| 1. |
- 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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| 2. |
- Martinsson, Klara, et al.
(författare)
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Elevated free secretory component in early rheumatoid arthritis and prior to arthritis development in patients at increased risk
- 2020
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 59:5, s. 979-987
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Considering growing evidence of mucosal involvement in RA induction, this study investigated circulating free secretory component (SC) in patients with either recent-onset RA or with ACPA and musculoskeletal pain. Methods. Two prospective cohorts were studied: TIRA-2 comprising 452 recent-onset RA patients with 3 years of clinical and radiological follow-up, and TIRx patients (n = 104) with ACPA IgG and musculoskeletal pain followed for 290 weeks (median). Blood donors and three different chronic inflammatory diseases served as controls. Free SC was analysed by sandwich ELISA. Results. Serum levels of free SC were significantly higher in TIRA-2 patients compared with TIRx and all control groups (P < 0.01). Among TIRx patients who subsequently developed arthritis, free SC levels were higher compared with all control groups (P < 0.05) except ankylosing spondylitis (P = 0.74). In TIRA-2, patients with ACPA had higher baseline levels of free SC compared with ACPA negative patients (P < 0.001). Free SC status at baseline did not predict radiographic joint damage or disease activity over time. In TIRx, elevated free SC at baseline trendwise associated with arthritis development during follow-up (P = 0.066) but this disappeared when adjusting for confounders (P = 0.72). Cigarette smoking was associated with higher levels of free SC in both cohorts. Conclusion. Serum free SC levels are increased in recent-onset RA compared with other inflammatory diseases, and associate with ACPA and smoking. Free SC is elevated before arthritis development among ACPA positive patients with musculoskeletal pain, but does not predict arthritis development. These findings support mucosal engagement in RA development.
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| 3. |
- Reckner Olsson, Åsa, 1965-, et al.
(författare)
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Aetiological factors of importance for the development of rheumatoid arthritis
- 2004
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 33:5, s. 300-306
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate exposure to external factors associated with risk or prevention of rheumatoid arthritis (RA).Methods: Two hundred and ninety‐three incident cases of RA and 1346 population‐based referents were included in a case‐referent study, in which previous exposure experiences were collected through a postal questionnaire.Results: An inverse association between RA and additional schooling after compulsory school was seen for men. Current smoking was associated with significantly increased risks of RA for men and women [odds ratio (OR) 2.9, 95% confidence interval (CI) 1.4–6.4, and OR 1.8, 95% CI 1.1–2.9, respectively], as was previous smoking for men (OR 2.3, 95% CI 1.2–4.4). There were also indications of relationships between previous use of a private well and RA in both men and women.Conclusion: Several previously published associations have been reproduced in the present study, which also generates some new hypotheses that suggest further research.
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| 4. |
- Reckner Olsson, Åsa, 1965-, et al.
(författare)
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Allergic manifestations in patients with rheumatoid arthritis
- 2003
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 111:10, s. 940-944
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Tidskriftsartikel (refereegranskat)abstract
- A functional dichotomy between Th1- and Th2-type immune responses has been suggested. This study was performed to investigate whether rheumatoid arthritis (RA), a disease with indications of Th1-deviated immune activation, is inversly related to atopic conditions which are Th2-mediated. Two hundred and sixty-three adult cases of RA, fulfilling the American Rheumatism Association (ARA) 1987 Revised Classification Criteria for RA, were identified in 1995 and compared with 541 randomly selected population referents. The presence of atopic manifestations was established through a postal questionnaire and by demonstrating circulating IgE antibodies to common allergens. RA was inversely associated with certain manifestations of rhinitis, which were regarded as the most reliable indicators of atopic disease in the present study. However, no negative association was seen between RA and asthma and eczema, respectively. The main results give some support for an inverse relationship between RA and rhinitis. The prevalence of circulating IgE antibodies was however similar in cases and controls, suggesting that the T-cell commitment mainly occurs in the affected organs.
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| 5. |
- Reckner Olsson, Åsa, 1965-, et al.
