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Article ; Online: Disease-modifying antirheumatic drugs and risk of thyroxine-treated autoimmune thyroid disease in patients with rheumatoid arthritis.

Waldenlind, Kristin / Delcoigne, Bénédicte / Saevarsdottir, Saedis / Askling, Johan

2023 Volume 295, Issue 3, Page(s) 313–321

Abstract: Background: Autoimmune thyroid disease (AITD) and rheumatoid arthritis (RA) share a genetic background, and the prevalence of AITD in RA patients is increased. Whereas immunomodulatory treatments are used in RA, they are rarely used in AITD.: ... ...

Abstract	Background: Autoimmune thyroid disease (AITD) and rheumatoid arthritis (RA) share a genetic background, and the prevalence of AITD in RA patients is increased. Whereas immunomodulatory treatments are used in RA, they are rarely used in AITD. Objectives: We hypothesized that disease-modifying antirheumatic drugs (DMARDs) as used in RA might lower the risk of incident AITD. Methods: A nationwide cohort study including 13,731 patients with new-onset RA from the Swedish Rheumatology Quality Register 2006-2018 and 63,201 matched general population comparators linked to national registers to identify AITD. We estimated relative risks (hazard ratios) of AITD after RA diagnosis in RA patients compared to the general population, and in relation to DMARD treatment, using Cox regression. Results: Following RA diagnosis, 321 (2.3%) of the RA patients and 1838 (2.9%) of the population comparators developed AITD, corresponding to an incidence of 3.7 versus 4.6 per 1000 person-years, hazard ratio, 0.81; 95% CI, 0.72-0.91. The decreased risk of incident AITD among RA patients compared to the general population was most pronounced among biologic DMARD (bDMARD) treated patients, with a hazard ratio of 0.54; 95% CI, 0.39-0.76. Among RA patients, subgrouped by bDMARD use, TNF-inhibitors were associated with the most pronounced decrease, hazard ratio, 0.67; 95% CI, 0.47-0.96. Conclusions: In contrast to the increased prevalence of AITD in RA patients at diagnosis, our results indicate that the risk of AITD decreases following RA diagnosis. This decrease is especially pronounced in RA patients treated with bDMARDs. These findings support the hypothesis that DMARDs might have a preventive effect on AITD.
MeSH term(s)	Humans ; Antirheumatic Agents/adverse effects ; Thyroxine/therapeutic use ; Cohort Studies ; Arthritis, Rheumatoid/complications ; Arthritis, Rheumatoid/drug therapy ; Thyroid Diseases/complications ; Thyroid Diseases/drug therapy ; Biological Products/therapeutic use
Chemical Substances	Antirheumatic Agents ; Thyroxine (Q51BO43MG4) ; Biological Products
Language	English
Publishing date	2023-11-22
Publishing country	England
Document type	Journal Article
ZDB-ID	96274-0
ISSN	1365-2796 ; 0954-6820
ISSN (online)	1365-2796
ISSN	0954-6820
DOI	10.1111/joim.13743
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Article ; Online: Comorbidities and chance of remission in patients with early rheumatoid arthritis receiving methotrexate as first-line therapy: a Swedish observational nationwide study.

Tidblad, Liselotte / Westerlind, Helga / Delcoigne, Bénédicte / Askling, Johan / Saevarsdottir, Saedis

RMD open

2023 Volume 9, Issue 4

Abstract: Objectives: This study aims to examine whether comorbidities affect the likelihood of reaching primary remission on methotrexate monotherapy as the first disease-modifying antirheumatic drug (DMARD) in early rheumatoid arthritis (RA).: Methods: We ... ...

