OP0029 MAINTENANCE TREATMENT FOR ANCA-ASSOCIATED VASCULITIS IN REAL WORLD PRACTICE IN EUROPE – REALITY OF VASCULITIS REMISSION AND RELAPSE AND SIGNIFICANT BURDEN OF DISEASE

Background:After successful remission induction, ANCA associated vasculitis (AAV) is a relapsing remitting long term condition and patients are at risk of organ damage from both active AAV and therapy in particular glucocorticoids (GC). The remission maintenance phase of AAV is critical for preventing relapse and ensuring organ protection.Objectives:This retrospective study aimed to examine the definition of maintenance start, therapy used and clinical outcomes in patients managed in routine clinical practice.Methods:1478 AAV patients (France, Germany, Italy, Spain and UK) managed by 493 physicians (37% Rheumatologists) who completed induction therapy for organ or life threatening AAV and initiated maintenance therapy between 2014-16 were studied. Data were collected at the time maintenance was determined to begin by the physician and then at 6, 12, 18 and 36 months.Results:49% had granulomatosis with polyangiitis,; mean age 54.2 years with 56% male. 49% had incident AAV and 51% were studied from a relapse. 70% received cyclophosphamide and GC and 30% received rituximab and GC. Physicians defined time of the start of maintenance from induction treatment start with mean of 5.7 months on basis of fixed time point 40%, starting new drug for maintenance 26%, reaching full remission 26% and no specific criteria 8%. At this time 43% were in full remission vs 50% in partial and 7% refractory. Various maintenance regimes were used, 21% received rituximab (88% 6 monthly and 8% 12 monthly, 4% other) at varying planned doses 34% 1g, 40% 500 mg and 23% 375 mg/m2, 4% other regime. Remission rates varied, relapse of different severity still occurs and many patients experienced adverse events (AE) and infections with prolonged GC use being common.Maintenance start6 months12 months18 months36 monthsRemission full/partial %43 / 5059 / 3867 / 3072 / 2574 / 22Total relapse / major %12/499 / 456/ 447 / 32Receiving GC%6561534639At least one AE %6652484342At least one infection %5442322726At the most recent clinic review patients had been followed for a mean of 50.7 months – 6% had died, 38% had relapsed at least once, and 11% required renal replacement therapy. 54% had no vasculitis activity, 26% were ANCA positive without active disease and 19% still experiencing active disease. 32% were still receiving GCs - 22% of them receiving > 5mg/ day. There was negative impact on functional status with 14% reducing working hours, 13% restricted social life, 6% leaving employment, 6% registered as disabled and 2% leaving full time education.Conclusion:The start of maintenance treatment in AAV is variably defined but typically at 6 months after start of remission induction therapy. Achieving full remission and preventing relapse are still clinical problems and many patients require ongoing GC therapy to maintain remission. Infectious complications and adverse events are common and there is significant negative impact on patient functional status over time.Disclosure of Interests:Peter Rutherford Shareholder of: Vifor Pharma, Employee of: Vifor Pharma, Baxter Healthcare, Dieter Götte Shareholder of: Vifor Pharma, Employee of: Vifor Pharma

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P178 Maintenance treatment for ANCA-associated vasculitis in real world practice in the UK: reality of vasculitis remission and relapse and burden of disease

Rheumatology ◽

10.1093/rheumatology/keaa111.173 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

David Worthington ◽

Peter Rutherford

Keyword(s):

