What are the next steps for a patient on Actemra (Tocilizumab), Cellcept (Mycophenolate Mofetil), intravenous (IV) Rituximab, high-dose intravenous immunoglobulin (IVIG), Prednisone, and Plaquenil (Hydroxychloroquine) with persistent active inflammation, neutrophilia, hypocomplementemia, and synovitis, despite previous failure of Methotrexate (MTX)?

From the Guidelines

For a patient with persistent active inflammation despite multiple immunosuppressive therapies, I recommend adding a JAK inhibitor, such as baricitinib (4mg daily) or tofacitinib (5mg twice daily), as the next step in management, considering the patient's extensive regimen has failed to achieve the desired outcome, as per the most recent guidelines 1. This patient has failed an extensive regimen including Actemra (tocilizumab), CellCept (mycophenolate mofetil), rituximab, IVIG, prednisone, Plaquenil (hydroxychloroquine), and previously methotrexate, yet continues to show active disease with synovitis, high neutrophils, and low complement levels.

• The patient's current regimen includes a biologic DMARD (tocilizumab) and other immunosuppressive agents, but the disease remains active.
• The 2020 EULAR recommendations suggest that if a bDMARD or tsDMARD has failed, treatment with another bDMARD or a tsDMARD should be considered 1.
• JAK inhibitors, such as baricitinib or tofacitinib, are targeted synthetic DMARDs (tsDMARDs) that have shown efficacy in patients with rheumatoid arthritis who have failed other treatments.
• Before adding new medications, ensure therapeutic drug monitoring of current agents to confirm adequate dosing and consider checking for anti-drug antibodies, particularly to rituximab.
• A comprehensive evaluation for infections or malignancy that might be driving inflammation is also warranted.
• The combination of low complement and neutrophilia suggests ongoing immune complex formation that might respond to plasma exchange (3-5 treatments) as a temporizing measure while adjusting the medication regimen. The most recent guidelines from 2020 1 provide the best evidence for this recommendation, as they outline the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs, and suggest the use of JAK inhibitors as a potential next step in patients who have failed other treatments.

From the Research

Treatment Options for Persistent Active Inflammation

The patient is currently on a regimen of Actemra (Tocilizumab), Cellcept (Mycophenolate Mofetil), intravenous (IV) Rituximab, high-dose intravenous immunoglobulin (IVIG), Prednisone, and Plaquenil (Hydroxychloroquine) with persistent active inflammation, neutrophilia, hypocomplementemia, and synovitis, despite previous failure of Methotrexate (MTX). Considering the treatment options, the following points can be noted:

• Combination therapy with methotrexate + sulfasalazine + hydroxychloroquine (triple therapy) or methotrexate + most biologic DMARDs or tofacitinib were similarly effective in controlling disease activity and generally well tolerated in methotrexate-naïve patients or after an inadequate response to methotrexate 2.
• Methotrexate + some biologic DMARDs were superior to methotrexate in preventing joint damage in methotrexate-naïve patients, but the magnitude of these effects was small over one year 2.
• Immunosuppressive and cytotoxic drugs, such as mycophenolate mofetil, can be used to treat severe and/or recalcitrant rheumatic skin diseases 3.
• Glucocorticoids, azathioprine, methotrexate, and hydroxyurea are traditional therapies used for treatment of inflammatory diseases, and they work by blocking many components that contribute to inflammatory and immune responses 4.

Next Steps for Treatment

Based on the current treatment regimen and the patient's condition, the next steps for treatment could be:

• Continuing the current regimen and monitoring the patient's response to treatment.
• Considering alternative biologic DMARDs or tofacitinib if the patient is not responding to the current treatment.
• Adding or substituting other immunosuppressive or cytotoxic drugs, such as azathioprine or cyclophosphamide, to the treatment regimen.
• Evaluating the patient's response to treatment and adjusting the regimen as needed to achieve optimal control of disease activity and prevention of joint damage.

Key Considerations

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

• The patient's previous failure of Methotrexate (MTX) and the current treatment regimen.
• The presence of persistent active inflammation, neutrophilia, hypocomplementemia, and synovitis.
• The potential benefits and risks of continuing or modifying the current treatment regimen.
• The need for ongoing monitoring and evaluation of the patient's response to treatment. 2, 3, 4, 5, 6