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Kim Hørslev-Petersen,
Merete Lund Hetland, Peter Junker,
Jan Pødenphant,
Torkell Ellingsen,
Palle Ahlquist,
Hanne Lindegaard,
Asta Linauskas,
Annette Schlemmer,
Mette Yde Dam,
Ib Hansen,
Hans Christian Horn,
Christian Gytz Ammitzbøll,
Anette Jørgensen,
Sophine B Krintel,
Johnny Raun,
Julia S Johansen,
Mikkel Ostergaard,
Kristian Stengaard-Pedersen
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ABSTRACT: OBJECTIVES: An investigator-initiated, double-blinded, placebo-controlled, treat-to-target protocol (Clinical Trials:NCT00660647) studied whether adalimumab added to methotrexate and intra-articular triamcinolone as first-line treatment in early rheumatoid arthritis (ERA) increased the frequency of low disease activity (DAS28CRP<3.2) at 12 months. METHODS: In 14 Danish hospital-based clinics, 180 disease-modifying anti-rheumatic drugs (DMARD)-naïve ERA patients (<6 months duration) received methotrexate 7.5 mg/week (increased to 20 mg/week within 2 months) plus adalimumab 40 mg every other week (adalimumab-group, n=89) or methotrexate+placebo-adalimumab (placebo-group, n=91). At all visits, triamcinolone was injected into swollen joints (max. four joints/visit). If low disease activity was not achieved, sulfasalazine 2 g/day and hydroxychloroquine 200 mg/day were added after 3 months, and open-label biologics after 6-9 months. Efficacy was assessed primarily on the proportion of patients who reached treatment target (DAS28CRP<3.2). Secondary endpoints included DAS28CRP, remission, Health Assessment Questionnaire (HAQ), EQ-5D and SF-12. Analysis was by intention-to-treat with last observation carried forward. RESULTS: Baseline characteristics were similar between groups. In the adalimumab group/placebo group the 12-month cumulative triamcinolone doses were 5.4/7.0 ml (p=0.08). Triple therapy was applied in 18/27 patients (p=0.17). At 12 months, DAS28CRP<3.2 was reached in 80%/76% (p=0.65) and DAS28CRP was 2.0 (1.7-5.2) (medians (5th/95th percentile ranges)), versus 2.6 (1.7-4.7) (p=0.009). Remission rates were: DAS28CRP<2.6: 74%/49%, Clinical Disease Activity Index≤2.8: 61%/41%, Simplified Disease Activity Index<3.3: 57%/37%, European League Against Rheumatism/American College of Rheumatology Boolean: 48%/30% (0.0008<p<0.014, number-needed-to-treat: 4.0-5.4). Twelve months HAQ, SF12PCS and EQ-5D improvements were most pronounced in the adalimumab group. Treatments were well tolerated. CONCLUSIONS: Adalimumab added to methotrexate and intra-articular triamcinolone as first-line treatment did not increase the proportion of patients who reached the DAS28CRP<3.2 treatment target, but improved DAS28CRP, remission rates, function and quality of life in DMARD-naïve ERA.
Annals of the rheumatic diseases 03/2013; · 8.11 Impact Factor
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Merete Lund Hetland,
Mikkel Østergaard,
Bo Ejbjerg,
Søren Jacobsen,
Kristian Stengaard-Pedersen, Peter Junker,
Tine Lottenburger,
Ib Hansen,
Lis Smedegaard Andersen,
Ulrik Tarp,
Anders Svendsen,
Jens Kristian Pedersen,
Henrik Skjødt,
Torkell Ellingsen,
Hanne Lindegaard,
Jan Pødenphant,
Kim Hørslev-Petersen
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ABSTRACT: To investigate the short-term and long-term efficacy of intra-articular betamethasone injections, and the impact of joint area, repeated injections, MRI pathology, anticyclic citrullinated peptide (CCP) and immunoglobulin M rheumatoid factor (IgM-RF) status in patients with early rheumatoid arthritis (RA).
