Rheumatoid Arthritis: Hørslev-Petersen K

Andresen PN, Hansen G, Hørslev-Petersen K. · Kong Christian X's Gigthospital, Gråsten. · Ugeskr Laeger. · Pubmed #11043056 No free full text.

Abstract: In 1999, leflunomide was introduced for the treatment of active rheumatoid arthritis. Leflunomide is a reversible inhibitor of "de novo" synthesis of pyrimidine, resulting in a restriction of lymphocyte proliferation. The pharmacodynamics are characterized by slow elimination. Leflunomide has shown an efficacy and a pattern of mild and serious side effects similar to methotrexate and sulphasalazine. Treatment is started with a loading dose of 100 mg orally for three days followed by 20 (10) mg daily. Regular haematological measurements, determination of serum chemistry and blood pressure should be performed every second week the first six months, subsequently every sixth week. If the treatment is to be terminated abruptly, a drug elimination procedure must be performed. Leflunomide will find its place in the treatment of rheumatoid arthritis. Leflunomide should follow an unsuccessful treatment attempt with methotrexate or sulphasalazine.

Christensen AF, Lottenburger T, Lindegaard H, Christgau S, Hørslev-Petersen K, Junker P. · Departments of Rheumatology, Odense University Hospital, Odense and Institute of Clinical Research, University of Southern Denmark, Denmark. · Clin Exp Rheumatol. · Pubmed #19473573 No free full text.

Abstract: OBJECTIVES: To determine the N-terminal propeptide of collagen IIA (PIIANP) in early and established rheumatoid arthritis (RA) and to study the association with collagen II degradation assessed by its C-telopeptide (CTX-II), x-ray status and disease activity measures. METHODS: Two cohorts of RA patients were included: A) a one-year prospective cohort including 45 patients with early, untreated RA and B) a cross-sectional study comprising 50 RA patients with advanced disease. Blood donors and healthy volunteers served as controls. PIIANP in serum and urine CTX-II were measured by ELISA. RESULTS: PIIANP did not differ from control levels at any time in patients with early RA (p=0.16 and p=0.89), but at one-year follow-up, PIIANP was decreased compared with baseline (p=0.046). In patients with longstanding RA, PIIANP was lower than in controls (p=0.002) and RA patients with a 12-month disease (p=0.01). PIIANP was unrelated to joint counts and CRP in both cohorts, but baseline PIIANP was lower among x-ray progressors than in non-progressors (p=0.04). CTX-II was persistently increased in both cohorts (p<0.001 and p<0.001). CTX-II was positively associated with joint counts and CRP but not with x-ray progression (p=0.84). There was no correlation between PIIANP and CTX-II. CONCLUSION: Declining PIIANP with increasing RA duration and persistently increased CTX-II indicate that cartilage anabolic and degradative pathways are unbalanced from clinical RA onset. Furthermore, that collagen II depletion in RA is both mediated by anti-anabolic effects unassociated with synovitis (decreased PIIANP) and by excess collagen II degradation linked to synovitis (increased CTX-II).

Jacobsen S, Garred P, Madsen HO, Heegaard NH, Hetland ML, Stengaard-Pedersen K, Junker P, Lottenburger T, Ellingsen T, Smedegaard Andersen L, Hansen I, Skjødt H, Pedersen JK, Lauridsen UB, Svendsen AJ, Tarp U, Pødenphant J, Lindegaard H, Vestergaard A, Østergaard M, Hørslev-Petersen K. · Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. · J Rheumatol. · Pubmed #19273450 No free full text.

Abstract: OBJECTIVE: To study the association between polymorphisms in the mannose-binding lectin gene (MBL2) and disease activity, physical disability, and joint erosions in patients with newly diagnosed rheumatoid arthritis (RA). METHODS: Patients with early RA (n=158) not previously treated with disease modifying antirheumatic drugs, participating in a treatment trial (CIMESTRA study) were examined at inclusion for MBL2 pooled structural genotypes (O/O, A/O, A/A), regulatory MBL2 promoter polymorphism in position -221 (XX, XY, YY), anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), disease activity by Disease Activity Score-28 (DAS28 score), physical disability by Health Assessment Questionnaire (HAQ) score, and erosive changes in hands and feet (Sharp-van der Heijde score). RESULTS: Eight patients were homozygous MBL2 defective (O/O), 101 belonged to an intermediate group, and 49 were MBL2 high producers (YA/YA). Anti-CCP was present in 93 patients (59%). High scores of disease activity, C-reactive protein-based DAS28 (p=0.02), and physical disability by HAQ (p=0.01) were associated with high MBL2 expression genotypes in a gene-dose dependent way, but only in anti-CCP-positive patients. At this early stage of the disease there was no association with erosion score from radiographs. CONCLUSION: The results point to a synovitis-enhancing effect of MBL in anti-CCP-positive RA, whereas such an effect was not demonstrated for joint erosions.

