Improvement in health-related quality of life in MPO-ANCA-associated vasculitis patients treated with cyclophosphamide plus prednisolone: an analysis of 18 months of follow-up data from the JMAAV study

Abstract

Objectives To examine the improvement in health-related quality of life (HRQOL) in association with disease activity in myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis patients treated with cyclophosphamide plus prednisolone.

Methods According to the Japanese Patients with MPO-ANCA-Associated Vasculitis (JMAAV) study protocol, a total of 48 patients with newly diagnosed MPO-ANCA-associated vasculitis received a standardized cyclophosphamide plus prednisolone regimen, and their clinical courses were followed for 18 months following their entry into the study. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS) 2003. HRQOL was assessed using MOS Short-Form 36 (SF-36) v2. BVAS new/worse, BVAS persistent, and SF-36 domain scores (norm-based) were calculated for the 32 eligible patients.

Results The mean SF-36 domain scores were significantly lower than the Japanese general population norm. Stepwise multiple linear regression analysis showed that the presence of new or worsening features of the nervous system was significantly associated with a deterioration in physical function. During the 18 months of follow-up, there were significant improvements in BVAS new/worse and all SF-36 domains except for general health and role emotional.

Conclusion MPO-ANCA-associated vasculitis patients experienced a considerable deterioration in HRQOL. The standardized cyclophosphamide plus prednisolone regimen of the JMAAV study induced remission in the majority of patients, and the induction of remission accompanied a recovery in HRQOL.     

Improvement in health-related quality of life in MPO-ANCA-associated vasculitis patients treated with cyclophosphamide plus prednisolone: an analysis of 18 months of follow-up data from the JMAAV study

Objectives

To examine the improvement in health-related quality of life (HRQOL) in association with disease activity in myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis patients treated with cyclophosphamide plus prednisolone.

Methods

According to the Japanese Patients with MPO-ANCA-Associated Vasculitis (JMAAV) study protocol, a total of 48 patients with newly diagnosed MPO-ANCA-associated vasculitis received a standardized cyclophosphamide plus prednisolone regimen, and their clinical courses were followed for 18?months following their entry into the study. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS) 2003. HRQOL was assessed using MOS Short-Form 36 (SF-36) v2. BVAS new/worse, BVAS persistent, and SF-36 domain scores (norm-based) were calculated for the 32 eligible patients.

Results

The mean SF-36 domain scores were significantly lower than the Japanese general population norm. Stepwise multiple linear regression analysis showed that the presence of new or worsening features of the nervous system was significantly associated with a deterioration in physical function. During the 18?months of follow-up, there were significant improvements in BVAS new/worse and all SF-36 domains except for general health and role emotional.

Conclusion

MPO-ANCA-associated vasculitis patients experienced a considerable deterioration in HRQOL. The standardized cyclophosphamide plus prednisolone regimen of the JMAAV study induced remission in the majority of patients, and the induction of remission accompanied a recovery in HRQOL.     

Severity-based treatment for Japanese patients with MPO-ANCA-associated vasculitis: the JMAAV study

Abstract

We (JMAAV [Japanese patients with MPO-ANCA-associated vasculitis] Study Group) performed a prospective, open-label, multi-center trial to evaluate the usefulness of severity-based treatment in Japanese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA)-associated vasculitis. Patients with MPO-ANCA-associated vasculitis received a severity-based regimen according to the appropriate protocol: low-dose corticosteroid and, if necessary, cyclophosphamide or azathioprine in patients with mild form; high-dose corticosteroid and cyclophosphamide in those with severe form; and the severe-form regimen plus plasmapheresis in those with the most severe form. We followed up the patients for 18 months. The primary end points were the induction of remission, death, and end-stage renal disease (ESRD). Fifty-two patients were registered, and 48 patients were enrolled in this study (mild form, n = 23; severe form, n = 23; most severe form, n = 2). Among the 47 patients who received the predefined therapies, 42 achieved remission within 6 months, 5 died, and 1 developed ESRD. Disease flared up in 8 of the 42 patients with remission during the 18-month follow-up period. The JMAAV trial is the first prospective trial for MPO-ANCA-associated vasculitis to be performed in Japan. The remission and death rates were comparable to those in several previous clinical trials performed in western counties. The regimen employed in this trial was tailor-made based on patients’ disease severity and disease type, and it seems that standardization can be consistent with treatment choices made according to severity.     

