Rheumatoid Arthritis: Tony HP

Kleinert S, Feuchtenberger M, Kneitz C, Tony HP. · Medizinische Klinik and Poliklinik II, Department of Rheumatology and Clinical Immunology, University of Wuerzburg, Klinikstrasse 6, D-97070 Würzburg, Germany. · Clin Dermatol. · Pubmed #18021887 No free full text.

Abstract: Psoriatic arthritis presents with a broad clinical spectrum of symptoms. Symmetrical polyarthritis with joint pain and joint swelling is one pattern of clinical manifestations that often indicates erosive progressive disease. Unlike in rheumatoid arthritis, the distal interphalangeal joints are regularly involved. Sometimes, the disease focuses on the larger joints of the lower extremities; iliosacral and intervertebral joints and tendons can also be involved. Thus, inflammatory back pain as well as any other prolonged joint pain in a patient with psoriasis is suspicious of psoriatic arthritis. This article reviews the clinical spectrum and diagnostic procedures that can lead to the diagnosis of psoriatic arthritis.

Feuchtenberger M, Kneitz C, Tony HP. · Schwerpunkt Rheumatologie/Klinische Immunologie, Medizinische Klinik mit Poliklinik II der Universität Würzburg, Klinikstrasse 6, 97070 Würzburg. · Z Rheumatol. · Pubmed #17522870 No free full text.

Abstract: Cytokine driven inflammation is a common feature in autoimmune diseases. Cytokines are needed under physiological conditions within the innate and adaptive immune systems to control infectious diseases and neoplastic disorders by regulation of the cell cycle and apoptosis. Cytokines can also be found in persistently increased concentrations in inflamed tissues within autoimmune diseases. Therefore, the modulation of cytokines seems to be a worthwhile therapeutic approach. With TNFalpha and Il-1, two key cytokines in rheumatoid arthritis have been identified. Their inhibition leads to a convincing clinical benefit. In the near future, inhibition of additional cytokines, such as Il-6 or Il-15, will likely open new beneficial strategies.

Palanichamy A, Roll P, Theiss R, Dörner T, Tony HP. · University of Würzburg, Würzburg, Germany. · Arthritis Rheum. · Pubmed #19035487 No free full text.

Abstract: OBJECTIVE: Transient B cell depletion by rituximab has recently gained more importance in the treatment of rheumatic disorders. Nevertheless, little is known about the reemerging B cells. We analyzed dynamic changes in the repopulating B cells, particularly the postswitch B cells, and studied the mutational patterns of Ig genes in antigen-experienced B cells. METHODS: Five patients with active rheumatoid arthritis (RA) were treated with rituximab. In 3 patients, B cell receptor (BCR) gene analysis was performed before treatment and during B cell recovery using genomic DNA. In 2 patients, B cell subsets were studied during the early recovery phase using single-cell technology. For comparison, immunophenotyping of B cell subsets was performed. RESULTS: Early B cell recovery was marked by a relatively expanded population of highly mutated B cells, which were correlated with B cells with a plasmablast phenotype on comparative immunophenotyping. Analysis of the mutational pattern in these cells revealed increased RGYW/WRCY (where R = A/G, Y = C/T, and W = A/T) hotspot targeting (44% before rituximab versus 59% after) and elevated ratios of replacement to silent mutations within the complementarity-determining regions in Ig genes (1.87 before rituximab versus 2.67 after; P < or = 0.0025). CONCLUSION: Our findings show that rituximab leads to qualitative changes in the imprints of highly mutated, antigen-experienced BCRs, representing the result of selection, whereas molecular processes such as Ig V rearrangements are not affected by this treatment.

Roll P, Dörner T, Tony HP. · University of Würzburg, Wurzburg, Germany. · Arthritis Rheum. · Pubmed #18512772 links to  free full text

