Interest of Procalcitonin in ANCA Vasculitides for Differentiation between Flare and Infections.

Procalcitonin (PCT) was established as a biomarker to discriminate bacterial infections from other proinflammatory conditions. Our objective was to determine whether PCT is effective in differentiating infection from antineutrophil-cytoplasmic-antibody (ANCA)-associated vasculitides (AAV) flare. In this retrospective, case-control study, PCT and other inflammatory biomarkers of patients with AAV relapse (relapsing group) were compared to infected AAV patients (infected group). In our population of 74 patients with AAV, PCT was significantly higher in the infected group than in the relapsing group (0.2 µg/L [0.08; 0.935] vs. 0.09 µg/L [0.05; 0.2], p < 0.001). Sensitivity and specificity were 53.4% and 73.6%, respectively, for an ideal threshold of 0.2 µg/L. C-reactive protein (CRP) was significantly higher in cases of infection than in relapse (64.7 mg/L [25; 131] vs. 31.5 mg/L, [10.6; 120], p = 0.001). Sensitivity and specificity for infections were 94.2% and 11.3%, respectively. Fibrinogen, white blood cell count, eosinophil count, and neutrophil count were not significantly different. In the multivariate analysis, the relative risk of infection was 2 [1.02; 4.5] (p = 0.04) for a PCT above 0.2 µg/L. In AAV, PCT may be useful for discriminating between infections and flare in patients suffering from AAVs.

Rituximab vs Cyclophosphamide Induction Therapy for Patients With Granulomatosis With Polyangiitis.

Importance: Results of randomized clinical trials have demonstrated rituximab's noninferiority to cyclophosphamide as induction therapy for antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV), with neither treatment having a specific advantage for granulomatosis with polyangiitis (GPA). However, post hoc analysis results have suggested that rituximab might be more effective than cyclophosphamide in inducing remission in patients with proteinase 3-positive AAV. Objective: To compare the effectiveness of rituximab and cyclophosphamide in inducing GPA remission in a large population of unselected patients. Design, Setting, and Participants: This comparative effectiveness study used multicenter target trial emulation observational data from 32 French hospitals in the French Vasculitis Study Group Registry. Groups were determined according to treatments received, without any intervention from the investigators. Inverse probability of treatment weighting was used to correct for baseline imbalance between groups. Participants included patients with newly diagnosed or relapsing GPA who satisfied American College of Rheumatology classification criteria and/or Chapel Hill Consensus Conference nomenclature. Data were analyzed from October 1, 2021, to May 31, 2022. Exposures: At least 1 infusion of rituximab or cyclophosphamide for induction therapy between April 1, 2008, and April 1, 2018. Main Outcomes and Measures: The primary outcome was remission rate at month 6 (±2 months), with remission defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 and prednisone dose of 10 mg/d or less. The BVAS is a validated tool for small-vessel vasculitis and used to assess the level of disease activity, with a numerical weight attached to each involved organ system. The BVAS has a range of 0 to 63 points; a score of 0 indicates no disease activity. Subgroup analyses included the primary outcome for patients with a new diagnosis, for most recently treated patients, and for patients with myeloperoxidase-ANCA positivity. Results: Among 194 patients with GPA included in the analysis (mean [SD] age, 54 [15] years; 110 men [56.7%]), 165 (85.1%) had a new diagnosis, and 147 of 182 with data available (80.8%) had proteinase 3-ANCA positivity. Sixty-one patients received rituximab and 133 received cyclophosphamide for induction therapy. In the weighted analysis, the primary outcome was reached for 73.1% of patients receiving rituximab vs 40.1% receiving cyclophosphamide (relative risk [RR], 1.82 [95% CI, 1.22-2.73]; risk difference, 33.0% [95% CI, 12.2%-53.8%]; E value for RR, 3.05). Similar results were observed in the subgroup of patients with newly diagnosed GPA and those with a more recent treatment. In the subset of 27 patients with myeloperoxidase-ANCA-positive GPA, 8 of 10 rituximab recipients and 8 of 17 cyclophosphamide recipients met the primary end point (unweighted RR, 1.73 [95% CI, 0.96-3.11]). Conclusions and Relevance: In this comparativeness effectiveness study using clinical data, rituximab induction therapy for GPA was more frequently associated with remission than cyclophosphamide. These results inform clinical decision-making concerning the choice of remission induction therapy for this subset of patients with AAV.