Long-term safety and efficacy of rituximab in 7 Japanese patients with ANCA-associated vasculitis

Abstract

Objectives. The safety and efficacy of rituximab were examined in a multicenter open-label pilot study in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan.

Methods. Patients with refractory AAV were administered a rituximab infusion at a weekly dose of 375 mg/m² for 4 weeks. All patients also received oral daily prednisolone. The primary outcome was complete remission, which was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 or 1.

Results. The mean age of the 7 patients was 57 (range, 34–71) years. The mean follow-up period after rituximab treatment was 62.9 (range, 4.8–81) months. The mean BVAS at entry was 16.7 (range, 2–34). Complete remission occurred in all cases, except in 1 case in which the patient died, with a significant decline in BVAS from baseline at 12 months after initiation of rituximab. Rituximab reduced granulomatous orbital involvement in a patient with granulomatosis with polyangiitis. Relapse occurred in five patients. Adverse events included de novo hepatitis B in one patient, cancer (hepatocellular carcinoma and prostate cancer) in two patients, and transient visual disturbance, atypical mycobacterial infection, urinary tract infection, sepsis, and cytomegalovirus infection. Two patients died due to recurrent infections and airway obstruction, caused by an AAV lesion.

Conclusions. Rituximab had a beneficial effect on refractory AAV in Japanese patients, but several adverse effects occurred during rituximab treatment.     

A retrospective study on the outcomes of MPO-ANCA-associated vasculitis in dialysis-dependent patients

Objectives. This study investigated the clinical course of myeloperoxidase-antineutrophil cytoplasm autoantibody (MPO-ANCA)-associated vasculitis after starting dialysis.

Methods. A retrospective review was conducted of the clinical charts of dialysis-dependent patients with MPO-ANCA-associated vasculitis who attended one of 8 associated clinics over the past 21 years.

Results. Eighty-nine patients were included in the study; 88 had microscopic polyangiitis (MPA) and 1 had granulomatosis with polyangiitis. Of the 88 patients with MPA, 18 had renal-limited vasculitis. Twenty-one relapses occurred among 13 patients (frequency, 0.05 relapses/person-year; 95% confidence interval, 0.03–0.08). Mean time from start of dialysis to relapse was 65 ± 59 months. Cox multivariate analysis showed that pulmonary involvement was a predictor of relapse (hazard ratio [HR], 21.4) and mortality (HR, 4.60), and that patient age (HR, 1.10) and cyclophosphamide use (HR, 0.20) were significant predictors of mortality. Postdialysis 1- and 5-year survival rates were 83.0% and 65.6%, respectively; infection was the most frequent cause of death.

Conclusion. Pulmonary involvement was a predictor of relapse and mortality. Although relapse can occur long after the start of dialysis, incidence was low among dialysis-dependent patients. Prolonged maintenance immunosuppressive therapy might be limited to patients with pulmonary involvement in dialysis-dependent ANCA-associated vasculitis.     

Difference in relapse-rate and clinical phenotype by autoantibody-subtype in Japanese patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Objective: To correlate the serotype specificity to myeloperoxidase (MPO) and proteinase-3 (PR3) with clinical characteristics in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods: Clinical characteristics and outcomes of patients with AAV in our division from 2005 to 2014 were retrospectively compared on the basis of ANCA subtype.

Results: We collected the data from 88 patients with MPO–ANCA vasculitis, and 17 with PR3-ANCA vasculitis. Patients with PR3-ANCA vasculitis were younger, and had higher involvement-rates in the eye, nose, and ear. In both MPO- and PR3-ANCA vasculitis, the most frequently involved organ was the respiratory system. Interstitial pneumonia was more frequent in MPO-ANCA vasculitis (52.3% versus 5.9%, p?p?p?=?0.02). There was no difference in the survival and the progression to end-stage kidney disease and respiratory failure between the two vasculitides.

