Rheumatoid Arthritis: Matteson EL

Dechant SA, Matteson EL. · No affiliation provided · Curr Opin Rheumatol. · Pubmed #15103241 No free full text.

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Matteson EL. · No affiliation provided · Arthritis Rheum. · Pubmed #12847668 links to  free full text

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Turesson C, Matteson EL. · Department of Rheumatology, Malmo University Hospital, Malmo, Sweden. · Curr Opin Rheumatol. · Pubmed #19077716 No free full text.

Abstract: PURPOSE OF REVIEW: To examine the occurrence and pathophysiology of vasculitis in rheumatoid arthritis (RA), describe the epidemiology and clinical features, and provide a therapeutic perspective. RECENT FINDINGS: With improved control of RA over the past two decades, the risk of severe outcomes such as vasculitis may be decreasing. Rheumatoid vasculitis continues to be associated with longstanding, erosive, seropositive disease, and it has recently been shown to be more frequent among patients with antibodies to cyclic citrullinated peptides. Apart from circulating immune complexes, expansion of cytotoxic CD28null T cells and circulating proinflammatory cytokines also play a role in the pathogenesis. The role of agents directed against the tumor necrosis factor (TNF) in the occurrence and management of rheumatoid vasculitis remains unclear, as rheumatoid vasculitis may be both associated with and treated with anti-TNF agents, once it has appeared. SUMMARY: Vasculitis in RA is generally associated with longstanding disease, has an important impact on a patient's well being, and markedly influences patient life expectancy. Advances in therapies for RA will likely continue to reduce the incidence of vasculitis, and improved management of cardiovascular comorbidity in patients with RA will be of particular benefit to those who suffer from vasculitis and other extraarticular manifestations.

Bongartz T, Warren FC, Mines D, Matteson EL, Abrams KR, Sutton AJ. · Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN, USA. · Ann Rheum Dis. · Pubmed #19019889 No free full text.

Abstract: PURPOSE: Tumour necrosis factor (TNF) plays an important role in inflammation and may affect tumour growth control. To assess the risk of malignancy with etanercept, a fusion protein that inhibits TNF action, a meta-analysis was performed using individual patient data from randomised controlled trials (RCT) in patients with rheumatoid arthritis (RA). METHODS: A search was conducted of bibliographic databases, abstracts from annual meetings and any unpublished studies on file with manufacturers of etanercept to December 2006. Only RCT of etanercept used for 12 weeks or more in patients with RA were included. Nine trials met the inclusion criteria. To adjudicate endpoints, the case narratives of potential cases were reviewed. Patient-level data were extracted from the clinical trials databases. RESULTS: The nine trials included 3316 patients, 2244 who received etanercept (contributing 2484 person-years of follow-up) and 1072 who received control therapy (1051 person-years). Malignancies were diagnosed in 26 patients in the etanercept group (incidence rate (IR) 10.47/1000 person-years) and seven patients in the control group (IR 6.66/1000 person-years). A Cox's proportional hazards, fixed-effect model stratified by trial yielded a hazard ratio of 1.84 (95% CI 0.79 to 4.28) for the etanercept group compared with the control group. CONCLUSIONS: In this analysis, the point estimate of malignancy risk was higher in etanercept-treated patients, although the results were not statistically significant. The approach of obtaining individual patient data of RCT in cooperation with trial sponsors allowed important insights into the methodological advantages and challenges of sparse adverse event data meta-analysis.

Turesson C, Jacobsson LT, Matteson EL. · Department of Rheumatology, Malmö University Hospital, Malmö, Sweden. · Vasc Health Risk Manag. · Pubmed #18827910 links to  free full text

Abstract: Patients with rheumatic disorders have an increased risk of cardiovascular disease (CVD). This excess co-morbidity is not fully explained by traditional risk factors. Disease severity is a major risk factor for CVD in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Shared disease mechanisms in atherosclerosis and rheumatic disorders include immune dysregulation and inflammatory pathways, which are potential targets for therapy. Lessons from RA and SLE may have implications for future research on the pathogenesis of atherosclerotic vascular disease in general. Recent data indicate that suppression of inflammation reduces the risk of CVD morbidity and mortality in patients with severe RA. The modest, but clinically relevant, efficacy of atorvastatin treatment in RA adds to the evidence for important anti-inflammatory properties for statins. There is increased recognition of the need for structured preventive strategies to reduce the risk of CVD in patients with rheumatic disease. Such strategies should be based on insights into the role of inflammation in CVD, as well as optimal management of life style related risk factors. In this review, the research agenda for understanding and preventing CVD co-morbidity in patients with rheumatic disorders is discussed.

