5 INDICATIONS

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 osteoporosis, Prolia® reduces the incidence of vertebral, See More

FOR THE TREATMENT OF GLUCOCORTICOID-INDUCED OSTEOPOROSIS IN MEN AND WOMEN AT HIGH RISK FOR FRACTURE

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Prolia® helps you treat patients at high risk for fracture with 5 indications

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Are your patients on glucocorticoid therapy at high risk for fracture?

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Alison depends on daily glucocorticoids.
  • She recently started glucocorticoid therapy for rheumatoid arthritis (6-month course of prednisone, 10 mg/day)
  • Recently diagnosed with osteoporosis, not on therapy
  • She has no known history of fracture
  • Recent DXA results: T-score -2.7 in total hip
  • Insurance type: Commercial
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Hypothetical patients.

Hank started taking more glucocorticoid therapy.
  • For chronic obstructive pulmonary disease, he started taking a daily dosage equivalent to 7.5 mg prednisone over the past 6 months
  • For osteoporosis, he takes risedronate (35 mg/week)
  • He has a history of fracture (vertebral)
  • Recent DXA results: T-score -2.5 in lumbar spine
  • Insurance type: Medicare Part B

Hypothetical patients.

Indication

Prolia® is indicated for the treatment of glucocorticoid-induced osteoporosis in men and women at high risk of fracture who are either initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and expected to remain on glucocorticoids for at least 6 months. High risk of fracture is defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy.

See what an impact glucocorticoid therapy may have on your patients' bones

What impact could glucocorticoid therapy have on your patients' bones?

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Patients on chronic glucocorticoid therapy have a higher fracture risk than those not taking glucocorticoid therapy1,2

  • Rapid bone mineral density (BMD) loss often begins in the first 6 to 12 months of glucocorticoid therapy1,3
  • Relative risk of fracture increases up to 17-fold at the spine and 7-fold at the hip among patients with continuous glucocorticoid use compared to nonusers1,*

*Retrospective review of patients using oral glucocorticoids > 10 mg/day for 90 days.

See the results of Prolia®  vs risedronate in a head-to-head BMD study

For the treatment of glucocorticoid-induced osteoporosis in men and women at high risk for fracture

Prolia® has been evaluated in a head-to-head BMD study of patients with glucocorticoid-induced osteoporosis 4

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12-Month Primary Analysis5

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Patient Randomization (1:1)5
  • Either an oral daily bisphosphonate (active control, risedronate 5 mg once daily) (n = 397), or
  • Prolia® 60 mg subcutaneously once every 6 months (n = 398) for one year
  • All patients were supplemented with daily calcium and vitamin D
Primary Endpoint:
  • Noninferiority to risedronate for percent change from baseline in lumbar spine BMD at 12 months6
Select Secondary Endpoints:
  • Superiority over risedronate for percent change from baseline in lumbar spine and total hip BMD at 12 months6
Select Exploratory Endpoint:
  • Percent change in lumbar spine BMD at 6 months6
Study Design6
  • 2-year, randomized, multicenter, double-blind, parallel-group, active-controlled study
  • 795 patients (70% women and 30% men) aged 20 to 94 years (mean age of 63.1 years)
Treatment Subpopulations5
  • Patients were either initiating (GC-I) or continuing (GC-C) glucocorticoid treatment with 7.5 mg/day oral prednisone (or equivalent):
    • - GC-I subpopulation: < 3 months prior to study enrollment and planning to continue glucocorticoids for a total of at least 6 months (n = 290)
    • - GC-C subpopulation: 3 months prior to study enrollment and planning to continue glucocorticoids for a total of at least 6 months (n = 505)
  • Some patients were also taking biologic or nonbiologic immunosuppressants
Inclusion Criteria5
  • Between 18 and 50 years of age with a history of osteoporotic fracture, or
  • 50 years of age (in the GC-C subpopulation) with a baseline BMD T-score of:
    • -< -2.0 at the lumbar spine, total hip, or femoral neck, or
    • -< -1.0 at the lumbar spine, total hip, or femoral neck and a history of osteoporotic fracture

In lumbar spine BMD, Prolia® demonstrated noninferiority and superiority at 12 months vs risedronate5

Prolia® delivers BMD gains to help you and your patients fight against glucocorticoid-induced osteoporosis1

Initiating Glucocorticoid Therapy

 

 

Q6M = every 6 months; QD = every day; BMD = bone mineral density; BL = baseline.