Conclusion: MPO-ANCA vasculitis was a predominant form of AAV in Japan. Classification based on ANCA subtype would be clinically relevant in the prediction of organ involvement and relapse.     

Autoreactive T-cell responses to myeloperoxidase in patients with antineutrophil cytoplasmic antibody-associated vasculitis and in healthy individuals

Abstract

The aim of this study was to evaluate the characteristics of autoreactive T cells to myeloperoxidase (MPO) in patients with MPO-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Peripheral blood T cells from 15 patients with MPO-ANCA-associated vasculitis and 14 healthy individuals were cultured with three recombinant proteins that together comprised the entire MPO sequence (L, all 112 amino acids (AA) of the light chain; HI, AA 1-227 of the heavy chain; HII, AA 212-467 of the heavy chain), and the antigen-specific T-cell proliferative response was measured by ³H-thymidine incorporation. T-cell responses to MPO-L and HI were both detected in four patients and three healthy donors, and responses to MPO-HII were detected in four patients and seven healthy donors. These findings indicate that at least three independent T-cell epitopes exist on the MPO molecule. Interestingly, the patients whose T cells showed these MPO-induced responses were mainly in remission. Peripheral blood T cells reactive with MPO were primarily of the HLA-DR-restricted CD4⁺ phenotype. In summary, we successfully used recombinant MPO fragments to detect autoreactive CD4⁺ T cells to multiple MPO epitopes in blood samples from patients with MPO-ANCA-associated vasculitis and healthy individuals.     

Association of five-factor score with the mortality in Japanese patients with polyarteritis nodosa

Aim: To determine mortality and its predictive factors in Japanese patients with polyarteritis nodosa (PAN).

Methods: This retrospective single-center study determined the mortality of 18 patients with PAN who were admitted to Juntendo University Hospital from 1994 to 2016. The variables at baseline, including patient demographics, clinical characteristics, and treatment, were analyzed for their association with mortality.

Results: The median age of onset was 57.0 years. The 1-year survival rate was 100% (16/16) and the 5-year survival rate was 80.0% (8/10). The relationship between mortality, as defined by the survival rate and each variable was evaluated by Cox univariate analysis. A higher 2009 five-factor score (FFS) was associated with increased mortality, with a hazard ratio of 2.34 (p?=?.04). Analysis of the secondary outcome of relapse-free survival time revealed an association with rapid progressive renal failure, Birmingham Vasculitis Activity Score (BVAS), the 1996 FFS, and the 2009 FFS, with hazard ratios of 7.28 (p?=?.048), 1.26 (p?=?.02), 2.32 (p?=?.03), and 1.82 (p?=?.04), respectively.

Conclusion: We investigated mortality, relapse-free survival, and their predictive factors in Japanese patients with PAN. The BVAS and the 1996 FFS at diagnosis may be prognostic factors for relapse-free survival, and the 2009 FFS at diagnosis may be a prognostic factor for both mortality and relapse-free survival.     

Cytapheresis for the treatment of myeloperoxidase antineutrophil cytoplasmic autoantibody-associated vasculitis: a pilot study of 21 patients

Twenty-one patients with myeloperoxidase-antineutrophil cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis were treated using cytapheresis. Of these, 17 were treated for glomerulonephritis and four were treated for pulmonary hemorrhage. The overall survival rate was 85.7% with a follow-up duration of 24.0 +/- 13.8 months. In the 17 patients with MPO-ANCA-associated glomerulonephritis, pretreatment creatinine was 3.2 +/- 1.6 mg/dL, and renal function recovered in 76.5%. Pulmonary hemorrhage was ameliorated in all four patients. Abdominal pain occurred in three of the 21 patients but symptoms resolved soon after the cytapheresis procedure was completed. No other adverse effects occurred during cytapheresis. From these results, cytapheresis can be considered a safe and effective treatment for MPO-ANCA-associated vasculitis. As for the mechanism of its action, soluble tumor necrosis factor receptor 1 (sTNFR), sTNFR2 and interleukin 1 receptor antagonist were elevated soon after cytapheresis and those levels 2 h after the cytapheresis procedure were higher than before the procedure in some cases. These elevations might be related to the efficacy of cytapheresis.     