Functional Status ◽

Induction Therapy ◽

Social Life ◽

Negative Impact ◽

Maintenance Phase ◽

Working Hours ◽

Fixed Time ◽

Remission Induction ◽

Full Time ◽

Full Remission

Abstract Background AAV is a relapsing remitting condition and patients are at risk of organ damage from active AAV and therapy especially glucocorticoids (GC). The maintenance phase of AAV is critical for good long-term outcomes. This retrospective study examined maintenance definition, therapy and outcomes in patients in routine clinical practice. Methods 300 AAV patients managed by 100 UK physicians (40% rheumatologists) who completed induction therapy for organ or life threatening AAV and initiated maintenance between 2014-16 were studied. Data were collected at time maintenance was determined to begin by the physician and at 6, 12, 18 and 36 months. Results 56% had granulomatosis with polyangiitis; mean age 55.4 years 54% male. 61% had incident AAV and 39% relapsed. Physicians defined time of start of maintenance from treatment start with mean of 4.5 months, on basis of fixed time point 47%, starting new maintenance drug 27%, reaching full remission 16% and no specific criteria 9%. At this time 45% were in full remission vs 49% in partial and 6% refractory. Various maintenance regimes were used, 11% received rituximab (84% 6 monthly and 16% 12 monthly) at varying planned doses 61% 1g, 19% 500 mg and 16% 375 mg/m2, 4% not recorded. Remission rates varied and many patients experienced adverse events (AE) and infections, prolonged GC use was common. At most recent review patients had been followed for a mean of 49.2 months - 6% had died, 30% relapsed at least once, and 10% required renal replacement therapy. 62% had no vasculitis activity and were ANCA negative with 14% still experiencing active disease. 35% still received GCs - 19% > 5mg/ day. There was negative impact on functional status with 13% reducing working hours, 13% restricted social life, 4% leaving employment, 3% registered as disabled and 2% leaving full time education. Conclusion Maintenance therapy is variably defined at 4-5 months from start of remission induction therapy. Achieving full remission and preventing relapse are still problems and many patients require GC therapy to maintain remission. Infectious complications are a problem and there is significant negative impact on patient functional status. Disclosures D. Worthington Corporate appointments; Employee of Vifor Pharma. P. Rutherford Corporate appointments; Employee of Vifor Pharma. Shareholder/stock ownership; Vifor Pharma.

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P0410SIGNIFICANT BURDEN OF DISEASE DURING MAINTENANCE TREATMENT OF ANCA-ASSOCIATED VASCULITIS (AAV) PATIENTS IN REAL WORLD PRACTICE IN EUROPE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0410 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Peter Rutherford ◽

Dieter Götte

Keyword(s):

Adverse Events ◽

Maintenance Therapy ◽

Induction Therapy ◽

Remission Induction ◽

Induction Treatment ◽

High Dose ◽

Full Remission ◽

Anca Associated Vasculitis ◽

Active Disease

Abstract Background and Aims ANCA associated vasculitis (AAV) is a relapsing remitting long term condition and patients are at risk of organ damage from both active AAV and its therapy in particular high dose and/or prolonged glucocorticoids (GC). The remission maintenance phase of AAV is critical for good long term outcomes including renal preservation as well as preventing AAV relapse. This retrospective study aimed to examine the definition of maintenance, therapy and clinical outcomes in patients managed in routine practice. Method 1478 AAV patients (France, Germany, Italy, Spain and UK) managed by 493 physicians (61% Nephrologists) who completed induction therapy for organ or life threatening AAV and initiated maintenance therapy between 2014-16 were studied. Data were collected retrospectively at the time maintenance was determined to begin by the physician and then at 6, 12, 18 and 36 months. Results 49% had granulomatosis with polyangiitis,; mean age 54.2 years with 56% male. 49% had incident AAV and 51% were studied from the time of a relapse requiring remission induction therapy. 70% received cyclophosphamide and GC and 30% received rituximab and GC as induction treatment with 28% receiving plasma exchange. Physicians defined time of the start of maintenance from induction treatment start with mean of 5.7 months on the basis of fixed time point 40%, starting new drug for maintenance 26%, reaching full remission 26% and no specific criteria 8%. At this time of maintenance start 43% were in full remission vs 50% in partial and 7% refractory. Various maintenance regimes were used, 21% received rituximab (88% 6 monthly and 8% 12 monthly, 4% other) at varying planned doses 34% 1g, 40% 500 mg and 23% 375 mg/m2, 4% other regime. Remission rates varied with patients experiencing disease relapse and many patients experienced adverse events (AE) and infections with prolonged GC use being common. Renal function was relatively unchanged and some patients had worsening eGFR, protein excretion or blood pressure. At the most recent clinical review patients had been followed for a mean of 50.7 months – 6% had died, 38% had relapsed at least once, and 11% required renal replacement therapy. 54% had no vasculitis activity, 26% were ANCA positive without active disease and 19% were still experiencing active disease. 32% were still receiving GCs - 22% of them receiving > 5mg/ day. Conclusion Maintenance therapy is variably defined but typically at 6 months from start of remission induction therapy. Achieving full remission and preventing relapse are still clinical problems and many patients require ongoing GC therapy to maintain remission. Infectious complications and adverse events are common and renal disease remains an ongoing clinical problem.