(författare)
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Comorbidity and lifestyle, reproductive factors, and environmental exposures associated with rheumatoid arthritis
- 2001
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 60:10, s. 934-939
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To evaluate the influence of lifestyle, reproduction, and some external factors on the development of rheumatoid arthritis (RA) and to describe its comorbidity.METHODS Cases were identified retrospectively from 1980 to 1995 at the University Hospital in Linköping, Sweden. The study comprised 422 cases and 859 randomly selected population referents. Data on possible aetiological factors and comorbidity were collected by postal questionnaire.RESULTS The response rates were 67% among cases and 59% among referents. A decrease in the occurrence of atopic allergy was seen in the cases (odds ratio (OR) 0.6, 95% confidence interval (CI) 0.4 to 1.0). There was a positive association between RA and insulin treatment (OR 10.2, 95% CI 1.7 to 60.8) in women, and women with a short fertile period had an increased risk of RA (OR 2.5, 95% CI 1.1 to 5.4). Current and previous smoking were associated with increased risks for RA in both sexes, and in men a dose-response relationship was found with number of tobacco pack years (p for trend <0.005). The risk for RA decreased with increasing level of education in both men and women. Increased risks were seen in men born into households with private wells (OR 2.8, 95% CI 1.5 to 5.2), residentially exposed to mould (OR 4.6, 95% CI 1.1 to 20.2), or exposed to farm animals (OR 3.3, 95% CI 0.7 to 16.6). In women there were positive associations between RA and reporting a previous joint injury (OR 2.5, 95% CI 1.0 to 6.6) and prolonged exposure to hair dyes (OR 1.9, 95% CI 0.8 to 4.5).CONCLUSIONS RA, a disease with features of T helper 1 (Th1) dominated immune response, was inversely associated with atopic allergy, a Th2 dominated condition, while there were indications of a strong positive association with Th1 related diabetes mellitus. The results support a causal relationship between smoking and RA. The level of education was inversely associated with RA, while there was a positive association between RA and certain residential factors in men and a short fertile period in women.
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| 6. |
- Reckner Olsson, Åsa, 1965-
(författare)
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Occupational and environmental aspects on the aetiology of rheumatoid arthritis
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Two questionnaire-based case-referent studies were performed to primarily assess the impact from occupational and environmental exposures on the aetiology of rheumatoid arthritis (RA). The two studies included prevalent and incident cases of RA, respectively. All determinants were evaluated separately for the two materials, and potential occupational risk factors were also analysed after pooling of the two studies. Most associations found between occupational exposures and RA regarded men. Increased risks for RA were seen for exposure to asphalt (OR 6.0, 95% CI 1.6-27.7), vibrations (OR 2.1, 95% CI 1.4-3.3), crops and/or forage (OR 2.0, 95% CI 1.3-3.0), mineral dust (OR 1.8, 95 % CI 1.0-3.2). and mineral oil (OR 1.5, 95 % CI 1.0-2.3 ), with dose-response relationships between RA and exposure to mineral dust and vibrations. Occupational categories at increased risk of RA among men were conductors, freight and transport workers (OR 4.6, 95 % CI 1.4-15.0), pulp and paper workers (OR 3.9, 95 % CI 1.2-12.8), and farmers (OR 2.3, 95 % CI 1.4-3.5). Regarding women, increased risks for RA were seen for exposure to meat (OR 2.2, 95 % CI 1.0-4.9), hairdressing chemicals (OR 1.7, 95 % CI 0.7-4.5), and for hairdressers (OR 1.7, 95 % CI 0.7-4.0). The results refer to the pooled material.Regarding leisure-time activities, an increased risk was seen for mineral oil exposure among men in the study with incident cases (OR 2.0, 95 % CI 0. 