Nannini C, Ryu JH, Matteson EL. · Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. · Curr Opin Rheumatol. · Pubmed #18388528 No free full text.

Abstract: PURPOSE OF REVIEW: To examine the role of lung disease in rheumatoid arthritis from a clinical, epidemiologic, pathophysiologic, and therapeutic perspective. RECENT FINDINGS: Lung disease in rheumatoid arthritis is pleomorphic and has a marked adverse impact on the morbidity and premature mortality of patients with this disease. Recent advances in the understanding of the pathophysiology of lung disease associated with rheumatoid arthritis reveal it to be characterized by more active cellular infiltrates of both T cells and B cells, as well as other immunologically active cells, including mast cells, than many of the other forms of interstitial lung disease. Satisfactory treatment is lacking; available biologic response modifiers have been reported to have both beneficial and adverse effects on the lung. Newer approaches targeting cellular immunologic dysfunction including T-cell-directed and B-cell-directed therapies hold the promise of reducing lung damage related to the underlying disease. SUMMARY: Lung disease in rheumatoid arthritis is a heterogeneous and oftentimes serious condition, with a profound impact on patient wellbeing and survival. Advances in the understanding of its etiology and targeted application of available, as well as development of new, more specific therapeutics will be of benefit to patients with rheumatoid arthritis who are suffering from lung disease.

Martinez JB, Valero JS, Bautista AJ, Restrepo JF, Matteson EL, Rondon F, Iglesias-Gamarra A. · Internal Medicine and Rheumatology, National University of Colombia, Bogota, Colombia. · Clin Exp Rheumatol. · Pubmed #17417990 No free full text.

Abstract: OBJECTIVE: To describe the occurrence of erosive arthropathy in systemic lupus erythematosus (SLE) and its relationship to anti-CCP antibodies. METHODS: Retrospective medical record review of a case series of five female patients with SLE and erosive arthropathies. RESULTS: The initial disease presentation in all patients was a polyarthritis. Anti-CCP antibodies were detected in 4 out of 5 (80%) patients, 2 of whom had a positive rheumatoid factor. CONCLUSION: Erosive arthritis was strongly associated with the presence of anti-CCP antibodies in these patients with SLE, who presented with polyarthritis. Anti-CCP in patients with SLE may be a marker of a more severe joint disease.

Turesson C, Matteson EL. · Department of Rheumatology, Malmö University Hospital, Malmö, Sweden. · Curr Opin Rheumatol. · Pubmed #17278937 No free full text.

Abstract: PURPOSE OF REVIEW: There is increased recognition of an excess risk of cardiovascular disease in patients with rheumatic disorders. Physical inactivity is a frequent complication of arthritis, and also common in the general population. In this review, we highlight recent findings on risk factors for cardiovascular disease in patients with rheumatic diseases, and explore the role of physical activity for the prevention of cardiovascular disease. RECENT FINDINGS: Inflammatory mechanisms are clearly involved in cardiovascular disease in patients with systemic lupus erythematosus and rheumatoid arthritis. In rheumatoid arthritis, disability is also a major predictor of cardiovascular disease. A sedentary lifestyle increases the risk of cardiovascular disease in the general population, and high physical activity prevents cardiovascular disease mortality and morbidity. Successful treatment of rheumatic disease with control of inflammation and improved functional capacity may also reduce the risk of cardiovascular disease. SUMMARY: As part of the effort to prevent vascular comorbidity, regular exercise should be encouraged in patients with rheumatic diseases, and structured interventions to reduce adverse lifestyle factors scientifically evaluated.

