BACKGROUND: Despite newer treatments with immunosuppressive agents, there still exists a considerable morbidity and mortality risk among patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Since 1994 the European Vasculitis Society (EUVAS) has aimed for an improved outcome for patients with AAV, conducting several prospective randomized controlled trials (RCTs). The aim for the present study was to further evaluate the long-term survival of patients with AAV included in seven RCTs conducted by the EUVAS as well as to identify potential prognostic factors. METHODS: Long-term follow-up data were collected from questionnaires sent to the principal investigators of the original RCTs (1995-2012): MEPEX, NORAM, CYCAZAREM, CYCLOPS, IMPROVE, RITUXVAS and MYCYC, comprising 848 patients, all newly diagnosed with AAV. Relative survival estimates are presented for the study cohorts. Demographic, clinical and laboratory characteristics at trial entry were studied as potential prognostic factors in multivariable models. RESULTS: A total of 478 (56%) patients had granulomatosis with polyangiitis (GPA) and 370 (44%) had microscopic polyangiitis (MPA) with a mean age at diagnosis of 58 ± 14 years. The median follow-up time was 8 years (interquartile range 2.9-13.6). During the observation period there were 305 deaths and the main causes were infections (26%), cardiovascular disease (14%) and malignancies (13%). When compared with a matched cohort (regarding country, age group and sex) from the background population there were 14.2% more deaths among our cohort of AAV patients at 5 years, 19.9% at 10 years, 28.8% at 15 years and 36.3% at 20 years. The excess mortality occurred in all age groups. The estimated median survival time (from diagnosis) was 17.8 years (95% confidence interval 15.7-20). Among variables measured at baseline, advanced age, male sex, low estimated glomerular filtration rate and low platelet count were identified as predictors of death in a multivariate Cox model. CONCLUSIONS: Patients with AAV still have an increased risk of mortality compared with the general population despite newer therapeutic regimens. Treatment complications and organ damage are the main causes of limited survival and infections remain the leading cause of mortality among patients with AAV.
- MeSH
- ANCA-asociované vaskulitidy * terapie farmakoterapie MeSH
- dospělí MeSH
- granulomatóza s polyangiitidou * diagnóza terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikroskopická polyangiitida * komplikace diagnóza MeSH
- předškolní dítě MeSH
- prognóza MeSH
- protilátky proti cytoplazmě neutrofilů MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- azathioprin terapeutické užití MeSH
- cyklofosfamid terapeutické užití MeSH
- granulomatóza s polyangiitidou komplikace farmakoterapie MeSH
- imunosupresiva terapeutické užití MeSH
- lidé MeSH
- mikroskopická polyangiitida komplikace farmakoterapie MeSH
- myeloblastin imunologie MeSH
- nemoci ledvin etiologie patofyziologie MeSH
- peroxidasa imunologie MeSH
- protilátky proti cytoplazmě neutrofilů * MeSH
- recidiva MeSH
- rituximab terapeutické užití MeSH
- udržovací chemoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Úvod: Cyklofosfamid (CFA) je lék ze skupiny alkylačních cytostatik s významnými imunosupresivními účinky. Těch se využívá v léčbě závažných orgánových projevů u nekrotizujících vaskulitid a difuzních onemocnění pojiva. Podávání CFA může být komplikováno jeho nežádoucími účinky (NÚ). Některé jsme schopni predikovat a ovlivnit, ale výskyt vzácných NÚ předpovědět nedokážeme. Jedním z nich je kardiální toxicita. Popis případu: Jedná se o kazuistiku 61leté ženy, u které se mikroskopická polyangiitida (MPA) v úvodu manifestovala těžkým pulmorenálním syndromem. Po dobré reakci na indukční léčbu došlo k rozvoji akutního levostranného srdečního selhání v časové návaznosti na podání CFA. Po vyloučení jiných důvodů akutního srdečního selhání byla stanovena příčina v toxickém působení CFA a léčba byla změněna na rituximab. Závěr: Zhoršení stavu u nemocného s vaskulitidou, který je léčený CFA, je složitým diferenciálně diagnostickým problémem. Může se jednat o projev základního nebo souběžně probíhajícího onemocnění, anebo o toxicitu podávané léčby. Při toxickém působení CFA může být alternativní medikací rituximab.
