Pavel Novikov

Position paper: Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis

Anti-neutrophil cytoplasmic antibodies (ANCAs) are valuable laboratory markers used for the diagnosis of well-defined types of small-vessel vasculitis, including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). According to the 1999 international consensus on ANCA testing, indirect immunofluorescence (IIF) should be used to screen for ANCAs, and samples containing ANCAs should then be tested by immunoassays for proteinase 3 (PR3)-ANCAs and myeloperoxidase (MPO)-ANCAs. The distinction between PR3-ANCAs and MPO-ANCAs has important clinical and pathogenic implications. As dependable immunoassays for PR3-ANCAs and MPO-ANCAs have become broadly available, there is increasing international agreement that high-quality immunoassays are the preferred screening method for the diagnosis of ANCA-associated vasculitis. The present Consensus Statement proposes that high-quality immunoassays can be used as the primary screening method for patients suspected of having the ANCA-associated vaculitides GPA and MPA without the categorical need for IIF, and presents and discusses evidence to support this recommendation.

Venous thromboembolic events in systemic vasculitis

In a population-base study published in the Annals of Rheumatic Disease , Avina-Zubieta et al 1 showed that there is almost 2.5-fold increase in risk of venous thromboembolism (VTE) in patients with giant cell arteritis (GCA) compared with that in the general population. Higher incidence of VTE is apparently not unique for GCA as a similar increase in risk of deep vein thrombosis (DVT) and pulmonary embolism was recently found in a meta-analysis of studies in patients with different inflammatory rheumatic diseases.2 We detected only two cases of venous thrombosis (orbital and retinal veins) in our series of 76 patients with GCA, though at least two-thirds of them have been followed for 2 years. At the same time, there were 30 cases of …

End-stage renal disease in ANCA-associated vasculitis

Abstract 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.

Rituximab as induction therapy in relapsing eosinophilic granulomatosis with polyangiitis: A report of 6 cases.

OBJECTIVE Recently few reports have suggested a potential benefit of rituximab in patients with eosinophilic granulomatosis with polyangiitis (EGPA). However, the current evidence is limited. We describe the efficacy and safety of rituximab in six patients with relapsing EGPA. METHODS Candidates for rituximab therapy were selected from a cohort of 118 patients with EGPA. The main indication for B-cells depletion was moderately severe or severe relapsing disease that was refractory to conventional immunosuppression. A primary end-point was a complete or partial remission within 3 to 6 months after rituximab administration. RESULTS All six patients (four ANCA-positive and two ANCA-negative) had active EGPA manifesting by severe lung disease and/or deteriorating peripheral neuropathy. The median duration of follow-up after the first rituximab dose administration was 10 months. All patients rapidly responded to rituximab treatment, e.g. disappearance of lung infiltrates, improvement of asthmatic symptoms, at least partial recovery of motor and sensory function. Within 3 to 6 months, complete (4/6) or partial (2/6) remission was achieved in all patients. After switching to rituximab all patients except one discontinued cyclophosphamide or other immunomodulators. Four patients continued maintenance treatment with rituximab. One patient developed severe bronchospasm during infusion and two patients presented with moderately severe purulent bronchitis that was successfully treated with intravenous antibiotics. CONCLUSION Our retrospective case series suggest that rituximab may be effective for induction of remission in selected EGPA patients. These data warrant further studies to evaluate safety and efficacy of rituximab in EGPA.

Bortezomib in refractory ANCA-associated vasculitis: a new option?

Bortezomib is a proteasome inhibitor approved for the treatment of multiple myeloma. Proteasome inhibition depletes short-lived and long-lived plasma cells and is a promising therapeutic approach to treat refractory antibody-mediated autoimmune diseases. In a small uncontrolled study from Charite (Berlin), recently published in the Annals of the Rheumatic Diseases , 12 patients with systemic lupus erythematosis (SLE) with persistent disease activity and autoantibody production despite immunosuppression were treated with bortezomib according to the approved protocol for multiple myeloma.1 Disease activity declined significantly, though adverse events occurred in 11 of 12 patients and resulted in discontinuation of bortezomib in seven of them. Resistance to immunosuppressive treatment, including cyclophosphamide (CYC) and …

HCV-associated cryoglobulinaemic vasculitis: triple/dual antiviral treatment and/or rituximab?

