Remission Of Vasculitis Research Articles

Correlation of Urinary Soluble CD163 Levels With Disease Activity and Treatment Response in IgA Nephropathy

BackgroundThe TESTING trial demonstrated that corticosteroids reduce the risk of kidney failure in IgA nephropathy (IgAN) patients but increase the risk of serious adverse events. Reliable noninvasive biomarkers are needed to identify patients who would benefit most from corticosteroid therapy. Previous studies suggest glomerular macrophage infiltration is associated with the response to immunosuppressive therapy in IgAN and urinary soluble CD163(u-sCD163, a marker of M2c macrophage) is correlated with clinical remission in vasculitis. This study aims to investigate the association between u-sCD163 and response of steroids therapy in IgAN. MethodsWe measured u-sCD163 in patients from a large IgAN cohort including China participants of the TESTING trial. The correlation of baseline or serial u-sCD163 and their response of corticosteroids therapy or kidney outcomes were investigated. ResultsIn cross-sectional analysis, u-sCD163 levels correlated with kidney macrophage infiltration, especially in crescentic areas, and with active lesions. Subgroup analysis of the TESTING cohort showed higher levels u-sCD163 were associated with greater benefits from corticosteroids therapy in proteinuria remission [OR, 35.56 (95% CI, 7.62-292.34) vs 3.94 (95% CI, 1.39-12.93), p for interaction 0.036]. Corticosteroids therapy significantly reduced u-sCD163 levels at 6th month compared to placebo group [79% (IQR 58%,91%) vs 37% (-11%,58%), P<0.001]. There was no difference in the suppressive effects on u-sCD163 by either dosage of corticosteroids (full and reduced-dose). The suppression of u-sCD163 was significantly associated with a reduced risk of kidney progression events (adjusted HR 0.52,95% CI 0.30 to 0.93, P=0.027). ConclusionsU-sCD163 is a reliable noninvasive biomarker associated with active pathological lesions in IgAN and can guide glucocorticoid therapy.

Maintenance of remission of ANCA vasculitis by rituximab based on B cell repopulation versus serological flare: a randomised trial

ObjectiveTo compare two long-term remission maintenance strategies for antineutrophil cytoplasmic antibody (ANCA) vasculitis.MethodsWe conducted a prospective, single-centre, open-label, randomised controlled trial of patients with ANCA vasculitis in remission after completing...

Pregnancy outcomes in patients with IgA vasculitis with nephropathy (Henoch–Schönlein purpura nephritis) and those with IgA nephropathy: Childhood purpura nephritis is high risk for preeclampsia

Objective: Childhood IgA vasculitis in remission is not a known risk factor for pregnancy but can lead to complications such as preeclampsia, even in women with a low risk of kidney function decline.Methods: This retrospective study compared pregnancy outcomes between patients with IgA vasculitis with nephropathy (Henoch–Schönlein purpura nephritis) and those with IgA nephropathy who delivered at Osaka University Hospital between 2010 and 2020.Results: Seven patients with purpura nephritis and 37 patients with IgA nephropathy had a total of 9 and 53 pregnancies, respectively. Purpura nephritis patients had an earlier gestational age at delivery and higher frequency of preterm birth, fetal growth restriction, and preeclampsia than IgA nephropathy patients, although differences were not significant. Among pregnancies at low risk of kidney function decline, 35 were with IgA nephropathy and 9 were with purpura nephritis. The incidence of preeclampsia was significantly higher with purpura nephritis (44%: 4/9) than with IgA nephropathy (9%: 3/35 including 2 with oocyte donation). Severe and early-onset preeclampsia was noted in 2 pregnancies with purpura nephritis.Conclusion: Patients with childhood purpura nephritis in remission may develop preeclampsia, with a higher risk of severe and early-onset preeclampsia than patients with IgA nephropathy.