Clinical characteristics of and risk factors for serious infection in Japanese patients within six months of remission induction therapy for antineutrophil cytoplasmic antibody-associated vasculitis registered in a nationwide,prospective, inception cohort study

Objectives: The purpose of this study was to identify the clinical characteristics and predictors of serious infections (SIs) in the RemIT-JAV, a nationwide, prospective, inception cohort study for Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).

Methods: We analyzed SIs within six months of remission induction therapy in 156 AAV patients. Hazard ratios with 95% confidence intervals (CIs) for SIs were calculated using the COX proportional hazard model.

Results: Sixty-three SIs in 42 patients were identified. The incidence rate (IR) of SIs was 87.59/100 patient-years. The median length of time to the onset of first SIs was 54 days. Hazard ratios (95%CI) for SIs were 1.97 (0.99–3.95) for age >65 years, 0.47 (0.25–0.89) for female sex, 2.11 (1.05–4.27) for the severe form of AAV, and 2.88 (1.49–5.88) for initial PSL >0.8?mg/kg/day in the first model, and 2.64 (1.39–5.01) for smoking and 3.27 (1.66–6.45) for initial PSL >0.8?mg/kg/day in the second model.

Conclusions: Lowering the IR of SIs in Japanese AAV patients is mandatory to improve the vital prognosis of these patients. For remission induction therapy of AAV patients with these risk factors, risk management of immunosuppressive treatment should be carefully considered.     

Severity-based treatment for Japanese patients with MPO-ANCA-associated vasculitis: the JMAAV study

We (JMAAV [Japanese patients with MPO-ANCA-associated vasculitis] Study Group) performed a prospective, open-label, multi-center trial to evaluate the usefulness of severity-based treatment in Japanese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA)-associated vasculitis. Patients with MPO-ANCA-associated vasculitis received a severity-based regimen according to the appropriate protocol: low-dose corticosteroid and, if necessary, cyclophosphamide or azathioprine in patients with mild form; high-dose corticosteroid and cyclophosphamide in those with severe form; and the severe-form regimen plus plasmapheresis in those with the most severe form. We followed up the patients for 18 months. The primary end points were the induction of remission, death, and end-stage renal disease (ESRD). Fifty-two patients were registered, and 48 patients were enrolled in this study (mild form, n = 23; severe form, n = 23; most severe form, n = 2). Among the 47 patients who received the predefined therapies, 42 achieved remission within 6 months, 5 died, and 1 developed ESRD. Disease flared up in 8 of the 42 patients with remission during the 18-month follow-up period. The JMAAV trial is the first prospective trial for MPO-ANCA-associated vasculitis to be performed in Japan. The remission and death rates were comparable to those in several previous clinical trials performed in western counties. The regimen employed in this trial was tailor-made based on patients' disease severity and disease type, and it seems that standardization can be consistent with treatment choices made according to severity.     

Characteristics and outcome of intractable vasculitis syndrome in children: Nation-wide survey in Japan

Objective: Primary systemic vasculitis (PSV) is a rare disorder in children and difficult to distinguish from other diseases. However, appropriate diagnosis and prompt treatment will affect on the morbidity and mortality of intractable PSV. In this study, we conducted a nationwide survey in Japan, to clarify epidemiology and clinical outcome of PSV.

Methods: We had sent survey questionnaires to most of the Japanese institutions that employed pediatricians, requesting the number of patients with refractory PSV who were diagnosed and treated between 2007 and 2011. Respondents were asked to provide detailed information on the clinical and laboratory features of each case they had managed. Those with Kawasaki disease or Henoch–Shönlein purpura vasculitis (IgA vasculitis) were excluded.

