16th January 2024

Management 

Untreated GPA has a poor prognosis; therefore, it is vital a diagnosis is made quickly and treatment begun. The first stage of treatment focuses on achieving remission from the disease, and the second stage focuses on maintaining remission and preventing disease relapse.

It is recognised that during active disease, irreversible damage to various organs may have occurred and will remain regardless of treatment. Therefore, the goal of remission is instead to ensure resolution of symptoms and signs, accepting that some measured parameters may permanently remain abnormal or take significant time to improve. Any recurrence of clinical symptoms/signs would be deemed indicative of relapse, regardless of the organ affected.

Achieving remission

Several medications are required to induce remission for people with GPA, as monotherapy is usually ineffective. Steroids such as prednisolone plus further immunosuppressive medications are the mainstay of this stage of treatment. For severe disease, remission can take up to 6 months to achieve after treatment begins; if remission does not occur, an alternative medication regimen should be trialled.

The induction regime used depends on the status of disease: non-severe, severe or refractory to treatment. Non-severe disease is defined by no evidence of organ or life-threatening disease, e.g., lack of evidence of progressive neuropathy or active bleeding in any organ. Severe disease is defined as disease-causing an active threat to organs or life, e.g., pulmonary or GI haemorrhage, active glomerulonephritis, pericarditis, etc. Refractory disease is disease that has failed to effectively respond to an approved induction therapy regime. The induction regimes commonly used to achieve remission in GPA are detailed below.

Adapted from: Molloy, E. (2022) BMJ Best Practice Granulomatosis with polyangiitis. Available at: https://bestpractice.bmj.com/topics/en-gb/327/pdf/327/Granulomatosis%20with%20polyangiitis.pdf (Accessed: January 15, 2023) and Merkel, P., Kaplan, A. and Falk, R. (2022) Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy. Edited by G. Appel et al. Up To Date. Available at: https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-induction-and-maintenance-therapy?search=gpa&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2 (Accessed: January 15, 2023). 

Maintaining remission

Patients can be commenced on an appropriate maintenance therapy regime of immunotherapy agents, usually initially with steroids. The regime used will be decided on how successful and tolerated the medications used during the induction phase of treatment were.

Suitable medications to maintain remission are rituximab, methotrexate or azathioprine. IV cyclophosphamide is only used to induce remission, so patients on this medication will need to be switched to an alternative medication to maintain remission about 6 months after their last intravenous dose. If methotrexate was used to induce remission, it can be continued for maintenance as well. Mycophenolate is usually only commenced/continued for remission for those who cannot tolerate other immunosuppressive medications or those with resistant disease.

Duration of therapy needed can vary, and current evidence suggests maintenance treatment should be continued for at least 2 years after remission is achieved. If any disease relapse occurs, lifelong maintenance therapy is advised, even if only one has occurred. To treat a relapse, another remission induction regime will need to be commenced until the GPA is controlled again.

The steroids started during the induction period can be slowly weaned down if symptoms remain well controlled, but this must take place over a significant period of time. It is preferable for patients to remain on a low-dose maintenance steroid if needed to reduce risk of relapse if no contraindications to this are present and suitable monitoring can take place.

Monitoring recommendations

Full blood count, renal and liver function, plus inflammatory markers and urinalysis, should be tested to monitor for side effects from treatment and any evidence of recurring disease approximately every 3 months. Some of the potential conditions that can develop as a result of the above immunosuppressive medications and steroids are osteoporosis, bone marrow toxicity, renal failure and infection.

Other treatment considerations

All of the treatment agents discussed in this section have toxicity risks, especially cyclophosphamide, which can have a number of serious side effects, such as increased risk of bladder cancer. It is also known to contribute to infertility; therefore, for those wishing to preserve their fertility, rituximab should be offered instead in the induction phase of treatment. Any patient receiving rituximab or cyclophosphamide should also be commenced on pneumocystis jirovecii prophylactic medication to prevent pneumocystis jirovecii pneumonia (PCP). Patients on a daily steroid dose of 20 milligrams or more, alongside methotrexate, azathioprine or mycophenolate therapy, should also be considered for PCP prophylaxis.

Methotrexate should not be given to those with an eGFR <60mL/min and is contraindicated in pregnancy. Azathioprine could be a suitable alternative agent in these cases.