David R W Jayne

Copenhagen University Hospital, København, Capital Region, Denmark

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Publications (103)784.38 Total impact

  • Miklos Perenyei, David R W Jayne, Oliver Floßmann
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    ABSTRACT: Gusperimus is an immunosuppressive drug with a unique mode of action. We review its effects on different arms of the immune system and the current evidence for clinical applications, particularly in the treatment of transplant rejection and ANCA-associated vasculitis.
    Rheumatology (Oxford, England) 02/2014; · 4.24 Impact Factor
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    ABSTRACT: Objectives. ANCA-associated vasculitis (AAV) commonly affects those of working age. Since survival rates have been transformed by immunotherapeutics, the measurement of other outcomes has become increasingly relevant. Work disability is an important outcome for both patient and society that has yet to be fully evaluated in AAV. We aimed to assess employment status in AAV patients and identify putative predictors of their work disability.Methods. A cross-sectional study was undertaken. AAV cases were recruited according to consecutive clinic attendance. Subjects completed a questionnaire that determined employment status and other psychosocial measures. Clinical factors were concurrently recorded by the attending physician. From the data of those subjects of working age, a multivariable model was developed using forward stepwise logistic regression to identify the independent associations of work disability, defined by those subjects reporting unemployment secondary to ill-health. Results are expressed as odds ratios (ORs) and 95% CIs.Results. Of the 410 participants (84.4% response rate), 149 (36.7%) were employed, 197 (48.6%) retired and 54 (13.3%) unemployed secondary to ill health. Of those of working age, 26.0% were considered work disabled. Fatigue (OR 7.1, 95% CI 1.5, 33.1), depression (OR 4.4, 95% CI 1.8, 10.8), severe disease damage [Vasculitis Damage Index (VDI) > 4 (OR 3.9, 95% CI 1.01, 14.7)] and being overweight (OR 3.4, 95% CI 1.3, 8.9) were independently associated with their unemployment.Conclusion. A quarter of working-age AAV subjects reported unemployment as a result of ill health and are characterized by high levels of fatigue, depression, disease damage and being overweight. These potentially modifiable factors may inform future multidisciplinary interventions aimed at alleviating work disability.
    Rheumatology (Oxford, England) 01/2014; · 4.24 Impact Factor
  • Mikkel Faurschou, David R W Jayne
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    ABSTRACT: Several monoclonal antibodies targeting B cells have been tested as therapeutics for inflammatory rheumatic diseases. We review important observations from randomized clinical trials regarding the efficacy and safety of anti-B cell antibody-based therapies for rheumatoid arthritis, systemic lupus erythematosus, antineutrophil cytoplasmic antibody-associated vasculitis, polymyositis/dermatomyositis, and primary Sjögren's syndrome. For some anti-B cell agents, clinical benefits have been convincingly demonstrated, while other B cell targeted therapies failed to improve outcomes when added to standard-of-care treatment or were associated with increased rates of adverse events. Although the risk-benefit balance seems to be acceptable for currently licensed anti-B cell agents, additional studies are required to fully assess the safety of treatment regimens involving prolonged interference with B cell counts and functions in rheumatic disorders. Future studies should also evaluate how to maintain disease control by means of conventional and/or biologic immunosuppressants after remission-induction with anti-B cell antibodies. Expected final online publication date for the Annual Review of Medicine Volume 65 is January 14, 2014. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
    Annual review of medicine 10/2013; · 9.94 Impact Factor
