What are the next steps for a patient with active inflammation, elevated neutrophils, and low complement levels, despite treatment with Actemra (Tocilizumab), Cellcept (Mycophenolate mofetil), intravenous Rituximab, high-dose intravenous Immunoglobulin (IVIG), Prednisone, and Plaquenil (Hydroxychloroquine), with persistent synovitis and previous failure of Methotrexate (MTX) and combination therapy with Xeljanz (Tofacitinib) and Leflunomide?

From the Guidelines

For a patient with persistent active inflammation despite multiple immunosuppressive therapies, I would recommend considering JAK inhibitor therapy with baricitinib (Olumiant) at 2-4mg daily or upadacitinib (Rinvoq) at 15mg daily, as these newer JAK inhibitors may be effective despite previous failure with Xeljanz, as suggested by the most recent EULAR recommendations 1. The patient's history of treatment with Actemra (Tocilizumab), Cellcept (Mycophenolate mofetil), intravenous Rituximab, high-dose intravenous Immunoglobulin (IVIG), Prednisone, and Plaquenil (Hydroxychloroquine), with persistent synovitis and previous failure of Methotrexate (MTX) and combination therapy with Xeljanz (Tofacitinib) and Leflunomide, indicates a need for alternative therapeutic approaches. Some key points to consider in this patient's management include:

• The importance of monitoring disease activity and adjusting therapy accordingly, as emphasized in the EULAR recommendations 1
• The potential benefits of JAK inhibitors in patients with refractory disease, as suggested by recent studies 1
• The need to consider alternative biologic agents, such as belimumab (Benlysta), which targets B-cell activating factor and may help address the low complement levels, as mentioned in the EULAR recommendations 1
• The possibility of optimizing the current regimen by increasing tocilizumab (Actemra) dosing or adjusting rituximab to a more frequent maintenance schedule, as suggested by the EULAR recommendations 1
• The consideration of cyclophosphamide (500-750mg/m² monthly for 3-6 months) as rescue therapy for patients with refractory disease, as mentioned in the EULAR recommendations 1 These recommendations target different inflammatory pathways, including:
• JAK inhibitors, which block multiple cytokine signals simultaneously
• Belimumab, which specifically targets B-cell survival factors
• Cyclophosphamide, which provides broad immunosuppression The persistent neutrophilia suggests ongoing innate immune activation, while low complement indicates immune complex formation, suggesting both arms of immunity remain active despite current therapy. Given the complexity of this patient's disease and the need for individualized care, it is essential to prioritize a shared decision-making approach, as emphasized in the EULAR recommendations 1, to ensure the best possible outcomes for the patient.

From the Research

Next Steps for Treatment

The patient has active inflammation, elevated neutrophils, and low complement levels, despite treatment with multiple medications. Considering the patient's history of failed treatments, including Methotrexate (MTX) and combination therapy with Xeljanz (Tofacitinib) and Leflunomide, the next steps for treatment could be:

• Abatacept (Orencia®) therapy, as it has been shown to be effective in patients with rheumatoid arthritis who have had an inadequate response to previous therapy with at least one conventional DMARD, including methotrexate or a TNF inhibitor 2
• Consideration of refractory rheumatoid arthritis diagnosis, as the patient has failed multiple treatments and has persistent synovitis, which is a key principle in identifying refractory cohorts 3, 4

Treatment Options

The following treatment options could be considered:

• Abatacept, which has been shown to be effective in patients with rheumatoid arthritis who have had an inadequate response to previous therapy 2
• Tocilizumab, which has been shown to be effective in patients with rheumatoid arthritis who have had an inadequate response to previous therapy, although dose optimization may be necessary 5
• Rituximab, which has been shown to be effective in patients with rheumatoid arthritis who have had an inadequate response to previous therapy, and may be associated with greater improvements in outcomes compared to abatacept 6

Key Considerations

When considering the next steps for treatment, the following key considerations should be taken into account:

• The patient's history of failed treatments, including Methotrexate (MTX) and combination therapy with Xeljanz (Tofacitinib) and Leflunomide
• The presence of active inflammation, elevated neutrophils, and low complement levels, despite treatment with multiple medications
• The potential for refractory rheumatoid arthritis diagnosis, and the need for careful consideration of treatment options in this context 3, 4