During 2 years of follow-up in the CIMESTRA trial, 160 patients received intra-articular betamethasone in up to four swollen joints/visit in combination with disease-modifying antirheumatic drugs. Short-term efficacy was assessed by EULAR good response. Long-term efficacy by Kaplan-Meier plots of the joint injection survival (ie, the time between injection and renewed flare). Potential predictors of joint injection survival were tested.
1373 Unique joints (ankles, elbows, knees, metacarpophalangeal (MCP), metatarsophalangeal, proximal interphalangeal (PIP), shoulders, wrists) were injected during 2 years. 531 Joints received a second injection, and 262 a third. At baseline, the median numbers of injections (dose of betamethasone) was 4 (28 mg), declining to 0 (0 mg) at subsequent visits. At weeks 2, 4 and 6, 50.0%, 58.1% and 61.7% had achieved a EULAR good response. After 1 and 2 years, respectively, 62.3% (95% CI 58.1% to 66.9%) and 55.5% (51.1% to 60.3%) of the joints injected at baseline had not relapsed. All joint areas had good 2-year joint injection survival, longest for the PIP joints: 73.7% (79.4% to 95.3%). 2-Year joint injection survival was higher for first injections: 56.6% (53.7% to 59.8%) than for the second: 43.4% (38.4% to 49.0%) and the third: 31.3% (25.0% to 39.3%). Adverse events were mild and transient. A high MRI synovitis score of MCP joints and anti-CCP-negativity were associated with poorer joint injection survival, whereas IgM-RF and C-reactive protein were not.
In early RA, intra-articular injections of betamethasone in small and large peripheral joints resulted in rapid, effective and longlasting inflammatory control. The cumulative dose of betamethasone was low, and the injections were well tolerated.
Annals of the rheumatic diseases 02/2012; 71(6):851-6. · 8.11 Impact Factor
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ABSTRACT: To investigate by magnetic resonance imaging (MRI) which bones in wrists and metacarpophalangeal (MCP) joints most frequently show bone erosions, and which most frequently demonstrate erosive progression, in early and established rheumatoid arthritis (RA).
MRI datasets from 258 RA patients [126 with early RA (disease duration < 6 months)] were analyzed, of whom 223, including 126 with early RA, had 1-year followup MRI. All patients had MRI of one wrist, whereas 86 patients had additional images of 2nd-5th MCP joints, and 46 patients additional images of the contralateral wrist. MRI were evaluated blinded by one reader, according to the OMERACT RA MRI scoring system (RAMRIS) for erosions, and presence/absence of erosions was noted in each bone, as was presence/absence of erosive progression.
The capitate, ulna, lunate, triquetrum, and scaphoid were the 5 bones with both most frequent baseline erosions and most frequently demonstrated erosive progression. No bones were without erosions. Patterns of erosions and progression were similar in early and established RA. No major difference between dominant and nondominant wrists was detected. In the fingers, the 2nd-3rd MCP joint most frequently displayed erosions and erosive progression.
The distribution and frequency of bone erosion and erosive progression as detected by MRI in RA wrists and MCP joints were identified. No pattern differences between early versus established disease and dominant versus nondominant sides were detected. No bones showed erosive progression. Thus, no self-evident simplification of the RAMRIS erosion score was identified. Bone involvement patterns may be considered, when joints are selected for MRI protocols for clinical trials and practice.
The Journal of Rheumatology 09/2011; 38(9):2014-7. · 3.69 Impact Factor
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Anne F Christensen,
Hanne Lindegaard,
Kim Hørslev-Petersen,
Merete L Hetland,
Bo Ejbjerg,
Kristian Stengaard-Pedersen,
Søren Jacobsen,
Tine Lottenburger,
Torkell Ellingsen,
Lis S Andersen,
Ib Hansen,
Henrik Skjødt,
Jens K Pedersen,
Ulrik B Lauridsen,
Anders Svendsen,
Ulrik Tarp,
Jan Pødenphant,
Mikkel Østergaard, Peter Junker
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ABSTRACT: Cyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative rheumatoid arthritis (RA) have been suggested as 2 distinctive disease subsets with respect to disease activity and prognosis. Previously, we proposed that anti-CCP antibodies might have a chondrocyte-suppressive effect. We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings.