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    ABSTRACT: Plasma exchange is used in the treatment of diseases mediated by pathogenic circulating proteins, or for transplant desensitisation. Its non-targeted nature results in the depletion of physiologically important molecules, and it is often complicated by hypocalcaemia. To determine the effects of plasma exchange onvitamin D binding proteinand associated vitamin D metabolites. Single-centre prospective cohort study of 11 patients. METHODS:DBP and vitamin D metabolites were measured before and immediately after 5 plasma exchanges, and 7 and 28 days after discontinuation of plasma exchange. RESULTS:Plasma exchange reduced plasma vitamin D binding proteinconcentrationfrom 196.9 ± 53.2 to 98.5 ± 34 μg/mL (p = 0.0001), 1,25-dihydroxyvitamin D from 103 ± 52 pmol/l to 42 ± 4pmol/l (p = 0.003), and 25-hydroxyvitamin D from 49.7 ± 29 to 22 ± 9.4 nmol/l (p = 0.0017), through their removal in effluent. After 7 days, DBP and 1,25-dihydroxyvitamin D were not significantly different from baseline, but 25-hydroxyvitamin D remained significantly lower after 7 days(26.4 ± 9.8 nmol/l, p = 0.02) and 28 days (30.8 ± 15.5 nmol/l, p = 0.048). Corrected calcium decreased from 2.23 ± 0.11 mmol/l to 1.98 ± 0.08 mmol/l(p=0.0007) immediately after 5 treatments.Plasma calcium was significantly associated with 1,25-dihydroxyvitamin D (r(2) = 0.79, p < 0.0001). Plasma exchange inducedan acute reversible decrease in plasma 1,25-dihydroxyvitamin D, DBP, calcium, and a sustained decrease in plasma 25-hydroxyvitamin D.
    QJM: monthly journal of the Association of Physicians 10/2013; · 2.36 Impact Factor
  • Federico Alberici, David R W Jayne
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    ABSTRACT: ANCA-associated vasculitis (AAV) is a subgrouping of autoimmune disorders characterized by a chronic relapsing course. Induction therapy is usually effective, but 70% of patients will relapse and 20% develop refractory disease. In the relapsing and refractory subgroups, treatment is complicated by the cumulative exposure to toxic drugs that contribute to poor long-term outcomes. The anti-CD20 monoclonal antibody rituximab (RTX) depletes B cells, and the success of this targeted therapy has contributed to the evidence supporting a central role for B cells in AAV pathogenesis. Initial proof of RTX effectiveness originated from small, prospective trials and retrospective surveys conducted in AAV patients with relapsing and refractory disease; high remission rates permitted the reduction of glucocorticoids (GCS) doses and withdrawal of immunosuppressives. There has been controversy over the effectiveness of RTX in patients with predominantly granulomatous manifestations, where response rates have varied between studies, in part due to different RTX dosing regimens. These studies were followed by comparison of RTX against cyclophosphamide (CYC) for remission induction of new or relapsing AAV in two randomized trials, which led to the licensing of RTX for this indication. Subsequent attention has been turned to the use of RTX as a relapse prevention agent, to the potential for GCS sparing and to RTX-associated toxicity. We will discuss the impact that the results of RTX clinical trials have had on the management of AAV patients.
    Nephrology Dialysis Transplantation 10/2013; · 3.37 Impact Factor
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    ABSTRACT: Objectives. To identify the determinants of fatigue among patients with ANCA-associated vasculitis (AAV).Methods. A multicentre cross-sectional study was conducted. Subjects fulfilling the European Medicines Agency criteria for granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis (Churg-Strauss) were approached according to consecutive clinic attendance and invited to complete a questionnaire assessing fatigue and putative biopsychosocial determinants of this symptom. Concurrently, potential clinical determinants were recorded. Independent associations of fatigue were identified using forward stepwise logistic regression modelling and their overall impact expressed as population attributable risk (PAR).Results. The majority (74.8%) of participants (n = 410) reported high levels of fatigue that were found to be significantly associated with numerous biopsychosocial and clinical factors. Sleep disturbance [odds ratio (OR) 5.3, 95% CI 2.7, 10.5] and pain (OR 3.8, 95% CI 2.0, 7.3) were the strongest independent associations of fatigue and, on a population level, each was more than twice as important as any other putative determinant (PAR 18.1% and 16.5%, respectively). Female gender (OR 2.1, 95% 1.1, 4.0), elevated CRP (OR 3.7, 95% CI 1.7, 8.1) and the dysfunctional coping strategies of behavioural disengagement (OR 2.4, 95% CI 1.04, 5.6) and denial (OR 2.4, 95% CI 0.9, 6.7) were also independently associated with fatigue.Conclusion. The data suggest that AAV-related fatigue is multifactorial in origin. Sleep disturbance and pain were found to be most important, although inflammation, as measured by CRP, was also associated. This study has identified potentially modifiable determinants that will inform future interventions aimed at alleviating fatigue.
