Citations

Significance Statement Efficacy of rituximab (RTX) in ANCA-associated vasculitis (AAV) in patients with severe renal involvement (eGFR<30 ml/min per 1.73 m 2 ) has not been addressed in clinical trials. This observational study did not find statistically significant differences between RTX and cyclophosphamide (CYC) for remission-induction therapy or any apparent benefit from the addition of plasma exchange (PLEX) to standard remission-induction therapy for patients with AAV and severe renal involvement. Although our analyses suggest that the benefits and risks of these therapeutic choices (RTX versus CYC with and without PLEX) are balanced, a randomized, controlled trial is needed to confirm these findings. Background Treatment of patients with ANCA-associated vasculitis (AAV) and severe renal involvement is not established. We describe outcomes in response to rituximab (RTX) versus cyclophosphamide (CYC) and plasma exchange (PLEX). Methods A retrospective cohort study of MPO- or PR3-ANCA–positive patients with AAV (MPA and GPA) and severe kidney disease (eGFR <30 ml/min per 1.73 m 2 ). Remission, relapse, ESKD and death after remission-induction with CYC or RTX, with or without the use of PLEX, were compared. Results Of 467 patients with active renal involvement, 251 had severe kidney disease. Patients received CYC ( n =161) or RTX ( n =64) for remission-induction, and 51 were also treated with PLEX. Predictors for ESKD and/or death at 18 months were eGFR <15 ml/min per 1.73 m 2 at diagnosis (IRR 3.09 [95% CI 1.49 to 6.40], P =0.002), renal recovery (IRR 0.27 [95% CI 0.12 to 0.64], P =0.003) and renal remission at 6 months (IRR 0.40 [95% CI 0.18 to 0.90], P =0.027). RTX was comparable to CYC in remission-induction (BVAS/WG=0) at 6 months (IRR 1.37 [95% CI 0.91 to 2.08], P =0.132). Addition of PLEX showed no benefit on remission-induction at 6 months (IRR 0.73 [95% CI 0.44 to 1.22], P =0.230), the rate of ESKD and/or death at 18 months (IRR 1.05 [95% CI 0.51 to 2.18], P =0.891), progression to ESKD (IRR 1.06 [95% CI 0.50 to 2.25], P =0.887), and survival at 24 months (IRR 0.54 [95% CI 0.16 to 1.85], P =0.330). Conclusions The apparent benefits and risks of using CYC or RTX for the treatment of patients with AAV and severe kidney disease are balanced. The addition of PLEX to standard remission-induction therapy showed no benefit in our cohort. A randomized controlled trial is the only satisfactory means to evaluate efficacy of remission-induction treatments in AAV with severe renal involvement.

AbstractImmunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder that has been recognized to involve virtually any organ in the body and typically manifests mass-like lesions (tumefactive). Although initial reports of this disease (autoimmune pancreatitis [AIP]) were described in the Japanese population, it has since been reported worldwide. It is most commonly seen in adults of middle age or older, more often men than women. The pathogenesis of IgG4-RD is largely unknown, but genetic factors, microorganisms, and autoimmunity are thought to play important roles. Serum IgG4 concentration is elevated in the majority of patients with IgG4-RD but is a nonspecific finding. Characteristic histopathologic features include dense lymphoplasmacytic infiltrate, fibrosis (often in storiform pattern), and obliterative phlebitis. Lung involvement in IgG4-RD was first reported in 2004 in two patients with AIP and coexisting interstitial lung disease. Since then, a wide spectrum of intrathoracic involvement has been reported and includes not only parenchymal lung diseases but also pleural, airway, vascular, and mediastinal lesions. Thoracic involvement in IgG4-RD is often found incidentally during the workup of extrathoracic lesions but can sometimes be the presenting abnormality. The diagnosis of IgG4-RD requires correlation of clinical, laboratory, imaging, and histopathologic features. Glucocorticoids are the first-line therapy but other options including B cell depletion are being investigated. IgG4-RD is generally associated with an indolent clinical course and most patients improve with glucocorticoid therapy.

Abstract Background True population-based clinical and outcomes data are lacking for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis (AAGN). Therefore we aimed to estimate the incidence, prevalence and mortality of AAGN, as well as the relationship between the grade of chronic renal damage at presentation and renal and non-renal outcomes. Methods Patients with AAGN were identified among a population-based incident cohort of 57 Olmsted County residents diagnosed with ANCA-associated vasculitis (AAV) in 1996–2015. Incidence rates were age and sex adjusted to the 2010 US white population. Age- and sex-adjusted prevalence was calculated for 1 January 2015. Survival rates were compared with expected rates in the Minnesota population. Chronic renal damage was assessed by chronicity score (CS) on biopsies performed at diagnosis. Results Thirty-four (60%) patients had AAGN. Of these, 65% had microscopic polyangiitis (MPA) and 74% were myeloperoxidase (MPO)-ANCA positive. The annual incidence of AAGN was 2.0/100 000 population [95% confidence interval (CI) 1.3–2.7] and the overall prevalence was 35/100 000 (95% CI 24–47). Mortality for AAGN was increased (P &lt; 0.001), whereas mortality for AAV without glomerulonephritis did not differ from the general population. Minimal to mild CS predicted recovery of renal function at 1 year; clinical diagnosis (granulomatosis with polyangiitis versus MPA) and ANCA specificity (proteinase 3 versus MPO) did not. This observation was replicated in an independent cohort of 38 newly diagnosed AAGN patients seen at our centre over the 1999–2014 period. Conclusions The annual incidence and prevalence of AAGN in Minnesota are 2.0/100 000 and 35/100 000, respectively. Mortality is worse compared with AAV patients without glomerulonephritis. More advanced renal damage at diagnosis predicts less renal recovery.