A total of 160 patients with newly diagnosed RA who were naive to disease-modifying antirheumatic drugs were included in the CIMESTRA trial. Ninety healthy blood donors served as controls. Demographic and disease measures including Disease Activity Score in 28 joints, IgM rheumatoid factor, anti-CCP, Health Assessment Questionnaire, visual analog scale scores for pain and global and physician assessment, and magnetic resonance imaging (MRI) of the nondominant hand were recorded at baseline. COMP in serum was measured by ELISA at inclusion and serially through 4 years.
Median baseline COMP was higher in patients with RA [9.8 U/l (interquartile range 8.96, 10.5)] compared with controls [8.3 U/l (IQR 7.84, 8.9); p < 0.001] and remained elevated at 4 years [10.8 U/l (IQR 10.2, 11.7); p < 0.001]. At baseline, anti-CCP-positive patients had lower COMP than anti-CCP-negative patients (p = 0.048). In anti-CCP-positive patients, COMP exhibited a parabolic course over 4 years, while COMP in anti-CCP-negative patients had an almost linear course. In anti-CCP-positive patients, COMP was associated with MRI edema and erosion score, while COMP was correlated with synovitis score in anti-CCP-negative individuals.
Our study provides additional evidence for the existence of different disease pathways in anti-CCP-positive and anti-CCP-negative subsets of RA, and evidence that anti-CCP antibodies may be implicated in the disease process by modifying cartilage metabolism.
The Journal of Rheumatology 05/2011; 38(8):1563-8. · 3.69 Impact Factor
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ABSTRACT: Rheumatoid arthritis (RA) is a chronic disease with autoimmune traits of unknown aetiology which primarily affects synovial joints. Glucocorticoids (GCs) are still widely used in RA treatment despite the expanding use of targeted and very efficient agents. The objective of this study was to assess the impact of treatment with tumour necrosis factor-α inhibitors (TNFi) on GC utilization in real-life practice among Danish RA patients.
The DANBIO registry is a nationwide rheumatologic database which collects demographic and clinical data. This retrospective study included RA outpatients from a tertiary rheumatologic department recruited from the DANBIO registry who initiated their first TNFi treatment between January 2000 and February 2010 (n = 171). GC dosing during the year before and the year after TNFi initiation were compared. Patients acted as their own control.
The median daily prednisolone dose was significantly decreased after initiation of TNFi treatment (p < 0.01). At TNFi initiation, 78 patients (46%) received prednisolone compared with 53 (31%) by the end of follow-up. After TNFi initiation, 30 patients (38%) discontinued prednisolone and in 34 (44%) prednisolone dose was reduced. Similarly, the number of GC injections decreased significantly at 13, 26 and 52 weeks following TNFi initiation (p < 0.01).
GC utilization is significantly reduced after initiation of TNFi treatment. Among patients on prednisolone at TNFi onset, prednisolone was withdrawn in one third and the dose was reduced in nearly half. Furthermore, the need for GC injections decreased.
Danish medical bulletin 04/2011; 58(4):A4257. · 0.75 Impact Factor
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ABSTRACT: A 27-year-old woman was admitted for intractable right-sided neck, ear, and jaw pain with gradual development of tinnitus and hearing loss. A cerebral MRI showed meningo-dural enhancement, and additional diagnostic workup revealed a right pulmonary infiltrate and positive PR-3 ANCA. Biopsies from nasal mucosa and lung showed chronic inflammation with granuloma formation. Based on these findings the patient was diagnosed with Wegener's granulomatosis with pachymeningitis. There was no clinical response to oral Prednisolone and Cyclophosphamide, but complete clinical and imaging remission was achieved by adding Rituximab.