    Rheumatology (Oxford, England) 06/2013; · 4.24 Impact Factor
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    ABSTRACT: Patients with antineutrophil cytoplasm antibody-associated vasculitis (AAV) requiring dialysis at diagnosis are at risk for developing end-stage renal disease (ESRD) or dying. Short-term results of a trial comparing plasma exchange (PLEX) to intravenous methylprednisolone (IV MeP) suggested PLEX improved renal recovery. Here we conducted long-term follow-up to see if this trend persisted. A total of 137 patients with newly diagnosed AAV and a serum creatinine over 500 μmol/l or requiring dialysis were randomized such that 69 received PLEX and 68 received IV MeP in addition to cyclophosphamide and oral glucocorticoids. The patients were followed for a median of 3.95 years. In each group there were 35 deaths, while 23 PLEX and 33 IV MeP patients developed ESRD. The hazard ratio for PLEX compared to IV MeP for the primary composite outcome of death or ESRD was 0.81 (95% confidence interval 0.53-1.23). The hazard ratio for all-cause death was 1.08 with a subhazard ratio for ESRD of 0.64 (95% confidence interval 0.40-1.05). Thus, although short-term results with PLEX are encouraging, the long-term benefits remain unclear. Further research is required to determine the role of PLEX in AAV. Given the poor outcomes of patients with severe AAV, improved treatment is urgently needed.Kidney International advance online publication, 24 April 2013; doi:10.1038/ki.2013.131.
    Kidney International 04/2013; · 7.92 Impact Factor
  • Shunsuke Furuta, David R W Jayne
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    ABSTRACT: Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a group of vasculitides characterized by small-to-medium-sized blood vessel vasculitis and the presence of ANCA. Although our understanding of the causes of AAV remains limited, new information supporting an autoimmune basis is emerging. This review highlights recent progresses in etiology, pathogenesis, classification, and treatment. A genome-wide association study has confirmed a role for genetic susceptibility in AAV, and links between environmental factors and AAV induction through abnormal neutrophil extracellular traps has been demonstrated. Ongoing international consensus initiatives have revised approaches to the classification of vasculitis that has been enhanced by the analysis of large-scale prospective clinical data sets. New autoantibodies to human lysosome-associated membrane protein-2 antibody, moesin, and plasminogen have been detected in AAV sera and a prognostic classification of renal biopsies developed. Clinical trial networks have extended the evidence base for the treatment of AAV, and rituximab has emerged as an alternative to cyclophosphamide for remission induction. Long-term outcomes following current treatment strategies have been determined and increased risks for cardiovascular and malignant disease reported.Kidney International advance online publication, 20 February 2013; doi:10.1038/ki.2013.24.