Introduction: Cyclophosphamide (CPA) is a drug from the group of alkylating cytostatics with significant immunosuppressive effects. These are used in the treatment of severe organ manifestations in necrotizing vasculitis and diffuse connective tissue diseases. The administration of CPA may be complicated by its side effects (AE). We are able to predict and influence some, but we cannot predict the occurrence of rare AE. One of them is cardiac toxicity. Case description: This is a case report of a 61-year-old woman with microscopic polyangiitis (MPA) initially manifested by a severe pulmonary-renal syndrome. Following a good response to induction therapy, acute left heart failure developed over time following CPA administration. After excluding other causes of acute heart failure, the cause of CPA toxicity was determined, and treatment was changed to rituximab. Conclusion: Deterioration in a patient with vasculitis treated with CPA is a complex differential diagnostic problem. It may be a manifestation of an underlying or concurrent disease or the toxicity of the administered treatment. In case of toxic effects of CPA, rituximab may be an alternative medication.
- MeSH
- bronchoskopie MeSH
- cyklofosfamid * aplikace a dávkování terapeutické užití toxicita MeSH
- diferenciální diagnóza MeSH
- dyspnoe MeSH
- kardiotoxicita * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikroskopická polyangiitida * diagnóza farmakoterapie komplikace MeSH
- rituximab aplikace a dávkování terapeutické užití MeSH
- srdeční selhání chemicky indukované diagnostické zobrazování terapie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
BACKGROUND AND OBJECTIVES: ANCA-associated vasculitis is commonly found in elderly patients, but there are few data concerning outcome and treatment in the highest age groups. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Consecutive patients (N=151) presenting between 1997 and 2009 were retrospectively included from local registries in six centers in Sweden, the United Kingdom, and the Czech Republic if diagnosed with microscopic polyangiitis or granulomatosis with polyangiitis at age ≥75 years during the study period. Patients were followed until 2 years from diagnosis or death. Data on survival and renal function were analyzed with respect to age, sex, ANCA specificity, renal function, C-reactive protein, comorbidities, and Birmingham Vasculitis Activity Score at diagnosis as well as treatment during the first month. RESULTS: Median follow-up was 730 days (interquartile range, 244-730). Overall 1-year survival was 71.5% and 2-year survival was 64.6%. Older age, higher creatinine, and lower Birmingham Vasculitis Activity Score were associated with higher mortality in multivariable analysis. Patients who were not treated with standard immunosuppressive therapy had significantly worse survival. Renal survival was 74.8% at 1 year. No new cases of ESRD occurred during the second year. High creatinine at diagnosis was the only significant predictor of renal survival in multivariable analysis. CONCLUSIONS: ANCA-associated vasculitis is a disease with substantial mortality and morbidity among elderly patients. This study showed a better prognosis for those who received immunosuppressive treatment and those who were diagnosed before having developed advanced renal insufficiency.
