C Antoni

Universitätsklinikum Erlangen, Erlangen, Bavaria, Germany

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Publications (37)191.87 Total impact

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    ABSTRACT: To assess the safety and efficacy of combination therapy with infliximab and leflunomide in adults with active rheumatoid arthritis (RA) despite leflunomide therapy. Adult patients with active RA who had received leflunomide for at least 16 weeks were eligible for this 30-week, open-label trial. All patients received ongoing oral leflunomide (20 mg/day) and 3 mg/kg infliximab administered IV at weeks 0, 2, 6, 14, and 22. The primary end point was the percentage of patients with adverse events that led to patient withdrawal and were at least possibly related to treatment. Descriptive evaluations of efficacy and other safety assessments were performed. Twelve out of 70 patients (17.1%; upper 90% CI 24.5%) withdrew due to treatment-related adverse events. Adverse events were reported in 69 of 72 patients (95.8%); the most common were nasopharyngitis, diarrhea, and pruritus. Serious adverse events occurred in 16 out of 72 patients (22.2%). Significant improvements were observed in efficacy assessments, including Disease Activity Score 28 (DAS28) and pain. At end point, 19.4% of the patients showed a good improvement in DAS28 score and 46.3% had a moderate improvement. American College of Rheumatology (ACR) 20, 50, and 70 responses were achieved by 47.1%, 21.4%, and 12.9% of the patients, respectively. The combination of infliximab and leflunomide neither increased the rate of toxicities nor resulted in unexpected adverse events. Treatment-related withdrawals occurred at an acceptable frequency. Patients experienced clinically significant improvements. Treatment with infliximab plus leflunomide benefits the majority of patients, but monitoring of adverse events is required.
    No preview · Article · Sep 2008 · Clinical and experimental rheumatology

  • No preview · Article · Dec 2007

  • No preview · Article · Nov 2007 · Arthritis & Rheumatology
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    ABSTRACT: To evaluate the effect of infliximab on progression of structural damage over 1 year in patients with active psoriatic arthritis (PsA) enrolled in the Induction and Maintenance Psoriatic Arthritis Clinical Trial 2. In this double-blind, placebo-controlled study, 200 patients with active PsA were randomly assigned (1:1 ratio) to receive infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, and 6, and every 8 weeks thereafter through week 54. At week 24, patients initially assigned to receive placebo crossed over to receive infliximab (5 mg/kg). Based on predefined criteria, patients randomized to receive placebo could enter early escape by receiving infliximab (5 mg/kg) starting at week 16, and patients randomized to receive infliximab could have the dose increased to 10 mg/kg starting at week 38. Patients were analyzed according to the treatment they were randomized to receive. Radiographs of hands and feet were obtained at baseline and at weeks 24 and 54. Two readers blinded to treatment assignment and radiograph sequence independently evaluated erosions and joint space narrowing using the Sharp/van der Heijde scoring method modified for PsA. At week 24, patients randomized to receive infliximab 5 mg/kg had significantly less radiographic progression compared with patients randomized to receive placebo, with mean +/- SD changes from baseline in the total Sharp/van der Heijde score of -0.70 +/- 2.53 and 0.82 +/- 2.62, respectively (P < 0.001). At week 54, mean +/- SD changes from baseline in the total Sharp/van der Heijde score were -0.94 +/- 3.40 in patients randomized to receive infliximab and 0.53 +/- 2.60 in those receiving placebo/infliximab (P = 0.001). Infliximab significantly inhibits radiographic progression in patients with PsA as early as 6 months after starting treatment, and the beneficial effect continues through 1 year of infliximab therapy.
