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Fibrosis-5 predicts end-stage renal disease in patients with microscopic polyangiitis and granulomatosis with polyangiitis without substantial liver diseases.

ABSTRACT: We previously reported that fibrosis-4 (FIB-4) was associated with poor outcomes of microscopic polyangiitis (MPA) and granuloma with polyangiitis (GPA). We also investigated the potential of FIB-5, a novel index, in predicting all-cause mortality and end-stage renal disease (ESRD) during follow-up in patients with MPA and GPA without substantial liver diseases. Clinical and laboratory data at diagnosis were collected by reviewing the medical records of 180 patients with MPA and GPA. FIB-5 was obtained by a following equation: FIB-5 = (serum albumin (g/L) × 0.3 + platelet count (10⁹/L) × 0.05) - (alkaline phosphatase (IU/L) × 0.014 + aspartate aminotransferase/alanine aminotransferase ratio × 6 + 14). The median age of the patients at diagnosis was 61.0 years. FIB-5 at diagnosis could not reflect the cross-sectional vasculitis activity. The cutoffs of FIB-5 for poor outcomes was set as 0.82 (the lowest tertile) and -0.42 (the lowest quartile) at diagnosis. In Kaplan-Meier survival analysis, patients with FIB-5 < 0.82 and those with FIB-5 < -0.42 exhibited lower ESRD-free survival rates than those without. However, it could not predict all-cause mortality. In multivariable Cox hazards analysis, both FFS (Hazard ratio (HR) 1.554) and FIB-5 < 0.82 (HR 2.096) as well as both FFS (HR 1.534) and FIB-5 < -0.42 (HR 2.073) at diagnosis independently predicted ESRD during follow-up. In conclusion, FIB-5 < 0.82 and FIB-5 < -0.42 at diagnosis could predict the occurrence of ESRD, but not all-cause mortality, during follow-up in patients with MPA and GPA without substantial liver diseases.

SUBMITTER: Kwon HC

PROVIDER: S-EPMC8266773 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Molecular targeted therapies for microscopic polyangiitis and granulomatosis with polyangiitis.

Project description:Clinical trials and observational studies have established cyclophosphamide (CY) or rituximab plus glucocorticoid (GC) as standard remission induction therapies in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). However, because these regimens are associated with serious adverse drug reactions, the development of drugs with novel mechanisms of actions are needed. Progress in basic and clinical research has identified novel candidate targeting molecules, including B-cell activating factor (BAF), C5a receptor, and interleukin-6. The combination of rituximab and BAF blockade in patients with MPA and GPA is under investigation in an effort to strike a better benefit-risk balance. Phase II clinical trials of avacopan (CCX168), an orally administered C5a receptor antagonist, have suggested a reduction in the dosage of concomitant GC or the replacement of GC in patients with MPA and GPA. The results from a currently ongoing phase III trial are awaited. Anecdotal case reports and an open-label pilot study have indicated the effectiveness of tocilizumab in patients with MPA and GPA. A randomized clinical trial comparing tocilizumab and intravenous CY in combination with GC is currently in progress. Molecular targeted therapy is expected to transform the treatment strategy for MPA and GPA to allow GC-free or at least less GC-dependent forms of therapy.

| S-EPMC6506735 | biostudies-literature

Fibrosis-4 index at diagnosis is associated with all-cause mortality in patients with microscopic polyangiitis and granulomatosis with polyangiitis.

Project description:BackgroundThe fibrosis-4 index (FIB-4) has been reported to be associated with all-cause mortality in several chronic diseases. In this study, we investigated whether at diagnosis could be associated with all-cause mortality in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).MethodsWe retrospectively reviewed the medical records of 132 MPA and GPA patients without chronic liver diseases. Conventional risk factors included old age (≥ 65 years), male gender, diabetes mellitus (DM) and hypertension (HTN) at diagnosis, and disease-related risk factor included GPA, antineutrophil cytoplasmic antibody, Birmingham vasculitis activity score (BVAS) and five factor score (FFS (2009)). The cut-off of FIB-4 for significant liver fibrosis (S2-4) was set at 1.45.ResultsThe mean age was 57.2 years and 27 patients (20.5%) had significant liver fibrosis (FIB-4 ≥ 1.45). Fifteen patients (11.4%) died during follow-up. In the univariable Cox Hazards model, age ≥ 65 years (Hazard ratio (HR) 5.055), DM (HR 3.446), HTN (HR 4.611), FFS (2009) ≥ 2 (HR 4.849) and FIB-4 ≥ 1.45 (HR 9.958) at diagnosis were significantly associated with all-cause mortality. In the multivariable Cox Hazards model, only FIB-4 at diagnosis ≥1.45 (HR 6.253, 95% confidence interval 1.398, 27.963) was associated with all-cause mortality during the follow-up in patients with MPA and GPA.ConclusionsFIB-4 at diagnosis ≥1.45 is an independent predictor of all-cause mortality during follow-up in patients with MPA and GPA, and furthermore its predictive potential is higher than those of conventional and AAV-related risk factors for all-cause mortality.

