Ronald F van Vollenhoven

Karolinska Institutet, Solna, Stockholm, Sweden

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Publications (322)2267.5 Total impact

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    ABSTRACT: Objectives: The correct identification of synovitis is critical for achieving optimal therapy results. Fluorescence optical imaging (FOI) is a novel modality based on the use of an intravenous fluorophore, which enables fluorescent imaging of the hands and wrists with increased focal optical signal intensities in areas of high perfusion and/or capillary leakage. The study objective was to determine the diagnostic utility of FOI in detecting apparent and clinically non-apparent active synovitis. Methods: Bilateral hand and wrist joints (n=872) of 26 patients with inflammatory arthritis assessed by standard clinical examination, musculoskeletal ultrasound (MSUS) and FOI were studied. Synovitis was defined as tender and swollen joints on clinical examination, presence of synovial thickening and intra-articular Doppler signals on MSUS, and abnormal focal optical signal intensities on FOI, respectively. Subclinical synovitis was defined as being clinically non-apparent, but positively inflamed on MSUS. Results: Depending on the standard used to define inflammation, FOI ranged from 73–83% sensitive and 83–95% specific for detecting manifest synovitis. For detecting clinically silent synovitis, the sensitivity, specificity and positive and negative predictive values of FOI were 80%, 96%, 77% and 97%, respectively. Conclusions: The high degree of agreement between MSUS and FOI suggest its use in clinical practice, especially when MSUS is not available, in order to identify synovitis earlier and with greater confidence. FOI may be particularly useful in identifying patients with clinically non-apparent joint inflammation of the hands and/or wrists. INTRODUCTION The timely identification and diagnostic precision of arthritis detection, especially subclin-ical synovitis, would be of critical importance in the early inflammatory arthritis (IA) process. 1–6 Imaging modalities such as MRI and musculoskeletal ultrasound (MSUS) are
    BMJ Open 05/2015; RMD Open 2015;1:1 e000106 doi:10.1136/rmdopen-2015-000106(RMD Open 2015;1:1 e000106 doi:10.1136/rmdopen-2015-000106):RMD Open 2015;1:1 e000106 doi:10.1136/rmdopen-2015-000106. DOI:10.1136/rmdopen-2015-000106 · 2.06 Impact Factor
  • Adrian Levitsky, Kristina Forslind, Ronald F van Vollenhoven
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    ABSTRACT: Objectives: The aim of this study was to apply a previously published method for evaluating radiographic progression, namely, predicted vs. observed radiographic progression in early rheumatoid arthritis (POPeRA), to the Swedish pharmacotherapy (SWEFOT) trial. Method: In SWEFOT, 487 patients with eRA were given methotrexate (MTX), and non-responders were randomized to group A [triple therapy: MTX + sulfasalazine (SSZ) + hydroxychloroquine (HCQ)] and group B [anti-tumour necrosis factor (anti-TNF) therapy: MTX + infliximab]. Responders continued on MTX. Predicted progression for 343 eligible patients was calculated based on the baseline total Sharp/van der Heijde score (SHS) divided by symptom duration, compared to observed progression at 12 and 24 months. Results: Observed radiographic progression was reduced from predicted by a mean of 50.1% (A), 72.3% (B), and 73.9% (MTX) at 12 months and by 87.2, 89.8, and 87.8% at 24 months, respectively. Among completers, reductions of 56.7% (A) and 76.5% (B) at 12 months and of 91.0% and 96.0% at 24 months, respectively, were observed. At 12 months, there were no significant between-group differences. At 24 months, progression was reduced more in group B than in group A (first quartile difference 8.5% favouring group B) and in MTX [n = 316, 89.8% (sd ± 32.0) vs. 87.2% (± 32.2), p = 0.021; vs. 87.8% (± 27.8), p = 0.013, respectively]. Conclusions: The POPeRA method confirms the original SWEFOT finding in that anti-TNF therapy was statistically marginally superior (2.6%) to triple therapy in preventing radiographic progression at 24 months among initial MTX non-responders. The simulation provided through POPeRA may facilitate comparisons of the relative efficacy of various treatments in preventing radiographic progression. Read More:
    Scandinavian Journal of Rheumatology 05/2015; 44(4):1-6. DOI:10.3109/03009742.2015.1019560 · 2.61 Impact Factor
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    ABSTRACT: A systematic literature review (SLR; 2009-2014) to compare a target-oriented approach with routine management in the treatment of rheumatoid arthritis (RA) to allow an update of the treat-to-target recommendations. Two SLRs focused on clinical trials employing a treatment approach targeting a specific clinical outcome were performed. In addition to testing clinical, functional and/or structural changes as endpoints, comorbidities, cardiovascular risk, work productivity and education as well as patient self-assessment were investigated. The searches covered MEDLINE, EMBASE, Cochrane databases and for the period between 2009 and 2012 and separately for the period of 2012 to May of 2014. Of 8442 citations retrieved in the two SLRs, 176 articles underwent full-text review. According to predefined inclusion/exclusion criteria, six articles were included of which five showed superiority of a targeted treatment approach aiming at least at low-disease activity versus routine care; in addition, publications providing supportive evidence were also incorporated that aside from expanding the evidence provided by the above six publications allowed concluding that a target-oriented approach leads to less comorbidities and cardiovascular risk and better work productivity than conventional care. The current study expands the evidence that targeting low-disease activity or remission in the management of RA conveys better outcomes than routine care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Annals of the rheumatic diseases 05/2015; DOI:10.1136/annrheumdis-2015-207526 · 9.27 Impact Factor
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    ABSTRACT: The aim of the Dose Reduction or Discontinuation of Etanercept in Methotrexate-Treated Rheumatoid Arthritis Patients Who Have Achieved a Stable Low Disease Activity-State study was to investigate the effect of etanercept (ETN) dose maintenance, reduction or withdrawal on patients with rheumatoid arthritis (RA) who had already achieved stable low disease activity (LDA) on ETN 50 mg+methotrexate (MTX). Patients with RA (n=91) and stable LDA with ETN 50 mg once weekly (QW)+MTX were included. After 8 weeks with unchanged treatment, 73 patients were randomised in a double-blind design to ETN 50 mg QW+MTX (ETN50), ETN 25 mg QW+MTX (ETN25) or placebo QW+MTX (PBO) for 48 weeks. Patients who flared were declared failures and treated with open-label ETN50 until week 48. The primary outcome was the proportion of patients on ETN50 versus PBO who were non-failures after 48 weeks. The proportion of non-failure patients was significantly lower with ETN50 (52%; p=0.007) and ETN25 (44%; p=0.044) versus PBO (13%). Median time to failure was significantly shorter with PBO (6 weeks) compared with ETN50 (48 weeks; p=0.001) and ETN25 (36 weeks; p<0.001). The majority of patients who flared regained LDA with open-label ETN50 quickly. Adverse events were consistent with the known side effect profiles of these medications. In patients with established RA who have achieved stable LDA on ETN50+MTX, continuing both is superior to PBO+MTX. Reduced dose ETN was also more effective than PBO in maintaining a favourable response, suggesting that a maintenance strategy with reduced dose ETN may be possible in a number of patients with established RA. NCT00858780. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Annals of the rheumatic diseases 04/2015; DOI:10.1136/annrheumdis-2014-205726 · 9.27 Impact Factor