    Full-text · Article · Aug 2007 · Arthritis & Rheumatology
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    ABSTRACT: To evaluate the efficacy and safety of infliximab through 1 year in patients with psoriatic arthritis (PsA) enrolled in the IMPACT 2 trial. In this double blind, placebo controlled, phase III study, 200 patients with active PsA were randomised to receive infusions of infliximab 5 mg/kg or placebo at weeks 0, 2, 6, and every 8 weeks thereafter through 1 year. Patients with persistent disease activity could enter early escape at week 16, and all remaining placebo patients crossed over to infliximab at week 24. Patients randomised to infliximab who had no response or who lost response could escalate their dose to 10 mg/kg starting at week 38. Clinical efficacy was assessed based on the proportion of patients achieving ACR 20 and PASI 75 responses. Major clinical response (that is, maintenance of ACR 70 response for 24 continuous weeks) was assessed for the first time in PsA. Through 1 year of treatment, 58.9% and 61.4% of patients in the randomised infliximab and placebo/infliximab groups, respectively, achieved ACR 20; corresponding figures for PASI 75 were 50.0% and 60.3%. At week 54, major clinical response was achieved by 12.1% of patients in the infliximab group. The safety profile of infliximab through week 54 was consistent with that seen through week 24. Two malignancies occurred: basal cell skin cancer (placebo) and stage I Hodgkin's lymphoma (infliximab). Infliximab maintains a high degree of clinical efficacy and continues to be well tolerated in patients with PsA through 1 year of treatment.
    Full-text · Article · May 2007 · Annals of the Rheumatic Diseases
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    ABSTRACT: Anti-TNF-alpha therapy with a chimeric monoclonal antibody (Infliximab, Remicade) has been shown to be highly effective in the treatment of skin lesions as well as arthritis in patients with psoriatic arthritis. In this study we investigated the molecular consequences of the in vivo TNF-alpha blockade with infliximab in psoriatic skin lesions of 6 patients with severe psoriatic arthritis. Biopsies from lesional and non-lesional skin were taken before and 10 weeks after the initiation of treatment. Immunohistochemistry and semiquantative RT-PCR were performed focusing on proinflammatory gene products. Immunohistochemistry, after three infusions, revealed a marked decrease in the expression of TNF-alpha, HLA-DR, CD3, CD15, ICAM-1 and LFA-1 positive cells. By semiquantitative RT-PCR, we analysed mRNA expression of IL-8, IL-20, TNF-R (TNF-R p60 and TNF-R p80), IL-1R I and IL-1R II, as well as ICAM-2. Before therapy, m-RNA for IL-8, IL-20, TNF-R p60, TNF-R p80, IL-1R II and ICAM-2 were detected in lesional skin. mRNA expression of IL-8 and IL-20 completely disappeared and mRNA expression of TNF-R p60 was reduced after therapy. This effect on IL-8 expression was paralleled by a decreased infiltration of leukocytes in psoriatic skin. These data suggest that the clinical response of anti-TNF-alpha therapy in patients with psoriasis or psoriatic arthritis may be, at least in part, caused by the inhibition of the production of proinflammatory cytokines and by the decreased expression of adhesion molecules with the consequence of an impaired migration of proinflammatory cells into the inflamed tissue. These data further support a critical role for TNF-alpha in the pathology of psoriasis.
    No preview · Article · Apr 2006 · International journal of immunopathology and pharmacology
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    ABSTRACT: To evaluate the effect of infliximab on health related quality of life (HRQoL) and physical function in patients with active psoriatic arthritis (PsA) in the IMPACT 2 trial. 200 patients with PsA unresponsive to conventional treatment were randomised to intravenous infusions of infliximab 5 mg/kg or placebo at weeks 0, 2, 6, 14, and 22; patients with inadequate response entered early escape at week 16. HRQoL was assessed using the Short Form-36 (SF-36) at weeks 0, 14, and 24. Functional disability was assessed using the Health Assessment Questionnaire (HAQ) at every visit through week 24. Associations between changes in quality of life (SF-36) and articular (American College of Rheumatology (ACR)) and dermatological (Psoriasis Area and Severity Index (PASI)) responses were examined. Mean percentage improvement from baseline in HAQ was 48.6% in the infliximab group compared with worsening of 18.4% in the placebo group at week 14 (p < 0.001). Furthermore, 58.6% and 19.4% of infliximab and placebo treated patients, respectively, achieved a clinically meaningful improvement in HAQ (that is, > or = 0.3 unit decrease) at week 14 (p < 0.001). Increases in physical and mental component summary (PCS and MCS) scores and all eight scales of the SF-36 in the infliximab group were greater than those in the placebo group at week 14 (p < or = 0.001). These benefits were sustained through week 24. Patients achieving ACR20 and PASI75 responses had the greatest improvements in PCS and MCS scores. In patients with PsA, infliximab 5 mg/kg significantly improved HRQoL and physical function compared with placebo through 24 weeks.