| S-EPMC6567497 | biostudies-literature

Long-Term Safety of Rituximab in Granulomatosis With Polyangiitis and in Microscopic Polyangiitis.

Project description:ObjectiveThe present study was undertaken to conduct a phase IV, open-label, prospective study to characterize the long-term safety of rituximab in a 4-year observational registry of adult patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) within the US.MethodsPatients initiating treatment with rituximab were evaluated every 6 months for up to 4 years. Outcomes included the incidence of serious adverse events (SAEs), infusion-related reactions (IRRs), and SAEs of specific interest, including serious infections, serious cardiac events, serious vascular events, and malignancies.ResultsOverall, 97 patients (72 with GPA and 25 with MPA) received rituximab through a median of 8 (range 1-28) infusions and were followed up for a median of 3.94 years (range 0.05-4.32 years). The estimated incidence rates (95% confidence interval [95% CI]) of serious infections, serious cardiac events, and serious vascular events were 7.11 (4.55-10.58), 5.03 (2.93-8.06), and 2.37 (1.02-4.67) per 100 patient-years (PYs), respectively. No IRRs or SAEs occurred within 24 hours of an infusion of rituximab. None of the 9 deaths reported (crude mortality rate 2.67 [95% CI 1.22-5.06] per 100 PYs) were considered to be related to use of rituximab.ConclusionThe safety profile of long-term treatment with rituximab in patients with GPA or MPA was consistent with that of rituximab administered for shorter durations and with rituximab's known safety profile in other autoimmune diseases for which it has received regulatory approval. These findings provide clinicians with long-term, practice-level safety data for rituximab in the treatment of GPA or MPA.

| S-EPMC8457173 | biostudies-literature

Place in therapy of rituximab in the treatment of granulomatosis with polyangiitis and microscopic polyangiitis.

Project description:Granulomatosis with polyangiitis and microscopic polyangiitis are small vessel vasculitides characterized by circulating antineutrophil circulating antibodies. Standard treatment for active severe disease has consisted of cyclophosphamide with glucocorticoids with or without plasmapheresis, which achieves approximately 75% sustained remission, but carries significant adverse effects such as malignancy, infertility, leukopenia, and infections. The role of B cells in the pathogenesis of anti-neutrophil circulating antibodies-associated vasculitis has been established, and as such, rituximab, a monoclonal anti-CD20 antibody, has been studied in treatment of active granulomatosis with polyangiitis and microscopic polyangiitis (induction) and in maintaining remission. Rituximab has been shown to be effective in inducing remission in several retrospective studies in patients with refractory disease or cyclophosphamide intolerance. The RAVE and RITUXVAS trials demonstrated rituximab is a noninferior alternative to standard cyclophosphamide-based therapy; however, its role in elderly patients and patients with severe renal disease warrants further investigation. Rituximab has been compared with azathioprine for maintaining remission in the MAINRITSAN trial and may be more efficacious in maintaining remission in patients treated with cyclophosphamide induction. Rituximab is not without risks and carries a similar adverse event risk rate as cyclophosphamide in randomized control trials. However, its use can be considered over cyclophosphamide in patients who have relapsing or refractory disease or in young patients seeking to preserve fertility.

| S-EPMC4918256 | biostudies-literature

Serum adipokine profiles in patients with microscopic polyangiitis and granulomatosis with polyangiitis: An exploratory analysis.