Nailfold video capillaroscopy as a useful diagnostic tool in systemic vasculitis

BackgroundNailfold video capillaroscopy (NVC) enables us a direct view of the microvasculature. Only several capillaroscopy studies in adult patients with vasculitis have been reported. AimTo characterize NVC changes in vasculitis. MethodsVasculitis patients and healthy controls were evaluated by NVC.NVC changes associated with vasculitis were assessed retrospectively in a cohort of 100 patients with Raynaud's phenomenon (RP). Results17 patients with active vasculitis and 8 patients with vasculitis in remission were compared to 25 age and sex-matched healthy controls. Active vasculitis patients demonstrated higher rates of neoangiogenesis and capillary loss in comparison to other groups. Two novel NVC abnormalities were observed in patients with vasculitis: “Rolling” (slow capillary flow) and “peri-capillary stippling” (PCS), small deposits that may represent capillary leak. PCS was observed exclusively in 5 of 17 patients with active vasculitis.Retrospectively, we were able to detect PCS also in 14 % of 100 patients that were evaluated for RP, of whom 64 % were diagnosed with scleroderma or a related disorder. ConclusionsPatients with active vasculitis demonstrate frequent capillary abnormalities. Although these abnormalities are non-specific, we suggest that their combination may aid the diagnosis of vasculitis. Future studies are needed to validate our findings.

Ocular Manifestations of COVID-19 in a Patient with ANCAAssociated Vasculitis Treated with Rituximab. A Case Report

The World Health Organization announced a new coronavirus pandemic on 11 March 2020. It is known that the most frequent clinical manifestation of a new coronavirus infection is lung damage with the evolution of pneumonia, as well as respiratory distress syndrome. The highest risk of severe traction and death is known to occur in the immunosuppressive group of patients. These patients include rheumatologically patients. Currently, there is no complete understanding of the pathogenesis of the development of covid-19, as well as the pathogenesis of the development of autoimmune diseases. In a pandemic, the question of how the coronavirus infection proceeds in patients on immunosuppressive therapy, in particular on anti-B cell, is relevant. In our case report presents a 69-year-old female with ANCA-associated vasculitis remission having received a B-cell-depleting therapy with rituximab (RTX), who had an ocular lesion as a clinical manifestation of Coronavirus disease 2019 (COVID-19). Two months after RTX treatment, COVID-19 was diagnosed. The patient had extrapulmonary manifestations including central nervous system involvement and ocular symptoms such as conjunctivitis, without respiratory pathology. In this clinical observation, the patient’s disease manifested itself with right-sided conjunctivitis, which is a rare manifestation as the first symptom. This article describes the features of the course and outcome of the disease, as well as, the protective effect of RTX in course of COVID-19 is discussed. A comparative analysis of cases of COVID-19 with eye damage is being carried out. This clinical observation is of great value for doctors of all specialties, especially ophthalmologists. A multidisciplinary approach is crucial to manage COVID-19.

Relapse of Hepatitis C Virus Cryoglobulinemic Vasculitis After Sustained Viral Response After Interferon-Free Direct-Acting Antivirals.

Direct-acting antiviral agents (DAAs) have modified the management of chronic hepatitis C virus (HCV) infection, including HCV-related cryoglobulinemic vasculitis (CryoVas). However, patients might experience vasculitis relapse, and no reliable predictors of CryoVas relapse after sustained virologic response (SVR) have been established. We aimed to describe HCV-CryoVas relapse rates and factors associated with it. An international multicenter cohort where patients with HCV-CryoVas from Egypt, France, and Italy treated with DAA were analyzed retrospectively. Factors associated with relapse-free survival were evaluated in a multivariate-adjusted model. Of 913 patients, 911 (99.8%) obtained SVR. After 35 months of the median follow-up, 798 patients (87.4%) had sustained remission of vasculitis, while 115 (12.6%) experienced CryoVas relapse. By the time of relapse, skin involvement was present in 100%, renal involvement in 85.2%, and peripheral neuropathy in 81.7%. Relapses were treated with glucocorticoids in 90.9%, associated with plasma exchange, cyclophosphamide, or rituximab in 50%, 37.3%, and 6.4%, respectively. The cumulative incidence of CryoVas relapse was 0.7% (95% CI 0.3-1.4), 12.3% (95% CI 10.2-14.6), and 13.1% (95% CI 11.0-15.5) at 12, 24, and 36 months after DAA treatment, respectively. Independent baseline risk factors associated with CryoVas relapse were male sex, skin ulcers, kidney involvement at baseline, and peripheral neuropathy at the end of DAA treatment. Death occurred in 11 relapsers, mainly due to infections. A substantial proportion of patients with CryoVas experience relapse after DAA-induced SVR. Relapses are moderate-to-severe and affect survival after 24 months, mainly due to infections. Independent risk factors for relapse or death were found.