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    ABSTRACT: To investigate whether disease activity at baseline influences health care costs in patients with RA initiating biologic treatment. In the Swedish Biologics Register, we identified patients with RA with baseline 28-joint DAS (DAS28) recorded and starting their first biologic in 2007-11 [n = 1638 with moderate disease activity (DAS28 3.2-5.1) and n = 1870 with high disease activity (DAS28 > 5.1)]. Data on inpatient and outpatient care and prescription drugs were retrieved from nationwide registers. Mean cost differences were estimated adjusted for age, sex and costs the year before treatment start. Patients with high (vs moderate) disease activity were older (60 vs 56 years; P < 0.001), but did not differ in sex distribution (75 vs 74% women; P = 0.99) or disease duration (10 vs 10 years; P = 0.13). The year after initiation of biologics, patients with high (vs moderate) baseline disease activity accumulated 9% higher health care costs, but the difference was not statistically significant after adjustment [€19 333 vs €17 810; adjusted difference €870 (95% CI -2, 1742)]. In the subgroup of patients with up to 4 years of follow-up data, decreasing costs were observed over the follow-up time, but no difference was found between patients with high compared with moderate baseline disease activity [€13 704 vs €12 349; adjusted difference 878 (95% CI -364, 2120)]. Irrespective of baseline disease activity, health care costs were approximately three times higher the year after initiation of biologics than the year before due to increased drug costs. Over up to 4 years of follow-up, no difference in health care costs was found after adjustment in patients starting their first biologic treatment with high vs moderate baseline disease activity. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email:
    Rheumatology (Oxford, England) 03/2015; DOI:10.1093/rheumatology/kev021 · 4.44 Impact Factor
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    ABSTRACT: To establish agreement on SLE treatment. SLE experts (n=69) were emailed scenarios and indicated preferred treatments. Algorithms were constructed and agreement determined (≥50% respondents indicating ≥70% agreement) Results: Initially 54% (N=37) responded suggesting treatment for scenarios; 13 experts rated agreement with scenarios. Fourteen of 16 scenarios had agreement. For: discoid lupus, first-line therapy was topical agents and hydroxychloroquine and/or glucocorticosteroids, then azathioprine and subsequently mycophenolate. (mofetil). Uncomplicated cutaneous vasculitis, initial treatment was glucocorticosteroids +/-hydroxychloroquine +/- methotrexate, followed by azathioprine or mycophenolate and then cyclophosphamide. Arthritis, initial therapy was hydroxychloroquine and/or glucocorticosteroids; then methotrexate and subsequently rituximab. Pericarditis, first-line therapy was NSAIDs then glucocorticosteroids with/without hydroxychloroquine, then azathioprine, mycophenolate or methotrexate and finally belimumab or rituximab; and/or a pericardial window. Interstitial lung disease/alveolitis, induction was glucocorticosteroids and mycophenolate or cyclophosphamide, then rituximab or IVIG; maintenance followed with azathioprine or mycophenolate. Pulmonary hypertension, glucocorticosteroids and mycophenolate or cyclophosphamide and an endothelin receptor antagonist were initial therapies; subsequent treatments were phosphodiesterase-5 inhibitors and then prostanoids and rituximab. Antiphospholipid antibody syndrome, standard anticoagulation with/without hydroxychloroqine then a thrombin inhibitor for venous thrombosis, versus adding aspirin or platelet inhibition drugs for arterial events. Mononeuritis multiplex and CNS vasculitis, first-line was glucocorticosteroids and cyclophosphamide followed by maintenance with azathioprine or mycophenolate, and then rituximab, IVIG or plasmapheresis. Serious lupus nephritis first-line was glucocorticosteroids and mycophenolate, then cyclophosphamide then rituximab. We established variable agreement on treatment approaches. For some treatment decisions there was good agreement between experts even if no RCT data were available. This article is protected by copyright. All rights reserved. © 2015 American College of Rheumatology.
