Is Simponi Aria (golimumab) IV infusion of 2mg/kg every 8 weeks medically indicated for a patient with moderate to severe rheumatoid arthritis (M06.89) who has a history of adverse effects from methotrexate (MTX), including increased liver enzymes, and has shown improvement with the current treatment?

Medical Necessity Determination for Simponi Aria Continuation

Simponi Aria (golimumab) continuation is NOT medically indicated based on the submitted documentation, as the FDA label explicitly requires combination therapy with methotrexate for rheumatoid arthritis, and the patient discontinued methotrexate without attempting alternative administration routes or adequate rechallenge strategies. 1

Critical Deficiencies in Medical Necessity

Mandatory Methotrexate Combination Therapy Requirement

• The FDA-approved indication for Simponi Aria in rheumatoid arthritis explicitly states it "should be given in combination with methotrexate" for RA patients. 1
• The 2021 ACR guidelines recommend biologic DMARDs like golimumab be used in combination with methotrexate for optimal efficacy in RA patients. 2
• Monotherapy with Simponi Aria for RA is not standard of care and deviates from FDA-approved prescribing information. 1

Inadequate Management of Methotrexate Hepatotoxicity

Before abandoning methotrexate entirely, subcutaneous administration should have been attempted, as it has higher bioavailability (78% vs 64%) and potentially fewer gastrointestinal and hepatic side effects than oral administration. 2

The documentation shows:

• Methotrexate was discontinued due to "increased liver enzymes" but provides no specific ALT/AST values, timing, or severity. 2
• No documentation that subcutaneous methotrexate was attempted before discontinuation. 2
• No evidence of dose reduction strategies (oral methotrexate should start at 10-15 mg/week with escalation of 5 mg every 2-4 weeks up to 20-30 mg/week). 2

Evidence on Methotrexate Hepatotoxicity Management

• Pre-treatment ALT elevation is the strongest predictor for recurrent elevations during therapy (adjusted OR 6.8), but recurrent elevations do not necessarily mandate permanent discontinuation. 3
• In patients with definite MTX-induced transaminitis, decreasing dose or discontinuing MTX led to enzyme normalization in 83% of cases, but continuing with dose reduction was often successful. 4
• Only 3% of RA patients permanently stopped MTX due to ALT elevation in long-term follow-up studies, and no patients developed hepatic failure. 3
• Severe liver disease occurs in less than 3% of RA patients treated with low-dose MTX. 5

Missing Clinical Documentation

Documentation of disease activity using validated measures (Clinical Disease Activity Index or Disease Activity Score) is necessary to establish moderate-to-severe disease and meet medical necessity criteria. 2

The submission lacks:

• Recent office visit notes or clinical assessments (explicitly noted as missing). 2
• Validated disease activity scores to confirm "moderate to severe RA." 2
• Specific documentation of how the patient "improved" on current treatment (no objective measures provided). 2
• Complete DMARD trial history, responses, and specific reasons for discontinuation. 2

Alternative Management Strategies Required Before Approval

Methotrexate Rechallenge Protocol

1. Obtain baseline liver function tests and assess for NAFLD risk factors (obesity, diabetes, hyperlipidemia). 6
2. Consider non-invasive liver fibrosis assessment (FIB-4 index, transient elastography) if NAFLD risk factors present. 6
3. Initiate subcutaneous methotrexate at 10-15 mg/week if oral route caused hepatotoxicity. 2
4. Monitor ALT/AST every 2-4 weeks initially, then every 8-12 weeks after 3 months, then every 12 weeks after 6 months. 6
5. If ALT elevation recurs, reduce dose rather than discontinue - 70% of patients have recurrent elevations but most can continue therapy with dose adjustments. 4, 3

If Methotrexate Truly Contraindicated

If methotrexate cannot be used despite subcutaneous trial and dose optimization, switching to a biologic with a different mechanism of action is more appropriate than continuing a TNF inhibitor without methotrexate. 2

Options include:

• IL-6 receptor inhibitors (tocilizumab, sarilumab). 2
• T-cell costimulation inhibitors (abatacept). 2
• B-cell depleting agents (rituximab). 2
• JAK inhibitors (tofacitinib, baricitinib, upadacitinib). 2

Combination Conventional Synthetic DMARD Therapy

Addition of other conventional synthetic DMARDs (dual or triple therapy with hydroxychloroquine and sulfasalazine) is conditionally recommended over biologic monotherapy and carries lower infection risk. 6

Common Pitfalls to Avoid

• Do not approve TNF inhibitor monotherapy for RA when methotrexate combination therapy is FDA-mandated and clinically superior. 1
• Do not accept "increased liver enzymes" as sufficient justification for permanent methotrexate discontinuation without documented subcutaneous trial. 2
• Do not approve continuation without validated disease activity measures demonstrating moderate-to-severe disease. 2
• Do not approve switching between biologics without documented adequate trial duration and dosing of current therapy. 2

Required Documentation for Approval

1. Specific ALT/AST values, timing, and severity of methotrexate-induced hepatotoxicity. 4, 3
2. Documentation that subcutaneous methotrexate was attempted or specific contraindication to this route. 2
3. Recent clinical assessment with validated disease activity score (CDAI, DAS28). 2
4. Liver fibrosis assessment if NAFLD risk factors present. 6
5. Complete prior DMARD trial history with responses and discontinuation reasons. 2

Without this documentation, approval would deviate from FDA labeling, ACR guidelines, and standard rheumatology practice. 6, 2, 1