AAV treatment

RTX was found to be non-inferior to daily CYC for the induction and maintenance of remission, but remission rates remain variable^1–3

• Patient achievement and maintenance of full remission remains variable with current therapies
• 1 in 3 patients fail to achieve remission at 6 months without use of GCs, and 1 in 2 fail to sustain remission at 12 months
• Non-severe relapse is an under-recognised clinical problem; these patients suffer subsequent relapses resulting in high GC exposure

CYC, cyclophosphamide; GC, glucocorticoid; RTX, rituximab

References 1. Stone JH, et al. N Engl J Med 2010;363(3):221–32. 2. Specks U, et al. N Engl J Med 2013;369(5):417–27. 3. Miloslavsky EM, et al. Arthritis Rheum 2015;67(6):1629–36.

Preliminary results show that a reduced GC dose can be effective for reinducing remission in AAV, and RTX was superior to AZA at maintaining remission^1,2

• Remission induction with a reduced GC dose should be considered clinically, as it was as effective as a typical GC dose regimen
• Initial findings show RTX to be superior to AZA in reducing relapses
• Relapses still occurred in both treatment groups. By 24 months, 13% of the RTX patients and 38% of the AZA patients experienced a relapse

AAV, ANCA-associated vasculitis; ANCA, anti-neutrophil cytoplasmic antibody; AZA, azathioprine; GC, glucocorticoid; RTX, rituximab

References 1. Smith RM, et al. Ann Rheum Dis 2020;79(9):1243–96. 2. Smith RM, et al. J Am Soc Nephrol 2019:30.

Reducing the GC dose in severe AAV patients did not significantly impact the primary outcome of death or ESRD, but did reduce the rate of infection (HR=0.69)¹

• Risk of death or ESRD with reduced GC dose was non-inferior to standard GC dose
• Reduced-dose regimen decreased the risk of serious infections (0.69; 95% CI, 0.52 to 0.93) without increasing the risk of other adverse events
• The continued use of a standard-dose GC regimen, even in patients with severe AAV should be re-evaluated
• Use of PLEX in this patient population provided no added benefit

AAV, ANCA-associated vasculitis; ANCA, anti-neutrophil cytoplasmic antibody; ESRD, end-stage renal disease; GC, glucocorticoid; HR, hazard ratio; PLEX, plasma exchange

Reference 1. Walsh M, et al. N Engl J Med 2020:382(7):622–31.

Avacopan-based regimen is superior at sustaining remission at Week 52 compared to a GC-based regimen¹

• At Week 26, avacopan-based regimen demonstrated non-inferiority in achieving clinical remission vs a GC-based regimen (p<0.001)
• At Week 52, avacopan-based regimen demonstrated superiority at sustaining clinical remission vs a GC-based regimen (p=0.007)
• Incidences of serious adverse events were similar in avacopan-based regimen and GC-based regimen groups (37.3% vs 39%, respectively)

GC, glucocorticoid

Reference 1. Jayne D, et al. N Engl J Med 2021;384(7):599–609.

RTX is more effective than AZA for maintenance of remission, but GC use and relapse remain common^1–4

• RTX was shown to be a more effective maintenance therapy than AZA for newly diagnosed AAV patients
• Minor and major relapses occurred throughout the maintenance phase of treatment. By Month 28, 17% of patients suffered a major relapse, increasing to 38% by Month 60
• GC use remained common amongst all patients throughout the 60-month follow-up period

AAV, ANCA-associated vasculitis; ANCA, anti-neutrophil cytoplasmic antibody; AZA, azathioprine; GC, glucocorticoid; RTX, rituximab

References 1. Guillevin L, et al. N Engl J Med 2014;371(19):1771–80. 2. Terrier B, et al. Ann Rheum Dis 2018;77(8):1150–6. 3. Terrier B, et al. Ann Rheum Dis 2018;77(8): 1150–6. [Supplementary appendix].
4. Guillevin L, et al. N Engl J Med 2014;371(19):1771–80. [Supplementary appendix].

Tailored and fixed-schedule RTX regimens are equally as effective at maintaining remission, but relapses still occur¹

• Relapse rates were similar with tailored and fixed-schedule RTX treatment
• The tailored regimen demonstrated that remission maintenance can be achieved with fewer RTX infusions
• Further research is required to establish reliable laboratory tests that can predict the appearance of relapse

RTX, rituximab

Reference 1. Charles P, et al. Ann Rheum Dis 2020;173(30):1143–9.

Extended maintenance therapy leads to better clinicaloutcomes¹

• Relapse rates were reduced in patients receiving long-term RTX treatment
  compared to standard maintenance therapy
• With standard maintenance therapy, relapse rates remain high. At month 28, 25% of patients experienced a relapse
• There was no difference in the incidence of AEs with long-term treatment

AE, adverse event; RTX, rituximab

Reference 1. Charles P, et al. Ann Intern Med 2020;173(30):179–87.