IgA vasculitis in patients with inflammatory bowel disease: new insights into the role of TNF-α blockers.

The association of IgA vasculitis (IgAV) and IBD is rarely described, mainly during anti-TNF-α therapy. We aimed to describe the association of IgAV and IBD. We retrospectively analysed the association of IgAV and IBD through the implication of the GETAID and FVSG networks. Characteristics of IBD and IgAV were collected using a standardized case report form. Forty-three cases were included. IBD [mainly Crohn's disease (CD) in 58%] preceded IgAV in 38 (88%), with median interval of 9.2 (IQR 5.4-15.4) years. In these 38 patients, at IgAV diagnosis, five (13%) had active IBD and 28 (74%) were treated with anti-TNF-α for a median duration of 31.5 (IQR 19-56) months. Main IgAV manifestations were purpura all patients (100%), joints in 20/35 (57%), renal in 15/35 (43%) and gastrointestinal in 11/35 (31%) involvement. IgAV was treated with glucocorticoids in 25 (66%), colchicine in six (16%), CYC in six (16%) and anti-TNF-α were discontinued in 15/28 (54%). No IgAV relapse occurred when TNF-α blockers were stopped, vs 23% in patients pursuing it. Conversely, five (33%) had IBD flare or complication after anti-TNF-α cessation vs one (8%) in those continuing biologics. Anti-TNF-α were resumed in six (40%), with subsequent IgAV relapse in four (67%). This large cohort suggests that TNF-α blockers may promote the onset of IgAV in IBD. Discontinuation of anti-TNF-α was associated with vasculitis remission but increased risk of IBD relapses, whereas continuation of anti-TNF-α was associated with IBD remission but vasculitis relapse.

POS-375 AVACOPAN IN ANCA-ASSOCIATED VASCULITIS: EVIDENCE FOR ELIMINATION OF DAILY PREDNISONE THERAPY AND REDUCTION IN GLUCOCORTICOID-RELATED TOXICITY FROM THE PHASE 3 ADVOCATE TRIAL