Abstract: OBJECTIVE: B cell depletion with the anti-CD20 antibody rituximab has proven efficacy in patients with rheumatoid arthritis (RA). The effects on B cell homeostasis after repeated treatments and the relationship of certain B cell subsets to clinical response or relapse are currently not known. METHODS: In this open-label study, 17 patients with RA refractory to standard therapy were treated with 1 cycle of rituximab. Of these 17 patients, 11 received a second cycle of rituximab therapy. Immunophenotyping was performed before therapy and during B cell recovery. RESULTS: Twelve of 17 patients showed a good European League Against Rheumatism response after receiving 1 cycle of rituximab therapy. At the time of B cell recovery, the IgD+,CD27+ memory B cell subset was significantly larger (P = 0.019) in the nonresponder group. Within the group of 12 responders, 6 patients, whose disease was characterized by a significantly higher proportion of overall CD27+ memory B cells before therapy, experienced an early relapse (weeks 24-40 posttreatment). Eleven patients were re-treated, again resulting in a good clinical response. B cell reconstitution followed a similar pattern after each cycle. The early reconstitution phase was characterized by immature CD38++,IgD+,CD10+ B cells, whereas the number of naive B cells increased continuously thereafter. The number of memory B cells was still reduced at the time of the second depletion but recovered to levels similar to those following the first cycle of therapy. CONCLUSION: Data derived from repeated B lymphocyte depletion with rituximab in patients with RA suggest that analysis of certain memory B cell subsets provides information on efficacy, response, and late as well as early relapse, consistent with the conclusion that targeting memory B cells is a key to its mechanism of action.

Kneitz C, Wilhelm M, Tony HP. · Medizinische Poliklinik der Universität Würzburg, Germany. · Scand J Rheumatol. · Pubmed #15163108 No free full text.

Abstract: OBJECTIVE: B cells are involved in the pathogenesis of rheumatoid arthritis (RA). To evaluate the effect of therapeutic B-cell depletion for treatment of RA, an open label study has been performed using the B-cell depleting anti-CD20 antibody rituximab. METHODS: Five patients with refractory RA were treated weekly with four infusions of rituximab (375 mg/m2) alone, or in combination with ongoing methotrexate (MTX). Patients were followed for at least 44 weeks and monitored for safety and tolerability of treatment. RESULTS: Treatment could be performed without serious side effects and resulted in peripheral B-cell depletion lasting between 36 weeks up to > 1 year. The follow-up revealed no significant treatment-associated side effects. At 22 weeks, 4/5 patients showed a significant improvement (> 1.2) of the Disease Activity Score (DAS28). The mean DAS28 of all patients declined from 6.2 to 4.1. At 44 weeks there was one drop-out, another patient still had a sustained response, and three patients showed slowly increasing disease activity (mean DAS28 of the remaining four patients: Week 0: 6.0; Week 22: 3.85; Week 44: 5.6). Despite relatively constant immunoglobulin levels, rheumatoid factor levels decreased parallel to disease activity. CONCLUSION: In patients with refractory RA, B-cell depletion with rituximab is safe and well tolerated. A reduction of disease activity could be observed, which eventually deteriorated after B-cell repopulation. The findings give more evidence for B-cell targeted therapies in RA.

Jahns R, Naito J, Tony HP, Inselmann G. · Department of Internal Medicine, Medizinische Poliklinik, University of Würzburg, Germany. · Cardiology. · Pubmed #10844388 No free full text.

Abstract: Systemic autoimmune disorders may affect several organs, including the heart. We analyzed two-dimensional and pulsed Doppler echocardiograms of patients (n = 37) with systemic lupus erythematosus (SLE, n = 24) or rheumatoid arthritis (RA, n = 13) to determine whether atrial ejection force (AEF) could represent a suitable parameter for detecting left ventricular filling abnormalities in SLE and RA. In both patient subgroups, AEF was significantly higher than in healthy controls (n = 40) matched for gender and age (14.0 +/- 5.4 vs. 11.0 +/- 3.5 kdyn, p < 0.01). Because conventional echocardiographic parameters of left ventricular function failed to detect such a difference, AEF might serve as an additional sensitive parameter for detecting left ventricular diastolic filling abnormalities early in the course of a systemic autoimmune disease.