Results: Of all the institutions surveyed, 1123 (37.3%) patients responded, finally, total of 49 patients with intractable PSV, defined by those with resistant to treatment and steroid-dependent, or with any complication associated with prognosis, were selected. The diagnosis was Takayasu arteritis in 31, polyarteritis nodosa in 11, granulomatosis with polyangitis in 2, microscopic polyangitis in 1, and ANCA negative microscopic polyangitis in 1. In those with Takayasu arteritis, 67% were treated with an immunosuppressive agent, 22% with biological modifiers, and 16% with surgical procedures. In other types of disease, 88% of the patients were treated with an immunosuppressive agent, and 12% with biological modifiers. Two with Takayasu arteritis died being terminally ill.

Conclusion: This nationwide survey establishes the heterogeneous characteristics of PSV in children. Although questionnaire-based, the results of our analysis should be useful in planning prospective studies to identify the most effective therapy for each subtype of multifaceted disease.     

Birmingham vasculitis activity and chest manifestation at diagnosis can predict hospitalised infection in ANCA-associated vasculitis

We investigated the development rate and time, risk factors, predictors, and aetiologies of hospitalised infection in Korean patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We retrospectively reviewed the medical records of 154 patients with AAV. Hospitalised infection was considered only when patients were admitted for serious infection related to AAV or AAV treatment. The gap-time was defined as the period from diagnosis to the first hospitalised infection or to the last visit for uninfected patients. We calculated Birmingham vasculitis activity score (BVAS) or BVAS for granulomatosis with polyangiitis (GPA) and five factor score (FFS (2009)) and reviewed medications administered. We set the optimal cut-offs of BVAS and that of FFS (2009) at diagnosis at 20.5 and 1.5. Forty-four patients (28.6%) were admitted for serious infection. One-, 5- and 10-year hospitalised infection free survival rates were 85.1, 77.9 and 72.7%, respectively. In multivariable logistic regression analysis of significant variables in comparison analysis, only chest manifestation at diagnosis (OR 2.692) was remarkably associated with hospitalised infection. In multivariable Cox hazard model analysis of significant variables in Kaplan-Meier analysis, BVAS at diagnosis ≥?20.5 (HR 2.375) and chest manifestation at diagnosis (HR 2.422) were independent predictors of hospitalised infection during the gap-time. Bacterial pneumonia was the most common infectious aetiology (N?=?29), followed by fungal infection including aspergillosis (N?=?6). BVAS and chest manifestation at diagnosis can predict hospitalised infection during the gap-time.     

Comparison of a novel chemiluminescence enzyme immunoassay (CLEIA) with enzyme-linked immunosorbent assay (ELISA) for the determination of MPO-ANCA in patients with ANCA-associated vasculitis

Abstract

Background. Myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (ANCA) represents the serological hallmark of ANCA-associated vasculitis (AAV). We evaluated the analytical and diagnostic accuracy of chemiluminescence enzyme immunoassay (CLEIA) versus enzyme-linked immunosorbent assay (ELISA) for the detection of MPO-ANCA.

Methods. A total of 242 sera obtained from 51 patients with AAV and 103 patients without AAV were tested for MPO-ANCA by ELISA (NephroScholor MPOANC II) and CLEIA (the STACIA MEBLux test). Disease activity in the patients with AAV was determined based on the Birmingham Vasculitis Activity Score. We analyzed the correlations between the MPO-ANCA titers determined by the CLEIA and those determined by the ELISA, and also between the MPO-ANCA titers and the disease activity.