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a life- or organ-threatening condition with systemic anti-neutrophil autoantibodies and small vessel inflammation. Therapy with high-dose glucocorticoids (GCs) improves the symptoms of acute vasculitis, but significant therapy-induced toxicities and comorbidities remain. Avacopan is a novel orally administered antagonist of the complement fragment C5a receptor (C5aR). A main study aim was to determine whether GC-induced toxicity could be reduced by replacing daily prednisone with avacopan while achieving high remission rates in ANCA patients. The ADVOCATE trial of avacopan was a randomized, double-blind, active-controlled, double-dummied, 52-week treatment Phase 3 trial of 331 patients with ANCA vasculitis. Subjects were randomized 1:1 to a standard prednisone regimen (daily dose starting at 60 mg tapered to 0 mg by week 21), or daily avacopan. Background therapy included cyclophosphamide followed by azathioprine or rituximab (RTX). Vasculitis remission was defined by a Birmingham Vasculitis Activity Score (BVAS) of zero. Overall GC exposure from all sources was assessed for both groups. Sources of non-study supplied GC included therapy received prior to randomization (which was tapered to 0 mg by wk 4) and GC co-administration with RTX infusions. Pre-randomization GC use and RTX therapy were balanced between the groups. Patients with worsening disease (major symptoms) could be treated with IV GCs for 3 days and/or oral tapering GCs. Non-major worsening disease could be treated with a short burst of oral GCs. GC-induced toxicity was evaluated using the Glucocorticoid Toxicity Index (GTI), employing both the Cumulative Worsening Score (CWS) which captures cumulative glucocorticoid toxicity regardless if it is permanent or transient, and the Aggregate Improvement Score (AIS) which measures both worsening and improvement in glucocorticoid toxicity. A lower score reflects less toxicity in each case. Avacopan therapy resulted in remission rates numerically superior to prednisone therapy at week 26 and statistically superior in sustained remission at week 52. The mean cumulative total GC dose from all sources (study- and non-study-supplied) over 52 wks was 3655 mg in the prednisone and 1349 mg for the avacopan groups. Most of the GC exposure was in the first 26 weeks: with mean cumulative GC dose being ~3-fold higher in the prednisone (3193 mg) than the avacopan group (1073 mg). The GTI-CWS at week 26 was 56.6 in the prednisone group and 39.7 in the avacopan group (P=0.0002), and GTI-AIS was 23.4 and 11.2 in the prednisone and avacopan groups, respectively (P=0.008). Other measures of GC-related adverse events (i.e., those based on EULAR-recommended adverse event terms or based on Investigator Assessment) also showed fewer events in the avacopan group vs. the prednisone group. While achieving and sustaining symptomatic remission, avacopan also allowed elimination of scheduled daily prednisone therapy and a reduced GC load from all sources. GC-induced toxicities were reduced with avacopan. These findings have important implications for the long-term health of ANCA-vasculitis patients through better overall disease control with reduced prednisone exposure and lessening of GC therapy-associated illnesses.

A Case of Seronegative Pulmonary-renal Syndrome: Diagnostic and Therapeutic Challenge

BACKGROUND: Pulmonary renal syndrome (PRS) is not a single entity but is caused by varied etiologies, including anti-neutrophil cytoplasmic antibody (ANCA), associated small vessel vasculitis (such as Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss vasculitis), Goodpasture’s syndrome, systemic lupus erythematosus, Henoch-Schonlein purpura, cryoglobulinemia, and rare causes such as druginduced vasculitis and subacute endocarditis.&#x0D; CASE REPORT: We report a case of a 51-year-old man who was referred to our hospital with a 2-month history of breathing difficulties, mild hemoptysis, and deteriorated renal function with a serum creatinine of 269 μmol/L. Serological testing was negative for anti-neutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (GBM) antibody, and also all cultures, including blood and urine, remained negative. In the renal biopsy, not linear deposition of IgG along the GBM and crescents at varying stages with extracapillary glomerulonephritis emphasizes the possibility of a double-seronegative pulmonary renal syndrome. Regarding therapeutic dilemmas, on the 3rd day of hospitalization, we initiated immunosuppression with cyclophosphamide and corticosteroids as well as plasma exchange (5 treatments). Under immunosuppressive therapy and plasma exchange, the patient’s status continually improved; there was no pulmonary bleeding, but the serum creatinine remained high and renal function remained in stage 4 chronic kidney disease. Four weeks later, he was hospitalized again, and we faced a new therapeutic dilemma because of the rapid relapse during immunosuppressive therapy and renal function deterioration that required hemodialysis treatment. Despite repeatedly negative results for anti-GBM and ANCA, initial immunosuppressive therapy with plasma exchange (9 treatments) was included again. The patient was discharged 30 days after admission in a stable general condition, with the maintenance immunosuppressive therapy with mycophenolate mofetil and hemodialysis 3 times/week. After 24 months, we have received information from the hemodialysis center that he is on regular hemodialysis and that he is in good condition.&#x0D; CONCLUSION: We think that in this atypical case, intensive plasma exchange and immunosuppressive therapy are crucial in the early stage and maintenance therapy is necessary for vasculitis in remission. This reported case has important clinical implications because pulmonary-renal syndrome with negative ANCAs and anti-GBM antibodies is extremely rare and no treatment recommendations have been established yet.

