Is anifrolumab-fnia (Saphnelo) medically necessary for a patient with progressive motor decline, spasticity, and hyperreflexia due to genetic variants in the FIG4 and UGT1A1 genes, without a diagnosis of systemic lupus erythematosus (SLE)?

Anifrolumab is NOT Medically Necessary for This Patient

Anifrolumab-fnia (Saphnelo) is not medically necessary and should be denied for this patient because the drug is FDA-approved exclusively for moderate-to-severe systemic lupus erythematosus (SLE), and this patient does not have SLE. 1, 2

Rationale for Denial

1. Absence of SLE Diagnosis

• This 18-month-old male presents with progressive motor decline, spasticity, hyperreflexia, and white matter lesions on MRI, with genetic variants in FIG4 and UGT1A1 genes 3
• The patient lacks any diagnostic criteria for SLE, including absence of autoantibodies (ANA, anti-dsDNA, anti-Sm, antiphospholipid antibodies) that are required before initiating anifrolumab therapy 4, 3
• The clinical presentation is consistent with a genetic leukodystrophy or neurometabolic disorder, not an autoimmune inflammatory condition 4

2. FDA-Approved Indication is Specific to SLE

• Anifrolumab is a type I interferon receptor antagonist approved only for adult patients with moderate-to-severe SLE who are receiving standard therapy 1, 2
• The mechanism of action targets type I interferon-mediated pathways that are central to SLE pathogenesis, not genetic neurological disorders 1, 5
• Clinical trials (TULIP-1 and TULIP-2) enrolled only patients meeting SLE classification criteria with positive autoantibodies and active disease despite standard SLE therapy 5, 2

3. Standard of Care Requirements Not Met

• Anifrolumab requires concurrent standard SLE treatment including glucocorticoids, antimalarials (hydroxychloroquine), or immunosuppressants (azathioprine, methotrexate, mycophenolate) 3, 2
• This patient has already failed IVIG and systemic steroids, but these were used empirically for an undefined neurological condition, not as part of an SLE treatment regimen 4, 3
• The lack of response to steroids and IVIG further supports that this is not an inflammatory autoimmune process amenable to interferon blockade 4

4. Treatment is Experimental for Non-SLE Conditions

• All indications outside of SLE are considered experimental, investigational, and unproven 3
• While case reports exist for cutaneous lupus erythematosus and dermatomyositis, there is zero evidence supporting anifrolumab use in genetic leukodystrophies or neurometabolic disorders 6
• The patient's genetic variants (heterozygous FIG4 associated with Charcot-Marie-Tooth disease type 4J and heterozygous UGT1A1 associated with hyperbilirubinemia syndromes) represent distinct pathophysiological mechanisms unrelated to type I interferon dysregulation 4

Appropriate Next Steps for This Patient

Diagnostic Workup

• Complete the leukodystrophy panel and pursue additional genetic testing to identify the underlying cause of progressive white matter disease 4
• Obtain metabolic screening including very long chain fatty acids, lysosomal enzyme panel, and amino/organic acids to exclude treatable metabolic disorders 4
• Consider repeat brain MRI with spectroscopy to characterize white matter lesions and assess for specific patterns associated with genetic leukodystrophies 4

Appropriate Therapeutic Considerations

• Referral to pediatric neurology and medical genetics for management of suspected genetic leukodystrophy 4
• Symptomatic management of spasticity with physical therapy, baclofen, or botulinum toxin injections 4
• Supportive care addressing nutritional needs, seizure management if present, and developmental support 4

Safety Concerns if Inappropriately Used

• Anifrolumab increases risk of herpes zoster (7.2% in trials) and respiratory infections (bronchitis in 12.2%), which would be particularly dangerous in a pediatric patient with progressive neurological disease 2, 7
• The drug has not been studied in pediatric populations, and safety data are limited to adults aged 18-70 years 5, 2
• Immunosuppression from anifrolumab could mask or worsen infectious complications in a child with an undefined neurological disorder 4, 3