    Full-text · Article · Apr 2006 · Annals of the Rheumatic Diseases
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    ABSTRACT: To compare drug continuation rates in patients with rheumatoid arthritis who start on a biological agent and in a control group of patients with a change in disease modifying antirheumatic drug (DMARD) treatment after previous DMARD failure. Patients with rheumatoid arthritis enrolled in the German biologics register between May 2001 and September 2003 were included in the study. Data were available for 511 patients treated with etanercept, 343 with infliximab, 70 with anakinra, and 599 controls. Propensity scores were used to select a subsample of patients from the control group who were likely to be treated with biological agents because of their disease severity, as well as comparable infliximab and etanercept cases. Treatment continuation after 12 months was similar for etanercept (68.6% (95% confidence interval, 62% to 75%)) and infliximab (65.4% (58% to 73%)) but lower for anakinra (59% (41% to 77%)). Treatment continuation was more likely for patients on combinations of biological agents and DMARDs than for those on infliximab or etanercept alone. Patients treated with biological agents were more severely ill than those in the control group and had more previous DMARD failures. After adjustment for baseline differences, the continuation rates were higher in patients treated with biological agents than in comparable control patients treated with leflunomide or leflunomide/methotrexate. Treatment continuation of biological agents in clinical practice is less likely than in randomised clinical trials but more likely than in comparable controls treated with conventional DMARDs.
    Full-text · Article · Oct 2005 · Annals of the Rheumatic Diseases
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    ABSTRACT: To evaluate further in a phase III, double blind trial the efficacy of infliximab in patients with active psoriatic arthritis (PsA), as observed in the smaller IMPACT trial. 200 patients with active PsA unresponsive to previous treatment were randomised to infusions of infliximab 5 mg/kg or placebo at weeks 0, 2, 6, 14, and 22. Patients with inadequate response entered early escape at week 16. The primary measure of clinical response was ACR20. Other measures included Psoriatic Arthritis Response Criteria (PsARC), Psoriasis Area and Severity Index (PASI), and dactylitis and enthesopathy assessments. At week 14, 58% of patients receiving infliximab and 11% of those receiving placebo achieved an ACR20 response and 77% of infliximab patients and 27% of placebo patients achieved PsARC (both p<0.001). Among the 85% of patients with at least 3% body surface area psoriasis involvement at baseline, 53/83 (64%) patients receiving infliximab had at least 75% improvement in PASI compared with 2/87 (2%) patients receiving placebo at week 14 (p<0.001). These therapeutic effects were maintained through the last evaluation (week 24). Fewer infliximab patients than placebo patients had dactylitis at week 14 (18% v 30%; p = 0.025) and week 24 (12% v 34%; p<0.001). Fewer infliximab patients (22%) than placebo patients (34%) had active enthesopathy at week 14 (p = 0.016); corresponding figures at week 24 were 20% and 37% (p = 0.002). Infliximab was generally well tolerated, with a similar incidence of adverse events in each group. Infliximab 5 mg/kg through 24 weeks significantly improved active PsA, including dactylitis and enthesopathy, and associated psoriasis.