    Kidney International 02/2013; · 7.92 Impact Factor
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    ABSTRACT: OBJECTIVES: To investigate the nature of the relationship between proteinase 3 anti-neutrophil cytoplasm autoantibody (PR3-ANCA) and relapse in patients with early systemic granulomatosis with polyangiitis (Wegener's) (GPA).METHODS: Clinical data from 16 relapsing and 12 non-relapsing patients with early systemic GPA from a randomised clinical trial were correlated to monthly PR3-ANCA values over 18 months. Each sample was examined using 9 different enzyme-linked immunosorbent assays (ELISAs) to ensure reliability of ANCA results. PR3-ANCA peaks were identified by the highest sum of logarithmic transformation values from all assays in samples after remission. RESULTS: A PR3-ANCA peak was identified in all relapsing and non-relapsing patients and coincided with relapse in all 14 evaluable relapsing patients. The monthly increment before the peak, however, was similar in relapsing and non-relapsing patients in all assays. Increments from remission to peak were higher in relapsing patients in 2/9 assays. PR3-ANCA values at entry and peak PR3-ANCA values were higher in relapsing patients in 3/9 and 2/9 assays, respectively. However, large overlaps of PR3-ANCA values prevented a distinction between relapsing and non-relapsing patients. The median time to reach peak values was 14 months in relapsing and 12 months in non-relapsing patients with scheduled termination of treatment at 12 months. CONCLUSIONS: The predictive value for relapses of PR3-ANCA determinations confirm and extend previous reports. Although all relapses were related to PR3-ANCA increases, reduction or withdrawal of immunosuppression without relapse was also related to increases and may explain the lack of predictive value of sequential PR3-ANCA determinations.
    Clinical and experimental rheumatology 02/2013; · 2.66 Impact Factor
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    ABSTRACT: BACKGROUND: Mycophenolate mofetil (MMF) frequently is used as an alternative to intravenous cyclophosphamide to treat lupus nephritis. Whether MMF is adequate for patients with severely decreased kidney function at the time of treatment is uncertain. STUDY DESIGN: We conducted a post hoc subgroup analysis of patients with low estimated glomerular filtration rates (eGFRs) from a large trial of MMF compared to cyclophosphamide in lupus nephritis. SETTINGS & PARTICIPANTS: We included all patients with an eGFR <30 mL/min/1.73 m(2) from the Aspreva Lupus Management Study (ALMS). INTERVENTION: MMF (target, 3 g/d) compared to monthly intravenous cyclophosphamide (0.5-1 g/m(2)). OUTCOMES: We compared the proportion of patients that responded to therapy and change in eGFR over 24 weeks. MEASUREMENTS: Response was evaluated by a decrease in proteinuria and stabilization or improvement of serum creatinine level. RESULTS: Of 370 patients in ALMS, 32 were included in the subgroup analysis: 20 randomly assigned to MMF and 12 randomly assigned to cyclophosphamide treatment. The patients included were similar at baseline between groups. Four (20.0%) patients treated with MMF responded compared with 2 (16.7%) patients treated with cyclophosphamide (risk ratio, 1.2; 95% CI, 0.3-5.1; P = 0.9). eGFR in the MMF group improved more quickly than in the cyclophosphamide group, by 1.51 (95% CI, 0.99-2.02) mL/min/1.73 m(2) each week (P < 0.001). Serious adverse events occurred in 9 (45.0%) MMF-treated patients and 7 (63.6%) cyclophosphamide-treated patients (P = 0.5). LIMITATIONS: Small sample size and post hoc subgroup of a larger trial. CONCLUSIONS: We did not detect a difference in the primary outcome of response in patients with low eGFR treated with MMF or cyclophosphamide. However, MMF may result in quicker recovery of kidney function compared with those treated with cyclophosphamide. Larger studies including more patients with poor kidney function are warranted.
    American Journal of Kidney Diseases 01/2013; · 5.29 Impact Factor
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    ABSTRACT: BACKGROUND: Granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis (MPA) are subgroups of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) defined historically by clinical and histological features. GPA and MPA are heterogeneous entities with overlapping phenotypes. To identify novel subgroupings, cluster analysis was used to explore the phenotypic spectrum of AAV. METHODS: This study used a dataset of patients newly diagnosed as having GPA and MPA enrolled in five clinical trials. One cluster model included nine clinical baseline variables as input variables, and a second cluster model additionally included ANCA specificities. The clustering process involved multiple correspondence analyses followed by hierarchical ascendant cluster analysis. The clinical relevance of the generated clusters was analysed by their summary characteristics and outcomes. RESULTS: The analyses involved data for 673 subjects: 396 (59%) with GPA and 277 (41%) with MPA. Both cluster models resulted in five partially redundant clusters of subjects, and the model including ANCA resulted in more pertinent separations. These clusters were named 'renal AAV with proteinase 3 (PR3)-ANCA' (40% of subjects), 'renal AAV without PR3-ANCA' (32%) and 'non-renal AAV' (12%), 'cardiovascular AAV' (9%) and 'gastrointestinal AAV' (7%). The five clusters had distinct death and relapse rates. On the basis of 4 variables, 651 subjects (97%) could be accurately allocated to 1 of the 5 classes. CONCLUSIONS: This analysis suggests that AAV encompasses five classes associated with different outcomes. As compared with the traditional GPA-MPA separation, this classification system may better reflect the phenotypic spectrum of AAV.