Comparative study of granulomatosis with polyangiitis subsets according to ANCA status: data from the French Vasculitis Study Group Registry.

OBJECTIVE: To investigate whether antineutrophil cytoplasm antibody (ANCA)-negative and myeloperoxidase (MPO)-ANCA-positive granulomatosis with polyangiitis (GPA) differ from proteinase-3 (PR3)-ANCA-positive GPA. METHODS: Diagnostic characteristics and outcomes of newly diagnosed French Vasculitis Study Group Registry patients with ANCA-negative, MPO-ANCA-positive or PR3-ANCA-positive GPA satisfying American College of Rheumatology criteria and/or Chapel Hill Conference Consensus Nomenclature were compared. RESULTS: Among 727 GPA, 62 (8.5%) were ANCA-negative, 119 (16.4%) MPO-ANCA-positive and 546 (75.1%) PR3-ANCA-positive. ANCA-negative patients had significantly (p<0.05) more limited disease (17.7% vs 5.8%) and less kidney involvement (35.5% vs 58.9%) than those PR3-ANCA-positive or MPO-ANCA-positive, with comparable relapse-free (RFS) and overall survival (OS). MPO-ANCA-positive versus PR3-ANCA-positive and ANCA-negative patients were significantly more often female (52.9% vs 42.1%), older (59.8 vs 51.9 years), with more frequent kidney involvement (65.5% vs 55.2%) and less arthralgias (34.5% vs 55.1%), purpura (8.4% vs 17.1%) or eye involvement (18.5% vs 28.4%); RFS was similar but OS was lower before age adjustment. PR3-positive patients' RFS was significantly lower than for ANCA-negative and MPO-positive groups combined, with OS higher before age adjustment. PR3-ANCA-positivity independently predicted relapse for all GPA forms combined but not when comparing only PR3-ANCA-positive versus MPO-ANCA-positive patients. CONCLUSIONS: Based on this large cohort, ANCA-negative versus ANCA-positive patients more frequently had limited disease but similar RFS and OS. MPO-ANCA-positive patients had similar RFS but lower OS due to their older age. PR3-ANCA-positive GPA patients' RFS was lower than those of the two other subsets combined but that difference did not persist when comparing only PR3 versus MPO-ANCA-positive patients.

Clonal haematopoiesis of indeterminate potential and cardiovascular events in systemic lupus erythematosus (HEMATOPLUS study).

OBJECTIVE: The detection of somatic mutations among the genes of myeloid cells in asymptomatic patients-defining clonal haematopoiesis of indeterminate potential (CHIP)-is associated with a predisposition to cardiovascular events (CVEs) in the general population. We aimed to determine whether CHIP was associated with CVEs in SLE patients. METHODS: The study is an ancillary study of the randomized, double-blind, placebo-controlled, multicentre PLUS trial conducted from June 2007 through August 2010 at 37 centres in France, involving 573 SLE patients. The search for somatic mutations by high-throughput sequencing of 53 genes involved in clonal haematopoiesis was performed on genomic DNA collected at PLUS inclusion. CHIP prevalence was assessed in SLE and in a retrospective cohort of 479 patients free of haematological malignancy. The primary outcome was an incident CVE in SLE. RESULTS: Screening for CHIP was performed in 438 SLE patients [38 (29-47) years, 91.8% female]. Overall, 63 somatic mutations were identified in 47 patients, defining a CHIP prevalence of 10.7% in SLE. Most SLE patients (78.7%) carried a single mutation. Most variants (62.5%) were located in the DNMT3A gene. CHIP frequency was related to age and to age at SLE diagnosis, and was associated with a lower frequency of aPLs. CHIP occurred >20 years earlier (P < 0.00001) in SLE than in controls. The detection of CHIP at inclusion was not found to be associated with occurrence of CVEs during follow-up [HR = 0.42 (0.06-3.21), P = 0.406]. CONCLUSION: The prevalence of CHIP is relatively high in SLE for a given age, but was not found to be associated with incident CVEs. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT05146414.

