What is the best course of action for a patient with a 15-year history of untreated autoimmune disease, now diagnosed, who continues to exhibit evidence of inflammation and active disease flare despite treatment with multiple immunosuppressants?

From the Guidelines

For a patient with a 15-year history of untreated autoimmune disease, now diagnosed, who continues to exhibit evidence of inflammation and active disease flare despite treatment with multiple immunosuppressants, I strongly recommend consulting with a rheumatologist about biologic therapy options, specifically considering TNF inhibitors, IL-6 inhibitors, or JAK inhibitors, as they have shown to be effective in refractory cases, as suggested by the 2019 American College of Rheumatology/National Psoriasis Foundation guideline 1.

When considering biologic therapy, it's essential to take into account the patient's specific autoimmune condition, as different biologics may be more effective for certain diseases. The 2014 EULAR recommendations for the management of rheumatoid arthritis suggest that biologics should be considered when the treatment target is not achieved with the first DMARD strategy, especially in the presence of poor prognostic factors 1.

Some key points to consider when selecting a biologic therapy include:

• The patient's previous response to immunosuppressants and any potential contraindications to certain biologics
• The presence of comorbidities, such as congestive heart failure or demyelinating disease, which may affect the choice of biologic
• The potential benefits and risks of each biologic option, including the risk of serious infections and other adverse events
• The importance of regular monitoring of inflammatory markers and organ-specific function tests to assess the effectiveness of the biologic therapy

In addition to biologic therapy, it's crucial to ensure the patient is taking the highest tolerated doses of their current medications and consider adding prednisone 10-20mg daily temporarily to control the flare, as suggested by the 2012 Mayo Clinic Proceedings article 1. Regular monitoring of the patient's condition and adjustment of the treatment plan as needed is essential to achieve the best possible outcome.

The 2019 American College of Rheumatology/National Psoriasis Foundation guideline provides conditional recommendations for switching to a different biologic or adding methotrexate to an existing biologic regimen, based on very-low-quality evidence 1. However, these recommendations should be considered in the context of the patient's individual situation and in consultation with a rheumatologist.

Ultimately, the goal of treatment should be to achieve remission or low disease activity, as recommended by the 2014 EULAR guidelines, and to improve the patient's quality of life, while minimizing the risk of adverse events and optimizing the use of available treatments 1.

From the FDA Drug Label

For RA, GPA and MPA, and PV patients, methylprednisolone 100 mg intravenously or its equivalent is recommended 30 minutes prior to each infusion The benefits of alternate day therapy should not encourage the indiscriminate use of steroids. Alternate day therapy is a therapeutic technique primarily designed for patients in whom long-term pharmacologic corticoid therapy is anticipated

The best course of action for a patient with a 15-year history of untreated autoimmune disease, now diagnosed, who continues to exhibit evidence of inflammation and active disease flare despite treatment with multiple immunosuppressants is to:

• Re-evaluate the current treatment regimen and consider alternative therapies, such as rituximab, in combination with glucocorticoids, like prednisone.
• Use glucocorticoids, such as methylprednisolone, to reduce inflammation and prevent infusion-related reactions.
• Consider alternate day therapy with prednisone to minimize the undesirable features of corticosteroid therapy, but carefully weigh the benefit-risk ratio for each patient. 2 3

From the Research

Treatment Options for Autoimmune Disease

The patient's 15-year history of untreated autoimmune disease, now diagnosed, with ongoing inflammation and active disease flare despite treatment with multiple immunosuppressants, presents a complex clinical scenario.

• The use of rituximab, a chimeric mouse/human monoclonal antibody directed against the B cell CD20 receptor, has been explored in the treatment of lupus nephritis (LN) and systemic lupus erythematosus (SLE) 4, 5.
• Studies have shown that rituximab may benefit certain patients with LN, but the evidence is not conclusive due to the heterogeneity of the studies and the lack of randomized controlled trials 4.
• Belimumab, an anti-B-cell activating factor antibody, has been approved for the treatment of auto-antibody positive SLE with a high degree of disease activity, and its combination with rituximab is being investigated in clinical trials 6.
• Mycophenolate mofetil (MMF) has been shown to reduce the rate of severe flare and lower the incidence of LN in patients with new-onset SLE and a high titer of anti-dsDNA antibody without major organ involvement 7.
• The primary goal of treatment is to achieve disease remission or quiescence, defined by minimal symptoms, low levels of autoimmune inflammatory markers, and minimal systemic glucocorticoid requirement while the patient is treated with maintenance doses of immunomodulatory or immunosuppressive medications 8.

Potential Treatment Strategies

Based on the available evidence, potential treatment strategies for the patient could include:

• Combination therapy with belimumab and rituximab, as investigated in the Synbiose 2 trial 6.
• The use of MMF, either as monotherapy or in combination with other immunosuppressants, to reduce the rate of severe flare and lower the incidence of LN 7.
• The optimization of current treatment regimens, including the adjustment of immunosuppressant doses and the addition of new therapies, such as voclosporin or anifrolumab, which have recently been approved for the treatment of SLE 8.