Is infliximab a suitable treatment option for a rheumatoid arthritis patient who has failed multiple DMARDs, including plaquenil, Orencia, and Enbrel, and is currently on Actemra and intermittent Medrol?

Infliximab is NOT Suitable Without Discontinuing Actemra

Infliximab cannot be initiated while the patient remains on Actemra (tocilizumab) due to the absolute contraindication against concurrent biologic therapy, which significantly increases serious infection risk. 1, 2, 3 The patient must discontinue Actemra before starting infliximab.

Critical Barrier: Concurrent Biologic Use

• EULAR guidelines explicitly state that biologics should not be used concurrently due to safety concerns, particularly increased serious infection rates. 3
• The patient is currently on weekly Actemra injections, which must be stopped and cleared before infliximab initiation. 3
• This represents a fundamental safety violation that supersedes all other considerations for medical necessity. 3

Missing Documentation Requirements

Before infliximab can be considered medically necessary, the following must be documented:

• Formal disease activity score (DAS28, CDAI, or SDAI) demonstrating moderate to severe active disease - currently absent from the clinical record. 2, 3
• Evidence that Actemra has failed after at least 3 months of therapy with inadequate response, or 6 months without reaching treatment target. 2, 3
• The case states "no documentation of any activity or disease assessment tools," which is insufficient for justifying biologic therapy escalation. 2

Treatment Sequencing Concerns

After failure of tocilizumab (an IL-6 pathway inhibitor), EULAR guidelines recommend switching to a biologic with a different mechanism of action. 3

• Infliximab (a TNF inhibitor) would be mechanistically appropriate given prior failure of Enbrel (etanercept, another TNF inhibitor), as switching between TNF inhibitors can still be effective. 1, 3
• However, the patient has already failed one TNF inhibitor (Enbrel), making the likelihood of response to infliximab uncertain. 4
• Alternative options with different mechanisms—such as rituximab (B-cell depletion) or JAK inhibitors (tofacitinib, baricitinib, upadacitinib)—may be preferable after both TNF inhibitor and IL-6 inhibitor failure. 3

The Methotrexate Problem

Infliximab requires methotrexate co-administration to prevent antibody formation and optimize efficacy. 2, 3, 5, 6

• EULAR and ACR guidelines state that infliximab should be combined with methotrexate—unlike other TNF inhibitors, infliximab should not be used as monotherapy. 2
• The patient declined methotrexate "due to social reasons," which creates a significant barrier to infliximab use. 3
• Without methotrexate, the patient faces 7-61% risk of developing anti-infliximab antibodies, leading to secondary response failure and increased infusion reactions. 5, 6
• Low infliximab levels at early treatment stages predict antibody development and later treatment failure. 6

What Would Make Infliximab Appropriate

If the clinical team wishes to pursue infliximab, the following steps are mandatory:

1. Discontinue Actemra and document adequate washout period (typically 4-8 weeks for tocilizumab). 3

2. Obtain formal disease activity measurement using DAS28-ESR/CRP, CDAI, or SDAI to establish baseline moderate-to-severe disease activity. 2, 3

3. Document Actemra failure with evidence of inadequate response after minimum 3 months of therapy. 2, 3

4. Reconsider methotrexate co-therapy - the patient must understand that infliximab without methotrexate has substantially higher failure rates and adverse event risks. 2, 3, 5, 6

5. Screen for active infection and tuberculosis before initiating infliximab, as infections (particularly tuberculosis) are increased in treated patients. 5

Alternative Recommendation

Given the patient's treatment history (failed TNF inhibitor, failed IL-6 inhibitor, declined methotrexate), a JAK inhibitor (tofacitinib, baricitinib, or upadacitinib) may be more appropriate. 1, 3

• JAK inhibitors can be used without mandatory methotrexate co-therapy, addressing the patient's refusal of methotrexate. 1
• They represent a different mechanism of action after failure of both TNF and IL-6 pathway inhibition. 3
• EULAR guidelines support JAK inhibitors after biologic failure. 1

Common Pitfalls to Avoid

• Never initiate a second biologic without discontinuing the first - this is the most critical safety error in this case. 3
• Never assume infliximab can be used effectively without methotrexate - the evidence strongly supports mandatory co-therapy. 2, 3, 5
• Never escalate to biologics without documented disease activity scores - this is required for both medical necessity determination and monitoring treatment response. 2, 3
• Do not ignore the patient's prior TNF inhibitor failure when selecting infliximab as the next agent. 4