Is Tocilizumab (Actemra) injection every 2 weeks medically necessary for a patient with Adult-Onset Still's Disease (AOSD) and Inflammatory Polyarthropathy, who experiences return of symptoms when spaced out to every 4 weeks?

Medical Necessity Review: Tocilizumab for Adult-Onset Still's Disease

Direct Recommendation

Tocilizumab (Actemra) at 8 mg/kg every 2 weeks is medically necessary for this patient with refractory Adult-Onset Still's Disease (AOSD) who has demonstrated symptom recurrence with 4-week dosing intervals. The patient meets Aetna criteria for continuation of therapy, though documentation of recent tuberculosis screening must be obtained to fully satisfy all policy requirements.

Criteria Analysis

Prescriber Specialty Requirement

• MET: Patient is under care of rheumatology (documented 2/7/24 and 4/28/25 notes) 1

Initial Approval Criteria

• MET: Patient has previously received multiple biologics and targeted therapies:
  • Failed Ilaris (canakinumab - IL-1 inhibitor)
  • Currently on methotrexate 15mg weekly
  • Previously on hydroxychloroquine (now discontinued)
  • Previously on sulfasalazine
  • High-dose corticosteroids with resultant adrenal insufficiency and cataracts 1

Continuation of Therapy Criteria

• MET: Patient demonstrates positive clinical response:
  • Currently documented as "in remission" on current regimen (2/7/24 note)
  • Stable vital signs throughout infusions (3/11/25)
  • Bilateral wrist synovitis improved compared to active disease state
  • Patient requires every 2-week dosing as symptoms return with 4-week spacing 2, 3, 4, 5, 6

Dosing Appropriateness

• MET: Patient receives 8 mg/kg every 2 weeks (550mg dose suggests ~69kg body weight)
• FDA-approved dosing for RA is 4-8 mg/kg every 4 weeks, with increases based on clinical response
• However, the every 2-week interval is clinically justified based on:
  • Patient's documented symptom recurrence with 4-week spacing
  • Literature supporting more frequent dosing in refractory cases 1, 5
  • One multicenter study specifically used 8 mg/kg every 2 weeks in 10 of 34 patients with refractory AOSD with excellent results 5

ICD-10 Code Coverage

• MET: M06.1 (Adult-Onset Still's Disease) is explicitly covered in the M05.00-M06.9 range per Aetna CPB 0799 1

Critical Gap: Tuberculosis Screening

PARTIALLY MET - REQUIRES DOCUMENTATION:

• Policy requires documented negative TB test within 12 months of initiating therapy for biologic-naïve patients
• Chart notes indicate TB testing was done in 2021 and "due in 2023" with no results provided
• This is a documentation issue, not a clinical contraindication
• Given patient has been on tocilizumab since at least 12/16/24 (per prior authorization history), recent TB screening should exist but was not included in submitted records 1

Clinical Evidence Supporting Tocilizumab in AOSD

Mechanism and Rationale

IL-6 is a key proinflammatory cytokine in AOSD pathogenesis, with serum levels highly elevated in both systemic and polyarticular phenotypes 1, 4. Tocilizumab blocks IL-6 signaling through IL-6 receptor antagonism 1, 2, 3, 4.

Efficacy Data

• Multicenter retrospective study (n=34): Tocilizumab produced rapid and maintained improvement in refractory AOSD patients, with joint manifestations decreasing from 97.1% to 32.4% at 1 year, fever from 58.8% to 5.9%, and median prednisone dose reduced from 13.8 mg/day to 2.5 mg/day 5

• Turkish cohort (n=16): Significant decreases in prednisolone dose, inflammatory markers, and improvement in all clinical complaints; three patients achieved remission and discontinued treatment without relapse 2

• Subcutaneous administration studies: Both weekly and every-2-week subcutaneous dosing showed marked efficacy with rapid defervescence (within 1 day) and normalization of inflammatory markers within 2 weeks 3, 6

Dosing Frequency Justification

While standard RA dosing is every 4 weeks, more frequent dosing (every 2 weeks) has been specifically studied and utilized in refractory AOSD 5. The patient's documented symptom recurrence with 4-week spacing provides clear clinical justification for the every-2-week regimen, which is supported by published literature showing this interval in refractory cases 1, 5.

Home Infusion (S9379) Medical Necessity

Home infusion is medically appropriate for this stable patient:

• Patient has demonstrated tolerance to tocilizumab with stable vital signs throughout infusions (3/11/25 note)
• No acute complications requiring hospital-based monitoring
• Established on therapy since at least 12/16/24
• Home infusion reduces healthcare costs and improves quality of life while maintaining safety 2, 3, 6

Safety Considerations

This patient has appropriate monitoring in place:

• Regular rheumatology follow-up (documented 2/7/24,4/28/25)
• Laboratory monitoring (CMP 3/11/25)
• Ophthalmology follow-up for pre-existing cataracts and glaucoma
• Caveat: Infectious complications are the primary concern with tocilizumab, occurring in 69% of patients in some series (predominantly bacterial) 1, 5. Patient should maintain vigilance for signs of infection.

Recommendation Summary

APPROVE tocilizumab 8 mg/kg (J3262 x560 units) every 2 weeks via home infusion (S9379) for DOS 3/11/25 and ongoing treatment, contingent on obtaining documentation of recent TB screening (within past 12 months or since biologic initiation).

The patient clearly meets medical necessity criteria:

1. Confirmed AOSD diagnosis (M06.1) under rheumatology care
2. Failed multiple prior therapies including another biologic (Ilaris)
3. Demonstrated clinical response to tocilizumab with disease in remission
4. Clinical necessity for every-2-week dosing due to symptom recurrence with 4-week intervals
5. Appropriate for home infusion setting given stability

Action Required: Request documentation of TB screening results from treating rheumatologist to complete the medical record and satisfy all policy requirements 1, 2, 3, 4, 5, 6.