7-6.2 ). In this study, an association was also seen for men for having ever used a private well (OR 1.5, 95 % CI 0.8-2.9). In the study with prevalent cases, associations were seen for both sexes for having been exposed to water from a private well at time of birth (OR 1.5, 95 % CI 0.9-2.4 for women, and OR 2.8, 95 % CI 1.5-5.2 for men). The risk of RA was increased for men with previous exposure to mould indoors (OR 4.6, 95 % CI 1,1-20.2 ), and an association was also seen for long time use of hair dyes and/or bleach among women (OR 1.9, 95 % CI 0.8-4.5). In the study with incident cases, the risk for RA was increased among men with previous use of skin lotion (OR 3.0, 95 % CI 0.9-9.8).For both sexes, increased risks for RA were seen for current and previous smoking, with even higher ORs for seropositive cases among men. In the study with incident cases, male subjects with more than 20 pack years of smoking had an OR of 2.5 (95 % CI 1.2-5.1), corresponding to an OR of 1.6 (95% CI 0.9-3.1) among women. There was a tendency towards increasing risks with increasing number of pack years for men in both studies, with significant tests for trend in the study with prevalent cases. For both sexes, higher schooling resulted in a decreased risk for RA.The relationship between RA and allergy was evaluated more extensively in a cross-sectional study, and negative associations between RA and certain manifestations of hay fever were found. An almost significantly decreased risk for allergy was found in the study with prevalent cases with both sexes included in the analysis (OR 0.6, 95 % CI 0.4-1.0). Regarding other comorbidity, there were positive associations between RA and self-repotted thyroid conditions (OR 3.5. 95 % CI 1.1-10.8) and previous treatment with insulin (OR 10.2, 95 % CI 1.7-60.8) among women in the study with prevalent cases. In the cross-sectional study, there was an association between RA and diabetes (OR 2.8. 95 & CI 0.9-8.9), with both sexes included in the analysis. Associations were seen between previous joint trauma and RA for women in both case-referent studies (OR 2.5, 95 % CI 1.0-6.6 in the study with prevalent cases) as well as for men in the study with incident cases (OR 2.2, 95% CI 0.6-7.1).Altogether, the determinants conveying the risk for RA differ between sexes. RA is a condition most often affecting women. but the present studies, as well as previous research, have established that most extemal factors evaluated so far seem to be of more importance for men than women.
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| 7. |
- Reckner Olsson, Åsa, 1965-, et al.
(författare)
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Occupations and exposures in the work environment as determinants for rheumatoid arthritis
- 2004
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 61:3, s. 233-238
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Several occupational categories have been associated with rheumatoid arthritis (RA); this study was conducted to further evaluate these associations.Methods: Lifelong occupational history together with exposure experiences were collected through a postal questionnaire answered by 293 incident cases and 1346 population based referents. Occupational determinants were evaluated through stratified and multivariate analyses; pooled analyses with previously gathered data on 422 prevalent cases and 858 referents were also performed.Results: In both materials, significantly increased logistic odds ratios (LORs) were seen for male conductors, freight and transport workers (LOR 17.8, 95% CI 1.5 to 207.8 and LOR 4.7, 95% CI 1.4 to 16.3, respectively), and farmers and farm workers (LOR 2.4, 95% CI 1.1 to 5.2, and LOR 2.2, 95% CI 1.3 to 3.5, respectively). Among women, increased LORs were seen in the separate and the pooled material for printmakers and process engravers (LOR 5.5, 95% CI 0.9 to 32.6, and LOR 3.0, 95% CI 0.9 to 10.3, respectively). Increased risks were seen in both materials for men exposed to asbestos (LOR 2.5, 95% CI 1.0 to 6.8, and LOR 1.6, 95% CI 0.8 to 3.3, respectively), and vibrations (LOR 2.0, 95% CI 0.9 to 4.4, and LOR 2.2, 95% CI 1.3 to 3.8, respectively). The risk for RA increased with increasing duration of exposure to vibrations and mineral dust, respectively.Conclusions: There was evidence of a causal relation between exposures to vibrations and mineral dust and development of RA among men. Occupational factors seem to be aetiologically more important for men, and most occupations at risk involve multiple exposures. Several exposures associated with an increased risk for RA are frequent among farmers, and some of the occupations at risk include exposure to organic dust.
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| 8. |
- Svärd, Anna, et al.
