Treatment of Systemic ANCA-Positive Vasculitides
The correct treatment components for systemic ANCA-positive vasculitis include induction therapy with intravenous cyclophosphamide (or rituximab), maintenance therapy with azathioprine or mycophenolic acid, and control of cardiovascular risk factors; however, high-dose intravenous corticosteroids are NOT used for "the first few months" but rather rapidly tapered, and TNF-α biologics are NOT part of standard treatment. 1
Induction Therapy (Option a - CORRECT)
Intravenous cyclophosphamide is a validated induction option for ANCA-associated vasculitis, typically dosed at 15 mg/kg at weeks 0,2,4,7,10, and 13, with dose reductions for age (12.5 mg/kg for age >60 years, 10 mg/kg for age >70 years) and renal impairment. 1
- Rituximab (375 mg/m² weekly for 4 weeks) is equally effective and increasingly preferred, particularly for relapsing disease. 1, 2
- Both cyclophosphamide and rituximab achieve remission rates of 70-90% when combined with glucocorticoids. 3, 4
Corticosteroid Dosing (Option c - INCORRECT as stated)
High-dose intravenous corticosteroids are NOT continued "for the first few months" - this is a critical misconception. 1
- The modern approach uses reduced-dose glucocorticoids (0.5-1 mg/kg/day prednisolone equivalent) that are rapidly tapered. 1, 5
- Recent evidence demonstrates that reduced-dose glucocorticoids (0.5 mg/kg/day) are noninferior to high-dose (1 mg/kg/day) for remission induction, with significantly fewer serious adverse events (18.8% vs 36.9%) and infections (7.2% vs 20.0%). 5
- Glucocorticoids should be tapered to 5-7.5 mg/day by 2 years, then reduced by 1 mg every 2 months. 1
Maintenance Therapy (Option d - CORRECT)
Maintenance therapy with azathioprine (1.5-2 mg/kg/day) or mycophenolate mofetil (2000 mg/day) is recommended after achieving remission. 1
- Azathioprine is preferred over mycophenolate mofetil based on the IMPROVE trial, which showed higher relapse rates with MMF (42 vs 30 patients, p<0.01). 1
- Rituximab maintenance is superior to azathioprine for preventing relapses, particularly in PR3-ANCA positive and relapsing disease (3 vs 17 major relapses in MAINRITSAN trial). 1, 2
- Optimal maintenance duration is 18 months to 4 years after induction of remission, individualized based on relapse risk factors (PR3-ANCA positivity, persistent ANCA positivity, cardiovascular/lung involvement). 1, 2
TNF-α Biologics (Option b - INCORRECT)
TNF-α directed biologics are NOT part of standard treatment for ANCA-associated vasculitis. 6
- While TNF-directed treatment has been explored in treatment-resistant cases, it is not recommended in current guidelines. 6
- The standard biologics for AAV are anti-CD20 agents (rituximab), not anti-TNF agents. 1
Cardiovascular Risk Factor Control (Option e - CORRECT)
Control of cardiovascular risk factors is an essential component of comprehensive AAV management, though not explicitly detailed in vasculitis-specific guidelines, this represents standard care for patients on chronic immunosuppression and glucocorticoids. 1
Key Clinical Pitfalls
- Avoid prolonged high-dose glucocorticoids - the evidence strongly supports rapid tapering to minimize toxicity without compromising efficacy. 5
- Do not use methotrexate as maintenance if GFR <60 ml/min/1.73 m². 1
- Consider plasma exchange only for severe renal impairment (creatinine >3.4 mg/dL or dialysis-dependent) or diffuse alveolar hemorrhage with hypoxemia, not routinely. 1
Answer: Options a, d, and e are correct; options b and c are incorrect.