Treatment outcomes

Treatment has improved, but treatment-related complications remain common.

Achieving and sustaining remission – What do clinical trial and real-world data show?

RAVE clinical trial: Remission rate is variable and patients often do not stay in full remission1,2*
In patients with organ- or life-threatening GPA (Granulomatosis with Polyangiitis, previously called Wegener’s) or MPA (Microscopic Polyangiitis), their response to standard of care treatment is variable and they do not always achieve, and remain in, full remission (BVAS/WG=0 and have stopped glucocorticoids):1,2*

Treatment outcomes Treatment outcomes Treatment outcomes

Early vasculitis control is a good predictor of long-term patient survival and renal outcomes3‡
Achieving early remission in the first 3 months of therapy induction and sustaining it to 6 months is associated with increased long-term cumulative survival over a median 5.7-year follow-up (N=354). In this study, remission was defined as a BVAS of 0, but patients could still be using glucocorticoids.3

Cox proportional hazard model for composite endpoint of mortality or ESRD3

Treatment outcomes

Figure adapted from Gopaluni S, et al. Arthritis Rheumatol 2019

Real-world reality: Many patients do not achieve or sustain full remission
Patient response to remission induction therapy is variable. After 12 months of therapy (N=929), 59% of GPA (Granulomatosis with Polyangiitis, previously called Wegener’s) and MPA (Microscopic Polyangiitis) patients achieve full remission, and >50% of patient continue glucocorticoid use.4 An unmet need exists, more patients need to achieve and sustain remission without prolonged glucocorticoid use.


Response to induction therapy is variable and many patients do not achieve full response even at 12 months4

>50% of patients continue to use glucocorticoids 12 months after starting induction therapy


Minor relapse – a major problem5**

AAV patients experience minor relapses when receiving remission induction therapy.
As a result, many patients still receive glucocorticoids long-term.5


Mean cumulative prednisone dose vs patients who achieve and maintain remission to 18 months

  • 6.7 g vs 3.8 g, p<0.01


  • Achieve remission before relapse: 91%
  • Mean time to 1st relapse: 7.5 months
  • Receiving prednisone at 1st relapse: 36%
  • Median prednisone dose at relapse: 5.0 mg/day
  • Most common manifestation: ENT (25%)
  • Renal involvement: 9%

Prednisone increase leading to remission: 80% of patients (n=35) Median prednisone dose to treat 1st non-severe relapse: 17.5 mg/day

Second non-severe relapse: n=17 Severe relapse: n=14

  • Mean time to 2nd relapse: 9.4 months after 1st relapse
  • Receiving prednisone at 2nd relapse: 52%
  • Median prednisone dose: 7.5 mg/day
  • Prednisone dose to treat 1st relapse: NS
  • Baseline characteristics or organ involvement at 1st relapse: NS

Mean 12.5 months after 1st non-severe relapse remained in remission:
n=13 ≥20 mg/day vs <20 mg/day prednisone: NS

After the initial minor relapse; glucocorticoid dose was increased, 31/44 patients could not achieve or maintain remission, 55% of these experienced a second minor relapse, typically treated with an increase in glucocorticoid dose.5

Minor relapse is an under-recognised clinical problem, leading to prolonged high dose glucocorticoid exposure in patients.

MAINRITSAN clinical trial: Relapses still occur in the maintenance phase with patients still receiving glucocorticoids6–9††

Many GPA and MPA patients experience major and minor relapses when receiving maintenance therapy, by Month 28 of maintenance therapy (N=115):6

• 29% of patients treated with azathioprine experience a major relapse and 16% experience a minor relapse.

• 5% of patients treated with rituximab experience a major relapse and 11% experience a minor relapse.

Long-term follow-up at Month 60 demonstrates that relapses are still prevalent, in patients previously relapse free, 19% of azathioprine patients and 23% of rituximab patients experience a major relapse.8 Patients continued to use glucocorticoids, with both treatment groups receiving a mean glucocorticoid dose of 3.3 mg/day at Month 60.9

Glucocorticoid use at Month 28 (N=115)7

Treatment outcomes Treatment outcomes

References & footnotes



Organ damage in AAV

GPA and MPA patients accumulate organ damage from a combination of vasculitis activity and glucocorticoid-related AEs1–3

Long-term and repeated high-dose glucocorticoid use is associated with an increased risk of new onset/worsening of diabetes mellitus, hypertension, osteoporosis, avascular necrosis of bone, malignancy, cataracts and other debilitating side effects.1,2* In a study following newly diagnosed GPA and MPA patients for up to 7 years, the frequency of damage, including potentially treatment-related damage, rose over time (p<0.01). Patients initially experience early increased damage following diagnosis (n=270), with 81.5% of patients ≥1 item in the VDI at 6 months, compared to 24.4% of patients at baseline, with renal (proteinuria and GFR <50 mL/minute) and cardiovascular (hypertension) damage the most frequent. Severe damage, a VDI score ≥5, increases over time, at long-term follow-up 33.7% of patients had severe damage. Hypertension was the most commonly reported item at long-term follow-up, demonstrating an accumulation of cardiovascular damage over time. At baseline, 4.8% of patients had hypertension, within 6 months this rose to 17.0%, at long-term follow-up 41.5% of patients had hypertension (p<0.01).2†

High levels of long-term vasculitis damage were independently associated with increased cumulative glucocorticoid use (p=0.016).3†
This serious morbidity is accompanied by a significantly increased long-term mortality risk, with a hazard ratio of 2.41 (95% CI: 1.74–3.34) in GPA patients compared with age- and sex-matched controls.2–4†‡

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References & footnotes Treatment outcomes

At a mean of 7 years post diagnosis in patients with GPA or MPA…2†

Treatment-related AEs

Treatment-related AEs are common during the initial stages of remission induction therapy, at this time patients typically receive high dose glucocorticoids in combination with cyclophosphamide or rituximab. AEs are highest during the first 3 months of therapy, and over 12 months the proportion of patients with ≥1 toxicity reaction / AE increases. The majority of patients continue to use glucocorticoids 12 months after starting remission induction.1*

Treatment outcomes Treatment outcomes

Treatment-related AEs are the leading cause of acute mortality.2,3 In the first year after a GPA or MPA diagnosis, 56 of 524 patients died, 59% of these patients' deaths were as a result of treatment-related AEs.2†

Treatment outcomes

A systematic literature review of glucocorticoid-related AEs in AAV clinical studies published between 1 January 2007 and 30 January 2018 identified mortality (33%) as the glucocorticoid-related serious AE with the highest frequency observed during early induction treatment. Other common glucocorticoid-related serious AEs experienced by patients include infections (20%), musculoskeletal (17%) and renal disorders (15%).3†

References & footnotes



New therapies and innovative strategies1,2

Treatment outcomes

“Ongoing advances in understanding ANCA disease mechanisms, and development of more effective, less toxic, and more targeted therapies, undoubtedly will lead to even better outcomes in the future.”3

– Jennette JC, Nachman PH. Clin J Am Soc Nephrol 2017

Treatment outcomes

“Biologic therapies that target specific cellular and molecular components of the autoimmune response and the mediators of inflammatory injury may be more effective and less toxic.”3

– Jennette JC, Nachman PH. Clin J Am Soc Nephrol 2017

References & footnotes