Indication for EVENITY®

EVENITY® is indicated for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy.  Read More The anabolic effect of EVENITY® wanes after 12 monthly doses of therapy. Therefore, the duration of EVENITY® use should be limited to 12 monthly doses. If osteoporosis therapy remains warranted, continued therapy with an antiresorptive agent should be considered.  Close

Indication for Prolia®

Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with... Read More osteoporosis, Prolia reduces the incidence of vertebral, nonvertebral, and hip fractures.  Close

Indication for EVENITY®

EVENITY® is indicated for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple... Read Morerisk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy.  
The anabolic effect of EVENITY® wanes after 12 monthly doses of therapy. Therefore, the duration of EVENITY® use should be limited to 12 monthly doses. If osteoporosis therapy remains warranted, continued therapy with an antiresorptive agent should be considered.  Close

Indication for Prolia

Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple... Read More risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, Prolia reduces the incidence of vertebral, nonvertebral, and hip fractures.  Close

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For the treatment of postmenopausal women with osteoporosis at high risk for fracture

The 2020 AACE guidelines for postmenopausal
osteoporosis include recommendations for both anabolics and
antiresorptives as initial therapy options for appropriate
patients1

AACE stratification criteria for fracture risk and treatment recommendations1

VERY HIGH RISK FOR FRACTURE:

  • Had a recent fracture (eg, within the past 12 months)
  • Had fracture while on approved therapy for osteoporosis
  • Had fractures while on drugs causing skeletal harm
  • Experienced multiple fractures
  • Very low T-score (eg, less than -3.0)
  • High risk for falls or history of injurious falls
  • Very high fracture probability per FRAX® (eg, > 30% major osteoporotic fracture, > 4.5% hip)

HIGH RISK FOR FRACTURE:

Consider patients who have been diagnosed with osteoporosis but aren’t at very high risk to be high risk.

  • T-score -2.5 or below in the lumbar spine, femoral neck, total proximal femur, or 1/3 radius
  • Low-trauma spine or hip fracture (regardless of bone mineral density)
  • T-score between -1.0 and -2.5 and a fragility fracture of proximal humerus, pelvis, or distal forearm
  • T-score between -1.0 and -2.0 and high FRAX® (or if available, TBS-adjusted FRAX®) fracture probability based on country-specific thresholds
ENDO and NAMS PMO management guidelines also offer criteria for stratifying patients according to fracture risk and recommend individualized treatment

Visit the PMO Portal to watch Michael McClung, MD and Dr Susan Bukata, MD discuss osteoporosis guidelines offering criteria for stratifying patients according to fracture risk

AACE = American Association of Clinical Endocrinologists; ENDO = Endocrine Society; FRAX® = fracture risk assessment tool; NAMS = North American Menopause Society; PMO= postmenopausal osteoporosis; TBS = trabecular bone score.

FRAX® is a trademark owned by the International Osteoporosis Foundation.

*Therapies listed are also recommended for patients unable to use oral therapies.

Patients requiring medication with spine-specific efficacy.

2020 AACE guidelines recommend EVENITY® and Prolia®
as initial therapy options for appropriate patients with PMO1
EVENITY® is recommended as initial therapy for use in appropriate patients at very high fracture risk and for those unable to use oral therapy.

Do you have patients ready for EVENITY® treatment?

Prolia® is recommended as initial therapy for use in appropriate patients at high fracture risk and very high fracture risk and for those unable to use oral therapy.

Do you have patients ready for Prolia® treatment?

A drug holiday is not recommended for denosumab, and treatment should be continued for as long as clinically appropriate.

The benefit of building bone with an anabolic

As a class, anabolics stimulate bone formation and improve degraded bone microarchitecture1,2

AACE guidelines recognize that anabolic agents may be preferable for patients at very high risk of fracture as initial therapy.1

Who are anabolics for?

AACE guidelines currently recommend an anabolic for women with postmenopausal osteoporosis if they

  • Are unable to use oral therapy and as initial therapy for patients at very high risk for fracture

What does the treatment sequence look like?

Current AACE guidelines recommend therapy with an antiresorptive agent upon discontinuation of an anabolic agent in order to prevent loss of BMD and fracture efficacy

Building bone with an anabolic may help provide patients with a strong foundation.3

EVENITY® is the first and only anabolic that works differently with a dual effect.

EVENITY® works to increase bone formation and to a lesser extent decrease resorption.

