Is infliximab (a biologic agent) medically indicated for a patient with rheumatoid arthritis (RA) who has failed multiple disease-modifying antirheumatic drugs (DMARDs), including Plaquenil (hydroxychloroquine), Orencia (abatacept), and Enbrel (etanercept), and is currently on Actemra (tocilizumab)?

Infliximab is NOT Medically Indicated for This Patient

This patient is currently on Actemra (tocilizumab), and adding infliximab would constitute concurrent treatment with two biologic drugs, which directly violates both the stated criteria and established clinical guidelines that prohibit simultaneous use of biologics due to increased infection risk without additional benefit. 1

Critical Issue: Concurrent Biologic Therapy

• The patient's criteria explicitly state "no concurrent treatment with other biologic drugs," and Actemra (tocilizumab) is an IL-6 receptor inhibitor biologic that she is currently receiving weekly 1
• EULAR guidelines clearly recommend that biologics should not be used concurrently due to safety concerns, particularly increased serious infection rates 1
• The patient must discontinue Actemra before initiating infliximab, or alternatively, optimize her current Actemra therapy before considering a switch 1

Assessment of Treatment Failure Documentation

• The patient has documented inadequate response to multiple DMARDs: Plaquenil (rash/intolerance), Orencia (abatacept - loss of efficacy), and Enbrel (etanercept - ineffective) 1
• However, there is no documentation of disease activity assessment tools (DAS28, CDAI, or SDAI) to objectively demonstrate that Actemra has failed or that the patient has moderate to severe active disease 1
• The absence of formal disease activity measurements makes it impossible to determine if the treatment target has been reached or if 3-6 months of adequate Actemra therapy has been completed 1

Appropriate Next Steps Before Considering Infliximab

1. Optimize Current Actemra Therapy

• Document disease activity using validated measures (DAS28-ESR/CRP, CDAI, or SDAI) to establish baseline and treatment response 1
• Ensure adequate duration of Actemra therapy (minimum 3 months for improvement, 6 months to reach target) before declaring treatment failure 1
• Consider increasing Actemra frequency or switching to intravenous formulation if subcutaneous injections are inadequate 1

2. Address the Methotrexate Gap

• The patient declined methotrexate for "social reasons," but methotrexate should be part of the treatment strategy and significantly enhances biologic efficacy while reducing immunogenicity 1, 2
• Methotrexate combination with biologics improves outcomes compared to biologic monotherapy, with infliximab particularly requiring methotrexate co-administration to prevent antibody formation 1, 2, 3
• Revisit the methotrexate discussion with the patient, addressing specific concerns and exploring alternative dosing schedules (weekly subcutaneous administration may be more acceptable) 2

3. Consider Alternative csDMARDs

• Since the patient is allergic to sulfasalazine and declined methotrexate, leflunomide should be considered as combination therapy with Actemra 1, 2
• Adding a conventional synthetic DMARD to the current biologic may improve disease control without requiring a biologic switch 1

If Actemra Has Truly Failed: Appropriate Biologic Sequencing

• After failure of tocilizumab (an IL-6 pathway inhibitor), EULAR guidelines recommend switching to a biologic with a different mechanism of action 1
• Infliximab (a TNF inhibitor) would be an appropriate choice given prior failure of etanercept (another TNF inhibitor), as switching between TNF inhibitors can still be effective 1
• However, the patient previously failed Enbrel (etanercept, a TNF inhibitor), which raises the question of whether another TNF inhibitor is optimal 1
• Alternative options with different mechanisms include rituximab (B-cell depletion) or a JAK inhibitor (tofacitinib, baricitinib, upadacitinib), which may be preferable after both TNF inhibitor and IL-6 inhibitor failure 1

Critical Documentation Requirements Before Approval

• Formal disease activity score (DAS28, CDAI, or SDAI) demonstrating moderate to severe active disease 1
• Documentation that Actemra has been discontinued or clear plan for discontinuation before infliximab initiation 1
• Evidence of at least 3 months of Actemra therapy with inadequate response, or 6 months without reaching treatment target 1
• Tuberculosis screening (PPD or IGRA) and chest X-ray before initiating infliximab 3, 4
• Hepatitis B screening, as TNF inhibitors can reactivate latent hepatitis B 2

Common Pitfalls to Avoid

• Never combine two biologic DMARDs simultaneously - this increases infection risk without improving efficacy 1
• Do not switch biologics without objective documentation of treatment failure using validated disease activity measures 1
• Avoid declaring biologic failure before adequate trial duration (3-6 months) 1
• Do not use infliximab without methotrexate co-therapy unless there is a documented contraindication, as this increases immunogenicity and reduces efficacy 1, 2, 3
• Failing to screen for latent tuberculosis before TNF inhibitor initiation can result in disseminated TB infection 3, 4