Pedersen JK, Svendsen AJ, Hørslev-Petersen K. · Research Unit, King Christian X Hospital for Rheumatic Diseases, Graasten, Denmark. · Open Rheumatol J. · Pubmed #19088896 links to  free full text

Abstract: We estimated the incidence of rheumatoid arthritis in the southern part of Denmark from 1995 to 2001. At a rheumatology hospital serving a population of about 200 000 people over the age of 15, medical records were scrutinized. As case definition we used the tree and list format of 1987 American College of Rheumatology criteria for rheumatoid arthritis. The mean annual incidence rate per 100 000 person years was 40 in females, 21 in males, and 31 in females and males combined. The incidence of rheumatoid arthritis in Denmark is in accordance with recent studies from North America, the UK, and Northern European countries. The aetiology of rheumatoid arthritis is unknown but this study indicates that in these populations the exposure to non-genetic host and environmental aetiological factors is similar.

Pedersen JK, Kjaer NK, Svendsen AJ, Hørslev-Petersen K. · Research Unit, King Christian X Hospital for Rheumatic Diseases, Graasten, Denmark. · Rheumatol Int. · Pubmed #18853167 No free full text.

Abstract: The aim of this study was to describe the mean incidence rate of rheumatoid arthritis over a 7-year period from 1995 to 2001 in a population in the southern part of Denmark, using the data from several sources. Cases fulfilling the 1987 American College of Rheumatology criteria for rheumatoid arthritis were identified at hospitals and private practising rheumatologists (referral centres), and in general practice. The observed incidence was 32/100,000 person-years (95% confidence interval 29-35). Using the ratio between the number of cases known only from general practice and the number known from general practice and referral centres, the estimated incidence was 35/100,000 person-years (95% confidence interval 32-38). We suggest that the estimated rate should be viewed as a plausible upper limit for the incidence of rheumatoid arthritis in the southern part of Denmark.

Sokka T, Hetland ML, Mäkinen H, Kautiainen H, Hørslev-Petersen K, Luukkainen RK, Combe B, Badsha H, Drosos AA, Devlin J, Ferraccioli G, Morelli A, Hoekstra M, Majdan M, Sadkiewicz S, Belmonte M, Holmqvist AC, Choy E, Burmester GR, Tunc R, Dimić A, Nedović J, Stanković A, Bergman M, Toloza S, Pincus T, Anonymous00028. · Jyväskylä Central Hospital, Jyväskylä, Finland, and Medcare Oy, Aänekoski, Finland. · Arthritis Rheum. · Pubmed #18759292 No free full text.

Abstract: OBJECTIVE: To compare the performance of different definitions of remission in a large multinational cross-sectional cohort of patients with rheumatoid arthritis (RA). METHODS: The Questionnaires in Standard Monitoring of Patients with RA (QUEST-RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4-page self-report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self-report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission). RESULTS: The overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was >/=15% in 10 countries, 5-14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission. CONCLUSION: The use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.

Linde L, Sørensen J, Ostergaard M, Hørslev-Petersen K, Hetland ML. · Department of Rheumatology, Copenhagen University Hospital, Hvidovre, Denmark. · J Rheumatol. · Pubmed #18484697 No free full text.