Abstract	Objectives: This study aims to examine whether comorbidities affect the likelihood of reaching primary remission on methotrexate monotherapy as the first disease-modifying antirheumatic drug (DMARD) in early rheumatoid arthritis (RA). Methods: We used nationwide Swedish clinical and quality registers to collect RA disease activity measures and comorbidity data for patients diagnosed with RA 2007-2020 (n=11 001). The primary outcome was failure to reach 28-joint Disease Activity Score (DAS28) remission at 3 months. Secondary outcomes included Boolean, Simplified Disease Activity Index/Clinical Disease Activity Index remission, European Alliance of Associations for Rheumatology response and no swollen joint count at 3 and 6 months. For each comorbidity, and for combinations thereof, we calculated adjusted relative risks (RRs) of failure to reach remission, using modified Poisson regression. Results: In total, 53% (n=4019/7643) failed to reach DAS28 remission after 3 months of methotrexate monotherapy, ranging from 66% (n=25/38) among patients with chronic kidney disease to 48% (n=154/319) in patients with previous cancer. The risk of not reaching DAS28 remission at 3 months (RR adjusted for sex and age) was increased among patients with endocrine (RR 1.08, 95% CI 1.01 to 1.15), gastrointestinal (RR 1.16, 95% CI 1.03 to 1.30), infectious (RR 1.21, 95% CI 1.06 to 1.38), psychiatric (RR 1.24, 95% CI 1.15 to 1.35) and respiratory comorbidities (RR 1.16, 95% CI 1.01 to 1.32). Having three or more comorbidity categories was associated with a 27% higher risk of DAS28 remission failure at 3 months. A similar pattern was observed for the secondary outcomes. Conclusions: Comorbidities decrease the chance of reaching remission on methotrexate as DMARD monotherapy in patients with early RA and are important to consider when assessing treatment outcomes.
MeSH term(s)	Humans ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/epidemiology ; Arthritis, Rheumatoid/chemically induced ; Comorbidity ; Drug Therapy, Combination ; Methotrexate/therapeutic use ; Sweden/epidemiology
Chemical Substances	Antirheumatic Agents ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2023-12-20
Publishing country	England
Document type	Journal Article ; Observational Study
ZDB-ID	2812592-7
ISSN	2056-5933 ; 2056-5933
ISSN (online)	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2023-003714
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Article ; Online: Evaluation of an individually tailored smoking-cessation intervention for patients with rheumatoid arthritis in an outpatient clinic.

Karlsson, M-L / Hertzberg-Nyquist, K / Saevarsdottir, S / Lundberg, I E / Demmelmaier, I / Pettersson, S / Chatzidionysiou, K

Scandinavian journal of rheumatology

2023 Volume 52, Issue 6, Page(s) 591–600

Abstract: Objective: The aim of this study was to evaluate an individually tailored smoking-cessation intervention delivered in rheumatology care and compare the characteristics of patients who quit smoking with those who did not.: Method: This was an open ... ...

Abstract	Objective: The aim of this study was to evaluate an individually tailored smoking-cessation intervention delivered in rheumatology care and compare the characteristics of patients who quit smoking with those who did not. Method: This was an open single-group prospective intervention study over 24 months, with assessments at baseline and at 6, 12, 18, and 24 months. Current smokers with rheumatoid arthritis (RA) were invited to a smoking-cessation programme including behavioural change support, with or without pharmacotherapy. Data on disease activity, medical treatment, and patient-reported outcomes were retrieved from the Swedish Rheumatology Quality Register. The primary outcome was the proportion of patients at month 24 who reported having quit smoking with self-reported 7 day smoking abstinence. Results: In total, 99 patients participated in the study. Median age was 58 years (interquartile range 50-64); 69% were female and 88% rheumatoid factor and/or anti-cyclic citrullinated peptide positive. At 24 months, 21% of the patients had quit smoking. At 6, 12, and 18 months, 12%, 12%, and 14% of patients, respectively, had quit smoking. For patients still smoking at 24 months, the median number of cigarettes per day was significantly reduced from 12 to 6 (p ≤ 0.001). Among patients who had quit smoking at 24 months, a smaller proportion reported anxiety at baseline compared to those still smoking (28% vs 58%, p = 0.02). Conclusion: A smoking-cessation intervention including behavioural change support with or without pharmacotherapy can be helpful for a substantial number of RA patients. Anxiety is associated with lower smoking-cessation success rates.
MeSH term(s)	Humans ; Female ; Middle Aged ; Male ; Prospective Studies ; Smoking Cessation ; Smoking/adverse effects ; Smoking/epidemiology ; Smoking/therapy ; Ambulatory Care Facilities ; Arthritis, Rheumatoid/therapy
Language	English
Publishing date	2023-02-23
Publishing country	England
Document type	Journal Article
ZDB-ID	121265-5
ISSN	1502-7732 ; 0300-9742
ISSN (online)	1502-7732
ISSN	0300-9742
DOI	10.1080/03009742.2023.2172903
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Article ; Online: Does autoimmune thyroid disease affect rheumatoid arthritis disease activity or response to methotrexate?