Cantaert T, De Rycke L, Bongartz T, Matteson EL, Tak PP, Nicholas AP, Baeten D. · University of Amsterdam, Amsterdam, The Netherlands. · Arthritis Rheum. · Pubmed #17075816 links to  free full text

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Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. · Division of Rheumatology and Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA. · JAMA. · Pubmed #16705109 links to  free full text

Abstract: CONTEXT: Tumor necrosis factor (TNF) plays an important role in host defense and tumor growth control. Therefore, anti-TNF antibody therapies may increase the risk of serious infections and malignancies. OBJECTIVE: To assess the extent to which anti-TNF antibody therapies may increase the risk of serious infections and malignancies in patients with rheumatoid arthritis by performing a meta-analysis to derive estimates of sparse harmful events occurring in randomized trials of anti-TNF therapy. DATA SOURCES: A systematic literature search of EMBASE, MEDLINE, Cochrane Library, and electronic abstract databases of the annual scientific meetings of both the European League Against Rheumatism and the American College of Rheumatology was conducted through December 2005. This search was complemented with interviews of the manufacturers of the 2 licensed anti-TNF antibodies. STUDY SELECTION: We included randomized, placebo-controlled trials of the 2 licensed anti-TNF antibodies (infliximab and adalimumab) used for 12 weeks or more in patients with rheumatoid arthritis. Nine trials met our inclusion criteria, including 3493 patients who received anti-TNF antibody treatment and 1512 patients who received placebo. DATA EXTRACTION: Data on study characteristics to assess study quality and intention-to-treat data for serious infections and malignancies were abstracted. Published information from the trials was supplemented by direct contact between principal investigators and industry sponsors. DATA SYNTHESIS: We calculated a pooled odds ratio (Mantel-Haenszel methods with a continuity correction designed for sparse data) for malignancies and serious infections (infection that requires antimicrobial therapy and/or hospitalization) in anti-TNF-treated patients vs placebo patients. We estimated effects for high and low doses separately. The pooled odds ratio for malignancy was 3.3 (95% confidence interval [CI], 1.2-9.1) and for serious infection was 2.0 (95% CI, 1.3-3.1). Malignancies were significantly more common in patients treated with higher doses compared with patients who received lower doses of anti-TNF antibodies. For patients treated with anti-TNF antibodies in the included trials, the number needed to harm was 154 (95% CI, 91-500) for 1 additional malignancy within a treatment period of 6 to 12 months. For serious infections, the number needed to harm was 59 (95% CI, 39-125) within a treatment period of 3 to 12 months. CONCLUSIONS: There is evidence of an increased risk of serious infections and a dose-dependent increased risk of malignancies in patients with rheumatoid arthritis treated with anti-TNF antibody therapy. The formal meta-analysis with pooled sparse adverse events data from randomized controlled trials serves as a tool to assess harmful drug effects.

Turesson C, Matteson EL. · Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA. · Mayo Clin Proc. · Pubmed #16438485 links to  free full text

Abstract: Rheumatoid arthritis (RA) is a heterogeneous autoimmune disorder of unknown cause with variable clinical expression. About 70% of patients are women. Genetic factors play an important role and likely account for about 60% of disease susceptibility and expression. The association with the HLA-DRB1 gene is the best understood, although several non-HLA loci have been linked to RA, including the 18q21 region of the TNFRSR11A gene, which encodes the receptor activator of nuclear factor kappaB, important in bone resorption in RA. Genetic factors are also important in the treatment of RA because the activity of enzymes relevant in the metabolism of drugs such as methotrexate and azathioprine, including methylenetetrahydrofolate reductase and thiopurine methyltransferase, are in part genetically determined.

Turesson C, Weyand CM, Matteson EL. · Mayo Clinic College of Medicine, Rochester, Minnesota, USA. · Arthritis Rheum. · Pubmed #15478157 links to  free full text

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Turesson C, Matteson EL. · Division of Rheumatology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. · Curr Opin Rheumatol. · Pubmed #15103246 No free full text.

Abstract: PURPOSE OF REVIEW: To discuss the rationale for various treatment strategies in rheumatoid arthritis with extra-articular manifestations, and to review advances in understanding the impact of extra-articular rheumatoid arthritis and its management. RECENT FINDINGS: Recent epidemiologic studies of extra-articular rheumatoid arthritis manifestations have emphasized their major role as predictors of premature mortality in patients with rheumatoid arthritis, and provide a rationale for aggressive ant-rheumatic treatment of extra-articular rheumatoid arthritis. Previous uncontrolled or nonrandomized studies favor the use of cyclophosphamide in patients with systemic rheumatoid vasculitis, and methotrexate in the case of other manifestations of extra-articular rheumatoid arthritis. Recent case reports indicate that patients with rheumatoid lung disease may respond to cyclosporine or tumor necrosis factor inhibitors, and that tumor necrosis factor blocking therapy also may be successful in cases of treatment-resistant vasculitis. By contrast, it has been suggested that tumor necrosis factor inhibitors may induce some manifestations of extra-articular rheumatoid arthritis. Data indicating a high risk of serious infections and cardiovascular disease in patients with extra-articular rheumatoid arthritis underline the importance of carefully monitoring such patients. SUMMARY: Extra-articular rheumatoid arthritis is a serious condition, and rheumatoid arthritis patients with extra-articular manifestations should be aggressively treated and monitored. Advances in the understanding of the pathogenesis of rheumatoid arthritis and developments of new, more specific drugs may be of particular benefit to patients with extra-articular disease.