Abstract: OBJECTIVE: To compare validity, reliability, and responsiveness of generic and disease specific health-related quality of life (HRQOL) instruments in rheumatoid arthritis (RA). METHODS: Two samples of patients completed the Medical Outcomes Study Short Form-36 Health Survey (SF-36), EuroQol (EQ)-5D, 15D, Rheumatoid Arthritis Quality of Life Scale (RAQoL), Health Assessment Questionnaire (HAQ), and visual analog scales (VAS) for pain, fatigue, and global RA. Validity (convergent, discriminant, and known-groups) was evaluated in a cross-section of 200 patients. Reliability was evaluated by agreement (intraclass correlation coefficient; baseline to 2 weeks) and internal consistency (Cronbach's alpha); and responsiveness by the standardized response mean stratified on improvement, status quo, or deterioration in health status after 6 months in 150 patients followed longitudinally. Followup questionnaires (at 2 weeks and 6 months) included questions about changes in health status since baseline. RESULTS: The cross-sectional sample included 77% women, median age 57 years (range 19-87), disease duration 6 years (0-58), with Disease Activity Score 28-joint count (DAS28) of 3.10 (1.21-6.47). The longitudinal sample included 80% women, median age 60 years (22-82). Validity: all instruments discriminated between low, moderate, and high DAS28. Reliability: RAQoL and HAQ displayed good repeatability (ICC > 0.95) and internal consistency (Cronbach's alpha > 0.90). Responsiveness: SF-36 bodily pain scale and VAS pain were responsive to both improvement and deterioration. CONCLUSION: All instruments were valid measures for HRQOL in RA. The RAQoL and HAQ displayed the best reliability, while the SF-36 bodily pain scale and VAS pain were the most responsive. The choice of instrument should depend on the study objectives.

Hetland ML, Ejbjerg B, Hørslev-Petersen K, Jacobsen S, Vestergaard A, Jurik AG, Stengaard-Pedersen K, Junker P, Lottenburger T, Hansen I, Andersen LS, Tarp U, Skjødt H, Pedersen JK, Majgaard O, Svendsen AJ, Ellingsen T, Lindegaard H, Christensen AF, Vallø J, Torfing T, Narvestad E, Thomsen HS, Ostergaard M, Anonymous00063. · Department of Rheumatology, Copenhagen University Hospital, Hvidovre, Denmark. · Ann Rheum Dis. · Pubmed #18388160 No free full text.

Abstract: OBJECTIVE: To identify predictors of radiographic progression in a 2-year randomised, double-blind, clinical study (CIMESTRA) of patients with early rheumatoid arthritis (RA). METHODS: Patients with early RA (n = 130) were treated with methotrexate, intra-articular betamethasone and ciclosporin/placebo-ciclosporin. Baseline magnetic resonance imaging (MRI) of the wrist (wrist-only group, n = 130) or MRI of wrist and metacarpophalangeal (MCP) joints (wrist+MCP group, n = 89) (OMERACT RAMRIS), x-ray examination of hands, wrists and forefeet (Sharp/van der Heijde Score (TSS)), Disease Activity Score (DAS28), anti-cyclic citrullinated peptide antibodies (anti-CCP), HLA-DRB1-shared epitope (SE) and smoking status were assessed. Multiple regression analysis was performed with delta-TSS (0-2 years) as dependent variable and baseline DAS28, TSS, MRI bone oedema score, MRI synovitis score, MRI erosion score, anti-CCP, smoking, SE, age and gender as explanatory variables. RESULTS: Baseline values: median DAS28 5.6 (range 2.4-8.0); anti-CCP positive 61%; radiographic erosions 56%. At 2 years: DAS28 2.0 (0.5-5.7), in DAS remission: 56%, radiographic progression 26% (wrist+MCP group, similar for wrist-only group). MRI bone oedema score was the only independent predictor of delta-TSS (wrist+MCP group: coefficient = 0.75 (95% CI 0.55 to 0.94), p<0.001; wrist-only group: coefficient = 0.59 (95% CI 0.40 to 0.77), p<0.001). Bone oedema score explained 41% of the variation in the progression of TSS (wrist+MCP group), 25% in wrist-only group (Pearson's r = 0.64 and r = 0.50, respectively). Results were confirmed by sensitivity analyses. CONCLUSION: In a randomised controlled trial aiming at remission in patients with early RA, baseline RAMRIS MRI bone oedema score of MCP and wrist joints (and of wrist only) was the strongest independent predictor of radiographic progression in hands, wrists and forefeet after 2 years. MRI synovitis score, MRI erosion score, DAS28, anti-CCP, SE, smoking, age and gender were not independent risk factors. TRIAL REGISTRATION NUMBER: NCT00209859.