Localized versus systemic granulomatosis with polyangiitis: data from the French Vasculitis Study Group Registry.

OBJECTIVE: To describe the main features at diagnosis and evolution over time of patients with localized granulomatosis with polyangiitis (L-GPA) compared with those of systemic GPA (S-GPA). METHODS: EULAR definitions of L-GPA, i.e. upper and/or lower respiratory tract involvement, and S-GPA were applied to patients from the French Vasculitis Study Group Registry. L-GPA and S-GPA patients' characteristics at diagnosis and long-term outcomes were analysed and compared. RESULTS: Among the 795 Registry patients, 79 (10%) had L-GPA. Their main clinical manifestations were rhinitis, lung nodules, sinusitis and otitis. L-GPA vs S-GPA patients at diagnosis, respectively, were younger, more frequently had saddle nose deformity or subglottic stenosis and were less often PR3-ANCA-positive. L-GPA vs S-GPA induction therapy less frequently included CYC but more often a combination of MTX and glucocorticoids; 64% of MTX-treated patients experienced disease progression within 18 months post-diagnosis. L- and S-GPA patients' estimated relapse-free-survival probabilities, relapse rates and refractory disease rates at each time point were comparable, but L-GPA patients had more frequent ENT and lung relapses, and higher overall survival rates (P<0.02). Over a median follow-up of 3.5 years, 18 (22.8%) L-GPA progressed to S-GPA, either as a relapse after a period in remission or more frequently in the context of refractory disease. L-GPA patients experienced more ENT-related damage. CONCLUSIONS: The relapse risks of L-GPA and S-GPA were similar, but relapse patterns differed and L-GPA overall survival rate was higher. About one-quarter of L-GPA patients developed S-GPA over time, but without end-stage organ involvement.

Significance of eosinophilia in granulomatosis with polyangiitis: data from the French Vasculitis Study Group Registry.

OBJECTIVE: To describe disease presentation and long-term outcome of granulomatosis with polyangiitis (GPA) patients according to blood eosinophils count (Eos) at vasculitis diagnosis. METHODS: Data from newly diagnosed GPA patients registered in the French Vasculitis Study Group database with available eosinophil count at diagnosis were reviewed. Disease characteristics, rate and type of relapses, and overall survival were analysed according to Eos, categorized as normal (<500/mm3), mild-to-moderate hypereosinophilia (HE) (between 500 and 1500/mm3) and severe HE (>1500/mm3). RESULTS: Three hundred and fifty-four patients were included. At diagnosis, 90 (25.4%) patients had HE ≥500/mm3; they were more likely male (73% vs 56%, P = 0.006) and had more frequent cutaneous manifestations (49% vs 33%, P = 0.01), peripheral neuropathy (32% vs 17%, P = 0.004) and higher BVAS (21 vs 18, P = 0.01), compared with those with Eos <500/mm3. Patients with severe HE (n = 28; median Eos 2355, range 1500-9114) had more frequent renal function worsening at presentation (P = 0.008). After a median follow-up of 3.95 (interquartile range 1.95-6.76) years, no difference was found in overall relapse rates according to baseline Eos, but those with HE experienced more neurological (P = 0.013) and skin (P = 0.024) relapses and had more frequently peripheral neuropathy as damage at last follow-up (P = 0.02). Overall survival was not significantly different in patients with normal Eos or HE at diagnosis. (P = 0.08). CONCLUSIONS: Blood HE at diagnosis, observed in about one-quarter of GPA patients, identifies a subgroup of patients with a more severe disease and higher rate of skin and neurological involvement both at presentation and during follow-up.