Results. The MPO-ANCA titers determined by the CLEIA (x) were strongly correlated with those determined by the ELISA (y). The correlation could be expressed by the following equation in this study: y = 1.8x + 7.7 (r = 0.96; p < 0.0001). At the cutoff value of 3.5 U/ml, the CLEIA yielded positive test results for MPO-ANCA in 73 of the 242 sera (30.2%), while at the cutoff value of 20 U/ml, ELISA yielded positive test results in 57 of the 242 sera (23.6%). The CLEIA yielded false-positive test results in 4 of the 120 sera obtained from the non-AAV patients (3.3%), whereas the ELISA yielded a false-positive result in only 1 of the 120 sera obtained from the non-AAV patients (0.8%). The sensitivity and specificity of the CLEIA for the diagnosis of AAV were 100% and 96.7%, respectively, while those of the ELISA were 94.3% and 99.2%, respectively. The sensitivity and specificity of the CLEIA for the prediction of active disease were 100% and 64.4%, respectively, while those of the ELISA were 94.3% and 73.6%, respectively.

Conclusion. The false positivity rate of the CLEIA for MPO-ANCA tended to be high as compared with that of the ELISA. Also, according to the correlation coefficient between the results of the CLEIA and the ELISA calculated in this study, it is necessary to pay attention to the differences in the sensitivity and specificity between CLEIA and ELISA.     

Birmingham vasculitis activity score, disease extent index and complement factor C3c reflect disease activity best in hepatitis C virus-associated cryoglobulinemic vasculitis

OBJECTIVE: Clinical measures of vasculitis activity (Birmingham vasculitis activity score = BVAS) and disease extent (Disease Extent Index = DEI), serological and immunological parameters were evaluated for the monitoring of hepatitis C virus (HCV)-associated cryoglobulinemic vasculitis (CV), treated with either cyclophosphamide or interferon-alpha 2b depending on disease severity. METHODS: Serial serum samples of 15 patients with HCV-associated CV were analyzed, and BVAS, DEI, serological and immunological parameters were recorded at diagnosis and during therapy. Eight patients were treated with interferon-alpha 2b and 7 patients with cyclophosphamide. RESULTS: A complete or partial response of the CV was seen in both treatment groups. BVAS, complement factor C3c, cryoglobulinemia, and rheumatoid factor significantly decreased in both treatment groups during 6 months (p < 0.05). DEI decrease was significant in the cyclophosphamide group (p < 0.05), and there was a trend in the interferon-alpha 2b group (p = 0.06). BVAS and DEI were significantly positively correlated, and both parameters were significantly negatively correlated with C3c levels in both treatment groups (interferon-alpha 2b/cyclophosphamide: r = -0.89, p = 0.001 versus r = -0.87, p < 0.001, respectively) whereas other parameters were not, e.g. ESR and CRP. CONCLUSIONS: Patients with different degrees of disease severity, treated with either cyclophosphamide or interferon-alpha 2b depending on their disease activity, achieved remission of their CV. BVAS, DEI and C3c were especially useful in the follow-up of HCV-associated CV. C3c correlated with BVAS and DEI during therapy and provided additional information about vasculitis activity that was not reflected by other serological or immunological parameters, e.g. ESR or CRP.     

Long-Term Follow-Up of Cyclophosphamide Compared with Azathioprine for Initial Maintenance Therapy in ANCA-Associated Vasculitis

Background and objectives

Treatment with azathioprine within 3 months of remission induction with cyclophosphamide is a common treatment strategy for patients with ANCA-associated vasculitis. This study comprised patients undergoing long-term follow-up who were randomly allocated to azathioprine after 3–6 months or after 12 months of cyclophosphamide treatment.

Design, setting, participants, & measurements

Patients from 39 European centers between 1995 and 1997 with a new diagnosis of ANCA-associated vasculitis that involved the kidneys or another vital organ were eligible. At the time of diagnosis, participants were randomly allocated to convert to azathioprine after 3–6 months (the azathioprine group) or after 12 months of cyclophosphamide (the cyclophosphamide group). Patients who did not achieve a remission within 6 months were excluded. This study assessed relapses, ESRD, and death during long-term follow-up.

