Is Evenity (Romosozumab) medically necessary for a postmenopausal female with age-related osteoporosis and no current pathological fracture?

Medical Necessity Determination for Evenity (Romosozumab)

DETERMINATION: NOT MEDICALLY NECESSARY

Evenity (romosozumab) is not medically necessary for this 71-year-old postmenopausal female with age-related osteoporosis because she does not meet the established criteria for very high fracture risk and has not attempted first-line bisphosphonate therapy, which is the guideline-recommended initial treatment. 1, 2

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Rationale for Denial

Critical Deficiency: No Trial of First-Line Therapy

• The American College of Physicians strongly recommends bisphosphonates as first-line pharmacologic treatment for postmenopausal women with osteoporosis (high-certainty evidence), with romosozumab reserved only for patients at very high fracture risk who have failed or are intolerant to other therapies 1

• Documentation shows the patient was "offered Fosamax" on 1/14/2025 but there is no evidence of an actual trial, failure, or documented intolerance to bisphosphonate therapy 2

• Bisphosphonates have the most favorable balance among benefits, harms, patient values, and cost compared to all other osteoporosis medications 1

Patient Does Not Meet "Very High Risk" Criteria

Fracture Risk Assessment:

• 10-year major osteoporotic fracture risk: 15% (below the 20% threshold typically defining very high risk) 1, 2
• 10-year hip fracture risk: 7.0% (elevated but not meeting very high risk criteria) 1
• No history of fragility fractures documented (a key criterion for romosozumab approval) 2, 3
• No recent major fracture within the past 2 years (the primary indication for romosozumab as first-line therapy) 4

Clinical Trial Context:

• Romosozumab clinical trials enrolled postmenopausal females with mean age >74 years who had very high fracture risk, representing only an estimated 10% of females over 50 years in the U.S. population 1, 2
• This patient's risk profile does not align with the populations studied in pivotal romosozumab trials 5, 3

Bone Mineral Density Analysis

T-Scores from 3/24/2025 DEXA:

• Lumbar spine (L1-L4 total): T-score -2.2 (osteoporosis range but not severe) 1
• Femoral neck: T-score -2.8 (osteoporosis) 1
• Total hip: T-score -2.4 (osteoporosis) 1

While these T-scores confirm osteoporosis diagnosis, they do not represent the severe osteoporosis (typically T-score ≤-3.0 or lower with fractures) that would justify bypassing first-line bisphosphonate therapy 2

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Critical Safety Concerns with Romosozumab

FDA Boxed Warning

The FDA label carries a BLACK BOX WARNING: "EVENITY may increase the risk of myocardial infarction, stroke, and cardiovascular death" 6

Specific contraindications include:

• Should not be initiated in patients who have had myocardial infarction or stroke within the preceding year 6
• Requires careful consideration in patients with cardiovascular risk factors 6

Cardiovascular Risk Data

• Romosozumab increased cardiovascular events compared to alendronate with a hazard ratio of 1.9 (95% CI: 1.1-3.1) 1, 2
• During year 1 of the ARCH trial, positively adjudicated serious cardiovascular adverse events occurred more often with romosozumab (2.5%) than with alendronate (1.9%) 3
• The American College of Rheumatology conditionally recommends against using romosozumab due to risk of myocardial infarction, stroke, or death except in patients intolerant of other agents 2

No cardiovascular risk assessment is documented in the submitted materials for this 71-year-old patient 6

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Cost-Effectiveness Analysis

• Romosozumab costs approximately $5,574 annually compared to $39-$2,700 for bisphosphonates 2
• Generic bisphosphonate formulations are available and should be prescribed when possible 1
• No cost-effectiveness analyses support romosozumab as first-line therapy in patients who have not tried bisphosphonates 2

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Guideline-Based Treatment Algorithm

Step 1: Initiate First-Line Bisphosphonate Therapy

The patient should begin oral bisphosphonate therapy (e.g., alendronate 70 mg weekly or risedronate) with:

• Adequate calcium (1000-1200 mg daily) and vitamin D (800-1000 IU daily) supplementation 1, 6
• Proper administration instructions to minimize gastrointestinal adverse effects 1
• Treatment duration of 3-5 years with periodic reassessment 1

Step 2: Monitor Response and Tolerance

Bisphosphonates should be continued unless the patient:

• Sustains an osteoporotic fracture despite adequate therapy 2
• Develops documented bisphosphonate intolerance or contraindication 2
• Shows progressive bone loss on serial DEXA scans despite adherence 1

Step 3: Consider Romosozumab Only After Bisphosphonate Failure

Romosozumab may be appropriate if:

• Patient experiences a fragility fracture while on adequate bisphosphonate therapy 2, 3
• Patient has documented contraindication to or intolerance of bisphosphonates 1
• Patient develops very high fracture risk (e.g., recent major fracture, T-score ≤-3.5 with multiple risk factors) 2, 4

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Evidence Quality Assessment

Highest Quality Evidence Supporting Bisphosphonates First

• The 2023 American College of Physicians Living Clinical Guideline provides HIGH to MODERATE certainty evidence that bisphosphonates reduce hip fractures (RR 0.64,95% CI 0.50-0.82) and clinical vertebral fractures (54-68% risk reduction) 1

• The 2024 Mayo Clinic Proceedings guideline confirms bisphosphonates as foundational therapy with strong evidence for fracture reduction 1

Romosozumab Evidence Limitations

• Romosozumab evidence is rated as MODERATE to LOW certainty for most outcomes 1
• No long-term data beyond 24 months of sequential therapy 1
• Romosozumab requires mandatory transition to antiresorptive therapy after 12 months, as the anabolic effect wanes 6, 4

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Required Documentation for Future Approval

If the patient is reconsidered for romosozumab after appropriate bisphosphonate trial, the following must be documented:

1. Minimum 12-month trial of oral bisphosphonate at therapeutic doses with documented adherence 2
2. Evidence of treatment failure (new fracture or progressive bone loss on DEXA) OR documented contraindication/intolerance 2
3. Comprehensive cardiovascular risk assessment ruling out recent MI/stroke and evaluating cardiovascular risk factors 6
4. Correction of any hypocalcemia prior to initiation 6
5. Plan for sequential antiresorptive therapy after 12 months of romosozumab 6, 3

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Common Pitfalls to Avoid

• Do not bypass first-line bisphosphonate therapy based solely on T-scores without documented treatment failure 2
• Do not assume patient preference or physician preference alone justifies deviation from evidence-based treatment algorithms 1
• Do not initiate romosozumab without cardiovascular risk stratification given the FDA boxed warning 6
• Do not continue romosozumab beyond 12 monthly doses, as efficacy wanes and requires transition to antiresorptive therapy 6

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Recommended Course of Action

DENY the request for Evenity (romosozumab) and recommend:

1. Initiate oral bisphosphonate therapy (alendronate 70 mg weekly or equivalent) with calcium and vitamin D supplementation 1, 2
2. Provide fall prevention counseling and encourage weight-bearing exercise 1
3. Repeat DEXA scan in 1-2 years to assess treatment response 1
4. Reconsider romosozumab only if patient sustains fracture on bisphosphonate therapy or develops documented contraindication/intolerance 2

This approach prioritizes patient safety, follows evidence-based guidelines, and ensures appropriate resource utilization while maintaining the option for romosozumab escalation if clinically warranted after first-line therapy trial 1, 2