Is infliximab medically indicated for a patient with rheumatoid arthritis who has failed multiple DMARDs?

Medical Necessity Assessment for Infliximab in Rheumatoid Arthritis

Infliximab is NOT medically indicated for this patient because she does not meet the mandatory requirement for concurrent methotrexate therapy, which is an absolute criterion for infliximab use in rheumatoid arthritis.

Critical Barrier to Approval

The patient has declined methotrexate for "social reasons," which creates an insurmountable barrier to infliximab approval. 1, 2 Unlike other TNF inhibitors that can be used as monotherapy, infliximab requires mandatory concurrent methotrexate administration to prevent anti-drug antibody formation and maintain therapeutic efficacy. 1, 2 The EULAR guidelines explicitly state that infliximab should not be used as monotherapy, and the ACR criteria require "concurrent treatment with methotrexate" as a non-negotiable requirement. 2

Why Methotrexate is Non-Negotiable for Infliximab

• Antibody formation occurs in 7-61% of patients on infliximab monotherapy, leading to secondary treatment failure and low drug trough levels. 3
• Methotrexate co-administration prevents immunogenicity and is the only recommended approach for infliximab use, distinguishing it from other TNF inhibitors. 2, 3
• The patient's stated criteria explicitly require "concurrent treatment with methotrexate" for infliximab approval. 2

Assessment Against Other Criteria

While the patient meets several other requirements, the methotrexate criterion is absolute:

✓ Criteria Met:

• Age requirement: 60 years old (≥18 years required) 2
• Clinical diagnosis: Confirmed rheumatoid arthritis with RF 146 and CCP IgG 95 (seropositive disease) 2
• DMARD failures: Has failed hydroxychloroquine (rash), plus two biologics—Actemra/tocilizumab (stopped working) and Kevzara/sarilumab (ineffective)—representing >3 months of inadequate DMARD response 1, 2
• No concurrent biologics: Currently only on intermittent Medrol 1

✗ Critical Criterion NOT Met:

• Concurrent methotrexate therapy: Patient declined for "social reasons" 1, 2

? Unclear/Missing:

• Disease activity score: No CDAI, DAS28, SDAI, PAS, or RAPID3 score documented to confirm "moderate to severe active disease" 1, 2
• Hepatitis B status: Not documented 2
• TB screening: Not documented 2, 3
• Active infection status: Not documented 2

Alternative Biologic Recommendations

Given the methotrexate contraindication, alternative TNF inhibitors that do NOT require mandatory methotrexate co-therapy should be considered instead:

Preferred Alternatives:

• Etanercept, adalimumab, golimumab, or certolizumab pegol can be used without mandatory methotrexate, though combination therapy is preferred when tolerated. 1, 4
• Non-TNF biologics such as abatacept or rituximab may be appropriate after multiple biologic failures (tocilizumab and sarilumab). 1, 5
• JAK inhibitors (tofacitinib, baricitinib, upadacitinib) represent another mechanism after IL-6 inhibitor failure and do not require methotrexate. 5

Sequencing Considerations:

• After failing tocilizumab (IL-6 inhibitor) and sarilumab (IL-6 inhibitor), EULAR guidelines recommend switching to a different mechanism of action. 1, 5
• The patient has not yet tried a TNF inhibitor, making etanercept, adalimumab, golimumab, or certolizumab reasonable next steps. 4, 2
• These alternatives would allow biologic therapy without the absolute methotrexate requirement. 1

Common Pitfall

The most critical error would be approving infliximab without addressing the methotrexate requirement. This would lead to:

• High risk of anti-drug antibody formation (up to 61% of patients) 3
• Secondary treatment failure 3
• Wasted healthcare resources on an expensive therapy likely to fail 2
• Potential denial of coverage upon utilization review 2

Required Actions Before Reconsideration

If the patient reconsiders methotrexate therapy, the following must be documented:

• Formal disease activity score (CDAI >10, DAS28 ≥3.2, SDAI >11, PAS ≥3.71, or RAPID3 >2) 1, 2
• Hepatitis B surface antigen testing (must be negative or on antiviral therapy) 2
• TB screening (must rule out latent/active TB) 2, 3
• Absence of active infection 2
• Commitment to concurrent methotrexate therapy at appropriate doses (typically 15-25 mg weekly with folic acid) 1, 2