Waldenlind, Kristin / Delcoigne, Bénédicte / Saevarsdottir, Saedis / Askling, Johan

RMD open

2020 Volume 6, Issue 2

Abstract: Objective: To investigate if autoimmune thyroid disease (AITD) impacts rheumatoid arthritis (RA) disease activity or response to methotrexate.: Methods: A nationwide register-based cohort study of 9 004 patients with new-onset RA from the Swedish ... ...

Abstract	Objective: To investigate if autoimmune thyroid disease (AITD) impacts rheumatoid arthritis (RA) disease activity or response to methotrexate. Methods: A nationwide register-based cohort study of 9 004 patients with new-onset RA from the Swedish Rheumatology Quality Register year 2006-2016, with linkage to other nationwide registers to identify comorbidity with AITD defined as thyroxine prescription before RA diagnosis, excluding non-autoimmune causes. We compared RA disease activity using 28-joint Disease Activity Score (DAS28) and its components, and EULAR response, between patients with and without AITD, using logistic regression. Results: At diagnosis, patient reported outcome measures (PROMs; patient global, Health Assessment Questionnaire Disability Index and pain) but not objective disease activity measures (erythrocyte sedimentation rate and swollen joint count) were significantly higher (p<0.05 for all PROMs) among RA patients with AITD compared with those without. The level of DAS28 was 5.2 vs 5.1. By contrast, AITD had little influence on EULAR response to methotrexate at 3 months (OR of non/moderate response=0.95, 95% CI 0.8 to 1.1), nor at 6 months. When stratified by age, however, AITD was more common among EULAR non/moderate responders at 3 and 6 months in patients below 45 years resulting in ORs of non/moderate response of 1.44 (0.76-2.76) and 2.75 (1.04-7.28). Conclusion: At diagnosis, RA patients with concomitant AITD score worse on patient reported but not on objective RA disease activity measures, while DAS28 was only marginally elevated. The overall chance of achieving a EULAR good response at 3 or 6 months remains unaffected, although among a limited subgroup of younger patients, AITD may be a predictor for an inferior primary response.
MeSH term(s)	Aged ; Aged, 80 and over ; Antirheumatic Agents/administration & dosage ; Antirheumatic Agents/adverse effects ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/complications ; Arthritis, Rheumatoid/diagnosis ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/epidemiology ; Autoimmune Diseases/complications ; Autoimmune Diseases/epidemiology ; Female ; Humans ; Male ; Methotrexate/administration & dosage ; Methotrexate/adverse effects ; Methotrexate/therapeutic use ; Middle Aged ; Patient Reported Outcome Measures ; Public Health Surveillance ; Registries ; Severity of Illness Index ; Sweden/epidemiology ; Thyroid Diseases/complications ; Thyroid Diseases/epidemiology ; Treatment Outcome
Chemical Substances	Antirheumatic Agents ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2020-09-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2812592-7
ISSN	2056-5933 ; 2056-5933
ISSN (online)	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2020-001282
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Article ; Online: Sleep problems in rheumatoid arthritis over 12 years from diagnosis: results from the Swedish EIRA study.

Lyne, Lauren / Åkerstedt, Torbjörn / Alfredsson, Lars / Lehtonen, Tiina / Saevarsdottir, Saedis / Klareskog, Lars / Westerlind, Helga

RMD open

2022 Volume 8, Issue 1

Abstract: Objective: Most studies of rheumatoid arthritis (RA) and sleep have focused on established RA. We here investigate sleep quality and sleep duration in patients with newly diagnosed RA and during 1-12 years after diagnosis.: Methods: Data were ... ...

