What monoclonal antibody is recommended as monotherapy for a patient with severe rheumatoid arthritis intolerant to methotrexate and with a history of adverse reaction to Rinvoq (upadacitinib)?

Tocilizumab is the Recommended Monoclonal Antibody for Severe RA as Monotherapy

For a patient with severe rheumatoid arthritis who is intolerant to methotrexate and previously had a bad reaction to Rinvoq (upadacitinib), tocilizumab is the most appropriate monoclonal antibody for monotherapy with the least risk profile.

Rationale for Tocilizumab Selection

Tocilizumab stands out as the optimal choice for several key reasons:

1. Superior Efficacy as Monotherapy: Unlike other biologics, tocilizumab has been repeatedly demonstrated to be superior as monotherapy over methotrexate or other conventional DMARDs 1. This is particularly important for patients who cannot tolerate methotrexate.

2. FDA Approval: Tocilizumab is specifically indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs) 2.

3. Established Safety Profile: Tocilizumab has a well-documented safety profile when used as monotherapy, making it suitable for patients with previous adverse reactions to other medications.

Comparison with Other Monoclonal Antibody Options

TNF Inhibitors

While TNF inhibitors are effective, they generally show better results when combined with methotrexate rather than as monotherapy. Since this patient is methotrexate-intolerant, these would not be the optimal first choice.

Abatacept

Abatacept (CTLA4-Ig) is an option with a good safety record 1, but:

• Has not consistently demonstrated superiority as monotherapy over methotrexate alone 1
• Works best in combination with methotrexate, which this patient cannot tolerate

Rituximab

Rituximab could be considered, particularly given its safety profile in patients with history of malignancy 3, but:

• Is typically recommended after inadequate response to at least one TNF inhibitor 1
• Has not demonstrated consistent superiority as monotherapy

Dosing and Administration

For tocilizumab monotherapy, the recommended dosing options are:

• Intravenous: 4 mg/kg every 4 weeks, with possible increase to 8 mg/kg based on clinical response 2
• Subcutaneous:
  • For patients <100 kg: 162 mg every other week, with possible increase to weekly dosing
  • For patients ≥100 kg: 162 mg weekly 2

Monitoring Recommendations

When initiating tocilizumab:

• Obtain baseline complete blood count and liver function tests
• Do not initiate if:
  • Absolute neutrophil count (ANC) is below 2000 per mm³
  • Platelet count is below 100,000 per mm³
  • ALT or AST is above 1.5 times the upper limit of normal 2
• Monitor for potential adverse events including:
  • Upper respiratory infections
  • Elevated liver enzymes
  • Neutropenia
  • Thrombocytopenia

Important Considerations and Precautions

• Tocilizumab should not be used concurrently with other biological DMARDs due to increased risk of immunosuppression 2
• Dose reduction from 8 mg/kg to 4 mg/kg (IV) or changing from weekly to every other week (SC) may be necessary to manage certain laboratory abnormalities
• Patients should be monitored for signs of infection, as with all biological therapies

By selecting tocilizumab for this patient with severe RA who cannot tolerate methotrexate and has had a previous adverse reaction to Rinvoq, you are providing an evidence-based option with proven efficacy as monotherapy and a manageable safety profile.