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ObjectivesEvaluation of rituximab and glucocorticoids as therapy to induce remission after relapse in ANCA-associated vasculitis (AAV) in a prospective observational cohort of patients enrolled into the induction phase of the RITAZAREM trial.MethodsPatients relapsing with granulomatosis with polyangiitis or microscopic polyangiitis were prospectively enrolled and received remission-induction therapy with rituximab (4×375 mg/m2) and a higher or lower dose glucocorticoid regimen, depending on physician choice: reducing from either 1 mg/kg/day or 0.5 mg/kg/day to 10 mg/day by 4 months. Patients in this cohort achieving remission were subsequently randomised to receive one of two regimens to prevent relapse.Results188 patients were studied: 95/188 (51%) men, median age 59 years (range 19–89), prior disease duration 5.0 years (range 0.4–34.5). 149/188 (79%) had previously received cyclophosphamide and 67/188 (36%) rituximab. 119/188 (63%) of relapses had at least one major disease activity item, and 54/188 (29%) received the higher dose glucocorticoid regimen. 171/188 (90%) patients achieved remission by 4 months. Only six patients (3.2% of the study population) did not achieve disease control at month 4. Four patients died in the induction phase due to pneumonia (2), cerebrovascular accident (1), and active vasculitis (1). 41 severe adverse events occurred in 27 patients, including 13 severe infections.ConclusionsThis large prospective cohort of patients with relapsing AAV treated with rituximab in conjunction with glucocorticoids demonstrated a high level of efficacy for the reinduction of remission in patients with AAV who have relapsed, with a similar safety profile to previous studies.

Background The European League Against Rheumatism (EULAR) Recommendation for primary and small vessel vasculitis were published in 2009. Objectives To update the 2009 recommendations with the focus being ANCA-Associated Vasculitis (AAV) using systematic literature review, as well as expert opinion where appropriate. Methods A combined taskforce from European League Against Rheumatism (EULAR), the European Renal Association (ERA-EDTA) and European Vasculitis Society (EUVAS) conducted a modified Delphi exercise to identify key areas of guideline for update. The identified themes were then used to generate keywords for literature searches. For the purpose of update a date period of 1st January 2007 to 1st February 2015 was chosen, to interrogate the main medical literature databases (MEDLINE, EMBASE, CENTRAL). From an initial 1,347 hits, 82 clinically relevant studies were identified. The evidence presented was discussed and summarized by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Results The 15 recommendations cover general aspects, such as attainment of remission and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting immunosuppressive therapy using a strategy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance. For remission induction of life or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy. Azathioprine, rituximab and methotrexate are the preferred choices for remission maintenance. The recommendations address plasma exchange which is recommended, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. To enable the recommendations to have maximum validity the voting process was also repeated amongst the members of EUVAS. Conclusions The recommendations have been updated and changes include; choice of drug therapy (both for induction, relapse and remission maintenance), monitoring for complications, the usefulness of repeated biopsy in those thought to having relapsing disease, monitoring for hypoimmunoglobulinaemia and recommendations on patient education. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations. Disclosure of Interest None declared