Matteson EL. · Division of Rheumatology and Internal Medicine, Mayo Clinic Rochester, Minn 55905, USA. · Mayo Clin Proc. · Pubmed #10630759 No free full text.

Abstract: The management of rheumatoid arthritis has changed considerably during the past 15 years. Current strategies emphasize the need for early diagnosis and therapeutic intervention based on the use of disease-modifying antirheumatic drugs. The advent of agents that are more tailored to inhibit the specific disease processes will profoundly affect management. Immunogenetic studies may eventually assist in identifying subgroups of patients with rheumatoid arthritis who have more aggressive disease and who require a more aggressive treatment approach.

Xia W, Hilgenbrink AR, Matteson EL, Lockwood MB, Cheng JX, Low PS. · Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA. · Blood. · Pubmed #18952896 No free full text.

Abstract: Previous work has demonstrated that a subset of macrophages expresses a folate receptor (FR) that can mediate internalization of folate-linked molecules, including imaging and therapeutic agents. To characterize this subset, macrophages were collected from peritoneal cavities of mice injected with saline, thioglycolate, zymosan, heat-killed or live bacteria, and cell-surface markers that coexpress with FR were identified. Virtually no F4/80(+) peritoneal macrophages from saline-injected mice expressed FR, whereas numerous macrophages from mice injected with each inflammatory stimulus expressed FR. Examination of cell differentiation antigens that are up-regulated in FR(+) macrophages revealed markers characteristic of an activated state (CD80, CD86, Ly-6C/G), whereas macrophages lacking these activation markers expressed few or no FR. FR(+) macrophages also produced tumor necrosis factor-alpha (TNF-alpha) and reactive oxygen species, and production of reactive oxygen species correlated linearly with expression of FR. Synovial macrophages collected from arthritic patients were found to bind and internalize folate-linked dyes. Moreover, a folate-linked radioimaging agent was shown to image inflamed joints of rheumatoid arthritic patients. These results suggest that FR constitutes a marker for macrophage activation and that FR(+) macrophages can be targeted with folate-linked drugs without promoting drug uptake by nonactivated macrophages. This trial was registered at www.clinicaltrials.gov as #NCT00588393.

Bryl E, Vallejo AN, Matteson EL, Witkowski JM, Weyand CM, Goronzy JJ. · Mayo Clinic College of Medicine, Rochester, Minnesota, USA. · Arthritis Rheum. · Pubmed #16200579 links to  free full text

Abstract: OBJECTIVE: The immune system of patients with rheumatoid arthritis (RA) is characterized by the accumulation of CD4+ T cells deficient in CD28 expression and the up-regulation of tumor necrosis factor alpha (TNFalpha). Previous in vitro studies have shown that TNFalpha induces transcriptional silencing of the CD28 gene. Because reduced expression of CD28 in T cells compromises immunocompetence, we examined whether CD28 expression is reduced in patients with RA in vivo and whether the reduction is related to TNFalpha. METHODS: Patients with RA and age-matched individuals were recruited. Peripheral blood mononuclear cells were stained for CD3, CD4, CD8, CD28, TNF receptor I (TNFRI), and TNFRII, and analyzed by quantitative flow cytometry. The number of CD28 and TNFR molecules was monitored in a subgroup of patients with RA undergoing treatment with anti-TNFalpha. RESULTS: In addition to higher frequencies of CD28null T cells, patients with RA had significantly reduced numbers of CD28 and TNFRI molecules on CD4+,CD28+ T cells. Normal expression could be restored in vitro by overnight culture, suggesting that CD28 in patients was modulated by exogenous factors. In contrast, treatment with TNFalpha in vitro resulted in further down-regulation. CD28 expression was normalized in patients undergoing TNFalpha-neutralizing therapy. CONCLUSION: Overproduction of TNFalpha in RA induces a global down-regulation of CD28 in CD4+ T cells and may cause reduced sensitivity to costimulatory signals in T cell responses.