New therapeutic strategies in lung vasculitis.

To summarize the latest publications and provide a practical overview of treatment strategies for lung vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). In patients with severe ANCA-associated vasculitis, plasma exchange, as adjunctive therapy to standard treatment, is not associated with improved survival or reduced risk of end-stage kidney disease. A regimen with reduced dose of glucocorticoids is equally effective to induce remission as a standard regimen. In patients without organ or life-threatening disease, mycophenolate mofetil can be used in combination with oral glucocorticoid therapy to induce remission, however, with a higher risk of relapse than when using rituximab or cyclophosphamide. For maintenance of remission, a tailored regimen of rituximab infusion was equivalent to a fixed regimen, with fewer perfusions. Belimumab, a human IgG1(Equation is included in full-text article.)monoclonal antibody against B-lymphocyte stimulator, did not decrease the relapse rate when added to azathioprine and glucocorticoids. Avacopan, a complement C5a receptor inhibitor, was effective in replacing high-dose glucocorticoids in achieving complete remission of vasculitis. Significant advances have been made in the treatment strategy to both induce remission and maintain remission in patients with ANCA-associated vasculitis. The choice should take into consideration efficacy, cost-effectiveness, safety profile, ease of use, and possibility of individual tailoring of treatment.

Urinary soluble CD163 as a biomarker of disease activity and relapse in antineutrophil cytoplasm antibody-associated glomerulonephritis.

BackgroundAntineutrophil cytoplasm antibody (ANCA)-associated vasculitis is a chronic relapsing and remitting autoimmune disease. Urinary soluble CD163 (usCD163) has been proposed as a biomarker of active renal vasculitis. We aimed to assess the potential usefulness of usCD163 for diagnosing renal relapse in patients with ANCA-associated glomerulonephritis.MethodsOne hundred and fifty-six samples from 47 patients with ANCA-associated glomerulonephritis belonging to two different cohorts (incident and prevalent) and 20 healthy controls were studied. Patients from the incident cohort were prospectively followed up, and usCD163 concentrations were measured every 3 months. Renal relapses were identified and changes in usCD163 concentrations were analysed.ResultsNormalized usCD163 concentrations were elevated at disease onset in all patients with active renal vasculitis, with a median concentration of 601 ng/mmol (interquartile range 221–1404 ng/mmol). On the other hand, usCD163 concentrations were undetectable among control patients with renal vasculitis in remission. Except for non-responders, usCD163 concentrations progressively decreased in all patients after treatment. In the presence of vasculitis relapse, there was a consistent increase in usCD163 concentrations, compared with previous values. The area under the receiver-operating characteristic curve of absolute and relative changes in usCD163 concentrations to identify relapse of ANCA-associated glomerulonephritis was 0.96 [95% confidence interval (CI) 0.91–1.00; P = 0.001] and 0.95 (95% CI 0.90–1.00; P = 0.001), respectively. Sensitivity and specificity for a relative increase of 20%, or an absolute increase of 20 ng/mmol, in usCD163 concentrations were 100% for both, and 89.3% and 87.5%, respectively. Urinary sCD163 concentrations significantly correlated with Birmingham Vasculitis Activity Score scores at Month 6 (r = 0.737; P = 0.006) and Month 12 (r = 0.804; P = 0.005).ConclusionsusCD163 represents an accurate biomarker for the detection of active renal vasculitis and relapse. Its close association with disease activity provides additional information for monitoring treatment response.