(författare)
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A Comparison Between IgG- and IgA-class Antibodies to Cyclic Citrullinated Peptides and to Modified Citrullinated Vimentin in Early Rheumatoid Arthritis and Very Early Arthritis
- 2011
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Ingår i: Journal of Rheumatology. - : Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 38:7, s. 1265-1272
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Because of their slightly higher sensitivity, it has been argued that antibodies to modified citrullinated vimentin (anti-MCV) are superior to antibodies to cyclic citrullinated peptides (anti-CCP), while others claim that anti-CCP is preferable because of higher diagnostic specificity for rheumatoid arthritis (RA). We evaluated IgG- and IgA-class anti-MCV and anti-CCP as diagnostic and prognostic markers in early arthritis. less thanbrgreater than less thanbrgreater thanMethods. Two Swedish arthritis populations were examined: 215 patients with early RA (andlt;= 12 months duration) from the Swedish TIRA-1 cohort, and 69 patients with very early arthritis (andlt;= 3 months duration) from the Kronoberg Arthritis Incidence cohort, in which 22% were diagnosed with RA. IgG anti-CCP and anti-MCV antibodies were analyzed with commercial kits. These tests were modified for IgA-class antibody detection. less thanbrgreater than less thanbrgreater thanResults were related to disease course, smoking habits, and shared epitope status. Results. In the TIRA-1 cohort, occurrence of IgG anti-MCV and IgG anti-CCP showed a 93% overlap, although IgG anti-MCV had higher diagnostic sensitivity. Twenty-four percent tested positive for IgA anti-MCV compared to 29% for IgA anti-CCP. In the Kronoberg Arthritis Incidence cohort, 15% tested positive for IgG anti-MCV and 6% for IgA anti-MCV, compared to 10% positive for IgG anti-CCP and 3% positive for IgA anti-CCP, revealing that anti-CCP had higher diagnostic specificity for RA. As previously reported for IgA anti-CCP, IgA anti-MCV antibodies occurred in a small proportion of high-level IgG antibody-positive sera and were associated with a more aggressive disease course. Smokers were more often positive for antibodies to citrullinated proteins, most strikingly among the patients who were IgA anti-MCV-positive. less thanbrgreater than less thanbrgreater thanConclusion. The occurrences of IgG-class anti-MCV and anti-CCP in early RA largely overlap. The sensitivity of anti-MCV is slightly higher, while the diagnostic specificity is higher for anti-CCP. In both instances a positive test predicts an unfavorable disease course, possibly slightly more so for anti-MCV. Although associated with a more active disease over time, IgA-class anti-CCP or anti-MCV do not add any diagnostic advantage.
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| 9. |
- Svärd, Anna, et al.
(författare)
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Presence and utility of IgA-class antibodies to cyclic citrullinated peptides in early rheumatoid arthritis : the Swedish TIRA project
- 2008
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe present study was carried out to assess whether IgA-class antibodies against cyclic citrullinated peptides (IgA anti-CCP) in recent-onset rheumatoid arthritis add diagnostic and/or prognostic information to IgG anti-CCP analysis.MethodsSerum samples were obtained from 228 patients with recent-onset (<12 months) rheumatoid arthritis at the time of inclusion in the Swedish TIRA cohort (Swedish Early Intervention in Rheumatoid Arthritis). Sera from 72 of these patients were also available at the 3-year follow-up. Disease activity and functional ability measures (erythrocyte sedimentation rate, serum C-reactive protein, 28-joint count Disease Activity Score, physician's assessment of disease activity, and the Swedish version of the Health Assessment Questionnaire) were registered at inclusion and at regular follow-ups during 3 years. An IgA anti-CCP assay was developed based on the commercially available IgG-specific enzyme immunoassay from EuroDiagnostica (Arnhem, the Netherlands), replacing the detection antibody by an anti-human-IgA antibody. A positive IgA anti-CCP test was defined by the 99th percentile among healthy blood donors.ResultsAt baseline, a positive IgA anti-CCP test was observed in 29% of the patient sera, all of which also tested positive for IgG anti-CCP at a higher average level than sera containing IgG anti-CCP alone. The IgA anti-CCP-positive patients had significantly higher disease activity over time compared with the IgA anti-CCP-negative patients. After considering the IgG anti-CCP level, the disease activity also tended to be higher in the IgA anti-CCP-positive cases – although this difference did not reach statistical significance. The proportion of IgA anti-CCP-positive patients was significantly larger among smokers than among nonsmokers.ConclusionAnti-CCP antibodies of the IgA class were found in about one-third of patients with recent-onset rheumatoid arthritis, all of whom also had IgG anti-CCP. The occurrence of IgA-class antibodies was associated with smoking, and IgA anti-CCP-positive patients had a more severe disease course over 3 years compared with IgA anti-CCP-negative cases. Although IgA anti-CCP analysis does not seem to offer any diagnostic information in addition to IgG anti-CCP analysis, further efforts are justified to investigate the prognostic implications.
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