ISRN rheumatology. 01/2011; 2011:608942.
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Anne Friesgaard Christensen,
Kim Hørslev-Petersen,
Stephan Christgau,
Hanne Merete Lindegaard,
Tine Lottenburger,
Kirsten Junker,
Merete Lund Hetland,
Kristian Stengaard-Pedersen,
Søren Jacobsen,
Torkell Ellingsen, [......],
Jens Kristian Pedersen,
Ulrik Birk Lauridsen,
Anders Jørgen Svendsen,
Ulrik Tarp,
Jan Pødenphant,
Niels H H Heegaard,
Aage Vestergaard,
Anne Grethe Jurik,
Mikkel Ostergaard, Peter Junker
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ABSTRACT: To investigate the relationship between markers of collagen II synthesis and degradation with disease activity measures, autoantibodies, and radiographic outcomes in a 4-year protocol on patients with early rheumatoid arthritis (RA) who are naïve to disease-modifying antirheumatic drugs.
One hundred sixty patients with newly diagnosed, untreated RA entered the Cyclosporine, Methotrexate, Steroid in RA (CIMESTRA) trial. Disease activity and radiograph status were measured at baseline and 4 years. The N-terminal propeptide of collagen IIA (PIIANP) and the cross-linked C-telopeptide of collagen II (CTX-II) were quantified at baseline by ELISA. PIIANP was also assayed at 2 and 4 years. Anticyclic citrullinated peptide (anti-CCP) was recorded at baseline. An uncoupling index for cartilage collagen metabolism was calculated from PIIANP and CTX-II measurements.
PIIANP was low at diagnosis and 4 years on (p < 0.001), irrespective of treatment and disease activity. PIIANP was lowest in anti-CCP positive patients (p = 0.006), and there was a negative correlation between PIIANP and anti-CCP titers (rho = -0.25, p 0.002). CTX-II was increased (p < 0.001) and correlated positively with disease activity and radiographic progression, but not with anti-CCP (p = 0.93). The uncoupling index was not superior to CTX-II in predicting radiographic changes.
These results suggest that cartilage collagen formation and degradation are unbalanced when RA is diagnosed. The different associations of collagen II anabolism (PIIANP) and collagen II degradation (CTX-II) with anti-CCP, synovitis, and radiographic progression indicate that at this early stage of RA, cartilage collagen degradation is mainly driven by synovitis, while anti-CCP antibodies may interfere with cartilage regeneration by inhibiting collagen IIA formation. Trial registration j.nr NCT00209859.
The Journal of Rheumatology 06/2010; 37(6):1113-20. · 3.69 Impact Factor
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Merete L Hetland,
Kristian Stengaard-Pedersen, Peter Junker,
Mikkel Østergaard,
Bo J Ejbjerg,
Søren Jacobsen,
Tine Lottenburger,
Ib Hansen,
Ulrik Tarp,
Lis S Andersen,
Anders Svendsen,
Jens K Pedersen,
Ulrik B Lauridsen,
Torkell Ellingsen,
Hanne Lindegaard,
Jan Pødenphant,
Aage Vestergaard,
Anne Grethe Jurik,
Kim Hørslev-Petersen
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ABSTRACT: At 5 years' follow-up of early (<6 months) rheumatoid arthritis patients to (1) investigate whether initial combination therapy with methotrexate (MTX) and ciclosporin (CSA) (n=80) is superior to initial monotherapy with MTX (n=80) with respect to prevention of radiographic progression, (2) investigate whether the favourable clinical and radiographic response reported at 2 years in the CIMESTRA trial can be maintained and (3) identify predictors of radiographic outcome.