    Arthritis Care and Research 03/2015; DOI:10.1002/acr.22589 · 4.04 Impact Factor
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    ABSTRACT: Background and objectives The objective detection and quantification of disease activity in its earliest pathophysiological stage is critical for achieving optimal therapy results. Fluorescence optical imaging (FOI) is a novel imaging modality for the hands and wrists, and automated quantification of the ensuing images using DACT (Disease ACTivity)-FOI as a novel algorithm representing activity. This study was designed to determine the utility of FOI as a diagnostic tool, and whether it could be used in lieu of colour/power Doppler ultrasound (US) to quantify and ascertain apparent and non-apparent active synovitis
    Annals of the Rheumatic Diseases 02/2015; 74(Suppl 1):A44-A44. DOI:10.1136/annrheumdis-2015-207259.101 · 9.27 Impact Factor
  • 01/2015; 1(1):e000044-e000044. DOI:10.1136/rmdopen-2014-000044
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    ABSTRACT: To determine the relationship between changes in antibody levels towards citrullinated peptides derived from different candidate autoantigens and therapeutic outcome in early rheumatoid arthritis (RA). Baseline and 3-month serum samples from 316 patients with early RA enrolled in the Swedish Farmacotherapy (SWEFOT) trial were analysed for antibodies against cyclic citrullinated peptides (CCP) and citrullinated peptides derived from vimentin (cVim), fibrinogen (cFib) and α-enolase (CEP-1). At 3-month follow-up, methotrexate monotherapy-inadequate responders were randomised to add-on therapy with sulfasalazine and hydroxychloroquine or infliximab. In these patients, anticitrullinated peptide antibodies (ACPA) were also assessed at 12 and 24 months. The proportion of antibody-positive patients and relative changes in antibody levels were compared across ACPA specificities and related to therapeutic response and radiographic progression. During the 2-year follow-up, the proportion of patients testing positive declined significantly regarding antibodies to cVim, cFib and CEP-1, while anti-CCP antibody occurrence remained stable over time. Turning anti-cVim antibody negative was most common, and anti-cVim antibody seroreversion during the first three months associated with significantly less 2-year radiographic progression compared with patients who remained positive. Median antibody levels of all tested ACPAs declined uniformly during initial methotrexate therapy and following response to add-on therapy, with no significant relation to treatment regimen or radiographic progression. The influence of early antirheumatic therapy on ACPA seroreversions was markedly different across specificities, and early disappearance of anti-cVim antibodies associated with better radiological outcome. Thus, these data suggest that the disappearance of particular ACPA reactivities may be beneficial in early RA. WHO database at the Karolinska institute: CT20080004; and NCT00764725. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Annals of the Rheumatic Diseases 12/2014; DOI:10.1136/annrheumdis-2014-205698 · 9.27 Impact Factor
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    ABSTRACT: The aetiology of amyotrophic lateral sclerosis (ALS) is poorly understood, and it is unclear if autoimmunity plays a role or if ALS is associated with inflammatory/autoimmune diseases such as rheumatoid arthritis (RA). There have been very few reports of patients with RA who develop ALS, and no epidemiological study examining the co-occurrence of the two diseases has been conducted.1-6 In December 2012, a cluster of ALS cases following treatment with tumour necrosis factor inhibitor (TNFi) was reported using data from the European system for reporting suspected adverse drug reactions, the EudraVigilance database.7 We sought to estimate the ALS rate in RA exposed and unexposed to TNFi using a nationwide, prospective, population-based cohort study design. We used Swedish national registers to identify patients with RA (National Patient Register inpatient care 1969-2011 and outpatient care 2001-2011 and the Swedish Rheumatology Quality Register 1996-2011) and TNFi exposures (Swedish Biologics Register ARTIS 1999-2011). General population comparators were selected from the total population register matched on age, sex, county and date of the matched diagnosis of patients with RA … [Full text of this article]
    Annals of the Rheumatic Diseases 10/2014; 73(11):2061-2062. DOI:10.1136/annrheumdis-2014-205622 · 9.27 Impact Factor
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    ABSTRACT: IntroductionThis study aimed to assess the utility of musculoskeletal ultrasound (MSUS) in patients with joint symptoms using a probabilistic approach.Methods One hundred and three patients without prior rheumatologic diagnosis and referred to our clinic for evaluation of inflammatory arthritis were included. Patients were assessed clinically including joint examination, laboratory testing including acute-phase reactants, rheumatoid factor (RF) and anti citrulinated protein antibody (ACPA), and radiographs of hands and feet if clinically indicated. A diagnostic assessment was then performed by the responsible rheumatologist where the probability of a) any inflammatory arthritis and b) rheumatoid arthritis was given on a 5-point scale ranging from 0 to 20% up to 80 to 100% probability. Subsequently, an ultrasound examination of the wrist, metacarpophalangeal (MCP), proximal interphalangeal (PIP) joints 2 to 5 in both hands, metatarsophalangeal (MTP) joints 2 to 5 in both feet and any symptomatic joints was performed and the results presented to the same rheumatologist. The latter then assessed the diagnostic probabilities again, using the same scale.ResultsThe rheumatologists¿ certainty for presence/absence of inflammatory arthritis and rheumatoid arthritis was increased significantly following ultrasound performance. The proportion of patient for whom diagnostic certainty for inflammatory arthritis was maximal was 33.0% before and 71.8% after musculoskeletal ultrasound (P <0.001). With regard to a diagnosis of RA, the proportions were 31.1% pre-test and 61.2% post-test (P <0.001). MSUS findings agreed with the final diagnosis in 95% of patients.Conclusion Musculoskeletal ultrasound, when added to routine rheumatologic investigation, greatly increases the diagnostic certainty in patients referred for the evaluation of inflammatory arthritis. The changes from pre-test to post-test probability quantify the diagnostic utility of musculoskeletal ultrasound in probabilistic terms.