    Annals of the rheumatic diseases 09/2012; · 8.11 Impact Factor
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    ABSTRACT: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis. A genomewide association study was performed in a discovery cohort of 1233 U.K. patients with ANCA-associated vasculitis and 5884 controls and was replicated in 1454 Northern European case patients and 1666 controls. Quality control, population stratification, and statistical analyses were performed according to standard criteria. We found both major-histocompatibility-complex (MHC) and non-MHC associations with ANCA-associated vasculitis and also that granulomatosis with polyangiitis and microscopic polyangiitis were genetically distinct. The strongest genetic associations were with the antigenic specificity of ANCA, not with the clinical syndrome. Anti-proteinase 3 ANCA was associated with HLA-DP and the genes encoding α(1)-antitrypsin (SERPINA1) and proteinase 3 (PRTN3) (P=6.2×10(-89), P=5.6×10(-12,) and P=2.6×10(-7), respectively). Anti-myeloperoxidase ANCA was associated with HLA-DQ (P=2.1×10(-8)). This study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyangiitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature of proteinase 3 ANCA-associated vasculitis. These data provide preliminary support for the concept that proteinase 3 ANCA-associated vasculitis and myeloperoxidase ANCA-associated vasculitis are distinct autoimmune syndromes. (Funded by the British Heart Foundation and others.).
    New England Journal of Medicine 07/2012; 367(3):214-23. · 51.66 Impact Factor
  • Jon W Gregersen, David R W Jayne
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    ABSTRACT: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is clinically heterogeneous and affects multiple organs. Lupus nephritis is the most frequent severe manifestation of SLE. Conventional immunosuppressive therapy has increased the life expectancy of patients diagnosed with lupus nephritis, but only 70-80% of patients respond to this treatment and its adverse effects are considerable. B cells are central to the pathogenesis of SLE and are, therefore, an attractive therapeutic target. B-cell depletion has been used successfully to treat other autoimmune diseases, such as rheumatoid arthritis and antineutrophil cytoplasmic antibody-associated vasculitis, and many case reports and small nonrandomized trials of B-cell-depleting agents in patients with lupus nephritis have reported positive results. By contrast, two large placebo-controlled trials designed to investigate the efficacy of the B-cell-depleting agents rituximab and ocrelizumab as a treatment for lupus nephritis, failed to meet their primary efficacy end points (LUNAR and BELONG, respectively). This Review discusses the current evidence on the use of B-cell depletion in the treatment of lupus nephritis, which is derived from case studies and clinical trials including a total of over 800 patients.