Feuchtenberger M, Kneitz C, Roll P, Kleinert S, Tony HP. · University of Würzburg, Dept. of Medicine II, Rheumatology and Clinical Immunology, Germany; Department of Medicine II, Klinikum Südstadt Rostock, Germany. · Open Rheumatol J. · Pubmed #19479056 links to  free full text

Abstract: OBJECTIVES: Approximately up to 40% of patients with rheumatoid arthritis (RA) fail to respond to tumor necrosis factor (TNF) inhibitors, lose response over time or are unable to tolerate treatment. MATERIALS AND METHODOLOGY: We report two female patients suffering from active, refractory rheumatoid arthritis despite TNF blocking agents who have been treated with rituximab added to ongoing therapy with etanercept. RESULTS: Combination therapy was tolerated without any acute side effects. Both patients improved with a significant, long lasting reduction of disease activity (DAS28, CRP). Evaluation of the immunological parameters showed the expected B-cell depletion and a transient reduction of immunoglobulin-levels. One patient developed four serious infections requiring antibiotic treatment (1 pneumonia, 3 exacerbations of her pre-existing chronic bronchitis) within follow up of 45 months. CONCLUSION: Combination therapy of rituximab and etanercept lead to a significant improvement of clinical disease activity and inflammatory parameters in two RA patients refractory to anti-TNF treatment.

Roll P, Tony HP. · Schwerpunkt Rheumatologie/Klinische Immunologie, Medizinische Klinik und Poliklinik II, Universität Würzburg, Würzburg. · Z Rheumatol. · Pubmed #19449019 No free full text.

Abstract: The anti-CD20 antibody Rituximab was the first B-cell-specific therapy approved for the treatment of rheumatoid arthritis patients. The basis for its approval in 2006 was the REFLEX study, which examined the administration of 1000 mg Rituximab at 2-week intervals combined with Methotrexat compared with placebo in patients with poor response to TNF-inhibitors in terms of all relevant clinical parameters. Radiological data show that Rituximab is capable of effectively arresting joint destruction. The treatment was well tolerated. The most common side effect, seen in up to 35% of patients, was infusion reactions, particularly during initial Rituximab administration. This could be reduced by approximately 30% with the use of steroid premedication. The serious infection rate in this randomised trial was slightly increased compared with the placebo group, as would also be expected for other biologicals. Data on re-treatment is currently available for up to five treatments and show sustained and/or improved efficacy with continued good tolerance.

Roll P, Tony HP. · Medizinische Klinik und Poliklinik II, Schwerpunkt Rheumatologie/Klinische Immunologie, Universität Würzburg, Klinikstr. 6, 97070, Würzburg, Deutschland. · Z Rheumatol. · Pubmed #19384549 No free full text.

Abstract: In recent years a growing body of evidence suggests a more central role for B-cells in the pathogenesis of several autoimmune diseases, apart from being the precursors of autoantibody-producing plasma cells. B-lymphocytes play an important role in the pathogenesis of various autoimmune diseases. In particular, the introduction of rituximab, a depleting antibody targeting CD20+ B cells and its clinical efficacy in rheumatoid arthritis, systemic lupus erythematosus, vasculitis and multiple sclerosis has stimulated further B-cell-targeted therapies. Other biologicals targeting CD20 are under clinical investigation. New strategies include targeting further B-cell surface markers such as CD22, as well as blocking B-cell-activating factors or their receptors.

Feuchtenberger M, Müller S, Roll P, Waschbisch A, Schäfer A, Kneitz C, Wiendl H, Tony HP. · University of Würzburg, Department of Medicine II, Rheumatology and Clinical Immunology, Germany. · Open Rheumatol J. · Pubmed #19156222 links to  free full text

Abstract: OBJECTIVES: Transient B cell depletion with the monoclonal anti-CD20 antibody rituximab has shown favourable clinical responses in patients with rheumatoid arthritis (RA). Recently a characteristic regeneration pattern of B cell subpopulations has been reported. However, little is known about the impact of B-cell depletion on peripheral T cells in particular regulatory T cells. MATERIALS AND METHODOLOGY: 17 patients with RA having failed anti-TNF were treated with rituximab. Four colour staining was performed using CD19, CD3, CD4, CD8, CD16, CD56, CD25, HLA-DR, HLA-G and intracellular Foxp3 at five time points spanning up to 12 months after rituximab. In addition, quantification of the soluble form of the HLA class I molecule HLA-G by ELISA has been performed. RESULTS: Peripheral B cell depletion lasted 6 to 9 months. The absolute number of CD3+, CD4+ and CD8+ lymphocytes showed no significant changes up to 1 year after B-cell depletion compared to before therapy. Only the relative frequency for CD3 and CD4 showed a significant increase (p < 0.05). In particular, CD4+CD25++ and Foxp3 positive regulatory T cells remained constant. The percentage of HLA-G positive cells in the CD4+ or CD8+ population did not change significantly either. The amount of sHLA-G remained without significant changes. CONCLUSION: Absolute T cell counts showed no significant changes after rituximab compared to the time point before therapy.In particular, the frequency of regulatory T cells with a CD4+CD25++ phenotype as well as positive Foxp3 expression were numerically stable. Additionally, HLA-G positive regulatory T cells and soluble levels of HLA-G showed no significant changes.

Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, Alecock E, Lee J, Kremer J. · Leeds Teaching Hospitals Trust, University of Leeds, Leeds, UK. · Ann Rheum Dis. · Pubmed #18625622 No free full text.

Abstract: OBJECTIVES: The phase III RADIATE study examined the efficacy and safety of tocilizumab, an anti-IL-6 receptor monoclonal antibody in patients with rheumatoid arthritis (RA) refractory to tumour necrosis factor (TNF) antagonist therapy. METHODS: 499 patients with inadequate response to one or more TNF antagonists were randomly assigned to receive 8 mg/kg or 4 mg/kg tocilizumab or placebo (control) intravenously every 4 weeks with stable methotrexate for 24 weeks. ACR20 responses, secondary efficacy and safety endpoints were assessed. RESULTS: ACR20 was achieved at 24 weeks by 50.0%, 30.4% and 10.1% of patients in the 8 mg/kg, 4 mg/kg and control groups, respectively (less than p<0.001 both tocilizumab groups versus control). At week 4 more patients achieved ACR20 in 8 mg/kg tocilizumab versus controls (less than p = 0.001). Patients responded regardless of most recently failed anti-TNF or the number of failed treatments. DAS28 remission (DAS28 <2.6) rates at week 24 were clearly dose related, being achieved by 30.1%, 7.6% and 1.6% of 8 mg/kg, 4 mg/kg and control groups (less than p = 0.001 for 8 mg/kg and p = 0.053 for 4 mg/kg versus control). Most adverse events were mild or moderate with overall incidences of 84.0%, 87.1% and 80.6%, respectively. The most common adverse events with higher incidence in tocilizumab groups were infections, gastrointestinal symptoms, rash and headache. The incidence of serious adverse events was higher in controls (11.3%) than in the 8 mg/kg (6.3%) and 4 mg/kg (7.4%) groups. CONCLUSION: Tocilizumab plus methotrexate is effective in achieving rapid and sustained improvements in signs and symptoms of RA in patients with inadequate response to TNF antagonists and has a manageable safety profile. TRIAL REGISTRATION NUMBER: NCT00106522.

Feuchtenberger M, Kneitz C, Tony HP. · Medizinische Klinik mit Poliklinik II der Universität Würzburg. · MMW Fortschr Med. · Pubmed #17621799 No free full text.

Abstract: In the hands of an experienced rheumatologist and in adherence to the contraindications named in the article, anticytokines such asTNF-alpha blockers or interleukin-1 antagonists are regarded as relatively reliable, are well tolerated and in many cases, are very effective. Especially when used in combination with methotrexate, they demonstratively lower the disease activity score and significantly slow the radiographic progression.Thus, anticytokines are currently the most effective therapy for RA. An additional advantage compared to conventional DMARD is the rapid onset of action (usually within two to four weeks).TNF-alpha blockers are also presently employed in numerous other chronic inflammatory diseases. The efficacy of anticytokines in psoriasis and psoriatic arthritis, ankylosing spondylitis, juvenile arthritis and Crohn's disease has been proven.

Roll P, Palanichamy A, Kneitz C, Dorner T, Tony HP. · University of Würzburg, Wurzburg, Germany. · Arthritis Rheum. · Pubmed #16869000 links to  free full text