    Arthritis Research & Therapy 10/2014; 16(5):448. DOI:10.1186/s13075-014-0448-6 · 4.12 Impact Factor
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    ABSTRACT: Anti-tumor necrosis factor (TNF) agents are effective in treating patients with rheumatoid arthritis (RA), but they are associated with (dose-dependent) adverse effects and high costs. To prevent overtreatment, several trials have assessed the effectiveness of down-titration compared with continuation of the standard dose.
    Cochrane database of systematic reviews (Online) 09/2014; 9:CD010455. DOI:10.1002/14651858.CD010455.pub2 · 5.70 Impact Factor
  • Sara Linder Ekö, Ronald F van Vollenhoven
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    ABSTRACT: Systemic lupus erythematosus (SLE) is a clinically diverse and potentially life-threatening auto-immune disease that can affect almost any organ system. Although much is still unknown regarding its pathogenesis, B cell abnormalities are thought to be central. A high relapse rate along with the toxicity associated with conventional treatments signify the need for more tailored approaches in this very heterogeneous disease. Both its mechanism targeting B cells and a relatively large number of case series and observational studies have suggested that the B cell-depleting agent rituximab could be a potent SLE drug. However, two randomized controlled trials failed to meet efficacy endpoints. Nevertheless, rituximab has continued to be used as an off-label alternative mainly in patients refractory to conventional immunosuppressive treatment. This article will review the current role of rituximab in SLE.
    Current Rheumatology Reports 09/2014; 16(9):444. DOI:10.1007/s11926-014-0444-5 · 2.45 Impact Factor
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    ABSTRACT: We appreciate Drs Yazici and Swearingen's1 interest in our paper.2 The multi-biomarker disease activity (MBDA) blood test has been validated as a quantitative measurement of rheumatoid arthritis (RA) disease activity.3 The research question addressed in our paper … [Full text of this article]
    Annals of the Rheumatic Diseases 08/2014; 73(11). DOI:10.1136/annrheumdis-2014-206383 · 9.27 Impact Factor
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    ABSTRACT: Objective. An association between 25-hydroxyvitamin D [25(OH)D, vitamin D] deficiency and increased cardiovascular risk factors (CVRF) and cardiovascular disease (CVD) has been shown in general population studies. Vitamin D deficiency has been noted in systemic lupus erythematosus (SLE), and cardiovascular disease is a major cause of morbidity and mortality in SLE. The objectives of this study are to estimate the associations of 25(OH)D levels with CVRF and determine whether low baseline 25(OH)D levels predict future cardiovascular events in patients participating in an international inception cohort. Methods. Data were collected on 890 participants including demographics, SLE activity and damage assessments, CVRF and events, medications, laboratory assessments of 25(OH)D levels and inflammatory markers. Multiple logistic and Cox regressions were used to estimate the associations of baseline 25(OH)D levels with baseline CVRF, and CVD events. The models were adjusted for age, sex, race, season, country, with and without body mass index. Results. Patients in the higher quartiles of 25(OH)D were less likely to have hypertension and hyperlipidemia, were more likely to have lower C-reactive protein, and lower Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) at baseline when compared with the first quartile. Vitamin D levels were not independently associated with CVD event incidence, however hazard ratios for CVD event incidence decreased with successively higher quartiles. Conclusion. Lower baseline 25(OH)D levels are associated with higher risk for CVRF and more active SLE at baseline. There may be a trend towards a lower likelihood of CVD events in those with higher baseline 25(OH)D levels. © 2014 American College of Rheumatology.