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Distinguishing active from quiescent disease in ANCA-associated vasculitis using attenuated total reflection Fourier-transform infrared spectroscopy

Scientific Reports ◽

10.1038/s41598-021-89344-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Adam D. Morris ◽

Camilo L. M. Morais ◽

Kássio M. G. Lima ◽

Daniel L. D. Freitas ◽

Mark E. Brady ◽

...

Keyword(s):

Fourier Transform ◽

Unmet Need ◽

Fourier Transform Infrared ◽

Total Reflection ◽

Attenuated Total Reflection ◽

Remission Induction ◽

Disease Remission ◽

Anca Associated Vasculitis ◽

Active Disease ◽

Quiescent Disease

AbstractThe current lack of a reliable biomarker of disease activity in anti-neutrophil cytoplasmic autoantibody (ANCA) associated vasculitis poses a significant clinical unmet need when determining relapsing or persisting disease. In this study, we demonstrate for the first time that attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy offers a novel and functional candidate biomarker, distinguishing active from quiescent disease with a high degree of accuracy. Paired blood and urine samples were collected within a single UK centre from patients with active disease, disease remission, disease controls and healthy controls. Three key biofluids were evaluated; plasma, serum and urine, with subsequent chemometric analysis and blind predictive model validation. Spectrochemical interrogation proved plasma to be the most conducive biofluid, with excellent separation between the two categories on PC2 direction (AUC 0.901) and 100% sensitivity (F-score 92.3%) for disease remission and 85.7% specificity (F-score 92.3%) for active disease on blind predictive modelling. This was independent of organ system involvement and current ANCA status, with similar findings observed on comparative analysis following successful remission-induction therapy (AUC > 0.9, 100% sensitivity for disease remission, F-score 75%). This promising technique is clinically translatable and warrants future larger study with longitudinal data, potentially aiding earlier intervention and individualisation of treatment.

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Treatment practices, response to therapy and adverse events in ANCA-associated vasculitis patients in Europe: top-line findings from a retrospective observational study

10.21203/rs.2.16847/v1 ◽

2019 ◽

Author(s):

Peter Rutherford ◽

Dieter Goette

Keyword(s):

Adverse Events ◽

Clinical Outcomes ◽

Real World ◽

Response To Therapy ◽

Remission Induction ◽

Induction Treatment ◽

Symptom Duration ◽

Similar Distribution ◽

Presenting Symptoms ◽

Anca Associated Vasculitis

Abstract Background ANCA-associated vasculitis patient outcome data in the real world setting is scarce. This study measures key clinical outcomes and adverse effects over the first 12 months of remission induction therapy.Methods This was a retrospective study of 929 newly diagnosed [ND] and 268 relapsing patients [RP] conducted online by 399 clinicians. Each clinician completed a survey for 3 patients meeting the following criteria: initiated remission induction treatment for new or relapsing disease between Nov 2014 and Feb 2017, ≥ 6 months of therapy including ≥ 1 course of induction therapy, under continuous care for ≥12 months. Data were collected relating to baseline presentation and at 1, 3, 6, and 12 months.Results 58% were >55 years old with more granulomatosis with polyangiitis (GPA, 54%) versus microscopic polyangiitis (MPA, 46%), and <20% of patients had Birmingham Vasculitis Activity Scoring (BVAS) performed. Median symptom duration prior to diagnosis was 6 to 7 weeks. Presenting symptoms were similar between ND and RP, noted differences (≥ 5%) were more fever, rash, and neuropathy, and less renal disease in RP. The majority (68% ND and 84% RP) had at least one comorbidity at diagnosis, with a similar distribution. Glucocorticoids (GC) were used by 83% ND and 76% RP; >50% were still receiving GC at 12 months. Most common treatments were cyclophosphamide+GC for ND (59%) and rituximab+GC for RP (44%). Many patients had slow and/or partial response to therapy, by 12 months >60% had a full response. 81% of patients with response by month 1 maintained full response through month 12. Adverse events and infections were common, especially during the first 3 months when GC use is highest.Conclusions Real world data show that both ND and RP ANCA-associated vasculitis patients respond variably to induction remission treatment and many experience adverse events and infections over the first 12 months of treatment. The presence of comorbidities at treatment initiation in most patients compounded the adverse impacts of disease and treatment. This study improves our understanding of the reality of clinical outcomes in ANCA-associated vasculitis and the need for targeted therapeutic approaches.