139 patients completed 5 years' follow-up with maintained double-blinding and a strict synovitis suppressive treatment strategy with intra-articular betamethasone injections (intra-articular glucocorticosteroid (GC)) and escalation of disease-modifying anti-rheumatic drug treatment. Disease activity, total Sharp-van der Heijde Score (TSS) of hands, wrists and forefeet were assessed at baseline and after 3, 4 and 5 years. MRI of the wrist and anti-cyclic citrullinated peptide (anti-CCP) were assessed at baseline.
At 5 years, TSS progression rate was <1 unit/year and 47% had not progressed radiographically since baseline. 78% were in Disease Activity Score remission, 56% in American College of Rheumatology remission and 17% withdrawn from treatment due to remission. There were no differences between initial treatment groups. MRI-bone marrow oedema, TSS and anti-CCP predicted radiographic progression at 5 years.
Early and strict synovitis suppressive treatment with MTX and intra-articular GC lead to high remission rates and halting of erosive progression at 5 years. No additional effect of initial combination therapy with CSA was found. The results parallel those reported for tumour necrosis factor α antagonists. Baseline MRI-bone oedema, TSS and anti-CCP predicted radiographic progression.
Annals of the rheumatic diseases 05/2010; 69(10):1789-95. · 8.11 Impact Factor
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Anne Friesgaard Christensen,
Grith Lykke Sørensen,
Kim Hørslev-Petersen,
Uffe Holmskov,
Hanne Merete Lindegaard,
Kirsten Junker,
Merete Lund Hetland,
Kristian Stengaard-Pedersen,
Søren Jacobsen,
Tine Lottenburger, [......],
Henrik Skjødt,
Jens Kristian Pedersen,
Ulrik Birk Lauridsen,
Anders Svendsen,
Ulrik Tarp,
Jan Pødenphant,
Aage Vestergaard,
Anne Grethe Jurik,
Mikkel Østergaard, Peter Junker
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ABSTRACT: Surfactant protein D (SP-D) is a collectin with immuno-regulatory functions, which may depend on oligomerization. Anti-microbial and anti-inflammatory properties have been attributed to multimeric SP-D variants, while trimeric subunits per se have been suggested to enhance inflammation. Previously, we reported low circulating SP-D in early rheumatoid arthritis (RA), and the present investigation aims to extend these data by serial SP-D serum measurements, studies on synovial fluid, SP-D size distribution and genotyping in patients with early RA.
One-hundred-and-sixty disease-modifying antirheumatic drug (DMARD) naïve RA patients with disease duration less than six months were studied prospectively for four years (CIMESTRA (Ciclosporine, Methotrexate, Steroid in RA) trial) including disease activity measures (C-reactive protein, joint counts and Health Assessment Questionnaire (HAQ) score), autoantibodies, x-ray findings and SP-D. SP-D was quantified by enzyme-linked immunosorbent assay (ELISA) and molecular size distribution was assessed by gel filtration chromatography. Further, SP-D Met11Thr single nucleotide polymorphism (SNP) analysis was performed.
Serum SP-D was significantly lower in RA patients at baseline compared with healthy controls (P < 0.001). SP-D increased slightly during follow-up (P < 0.001), but was still subnormal at four years after adjustment for confounders (P < 0.001). SP-D in synovial fluid was up to 2.5-fold lower than in serum. While multimeric variants were detected in serum, SP-D in synovial fluid comprised trimeric subunits only. There were no significant associations between genotype distribution and SP-D. Baseline SP-D was inversely associated to CRP and HAQ score. A similar relationship was observed regarding temporal changes in SP-D and CRP (zero to four years). SP-D was not associated to x-ray findings.
This study confirms that circulating SP-D is persistently subnormal in early and untreated RA despite a favourable therapeutic response obtained during four years of follow-up. SP-D correlated negatively to disease activity measures, but was not correlated with x-ray progression or SP-D genotype. These observations suggest that SP-D is implicated in RA pathogenesis at the protein level. The exclusive presence of trimeric SP-D in affected joints may contribute to the maintenance of joint inflammation.