Matteson EL, Weyand CM, Fulbright JW, Christianson TJ, McClelland RL, Goronzy JJ. · Division of Rheumatology, Mayo Clinic and Mayo Graduate School of Medicine, Rochester, MN 55905, USA. · Rheumatology (Oxford). · Pubmed #14983105 links to  free full text

Abstract: OBJECTIVE: To determine what baseline factors might be associated with response to an initial mild treatment regimen in patients with early rheumatoid arthritis (RA). METHODS: Open label 2-yr study of 111 consecutive patients with early RA of duration less than 1 yr. None of the patients had previously received disease-modifying anti-rheumatic drugs (DMARDs). All patients were assigned to receive hydroxychloroquine (HCQ) at enrollment, and could also take non-steroidal anti-inflammatory drugs (NSAIDs) and prednisone. At any point during follow-up, patients not fulfilling the American College of Rheumatology (ACR) 50 criteria for improvement and/or who were taking prednisone > 10 mg/day were considered treatment failures and therapy changed to methotrexate (MTX), 7.5-20 mg/week. Clinical, laboratory and immunogenetic factors potentially predictive of treatment assignment at month 24 were evaluated. RESULTS: After 24 months of follow-up, a majority of patients (56/94) were either still on solo DMARD therapy with HCQ (n = 49) or off DMARD therapy with controlled/quiescent disease (n = 4), and 38 patients were taking MTX (including 11 in combination with other DMARDs). At month 24, all but 9 patients met ACR50 criteria for treatment response. Features present at enrollment which were predictors of MTX therapy at month 24 were high pain score, baseline rheumatoid factor titre > 1:40, higher number of swollen joints, and poor patient global assessment. The presence of HLA-C7xx at enrollment was also predictive of need for MTX therapy. CONCLUSIONS: This study suggests that even milder treatment with HCQ is greatly beneficial in patients with early RA. There continue to be very few consistently reliable predictors of treatment needs in patients with this disease.

Bunch TW, Erlichman C, Luthra HS, Matteson EL. · No affiliation provided · J Rheumatol. · Pubmed #12022338 links to  free full text

This publication has no abstract.

Felson DT, LaValley MP, Baldassare AR, Block JA, Caldwell JR, Cannon GW, Deal C, Evans S, Fleischmann R, Gendreau RM, Harris ER, Matteson EL, Roth SH, Schumacher HR, Weisman MH, Furst DE. · Boston University School of Medicine, Massachusetts, USA. · Arthritis Rheum. · Pubmed #10524687 links to  free full text

Abstract: OBJECTIVE: To evaluate the efficacy and safety of the Prosorba column as a treatment for rheumatoid arthritis (RA) in patients with active and treatment-resistant (refractory) disease. METHODS: A sham-controlled, randomized, double-blind, multicenter trial of Prosorba versus sham apheresis was performed in patients with RA who had failed to respond to treatment with methotrexate or at least 2 other second-line drugs. Patients received 12 weekly treatments with Prosorba or sham apheresis, with efficacy evaluated 7-8 weeks after treatment ended. Patients were characterized as responders if they experienced improvement according to the American College of Rheumatology (ACR) response criteria at the efficacy time point. A data safety monitoring board (DSMB) evaluated interim analyses for the possibility of early completion of the trial. RESULTS: Patients in the trial had RA for an average of 15.5 years (range 1.7-50.6) and had failed an average of 4.2 second-line drug treatments prior to entry. After the completion of treatment of 91 randomized patients, the DSMB stopped the trial early due to successful outcomes. Of the 47 patients in the Prosorba arm, 31.9% experienced ACR-defined improvement versus 11.4% of the 44 patients in the sham-treated arm (P = 0.019 after adjustment for interim analysis). When results from 8 additional patients, who had completed blinded treatments at the time of DSMB action, were added to the analysis (n = 99), results were unchanged. The most common adverse events were a short-term flare in joint pain and swelling following treatment, a side effect that occurred in most subjects at least once in both treatment arms. Other side effects, although common, occurred equally as frequently in both treatment groups. CONCLUSION: Apheresis with the Prosorba column is an efficacious treatment for RA in patients with active disease who have failed other treatments.