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P179 Glucocorticoid exposure and link to serious adverse events in patients with ANCA-associated vasculitis

Rheumatology ◽

10.1093/rheumatology/keaa111.174 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Philip Spearpoint ◽

Cormac Sammon ◽

Antonio Ramirez de ◽

Arellano Serna ◽

Peter Rutherford

Keyword(s):

Cardiovascular Disease ◽

Adverse Events ◽

Renal Disease ◽

Real World ◽

Low Dose ◽

Remission Induction ◽

High Dose ◽

Anca Associated Vasculitis ◽

Increased Risk ◽

New Onset

Abstract Background Remission induction in ANCA-associated vasculitis (AAV) is with high dose glucocorticoids (GC) and immunosuppressants. Patients are exposed to high GC dose and/or prolonged low dose. EULAR/EDTA guidelines target 7.5-10mg at 3 months but acknowledge this is often achieved later. This study used UK real world practice data to examine the scale of GC exposure and associated clinical risks in AAV. Methods The study utilised the Clinical Practice Research Datalink (CPRD) - Hospital Episode Statistics (HES) linked database. AAV patients were identified using specific READ and ICD codes and followed between 01/01/1997 and 01/01/2018. GP prescriptions were used to describe periods of continuous GC use, stop and restart and when high dose (> 30mg/day) and low dose (<30mg/day) was prescribed. Diagnostic codes indicative of infections and adverse events linked to GCs were used to estimate rates in the AAV population using a generalized linear model with a Poisson distribution. Results 450 AAV patients with at least one GC prescription were analysed. The median dose decreased to 9.3 mg (IQR 5.0 - 17.0) at 6 months and 5.1 mg (0.00 - 10.0) at 12 months,50% patients were taking > 10mg at 5 months and 25% were still > 10mg at 12 months. However, within 6 months of achieving 10mg/day, 50% relapse to needing dose >10mg, 75% within 2 years and 90% within 6 years. In adjusted Poisson model (age, gender, year of diagnosis before/after 2013) the rate of infection in AAV patients taking high dose was 2.59 times (CI95 1.95, 3.45) that of those on low dose and lower in those not taking GCs (IRR 0.27 (0.22-0.34)). Increased risk of new onset cardiovascular disease (IRR 2.55 (0.92, 7.04)) and new onset renal disease (IRR 3.4 (1.29-8.96)) were higher in patients receiving high dose. Conclusion AAV patients have significant exposure to high dose GCs and in real world practice, GC dose remains higher than recommended in current clinical guidelines. High dose GCs are associated with high risk of infection and new cardiovascular disease and renal disease. This creates a significant patient burden and has implications for healthcare resource use. Disclosures P. Spearpoint: Corporate appointments; Employee of Vifor Pharma. C. Sammon: Corporate appointments; Employee of PHMR. A. Ramirez de Arellano Serna: Corporate appointments; Employee of Vifor Pharma. P. Rutherford: Corporate appointments; Employee of Vifor Pharma. Shareholder/stock ownership; Vifor Pharma.

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The Role of Mycophenolate Mofetil for the Induction of Remission in ANCA-Associated Vasculitis: A Meta-Analysis

Frontiers in Medicine ◽

10.3389/fmed.2021.609924 ◽

2021 ◽

Vol 8 ◽

Author(s):

Anji Xiong ◽

Chen Xiong ◽

Guancui Yang ◽

Yu Shuai ◽

Deng Liu ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Induction Therapy ◽

Remission Rate ◽

Meta Analysis ◽

Statistical Significance ◽

Renal Involvement ◽

Random Effect ◽

Cochrane Library ◽

Remission Induction ◽

Anca Associated Vasculitis

Objectives: The successful introduction of mycophenolate mofetil (MMF) as a treatment for renal allograft reduced the incidence of acute rejection. The inspiring effects obtained by the MMF have led to an evaluation of its therapeutic potency on ANCA-associated vasculitis (AAV). However, there is little evidence of the MMF's efficacy on the AAV. The meta-analysis is carried out to evaluate the efficacy of MMF as a remission induction therapy in AAV.Methods: Up to June 30th, 2020, PubMed, Cochrane Library, and Embase have been searched comprehensively. According to heterogeneity, the pooled remission rates are synthesized by either fixed-effect or random-effect models.Results: The eight included studies comprising 230 patients who were treated with MMF as induction therapy are included in our analysis. The pooled overall remission rate is 74% (95% CI: 0.68–0.80). The remission rate, the infection rate and the rate of leukopenia of four randomized controlled trials aimed at comparing the effects of MMF with cyclophosphamide (CYC) during induction therapy for AAV have no statistical significance (P > 0.05).Conclusion: MMF may be an alternative to CYC for remission induction therapy in AAV with MPO-ANCA, mild to moderate renal involvement and non-life-threatening state. Whether to observe the effect of MMF in AAV or to compare the difference between MMF and CYC in the future studies, risk stratification and subgrouping of AAV patients should be first carried out to correctly identify the AAV subgroup suitable for MMF.

