Infliximab (Inflectra) and Methotrexate Combination for Rheumatoid Arthritis
Yes, you must take Inflectra (infliximab) together with methotrexate for appropriate rheumatoid arthritis treatment. The FDA label explicitly states that infliximab "should be given in combination with methotrexate" for RA, and EULAR guidelines confirm that biological DMARDs, including infliximab, should be used preferentially in combination with methotrexate rather than as monotherapy 1, 2.
Why Combination Therapy Is Required
Infliximab monotherapy has never been shown to be superior to methotrexate alone, whereas combination therapy consistently demonstrates superior efficacy 1. The evidence is unequivocal:
- In the landmark ATTRACT trial, 51.8% of patients achieved clinical response with infliximab plus methotrexate versus only 17.0% with methotrexate alone (P<0.001) 3
- Combination therapy halted radiographic progression of joint damage (mean change 0.6) compared to continued progression with methotrexate alone (mean change 7.0, P<0.001) 3
- A dose of 10 mg methotrexate or more per week is effective and appropriate for use with infliximab 1
The Critical Role of Methotrexate with Infliximab
Methotrexate reduces the formation of antibodies to infliximab (ATI), which is essential for maintaining drug efficacy 4. In Japanese patients:
- Only 11.6% of patients with detectable serum infliximab developed ATI when continuing combination therapy 4
- 62.2% of patients without serum infliximab (suggesting prior antibody formation) developed ATI 4
- 43.9% of patients who received placebo instead of infliximab in the initial phase developed ATI when starting infliximab later 4
This means stopping methotrexate dramatically increases your risk of developing antibodies that render infliximab ineffective.
Optimal Methotrexate Dosing with Infliximab
- The recommended methotrexate dose is at least 10 mg per week, with 15-25 mg weekly being optimal 1, 5
- If oral methotrexate is not tolerated, switch to subcutaneous administration before declaring treatment failure 5
- Always supplement with folic acid (at least 5 mg weekly on a non-methotrexate day) to reduce toxicity 5
When Monotherapy Might Be Considered
Only tocilizumab has been repeatedly demonstrated to be superior as monotherapy over methotrexate or other conventional DMARDs 1. For all TNF inhibitors including infliximab, monotherapy is not recommended 1.
The only scenario where continuing infliximab without methotrexate might be acceptable is if you have already achieved stable disease control on combination therapy and develop a contraindication to methotrexate 1. However, clinical response is usually maintained even after methotrexate withdrawal in established therapy, but there is rarely a reason to withdraw methotrexate since it is usually well tolerated once therapy is established 1.
Critical Pitfalls to Avoid
- Never start infliximab as monotherapy for RA – the FDA label and all guidelines require combination with methotrexate 2, 1
- Do not stop methotrexate once infliximab is working – this increases antibody formation and treatment failure risk 4
- Ensure methotrexate dose is adequate (≥10 mg/week, preferably 15-25 mg/week) before adding infliximab 1, 5
Monitoring Requirements
When on combination therapy, monitor:
- Complete blood count, liver enzymes, and creatinine every 1-3 months 5
- Disease activity (DAS28, SDAI, or CDAI) every 1-3 months during active disease 5
- Target remission (SDAI ≤3.3) or low disease activity (SDAI ≤11) within 6 months 5
The evidence overwhelmingly supports that infliximab plus methotrexate provides superior clinical, radiographic, and functional outcomes compared to either agent alone 3, 6, 7. Attempting monotherapy with infliximab for RA contradicts FDA labeling, violates guideline recommendations, and substantially increases the risk of treatment failure.