Results

Patients were allocated to the azathioprine group (n=71) and the cyclophosphamide group (n=73). Of these patients, 63 (43.8%) developed a relapse, 35 (24.3%) developed a renal relapse, 13 (9.0%) developed ESRD, and 21 (14.6%) died. Although there were worse outcomes in the azathioprine group, none were statistically significant. The subdistribution hazard ratio [sHR] for relapse was 1.63 (95% confidence interval [95% CI], 0.99 to 2.71), the composite of relapse or death hazard ratio [HR] was 1.59 (95% CI, 1.00 to 2.54), the ESRD sHR was 1.71 (95% CI, 0.56 to 5.19), and the death HR was 0.75 (95% CI, 0.32 to 1.79).

Conclusions

It remains uncertain whether converting to azathioprine after 3–6 months of induction cyclophosphamide therapy is as effective as converting after 12 months. Outcomes are still poor for this group of patients and further research is required to determine the optimal timing of maintenance therapy.     

Effects of cytapheresis on tumor necrosis factor receptor and on expression of CD63 in myeloperoxidase--antineutrophil cytoplasmic autoantibody-associated vasculitis

To evaluate the therapeutic potential of cytapheresis in myeloperoxidase-antineutrophil cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis, plasma levels of soluble tumor necrosis factor receptors (sTNFR1, sTNFR2) and the expression of TNFR1, TNFR2, and CD63 on granulocytes were measured. The levels of sTNFR1 and sTNFR2, and the expression of TNFR1 and TNFR2 were significantly higher in MPO-ANCA-associated vasculitis patients than in normal controls. The levels of sTNFR1 and sTNFR2 increased significantly after cytapheresis (P < 0.001). The expression of TNFR1 showed a tendency to decrease after cytapheresis (P = 0.0535). The expression of CD63 decreased significantly after cytapheresis (P < 0.05). Because sTNFR1 and sTNFR2 act as TNF-antagonists, the increases of sTNFR1 and sTNFR2 after cytapheresis might contribute to inhibit the action of TNF-alpha. The decreased expression of TNFR1, which mediates the signal for polymorphonuclear cell respiratory burst, might also contribute to the reduction of inflammation. From these results, the inhibition of TNF action and removal of degranulated granulocytes appear to be related to the mechanism whereby cytapheresis can exert a beneficial and therapeutic function in the treatment of MPO-ANCA-associated vasculitis.     

Long‐term followup of polyarteritis nodosa,microscopic polyangiitis,and Churg‐Strauss syndrome: Analysis of four prospective trials including 278 patients

Objective

To determine the long‐term outcome of patients with polyarteritis nodosa (PAN), microscopic polyangiitis (MPA), and Churg‐Strauss syndrome (CSS), to compare the long‐term outcome with the overall French population, to evaluate the impact on outcome of the type of vasculitis, prognostic factors, and treatments administered at diagnosis, and to analyze treatment side effects and sequelae.

Methods

Data from PAN, MPA, and CSS patients (n = 278) who were enrolled between 1980 and 1993 were collected in 1996 and 1997 and analyzed. Two prognostic scoring systems, the Five‐Factors Score (FFS) and the Birmingham Vasculitis Activity Score (BVAS), were used to evaluate all patients at the time of diagnosis.

Results

The mean (±SD) followup of the entire population was 88.3 ± 51.9 months (range 3 days to 192 months). Of the 85 deaths recorded, at least 41 were due to progressive vasculitis or its consequences. Death rates reflected disease severity, as assessed by the FFS (P = 0.004) and the BVAS (P < 0.0002), and the 2 scores were correlated (r = 0.69). Relapses, rarer in hepatitis B virus (HBV)–related PAN (7.9%) than in MPA (34.5%) (P = 0.004), occurred in 56 patients (20.1%) and did not reflect disease severity. Survival curves were similar for the subpopulation of 215 patients with CSS, MPA, and non–HBV‐related PAN who were given first‐line corticosteroids (CS) with or without cyclophosphamide (CYC). However, CS with CYC therapy significantly prolonged survival for patients with FFS scores ≥2 (P = 0.041). Relapse rates were similar regardless of the treatment regimen; only patients treated with CS alone had uncontrolled disease. CYC was associated with a greater frequency of side effects (P < 0.00001).