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PSY4 - RESPONSE TO INDUCTION THERAPY, TREATMENT ADVERSE EVENTS AND HEALTHCARE RESOURCE USE IN INCIDENT ANCA-ASSOCIATED VASCULITIS (AAV) PATIENTS

Value in Health ◽

10.1016/j.jval.2018.09.2581 ◽

2018 ◽

Vol 21 ◽

pp. S436

Author(s):

P. Spearpoint ◽

D. Goette ◽

J. Chaussy ◽

P. Rutherford

Keyword(s):

Adverse Events ◽

Induction Therapy ◽

Resource Use ◽

Healthcare Resource ◽

Healthcare Resource Use ◽

Anca Associated Vasculitis ◽

Therapy Treatment

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P0374TREATMENT EFFICACY OF BIOSIMILAR RITUXIMAB (TRUXIMA) COMPARED TO THE ORIGINATOR (MABTHERA) IN PATIENTS WITH ANCA ASSOCIATED VASCULITIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0374 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

PEK GHE TAN ◽

Jennifer O'Brien ◽

Rachna Bedi ◽

Megan Griffith ◽

Marie Condon ◽

...

Keyword(s):

Overall Survival ◽

Adverse Events ◽

B Cell ◽

Induction Therapy ◽

Subgroup Analysis ◽

Treatment Efficacy ◽

Cell Depletion ◽

B Cell Depletion ◽

Anca Associated Vasculitis ◽

Infusion Reactions

Abstract Background and Aims Truxima is a biosimilar version of rituximab. It was licensed & launched in the United Kingdom in April 2017. A biosimilar medicine is made to be highly similar in quality, safety and efficacy to existing licensed “reference” biological medicine and the cost is often significantly lower. A recent systematic review showed comparable long-term efficacy and safety of biosimilar rituximab to the originator drug in treatment of rheumatoid arthritis and non-hodgkin’s lymphoma. Fewer data are available in regards to the efficacy of biosimilar rituximab in treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). A retrospective study was thus conducted in our centre to examine the efficacy of Truxima when compared to the reference rituximab (MabThera) in the treatment of patients with AAV. Method All patients with new or relapsing AAV who received first ever rituximab therapy between 1/1/2016 and 31/12/2018 were identified via hospital dispensing database. Patients were stratified into Truxima or MabThera treatment group depending on the version of rituximab administered. Primary outcomes that were assessed include: time to B cell depletion (defined as absolute B cell count (ABC) ≤10) and repletion (i.e ABC >10 and >20); time to antimyeloperoxidase(MPO)/antiproteinase 3(PR3)-ANCA negativity; Secondary outcomes assessed include: overall survival, time to major relapse (defined as relapse requiring further course of rituximab for remission induction); adverse events including episodes of neutropenia, hypogammaglobulinemia and major infusion reactions. Subgroup analysis in patients who received concomitant cyclophosphamide and rituximab or other induction therapy was performed to examine if it impacts on the treatment efficacy. Results 59 and 60 patients received Truxima and MabThera respectively for treatment of new or relapsing AAV. The baseline characteristic (age, gender, entry estimated Glomerular Filtration Rate, proportion of patients received concomitant cyclophosphamide, ANCA serology and organ involvement) of both group were comparable. All patients achieved clinical remission following induction treatment. Using Kaplan Meier analysis and log rank test, no difference was identified in time to B cell depletion or repletion (Figure 1&2), MPO/PR3-ANCA negativity (Figure 3), overall survival or major relapses requiring further rituximab as induction therapy. Treatment efficacy of Truxima and MabThera did not differ in subgroup analysis. However we observed that patients who received concurrent cyclophosphamide during induction therapy achieved MPO/PR3-ANCA negativity more rapidly compared to those who did not irrespective of the version of rituximab received. No difference in adverse events such as major infusion reactions was seen in either group upon first rituximab exposure. Two patients in each group developed reactions following repeated dosing of rituximab. Conclusion Biosimilar rituximab Truxima appears to have comparable treatment efficacy compared to the reference drug in our cohort of patients with AAV.

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