Building bone with EVENITY® may help provide patients with a strong foundation
AACE = American Association of Clinical Endocrinologists; BMD = bone mineral density; PMO = postmenopausal osteoporosis; MOA = mechanism of action.
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IMPORTANT SAFETY INFORMATION FOR EVENITY®

POTENTIAL RISK OF MYOCARDIAL INFARCTION, STROKE, AND CARDIOVASCULAR DEATH

EVENITY® may increase the risk of myocardial infarction, stroke and cardiovascular death.

IMPORTANT SAFETY INFORMATION FOR PROLIA®

SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE:

Patients with advanced chronic kidney disease are at greater risk of severe hypocalcemia

IMPORTANT SAFETY INFORMATION FOR EVENITY®

POTENTIAL RISK OF MYOCARDIAL INFARCTION, STROKE, AND CARDIOVASCULAR DEATH

EVENITY® may increase the risk of myocardial infarction, stroke and cardiovascular death. EVENITY® should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year. Consider whether the benefits outweigh the risks in patients with other cardiovascular risk factors. Monitor for signs and symptoms of myocardial infarction and stroke and instruct patients to seek prompt medical attention if symptoms occur. If a patient experiences a myocardial infarction or stroke during therapy, EVENITY® should be discontinued.

In a randomized controlled trial in postmenopausal women, there was a higher rate of major adverse cardiac events (MACE), a composite endpoint of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke, in patients treated with EVENITY® compared to those treated with alendronate.

Contraindications: EVENITY® is contraindicated in patients with hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating therapy with EVENITY®. EVENITY® is contraindicated in patients with a history of systemic hypersensitivity to romosozumab or to any component of the product formulation. Reactions have included angioedema, erythema multiforme, and urticaria.

Hypersensitivity: Hypersensitivity reactions, including angioedema, erythema multiforme, dermatitis, rash, and urticaria have occurred in EVENITY®-treated patients. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of EVENITY®.

Hypocalcemia: Hypocalcemia has occurred in patients receiving EVENITY®. Correct hypocalcemia prior to initiating EVENITY®. Monitor patients for signs and symptoms of hypocalcemia, particularly in patients with severe renal impairment or receiving dialysis. Adequately supplement patients with calcium and vitamin D while on EVENITY®.

Osteonecrosis of the Jaw (ONJ): ONJ, which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, and has been reported in patients receiving EVENITY®. A routine oral exam should be performed by the prescriber prior to initiation of EVENITY®. Concomitant administration of drugs associated with ONJ (chemotherapy, bisphosphonates, denosumab, angiogenesis inhibitors, and corticosteroids) may increase the risk of developing ONJ. Other risk factors for ONJ include cancer, radiotherapy, poor oral hygiene, pre-existing dental disease or infection, anemia, and coagulopathy.

For patients requiring invasive dental procedures, clinical judgment should guide the management plan of each patient. Patients who are suspected of having or who develop ONJ should receive care by a dentist or an oral surgeon. In these patients, dental surgery to treat ONJ may exacerbate the condition. Discontinuation of EVENITY® should be considered based on benefit-risk assessment.

Atypical Femoral Fractures: Atypical low-energy or low trauma fractures of the femoral shaft have been reported in patients receiving EVENITY®. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated.

During EVENITY® treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be evaluated to rule out an incomplete femur fracture. Interruption of EVENITY® therapy should be considered based on benefit-risk assessment.

Adverse Reactions: The most common adverse reactions (≥ 5%) reported with EVENITY® were arthralgia and headache.

EVENITY® is a humanized monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity.

Please see EVENITY® full Prescribing Information, including Medication Guide.

IMPORTANT SAFETY INFORMATION FOR PROLIA®

SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE:

Patients with advanced chronic kidney disease are at greater risk of severe hypocalcemia following Prolia (denosumab) administration. Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported. The presence of chronic kidney disease-mineral bone disorder (CKD-MBD) markedly increases the risk of hypocalcemia. Prior to initiating Prolia in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with Prolia in these patients should be supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD.

Contraindications: Prolia® is contraindicated in patients with hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating Prolia®. Prolia® is contraindicated in women who are pregnant and may cause fetal harm. In women of reproductive potential, pregnancy testing should be performed prior to initiating treatment with Prolia®. Prolia® is contraindicated in patients with a history of systemic hypersensitivity to any component of the product. Reactions have included anaphylaxis, facial swelling and urticaria.

