From the Guidelines
For the treatment of granulomatosis with polyangiitis (GPA), rituximab (RTX) is recommended over cyclophosphamide (CYC) for remission induction, especially in patients with active severe GPA, according to the 2021 American College of Rheumatology/Vasculitis Foundation guideline 1.
Treatment Approach
The treatment approach for GPA typically involves a two-phase strategy: induction of remission followed by maintenance therapy.
- For induction, the combination of high-dose glucocorticoids (GC) plus either RTX or CYC is recommended, with RTX being preferred over CYC for active severe GPA, as it has shown better outcomes in terms of reducing the risk of relapse and improving quality of life 1.
- The use of reduced dose GC over standard dose GC is also recommended, as it can help minimize the side effects associated with long-term GC use 1.
Maintenance Therapy
Once remission is achieved, usually within 3-6 months, maintenance therapy follows with less toxic medications such as:
- RTX, which is the first choice for remission maintenance, due to its efficacy in preventing relapses and its relatively favorable side effect profile 1.
- Methotrexate (MTX) or azathioprine (AZA), which are also effective for maintaining remission and can be used as alternatives to RTX 1.
- Mycophenolate mofetil (MMF) or leflunomide (LEF) can be considered as third-line options for remission maintenance 1.
Monitoring and Prophylaxis
Regular monitoring of kidney function, complete blood counts, and urinalysis is essential to detect any potential side effects of the medications or signs of disease relapse.
- Patients should also receive Pneumocystis pneumonia prophylaxis with trimethoprim-sulfamethoxazole during immunosuppressive therapy to prevent opportunistic infections 1.
Disease Management
The disease involves ANCA (anti-neutrophil cytoplasmic antibody) autoantibodies, particularly PR3-ANCA, which activate neutrophils and cause vascular damage.
- Without treatment, GPA has a poor prognosis with high mortality, but with appropriate therapy, most patients achieve remission, though relapses may occur and require long-term monitoring 1.
From the FDA Drug Label
In the 6-month remission induction phase, 197 patients with GPA and MPA were randomized to either RITUXAN 375 mg/ m2 once weekly for 4 weeks plus glucocorticoids, or oral cyclophosphamide 2 mg/kg daily (adjusted for renal function, white blood cell count, and other factors) plus glucocorticoids to induce remission The primary analysis was at the end of the 6 month remission induction period and the safety results for this period are described below The main outcome measure for both GPA and MPA patients was achievement of complete remission at 6 months defined as a BVAS/GPA of 0, and off glucocorticoid therapy The study demonstrated non-inferiority of RITUXAN to cyclophosphamide for complete remission at 6 months As shown in Table 22, the study demonstrated non-inferiority of RITUXAN to cyclophosphamide for complete remission at 6 months Rate64% of patients in the RITUXAN group achieved complete remission at 6 months, compared to 53% of patients in the cyclophosphamide group
Rituximab is effective in treating Granulomatosis with Polyangiitis (GPA).
- 64% of patients in the RITUXAN group achieved complete remission at 6 months, compared to 53% of patients in the cyclophosphamide group.
- The study demonstrated non-inferiority of RITUXAN to cyclophosphamide for complete remission at 6 months 2.
- The main outcome measure for both GPA and MPA patients was achievement of complete remission at 6 months defined as a BVAS/GPA of 0, and off glucocorticoid therapy 3.
From the Research
Definition and Symptoms of Granulomatosis with Polyangitis
- Granulomatosis with polyangiitis (GPA) is a systemic vasculitis that affects blood vessels and presents with vague constitutional symptoms, but more serious manifestations can develop, including pulmonary complications and glomerulonephritis 4.
- GPA can present with multi-organ involvement, including the upper and lower respiratory tracts and kidneys, and central nervous system involvement is reported in less than 11% of cases 5.
- The disease evolves stage-wise and typically starts as inflammation of the respiratory tract followed by development of systemic vasculitis manifestations 6.
Treatment of Granulomatosis with Polyangitis
- Currently, there are no definitive treatment guidelines for GPA, but treatment is evidence-based and adapted according to activity and disease stage 6.
- Rituximab is an effective remission-inducing agent in GPA, and the addition of a conventional maintenance agent to rituximab and glucocorticoids decreased the incidence of relapse and did not result in a higher incidence of adverse events 7.
- For remission induction, rituximab was shown to be noninferior to cyclophosphamide, and the addition of plasma exchange to induction therapy in severe disease did not improve the composite end point of death or end stage renal disease 8.
- For maintenance of remission, methotrexate and azathioprine showed no difference in the risk of relapse, but rituximab was superior to a tapering azathioprine strategy in major relapse-free survival 8.
Prognosis and Complications of Granulomatosis with Polyangitis
- Early mortality during the first year of treatment poses one of the main problems and is a result of infections under immunosuppressive treatment 6.
- Treatment of refractory disease activity, which is often represented by granulomatous manifestations, is still a challenge and may result in significant organ damage if not treated successfully 6.
- A prompt diagnosis is necessary to initiate treatment and preserve organ function, and more research is needed to determine which combination therapies are the best treatment modalities in cases of severe multi-organ system involvement 4.