    Full-text · Article · Sep 2005 · Annals of the Rheumatic Diseases
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    Full-text · Article · May 2005 · Value in Health
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    D D Gladman · C Antoni · Mease PJ · D O Clegg · P Nash
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    ABSTRACT: Psoriatic arthritis (PsA) has been defined as a unique inflammatory arthritis associated with psoriasis. Its exact prevalence is unknown, but estimates vary from 0.3% to 1% of the population. The clinical features described initially are recognised by most experienced clinicians, although they are most distinct in early disease. Initially, PsA typically presents as an oligoarticular and mild disease. However, with time PsA becomes polyarticular, and it is a severe disease in at least 20% of patients. Patients with PsA who present with polyarticular disease are at risk for disease progression. In addition to progression of clinical and radiological damage, health related quality of life is reduced among patients with PsA. It important to note that patients included in recent drug trials resemble patients followed prospectively in a clinic.
    Full-text · Article · Apr 2005 · Annals of the Rheumatic Diseases
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    D D Gladman · V Strand · P J Mease · C Antoni · P Nash · A Kavanaugh
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    ABSTRACT: Outcome Measures in Rheumatology (OMERACT) conferences have developed a process by which outcome measures to be included in clinical trials are identified by consensus. During OMERACT 7, held in Asilomar, CA, USA, in May 2004, a workshop on outcome measures in psoriatic arthritis was held. Information derived through a previous Delphi exercise and nominal group process was shared with the participants, as were the results from a study using completed clinical trials with biological therapies. On the basis of the evidence presented and discussions in breakout groups at the OMERACT conference, a set of domains to be included in clinical trials in psoriatic arthritis was developed and a research agenda for further studies in psoriatic arthritis proposed.
    Full-text · Article · Apr 2005 · Annals of the Rheumatic Diseases
  • D L Scott · C Antoni · E H Choy · P C L M Van Riel

    No preview · Article · Sep 2003 · Rheumatology
  • C Antoni · B Manger
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    ABSTRACT: The proinflammatory cytokine TNF alpha is in the pathogenesis of PsA as important as in RA. TNF-alpha is increased in the psoriatic skin lesion and in the synovium of the inflamed joint. The TNF alpha blockage has been tested in double blind trials with etanercept and infliximab. All studies proved a significant and durable response in the reduction of synovitis in a comparable extend in both drugs. Etanercept showed after 12 weeks an ACR20 response in 59% of the patients versus 15% in the placebo arm. Infliximab had after 14 weeks a 69% ACR20 response versus 8% placebo response. The psoriatic skin lesion improved with both drugs. The PASI was reduced by 47% with etanercept and by 81% with infliximab. The safety-profile was similar to the RA-trials. For etanercept the one year data have shown a reduction in x-ray progression. Etanercept has been approved in the USA and in Europe.
    No preview · Article · Jul 2003 · Zeitschrift für Rheumatologie
  • C. Antoni · B. Manger
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    ABSTRACT: Zusammenfassung. Das proinflammatorische Zytokin TNFα spielt bei der Psoriasisarthritis sowie bei der rheumatoiden Arthritis eine wesentliche Rolle in der Pathogenese der Erkrankung. Sowohl in der Hautläsion der Psoriasis, als auch in der Synovitis ist eine vermehrte Expression von TNF-α feststellbar. Die Blockierung von TNFα als Therapieprinzip wurde mit den zwei Medikamenten Etanercept und Infliximab im Rahmen von doppelblinden, randomisierten und placebokontrollierten klinischen Studien untersucht. In allen Studien wurde die Entzündungsaktivität in den Gelenken anhaltend reduziert, wobei der Therapieeffekt z.T. noch deutlicher als bei Patienten mit rheumatoider Arthritis war. Die Ansprechraten beider Medikamenten waren sehr ähnlich. Nach 12 Wochen zeigte Etanercept ein Ansprechen nach den ACR20-Kriterien bei 59% der Patienten versus 15% mit Placebo und mit Infliximab wurde nach 14 Wochen bei 69% der Patienten das Kriterium ACR20 erreicht versus 8% im Placeboarm. Die Hautläsionen besserten sich unter beiden Medikamenten. Mit Etanercept reduzierte sich der “psoriasis acticity and severity index (PASI)” im Mittel um 47% und bei Infliximab um 81%, während sich die Haut in beiden Placeboarmen nicht verbesserte, sondern sich sogar verschlechterte (−35% bei Infliximab). Das Sicherheitsprofil entsprach bei beiden Medikamenten dem der Studien bei Patienten mit rheumatoider Arthritis. Für Etanercept wurde eine Hemmung der radiologischen Progression gezeigt. Etanercept wurde inzwischen für die Behandlung der PsA in den USA und Europa zugelassen.
