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- Hetland, M. L., et al.
(författare)
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Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial
- 2020
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 371
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. DESIGN Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. SETTING Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018. PARTICIPANTS Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein. INTERVENTIONS Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intraarticular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab. MAIN OUTCOME MEASURES The primary outcome was adjusted clinical disease activity index remission (CDAI <= 2.8) at 24 weeks with active conventional treatment as the reference. Key secondary outcomes and analyses included CDAI remission at 12 weeks and over time, other remission criteria, a non-inferiority analysis, and harms. RESULTS 812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval -5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and -0.6% (-10.1% to 8.9%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. CONCLUSIONS All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis.
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| 3. |
- Van Bentum, R, et al.
(författare)
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MICROVASCULAR CHANGES OF THE RETINA IN ANKYLOSING SPONDYLITIS, AND THE ASSOCIATION WITH CARDIOVASCULAR DISEASE - THE EYE FOR A HEART STUDY.
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 1654-1654
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Patients with ankylosing spondylitis (AS) have an increased risk at cardiovascular disease (CVD). Microvasculature changes might precede overt CVD, but have been poorly studied in AS. The small vessels of the retina are accessible for non-invasive visualization, and microvascular changes (retinal arteriolar narrowing, venular widening, loss of tortuosity) are described in association with CVD in other diseases.Objectives:The aim of this study was to compare the retinal microvasculature of AS patients with healthy controls, and to assess gender differences.Methods:A cross-sectional, case-control study comparing AS patients (fulfilling the modified New York criteria, Rheumatology outpatient clinic of Reade and Amsterdam UMC) with healthy controls (EMIF-AD PreClinAD cohort of the Dutch Twins Register(1)), men:women=1:1. Most important inclusion criteria were: age 50-75 years, diabetes mellitus was excluded. All subjects underwent Optical Coherence Tomography Angiography and fundus photography (≥1 eye), analyzed with Singapore I Vessel Assessment software (Table 2). Differences between AS and controls were evaluated with generalised estimating equations (GEE), adjusted for demographics and cardiovascular risk, and stratified for gender.Results:In total, 59 AS patients (mean disease duration 36 years) and 105 controls were included. Controls were significantly older than patients, but did not differ in cardiovascular profile (Table 1). Patients had a significantly lower retinal arteriolar tortuosity (β-0.1;p=0.02), and higher vessel density (β 0.5,p=0.02), than controls (Table 2). Also, male AS patients showed a lower arteriovenular ratio compared to male controls (β -0.03,p=0.04). There were no differences between women with and without AS. In AS, a high disease activity was associated with a wider (unfavorable) venular diameter (p=0.05), whereas biologic use showed a wider (more favorable) arteriolar diameter (p<0.01).Conclusion:This study detected several retinal microvascular changes, in AS patients compared to controls, of which some are associated with CVD based on previous studies. Some changes were only observed in male-, but not in female, patients. A new finding was an increased capillary density in AS, of which the association with CVD-risk has not yet been studied before.References:[1]Konijnenberg E et al. The EMIF-AD PreclinAD study: study design and baseline cohort overview. Alzheimers Res Ther. 2018; 10:75.Table 1.Patient characteristics AS (n=57) and controls (n=105)ASControlspGender, women (%)30 (51)52 (50)nsAge, mean yrs (SD)60 (6)68 (4)<0.01Smoking currently, yes (%)11 (19)8 (8)0.06Body mass index, mean (SD)26 (4)26 (3)nsHypertension, yes (%)23 (39)39 (37)nsDyslipidemia, yes (%)9 (15)18 (17)nsCardiovascular disease history, yes (%)9 (15)15 (14)nsNSAIDS (%)24 (41)6 (6)<0.01Biological (mostly TNF inhibitor)* (%)29 (49)0 (0)<0.01AS Disease Activity Score, mean (SD)2.1 ±0.9Table 2.Retinal vascular parameters, differences AS and Control subjectsCrudeAdjusted for:Age, gender, BMI smoking, hypertension, dyslipidemiaRetinal vascular parametersβ(95%CI)pβ(95%CI)pDiameterArteriolar1.6(-2.0, 5.2)0.37-0.2(-4.8, 4.4)0.92Venular5.4(-0.66, 11.5)0.082.5(-5.4, 10.4)0.53Arteriovenular ratio-0.01(-0.03, 0.01)0.43-0.01(-0.03, 0.02)0.65TortuosityArteriolar-0.05(-0.12, 0.03)0.19-0.1(-0.2, -0.01)0.02ComplexityFractal dimension0.01(0.00, 0.03)0.040.0(-0.02, 0.02)0.88Vessel DensityInner ring0.8(0.5, 1.1)<0.0010.5(0.1, 0.9)0.02Outer ring0.7(0.4, 1.0)<0.0010.2(-0.2, 0.6)0.42Disclosure of Interests:Rianne van Bentum: None declared, Milad Baniaamam: None declared, Buket Kinaci-Tas: None declared, Jacoba van de Kreeke: None declared, Pieter Jelle Visser: None declared, Erik Serné: None declared, Michael Nurmohamed Grant/research support from: Not related to this research, Consultant of: Not related to this research, Speakers bureau: Not related to this research, Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma
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