Project description:ObjectivesPrevious studies have shown that adipokines may serve as potential biomarkers reflecting disease activity in various autoimmune diseases. Here, we investigated the relationship between four adipokines and clinical/laboratory findings in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).MethodsSera from 63 patients with MPA and GPA who were registered in a prospective cohort were used to detect serum levels of adiponectin, chemerin, resistin, and vaspin using commercial enzyme-linked immunosorbent assay kits. Associations between adipokines and clinical and laboratory data was assessed using Pearson's correlation analysis.ResultsThe median age was 65.0 years, 24 patients were male, and 42 patients were diagnosed with MPA. The median levels of adiponectin, chemerin, resistin, and vaspin in patient sera were 13.9 ng/mL, 9.2 ng/mL, 23.7 ng/mL, and 0.1 ng/mL, respectively. A significant correlation between chemerin level and five-factor score (FFS) was found (r = 0.320, p = 0.011), and resistin was correlated with both Birmingham vasculitis activity score and FFS (r = 0.256, p = 0.043 and r = 0.320, p = 0.011). Regarding laboratory data, adiponectin level was associated with creatinine, and chemerin level was associated with creatinine, albumin, and erythrocyte sedimentation rate (ESR). On the other hand, resistin was found to be associated with white blood cell count, creatinine, ESR, and C-reactive protein. Age did not have a significant impact on the levels of adipokines.ConclusionsThe expression of adipokines in the sera of patients with MPA and GPA differs depending on clinical and laboratory features, and serum resistin may be suggested as a potential biomarker reflecting disease activity.

| S-EPMC8270208 | biostudies-literature

Current therapy of granulomatosis with polyangiitis and microscopic polyangiitis: the role of rituximab.

Project description:Granulomatosis with polyangiitis and microscopic polyangiitis are anti-neutrophil cytoplasmic antibody-associated vasculitides (AAVs) that are prone to cycles of remission and relapse. The introduction of cytotoxic therapy has changed the prognosis for these diseases from typically fatal to manageable chronic illnesses with a relapsing course. Despite improvements in outcomes, recurrence of disease and drug-related toxicity continue to produce significant morbidity and mortality. Better understanding of the pathogenesis of AAV and the mechanism of action of cyclophosphamide has led to investigation of therapies that target B cells. Two randomized controlled trials have shown that rituximab is not inferior to cyclophosphamide for induction of remission in severe AAV, with no significant difference in the incidence of overall adverse events in rituximab- versus cyclophosphamide-treated patients. Data from ongoing clinical trials will determine the role of rituximab in the maintenance of remission.

| S-EPMC4322237 | biostudies-other

Fc receptor-like 5 and anti-CD20 treatment response in granulomatosis with polyangiitis and microscopic polyangiitis.

Project description:BACKGROUNDBaseline expression of FCRL5, a marker of naive and memory B cells, was shown to predict response to rituximab (RTX) in rheumatoid arthritis. This study investigated baseline expression of FCRL5 as a potential biomarker of clinical response to RTX in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).METHODSA previously validated quantitative PCR-based (qPCR-based) platform was used to assess FCRL5 expression in patients with GPA/MPA (RAVE trial, NCT00104299).RESULTSBaseline FCRL5 expression was significantly higher in patients achieving complete remission (CR) at 6, 12, and 18 months, independent of other clinical and serological variables, among those randomized to RTX but not cyclophosphamide-azathioprine (CYC/AZA). Patients with baseline FCRL5 expression ? 0.01 expression units (termed FCRL5hi) exhibited significantly higher CR rates at 6, 12, and 18 months as compared with FCRL5lo subjects (84% versus 57% [P = 0.016], 68% versus 40% [P = 0.02], and 68% versus 29% [P = 0.0009], respectively).CONCLUSIONOur data taken together suggest that FCRL5 is a biomarker of B cell lineage associated with increased achievement and maintenance of complete remission among patients treated with RTX and warrant further investigation in a prospective manner.FUNDINGThe analysis for this study was funded by Genentech Inc.

| S-EPMC7526555 | biostudies-literature

The Efficacy of Mycophenolate Mofetil in Remission Maintenance Therapy for Microscopic Polyangiitis and Granulomatosis with Polyangiitis.