    No preview · Article · Jan 2003 · Zeitschrift für Rheumatologie
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    C Antoni · B Manger
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    ABSTRACT: Tumor Necrosis Factor alpha (TNF) as proinflammatory cytokine plays in the pathogenesis of many diseases an important role. In psoriasis and in psoriatic arthritis TNF is up-regulated in the skin lesion and in the synovitis. Recent trials showed that the blockade of TNF with the chimeric antibody infliximab is able to improve both, the skin lesions and the synovitis of the joints. In psoriasis in 82% of patients treated with infliximab achieved an over 75% response in the PASI index. In Psoriatic arthritis the skin improvement was correlating with the reduction of synovitis and in a small MRI controlled study all patients achieved an ACR 20 response within 10 weeks. Patients with psoriatic arthritis, who have been included in spondylarthopathy trials showed similar improvement rates. In all trials unexpected safety problems have not been reported, but the trials have been small in population and short in duration. Infliximab was used between 5 and 10 mg/kg at week 0, 2, 6 and every 8 week. It some trials the retreatment periods varied. In contrast to the treatment of rheumatoid arthritis with infliximab methotrexate was not always used as comedication. In some cases infliximab has been used in combination with other DMARDs but no trial did evaluate the combination treatment vs. the monotherapy.
    Preview · Article · Nov 2002 · Clinical and experimental rheumatology
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    H G Kraetsch · C Antoni · J R Kalden · B Manger
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    ABSTRACT: To test the efficacy of infliximab in the treatment of patients with severe and active adult onset Still's syndrome (AOSD) despite conventional immunosuppressive therapy. Six patients with the diagnosis of AOSD according to the Yamagushi criteria of 1992 were treated with infliximab. All patients had severe disease with high clinical and serological activity. Patients were treated initially with high dose steroids or more intensive immunosuppressive therapy. Two patients had a history of multiple disease modifying antirheumatic drug (DMARD) treatments. One patient had a history of three years of AOSD with fever, chills, pleural and pericardial effusions, and hepatosplenomegaly. Despite these treatments, he developed increasing serological signs of inflammation and arthritis of both hips and peripheral joints. Another patient had a history of five years of AOSD with oligoarthritis, myalgias, and recurrent fever despite multiple DMARD treatment, including cyclophosphamide pulse therapy. Our patients with AOSD presented with massive polyarthralgias, polyarthritis, splenomegaly or hepatomegaly, the typical rash, sore throat, weight loss, serositis, continuing fever, leucocytosis, and raised C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and ferritin levels. Four patients with early onset of the disease, fulfilling the diagnostic criteria for AOSD and a clinical and serological high disease activity, were included in our pilot study without any further DMARD treatment apart from the initial steroid treatment. Reduction of established treatment, mainly with steroids, caused a relapse of the disease in all our patients. Patients then received 3-5 mg/kg infliximab on weeks 0, 2, and 6, continuing with intervals of 6-8 weeks depending on the patient's individual disease activity. In all patients, fever, arthralgias, myalgias, hepatosplenomegaly, and the rash resolved after the first courses of treatment with infliximab. All serological variables (CRP, ESR, hyperferritinaemia) returned to normal. After three courses of infliximab infusions, splenomegaly could not be detected in any of our patients. One caused by hip postarthritic osteoarthrosis, requiring hip replacement. After three courses of treatment with infliximab, splenomegaly could not be detected in any of our patients. Up to now, our patients have received infliximab infusion treatment for between five and 28 months. Throughout this period all patients have continued to benefit from this treatment, with improvement in their clinical symptoms, joint counts, and serological disease activity. One of our patients had a moderate infusion reaction during the second treatment. The infusion was discontinued for one hour and then was resumed with no further problems. The disease improved remarkably in all six patients with AOSD after treatment with infliximab, also in the early stage of AOSD. These preliminary data suggest the potential therapeutic benefit of anti-tumour necrosis factor alpha treatment in AOSD.
