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

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.

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

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 21-22
Author(s):  
P. Rutherford ◽  
D. Götte
Keyword(s):  
Adverse Events ◽  
Functional Status ◽  
Induction Therapy ◽  
Maintenance Treatment ◽  
Negative Impact ◽  
Remission Induction ◽  
Full Time ◽  
Full Remission ◽  
Anca Associated Vasculitis ◽  
Active 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

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

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.

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

Rheumatology ◽  
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 (&gt; 30mg/day) and low dose (&lt;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 &gt; 10mg at 5 months and 25% were still &gt; 10mg at 12 months. However, within 6 months of achieving 10mg/day, 50% relapse to needing dose &gt;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.

scholarly journals POS1230 OUTCOME FOLLOWING COVID-19 INFECTION IN ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY (ANCA)-ASSOCIATED VASCULITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 898.2-898
Author(s):  
A. Antovic ◽  
B. Lövström ◽  
A. Hugelius ◽  
O. Borjesson ◽  
A. Bruchfeld ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Immunosuppressive Therapy ◽  
Granulomatosis With Polyangiitis ◽  
Renal Involvement ◽  
Data Retrieval ◽  
Induction Treatment ◽  
High Dose ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Upper Airways ◽  
Anca Associated Vasculitis

Background:Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) require immunosuppressive therapy for disease control and reduction of disease relapse and may be at risk for complications during Sars-CoV-2 (COVID-19) infection.Objectives:To analyze the consequences of COVID-19 in a large cohort of AAV patients regarding occurrence, need of hospitalization, treatment at the intensive care units (ICU), or death.Methods:Data were retrieved from March 2020 to mid-January 2021 from medical records from the AAV cohort (n=233). Patients diagnosed with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) or eosinophilic granulomatosis with polyangiitis (EGPA) were included. Data included age, gender, diagnosis, ongoing immunosuppressive medication at onset of COVID-19 or at last follow-up in non-COVID individuals. Renal involvement (ever) and estimated glomerular filtration rate (eGFR) were included. COVID-19 was confirmed either by a positive PCR test in the upper airways or by serology. Severe COVID-19 was defined as need of non-invasive ventilation, ICU care, and/or death.Results:The cohort comprised of 172 patients with GPA, 50 with MPA and 11 with EGPA. There were 121 females (52%). During the study period, 20 patients (8.6%) were diagnosed with COVID-19. The median age at data retrieval in all patients was 68 years (21-93), in the COVID-19 group 63 (29-93) and 68.5 (21-90) years in the non-COVID patients.Fourty-three patients in all (18%) were hospitalized during the study period of which 11 (4.7%) due to COVID-19 infection. In all, 8 deaths occurred of which 3 were related to COVID-19.At data retrieval, 110 (47%) patients were on prednisolone treatment, 10/20 (50%) in the COVID-19 group and 100 (47%) in the non-COVID-19 group (p=0.5), with significantly higher doses in COVID-19 patients (p<0.001). In patients hospitalized with COVID-19, 6/11 (54.5%) were on prednisolone, median dose 5 mg/day (0-50). In the total group 112 (48%) were on disease modifying anti-rheumatic drugs (DMARD) and 64 (27.5%) on rituximab as maintenance therapy. Eight patients were on induction treatment with either cyclophosphamide or rituximab.Of the 20 COVID-19 cases, 8 had severe COVID-19. Of these, 2 were inactive without immunosuppressive treatment, 4 had stable disease with prednisolone (5-7.5 mg/day) in combination with DMARDs, and 2 were active treated with high dose prednisolone (25-50 mg/day) in combination with cyclophosphamide and rituximab (n=1) or rituximab (n=1).A higher proportion of patients had active AAV (p=0.03) in the severe COVID-19 then in the non-COVID group (10/213 patients).In the group with the severe COVID-19, 1/8 (12%) patient had rituximab as maintenance therapy, compared to 61/213 (28.6%) in the group of non-COVID-19 patients (p=0.5).Renal involvement (ever) was present in 144 patients (62%), in 6 patients (30%) with COVID- 19, from which 5 (62%) were in the group of severe COVID-19 patients. Median eGFR did not differ between severe COVID-19 and remaining patients with renal involvement independently of COVID-19 infection.Conclusion:We found a high rate of severe COVID-19 infection in our cohort of AAV patients which indicates risk for serious complications, especially in patients with active disease and intense immunosuppressive therapy. Maintenance therapy with rituximab did not seem to increase the risk for severe COVID-19. The findings stress the need for continued shielding and early vaccination in AAV patients.Disclosure of Interests:None declared

scholarly journals P412 Maintenance therapy of vedolizumab (VDZ) after induction of remission by tacrolimus (TAC) in patients with refractory ulcerative colitis (UC)

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S377-S378
Author(s):  
A Ito ◽  
M Shun ◽  
O Teppei ◽  
T Katsutoshi
Keyword(s):  
Ulcerative Colitis ◽  
Side Effects ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Relapse Rate ◽  
Remission Induction ◽  
Symptom Improvement ◽  
Combined Use ◽  
Number Of Patients

Abstract Background The number of patients with ulcerative colitis (UC) is increasing. As the number of patients increases, patient backgrounds become diverse, and treatment choices that match the background are required. Most UCs are mild, but about 30% are more than moderate. UCs with moderate or higher illness have resistance/dependence to steroids and are difficult to introduce remission. In recent years, many new drugs have appeared for remission induction therapy. However, in UC treatment, maintenance therapy that suppresses relapse after induction of remission is important. Maintaining long-term remission prevents deterioration in the quality of life and reduces the incidence of UC-related colorectal cancer. To that end, it is important to consider remission maintenance therapy. In patients with intractable UC who have been in remission with tacrolimus (TAC) and used vedolizumab (VDZ) as maintenance therapy, patient background, relapse rate (observation period 181.5 ± 25.9 days), (3) safety of TAC and VDZ combination The sex was examined. Methods Seven patients who received remission with TAC and maintained remission with VDZ between November 2018 and June 2019 were included. (1) Patient background at the time of introduction of TAC and VDZ, TAC administration period (day) until the start of VDZ, (2) Relapse rate, (3) AZA use history, side effects, and adverse events caused by the combined use of VED. Results (1) Patient background was age at TAC introduction (age) 44.4 ± 19.7, sex (male / female) 3/4, disease duration (year) 12 ± 11.5, CAI 14.4 ± 2.9, Hb 11 ± 0.8, CRP 5.5 ± 3.6, Endoscopic score (Mayo 3 ± 0, UCEIS 7 ± 1.1), CAI at the time of VDZ introduction 6 ± 3.3, Hb 11.3 ± 2.0, CRP 0.4 ± 0.5, TAC administration period until VDZ start 140 ± It was 155. (2) Six patients had a history of AZA use. 4 out of 6 cases with AZA history side effect due to AZA was observed. The side effects of AZA were leukopenia in 2 cases, headache in 2 cases, and liver injury in 1 case. (There were duplicate cases) (3) No adverse events were observed due to the combined use of TAC and VDZ. Conclusion TAC has clinical remission or symptom improvement for refractory UCVDZ had been administered since then. In cases where administration of AZA was difficult, VDZ was selected as maintenance therapy. There were no serious side effects from the combined use of TAC and VDZ. TAC is a drug that has a rapid effect. However, long-term administration of TAC is at risk for kidney damage. Therefore, we considered that maintenance therapy with VDZ after TAC is effective.

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

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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