Smolen JS, Kay J, Doyle MK, Landewé R, Matteson EL, Wollenhaupt J, Gaylis N, Murphy FT, Neal JS, Zhou Y, Visvanathan S, Hsia EC, Rahman MU, Anonymous00042. · Medical University of Vienna and Hietzing Hospital, Division of Rheumatology, Department of Internal Medicine III, Vienna, Austria. · Lancet. · Pubmed #19560810 No free full text.

Abstract: BACKGROUND: Tumour necrosis factor alpha (TNFalpha) inhibitors are frequently used to treat rheumatoid arthritis, but whether use of a different TNFalpha inhibitor can improve patient response is unknown. We assess the efficacy and safety of the TNFalpha inhibitor golimumab in patients with active rheumatoid arthritis who had previously received one or more TNFalpha inhibitors. METHODS: 461 patients with active rheumatoid arthritis from 82 sites in 10 countries were randomly allocated by interactive voice response system, stratified by study site and methotrexate use, to receive subcutaneous injections of placebo (n=155), 50 mg golimumab (n=153), or 100 mg golimumab (n=153) every 4 weeks between Feb 21, 2006, and Sept 26, 2007. Allocation was double-blind. Eligible patients had been treated with at least one dose of a TNFalpha inhibitor previously. Patients continued stable doses of methotrexate, sulfasalazine, hydroxychloroquine, oral corticosteroids, and non-steroidal anti-inflammatory drugs. The primary endpoint was achievement at week 14 of 20% or higher improvement in American College of Rheumatology criteria for assessment of rheumatoid arthritis (ACR20). At week 16, patients who had less than 20% improvement in tender and swollen joint counts were given rescue therapy and changed treatment from placebo to 50 mg golimumab, or from 50 mg to 100 mg golimumab. Drug efficacy was assessed by intention to treat and safety was assessed according to the study drug given. This study is registered with ClinicalTrials.gov, number NCT00299546. FINDINGS: Patients had discontinued previous TNFalpha inhibitors because of lack of effectiveness (269 [58%] patients) or reasons unrelated to effectiveness (246 [53%] patients), such as intolerance and accessibility issues. Patients had active disease, which was indicated by a median of 14.0 (IQR 9.0-22.0) swollen and 26.0 (16.0-41.0) tender joints for the whole group. 28 (18%) patients on placebo, 54 (35%) patients on 50 mg golimumab (odds ratio 2.5 [95% CI 1.5-4.2], p=0.0006), and 58 (38%) patients on 100 mg golimumab (2.8 [1.6-4.7], p=0.0001) achieved ACR20 at week 14. Two patients were never treated, and 57 patients did not complete the study because of adverse events, unsatisfactory treatment effect, loss to follow-up, death, or other reasons. 155 patients on placebo, 153 on 50 mg golimumab, and 153 on 100 mg golimumab were assessed for drug efficacy. For weeks 1-16, serious adverse events were recorded in 11 (7%) patients on placebo, 8 (5%) on 50 mg golimumab, and 4 (3%) on 100 mg golimumab. For weeks 1-24, after some patients were given rescue therapy, serious adverse events were recorded in 15 (10%) patients on placebo, 14 (5%) on 50 mg golimumab, and 8 (4%) on 100 mg golimumab. INTERPRETATION: Golimumab reduced the signs and symptoms of rheumatoid arthritis in patients with active disease who had previously received one or more TNFalpha inhibitors. FUNDING: Centocor Research and Development and Schering-Plough Research Institute.

Visvanathan S, Wagner C, Rojas J, Kay J, Dasgupta B, Matteson EL, Mack M, Baker DG, Rahman MU. · Centocor Research and Development, Inc., Malvern, Pennsylvania, USA. · J Rheumatol. · Pubmed #19487269 No free full text.