Mixed cryoglobulinaemia (MC) vasculitis is a relatively uncommon systemic vasculitis that may be primary or associated with hepatitis C virus (HCV). We have found MC and cryoglobulinaemic vasculitis in 420 (31%) and 65 (5%) of 1351 patients with HCV infection, respectively. Two recent randomised controlled trials have established the superiority of rituximab over conventional immunosuppressive treatment in patients with MC vasculitis1 ,2 while Saadoun et al 3 have previously shown that dual antiviral treatment with interferon α and ribavirin had induced remission of HCV-associated MC vasculitis in 63% of 72 consecutive patients and sustained virological response in 58% of cases. In a study recently published in the Annals of the Rheumatic Diseases ,4 the same authors suggested that triple antiviral treatment with peginterferon-α–ribavirin–protease inhibitor was highly …

Brief Report : Rituximab for the Treatment of Adult-Onset IgA Vasculitis (Henoch-Schönlein)

Adult‐onset IgA vasculitis (Henoch‐Schönlein) (IgAV) is a rare systemic vasculitis characterized by IgA1‐dominant deposits. The treatment of adult‐onset IgAV is controversial and is based on the combination of glucocorticoids and immunosuppressive agents, but many patients have refractory or relapsing disease despite treatment. Rituximab (RTX) is a B cell–depleting antibody of proven efficacy in antineutrophil cytoplasmic antibody–associated vasculitis. We undertook this study to test the efficacy and safety of RTX in a multicenter cohort of patients with adult‐onset IgAV.

Biological agents for giant cell arteritis: treat to target

In a case series published in the Annals of the Rheumatic Diseases , Conway et al 1 reported a significant steroid-sparing effect of ustekinumab (monoclonal antibody to interleukin (IL)-12 and IL-23) in 14 patients with giant cell arteritis (GCA). Recently, Ferfar et al 2 summarised current evidence showing the efficacy of tocilizumab and abatacept in patients with GCA. In the ongoing multicentre, randomised GiACTA trial (NCT01791153), the efficacy and safety of tocilizumab will be evaluated in approximately 250 patients with active GCA. Another randomised, placebo-controlled trial (NCT02531633) aims to study sirukumab (a fully human anti-IL-6 immunoglobulin G1κ) in approximately 204 subjects with a diagnosis of GCA. Therefore, in the nearest future we will probably face a wider use of biological agents as a second-line treatment for relapsing GCA and maybe as a first line in patients with more unfavourable prognosis. Should we welcome biologics in the current framework of treatment? On the one hand, the steroid-sparing effect of these medications is particularly valuable for the elderly patients with GCA who usually develop adverse events related to glucocorticoids and frequently relapse during tapering the dose of prednisone. Furthermore, it is expected that certain biological agents may have antiatherosclerotic effect that is currently under investigation in the randomised controlled trials (eg, the Canakinumab Antiinflammatory Thrombosis Outcomes Study (NCT01327846) that will evaluate canakinumab in 17 200 patients with coronary artery disease and persistently elevated C reactive protein). On the other hand, glucocorticoids are cheap and effective in a significant proportion of patients while the safety of …

Five Factor Score in patients with eosinophilic granulomatosis with polyangiitis (Churg–Strauss; EGPA): to use or not to use?

In the excellent study recently published in the Annals of the Rheumatic Diseases , F Moosig et al 1 evaluated the individualised and more aggressive strategy of immunosuppressive treatment in 150 patients with EGPA. Over the last decade, we used the same approach in our cohort of 117 patients with EGPA. For induction of remission the authors used cyclophosphamide in patients with Five Factor Score (FFS) of 0 and with other organ-threatening or life-threatening manifestations, for example, active peripheral nervous system involvement, alveolar haemorrhage or severe eosinophilic alveolitis. FFS was developed in 1996 as a predictor of poor prognosis in patients with systemic vasculitides.2 It was revised in 2009.3 FFS was used in several trials performed by French Vasculitis Study Group as a guide to choosing …

Positron emission tomography in giant cell arteritis: a new diagnostic tool?

In a prospective case–control study recently published in the Annals of Rheumatic Diseases , Prieto-Gonzalez et al 1 have shown a high sensitivity and specificity of positron emission tomography (PET)/CT with 18fluorodeoxyglucose (FDG) in 32 patients with newly diagnosed, biopsy-proven giant cell arteritis (GCA). Using receiver–operator characteristic curves (ROC) analysis, the authors determined cut-off maximal standardised uptake values (SUVm) to detect vascular inflammation by PET/CT. The sensitivity and specificity of PET/CT obtained in this study was close to that calculated in a recent meta-analysis of mostly retrospective studies.2 We used PET with FDG for diagnosis and assessment of …