Abstract: OBJECTIVE: Transient B cell depletion with the monoclonal anti-CD20 antibody rituximab has resulted in favorable clinical responses in patients with rheumatoid arthritis (RA). However, little is known about the regeneration profile of different peripheral B cell subpopulations. The aim of this study was to delineate the regeneration profile of different B cell subsets in the peripheral blood after selective anti-CD20-mediated B cell depletion. METHODS: Seventeen patients with RA refractory to standard therapy were treated with rituximab. Patients 1-6 received 4 weekly infusions of rituximab at a dose of 375 mg/m2, and patients 7-17 received 2 infusions of rituximab (1,000 mg), 2 weeks apart. Four-color staining was performed at several time points, using CD38, IgD, and CD27 in addition to other cell surface markers. In one patient, the mutational status of the immunoglobulin receptor was examined. RESULTS: The analysis revealed a distinct pattern of B cell regeneration. The first wave of repopulating B cells were immature B cells (CD38high,IgD+,CD10+,CD24high), the immunoglobulin receptors of which were not yet somatically mutated. In parallel, a recirculation of plasma cells was observed. Later, the number of naive B cells increased, and these cells predominated in the peripheral blood B cell pool. CD27+ memory B cells showed a slow and delayed repopulation, and the level of these cells stayed significantly reduced (<50%) compared with baseline values, for more than 2 years. CONCLUSION: Our findings provide evidence for a characteristic regeneration pattern of B cell subpopulations, with long-lasting modulation of B cell subset composition, after selective anti-CD20-mediated B cell depletion.

Kneitz C, Tony HP, Krüger K. · Schwerpunkt Rheumatologie und Klinische Immunologie, Medizinische Klinik und Poliklinik II der Universität, Würzburg. · Internist (Berl). · Pubmed #16557412 No free full text.

Abstract: NSAIDs (non steroidal anti-inflammatory drugs) are a crucial component for the therapy of pain induced by inflammatory and degenerative joint diseases. Nevertheless their known therapeutic efficacy is contrasted by significant side effects. The recently developed selective COX-2-inhibitors appear to have a better gastrointestinal safety profile, especially relevant to patients with an increased risk for gastrointestinal ulcers and bleeding. However, this effect may similarly be reached by the combination of NSAIDs with proton pump inhibitors. Recent data relate to an elevated myocardial infarction rate in patients using COX-2-inhibitors. This risk may also occur in conventional NSAIDs. Therefore an individual risk calculation is necessary before COX-2-inhibitors or NSAIDs are used. Treatment should be performed with the lowest dosage for the shortest time possible. Combination therapy with salicylic acid seems to abolish the protective effect of COX-2-inhibitors in the GI-tract. Definite risk factors for the treatment with NSAIDs and COX-2-inhibitors have to be defined in further studies providing the best treatment schedule for an individual patient.

Kneitz C, Suerbaum S, Beer M, Müller J, Jahns R, Tony HP. · Department of Clinical Immunology and Rheumatology, Medizinische Poliklinik, University of Würzburg, Germany. · Scand J Rheumatol. · Pubmed #16095013 No free full text.

Abstract: A 34-year-old man with chronic inflammatory joint disease and recurrent fever over 6 years was diagnosed as having Still's disease. Treatment with corticosteroids and azathioprine was ineffective. Therefore, infliximab/ methotrexate was started. The patient subsequently developed a wasting disease with rapid weight loss, erythema nodosum, diarrhoea, progressive lymph node enlargement, and a sigmoido-vesical fistula. Histological analysis of several enlarged lymph nodes, the margins of the fistula, and the small bowel established the diagnosis of Whipple's disease (WD). The presence of Tropheryma whipplei (Tw) DNA in the tissues was confirmed by polymerase chain reaction (PCR). Careful re-evaluation of biopsies taken from the ileum and the liver 2 years earlier, which at that time was not judged to be diagnostic for WD, retrospectively showed subtle histological signs of WD and were positive for Tw DNA. In summary, infliximab treatment seems to increase the risk of exacerbation of WD. WD should be carefully ruled out prior to application of tumour necrosis factor-alpha (TNF-alpha) blockade.

Rouzière AS, Kneitz C, Palanichamy A, Dörner T, Tony HP. · Department of Medicine II, Rheumatology and Clinical Immunology, University of Wuerzburg, Germany. · Arthritis Res Ther. · Pubmed #15987473 links to  free full text