Abstract: OBJECTIVE: To assess the effect of golimumab (human monoclonal antibody to tumor necrosis factor-alpha) plus methotrexate (MTX) on selected inflammatory biomarkers, and to determine if these effects predict clinical response in rheumatoid arthritis (RA). METHODS: Sera from adults with active RA despite MTX therapy, who received subcutaneous injections of placebo + MTX (MTX alone, n = 34) or golimumab 50 or 100 mg every 2 or 4 weeks + MTX (n = 137), were analyzed for levels of C-reactive protein (CRP), serum amyloid A (SAA), interleukin 18 (IL-18), E-selectin, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1). RESULTS: Golimumab + MTX treatment significantly decreased serum CRP, SAA, IL-18, E-selectin, TIMP-1, and MMP-9 levels (median percent changes of -4.1% to -74.3% across treatment groups) versus MTX alone (-5.8% to 9.7%) when first measured at Week 4; decreases were sustained through Week 16. Larger magnitudes of decrease in all biomarkers were observed for clinical responders versus nonresponders. For golimumab + MTX, regression analyses including all biomarkers and select clinical measures showed that reductions in levels of several markers (SAA, E-selectin, MMP-9) as early as Week 4 correlated significantly with improvement in swollen joint count (SJC) at Week 16, as did reductions in E-selectin with improvement in tender joint count at Week 16. After accounting for the biomarkers, however, treatment group was no longer significant for SJC. CONCLUSION: Significant decreases in several inflammatory biomarkers were associated with golimumab + MTX therapy. Decreases in serum levels of SAA, E-selectin, and MMP-9 at Week 4 may be useful in predicting clinical response at Week 16.

Matteson EL, Lowe VJ, Prendergast FG, Crowson CS, Moder KG, Morgenstern DE, Messmann RA, Low PS. · Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. · Clin Exp Rheumatol. · Pubmed #19473565 No free full text.

Abstract: OBJECTIVES: Development of a simple and accurate technique for detecting active inflammation in the joints and other tissues of patients with inflammatory disorders is an unmet need in rheumatic diseases. This study is a preliminary assessment of the safety and usage of a radiopharmaceutical, FolateScan (Technetium-99m EC20; 99mTc-EC20), for detecting disease activity in patients with rheumatoid arthritis. METHODS: EC20 is a folate-targeted diagnostic radiopharmaceutical which binds to the folate receptor and is preferentially taken up by activated macrophages. In this open-label, cross-sectional study, a total of 40 patients with RA (26 with one or more swollen joints, 14 with clinically quiescent joint disease; 0/66 joint count) as well as 6 patients with osteoarthritis, 12 patients with other inflammatory conditions and 5 healthy subjects received 0.1 mg of EC20 labeled with 20-25mCi of technetium-99m. Disease activity was scored in each joint and other target tissues by a radiologist blinded to the clinical assessment, and results were compared to the rheumatologist's physical examination, which served as the test standard. RESULTS: The 40 patients (78% female) with RA had a mean age of 56.9 years. Assessment of uptake of 99mTc-EC20 in joints of patients with RA based on image analysis was compared to the clinical examination. FolateScan detected more actively involved joints in 27 patients (68%) than joints recorded as "swollen", and more actively involved joints in 25 patients (63%) than joints recorded as "painful and/or swollen". The number of swollen joints by clinical exam was correlated with ESR (r=0.43; p=0.006) and C-rp (r=0.35; p=0.03). The number of actively involved joints by FolateScan was also correlated with ESR (r=0.47; p=0.002) and C-rp (r=0.36; p=0.02). Joint uptake was also seen in patients with osteoarthritis. CONCLUSION: FolateScan is a potentially useful tool for detection of disease activity in patients with RA and may be more sensitive than the physical examination.

Itty S, Pulido JS, Bakri SJ, Baratz KH, Matteson EL, Hodge DO. · Mayo Medical School, Mayo Clinic, Rochester, Minnesota, USA. · Trans Am Ophthalmol Soc. · Pubmed #19277223 links to  free full text

Abstract: PURPOSE: To correlate the presence of anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF) with ocular symptoms typical of rheumatoid arthritis (RA). METHODS: The records of 451 patients who had been examined by an ophthalmologist and tested for anti-CCP antibodies over a 3-year period at the Mayo Clinic were reviewed. Records of 255 patients with titers of anti-CCP and RF were analyzed for ocular surface and inflammatory disease associated with ocular RA. RESULTS: Of the 33 anti-CCP+/RF+ patients, all were diagnosed with RA; ocular surface disease was present in 11 (33%) and inflammatory disease in 7 (21%). Of the 17 anti-CCP-/RF+ patients, 4 were diagnosed with an unspecified inflammatory arthritis and 1 with rheumatoid arthritis; a separate 5 (29%) had ocular surface disease. Out of 5 anti-CCP+/RF- patients, 3 were diagnosed with RA but none had ocular symptoms. Out of 200 anti-CCP-/RF- patients, 32 (16%) had ocular surface disease and 2 (1%) had ocular inflammation. Of the 74 patients diagnosed with any form of inflammatory arthritis, anti-CCP+/RF+ patients had more and worse inflammatory ocular RA disease compared to the other groups. CONCLUSIONS: Patients who were both anti-CCP and RF positive tended to have more and worse ocular disease. In patients diagnosed with an inflammatory arthritis, the presence of anti-CCP antibodies and RF provides useful information to ophthalmologists for identifying patients most at risk for inflammatory ocular disease.