Naranjo A, Sokka T, Descalzo MA, Calvo-Alén J, Hørslev-Petersen K, Luukkainen RK, Combe B, Burmester GR, Devlin J, Ferraccioli G, Morelli A, Hoekstra M, Majdan M, Sadkiewicz S, Belmonte M, Holmqvist AC, Choy E, Tunc R, Dimic A, Bergman M, Toloza S, Pincus T, Anonymous00244. · Hospital de Gran Canaria Dr, Negrin, University of Las Palmas de Gran Canaria, Barranco de la Ballena s/n 35011, Spain. · Arthritis Res Ther. · Pubmed #18325087 links to  free full text

Abstract: INTRODUCTION: We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care. METHODS: The study involved a clinical assessment by a rheumatologist and a self-report questionnaire by patients. The clinical assessment included a review of clinical features of RA and exposure to DMARDs over the course of RA. Comorbidities were recorded; CV morbidity included myocardial infarction, angina, coronary disease, coronary bypass surgery, and stroke. Traditional risk factors recorded were hypertension, hyperlipidemia, diabetes mellitus, smoking, physical inactivity, and body mass index. Unadjusted and adjusted hazard ratios (HRs) (95% confidence interval [CI]) for CV morbidity were calculated using Cox proportional hazard regression models. RESULTS: Between January 2005 and October 2006, the QUEST-RA project included 4,363 patients from 48 sites in 15 countries; 78% were female, more than 90% were Caucasian, and the mean age was 57 years. The prevalence for lifetime CV events in the entire sample was 3.2% for myocardial infarction, 1.9% for stroke, and 9.3% for any CV event. The prevalence for CV risk factors was 32% for hypertension, 14% for hyperlipidemia, 8% for diabetes, 43% for ever-smoking, 73% for physical inactivity, and 18% for obesity. Traditional risk factors except obesity and physical inactivity were significantly associated with CV morbidity. There was an association between any CV event and age and male gender and between extra-articular disease and myocardial infarction. Prolonged exposure to methotrexate (HR 0.85; 95% CI 0.81 to 0.89), leflunomide (HR 0.59; 95% CI 0.43 to 0.79), sulfasalazine (HR 0.92; 95% CI 0.87 to 0.98), glucocorticoids (HR 0.95; 95% CI 0.92 to 0.98), and biologic agents (HR 0.42; 95% CI 0.21 to 0.81; P < 0.05) was associated with a reduction of the risk of CV morbidity; analyses were adjusted for traditional risk factors and countries. CONCLUSION: In conclusion, prolonged use of treatments such as methotrexate, sulfasalazine, leflunomide, glucocorticoids, and tumor necrosis factor-alpha blockers appears to be associated with a reduced risk of CV disease. In addition to traditional risk factors, extra-articular disease was associated with the occurrence of myocardial infarction in patients with RA.

Hetland ML, Christensen IJ, Lottenburger T, Johansen JS, Svendsen MN, Hørslev-Petersen K, Nielsen L, Nielsen HJ. · Department of Rheumatology, Copenhagen University Hospital, Hvidovre, Denmark. · Dis Markers. · Pubmed #18057530 No free full text.

Abstract: BACKGROUND: Soluble vascular endothelial growth factor (VEGF) is a promising biomarker in monitoring rheumatoid arthritis (RA), but studies of pre-analytical and biologic variability are few. METHODS: VEGF was measured by ELISA methods in serum and plasma from healthy persons and RA patients. Pre-analytical factors were investigated. A reference interval for VEGF was established in serum and plasma from 306 healthy persons. Diurnal, day-to-day, week-to-week, long-term variability, and impact of exercise were evaluated. RESULTS: Delayed processing time, room temperature, low centrifugal force and contamination of plasma with cellular elements lead to significant increases in VEGF levels, whereas storage for up to 2 years at -80 degrees C or up to 10 freeze/thaw cycles did not affect VEGF levels. Serum VEGF levels were 7-10 fold higher than plasma VEGF levels. Reference intervals for VEGF (plasma: 45 pg/ml (range: non-detectable to 352); serum: 328 pg/ml (53-1791)) were independent of gender and age. Short- and long-term biologic variability included diurnal variation (sampling should take place after 7 AM) and impact of exercise (increased VEGF immediately after bicycling normalised within 1 hour). CONCLUSIONS: Pre-analytical factors and biologic variability including diurnal variation and impact of exercise should be accounted for in future studies that include circulating VEGF as a biological marker.

Hetland ML, Stengaard-Pedersen K, Junker P, Lottenburger T, Hansen I, Andersen LS, Tarp U, Svendsen A, Pedersen JK, Skjødt H, Lauridsen UB, Ellingsen T, Hansen GV, Lindegaard H, Vestergaard A, Jurik AG, Østergaard M, Hørslev-Petersen K, Anonymous00425. · Department of Rheumatology, Copenhagen University Hospital, Hvidovre, Denmark. · Ann Rheum Dis. · Pubmed #17878209 No free full text.