    Preview · Article · Dec 2001 · Annals of the Rheumatic Diseases
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    C Antoni · J Braun
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    ABSTRACT: The development of the anti-TNF therapies is a milestone in the therapy of rheumatic diseases. As in all new treatment opportunities it is of concern whether all potential undesired side effects have been evaluated within the clinical trials which have lead to approval of the drugs. Postmarketing experience and pharmacovigilance programs are necessary to determine the overall safety profile of the new agents. From the clinical trials and the practical experience of the first years we know that side effects have occurred in patients treated with anti-TNF agents. Sufficient knowledge about these partly specific side effects is critical for rheumatologists who treat their patients with these very effective biologic drugs.
    Preview · Article · Nov 2001 · Clinical and experimental rheumatology
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    ABSTRACT: In inflamed skin, keratinocytes and inflammatory cells both produce large amounts of tumour necrosis factor (TNF) -alpha, a cytokine with broad effects that are relevant to inflammation. Blockade of this proinflammatory cytokine by a monoclonal anti-TNF-alpha antibody might be effectively used in the treatment of inflammatory skin diseases. To gather information about the efficacy of an anti-TNF-alpha antibody (infliximab) in the treatment of skin lesions of psoriatic arthritis. Six patients with progressive joint disease and psoriatic skin lesions unresponsive to methotrexate therapy were treated with anti-TNF-alpha antibody. The Psoriasis Area and Severity Index was determined before and 10 weeks after initiation of therapy. Improvement of psoriatic skin lesions was observed in all patients. In addition, a marked improvement of the joint disease was noted. Therapy with anti-TNF-alpha antibody may be an effective treatment regimen for both psoriatic arthritis and psoriatic skin lesions.
    No preview · Article · Apr 2001 · British Journal of Dermatology
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    ABSTRACT: Background In inflamed skin, keratinocytes and inflammatory cells both produce large amounts of tumour necrosis factor (TNF) -α, a cytokine with broad effects that are relevant to inflammation. Blockade of this proinflammatory cytokine by a monoclonal anti-TNF-α antibody might be effectively used in the treatment of inflammatory skin diseases. Objectives To gather information about the efficacy of an anti-TNF-α antibody (infliximab) in the treatment of skin lesions of psoriatic arthritis. Methods Six patients with progressive joint disease and psoriatic skin lesions unresponsive to methotrexate therapy were treated with anti-TNF-α antibody. The Psoriasis Area and Severity Index was determined before and 10 weeks after initiation of therapy. Results Improvement of psoriatic skin lesions was observed in all patients. In addition, a marked improvement of the joint disease was noted. Conclusions Therapy with anti-TNF-α antibody may be an effective treatment regimen for both psoriatic arthritis and psoriatic skin lesions.
    No preview · Article · Mar 2001 · British Journal of Dermatology

Publication Stats

3k Citations
191.87 Total Impact Points

Institutions

  • 1995-2008
    • Universitätsklinikum Erlangen
      • Department of Dermatology
      Erlangen, Bavaria, Germany
  • 2007
    • University of California, San Diego
      • Division of Rheumatology, Allergy and Immunology
      San Diego, California, United States
  • 1993-2006
    • Friedrich-Alexander-University of Erlangen-Nürnberg
      • Rheumatology and Immunology Clinic
      Erlangen, Bavaria, Germany