Prolia® delivered significantly greater improvements in lumbar spine BMD as early as 6 months5

  • Percentage change from baseline in lumbar spine BMD with Prolia® vs risedronate in patients initiating (1.9% vs 0.5%) glucocorticoids5

BMD data results are not meant to imply fracture efficacy and should not be extrapolated to predict differences in fracture efficacy. Head-to-head fracture studies have not been conducted.

*Primary endpoint.

†95% CI 2.0% - 3.9%, p < 0.001.

‡Based on ANCOVA model adjusting for treatment, gender, baseline BMD value, machine type, and baseline BMD value-by-machine type interaction; additionally, includes duration of prior glucocorticoid use (< 12 months versus 12 months) for GC-C subpopulation.

Continuing Glucocorticoid Therapy

 

Q6M = every 6 months; QD = every day; BMD = bone mineral density; BL = baseline.

Prolia® delivered significantly greater improvements in lumbar spine BMD as early as 6 months6

  • Percentage change from baseline in lumbar spine BMD with Prolia® vs risedronate in patients continuing glucocorticoids (3.1% vs 2.0%)5

BMD data results are not meant to imply fracture efficacy and should not be extrapolated to predict differences in fracture efficacy. Head-to-head fracture studies have not been conducted.

*Primary endpoint.

†95% CI 2.0% - 3.9%, p < 0.001.

‡Based on ANCOVA model adjusting for treatment, gender, baseline BMD value, machine type, and baseline BMD value-by-machine type interaction; additionally, includes duration of prior glucocorticoid use (< 12 months versus 12 months) for GC-C subpopulation.

Prolia® demonstrated superiority in total hip BMD at 12 months vs risedronate6

Initiating Glucocorticoid Therapy

 

BL = baseline; BMD = bone mineral density.

  • Percentage change from baseline in total hip BMD vs risedronate (1.7% vs 0.2% in GC-I population; p < 0.001)5

BMD data results are not meant to imply fracture efficacy and should not be extrapolated to predict differences in fracture efficacy. Head-to-head fracture studies have not been conducted.

*95% CI 0.8% - 2.1%, p < 0.001.

†Based on ANCOVA model adjusting for treatment, gender, baseline BMD value, machine type, and baseline BMD value-by-machine type interaction; additionally includes duration of prior glucocorticoid use (< 12 months versus 12 months) for GC-C subpopulation.

Continuing Glucocorticoid Therapy

 

BMD data results are not meant to imply fracture efficacy and should not be extrapolated to predict differences in fracture efficacy. Head-to-head fracture studies have not been conducted.

*95% CI 0.8% - 2.1%, p < 0.001.

†Based on ANCOVA model adjusting for treatment, gender, baseline BMD value, machine type, and baseline BMD value-by-machine type interaction; additionally includes duration of prior glucocorticoid use (< 12 months versus 12 months) for GC-C subpopulation.

Prolia® safety profile in patients with glucocorticoid-induced osteoporosis (GIOP)1

The incidence of serious adverse events was similar for both Prolia® and risedronate groups (16% and 17%)1

ADVERSE REACTIONS IN 2% OF PATIENTS WITH GLUCOCORTICOID-INDUCED
OSTEOPOROSIS AND MORE FREQUENTLY WITH PROLIA®1

Risedronate (N = 384)
n (%) 		Prolia® (denosumab) (N = 394)
n (%)
Back pain 17 (4.4) 18 (4.6)
Hypertension 13 (3.4) 15 (3.8)
Bronchitis 11 (2.9) 15 (3.8)
Headache 7 (1.8) 14 (3.6)
Dyspepsia 10 (2.6) 12 (3.0)
Urinary tract infection 8 (2.1) 12 (3.0)
Abdominal pain upper 7 (1.8) 12 (3.0)
Upper respiratory tract infection 10 (2.6) 11 (2.8)
Constipation 6 (1.6) 11 (2.8)
Vomiting 6 (1.6) 10 (2.5)
Dizziness 8 (2.1) 9 (2.3)
Fall 7 (1.8) 8 (2.0)
Polymyalgia rheumatica* 1 (0.3) 8 (2.0)

*Events of worsening of underlying polymyalgia rheumatica.