Abstract: B-cell depletive therapies have beneficial effects in patients suffering from rheumatoid arthritis. Nevertheless, the role of B cells in the pathogenesis of the disease is not clear. In particular, it is not known how the regeneration of the B-cell repertoire takes place. Two patients with active rheumatoid arthritis were treated with rituximab, and the rearranged immunoglobulin heavy-chain genes (Ig-VH) were analysed to follow the B-cell regeneration. Patient A was treated with two courses of rituximab, and B-cell regeneration was followed over 27 months by analysing more than 680 Ig-VH sequences. Peripheral B-cell depletion lasted 7 months and 10 months, respectively, and each time was accompanied by a clinical improvement. Patient B received one treatment course. B-cell depletion lasted 5 months and was accompanied by a good clinical response. B cells regenerated well in both patients, and the repopulated B-cell repertoire was characterised by a polyclonal and diverse use of Ig-VH genes, as expected in adult individuals. During the early phase of B-cell regeneration we observed the expansion and recirculation of a highly mutated B-cell population. These cells expressed very different Ig-VH genes. They were class-switched and could be detected for a short period only. Patient A was followed long term, whereby some characteristic changes in the VH2 family as well as in specific mini-genes like VH3-23, VH 4-34 or VH 1-69 were observed. In addition, rituximab therapy resulted in the loss of clonal B cells for the whole period.Our data show that therapeutic transient B-cell depletion by anti-CD20 antibodies results in the regeneration of a diverse and polyclonal heavy-chain repertoire. During the early phase of B-cell regeneration, highly mutated B cells recirculate for a short time period in both the patients analysed. The longitudinal observation of a single patient up to 27 months shows subtle intraindividual changes, which may indicate repertoire modulation.

Hau M, Kneitz C, Tony HP, Keberle M, Jahns R, Jenett M. · Medizinische Poliklinik, Universität Würzburg, Germany. · Ann Rheum Dis. · Pubmed #11779760 links to  free full text

Abstract: OBJECTIVE: High resolution ultrasound (HRUS) was used to investigate the effects of tumour necrosis factor alpha (TNFalpha) blockade on pannus formation and vascularisation of small finger joints in patients with active rheumatoid arthritis (RA). METHODS: Five patients with active RA were treated with etanercept, a soluble TNFalpha receptor protein, for one month. Before, during, and after treatment the patients were followed up by clinical rheumatological examination, determination of their subjective pain score, blood chemistry, and by HRUS of the second metacarpophalangeal (MCP) joint of the right hand. RESULTS: One month after treatment with etanercept, rheumatological examination showed a significant decrease in a modified single joint rheumatic disease activity index (from 2.9 (SD 0.2) to 1.2 (0.7); p<0.05) in all patients. Moreover, a significant decrease in the general pain score (from 4.7 (0.4) to 1.8 (0.6); p<0.05) and in C reactive protein (CRP) levels was seen (from 3.02 (0.9) to 0.24 (0.1); p<0.05). Concordantly, HRUS showed a significant reduction in pannus vascularisation of the MCPII joints (from 23,602 (5339) to 2907 (1609) colour signals/region of interest, CS/ROI; p<0.001). Pearson's correlation coefficient between the results obtained by HRUS and the clinical response was 0.85. CONCLUSION: HRUS is promising as an additional useful method in the assessment of RA activity, and probably also in monitoring therapeutic responses.

Kneitz C, Tony HP. · Medizinische Poliklinik, Universität Würzburg Klinikstr. 6, D-97070 Würzburg. · MMW Fortschr Med. · Pubmed #11721668 No free full text.

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Hau M, Schultz H, Tony HP, Keberle M, Jahns R, Haerten R, Jenett M. · Institut für Röntgendiagnostik, Universität Würzburg, Germany. · Arthritis Rheum. · Pubmed #10555024 links to  free full text

Abstract: OBJECTIVE: To evaluate the extent of intraarticular vascularization and pannus formation in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of patients with rheumatoid arthritis (RA) by high-resolution ultrasound (US). METHODS: A newly developed, high-resolution multidimensional linear array US was utilized to obtain longitudinal and transverse scans of joints with active RA (n = 21), moderately active RA (n = 39), or inactive RA (n = 93), and of joints from healthy controls (n = 120). RESULTS: Healthy joints had no detectable pannus, whereas pannus could be detected in 52% of the joints with active RA, 82% of the joints with moderately active RA, and 67% of the joints with inactive RA. There was a significant difference in vascularization in the joints of all subgroups of RA patients and those of healthy subjects (P < 0.001). Moreover, vascularization differed significantly among the RA subgroups: inactive versus moderately active RA (P < 0.02) and inactive versus active RA (P < 0.05). Both pannus and vascularization appeared to be localized preferentially on the radial side of the joints. CONCLUSION: Evaluation of pannus and the extent of vascularization within the joints of patients with RA by high-resolution US might be helpful in the assessment of disease activity, and thus influence therapeutic strategies.