What is the next step in managing a patient with severe autoimmune disease, who has shown improvement but still has active disease after 6 months on combination biologics (biologic disease-modifying antirheumatic drugs) immunosuppression, without evidence of infections or cytopenia?

From the Guidelines

For a patient with severe autoimmune disease on combination biologic immunosuppression for 6 months who has shown improvement but still has active disease, without infections or cytopenias, I recommend switching to an alternative biologic agent, such as anti-TNF, CTLA4:Ig (abatacept), anti–IL-6R-mAb (tocilizumab), anti-CD20 (rituximab), or IL-1ra (anakinra), as the next step in management. This approach is supported by the treatment guidelines outlined in the study published in the Mayo Clinic Proceedings 1, which suggests switching to an alternative biologic agent after inadequate response to the current regimen.

When considering the switch, it's essential to evaluate the patient's current disease activity and adjust the treatment plan accordingly. The study published in the Mayo Clinic Proceedings 1 provides a framework for treatment modification based on disease activity, suggesting options such as adding sulfasalazine (SSZ) and hydroxychloroquine (HCQ) or switching to subcutaneous methotrexate (MTX) for patients with a Disease Activity Score (SDAI) >11 to ≤26. However, given the patient's ongoing active disease despite 6 months of combination biologic immunosuppression, switching to a biologic with a different mechanism of action is likely the most appropriate next step.

Some key considerations when switching biologic agents include:

• Ensuring the patient has not had an adequate response to at least one anti-TNF agent before switching to alternative biologics like abatacept, tocilizumab, or rituximab 1
• Monitoring disease activity using validated measures specific to the autoimmune condition
• Maintaining vigilance for potential adverse effects with more frequent laboratory monitoring (CBC, liver function, renal function every 4-8 weeks)
• Considering the addition of conventional synthetic DMARDs like methotrexate or leflunomide to enhance efficacy through synergistic mechanisms if the patient can tolerate them.

From the FDA Drug Label

Subsequent courses should be administered every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks. The patient has been on the combination biologics immunosuppression regimen for 6 months with no infections or cytopenia, and has shown improvement but still has active disease. The next step would be to continue the current treatment regimen, as the patient has not achieved complete disease control, and re-evaluate the patient's condition every 24 weeks or based on clinical evaluation to determine the best course of action [ 2 ]. Key considerations include:

• The patient's disease activity and response to treatment
• The risk of infections and cytopenia
• The need for adjustments to the treatment regimen to achieve optimal disease control.

From the Research

Combination Biologics Immunosuppression

• The patient has been on combination biologics immunosuppression for 6 months with no infections or cytopenia, but still has active disease 3, 4.
• Studies have shown that combination therapy with rituximab and mycophenolate can be effective in treating refractory dermatomyositis with multiple autoimmune disorders 4.
• Abatacept, a fusion protein with a CTLA-4 domain, has been used as salvage therapy for life-threatening refractory autoimmune hemolytic anemia, and its application in refractory AIHA might be reasonable 3.
• Maintenance immunosuppression in myasthenia gravis can include options such as corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, methotrexate, rituximab, cyclophosphamide, intravenous immunoglobulin, plasmapheresis, and thymectomy 5, 6.

Next Steps

• Consider adding another immunosuppressive medication, such as azathioprine, to the current regimen, as seen in the case of abatacept and azathioprine combination therapy 3.
• Rituximab has been shown to be effective in treating various autoimmune diseases, including those that are refractory to other treatments, and may be considered as an alternative to intravenous immune globulin 7.
• The choice of next steps should be guided by the patient's specific disease subtype and severity, as well as their co-morbidities and potential adverse effects of the treatments 5, 6.