  • Osteonecrosis of the Jaw (ONJ): No cases of ONJ were reported1
  • Atypical Femoral Fractures (AFF): AFF were reported in 1 patient treated with Prolia®. The duration of Prolia® exposure to time of AFF diagnosis was at 8.0 months1
  • Serious Infections: Serious infection was reported in 15 patients (3.9%) in the active-control group and 17 patients (4.3%) in the Prolia® group1
  • Dermatologic Reactions: Epidermal and dermal adverse events (such as dermatitis, eczema, and rashes) were reported in 16 patients (4.2%) in the active-control group and 15 patients (3.8%) in the Prolia® group1

What dosing schedule should you follow for patients on Prolia®?

For the treatment of glucocorticoid-induced osteoporosis in men and women at high risk for fracture

Be confident your Prolia® patients are receiving 6 months of therapy with each injection1

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Single-use prefilled 1 mL syringe

The image above is for illustration purposes only and represents a snapshot in time. Actual dosing and duration of a particular patient's therapy should be based upon the product's approved labeling and the independent clinical decision of the provider.

Important Safety Information

Following discontinuation of Prolia® treatment, fracture risk increases, including the risk of multiple vertebral fractures. Evaluate an individual's benefit/risk before initiating treatment with Prolia®. If Prolia® treatment is discontinued, consider transitioning to an alternative anti-resorptive therapy.

Prolia® is administered as 1 shot every 6 months1

  • 60 mg subcutaneous injection in the upper arm, upper thigh, or abdomen by a healthcare professional
    • – Pre-existing hypocalcemia must be corrected prior to initiating therapy with Prolia®
    • – Adequately supplement all patients with calcium and vitamin D
    • – Pregnancy must be ruled out prior to administration of Prolia®
    • – Multiple vertebral fractures have been reported following Prolia® discontinuation
  • As a subcutaneous injection, Prolia® does not undergo first-pass metabolism7
  • May lessen patient pill burden

IMPORTANT SAFETY INFORMATION

SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE:

Patients with advanced chronic kidney disease are at greater risk of severe hypocalcemia following Prolia 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 to14 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, consider transitioning 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: In the same clinical trial in women with postmenopausal osteoporosis, 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) in women with postmenopausal osteoporosis are back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis. The most common adverse reactions (>5% and more common than placebo) in men with osteoporosis are back pain, arthralgia, and nasopharyngitis. Pancreatitis has been reported with Prolia®.

In women with postmenopausal osteoporosis, the overall incidence of new malignancies was 4.3% in the placebo group and 4.8% in the Prolia® group. In men with osteoporosis, new malignancies were reported in no patients in the placebo group and 4 (3.3%) patients in the Prolia® group. A causal relationship to drug exposure has not been established.

The most common adverse reactions (>3% and more common than active-control group) in patients with glucocorticoid-induced osteoporosis are back pain, hypertension, bronchitis, and headache.

The most common (per patient incidence 10%) adverse reactions reported with Prolia® in patients with bone loss receiving ADT for prostate cancer or adjuvant AI therapy for breast cancer are arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials. Additionally, in Prolia®-treated men with nonmetastatic prostate cancer receiving ADT, a greater incidence of cataracts was observed.

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.

IMPORTANT SAFETY INFORMATION
SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE: Patients with advanced chronic kidney disease are at greater risk of severe hypocalcemia following Prolia 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
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References: 1. Weinstein RS. Glucocorticoid-induced osteoporosis and osteonecrosis. Endocrinol Metab Clin North Am. 2012;41:595-611. 2. Steinbuch M, Youket TE, Cohen S. Oral glucocorticoid use is associated with an increased risk of fracture. Osteoporos Int. 2004;15:323-328. 3. Van Staa TP, Laan RF, Barton IP, et al. Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum. 2003;48(11):3224-3229. 4. Prolia® (denosumab) prescribing information, Amgen. 5. Saag KG, Wagman RB, Geusens P, et al. Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study. Lancet Diabetes Endocrinol. 2018;6:445-454. 6. Data on file, Amgen. 2016. 7. Turner PV, Brabb T, Pekow C, Vasbinder MA. Administration of substances to laboratory animals: routes of administration and factors to consider. J Am Assoc Lab Anim Sci. 2011;50:600–613.