Background Mepolizumab reduces blood eosinophils with concomitant clinical improvement in some hypereosinophilic syndromes and eosinophilic asthma. Objectives To investigate the efficacy and safety of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss). Methods We conducted a Phase III, randomised, placebo-controlled, double-blind, parallel group, multi-centre study (NCT02020889) in patients with EGPA and a history of relapsing or refractory disease on stable therapy with prednisolone/prednisone ≥7.5–≤50mg/day with or without additional immunosuppressive therapy for ≥4 weeks. Patients were randomised 1:1 to receive mepolizumab 300mg or placebo subcutaneously, in addition to standard of care, every 4 weeks for 52 weeks. After Week 4, glucocorticoid dose could be tapered, per physician judgment, according to a suggested standard of care protocol. Co-primary endpoints (intent-to-treat [ITT] analysis) were accrued duration of remission (Birmingham Vasculitis Activity Score [BVAS]=0, prednisolone/prednisone dose ≤4mg/day) over 52 weeks; and the proportion of patients in remission at both Weeks 36 and 48. Secondary endpoints included average glucocorticoid dose during Weeks 49–52 and time to first EGPA relapse. Safety was also assessed. Results The ITT population included 136 randomised patients (mepolizumab n=68, placebo n=68). Baseline characteristics were similar between groups. Duration of remission accrued over 52 weeks was significantly prolonged with mepolizumab vs placebo (odds ratio: 5.91 [95% confidence interval [CI]: 2.68,13.03]; p Conclusions Treatment with mepolizumab significantly increased the likelihood and duration of remission, while reducing glucocorticoid use, in patients with EGPA, with a safety profile consistent with previous studies in severe asthma and EGPA. This demonstrates consistent and meaningful clinical benefits of mepolizumab in patients with EGPA. Acknowledgements Funding: GSK [115921] in collaboration with NIAID [U01 AI097073] and the Division of Intramural Research, NIAID, NIH). Abstract submitted to ATS 2017. Disclosure of Interest M. Wechsler Consultant for: Teva, AstraZeneca, BSCI, GSK, Novartis, sanofi, Vectura, Sunovion, Regeneron, Ambit bioscience, Meda, Mylan, Gliacure, Tunitas, Genentech, Theravance, Neurotronic, Sentien, P. Akuthota Grant/research support from: National Institutes of Health, Consultant for: Ambrx, Employee of: University of California San Diego, D. Jayne Grant/research support from: GSK, Consultant for: GSK, P. Khoury: None declared, A. Klion: None declared, C. Langford Grant/research support from: GlaxoSmithKline, Bristol-Myers Squibb, Genentech, P. Merkel: None declared, F. Moosig Grant/research support from: Roche, Consultant for: Roche, Chuagi, Lilly, GSK, U. Specks: None declared, M. Cid Consultant for: GSK, Novartis, Roche, Boehringer-Inhelheim, R. Luqmani Grant/research support from: Roche, GSK, Consultant for: Roche, GSK, J. Brown Shareholder of: GSK, Employee of: GSK, S. Mallett Shareholder of: GSK, Employee of: GSK, R. Philipson Employee of: Trizell Ltd, S. Yancey Shareholder of: GSK, Employee of: GSK, J. Steinfeld Shareholder of: GSK, Employee of: GSK, P. Weller: None declared, G. Gleich Shareholder of: Mutual funds, Grant/research support from: NIH, Consultant for: Genentech, Employee of: VAH, U Utah

Podeu consultar la correcció d'errades a: http://dx.doi.org/10.1136/annrheumdis-2016-209133corr1, In this article, the 2009 European League Against Rheumatism (EULAR) recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated. The 2009 recommendations were on the management of primary small and medium vessel vasculitis. The 2015 update has been developed by an international task force representing EULAR, the European Renal Association and the European Vasculitis Society (EUVAS). The recommendations are based upon evidence from systematic literature reviews, as well as expert opinion where appropriate. The evidence presented was discussed and summarised by the experts in the course of a consensus-finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) determined. In addition to the voting by the task force members, the relevance of the recommendations was assessed by an online voting survey among members of EUVAS. Fifteen recommendations were developed, covering general aspects, such as attaining remission and the need for shared decision making between clinicians and patients. More specific items relate to starting immunosuppressive therapy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance; for remission induction in life-threatening or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy; plasma exchange which is recommended, where licensed, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations.

The Patient-Centered Outcomes Research Institute (PCORI) recently launched PCORnet to establish a single inter-operable multicenter data research network that will support observational research and randomized clinical trials. This paper provides an overview of the patient-powered research networks (PPRNs), networks of patient organizations focused on a particular health condition that are interested in sharing health information and engaging in research. PPRNs will build on their foundation of trust within the patient communities and draw on their expertise, working with participants to identify true patient-centered outcomes and direct a patient-centered research agenda. The PPRNs will overcome common challenges including enrolling a diverse and representative patient population; engaging patients in governance; designing the data infrastructure; sharing data securely while protecting privacy; prioritizing research questions; scaling small networks into a larger network; and identifying pathways to sustainability. PCORnet will be the first distributed research network to bring PCOR to national scale.

Objective To identify circulating proteins that distinguish between active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and remission in a manner complementary to markers of systemic inflammation.Methods Twenty-eight serum proteins representing diverse aspects of the biology of AAV were measured before and 6months after treatment in a large clinical trial of AAV. Subjects (n=186) enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were available for comparison. The primary outcome was the ability of markers to distinguish severe AAV (Birmingham Vasculitis Activity Score for Wegener's granulomatosis (BVAS/WG)3 at screening) from remission (BVAS/WG=0 at month 6), using areas under receiver operating characteristic (ROC) curve (AUC).Results All subjects had severe active vasculitis (median BVAS/WG=8) at screening. In the 137 subjects in remission at month 6, 24 of the 28 markers showed significant declines. ROC analysis indicated that levels of CXCL13 (BCA-1), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases-1 (TIMP-1) best discriminated active AAV from remission (AUC>0.8) and from healthy controls (AUC>0.9). Correlations among these markers and with ESR or CRP were low.Conclusions Many markers are elevated in severe active AAV and decline with treatment, but CXCL13, MMP-3 and TIMP-1 distinguish active AAV from remission better than the other markers studied, including ESR and CRP. These proteins are particularly promising candidates for future studies to address unmet needs in the assessment of patients with AAV.