Abstract	Objective: Most studies of rheumatoid arthritis (RA) and sleep have focused on established RA. We here investigate sleep quality and sleep duration in patients with newly diagnosed RA and during 1-12 years after diagnosis. Methods: Data were collected on sleep 1-12 years after diagnosis from patients diagnosed 1998-2018 in the Swedish study Epidemiological Investigation of RA. Six sleep domains (sleep problems, non-restorative sleep, insomnia, insufficient sleep, sleep quality perceived as poor and sleep considered a health problem); a global sleep score and time spent in bed were estimated. Using logistic regression, ORs were calculated for each sleep outcome by disease duration. We explored whether pain (low (Visual Analogue Scale=0-20 mm, reference), intermediate=21-70, high=71-100) or functional impairment (Health Assessment Questionnaire>1.0) was associated with problems. Results: We had sleep data on 4131 observations (n=3265 individuals). Problems with ≥1 sleep domain (global sleep score) was reported in 1578 observations (38%) and increased with disease duration (OR 1.04, 95% CI 1.02 to 1.07). Median time in bed was 8 hours (Q1-Q3: 7.5-9.0). High-grade pain increased the likelihood of sleep problems ~3-9 fold, and increased functional impairment ~4-8 fold. Conclusion: In this cohort of newly diagnosed patients with RA with access to the current treatment from diagnosis, we did not find any major problems with sleep, and existing sleep problems related mainly to pain and reduced function. Treatment of sleep problems in RA should be guided towards treating the underlying problem causing the sleep disturbance.
MeSH term(s)	Arthritis, Rheumatoid/complications ; Arthritis, Rheumatoid/diagnosis ; Arthritis, Rheumatoid/epidemiology ; Humans ; Pain Measurement ; Sleep ; Sleep Wake Disorders/diagnosis ; Sleep Wake Disorders/epidemiology ; Sleep Wake Disorders/etiology ; Sweden/epidemiology
Language	English
Publishing date	2022-01-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2812592-7
ISSN	2056-5933 ; 2056-5933
ISSN (online)	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2021-001800
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Article ; Online: Does persistence to methotrexate treatment in early rheumatoid arthritis have a familial component?

Sysojev, Anton Öberg / Frisell, Thomas / Delcoigne, Bénédicte / Saevarsdottir, Saedis / Askling, Johan / Westerlind, Helga

Arthritis research & therapy

2022 Volume 24, Issue 1, Page(s) 185

Abstract: Objectives: To assess whether persistence to treatment with methotrexate (MTX) in early rheumatoid arthritis (RA) is shared among first-degree relatives with RA and to estimate any underlying heritability.: Methods: First-degree relative pairs ... ...

Abstract	Objectives: To assess whether persistence to treatment with methotrexate (MTX) in early rheumatoid arthritis (RA) is shared among first-degree relatives with RA and to estimate any underlying heritability. Methods: First-degree relative pairs diagnosed with RA 1999-2018 and starting MTX (in monotherapy) as their first disease-modifying anti-rheumatic drug (DMARD) treatment were identified by linking the Swedish Rheumatology Quality Register to national registers. Short- and long-term persistence to MTX was defined as remaining on treatment at 1 and 3 years, respectively, with no additional DMARDs added. We assessed familial aggregation through relative risks (RR) using log-binomial regression with robust standard errors and estimated heritability using tetrachoric correlations. We also explored the familial aggregation of EULAR treatment response after 3 and 6 months. To mimic the clinical setting, we also tested the association between having a family history of MTX persistence and persistence within the index patient. Results: Familial persistence was not associated with persistence at 1 (RR=1.02, 95% CI 0.87-1.20), only at 3 (RR=1.41, 95% CI 1.14-1.74) years. Heritability at 1 and 3 years was estimated to be 0.08 (95% CI 0-0.43) and 0.58 (95% CI 0.27-0.89), respectively. No significant associations were found between family history and EULAR response at 3 and 6 months, neither overall nor in the clinical setting analysis. Conclusions: Our findings imply a familial component, including a possible genetic element, within the long-term persistence to MTX following RA diagnosis. Whether this component is reflective of characteristics of the underlying RA disease or determinants for sustained response to MTX in itself will require further investigation.
MeSH term(s)	Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/genetics ; Drug Therapy, Combination ; Humans ; Methotrexate/therapeutic use ; Treatment Outcome
Chemical Substances	Antirheumatic Agents ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2022-08-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2107602-9
ISSN	1478-6362 ; 1478-6354
ISSN (online)	1478-6362
ISSN	1478-6354
DOI	10.1186/s13075-022-02873-z
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Zs.A 5490: Show issues