(j.nr NCT00209859).
Arthritis research & therapy 03/2010; 12(2):R39. · 4.27 Impact Factor
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ABSTRACT: Deficiencies of innate immune molecules like mannan binding lectin (MBL) have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Surfactant protein D (SP-D) and MBL belong to the same family of innate immune molecules - the collectins, which share important structural and functional properties. We aimed to compare concentrations of serum SP-D in patients with SLE and in healthy controls, and to investigate if SP-D is associated with selected disease indicators. We investigated the possible association of the Met11Thr polymorphism with disease, since this polymorphism is an important determinant for serum level, oligomerization pattern, and function of SP-D.
Serum SP-D was measured using a 5-layer ELISA in 70 SLE patients and 1476 healthy subjects. DNA was genotyped for the Met11Thr variant.
Median SP-D level in serum was 911 ng/ml (95% CI 776-1118) in patients and 1068 ng/ml (95% CI 901-1246) in controls (p = 0.0004). Circulating SP-D did not differ significantly in patients with high, intermediate, or low SLE disease activity. Similarly, SP-D did not correlate with C-reactive protein, erythrocyte sedimentation rate, and anti-dsDNA seropositivity. Genetic analysis did not support an association of the Met11Thr genotype with SLE.
These findings suggest that low SP-D, unrelated to conventional disease indicators, represents an aspect of SLE etiopathogenesis.
The Journal of Rheumatology 11/2009; 36(11):2449-53. · 3.69 Impact Factor
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ABSTRACT: Surfactant protein D (SP-D) is an oligomeric calcium-dependent lectin with important roles in innate host defence against infectious microorganisms. Several studies have shown that patients with inflammatory lung disease have elevated levels of circulating SP-D, and serum SP-D has been suggested to be used as a biomarker for disease e.g. in COPD. We aimed to investigate the variation of circulating SP-D in healthy individuals in and between days for 6 months. In addition, we studied the SP-D response to a standardized physical exercise programme. SP-D was measured in serum using a 5-layered ELISA technique. We found that circulating SP-D remained constant over a 6-month period. However, during the course of one day SP-D varied significantly. Median SP-D peaked at 10 a.m. at 1009 ng/ml (95% CI: 803-1497), subsequently decreasing to nadir at 10 p.m. at 867 ng/ml (95% CI: 650-1148)(P<0.00005). Median pre-exercise level of SP-D was 746 ng/ml (95% CI: 384-2035), and immediately after cessation of physical activity the median SP-D level was 767 ng/ml (95% CI: 367-1885) (P=0.248). Our findings underscore the importance of standardized blood sampling conditions in future studies on the potential role of SP-D as a biomarker. Importantly, stable measures of systemic SP-D over a prolonged period support that SP-D is suitable for biomarker studies.
Immunobiology 06/2009; 215(4):314-20. · 3.20 Impact Factor
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Søren Jacobsen,
Peter Garred,
Hans Ole Madsen,
Niels H H Heegaard,
Merete Lund Hetland,
Kristian Stengaard-Pedersen, Peter Junker,
Tine Lottenburger,
Torkel Ellingsen,
Lis Smedegaard Andersen, [......],
Henrik Skjødt,
Jens Kristian Pedersen,
Ulrik Birk Lauridsen,
Anders J Svendsen,
Ulrik Tarp,
Jan Pødenphant,
Hanne Lindegaard,
Aage Vestergaard,
Mikkel Østergaard,
Kim Hørslev-Petersen
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ABSTRACT: 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).
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).
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.
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.
The Journal of Rheumatology 05/2009; 36(4):731-5. · 3.69 Impact Factor
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ABSTRACT: To investigate the issue of conjoint reliability over time.