Conclusion

Rates of mortality due to PAN (related or unrelated to HBV), MPA, and CSS reflected disease severity and were higher than the mortality rate in the general population (P < 0.0004). Rates of relapse, more common in MPA than HBV‐related PAN patients, did not reflect disease severity. Survival rates were better among the more severely ill patients who had received first‐line CYC. Based on these findings, we recommend that the intensity of the initial treatment be consistent with the severity of the disease. The use of the FFS and BVAS scores improved the ability to evaluate the therapeutic response.

     

Predictive factors for mortality in elderly Japanese patients with severe microscopic polyangiitis: A retrospective single-center study

Purpose: To determine mortality and its predictive factors in elderly Japanese patients with severe microscopic polyangiitis (MPA).

Method: This retrospective single-center study determined the mortality of 52 patients with MPA who were admitted to our geriatric medical center from 2002 to 2014. The variables at baseline, including patient demographics, clinical characteristics, and treatment, were analyzed for their association with mortality.

Result: Mean age at onset of MPA was 73.2 years, and the one-year survival rate was 65.9%. Relapse was observed in 32.7%. Among variables at diagnosis, age, cardiomyopathy, central nervous system (CNS) involvement, alveolar hemorrhage, disease severity, the 1996 Five-Factor Score (FFS), and the 2009 FFS were associated with mortality in univariate analysis. Cardiomyopathy, CNS involvement, age?>65 years, disease severity, Birmingham Vasculitis Activity Score, the 1996 FFS, and the 2009 FFS were associated with relapse-free survival in univariate analysis.

Conclusion: We investigated mortality and relapse-free survival and their predictive factors in elderly Japanese patients with severe MPA. Age, disease severity, the 1996 FFS, and the 2009 FFS at diagnosis were prognostic factors for both mortality and relapse-free survival.     

Outcome of patients with small-vessel vasculitis admitted to a medical ICU

PURPOSES: This study aims to describe the clinical course and prognostic factors of patients with small-vessel vasculitis admitted to a medical ICU. METHODS: We reviewed the clinical records of 38 patients with small-vessel vasculitis admitted consecutively to the ICU between January 1997 and May 2004. The APACHE (acute physiology and chronic health evaluation) III prognostic system was used to determine the severity of illness on the first ICU day; the sequential organ failure assessment (SOFA) score was used to measure organ dysfunction, and the Birmingham vasculitis activity score for Wegener granulomatosis (BVAS/WG) was used to assess vasculitis activity. Outcome measures were the 28-day mortality and ICU length of stay. RESULTS: Nineteen patients (50%) had Wegener granulomatosis, 16 patients (42%) had microscopic polyangiitis, 2 patients had CNS vasculitis, and 1 patient had Churg-Strauss syndrome. Reasons for ICU admission included alveolar hemorrhage in 14 patients (37%), sepsis in 5 patients (13%), seizures in 3 patients (8%), and pneumonia in 2 patients (5%). The median ICU length of stay was 4.0 days (interquartile range, 2.0 to 6.0 days). The APACHE III score was lower in survivors than nonsurvivors (p = 0.010). The predicted hospital mortality was 54% for nonsurvivors and 21% for survivors (p = 0.0038). The mean SOFA score was 11.6 (SD, 2.6) in nonsurvivors, compared to 6.9 (SD, 2.4) in survivors (p = 0.0004). Mean BVAS/WG scores were 8.6 (SD, 3.6) in nonsurvivors and 4.7 (SD, 4.6) in survivors (p = 0.0889). Twenty-six percent of the patients received invasive mechanical ventilation, and 33% underwent dialysis. The 28-day and 1-year mortality rates were 11% and 29%, respectively. CONCLUSIONS: The mortality of patients with small-vessel vasculitis admitted to the ICU is lower than predicted, and alveolar hemorrhage is the most common reason for ICU admission.