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Article ; Online: Combined Conventional Synthetic Disease Modifying Therapy vs. Infliximab for Rheumatoid Arthritis: Emulating a Randomized Trial in Observational Data.

Barbulescu, Andrei / Askling, Johan / Saevarsdottir, Saedis / Kim, Seoyoung C / Frisell, Thomas

Clinical pharmacology and therapeutics

2022 Volume 112, Issue 4, Page(s) 836–845

Abstract: Observational studies are often considered unreliable for evaluating relative treatment effectiveness, but it has been suggested that following target trial protocols could reduce bias. Using observational data from patients with rheumatoid arthritis (RA) ...

Abstract	Observational studies are often considered unreliable for evaluating relative treatment effectiveness, but it has been suggested that following target trial protocols could reduce bias. Using observational data from patients with rheumatoid arthritis (RA) in the Swedish Rheumatology Quality Register (SRQ), between 2006 and 2020, we emulated the protocol of the Swedish Farmacotherapy trial (SWEFOT) and compared the results. SWEFOT was a pragmatic trial nested in SRQ, between 2002 and 2005, where methotrexate (MTX) insufficient responders were randomized to receive additional infliximab or sulfasalazine (SSZ) + hydroxychloroquine (HCQ). Patients with RA initiating infliximab (N = 313) or SSZ + HCQ (N = 196) after MTX were identified in SRQ and the Prescribed Drugs Register, mimicking the SWEFOT eligibility criteria. The primary outcome was the proportion of European Alliance of Associations for Rheumatology (EULAR) good responders at 9 months, classifying patients who discontinued treatment as "nonresponders." Through sensitivity analyses, we assessed the impact of relaxing eligibility criteria. The observed proportions reaching EULAR good response were close to those reported in SWEFOT: 39% (vs. 39% in SWEFOT) for infliximab and 28% (vs. 25%) for SSZ + HCQ. The crude observed response ratio was 1.39 (95% confidence interval (CI) 1.04-1.86), increasing to 1.48 (95% CI 0.98-2.24) after confounding adjustment, compared to 1.59 (95% CI 1.10-2.30) in SWEFOT. Results remained close to SWEFOT when relaxing eligibility criteria until allowing prior disease-modifying anti-rheumatic drug (DMARD) use which reduced the observed difference between treatments. By applying a prespecified trial emulation protocol to observational clinical registry data, we could replicate the results of SWEFOT, favoring infliximab over SSZ + HCQ combination therapy at 9 months.
MeSH term(s)	Antirheumatic Agents/adverse effects ; Arthritis, Rheumatoid/diagnosis ; Arthritis, Rheumatoid/drug therapy ; Drug Therapy, Combination ; Humans ; Hydroxychloroquine/adverse effects ; Infliximab/adverse effects ; Methotrexate/adverse effects ; Sulfasalazine/adverse effects ; Treatment Outcome
Chemical Substances	Antirheumatic Agents ; Sulfasalazine (3XC8GUZ6CB) ; Hydroxychloroquine (4QWG6N8QKH) ; Infliximab (B72HH48FLU) ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2022-06-23
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	123793-7
ISSN	1532-6535 ; 0009-9236
ISSN (online)	1532-6535
ISSN	0009-9236
DOI	10.1002/cpt.2673
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Zs.A 20: Show issues

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Article ; Online: The importance of differences; On environment and its interactions with genes and immunity in the causation of rheumatoid arthritis.