    Nature Reviews Nephrology 07/2012; 8(9):505-14. · 7.94 Impact Factor
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    ABSTRACT: The NORAM (Nonrenal Wegener's Granulomatosis Treated Alternatively with Methotrexate [MTX]) trial demonstrated that MTX can replace cyclophosphamide (CYC) as remission-inducing treatment for patients with newly diagnosed early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Duration of relapse-free survival was longer among CYC-treated patients than among MTX-treated patients during short-term followup. The aim of the present study was to describe the long-term outcome in patients enrolled in the randomized clinical trial. Outcome questionnaires were sent to investigators who had recruited patients for the NORAM trial. Patients treated with MTX for induction of remission (n = 49) were compared to CYC-treated patients (n = 46) with respect to immunosuppressive therapy during followup, relapse-free survival, mortality, and occurrence of other clinical events. The median duration of followup was 6 years (range 0.1-10.8 years). One patient developed end-stage renal disease, and 11 died. The number of patients affected by serious infection, malignancy, or severe organ failure did not differ between treatment groups, and no difference in survival rate was observed. The duration of corticosteroid therapy was longer in the MTX group during the 18 months of the trial (P = 0.005). During subsequent followup, patients who were in the MTX group in the NORAM trial received corticosteroids, CYC, and other immunosuppressive agents (azathioprine, MTX, and/or mycophenolate mofetil) for longer periods than those who were in the CYC group (P = 0.004, P = 0.037, and P = 0.031, respectively). The cumulative relapse-free survival tended to be lower in the MTX group (P = 0.056). In the NORAM cohort, no difference in occurrence of major adverse events was observed between treatment groups during long-term followup. However, first-line treatment with MTX was associated with less effective disease control than CYC-based induction therapy.
    Arthritis & Rheumatology 05/2012; 64(10):3472-7. · 7.48 Impact Factor
  • Rona M. Smith, David R.W. Jayne
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    ABSTRACT: The important role of B cells in the pathogenesis of systemic vasculitis has become increasingly clear over recent years. B cell directed therapies offer an exciting new approach to the treatment of these conditions, in which there has been little change in the options available to managing clinicians since the advent of traditional immunosuppressive therapy. The introduction of conventional immunosuppression has transformed survival in systemic vasculitis, particularly ANCA-associated vasculitis, but at the expense of significant toxicity, and with suboptimal efficacy. B cell therapies offer the possibility of targeted, individually tailored immunotherapy, which by improving efficacy, and reducing toxicity will improve clinical outcomes in systemic vasculitis. However, the heterogeneity of vasculitic syndromes suggests that one agent is unlikely to be effective in all situations. The precise indications and optimal combination of B cell directed with other therapies will need to be determined.
    Current Immunology Reviews 10/2011; 7(4):415-422.
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    ABSTRACT: To describe the incidence and prevalence of peripheral neuropathy in ANCA-associated vasculitis (AAV); to evaluate the correlation of neuropathy with other clinical manifestations; and to review the long-term outcome of treated neuropathy. Presence of neuropathy was determined using items from the BVAS and vasculitis damage index (VDI) during 5 years from enrollment into clinical trials conducted by the European Vasculitis Study Group (EUVAS). Forty (8%) of 506 patients had vasculitic neuropathy at baseline. Incidence of vasculitic motor-involving neuropathy was identical between microscopic polyangiitis (MPA) [16 (7%) out of 237] and granulomatosis with polyangiitis (Wegener's) [19 (7%) out of 269], P = 0.94. Pure sensory neuropathy was reported in 5 (2%) out of 269 patients with granulomatosis with polyangiitis, but not in patients with MPA, P = 0.065. Vasculitic neuropathy at baseline was associated with systemic [odds ratio (OR) = 1.81], cutaneous (OR = 1.29), mucous membranes (OR = 1.21) and ENT (OR = 1.14) manifestations of vasculitis (P < 0.05 for all). There was no association between neuropathy and renal, chest, cardiovascular or abdominal vasculitis or with overall mortality. Of the 40 patients with vasculitic neuropathy at baseline, 35% had complete resolution within 6 months. The cumulative prevalence of chronic neuropathy at any time up to 5 years was 15% (75 of 506). Chronic neuropathy was associated with older age [hazard ratio (HR) = 1.03], higher BVAS (HR = 1.07) and lower baseline creatinine (HR = 0.82) (P < 0.01 for all). Peripheral neuropathy is an occasional accompaniment of AAV that typically remits in concert with non-neuropathic manifestations, usually involves motor nerves, often produces long-lasting symptoms and is not associated with life-threatening organ involvement.
