescribing information states that angioedema, erythema multiforme, dermatitis, rash and urticaria have occurred in Evenity-treated patients, and that Evenity should be discontinued if a clinically significant allergic reaction occurs [1]. A history of systemic hypersensitivity to romosozumab-aqqg or to any component of the product, with reactions including angioedema, erythema multiforme and urticaria, is listed as a contraindication [1].

For injection-site reactions, the administration instructions address technique rather than treatment. The label says to let the prefilled syringe sit at room temperature for at least 30 minutes before injecting and not to warm it any other way; to clean the sites with alcohol wipes and let the skin dry; to choose a different site each time, and if reusing a site, not the same spot; and not to inject into skin that is tender, bruised, red or hard, or into areas with scars or stretch marks [1]. The two injections go into the thigh, the abdomen (except a two-inch area around the navel) or the outer upper arm [1].

The boxed warning concerns the heart, not the skin

The Evenity prescribing information carries a boxed warning about myocardial infarction, stroke and cardiovascular death. It states that treatment should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year, that the benefits and risks should be weighed in patients with other cardiovascular risk factors, and that Evenity should be discontinued if a myocardial infarction or stroke occurs during therapy [1].

In the alendronate-controlled ARCH trial, positively adjudicated major adverse cardiac events were 2.0% (41 of 2,040) versus 1.1% (22 of 2,014), hazard ratio 1.87 (95% CI 1.11 to 3.14) [1]. In the placebo-controlled FRAME trial, the same composite was 0.8% (30) versus 0.8% (29), hazard ratio 1.03 (95% CI 0.62 to 1.72) [1].