Klareskog, L / Rönnelid, J / Saevarsdottir, S / Padyukov, L / Alfredsson, L

Journal of internal medicine

2020 Volume 287, Issue 5, Page(s) 514–533

Abstract: The current review uses rheumatoid arthritis (RA) as a prominent example for how studies on the interplay between environmental and genetic factors in defined subsets of a disease can be used to formulate aetiological hypotheses that subsequently can be ... ...

Abstract	The current review uses rheumatoid arthritis (RA) as a prominent example for how studies on the interplay between environmental and genetic factors in defined subsets of a disease can be used to formulate aetiological hypotheses that subsequently can be tested for causality using molecular and functional studies. Major discussed findings are that exposures to airways from many different noxious agents including cigarette smoke, silica dust and more interact with major susceptibility genes, mainly HLA-DR genetic variants in triggering antigen-specific immune reactions specific for RA. We also discuss how several other environmental and lifestyle factors, including microbial, neural and metabolic factors, can influence risk for RA in ways that are different in different subsets of RA.The description of these processes in RA provides the best example so far in any immune-mediated disease of how triggering of immunity at one anatomical site in the context of known environmental and genetic factors subsequently can lead to symptoms that precede the classical inflammatory disease symptoms and later contribute also to the classical RA joint inflammation. The findings referred to in the review have led to a change of paradigms for very early therapy and prevention of RA and to efforts towards what we have named 'personalized prevention'. We believe that the progress described here for RA will be of relevance for research and practice also in other immune-mediated diseases.
MeSH term(s)	Arthritis, Rheumatoid/etiology ; Arthritis, Rheumatoid/genetics ; Arthritis, Rheumatoid/immunology ; Gene-Environment Interaction ; Genetic Predisposition to Disease/genetics ; Humans ; Life Style ; Risk Factors
Language	English
Publishing date	2020-03-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	96274-0
ISSN	1365-2796 ; 0954-6820
ISSN (online)	1365-2796
ISSN	0954-6820
DOI	10.1111/joim.13058
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Ua VI Zs.44: Show issues

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Article ; Online: The impact of autoantibodies on the efficacy of biological disease-modifying anti-rheumatic drugs in rheumatoid arthritis: meta-analysis of randomized controlled trials.

Takase-Minegishi, Kaoru / Böhringer, Stefan / Nam, Jackie L / Kaneko, Yuko / Behrens, Frank / Saevarsdottir, Saedis / Detert, Jacqueline / Leirisalo-Repo, Marjatta / van der Heijde, Désirée / Landewé, Robert / Ramiro, Sofia / van der Woude, Diane

Rheumatology (Oxford, England)

2024

Abstract: Objective: To investigate the efficacy of bDMARDs in patients with RA with RF/ACPA compared with patients without these autoantibodies.: Methods: Previous systematic literature reviews performed by EULAR RA management task forces were searched for ... ...

Abstract	Objective: To investigate the efficacy of bDMARDs in patients with RA with RF/ACPA compared with patients without these autoantibodies. Methods: Previous systematic literature reviews performed by EULAR RA management task forces were searched for qualifying RCTs. RCTs investigating the efficacy of bDMARDs and including both autoantibody-positive (≤80% of total population) and -negative RA patients were eligible. For trials comparing bDMARD+csDMARD vs csDMARD, relative risks (RR) comparing two groups (RF + vs RF-, ACPA+ vs ACPA-) were calculated for efficacy outcomes for each arm. Subsequently, relative risk ratios (RRRs) were computed, as the ratio of RR of the bDMARD-arm and the RR from the non-bDMARD-arm. Pooled effects were obtained with random effect meta-analyses. Results: Data from 28 eligible RCTs were analyzed, pooling 23 studies in three subgroups: 6 including csDMARD-naïve patients, 14 csDMARD-IR, and 3 TNFi-IR patients. In csDMARD-naïve and csDMARD-IR patients, seropositivity was not associated with a better response to bDMARDs: pooled 6-month ACR20 RRRs 1.02 (0.88-1.18) and 1.09 (0.90-1.32), respectively. Other outcomes showed no difference between groups either. In TNFi-IR patients, based on 3 trials, the 6-month ACR20 RRR was 2.28 (1.31-3.95), favoring efficacy in seropositive patients. Other outcomes mostly showed no significant difference between the groups. Based on the mode of action, efficacy was comparable between RF-positive and RF-negative patients for both TNFi and non-TNFi treatment and also for the individual bDMARDs. Conclusion: The effect of bDMARDs is generally comparable in patients with and without RF/ACPA, regardless of the patient population, the mechanism of action or individual drug used.
Language	English
Publishing date	2024-02-16
Publishing country	England
Document type	Journal Article
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keae113
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Zs.B 240: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 497: Show issues