Abstract: OBJECTIVE: To investigate whether clinical and radiographic disease control can be achieved and maintained in patients with early, active rheumatoid arthritis (RA) during the second year of aggressive treatment with conventional disease-modifying antirheumatic drugs (DMARDs) and intra-articular corticosteroid. This paper presents the results of the second year of the randomised, controlled double-blind CIMESTRA (Ciclosporine, Methotrexate, Steroid in RA) study. METHODS: 160 patients with early RA (duration <6 months) were randomised to receive intra-articular betamethasone in any swollen joint in combination with step-up treatment with either methotrexate and placebo-ciclosporine (monotherapy) or methotrexate plus ciclosporine (combination therapy) during the first 76 weeks. At week 68 hydroxychlorochine 200 mg daily was added. From week 76-104 ciclosporine/placebo-ciclosporine was tapered to zero. RESULTS: American College of Rheumatology 20% improvement (ACR20), ACR50 and ACR70 levels were achieved in 88%, 79% and 59% of patients in the combination vs 72%, 62% and 54% in the monotherapy group (p = 0.03, 0.02 and 0.6 between groups). The patients globally declined from 50 to 12 vs 52 to 9, with 51% and 50% in Disease Activity Score (DAS) remission, respectively. Mean (SD) progressions in total Sharp-van der Heijde scores were 1.42 (3.52) and 2.03 (5.86) in combination and monotherapy groups, respectively (not significant). Serum creatinine levels increased by 7% in the combination group (4% in monotherapy), but hypertension was not more prevalent. CONCLUSION: Continuous methotrexate and intra-articular corticosteroid treatment resulted in excellent clinical response and disease control at 2 years, and the radiographic erosive progression was minimal. Addition of ciclosporine during the first 76 weeks resulted in significantly better ACR20 and ACR50 responses, but did not have any additional effect on remission rate and radiographic outcome.

Knudsen LS, Christensen IJ, Lottenburger T, Svendsen MN, Nielsen HJ, Nielsen L, Hørslev-Petersen K, Jensen JE, Kollerup G, Johansen JS. · Department of Rheumatology Q 107, Herlev Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark. · Biomarkers. · Pubmed #17852075 No free full text.

Abstract: Interleukin (IL)-6, a key player in the inflammatory response, may be a useful biomarker in rheumatoid arthritis (RA). The aim was to determine analytical variability, a reference interval in healthy subjects, and long- and short-term variation in serum and plasma IL-6 in healthy subjects and RA patients. An enzyme-linked immunosorbent assay from R&D was used for determination of serum and plasma IL-6. The IL-6 concentration did not depend on the type of anticoagulant used or the 3-h time delay between sampling and processing or repeated freeze-thaw cycles. The median plasma and serum IL-6 in 318 healthy subjects were 1.3 pg ml(-1) (range 0.33-26) and 1.4 pg ml(-1) (range 0.25-23), respectively. The median coefficient of variation in plasma IL-6 in 27 healthy subjects during 1 month, and repeated after 6 and 12 months were 27%, 31% and 26%, respectively. No significant long-term changes were observed in serum IL-6 over a 3-year period (14%, p = 0.33). Exercise (cycling) increased serum IL-6 in healthy subjects but not in RA patients. In conclusion, circulating IL-6 is stable regarding sample handling and shows little variation over time. Changes in IL-6 concentrations > 60% (2 times the biological variation) are likely to reflect changes in disease activity and not only pre-analytical or normal biological variability.

Duer A, Østergaard M, Hørslev-Petersen K, Vallø J. · Department of Rheumatology, Copenhagen University Hospital at Hvidovre, Copenhagen, Denmark. · Ann Rheum Dis. · Pubmed #17289759 No free full text.