P0434COST-EFFECTIVENESS OF MAINTANCE THERAPY WITH AZATHIOPRIME VERSUS RITUXIMAB (TAILORED OR FIXED-SCHEDULE) IN ADULTS WITH GENERALIZED ANCA VASCULITIS IN COLOMBIA

Abstract Background and Aims Azathioprine has been for decades the drug of choice for maintenance therapy in patients with generalized ANCA vasculitis in remission. However, recent studies show that rituximab, a high-cost biological agent, which can be administrated in two different schedules, might be more effective, so it is necessary to know the cost- effectiveness. Our goal was to compare the cost-effectiveness of the 3 maintenance schemes: standard therapy with azathioprine; fixed-dose rituximab and rituximab tailored according to CD19 lymphocyte level and ANCA titres, from the perspective of the Colombian healthcare system. Method We designed a 5-year annual cycle Markov model with the following stages: remission, minor relapse, mayor relapse and death. Transition probabilities were obtained from a systematic review of the literature (Scopus and Pubmed). Following national guidelines for economic studies, costs (in 2018, 1 euro = 3489 Colombian pesos) were estimated based on national drug registries, and official tariff manuals for procedures and other resources. Main outcome was quality-adjusted life years (QALY), using lupus nephropathy as a proxy; values were obtained from Tufts CEA Registry and validated by local expert panel through a modified Delphi technique. Cost-effectiveness threshold was three-times per capita GDP (16.872 euros). Discount rate was 5%. Univariate and probabilistic sensitivity analyses were performed. Results Overall discounted 5-years costs were € 1149 for azathioprine; € 4025 for tailored rituximab and € 5221 for fixed rituximab. QALY gains were 2.94, 3.63 and 3.64, respectively. Both tailored and fixed rituximab were cost-effective (cost per QALY gained: € 4168 and € 5817 respectively), but tailored dosing was preferable due to its lower cost. Sensitivity analyses did not modify these results significantly. Conclusion To our knowledge this is the first economic evaluation that compare azathioprine with tailored and fixed rituximab regimens as a vasculitis maintenance treatment in adults with ANCA generalized. Due to its lower effectiveness azathioprine should not be the first line of treatment. Tailored rituximab should be a better option than fixed schedule due to its lower cost with similar effectiveness.

Vascularite à IgA satellite d’une pneumopathie abcédée à Klebsiella pneumoniae

IgA vasculitis is a leucocytoclastic vasculitis of small vessels with immune deposits of IgA. It tends to occur in a post-infectious context, though the pathogenic agent is rarely found. We report, for the first time, the case of an 81-year old patient who presented with an acute IgA vasculitis with cutaneous and joint involvement during a Klebsiella pneumoniae respiratory infection. Remission of vasculitis was observed after antibiotic therapy alone. This observation reminds us of the need to search carefully for any pathogenic agent that may be driving IgA vasculitis as this may be important both for understanding aetiology and for treatment.

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

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

A large superior mesenteric artery aneurysm and ileal obstruction: a rare presentation of polyarteritis nodosa in an infant.

Polyarteritis nodosa (PAN) is a rare form of vasculitis that occurs in childhood and affects small- and medium-sized arteries. Large aneurysms due to PAN can induce fatal complications like rupturing or occlusion of the affected arteries. Here, we report a case of a 4-month-old girl with PAN complicated by a large superior mesenteric artery aneurysm and ileal obstruction. We controlled her blood pressure to prevent the artery from rupturing. A combination of prednisolone, intravenous cyclophosphamide, and plasma exchange reduced the inflammation. She developed mechanical ileus due to ileum stricture and underwent bowel resection. Histopathological examinations revealed reparative arteritis around the healed ulcer. Her postoperative course was uneventful without further dilatation of the aneurysm. This case highlights the importance of intensive immunosuppressive therapy and appropriate blood pressure control in pediatric patients with PAN complicated by large aneurysms. Mechanical ileus can develop and may require surgical management even after remission of vasculitis.

In ANCA-associated vasculitis in remission, tailored vs fixed-schedule rituximab did not differ for relapse at 28 months.

Source Citation Charles P, Terrier B, Perrodeau E, et al; French Vasculitis Study Group. Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasc...

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)

ObjectiveTo 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).MethodsPatients with newly diagnosed or relapsing granulomatosis...