Granulomatosis with polyangiitis: Study of 795 patients from the French Vasculitis Study Group registry.

OBJECTIVE: To describe the characteristics and long-term outcomes of patients with granulomatosis with polyangiitis (GPA) from the French Vasculitis Study Group database. METHODS: Patients' clinical and laboratory characteristics, Birmingham Vasculitis Activity Score (BVAS)-assessed disease activity, malignancies, opportunistic infections, and vital status were collected at diagnosis and each visit. Estimated probabilities and predictors of overall (OS) and relapse-free survival (RFS) were analyzed by Cox regression. RESULTS: We enrolled 795 newly diagnosed patients, followed for a median of 3.5 years. Initial clinical manifestations involved ear, nose & throat (ENT; 80%), lungs (68%) and kidneys (56%). Among the 728 available ELISA results, 75.0% were PR3-ANCA-positive, 16.5% MPO-ANCA-positive and 62 (8.5%) ANCA-negative. Relapses occurred in 394 (50%) patients, involving ≥1 organ(s) affected at onset in 179 (46%), mainly ENT, lungs and kidneys, with mean BVAS 10.2 points below that at diagnosis (p<0.001). Five- and 10-year RFS rates were 37% and 17%, respectively. PR3-ANCA-positivity independently predicted relapse (p = 0.05) and prolonged survival (p = 0.038). OS-but not RFS-improved significantly over time (p<0.001); 10-year OS reached 88.2% (95% CI 83.9 to 92.7) for the 660 patients diagnosed after 2000. Infections were the main causes of death. Malignancy or opportunistic infection each occurred in ≤5% of the patients. CONCLUSION: Survival has improved dramatically over the last decades but the high relapse rate remains a major concern for GPA patients, once again stressing the need for therapeutic strategy optimization to lower it. PR3-ANCA-positivity was associated with increased probability of relapse and survival.

Temporal Arteritis Revealing Antineutrophil Cytoplasmic Antibody-Associated Vasculitides: A Case-Control Study.

OBJECTIVE: Temporal arteritis (TA) is a typical manifestation of giant cell arteritis (GCA). Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are rarely revealed by TA manifestations, leading to a risk of misdiagnosis of GCA and inappropriate treatments. This study was undertaken to describe the clinical, biologic, and histologic presentations and outcomes in cases of TA revealing AAV (TA-AAV) compared to controls with classic GCA. METHODS: In this retrospective case-control study, the characteristics of patients with TA-AAV were compared to those of control subjects with classic GCA. Log-rank test, with hazard ratios (HRs) and 95% confidence intervals (95% CIs), was used to assess the risk of treatment failure. RESULTS: Fifty patients with TA-AAV (median age 70 years) were included. Thirty-three patients (66%) presented with atypical symptoms of GCA (ear, nose, and throat involvement in 32% of patients, and renal, pulmonary, and neurologic involvement in 26%, 20%, and 16% of patients, respectively). Blood samples were screened for ANCAs at the time of disease onset in 33 patients, and results were positive in 88%, leading to a diagnosis of early TA-AAV in 20 patients. The diagnosis of AAV was delayed a median interval of 15 months in 30 patients. Compared to controls with GCA, patients with TA-AAV were younger (median age 70 years versus 74 years), were more frequently men (48% versus 30%), and had high frequencies of atypical manifestations and higher C-reactive protein levels (median 10.8 mg/dl versus 7.0 mg/dl). In patients with TA-AAV, temporal artery biopsy (TAB) showed fibrinoid necrosis and small branch vasculitis in 23% of patients each, whereas neither of these characteristics was evident in controls with GCA. Treatment failure-free survival was comparable between early TA-AAV cases and GCA controls, whereas those with delayed TA-AAV had a significantly higher risk of treatment failure compared to controls (HR 3.85, 95% CI 1.97-7.51; P < 0.0001). CONCLUSION: TA-AAV should be considered diagnostically in cases of atypical manifestations of GCA, refractoriness to glucocorticoid treatment, or early relapse. Analysis of TAB specimens for the detection of small branch vasculitis and/or fibrinoid necrosis could be useful. Detection of ANCAs should be performed in cases of suspected GCA with atypical clinical features and/or evidence of temporal artery abnormalities on TAB.