Project description:PurposeThe present study compared the efficacy of mycophenolate mofetil (MMF) with that of azathioprine (AZA) in Korean patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).Materials and methodsThe medical records of 69 patients with MPA and GPA who received cyclophosphamide and subsequently received AZA or MMF for remission maintenance therapy were reviewed. All-cause mortality, relapse, end-stage renal disease (ESRD), cerebrovascular accident, and cardiovascular disease were evaluated as poor outcomes. Having a lower Birmingham Vasculitis Activity Score (BVAS) was defined as the lowest tertile of BVAS (BVAS ≤11 in this study).ResultsIn comparative analysis of the occurrence of poor outcomes among patients taking AZA only, MMF only, and MMF after AZA, patients taking MMF only exhibited a significantly lower cumulative ESRD-free survival rate than patients taking AZA only (p=0.028). In terms of ESRD occurrence between the groups based on BVAS at diagnosis, among patients with MPA and GPA with higher BVAS at diagnosis, patients taking MMF only exhibited a significantly lower cumulative ESRD-free survival rate than those taking AZA only (p=0.047). Among patients with MPA and GPA with the lowest tertile of BVAS at diagnosis, cumulative ESRD-free survival rates did not differ.ConclusionWith regard to ESRD occurrence, the efficacy of MMF in remission maintenance therapy was less effective than AZA in patients with MPA and GPA. However, among patients with lower BVAS, there was no difference in the occurrence of poor outcomes between patients taking MMF and those taking AZA.

| S-EPMC8149928 | biostudies-literature

Project description:PURPOSE:There has been no extensive study to compare the efficacy between rituximab originator (Mabthera®) and its biosimilar (Truxima®) for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Here, we investigated the clinical effects of rituximab on poor outcomes of MPA and GPA in Korean patients, and compared those between Mabthera® and Truxima®. MATERIALS AND METHODS:We retrospectively reviewed the medical records of a total of 139 patients, including 97 MPA patients and 42 GPA patients. At diagnosis, antineutrophil cytoplasmic antibody positivity and comorbidities were assessed. During follow-up, all-cause mortality, relapse, end-stage renal disease, cerebrovascular accident and acute coronary syndrome were evaluated as poor outcomes. In this study, rituximab was used as either Mabthera® or Truxima®. RESULTS:The median age at diagnosis was 60.1 years and 46 patients were men (97 MPA and 42 GPA patients). Among poor outcomes, patients receiving rituximab exhibited a significantly lower cumulative relapse-free survival rate compared to those not receiving rituximab (p=0.002). Nevertheless, rituximab use did not make any difference in other poor outcomes of MPA and GPA except for relapse, which might be a rebuttal to the fact that rituximab use after relapse eventually led to better prognosis. There were no significant differences in variables at diagnosis and during follow-up between patients receiving Mabthera® and those receiving Truxima®. Patients receiving Truxima® exhibited a similar pattern of the cumulative survival rates of each poor outcome to those receiving Mabthera®. CONCLUSION:Truxima® prevents poor outcomes of MPA and GPA as effectively as does Mabthera®.

| S-EPMC7393299 | biostudies-literature

Costs of Disease Relapses Among Individuals with Granulomatosis, with Polyangiitis, or Microscopic Polyangiitis in the United States.

Project description:IntroductionGranulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are two related forms of systemic vasculitis. Patients with these conditions often experience relapses affecting various body systems. Here we describe rates of relapse and review healthcare costs resulting from relapse among patients with GPA/MPA.MethodsTwo groups of patients with GPA and MPA were selected from the MarketScan claims databases between 2011 and 2013 based on diagnosis codes. Patients were followed for 12 months to identify relapses based on an algorithm of diagnoses in medical and medication claims. Relapses were categorized into one of the following groups: renal relapse, pulmonary relapse, other relapse-associated condition relapse, GPA or MPA utilization relapse, and mixed relapse.ResultsThe final sample of patients with GPA and MPA consisted of 2707 and 740 patients, respectively. In both groups, approximately one-quarter of patients experienced relapse during the 12-month follow-up period. The mean all-cause healthcare costs in the 4-month period after relapse were $38,313 (SD, $54,120) for patients with GPA and $35,947 (SD, $48,065) for patients with MPA. In both groups, renal relapses were the costliest. Costs during the 4 months immediately following relapses were substantially higher than what could be expected over a 4-month follow-up among patients who did not experience relapse based on 12-month all-cause costs (GPA, $32,005 [SD, $64,570]; MPA, $61,044 [SD, $125,093]).ConclusionsRelapses are common among patients with GPA and MPA, and treatment of relapses can be costly. More effective therapies are needed to prevent relapses.FundingGenentech, Inc.

| S-EPMC5935630 | biostudies-literature

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