Granulomatosis with Polyangiitis (GPA, formerly Wegener Granulomatosis) Guidelines

Updated: Aug 31, 2021
  • Author: Christopher L Tracy, MD; Chief Editor: Herbert S Diamond, MD  more...
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Guidelines

Guidelines Summary

The American College of Rheumatology/Vasculitis Foundation has published a guideline for the management of antineutrophil cytoplasmic antibody–associated vasculitis, including granulomatosis with polyangiitis (GPA). The guideline contains recommendations and ungraded position statements; all the recommendations are conditional, as the level of supporting evidence ranges from very low to moderate. Recommendations and position statements regarding GPA also apply to microscopic polyangiitis. [7]

Remission induction for active, severe GPA

Conditional recommendations for induction of remission in patients with active, severe disease include the following [7] :

  • Rituximab is preferred to cyclophosphamide.
  • In patients with active glomerulonephritis, do not routinely add plasma exchange
  • Use a reduced-dose glucocorticoid regimen rather than a standard-dose regimen.

As a position statement, the guideline notes that either IV pulse or high-dose oral glucocorticoids may be prescribed as part of initial therapy.

Remission induction for active, nonsevere GPA

For induction of remission in patients with active, severe disease, the guideline conditionally recommends initiating treatment with methotrexate and glucocorticoids rather than with glucocorticoids alone, azathioprine and glucocorticoids, mycophenolate mofetil and glucocorticoids, or trimethoprim/sulfamethoxazole and glucocorticoids. [5]

Remission maintenance

Conditional recommendations for remission maintenance are as follows [5] :

  • For patients with severe GPA whose disease has entered remission after treatment with cyclophosphamide or rituximab, use rituximab rather than methotrexate or azathioprine.
  • For patients with GPA who are receiving rituximab for remission maintenance, provide scheduled re-dosing rather than using ANCA titers or CD19+ B-cell counts to guide re-dosing.
  • For patients with severe GPA whose disease has entered remission after treatment with cyclophosphamide or rituximab, use methotrexate or azathioprine rather than mycophenolate mofetil or leflunomide.
  • For patients with GPA whose disease has entered remission, use methotrexate or azathioprine in preference to trimethoprim/ sulfamethoxazole.
  • Do not add trimethoprim/sulfamethoxazole to other therapies (eg, rituximab, azathioprine, methotrexate) for the purpose of remission maintenance.
  • For patients receiving remission maintenance therapy with rituximab who have hypogammaglobulinemia (eg, IgG < 3 g/L) and recurrent severe infections, provide immunoglobulin supplementation.

As a position statement, the guideline advises that the duration of remission maintenance therapy (glucocorticoid or non-glucorticoid) should be guided by the patient’s clinical condition, preferences, and values.

Treatment of disease relapse

Conditional recommendations for patients with GPA who experience relapse with severe disease manifestations are as follows [7] :

  • In patients who are not receiving rituximab for remission maintenance, use rituximab rather than cyclophosphamide for remission re-induction.
  • In patients receiving rituximab for remission maintenance, switch from rituximab to cyclophosphamide rather than giving additional rituximab.

Treatment of refractory disease

Conditional recommendations for patients with refractory GPA are as follows [7] :

  • For severe GPA that is refractory to remisison induction with rituximab or cyclophosphamide, switch treatment to the other therapy rather than combining the 2 therapies.
  • For patients with GPA that is refractory to remission induction therapy, add IVIG to current therapy.

Treatment of sinonasal, airway, and mass lesions

As a position statement, the guideline notes that nasal rinses and topical nasal therapies (antibiotics, lubricants, and glucocorticoids) may be beneficial for patients with sinonasal involvement in GPA.

Conditional recommendations include the following:

  • For patients with GPA in remission who have nasal septal defects and/or nasal bridge collapse, reconstructive surgery, if desired by the patient, is recommended.
  • For patients with GPA who have actively inflamed subglottic and/or endobronchial tissue with stenosis, treat with immunosuppressive therapy in preference to surgical dilation with intralesional glucocorticoid injection alone.
  • For patients with GPA and mass lesions (eg, orbital pseudotumor or masses of the parotid glands, brain, or lungs), treat with immunosuppressive therapy in preference to surgical removal of the mass lesion with immunosuppressive therapy.

Other considerations

Conditional recommendations include the following:

  • Do not dose immunosuppressive therapy on the basis of ANCA titer results alone.
  • In patients who are receiving rituximab or cyclophosphamide, provide prophylaxis against  Pneumocystis jirovecii pneumonia.
  • For patients with GPA in remission and stage 5 chronic kidney disease, evaluate for kidney transplantation.
  • For patients with active GPA who are unable to receive other immunomodulatory therapy, administer IVIG.

As a position statement, the guideline notes that the optimal duration of anticoagulation is unknown for patients with GPA who experience venous thrombotic events.