ANCA-associated vasculitides: Recommendations of the French Vasculitis Study Group on the use of immunosuppressants and biotherapies for remission induction and maintenance.

Treatment of vasculitides associated with anti-neutrophil cytoplasm antibodies (ANCA) (AAVs) has evolved dramatically in recent years, particularly since the demonstration of rituximab efficacy as remission induction and maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis. In 2013, the French Vasculitis Study Group (FVSG) published recommendations for its use by clinicians. Since then, new data have made it possible to better specify and codify prescription of rituximab to treat AAVs. Herein, the FVSG Recommendations Committee, an expert panel comprised of physicians with extensive experience in the treatment and management of vasculitides, presents its consensus guidelines based on literature analysis, the results of prospective therapeutic trials and personal experience.

Reducing the initial number of rituximab maintenance-therapy infusions for ANCA-associated vasculitides: randomized-trial post-hoc analysis.

OBJECTIVE: The randomized, controlled MAINRITSAN2 trial was designed to compare the capacity of an individually tailored therapy [randomization day 0 (D0)], with reinfusion only when CD19+ lymphocytes or ANCA had reappeared, or if the latter's titre rose markedly, with that of five fixed-schedule 500-mg rituximab infusions [D0 + D14, then months (M) 6, 12 and 18] to maintain ANCA-associated vasculitis (AAV) remissions. Relapse rates did not differ at M28. This ancillary study was undertaken to evaluate the effect of omitting the D14 rituximab infusion on AAV relapse rates at M12. METHODS: MAINRITSAN2 trial data were subjected to post-hoc analyses of M3, M6, M9 and M12 relapse-free survival rates in each arm as primary end points. Exploratory subgroup analyses were run according to CYC or rituximab induction and newly diagnosed or relapsing AAV. RESULTS: At M3, M6, M9 and M12, respectively, among the 161 patients included, 79/80 (98.8%), 76/80 (95%), 74/80 (92.5%) and 73/80 (91.3%) from D0, and 80/81 (98.8%), 78/81 (96.3%), 76/81 (93.8%) and 76/81 (93.8%) from D0+D14 groups were alive and relapse-free. No between-group differences were observed. Results were not affected by CYC or rituximab induction, or newly diagnosed or relapsing AAV. CONCLUSIONS: We were not able to detect a difference between the relapse-free survival rates for up to M12 for the D0 and D0+D14 rituximab-infusion groups, which could suggest that omitting the D14 rituximab remission-maintenance dose did not modify the short-term relapse-free rate. Nevertheless, results at M12 may also have been influenced by the rituximab-infusion strategies for both groups.

Relapses in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a retrospective study.

