Rheumatoid Arthritis: Pedersen JK

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.

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.

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.

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.