A discrete choice experiment was applied using scenarios that describe the effect of treating rheumatoid arthritis patients with TNF-alpha inhibitors, a novel class of highly effective, but expensive antirheumatic agents. Respondents participated in three face-to-face interviews over a period of 4 months. Reliability was measured both at the input level, where the consistency of matches made by respondents to the Discrete Choice Experiment (DCE) question between replications was determined, and at the output level, where the parameters of the conjoint model were estimated and tested for joint significance and willingness to pay (WTP) confidence intervals were calculated.
Input level: Of the 1661 choices made in survey 1, 1316 were repeated in survey 2. Based on the observed number of consistently repeated choices and the expected number by chance, a fair agreement between the choices in the two surveys (chi2 = 324) was found. Of the 998 consistently repeated choices from survey 1 to survey 2, 818 were repeated in survey 3. There was again a high level of consistency between the choices in surveys 1 and 2 and the final choice in survey 3. Output level: The confidence intervals for WTP figures in surveys 1 and 2 and 1 and 3 were overlapping, implying that the DCE was reliable at the output level over time.
The proportion of consistent responses was higher than would be expected by chance. Conjoint reliability over time was found both at the input and output level.
Value in Health 01/2009; 12(1):153-8. · 2.19 Impact Factor
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ABSTRACT: Rheumatoid arthritis (RA) is a chronic disabling inflammatory joint disease of unknown aetiology. Genetic and environmental factors are implicated in its pathogenesis. We performed a literature search on MEDLINE, the Cochrane database and EMBASE on the interaction between smoking and RA. It is concluded that previous and current smoking constitute a risk factor for RA development. Smoking acts synergistically with other RA risk factors, including IgM-rheumatoid factor, anti-CCP and shared epitopes. The effect of smoking on the course of RA has not been described in sufficient detail.
Ugeskrift for laeger 10/2008; 170(37):2864-9.
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ABSTRACT: To study serum levels of serum amyloid P component (SAP) and SAP-DNA complexes in a population-based cohort of patients with systemic lupus erythematosus (SLE).
The study population comprised 82 unselected patients of predominantly Scandinavian ancestry with SLE according to current classification criteria. Serum samples were collected at baseline and serially for up to 2 years. SAP component and SAP-DNA complexes were measured by ELISA. Associations between SAP-DNA and clinical manifestations or serological findings were analyzed. Ninety healthy, age-matched blood donors served as controls.
SLE patients had normal serum concentrations of SAP, whereas SAP-DNA complexes were decreased. Two-thirds of the SLE patients tested persistently SAP-DNA complex-negative. There was no relationship between the occurrence of SAP-DNA complexes and clinical manifestations. SAP-DNA-negative patients tended to have lower leukocyte counts and complement C3 levels, and higher erythrocyte sedimentation rates and C3d levels versus SAP-DNA-positive patients. There was an inverse association between the occurrence of anti-double-stranded DNA (anti-dsDNA) antibodies and SAP-DNA complexes. Co-occurrence of SAP-DNA complexes and anti-dsDNA antibodies was demonstrated in only one SLE patient, implying that 81/82 patients were discordant for the presence of anti-dsDNA antibodies and SAP-DNA complexes.
The decreased level of SAP-DNA complexes in SLE patients and the inverse relationship between these complexes and anti-dsDNA antibody supports the concept that SAP component is implicated in the clearance of cell nuclear debris.
The Journal of Rheumatology 05/2008; 35(4):625-30. · 3.69 Impact Factor
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M L Hetland,
B Ejbjerg,
K Hørslev-Petersen,
S Jacobsen,
A Vestergaard,
A G Jurik,
K Stengaard-Pedersen, P Junker,
T Lottenburger,
I Hansen, [......],
O Majgaard,
A J Svendsen,
T Ellingsen,
H Lindegaard,
A F Christensen,
J Vallø,
T Torfing,
E Narvestad,
H S Thomsen,
M Ostergaard
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ABSTRACT: To identify predictors of radiographic progression in a 2-year randomised, double-blind, clinical study (CIMESTRA) of patients with early rheumatoid arthritis (RA).