OBJECTIVE: To investigate the activity of relapsing events (RE) and their mode of presentation in patients with anti-neutrophil cytoplasmic (ANCA)-associated vasculitis (AAV). METHODS: Patients diagnosed with AAV between 1990 and 2015 experiencing at least one RE were investigated. The different organ involvements were registered during each RE. Presentation at initial onset (IO) and RE were compared. The Birmingham Vasculitis Activity Score was used to assess the activity. RESULTS: Ninety-nine patients were followed: 54 patients with 96 RE and 45 patients with none. The rate of RE was 53% with a median time of follow-up of 6.8 years. The mean time to first RE was 2.8 years. Thirty patients experienced one single RE, 15 had 2, 5 had 3, 2 had 4, and 2 had, respectively, 7 and 8. Fifty-five percent of RE had the same features as IO. Compared to IO, some clinical manifestations were less present: constitutional symptoms (29% vs 69%), ear-nose-throat (50% vs 76%), lung involvement (59% vs 76%), peripheral neuropathies (14% vs 24%), arthritis (7% vs 27%), kidney (25% vs 41%), and heart (4% vs 20%) (p < 0.001). Skin, eye, and bowel manifestations were not significantly less involved during RE. The mean Birmingham Vasculitis Activity Score at IO was 9.02 and 5.11 at relapse (p < 0.0001). Among the 96 RE, 46% had a new organ involvement compared to IO: none were life-threatening. CONCLUSION: Global activity of RE in AAV patients is lower than that of IO. Fewer organs are involved in relapses. RE turned out to begin with the same manifestations as IO in most cases.Key Points•First study looking into clinical characteristics of relapses including mostly granulomatosis with polyangiitis.•Around half of patients with AAV seemed to relapse in a similar way compared to the initial diagnosis.•The activity score during relapsing events is less important.

Orbital mass in ANCA-associated vasculitides: data on clinical, biological, radiological and histological presentation, therapeutic management, and outcome from 59 patients.

OBJECTIVE: Orbital mass is a rare and sight-threatening manifestation of ANCA-associated vasculitides, which remains a therapeutic challenge. We aimed to describe the presentation, therapeutic management and outcome of ANCA-associated vasculitides-related orbital mass. METHODS: We conducted a French nationwide retrospective study of patients with orbital mass in the setting of ANCA-associated vasculitides according to ACR criteria and/or Chapel Hill Consensus Conference definitions. RESULTS: Fifty-nine patients [33 women, median age 46 (range 7-90) years] were included. Fifty-six (95%) patients had granulomatosis with polyangiitis, two eosinophilic granulomatosis with polyangiitis and one microscopic polyangiitis. Orbital mass was unilateral in 47 (80%) cases, and seemed to develop from ENT involvement in most cases. Orbital mass biopsy was available in 32 (54%) patients, showing lymphoplasmacytic infiltration in 65%, fibrosis in 55%, granulomas in 48% and vasculitis in 36%. All patients but one received glucocorticoids as first-line therapy associated with immunosuppressive agents in 82%, mainly cyclophosphamide. Response to therapy was noted in 52% of patients treated with cyclophosphamide compared with 91% of those treated with rituximab. Twenty-seven (46%) patients required a second-line therapy because of relapse (59%) or refractory course (41%). Sequelae included visual impairment in 28%, with definitive blindness in 17%. Refractory course was associated with PR3-ANCA positivity, visual loss and contiguous pachymeningitis. CONCLUSION: Orbital mass is associated with refractory course and high frequency of sequelae, especially blindness. Refractory course is associated with PR3-ANCA positivity, visual loss and contiguous pachymeningitis.

Long-term efficacy of remission-maintenance regimens for ANCA-associated vasculitides.

