What treatment approach is recommended for a patient with Granulomatosis with Polyangiitis (GPA) (also known as Wegener's granulomatosis) experiencing a gap in treatment?

Treatment Approach for Granulomatosis with Polyangiitis (GPA) After a Gap in Treatment

For patients with Granulomatosis with Polyangiitis (GPA) experiencing a gap in treatment, the recommended approach is to restart treatment with rituximab for remission re-induction, particularly if the patient previously had severe disease manifestations and was not receiving rituximab for maintenance therapy. 1

Assessment and Stratification

• First, assess the current disease activity and determine if the patient is experiencing a relapse with severe or non-severe manifestations 1
• Severe disease is characterized by organ- or life-threatening manifestations such as alveolar hemorrhage, rapidly progressive glomerulonephritis, or central nervous system involvement 1
• Non-severe disease includes manifestations that are not immediately life-threatening, such as mild upper airway disease, arthritis, or limited cutaneous involvement 1

Treatment Recommendations Based on Disease Severity

For Patients with Severe Disease Relapse:

• First-line therapy: Rituximab 375 mg/m² once weekly for 4 weeks plus glucocorticoids for remission re-induction 1, 2
• If the patient experienced relapse while receiving rituximab for maintenance, switch to cyclophosphamide for remission re-induction 1
• Consider reduced-dose glucocorticoid regimen (starting with pulse methylprednisolone followed by tapering oral dose) to minimize toxicity while maintaining efficacy 1
• Pneumocystis jirovecii pneumonia prophylaxis is recommended for patients receiving rituximab or cyclophosphamide 1, 3

For Patients with Non-Severe Disease Relapse:

• Rituximab plus glucocorticoids is still preferred over methotrexate plus glucocorticoids 1
• Methotrexate can be considered as an alternative if rituximab is contraindicated 1
• For patients who cannot receive standard immunomodulatory therapy, IVIG (2 g/kg divided over 5 days) may be administered 1, 4

Remission Maintenance After Re-induction

• After achieving remission, initiate maintenance therapy with:
  • First choice: Rituximab (500 mg every 6 months) 1, 2
  • Alternatives: Methotrexate or azathioprine 1
  • Third-line options: Mycophenolate mofetil or leflunomide 1
• If remission was achieved with rituximab, maintenance therapy should begin within 24 weeks after the last induction dose, but no sooner than 16 weeks 2
• If remission was achieved with other agents, maintenance therapy should begin within 4 weeks of achieving disease control 2

Important Considerations and Pitfalls

• Do not base treatment decisions solely on ANCA titer results 1
• The duration of maintenance therapy should be guided by the patient's clinical condition, preferences, and values rather than a fixed time period 1
• For refractory disease not responding to either rituximab or cyclophosphamide, switch to the other agent rather than combining them 1
• Venous thrombotic events in patients with active GPA can be considered provoked events with transient risk factors, potentially allowing for short-term rather than lifelong anticoagulation 1
• Delaying treatment reinitiation after a gap can significantly worsen outcomes due to the potentially rapid progression of the disease 3

Special Situations

• For patients with sinonasal involvement, consider adding nasal rinses and topical nasal therapies (antibiotics, lubricants, and glucocorticoids) to systemic treatment 1
• For patients with subglottic or endobronchial stenosis, immunosuppressive therapy is preferred over surgical dilation with intralesional glucocorticoid injection alone 1
• For patients with mass lesions (orbital, parotid, brain, or lung), immunosuppressive therapy is recommended over surgical removal 1
• For patients who cannot receive standard immunomodulatory therapy (e.g., due to severe infection or pregnancy), IVIG can be used as a short-term intervention 4

By following these evidence-based recommendations, clinicians can effectively manage patients with GPA experiencing a gap in treatment, minimizing the risk of disease progression while optimizing outcomes related to morbidity, mortality, and quality of life.