Severe Hypocalcemia and Mineral Metabolism Changes: Prolia can cause severe hypocalcemia and fatal cases have been reported. Pre-existing hypocalcemia must be corrected prior to initiating therapy with Prolia. Adequately supplement all patients with calcium and vitamin D. In patients without advanced chronic kidney disease who are predisposed to hypocalcemia and disturbances of mineral metabolism (e.g. treatment with other calcium-lowering drugs), assess serum calcium and mineral levels (phosphorus and magnesium) 10 to 14 days after Prolia injection.

Same Active Ingredient: Prolia® contains the same active ingredient (denosumab) found in XGEVA®. Patients receiving Prolia® should not receive XGEVA®.

Hypersensitivity: Clinically significant hypersensitivity including anaphylaxis has been reported with Prolia®. Symptoms have included hypotension, dyspnea, throat tightness, facial and upper airway edema, pruritus and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of Prolia®.

Osteonecrosis of the Jaw (ONJ): ONJ, which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, and has been reported in patients receiving Prolia®. An oral exam should be performed by the prescriber prior to initiation of Prolia®. A dental examination with appropriate preventive dentistry is recommended prior to treatment in patients with risk factors for ONJ such as invasive dental procedures, diagnosis of cancer, concomitant therapies (e.g. chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, and co-morbid disorders. Good oral hygiene practices should be maintained during treatment with Prolia®. The risk of ONJ may increase with duration of exposure to Prolia®.

For patients requiring invasive dental procedures, clinical judgment should guide the management plan of each patient. Patients who are suspected of having or who develop ONJ should receive care by a dentist or an oral surgeon. Extensive dental surgery to treat ONJ may exacerbate the condition. Discontinuation of Prolia® should be considered based on individual benefit-risk assessment.

Atypical Femoral Fractures: Atypical low-energy, or low trauma fractures of the shaft have been reported in patients receiving Prolia®. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with antiresorptive agents.

During Prolia® treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be evaluated to rule out an incomplete femur fracture. Interruption of Prolia® therapy should be considered, pending a risk/benefit assessment, on an individual basis.

Multiple Vertebral Fractures (MVF) Following Discontinuation of Prolia® Treatment: Following discontinuation of Prolia® treatment, fracture risk increases, including the risk of multiple vertebral fractures. New vertebral fractures occurred as early as 7 months (on average 19 months) after the last dose of Prolia®. Prior vertebral fracture was a predictor of multiple vertebral fractures after Prolia® discontinuation. Evaluate an individual’s benefit/risk before initiating treatment with Prolia®. If Prolia® treatment is discontinued, patients should be transitioned to an alternative antiresorptive therapy.

Serious Infections: In a clinical trial (N = 7808), serious infections leading to hospitalization were reported more frequently in the Prolia® group than in the placebo group. Serious skin infections, as well as infections of the abdomen, urinary tract and ear, were more frequent in patients treated with Prolia®.

Endocarditis was also reported more frequently in Prolia®-treated patients. The incidence of opportunistic infections and the overall incidence of infections were similar between the treatment groups. Advise patients to seek prompt medical attention if they develop signs or symptoms of severe infection, including cellulitis.

Patients on concomitant immunosuppressant agents or with impaired immune systems may be at increased risk for serious infections. In patients who develop serious infections while on Prolia®,  prescribers should assess the need for continued Prolia® therapy.

Dermatologic Adverse Reactions: Epidermal and dermal adverse events such as dermatitis, eczema and rashes occurred at a significantly higher rate with Prolia® compared to placebo. Most of these events were not specific to the injection site. Consider discontinuing Prolia® if severe symptoms develop.

Musculoskeletal Pain: Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking Prolia®.  Consider discontinuing use if severe symptoms develop.

Suppression of Bone Turnover: Prolia® resulted in significant suppression of bone remodeling as evidenced by markers of bone turnover and bone histomorphometry. The significance of these findings and the effect of long-term treatment are unknown. Monitor patients for consequences, including ONJ, atypical fractures, and delayed fracture healing.

Adverse Reactions: The most common adverse reactions (>5% and more common than placebo) are back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis. Pancreatitis has been reported with Prolia®.

The overall incidence of new malignancies was 4.3% in the placebo group and 4.8% in the Prolia® group. A causal relationship to drug exposure has not been established. Denosumab is a human monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity.

Please see Prolia® full Prescribing Information, including Medication Guide.

References:

  1. 1. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists/American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis—2020 Update. Endocr Pract. 2020;26(suppl 1):1-46.
  2. 2. Cosman F, Dempster DW. Anabolic agents for postmenopausal osteoporosis: how do you choose? Curr Osteoporos Rep. 2021;19:189-205.
  3. 3. EVENITY® (romosozumab-aqqg) prescribing information, Amgen.