Abstract: OBJECTIVES: To investigate the value in clinical practice of hand magnetic resonance imaging (MRI) and whole body bone scintigraphy in the differential diagnosis of patients with unclassified arthritis. METHODS: 41 patients with arthritis (> or = 2 swollen joints, > 6 months' duration) which remained unclassified despite conventional clinical, biochemical and radiographic (hands and feet) examinations were studied. Patients who fulfilled the ACR criteria for rheumatoid arthritis (RA) or had radiographic bone erosions were excluded. Contrast enhanced MRI of the wrist and metacarpophalangeal joints of the most symptomatic hand and whole body bone scintigraphy were performed. Two rheumatologists agreed on the most likely diagnosis and the patients were treated accordingly. A final diagnosis was made by another specialist review 2 years later. RESULTS: Tentative diagnoses after MRI and bone scintigraphy were: RA (n = 13), osteoarthritis (n = 8), other inflammatory diseases (n = 11), arthralgias without inflammatory or degenerative origin (n = 9). Two years later 11 of 13 patients with an original tentative diagnosis of RA had fulfilled the ACR criteria while two were reclassified (one to psoriatic arthritis (RF negative + psoriasis); one to non-specific self-limiting arthritis). No patients classified as non-RA at baseline had fulfilled the ACR criteria after 2 years. The presence of MRI synovitis, MRI erosion and bone scintigraphic pattern compatible with RA showed 100% specificity for a diagnosis of RA at 2 year follow-up. CONCLUSIONS: In patients with arthritis unclassified despite conventional clinical, biochemical and radiographic examinations, MRI and scintigraphy allowed correct classification as RA or non-RA in 39 of 41 patients when fulfilment of ACR criteria 2 years later was considered the standard reference.

Hetland ML, Stengaard-Pedersen K, Junker P, Lottenburger T, Ellingsen T, Andersen LS, Hansen I, Skjødt H, Pedersen JK, Lauridsen UB, Svendsen A, Tarp U, Pødenphant J, Hansen G, Lindegaard H, de Carvalho A, Østergaard M, Hørslev-Petersen K, Anonymous00339. · Copenhagen University Hospital, Hvidovre, Denmark. · Arthritis Rheum. · Pubmed #16645967 links to  free full text

Abstract: OBJECTIVE: To investigate whether disease control can be achieved in early active rheumatoid arthritis (RA) by treatment with methotrexate and intraarticular betamethasone, and whether the addition of cyclosporine to the regimen has any additional effect. METHODS: Patients (n = 160) were randomized to receive methotrexate 7.5 mg/week plus cyclosporine 2.5 mg/kg of body weight/day (combination therapy) or methotrexate plus placebo-cyclosporine (monotherapy). At weeks 0, 2, 4, 6, and 8 and every 4 weeks thereafter, betamethasone was injected into swollen joints (maximum 4 joints or 4 ml per visit). Beginning at week 8, if synovitis was present, the methotrexate dosage was increased stepwise up to 20 mg/week, with a subsequent stepwise increase in the cyclosporine or placebo-cyclosporine dosage up to 4 mg/kg. RESULTS: At 52 weeks, 20% improvement according to the American College of Rheumatology criteria (ACR20) was achieved in 85% of the combination therapy group versus 68% of the monotherapy group (P = 0.02). The median individual overall ACR response (ACR-N) in the 2 groups was 80.0% (interquartile range 40.1-91.8%) and 54.5% (interquartile range 2.4-87.8%), respectively (P = 0.025). At 48 and 52 weeks, ACR remission criteria were met in 35% of the combination therapy group and 28% of the monotherapy group. Progression in the Larsen score at 52 weeks was -0.2 +/- 6.5 and 0.4 +/- 6.9 (mean +/- SD) in the combination therapy and monotherapy groups, respectively. Serum creatinine levels increased by 7%, and hypertrichosis was more prevalent, in the combination therapy group. CONCLUSION: Combined treatment with methotrexate and intraarticular glucocorticoid showed excellent disease control and stopped the progression of erosions in patients with early active RA, who had a poor prognosis. Addition of cyclosporine improved the ACR20 and ACR-N responses, whereas the ACR50 and ACR70 responses, remission rates, and radiographic changes did not differ between the 2 study groups.

Lindegaard HM, Vallø J, Hørslev-Petersen K, Junker P, Østergaard M. · Department of Internal Medicine C, Section of Rheumatology, Odense University Hospital, Søndre Boulevard 29, Dk-5000 Odense C, Denmark. · Ann Rheum Dis. · Pubmed #16540550 No free full text.