OBJECTIVE: To compare long-term efficacy of remission-maintenance regimens in patients with newly diagnosed or relapsing antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides. METHODS: The 28-month Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis trial compared rituximab with azathioprine to maintain remission in patients with newly diagnosed or relapsing granulomatosis with polyangiitis, microscopic polyangiitis or renal-limited ANCA-associated vasculitis. Thereafter, prospective patient follow-up lasted until month 60. The primary endpoint was the major-relapse rate at month 60. Relapse and serious adverse event-free survival were also assessed. RESULTS: Among the 115 enrolled patients, only one was lost to follow-up at month 60. For the azathioprine and rituximab groups, respectively, at month 60, the major relapse-free survival rates were 49.4% (95% CI 38.0% to 64.3%) and 71.9% (95% CI 61.2% to 84.6%) (p=0.003); minor and major relapse-free survival rates were 37.2% (95% CI 26.5% to 52.2%) and 57.9% (95% CI 46.4% to 72.2%) (p=0.012); overall survival rates were 93.0% (95% CI 86.7% to 99.9%) and 100% (p=0.045) and cumulative glucocorticoid use was comparable. Quality-adjusted time without symptoms and toxicity analysis showed that rituximab-treated patients had 12.6 months more without relapse or toxicity than those given azathioprine (p<0.001). Antiproteinase-3-ANCA positivity and azathioprine arm were independently associated with higher risk of relapse. HRs of positive ANCA to predict relapse increased over time. CONCLUSION: The rate of sustained remission for ANCA-associated vasculitis patients, following rituximab-based or azathioprine-based maintenance regimens, remained superior over 60 months with rituximab, with better overall survival. TRIAL REGISTRATION NUMBER: NCT00748644.

Mortality in systemic necrotizing vasculitides: A retrospective analysis of the French Vasculitis Study Group registry.

OBJECTIVE: The aim of the study was to describe the evolution of mortality and cause-specific mortality over time in patients with systemic necrotizing vasculitides (SNV), including polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Patients with SNV from the French Vasculitis Study Group registry were divided into 5 groups according to the date of diagnosis: <1980, 1980-1989, 1990-1999, 2000-2010, and ≥ 2010. The causes of death were classified as vasculitis, infection, cardiovascular, malignancy, miscellaneous, or unknown. RESULTS: Among the 2217 patients included (PAN 16.1%, GPA 41.7%, EGPA 22.6%, MPA 19.6%), overall incidence of death was 2.26 per 100 person-years. The overall survival improved during each period considered. The 5-year survival rate increased from 72.2% (95% confidence interval [CI] 59.7-87.2) for patients diagnosed before 1980 to 94.5% (95% CI 90.4-98.8) after 2010 (p < 0.001). Periods of diagnosis, age, and male gender were independently associated with a poor survival with a non-significant difference between vasculitis. The incidence of mortality between the 1980s and after 2010 significantly decreased for vasculitis-related (p = 0.03) and cardiovascular-related deaths (p = 0.04). Incidence of death by infection remained stable between the 1980s and the 2000s but no death by infection occurred after 2010. The incidence of death by malignancy remained stable over time. CONCLUSION: Overall survival of SNV patients has improved since the 1980s with the decrease of vasculitis- and cardiovascular-related deaths, but cancer-related mortality remained stable. These results highlight malignancy as the current target to improve the overall prognosis.

Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2).

OBJECTIVE: To compare individually tailored, based on trimestrial biological parameter monitoring, to fixed-schedule rituximab reinfusion for remission maintenance of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAVs). METHODS: Patients with newly diagnosed or relapsing granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in complete remission after induction therapy were included in an open-label, multicentre, randomised controlled trial. All tailored-arm patients received a 500 mg rituximab infusion at randomisation, with rituximab reinfusion only when CD19+B lymphocytes or ANCA had reappeared or ANCA titre rose markedly based on trimestrial testing until month 18. Controls received a fixed 500 mg rituximab infusion on days 0 and 14 postrandomisation, then 6, 12 and 18 months after the first infusion. The primary endpoint was the number of relapses (new or reappearing symptom(s) or worsening disease with Birmingham Vasculitis Activity Score (BVAS)>0) at month 28 evaluated by an independent Adjudication Committee blinded to treatment group. RESULTS: Among the 162 patients (mean age: 60 years; 42% women) included, 117 (72.2%) had GPA and 45 (27.8%) had MPA. Preinclusion induction therapy included cyclophosphamide for 100 (61.7%), rituximab for 61 (37.6%) and methotrexate for 1 (0.6%). At month 28, 21 patients had suffered 22 relapses: 14/81 (17.3%) in 13 tailored-infusion recipients and 8/81 (9.9%) in 8 fixed-schedule patients (p=0.22). The tailored-infusion versus fixed-schedule group, respectively, received 248 vs 381 infusions, with medians (IQR) of 3 (2-4) vs 5 (5-5) administrations. CONCLUSION: AAV relapse rates did not differ significantly between individually tailored and fixed-schedule rituximab regimens. Individually tailored-arm patients received fewer rituximab infusions. TRIAL REGISTRATION NUMBER: NCT01731561; Results.