    Rheumatology (Oxford, England) 09/2011; 50(12):2214-22. · 4.24 Impact Factor
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    Arthritis & Rheumatology 09/2011; 63(9):2837. · 7.48 Impact Factor
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    ABSTRACT: The epidemiological manifestations of ANCA-associated vasculitis (AAV) differ geographically. However, there have been no prospective studies comparing the incidence of AAV between Japan and Europe over the same time period using the same case definitions. The incidence of AAV was determined by a population-based method in Miyazaki prefecture, Japan, and Norfolk, U.K., between 2005 and 2009. Patients with AAV were defined and classified according to the European Medicines Agency (EMEA) algorithm. The number of incident cases of AAV in Japan and the U.K. were 86 and 50, respectively, and the average annual incidence over the 5-year period was 22.6/million (95% CI 19.1, 26.2) and 21.8/million (95% CI 12.6, 30.9) in Japan and the U.K., respectively. The average age was higher in patients in Japan than in patients in the U.K. [mean (median), 69.7 (72) vs. 60.5 (61) years]. Microscopic polyangiitis (MPA) was the predominant subtype in Japan (83%), while granulomatosis with polyangiitis (Wegener's) was more frequent in the U.K. (66%). As for the pattern of ANCA positivity, >80% of Japanese patients were pANCA/MPO positive, whereas two-thirds of U.K. patients were cANCA/PR3 positive. Renal involvement in MPA was very common in both countries, but was much less common in granulomatosis with polyangiitis in Japan compared with the U.K. There was no major difference in AAV incidence between Japan and the U.K., but this prospective study found MPA and MPO-ANCA to be more common in Japan and granulomatosis with polyangiitis and PR3-ANCA to be more common in the U.K., in line with earlier reports.
    Rheumatology (Oxford, England) 07/2011; 50(10):1916-20. · 4.24 Impact Factor
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    ABSTRACT: To perform a literature review and develop recommendations for the use of rituximab in ANCA-associated vasculitis. A committee of experts (five rheumatologists, five nephrologists and one paediatrician) conducted a modified Delphi exercise to identify five topics for a systematic literature search. The evidence was then reviewed, categorized according to international criteria and assimilated to form five recommendations statements and a research agenda. Forty-three studies met the review criteria. These included two randomized controlled trials and a predominance of small, uncontrolled series. In refractory ANCA-associated vasculitis, remission rates of >80% are obtained with rituximab. In newly diagnosed disease, rituximab is at least as effective as conventional therapy. Fifteen recommendations were made. Their strength was restricted by the low quality of the evidence. Six areas for future research were identified. On the basis of the available evidence and expert consensus, recommendations have been made for the use of rituximab as a treatment of ANCA-associated vasculitis. Further questions, in particular regarding long-term outcomes, remain to be explored.
    Rheumatology (Oxford, England) 05/2011; 51(4):634-43. · 4.24 Impact Factor
  • Arthritis & Rheumatology 04/2011; 63(4):863-4. · 7.48 Impact Factor

Publication Stats

4k Citations
784.38 Total Impact Points


  • 2012–2013
    • Copenhagen University Hospital
      København, Capital Region, Denmark
    • Aarhus University Hospital
      Aarhus, Central Jutland, Denmark
  • 2011–2013
    • McMaster University
      Hamilton, Ontario, Canada
  • 1990–2013
    • University of Cambridge
      • • Division of Renal Medicine
      • • Department of Medicine
      Cambridge, England, United Kingdom
  • 2009–2012
    • Cambridge Institute for Medical Research
      Cambridge, England, United Kingdom
  • 2010
    • Nottinghamshire Healthcare NHS Trust
      Nottigham, England, United Kingdom
  • 2007
    • Free University of Brussels
      Bruxelles, Brussels Capital Region, Belgium
  • 2005
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
  • 2000–2002
    • Epsom and St Helier University Hospitals NHS Trust
      Эпсом, England, United Kingdom
  • 2001
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 1997–1998
    • St. George's School
      • Division of Renal Medicine
      Middletown, Rhode Island, United States
  • 1996
    • University of London
      Londinium, England, United Kingdom