Abstract: OBJECTIVE: To study the ability of low-cost low-field dedicated extremity magnetic resonance imaging (E-MRI) to assess and predict erosive joint damage in the wrist and metacarpophalangeal (MCP) joints of patients with early rheumatoid arthritis. METHODS: 24 previously untreated patients with rheumatoid arthritis with joint symptoms for <1 year were evaluated at the time of diagnosis and after 6 and 12 months of methotrexate treatment with conventional clinical or biochemical examinations, x rays of both hands and wrists, and E-MRI of the dominant wrist and MCP joints. RESULTS: At baseline, all patients showed magnetic resonance imaging (MRI) synovitis, and MRI erosions were detected in 21 bones (10 patients). 6 (29%) of these, distributed among two patients, were seen on x ray. One x ray erosion was not detected by MRI. At 1 year, MRI and x ray detected 15 and 8 new erosions, respectively, and 19% of MRI erosions at baseline had progressed to x ray erosions. In bones with MRI erosions at baseline, the relative risk of having x ray erosions at the 1-year follow-up was 12.1, compared with bones without baseline MRI erosions (lesion-centred analysis). If bones with baseline x ray erosions were excluded, the relative risk was 5.2. In patients with baseline MRI bone erosion or oedema, the relative risk of having x ray erosions at 1 year was 4.0, compared with patients without these signs at baseline (patient-centred analysis). CONCLUSION: In this group of patients with early rheumatoid arthritis who were treated uniformly, baseline E-MRI erosions in MCP or wrist bones markedly increased the risk of x ray erosions at the 1-year follow-up. Low-cost, low-field dedicated extremity MRI is promising for assessment and prognostication of early rheumatoid arthritis.

Lindegaard HM, Hørslev-Petersen K, Junker P. · Odense Universitetshospital, Medicinsk Afdeling C, Reumatologisk Sektion, Odense C. · Ugeskr Laeger. · Pubmed #16305765 No free full text.

Abstract: INTRODUCTION: Our aim was to describe the referral pattern among patients admitted to early arthritis clinics (EAC) in the counties of Funen and South Jutland, Denmark. MATERIALS AND METHODS: In order to accelerate the diagnostic workup of patients with suspected rheumatoid arthritis (RA), general practitioners, rheumatology specialists and neighbouring hospital departments were invited to refer to the EAC patients who had synovitis in at least one joint lasting more than 6 weeks but less than 12 months. RESULTS: 226 patients were admitted. The median total lag time from onset of joint complaints to visiting the EAC was 89 days (IQ 57-154). The average lag time between receipt of the referral to the first visit to the EAC was 18 days (IQ 5-31). 91 (40%) of the patients had synovitis upon clinical examination. 51 (23%) of these fulfilled the ACR 1987 classification criteria for RA, and 40 (17%) had synovitis of other aetiologies than RA. Compared with non-RA patients, the RA subset was characterised by older age, female preponderance, higher joint counts and disability and a more pronounced acute phase response. Despite the short duration of the disease, 17% of the RA patients had X-ray erosions. DISCUSSION: In spite of the rigid criteria for referral to the EAC, synovitis was demonstrated by clinical examination in only 40% of the patients. Half of these were classified as RA. The total median lag time of three months from the onset of joint symptoms to the first visit to the EAC accords with current recommendations. Standardised criteria for referral to EACs should be prepared and combined with educational efforts to improve joint assessment skills.

Østergaard M, Duer A, Hørslev-Petersen K. · Department of Rheumatology, Copenhagen University Hospital, Hvidovre, Denmark. · Arthritis Res Ther. · Pubmed #16277699 links to  free full text

Abstract: A high sensitivity for the detection of inflammatory and destructive changes in inflammatory joint diseases makes magnetic resonance imaging potentially useful for assigning specific diagnoses, such as rheumatoid arthritis and psoriatic arthritis in arthritides, that remain undifferentiated after conventional clinical, biochemical and radiographic examinations. With recent data as the starting point, the present paper describes the current knowledge on magnetic resonance imaging in the differential diagnosis of undifferentiated arthritis.

Lindegaard H, Vallø J, Hørslev-Petersen K, Junker P, Østergaard M. · Department of Internal Medicine C, Section of Rheumatology, Odense University, Denmark. · Ann Rheum Dis. · Pubmed #11454641 links to  free full text