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Article ; Online: In early rheumatoid arthritis, anticitrullinated peptide antibodies associate with low number of affected joints and rheumatoid factor associates with systemic inflammation.

Pertsinidou, Eleftheria / Saevarsdottir, Saedis / Manivel, Vivek Anand / Klareskog, Lars / Alfredsson, Lars / Mathsson-Alm, Linda / Hansson, Monika / Cornillet, Martin / Serre, Guy / Holmdahl, Rikard / Skriner, Karl / Jakobsson, Per-Johan / Westerlind, Helga / Askling, Johan / Rönnelid, Johan

Annals of the rheumatic diseases

2024 Volume 83, Issue 3, Page(s) 277–287

Abstract: Objectives: To investigate how individual rheumatoid arthritis (RA) autoantibodies associate with individual signs and symptoms at the time of RA diagnosis.: Methods: IgA, IgG, IgM rheumatoid factor (RF), antibodies against cyclic citrullinated ... ...

Abstract	Objectives: To investigate how individual rheumatoid arthritis (RA) autoantibodies associate with individual signs and symptoms at the time of RA diagnosis. Methods: IgA, IgG, IgM rheumatoid factor (RF), antibodies against cyclic citrullinated peptide version 2 (anti-CCP2) and 16 individual antibodies against citrullinated protein (ACPA) reactivities were analysed centrally in baseline sera from 1600 patients with RA classified according to the 1987 American College of Rheumatology (ACR) criteria. These results were related to C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), number of swollen and tender joints (SJC and TJC), 28-joint disease activity scores (DAS28 and DAS28CRP), global disease activity evaluated by the patients and Health Assessment Questionnaire, all obtained at baseline. Results: Individually, all autoantibodies except immunoglobulin G (IgG) RF associated with low SJC and TJC and with high ESR. In IgM RF-negative patients, ACPA associated strictly with low number of swollen and tender joints. This association persisted in multiple regression and stratified analyses where IgM and IgA RF instead associated with inflammation expressed as ESR. Among subjects without any ACPA peptide reactivity, there was no association between RF isotypes and ESR. The effect of RF on ESR increased with the number of ACPA reactivities, especially for IgM RF. In patients fulfilling the 1987 ACR criteria without taking RF into account, associations between IgM RF and high ESR, as well as between ACPA and low joint counts, remained. Conclusion: Whereas ACPA associate with low counts of affected joints in early RA, RF associates with elevated measures of systemic inflammation in an ACPA-dependent manner. This latter finding corroborates in vitro models of ACPA and RF in immune complex-induced inflammation. These phenotypic associations are independent of classification criteria.
MeSH term(s)	Humans ; Rheumatoid Factor ; Arthritis, Rheumatoid ; Inflammation ; Autoantibodies ; Peptides, Cyclic ; Immunoglobulin G ; Immunoglobulin M ; Immunoglobulin A
Chemical Substances	Rheumatoid Factor (9009-79-4) ; Autoantibodies ; Peptides, Cyclic ; Immunoglobulin G ; Immunoglobulin M ; Immunoglobulin A
Language	English
Publishing date	2024-02-15
Publishing country	England
Document type	Journal Article
ZDB-ID	7090-7
ISSN	1468-2060 ; 0003-4967
ISSN (online)	1468-2060
ISSN	0003-4967
DOI	10.1136/ard-2023-224728
Database	MEDical Literature Analysis and Retrieval System OnLINE

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