- MeSH
- časové faktory MeSH
- chronické selhání ledvin etiologie MeSH
- granulomatóza s polyangiitidou komplikace diagnóza farmakoterapie mortalita MeSH
- imunosupresiva terapeutické užití MeSH
- Kaplanův-Meierův odhad MeSH
- komorbidita MeSH
- lidé MeSH
- mikroskopická polyangiitida komplikace diagnóza farmakoterapie mortalita MeSH
- multivariační analýza MeSH
- progrese nemoci MeSH
- proporcionální rizikové modely MeSH
- renální insuficience etiologie MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- věkové faktory MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
OBJECTIVES: To analyse the differences between patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) entered into randomised clinical trials (RCTs) and those followed in large observational cohorts. METHODS: The main characteristics and outcomes of patients with generalised and/or severe GPA or MPA with a five-factor score ≥ 1 enrolled in the French Vasculitis Study Group (FVSG) or the US-Canadian-based Vasculitis Clinical Research Consortium cohorts were compared to those enrolled in one of 2 FVSG clinical RCTs (WEG91, WEGENT) or 3 European Vasculitis Society clinical trials (CYCLOPS, CYCAZAREM, IMPROVE). RESULTS: 657 patients (65.3% with GPA) in RCTs were compared to 437 in cohorts (90.6% with GPA). RCT patients were older at diagnosis than the cohort patients (56.6 ± 13.9 vs. 46.8 ± 17.3 years), had higher Birmingham vasculitis activity score (19.5 ± 9.1 vs. 16.9 ± 7.4), and more frequent kidney disease (84.0% vs. 54.9%) but fewer ear, nose, and throat symptoms (56.8% vs. 72.2%). At 56 months post-diagnosis, mortality and relapse rates, adjusted for age and renal function, were higher for patients with GPA in RCTs vs. cohorts (10.7% vs. 2.5% [p=0.001] and 22.5% vs. 15.6% [p=0.03], respectively) but similar for patients with MPA (6.2% vs. 6.6% [p=0.92] and 16.6% vs. 10.1% [p=0.39], respectively). CONCLUSIONS: Patients with GPA or MPA in RCTs and those in observational cohorts show important differences that should be remembered when interpreting results based on these study populations.
- MeSH
- dospělí MeSH
- granulomatóza s polyangiitidou komplikace epidemiologie imunologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikroskopická polyangiitida komplikace epidemiologie imunologie MeSH
- myeloblastin imunologie MeSH
- nemoci ledvin etiologie MeSH
- otorinolaryngologické nemoci etiologie MeSH
- peroxidasa imunologie MeSH
- pozorovací studie jako téma * MeSH
- protilátky proti cytoplazmě neutrofilů imunologie MeSH
- randomizované kontrolované studie jako téma * MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- věkové rozložení MeSH
- výběr pacientů MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
OBJECTIVES: The RITUXVAS trial reported similar remission induction rates and safety between rituximab and cyclophosphamide based regimens for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis at 12 months; however, immunosuppression maintenance requirements and longer-term outcomes after rituximab in ANCA-associated renal vasculitis are unknown. METHODS: Forty-four patients with newly diagnosed ANCA-associated vasculitis and renal involvement were randomised, 3:1, to glucocorticoids plus either rituximab (375 mg/m(2)/week×4) with two intravenous cyclophosphamide pulses (n=33, rituximab group), or intravenous cyclophosphamide for 3-6 months followed by azathioprine (n=11, control group). RESULTS: The primary end point at 24 months was a composite of death, end-stage renal disease and relapse, which occurred in 14/33 in the rituximab group (42%) and 4/11 in the control group (36%) (p=1.00). After remission induction treatment all patients in the rituximab group achieved complete B cell depletion and during subsequent follow-up, 23/33 (70%) had B cell return. Relapses occurred in seven in the rituximab group (21%) and two in the control group (18%) (p=1.00). All relapses in the rituximab group occurred after B cell return. CONCLUSIONS: At 24 months, rates of the composite outcome of death, end-stage renal disease and relapse did not differ between groups. In the rituximab group, B cell return was associated with relapse. TRIAL REGISTRATION NUMBER: ISRCTN28528813.
- MeSH
- ANCA-asociované vaskulitidy komplikace farmakoterapie imunologie MeSH
- azathioprin terapeutické užití MeSH
- B-lymfocyty cytologie MeSH
- chronická renální insuficience farmakoterapie etiologie imunologie MeSH
- chronické selhání ledvin etiologie MeSH
- cyklofosfamid terapeutické užití MeSH
- glukokortikoidy terapeutické užití MeSH
- granulomatóza s polyangiitidou komplikace farmakoterapie imunologie MeSH
- imunosupresiva terapeutické užití MeSH
- kombinovaná farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikroskopická polyangiitida komplikace farmakoterapie imunologie MeSH
- myší monoklonální protilátky terapeutické užití MeSH
- počet lymfocytů MeSH
- přežití po terapii bez příznaků nemoci MeSH
- progrese nemoci MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