Abstract: OBJECTIVE: To compare a low field dedicated extremity magnetic resonance imaging system (E-MRI) with x ray and clinical examination, in the detection of inflammation and erosive lesions in wrist and metacarpophalangeal (MCP) joints in newly diagnosed, untreated rheumatoid arthritis (RA). PATIENTS AND METHODS: Twenty five patients (disease duration < or =1 year) and three healthy controls entered the study. An x ray examination and MRI (before and after intravenous injection of a contrast agent) of the 2nd-5th MCP joints and the wrist was performed. The number of erosions on x ray examination and MRI was calculated, and synovitis in the MCP joints and wrists was graded semiquantitatively. RESULTS: E-MRI detected 57 bone erosions, whereas only six erosions were disclosed by x ray examination (ratio 9.5:1). Synovial hypertrophy grades were significantly higher in RA joints with clinical signs of joint inflammation-that is, swelling and/or tenderness (median 3, 5th-95th centile 1-4) than without these clinical signs (median 2, 5th-95th centile 1-3), p < 0.001. 51% of the joints without clinical signs of synovitis showed synovial hypertrophy on E-MRI. There was a positive correlation between MRI scores of synovitis and the number of erosions detected by MRI in the MCP joints (Spearman r(s) = 0.31, p < 0.01). No healthy controls had erosions or synovitis on MRI. CONCLUSION: Joint destruction starts very early in RA and E-MRI allows detailed evaluation of inflammatory and destructive changes in wrists and MCP joints in patients with incipient RA.

Nielsen H, Petersen AA, Skjødt H, Hørslev-Petersen K, Bendtzen K. · Institute for Inflammation Research, Rigshospitalet National University Hospital, Copenhagen, Denmark. · APMIS. · Pubmed #10660143 No free full text.

Abstract: The adhesion molecules CD11b (a beta2-integrin component) and CD54 (ICAM-1) on blood leukocytes were studied by flow cytometry in patients with rheumatoid arthritis (RA). The fractions of CD4+ cells co-expressing CD11b were elevated in 16 patients with active RA compared with those in 16 RA patients who improved during therapy and 8 healthy controls: 0.8+/-0.12% (mean+/-SEM) versus 0.3+/-0.06% (p<0.002) and 0.3+/-0.06% (p<0.005), respectively. Increased levels of CD11b+CD45R0+ cells were observed in patients with active RA compared to those with improved RA and controls: 12.6+/-3.9% versus 4.8+/-2.7% (p<0.002) and 6.1+/-1.2% (p<0.003), respectively. Disease activity, determined by C-reactive protein, correlated with the numbers of CD11b+CD45R0+ cells: r=0.62 (p<0.001). Seven patients were followed during induction of remission with methotrexate and glucocorticoids. The numbers of CD11b+CD4+ and CD11b+CD45R0+ cells fell significantly after clinical improvement. The levels of CD11b+CD14+ cells (monocytes) did not differ between the groups. The number of CD11b+CD15+ cells (neutrophils) was elevated in patients with RA irrespective of disease activity. The levels of CD54+ cells were not different between the RA and control groups. We conclude that the increased numbers of CD11b+ memory T cells may arise from exposure to stimuli outside the synovial compartment.

Johansen JS, Stoltenberg M, Hansen M, Florescu A, Hørslev-Petersen K, Lorenzen I, Price PA. · Department of Rheumatology, Hvidovre Hospital, Denmark. · Rheumatology (Oxford). · Pubmed #10461474 links to  free full text

Abstract: OBJECTIVE: YKL-40, also called human cartilage glycoprotein-39, is secreted by chondrocytes, synovial cells, macrophages and neutrophils. Studies have shown that YKL-40 is an autoantigen in rheumatoid arthritis (RA). We evaluated whether serum YKL-40 was related to disease activity in patients with RA. METHODS: Serum YKL-40 was determined by radioimmunoassay in 156 patients with RA during a 1 yr longitudinal study. RESULTS: Serum YKL-40 was increased in 54% of the patients with clinically active disease. Patients with clinically active disease initially who became inactive after 12 months had a significant decrease in serum YKL-40 (-30%, P < 0.002) and patients who changed from inactive to active disease had an increase in serum YKL-40. Patients who remained active had unchanged serum YKL-40 during the study. Serum YKL-40 decreased rapidly (-24% after 7 days, P < 0.01) during prednisolone therapy, and more slowly in patients treated with methotrexate only (-15% after 60 days, P < 0.01). Patients with early RA (disease duration < 3 yr, n = 50) and a persistently elevated serum YKL-40 were at risk of radiological disease progression as determined by Larsen score. CONCLUSION: Serum YKL-40 varies according to disease activity in RA, but provides in some respect information different from conventional markers. Our previous studies are consistent with a local release of YKL-40 in the arthritic joint followed by a secondary increase in serum YKL-40. YKL-40 may prove to be a new tool for the study of disease activity and pathophysiology of RA.

Jacobsen S, Skjødt H, Hørslev-Petersen K, Hansen TM, Sørensen SF, Petersen J, Junker P, Stengaard-Pedersen K. · No affiliation provided · Ugeskr Laeger. · Pubmed #11894713 No free full text.

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