Will intravenous (IV) infliximab (Infliximab) therapy demonstrate improved outcomes in a patient with rheumatoid arthritis who has failed subcutaneous (Subcutaneous) certolizumab (Certolizumab) and other biologic therapies, including tofacitinib (Xeljanz), upadacitinib (Rinvoq), abatacept (Orencia), and sarilumab (Kevzara)?

From the Guidelines

Switching to infliximab may potentially benefit your patient with rheumatoid arthritis despite prior failure with certolizumab, as the IV administration of infliximab provides more rapid and complete drug exposure, which may overcome resistance mechanisms, as suggested by the 2020 EULAR recommendations for the management of rheumatoid arthritis 1. The patient has already tried various biologic therapies, including Xeljanz, Rinvoq, Orencia, Kevzara, and Cimzia, and the prescriber wants to consider infliximab as the next option.

• The 2020 EULAR recommendations suggest that if a bDMARD or tsDMARD has failed, treatment with another bDMARD or a tsDMARD should be considered, and if one TNF inhibitor therapy has failed, patients may receive an agent with another mode of action or a second TNF inhibitor 1.
• The IV administration of infliximab provides more rapid and complete drug exposure, which may overcome resistance mechanisms, and some patients respond differently to various TNF inhibitors despite their similar mechanisms of action.
• The typical infliximab regimen for rheumatoid arthritis is 3 mg/kg IV at weeks 0,2, and 6, then every 8 weeks thereafter, often combined with methotrexate, and if inadequate response occurs, consider dose escalation up to 10 mg/kg or shortening the interval to every 4-6 weeks.
• Monitor for infusion reactions, infections, and other TNF inhibitor class effects, and the likelihood of response is modest (approximately 10-20% of patients may respond to a second TNF inhibitor after failing the first), but given the limited remaining options, a trial of infliximab is reasonable before considering experimental therapies or JAK inhibitors not already tried. The 2014 EULAR recommendations also support the use of TNF inhibitors, including infliximab, as an option for patients who have failed other therapies 1.
• However, the 2020 recommendations are more recent and provide more updated guidance on the use of biologic therapies in rheumatoid arthritis, and therefore, the 2020 recommendations should be prioritized 1.

From the FDA Drug Label

In rheumatoid arthritis, treatment with infliximab products reduced infiltration of inflammatory cells into inflamed areas of the joint as well as expression of molecules mediating cellular adhesion [E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)], chemoattraction [IL-8 and monocyte chemotactic protein (MCP-1)] and tissue degradation [matrix metalloproteinase (MMP) 1 and 3].

The FDA drug label does not provide a direct comparison between IV infused therapy and subcutaneous therapy in terms of outcomes or management for a patient who has already tried certolizumab subcutaneously. Therefore, no conclusion can be drawn regarding whether an IV infused therapy will show better outcomes or management for this patient. 2, 2, and 2 do not provide the necessary information to answer this question.

From the Research

Efficacy of Infliximab in Rheumatoid Arthritis

• The patient has already tried various biologic therapies, including certolizumab, which is a subcutaneous treatment 3.
• A study comparing the efficacy and safety of infliximab-biosimilar to other biologics in rheumatoid arthritis found no significant difference between infliximab-biosimilar and other biologics, including certolizumab, in terms of clinical efficacy and safety 3.
• Another study compared the effectiveness of certolizumab pegol, abatacept, and biosimilar infliximab in patients with rheumatoid arthritis and found that biosimilar infliximab had similar effectiveness to certolizumab pegol and abatacept in achieving remission rates and treatment retention 4.

IV Infused Therapy vs Subcutaneous Treatment

• There is limited evidence directly comparing the efficacy of IV infused therapy (such as infliximab) to subcutaneous treatment (such as certolizumab) in patients with rheumatoid arthritis who have already tried subcutaneous biologics.
• However, a study on dual biologic therapy in patients with inflammatory bowel disease suggests that combination therapy with biologics targeting different pathways may be effective in patients with refractory disease 5, 6.
• It is unclear whether IV infused therapy would show better outcomes or management in this patient, as the evidence is limited and indirect.

Considerations for Treatment Decision

• The decision to switch to infliximab should be based on individual patient factors, such as disease activity, comorbidities, and previous treatment responses.
• The prescriber should consider the potential benefits and risks of infliximab, including the possibility of improved efficacy and the risk of adverse events.
• Further studies are needed to determine the efficacy and safety of infliximab in patients with rheumatoid arthritis who have already tried subcutaneous biologics 7, 3, 4.