Medical Necessity Review: Vutrisiran Continuation
Recommendation: Deny Continuation of Vutrisiran
Based on the available clinical evidence, continuation of vutrisiran (Amvuttra) is NOT medically necessary for this patient, as she has failed to demonstrate a beneficial treatment response compared to baseline after 9 months of therapy. 1
Rationale for Non-Continuation
Objective Evidence of Treatment Failure
The Norfolk Quality of Life scale worsened from 47 at baseline (March 2024) to 56 at 9-month follow-up (December 2024), representing a 9-point deterioration rather than improvement 1
The American College of Cardiology guidelines explicitly require demonstration of a beneficial response to treatment with TTR silencers like vutrisiran, which must show stabilization or reversal of disease progression relative to pretreatment baseline 1
The Aetna continuation criteria (CPB 0939) specifically mandate "demonstrated beneficial response to treatment with the requested medication compared to baseline" using measures including Norfolk QoL-DN total score 1
Subjective Clinical Deterioration
The patient reports persistent severe neuropathic pain in legs, feet, hands, and right hip occurring 5 out of 7 nights, with this pattern emerging over the past 3 months while on vutrisiran 1
The patient explicitly expressed uncertainty about vutrisiran efficacy, stating "it has not alleviated her neuropathy" 1
New symptom onset (right hip pain radiating to buttock) occurred during vutrisiran treatment, requiring nightly diclofenac use for 3 months 1
Treatment Duration Adequate for Assessment
The patient has completed 4 doses of vutrisiran over 9 months (March 2024 through December 2024), which represents adequate time to assess treatment response 2, 3
Clinical trial data demonstrate that vutrisiran shows significant improvements in Norfolk QoL-DN scores by 9 months in treatment responders 3, 4
The pivotal HELIOS-A study showed mean improvements (not worsening) in Norfolk QoL-DN scores at both 9 and 18 months in vutrisiran-treated patients 3
Critical Missing Information
Vitamin A Supplementation Status
All patients receiving vutrisiran must take daily vitamin A supplementation (3,000 IU recommended daily allowance) as TTR silencers reduce serum vitamin A levels 5, 2
The clinical documentation mentions the patient "is currently taking vitamin A supplements" but does not confirm adherence or dosing 1
Vitamin A deficiency can independently worsen neuropathy symptoms and must be ruled out before definitively attributing treatment failure to vutrisiran 1, 5
Confounding Conditions
The patient has concurrent orthopedic issues (possible bursitis diagnosed by orthopedist, received injection one year ago) that may contribute to pain symptoms 1
Elevated light chains were noted, raising concern for concurrent plasma cell dyscrasia given family history of multiple myeloma, which could cause additional neuropathy 1
The ordered comprehensive blood work (including serum immunofixation electrophoresis, serum protein electrophoresis, kappa lambda free light chains) has not been completed or results not provided 1
Recommended Next Steps Before Final Determination
Documentation Required for Reconsideration
Confirmation of vitamin A supplementation adherence at 3,000 IU daily throughout the entire treatment period 5, 2
Results of the comprehensive blood work ordered at the December 2024 visit, particularly serum immunofixation and free light chains to rule out concurrent plasma cell dyscrasia 1
Cardiology evaluation results to assess for cardiac amyloid involvement, as this can affect prognosis and treatment decisions 5
Ophthalmology evaluation to assess for vitamin A deficiency-related ocular symptoms 2
Alternative Management Considerations
If vitamin A deficiency is confirmed, correcting this deficiency and reassessing after 3 months may be appropriate before permanently discontinuing vutrisiran 5, 2
Aggressive symptomatic management with gabapentin (already prescribed 100 mg nightly) should be optimized; pregabalin or duloxetine are alternative first-line options for neuropathic pain 5
If treatment failure is confirmed after ruling out confounding factors, alternative TTR silencers (patisiran 0.3 mg/kg IV every 3 weeks or inotersen subcutaneous) or TTR stabilizers could be considered 5
Evidence Quality Assessment
Guideline Support for Denial
The American College of Cardiology 2023 expert consensus specifically addresses that TTR silencers should demonstrate beneficial response, and this patient objectively fails to meet this criterion 6, 1
FDA labeling for vutrisiran indicates efficacy in clinical trials but does not mandate continuation in non-responders 2
Clinical Trial Context
In the HELIOS-A trial, vutrisiran demonstrated significant improvements with mean Norfolk QoL-DN score changes of -21.0 points compared to external placebo at 18 months 3, 4
This patient's 9-point worsening in Norfolk QoL-DN score represents progression similar to untreated disease rather than treatment response 1, 3
Patients with earlier disease stage (PND I-II) showed most pronounced benefit, and this patient was Stage 1 at baseline, making treatment failure more concerning 7, 4
Common Pitfalls to Avoid
Do not approve continuation based solely on FDA indication without documented treatment response - the indication establishes appropriateness for initiation, not continuation in non-responders 2
Do not confuse "continuity of care" with medical necessity - prior authorization does not obligate continued coverage without demonstrated benefit 1
Do not overlook vitamin A supplementation non-adherence as a reversible cause of apparent treatment failure - this must be confirmed before final denial 5, 2