ANCA-Associated Vasculitis Management (ACR/VF 2021)

Algorithm Steps

1. ▶

   Start

   Suspected/Confirmed ANCA-Associated Vasculitis

   Clinical features and ANCA positivity suggesting AAV

   1. ●

      Action

      Confirm Diagnosis

      Establish AAV type and severity

      • ANCA testing: PR3-ANCA (c-ANCA) vs MPO-ANCA (p-ANCA)
      • Tissue biopsy when feasible (kidney, lung, sinus, skin)
      • Classify: GPA, MPA, or EGPA
      • Assess organ involvement: kidney, lung, ENT, skin, neuro, cardiac
      1. ◆

         Decision

         Disease Severity?

         Severe vs non-severe manifestations

         • SEVERE: Life/organ-threatening (DAH, RPGN, cardiac, CNS, GI, ocular)
         • NON-SEVERE: No immediate threat to life or organ function
         • EGPA assessed separately due to different management
         1. ●

            Action

            Severe GPA/MPA: Remission Induction

            Strong recommendation

            • Rituximab PREFERRED over cyclophosphamide (Strong)
            • RTX: 375 mg/m² weekly x4 OR 1000mg x2 (days 0, 14)
            • PLUS glucocorticoids: prednisone 1 mg/kg/day (max 80mg) or IV pulse
            • Alternative: Cyclophosphamide (oral or IV) + GC
            1. ●

               Action

               Glucocorticoid Protocol

               Taper to minimize toxicity

               • Start: Prednisone 1 mg/kg/day (max 80mg) OR IV pulse 500-1000mg x3 days
               • Reduce by ~25% per 2 weeks initially
               • Target: ≤10 mg/day by 3-6 months
               • Goal: Discontinue or ≤5 mg/day if possible
               • May use avacopan (C5a inhibitor) to reduce GC exposure
               1. ⚠

                  Warning

                  ⚠️ Infection Prophylaxis

                  During remission induction

                  • PCP prophylaxis: TMP-SMX DS 3x/week (Strong)
                  • Consider PPI for GI protection
                  • Vaccinations before rituximab if possible
                  • Monitor for infections closely
                  1. ◆

                     Decision

                     Remission Achieved?

                     Absence of active vasculitis signs/symptoms

                     1. ●

                        Action

                        Remission Maintenance

                        For GPA/MPA (Strong recommendations)

                        • Rituximab PREFERRED for GPA/MPA maintenance (Strong)
                        • RTX: 500mg q6mo OR 1000mg q4-6mo (various protocols)
                        • Duration: At least 2 years; longer if relapse risk
                        • Alternative: Azathioprine or MTX (if RTX contraindicated)
                        • Continue GC taper during maintenance
                        1. ✓

                           Outcome

                           AAV Controlled

                           Sustained remission on maintenance therapy

                     2. ●

                        Action

                        EGPA Maintenance

                        Differs from GPA/MPA

                        • Mepolizumab continuation for relapsing/steroid-dependent
                        • Alternative: Azathioprine, MTX, or MMF + low-dose GC
                        • Monitor for asthma/sinusitis control
                        • Cardiac follow-up if prior involvement
                     3. ●

                        Action

                        Refractory/Relapsing Disease

                        Failure of standard induction or maintenance

                        • Switch rituximab ↔ cyclophosphamide
                        • Increase rituximab frequency
                        • Consider avacopan if not already used
                        • Plasma exchange for severe renal/pulmonary disease
                        • Clinical trial or specialist vasculitis center
                        1. ⚠

                           Warning

                           Vasculitis Specialist Referral

                           Refractory disease, life-threatening manifestations, complex cases

               2. ⚠

                  Warning

                  ⚠️ Avacopan (Tavneos)

                  C5aR inhibitor - FDA approved for severe AAV

                  • 30 mg PO BID with rituximab or cyclophosphamide
                  • Allows reduced glucocorticoid exposure
                  • Monitor LFTs (hepatotoxicity risk)
                  • Alternative for GC-sparing in appropriate patients
         2. ●

            Action

            Non-Severe GPA/MPA: Remission Induction

            Conditional recommendation

            • Rituximab OR methotrexate + glucocorticoids
            • MTX: 15-25 mg/week (if no significant renal impairment)
            • Consider organ involvement and patient factors
            • GC taper similar to severe disease
         3. ◆

            Decision

            EGPA: Severe or Non-Severe?

            Eosinophilic GPA has distinct management

            1. ●

               Action

               Severe EGPA

               Life/organ-threatening manifestations

               • Rituximab OR cyclophosphamide + glucocorticoids
               • High-dose glucocorticoids initially
               • Consider mepolizumab after initial control
               • Address cardiac involvement urgently
            2. ●

               Action

               Non-Severe EGPA

               Conditional recommendation

               • Mepolizumab (anti-IL5) PREFERRED (Conditional)
               • Mepolizumab 300mg SC q4 weeks
               • Plus glucocorticoids (enables GC reduction)
               • Alternative: MTX or azathioprine + GC