Bongartz T, Halligan CS, Osmon DR, Reinalda MS, Bamlet WR, Crowson CS, Hanssen AD, Matteson EL. · Mayo Clinic College of Medicine, Division of Rheumatology, Rochester, Minnesota 55905, USA. · Arthritis Rheum. · Pubmed #19035425 No free full text.

Abstract: OBJECTIVE: Prosthetic joint infection is one of the most dreaded complications after total joint arthroplasty, a common procedure in patients with rheumatoid arthritis (RA). We conducted a study to evaluate potential risk factors of prosthetic joint infection and to clarify if RA is an independent predictor of this complication. METHODS: This study included all patients with RA who underwent total hip or knee replacement at the Mayo Clinic Rochester between January 1996 and June 2004. The association of potential risk factors with prosthetic joint infection was examined using Cox models. A matched cohort of patients with osteoarthritis (OA) was assembled to determine whether RA is an independent risk factor for prosthetic joint infection. RESULTS: We identified 462 patients with RA who underwent a total of 657 hip or knee replacements. Overall, 23 (3.7%) joint arthroplasties were complicated by an infection during a mean +/- SD followup of 4.3 +/- 2.4 years. Revision arthroplasty (hazard ratio [HR] 2.99, 95% confidence interval [95% CI] 1.02-8.75) and a previous prosthetic joint infection of the replaced joint (HR 5.49, 95% CI 1.87-16.14) were significant predictors of postoperative prosthetic joint infection. Comparison of RA patients with a matched cohort of OA patients identified an increased risk of prosthetic joint infections (HR 4.08, 95% CI 1.35-12.33) in patients with RA. CONCLUSION: Patients with RA who undergo total hip or knee replacement are at increased risk of prosthetic joint infection, which is further increased in the setting of revision arthroplasty and a previous prosthetic joint infection. These findings highlight the importance of perioperative prophylactic measures and vigilance during the postoperative period.

Icen M, Nicola PJ, Maradit-Kremers H, Crowson CS, Therneau TM, Matteson EL, Gabriel SE. · Department of Health Sciences Research, Mayo Foundation, 200 First St. SW, Rochester, MN 55905, USA. · J Rheumatol. · Pubmed #19004043 No free full text.

Abstract: OBJECTIVE: Features of systemic lupus erythematosus (SLE) are commonly observed in patients with rheumatoid arthritis (RA). However, their frequency and clinical significance are uncertain. We examined the frequency of SLE features in RA and their effect on overall mortality. METHODS: We assembled a population-based incidence cohort of subjects aged >or=18 years first diagnosed with RA [1987 American College of Rheumatology (ACR) criteria] between 1955 and 1995. Information regarding disease characteristics, therapy, comorbidities, and SLE features (1982 ACR criteria) were collected from the complete inpatient and outpatient medical records. Cox regression models were used to estimate the mortality risk associated with lupus features. RESULTS: The study population comprised 603 subjects with incident RA (mean age 58 yrs, 73% women) with a mean followup time of 15 years. By 25 years after RA incidence, >or=4 SLE features were observed in 15.5% of the subjects with RA. After adjustment for age and sex, occurrence of >or=4 SLE features was associated with increased overall mortality [hazard ratio (HR) 5.54, 95% confidence interval (CI) 3.59-8.53].With further adjustment for RA characteristics, therapy, and comorbidities, the association weakened but remained statistically significant (HR 2.56, 95% CI 1.60-4.08). After adjustment for age, sex, RA characteristics, therapy, and comorbidities, thrombocytopenia (2.0, 95% CI 1.2, 3.1) and proteinuria (1.8, 95% CI 1.3, 2.6) were significantly associated with mortality. CONCLUSION: SLE features were common in RA, given sufficient observation time. Subjects with RA who developed >or=4 SLE features had an increased risk of death. Proteinuria and thrombocytopenia were individually associated with an increased mortality risk.