Financial impact of intravenous iron treatments on the management of anaemia inpatients: a 1 year observational study.

Background Intravenous (IV) iron preparations bypass the difficulties (malabsorption and side effects) associated with oral iron for the treatment of iron deficiency anaemia (IDA). Ferric carboxymaltose (FCM) can be administered as a single infusion over short periods of time but is more expensive than iron sucrose (IS) when the patients are hospitalized. Objectives To evaluate the appropriateness of FCM prescriptions and to establish the economic impact of this management (including disease coding) compared to the use of IV IS. Setting This study was conducted for inpatients in all departments (orthopaedic department, gastroenterology department and two units of the internal medicine department) where FCM was widely prescribed. Method We retrospectively identified 224 patients, diagnosed with IDA using laboratory parameters and/or disease coding, who received FCM between January and December 2014. Main outcome measure The primary outcome was the rate of appropriateness of FCM prescriptions and the financial impact compared to IV IS. Results 89 Patients were included. The total additional cost for an inappropriate prescription of IV FCM (68% of cases) was of 6053 €. The total incremental cost of unsuitable disease coding was estimated at 31,688 €. Indications for IV FCM were categorized: intestinal bleeding (31%), malabsorption (17%), intolerance (9%) and refractory to oral iron (7%). The majority of patients (62%) received 1000 mg of FCM per week. The average length of hospital stay was of 10 days. Conclusion The prescription of IV iron was appropriate in most cases but did not necessarily require FCM. The use of IV IS, in many cases, could present a cost-saving option for inpatients with IDA. The lack of an IDA coding generated incremental costs.

Clinical and pathological significance of cutaneous manifestations in ANCA-associated vasculitides.

OBJECTIVES: Cutaneous manifestations (CM) in ANCA-associated vasculitides (AAV) are frequent, but data on clinical significance and clinical-pathological correlations are lacking. METHODS: We conducted a multicenter, retrospective study including 1553 AAV patients. Clinical, biological and pathological features have been analyzed, and tissue samples from 46 biopsies were reviewed in a blind manner. RESULTS: CM were more frequent in EGPA (53.0%) and MPA (51.9%) than in GPA (36.7%). Lesions more frequently associated with GPA were oral ulcers (4.6% vs. 2.5% in EGPA and 0.3% in MPA), while pyoderma gangrenosum and palpebral xanthoma were specific to GPA. Lesions associated with MPA were segmentary edema (19.5% vs. 12.7% in EGPA and 4.3% in GPA) and livedo (12.4% vs. 0.5% and 2.6%, respectively), whereas those associated with EGPA were urticarial lesions (11.5% vs. 1.9% in GPA and 3.5% in MPA) and nodules (12,2% vs. 8.9% in GPA and 4.7% in MPA). In GPA, CM patients had more frequent vasculitis than granulomatous phenotype, and poorer relapse-free and overall survival. Pathological analysis showed vasculitis and/or granulomatous infiltrates in 87.5% of GPA, in 61.1% of EGPA and in all MPA. Vasculitis was more frequently observed in purpura and nodules, while granulomas were differently located and organized within vessels or interstitium according to the type of lesions. CONCLUSION: Each AAV seemed to be associated with a peculiar pattern of cutaneous lesions. CM are associated with poorer prognosis in GPA. Clinical-pathological correlations showed no specific feature of each AAV, whereas granulomatous infiltrates differ according to the type of lesions.