Efficacy and Safety of Sofosbuvir Plus Daclatasvir for Treatment of HCV-Associated Cryoglobulinemia Vasculitis

Circulating mixed cryoglobulins are detected in 40%-60% of patients with hepatitis C virus (HCV) infection, and overt cryoglobulinemia vasculitis (CryoVas) develops in approximately 15% of patients. Remission of vasculitis has been associated with viral clearance, but few studies have reported the effectiveness of direct-acting antiviral drugs in these patients. We performed an open-label, prospective, multicenter study of the effectiveness and tolerance of an all-oral, interferon- and ribavirin-free regimen of sofosbuvir plus daclatasvir in patients with HCV-associated CryoVas. Forty-one consecutive patients with active HCV-associated CryoVas (median age, 56 y; 53.6% women) were recruited from hospitals in Paris, France, from 2014 through 2016. They received sofosbuvir (400 mg/day) plus daclatasvir (60 mg/day) for 12 weeks (n= 32) or 24 weeks (n= 9), and were evaluated every 4 weeks until week 24 and at week 36. Blood samples were analyzed for complete blood count, serum chemistry profile, level of alanine aminotransferase, rheumatoid factor activity, C4 fraction of complement, and cryoglobulin; peripheral blood mononuclear cells were isolated for flow cytometry analysis. Thirty-seven patients (90.2%) had a complete clinical response (defined by improvement of all the affected organs involved at baseline and no clinical relapse) after a median time of 12 weeks of therapy; all had a sustained virologic response (no detectable serum HCV RNA 12 weeks after the end of antiviral therapy). Patients' mean cryoglobulin level decreased from 0.56 ± 0.18 at baseline to 0.21 ± 0.14 g/L at week 36, and no cryoglobulin was detected in 50% of patients at this time point. After antiviral therapy, patients had increased numbers of T-regulatory cells, IgM+CD21-/low-memory B cells, CD4+CXCR5+ interleukin 21+ cells, and T-helper 17 cells, compared with before therapy. After a median follow-up period of 26 months (interquartile range, 20-30 mo), no patients had a serious adverse event or relapse of vasculitis.

End-stage renal disease in ANCA-associated vasculitis.

The outcomes in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis have improved significantly over the past decades, although a significant proportion of them still reach end-stage renal disease (ESRD). Renal replacement therapy (RRT) is associated with a relatively low risk of relapsing vasculitis as a result of anti-rejection treatment after kidney transplantation or quiescence of the autoimmune process in haemodialysis patients, but a flare of vasculitis in the latter setting presents a challenge because the treatment is poorly tolerated. There are benefits of rituximab in haemodialysed patients, as it is more steroid sparing in the treatment of extrarenal disease. More favourable outcomes of kidney transplantation compared with haemodialysis support its use as a preferable method of RRT in patients with vasculitis remission or low disease activity.

Dramatic effects of eculizumab in a child with diffuse proliferative lupus nephritis resistant to conventional therapy

Treatment of systemic lupus erythematosus (SLE) with severe diffuse proliferative nephritis is often challenging, particularly in small children in whom a genetic conditioning is likely to play a role. The effectiveness of standard therapy based on glucocorticoid and immunosuppressive drugs is often unsatisfactory. A 4 year-old girl, whose parents were first-grade cousins of Moroccan ancestry, developed SLE that progressed to severe renal involvement despite standard therapy. She had persistently undetectable serum C4 levels and very low C3 levels (<30 mg/dl), and extremely high anti-DNA titers (>1:640) that remained unmodified during 2 years of follow-up. No mutations of genes encoding for complement inhibitors were detected. Despite aggressive therapy based on prednisone, plasma exchanges, and cyclosporine, the child worsened and eventually developed features of atypical hemolytic uremic syndrome (aHUS). Treatment with eculizumab provided prompt remission of vasculitis, proteinuria, and hematuria, with normalization of renal function. Two attempts to withdraw eculizumab were followed by severe relapses and rescued by reinstating treatment. The child has been treated with eculizumab for > 17 months without relevant side effects. C5 inhibition by eculizumab completely reversed clinical symptoms and laboratory renal signs of severe lupus nephritis. Blocking complement-system activation with the use of targeted drugs may be a new and exciting strategy to treat SLE patients unresponsive to conventional therapy.