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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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- Gonzalez-Gay, MA, et al.
(författare)
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Timing of onset affects arthritis presentation pattern in antisynthetase syndrome
- 2018
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Ingår i: Clinical and Experimental Rheumatology. - 1593-098X. ; 36:1, s. 44-49
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate if the timing of appearance with respect to disease onset may influence the arthritis presentation pattern in antisynthetase syndrome (ASSD). Methods The patients were selected from a retrospective large international cohort of ASSD patients regularly followed-up in centres referring to AENEAS collaborative group. Patients were eligible if they had an antisynthetase antibody testing positive in at least two determinations along with arthritis occurring either at ASSD onset (Group 1) or during the course of the disease (Group 2). Results 445 (70%; 334 females, 110 males, 1 transsexual) out of the 636 ASSD we collected had arthritis, in the majority of cases (367, 83%) from disease onset (Group 1). Patients belonging to Group 1 with respect to Group 2 had an arthritis more commonly polyarticular and symmetrical (p=0.015), IgM-Rheumatoid factor positive (p=0.035), erosions at hands and feet plain x-rays (p=0.036) and more commonly satisfying the 1987 revised classification criteria for rheumatoid arthritis (RA) (p=0.004). Features such as Raynaud's phenomenon, mechanic's hands and fever (e.g. accompanying findings) were more frequently reported in Group 2 (p=0.005). Conclusion In ASSD, the timing of appearance with respect to disease onset influences arthritis characteristics. In particular, RA features are more common when arthritis occurs from ASSD onset, suggesting an overlap between RA and ASSD in these patients. When arthritis appears during the follow-up, it is very close to a connective tissue disease-related arthritis. Also, the different prevalence of accompanying features between these two groups is in line with this possibility. © Clinical and Experimental Rheumatology 2018.
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- Liukkonen, J, et al.
(författare)
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PREDICTORS OF CHANGE IN DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS AFTER START OF TREATMENT WITH ABATACEPT
- 2021
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 552-553
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Abatacept is a biologic disease-modifying anti-rheumatic drug (bDMARD) used to treat rheumatoid arthritis (RA) since 2006, acting by inhibition of T-cell co-stimulation. There are limited data on factors predicting clinical outcomes in RA after start of treatment with abatacept.Objectives:The primary aim was to identify predictors of change in disease activity in RA-patients after start of treatment with abatacept.Methods:This cohort study was based on data from the Swedish Rheumatology Quality register (SRQ). All patients with RA who started treatment with abatacept between 2006 and 2017 were included. Clinical data from the SRQ included demographics, disease characteristics and antirheumatic treatment. Disease activity was measured according to DAS28-ESR (Disease Activity Score of 28 joints based on erythrocyte sedimentation rate) at inclusion and at follow-up visits at 6 and 12 months from start of treatment with abatacept. Baseline predictors of change in disease activity were investigated using linear regression models bivariately and adjusted for baseline values of DAS28. Covariates with a p-value of <0.1 were retained for the final multivariate model. In case of covariates with major collinearity, the one with the stronger association with change of DAS28 was selected.Results:In a total of 2716 patients, 872 had data on change in DAS28 at 12 months. Among these, most patients were women (79.6%) and the mean age at start of abatacept was 58.4 years (SD 13.6). The majority of patients had established RA, with a mean disease duration of 13.5 years (SD 11.1). Most patients had severe, active disease, with substantial pain and disability, despite extensive treatment. The mean number of bDMARDs that a patient had been exposed to was 1.90 (SD 1.32). DAS28 decreased significantly over the first year (mean 1.22: 95 % CI 1.12, 1.32). The greatest decrease in DAS28 (mean 1.09) occurred during the first 6 months from start of abatacept. The multivariate regression model identified male sex and limited previous bDMARD exposure as independent predictors of change in DAS28 at 12 months from start of abatacept – adjusted for baseline DAS28, RA duration and current treatment with methotrexate or prednisolone (Table 1).Table 1.Determinants for retransitioningBivariateAdjusted for baseline DAS28MultivariateVariablesB95% CIP-valueB95% CIP-valueB95% CIP-valueMale sex0.39[0.13, 0.64]0.0030.43[0.20, 0.66]<0.0010.42[0.19, 0.64]<0.001Age (per SD)0.10[-0.004, 0.21]0.0580.044[-0.051, 0.14]0.37N/ARA duration (per SD)-0.14[-0.25, -0.037]0.008-0.11[-0.21, -0.016]0.022-0.030[-0.13, 0.065]0.54HAQ (per SD)0.12[0.007, 0.23]0.037-0.24[-0.35, -0.13]<0.001N/AVAS pain (per SD)0.26[0.15, 0.37]<0.001-0.058[-0.17, 0.054]0.31MTX10.20[-0.013, 0.41]0.0660.17[-0.018, 0.36]0.0760.11[-0.076, 0.29]0.25Prednisolone1-0.19[-0.41, 0.017]0.072-0.17[-0.36, 0.024]0.087-0.14[-0.33, 0.043]0.13bDMARDs2 (per SD)-0.30[-0.40, -0.20]<0.001-0.32[-0.41, -0.23]<0.001-0.31[-0.40, -0.21]<0.001B=beta coefficient; N/A=not applicable; SD=standard deviation; CI=confidence interval. Bold text indicates significant associations.DAS28, Disease activity Score of 28 joints; RA, rheumatoid arthritis; HAQ, Health Assessment Questionnaire; VAS, visual analogue scale; MTX, methotrexate; bDMARD, biologic disease-modifying antirheumatic drug.1Current treatment2Number of previous bDMARDsConclusion:In this national register study, male sex and limited previous exposure to bDMARDs were independent predictors of reduction of disease activity one year after start of treatment with abatacept for RA, possibly reflecting a better prognosis overall in such patients.Disclosure of Interests:Julia Liukkonen: None declared, Giovanni Cagnotto: None declared, Jan-Åke Nilsson: None declared, Saedis Saevarsdottir: None declared, Carl Turesson Speakers bureau: Abbvie, Bristol Myers-Squibb, Medac, Pfizer, Roche., Consultant of: Roche, Grant/research support from: This study was supported by an unrestricted grant from Bristol-Myers Squibb
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