    08/2014; 66(8). DOI:10.1002/acr.22291
  • 69th Annual Meeting of the Canadian-Rheumatology-Association (CRA); 07/2014
  • 69th Annual Meeting of the Canadian-Rheumatology-Association (CRA); 07/2014
  • 69th Annual Meeting of the Canadian-Rheumatology-Association (CRA); 07/2014
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    ABSTRACT: Background Methotrexate is the most frequently used first-line antirheumatic drug. We report the findings of a phase 3 study of monotherapy with tofacitinib, an oral Janus kinase inhibitor, as compared with methotrexate monotherapy in patients with rheumatoid arthritis who had not previously received methotrexate or therapeutic doses of methotrexate. Methods We randomly assigned 958 patients to receive 5 mg or 10 mg of tofacitinib twice daily or methotrexate at a dose that was incrementally increased to 20 mg per week over 8 weeks; 956 patients received a study drug. The coprimary end points at month 6 were the mean change from baseline in the van der Heijde modified total Sharp score (which ranges from 0 to 448, with higher scores indicating greater structural joint damage) and the proportion of patients with an American College of Rheumatology (ACR) 70 response (≥70% reduction in the number of both tender and swollen joints and ≥70% improvement in three of five other criteria: the patient's assessment of pain, level of disability, C-reactive protein level or erythrocyte sedimentation rate, global assessment of disease by the patient, and global assessment of disease by the physician). Results Mean changes in the modified total Sharp score from baseline to month 6 were significantly smaller in the tofacitinib groups than in the methotrexate group, but changes were modest in all three groups (0.2 points in the 5-mg tofacitinib group and <0.1 point in the 10-mg tofacitinib group, as compared with 0.8 points in the methotrexate group [P<0.001 for both comparisons]). Among the patients receiving tofacitinib, 25.5% in the 5-mg group and 37.7% in the 10-mg group had an ACR 70 response at month 6, as compared with 12.0% of patients in the methotrexate group (P<0.001 for both comparisons). Herpes zoster developed in 31 of 770 patients who received tofacitinib (4.0%) and in 2 of 186 patients who received methotrexate (1.1%). Confirmed cases of cancer (including three cases of lymphoma) developed in 5 patients who received tofacitinib and in 1 patient who received methotrexate. Tofacitinib was associated with increases in creatinine levels and in low-density and high-density lipoprotein cholesterol levels. Conclusions In patients who had not previously received methotrexate or therapeutic doses of methotrexate, tofacitinib monotherapy was superior to methotrexate in reducing signs and symptoms of rheumatoid arthritis and inhibiting the progression of structural joint damage. The benefits of tofacitinib need to be considered in the context of the risks of adverse events. (Funded by Pfizer; ORAL Start number, NCT01039688 .).
    New England Journal of Medicine 06/2014; 370(25):2377-2386. DOI:10.1056/NEJMoa1310476 · 54.42 Impact Factor
  • Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):505-506. DOI:10.1136/annrheumdis-2014-eular.2571 · 9.27 Impact Factor

Publication Stats

11k Citations
2,267.50 Total Impact Points


  • 2004–2015
    • Karolinska Institutet
      • Department of Medicine, Huddinge
      Solna, Stockholm, Sweden
  • 2000–2015
    • Karolinska University Hospital
      • Department of Rheumatology
      Tukholma, Stockholm, Sweden
  • 2012
    • Università di Pisa
      Pisa, Tuscany, Italy
  • 2009–2011
    • Capital District Health Authority of Nova Scotia
      Halifax, Nova Scotia, Canada
  • 2010
    • Medical University of Vienna
      Wien, Vienna, Austria
  • 2006
    • Uppsala University
      • The Rudbeck Laboratory
      Uppsala, Uppsala, Sweden
  • 2005
    • University of Innsbruck
      Innsbruck, Tyrol, Austria
  • 1994–2002
    • Stanford Medicine
      • Division of Immunology and Rheumatology
      Stanford, California, United States
  • 1998
    • Stanford University
      • Division of Rheumatology
      Palo Alto, CA, United States