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.
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.
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.
NCT00209859.
Annals of the rheumatic diseases 04/2008; 68(3):384-90. · 8.11 Impact Factor
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ABSTRACT: A nationwide unselected twin population to estimate the relative importance of genetic and environmental effectors in the aetiopathogenesis of psoriatic arthritis (PsA).
The study comprised three Danish nationwide twin cohorts. In 1994 and 2002 a total of 37 388 and 46 418 Danish twin individuals respectively were asked by questionnaire if they had PsA. Twins reporting PsA were invited to participate in a clinical examination. Patients were classified according to the Moll and Wright and the CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria. Heritability was estimated by probandwise concordance rates and variance component analysis.
228 twin individuals reported PsA. Following diagnostic validation in 164 (70%), 50 probands were diagnosed with PsA according to the Moll and Wright criteria. Five of their co-twins were either dead, had emigrated, or did not participate in the twin study and nine did not respond, resulting in 36 complete pairs. A total of one of 10 monozygotic pairs and one of 26 dizygotic pairs were concordant for PsA, yielding a 6.2% difference in proportions (95% CI: -11%, 37%). Five of 10 monozygotic pairs and four of 26 dizygotic pairs were concordant for psoriatic skin disease implying a 35% difference (95% CI: 2%, 60%, p<0.05).
This first twin study on PsA confirms that genes are important in the causation of psoriatic skin disease. Despite the limited statistical power, the almost identical concordance rates for PsA in monozygotic and dizygotic twins stresses the importance of the continued search for non-genetic effectors in PsA.
Annals of the rheumatic diseases 02/2008; 67(10):1417-21. · 8.11 Impact Factor
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ABSTRACT: To apply and compare different classification criteria on a representative nationwide sample of psoriatic arthritis (PsA) twins and to estimate the prevalence and incidence of PsA.
The study comprised three Danish nationwide twin cohorts. In 1994 37 388 Danish twin individuals and in 2002 46 418 twin individuals received a questionnaire, including questions on rheumatic diseases. Twins reporting PsA and their co-twins were classified according to the Moll and Wright and CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria based on interview, clinical examination and scrutiny of medical records.
228 twin individuals reported PsA and 164 (72%) participated in clinical validation. By using the Moll and Wright and CASPAR criteria, 54 and 50 cases were diagnosed with PsA respectively. The positive predictive value of self-reported PsA was 31%. According to the Moll and Wright and CASPAR criteria the prevalence was 0.15% (95% CI: 0.13%, 0.22%) and 0.14% (95% CI: 0.11%, 0.19%) respectively. The annual incidence rate based on new self-reported cases in 2002 was 6/100 000 person-years (95% CI: 3/100 000 person-years, 11/100 000 person-years).
The positive predictive value of self-reported PsA was 31%. The prevalence and incidence figures of PsA were equivalent to the previously reported occurrence in population- and hospital-based studies.
Annals of the rheumatic diseases 02/2008; 67(10):1422-6. · 8.11 Impact Factor
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Merete Lund Hetland,
Kristian Stengaard-Pedersen, Peter Junker,
Tine Lottenburger,
Torkell Ellingsen,
Lis Smedegaard Andersen,
Ib Hansen,
Henrik Skjødt,
Jens Kristian Pedersen,
Ulrik Birk Lauridsen,
Anders Svendsen,
Ulrik Tarp,
Jan Pødenphant,
Gert Hansen,
Hanne Lindegaard,
Anselmo de Carvalho,
Mikkel Østergaard,
Kim Hørslev-Petersen
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ABSTRACT: 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.
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.
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.
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.
Arthritis & Rheumatism 06/2006; 54(5):1401-9. · 7.87 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Ugeskrift for laeger 12/2005; 167(47):4458-61.
