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- Innala, Lena, et al.
(författare)
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Age at onset determines severity and choice of treatment in early rheumatoid arthritis : a prospective study
- 2014
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Ingår i: Arthritis Research & Therapy. - : BioMed Central. - 1478-6362 .- 1478-6354. ; 16:2, s. R94-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Disease activity, severity and co-morbidity contribute to increased mortality in patients with rheumatoid arthritis (RA). We evaluated the impact of age at disease onset on prognostic risk factors and treatment in early disease.METHODS: In this study, 950 RA patients were followed regularly from inclusion (<12 months from symptom onset) for disease activity (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender/swollen joints, visual analogue scale (VAS) pain/global, disease activity score (DAS28)) and function (health assessment questionnaire (HAQ)). Disease severity, measured by radiographs of hands/feet (erosions, Larsen score), extra-articular disease, nodules and co-morbidities and treatment (disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, biologics, nonsteroidal anti-inflammatory drugs (NSAIDs)) were recorded at inclusion and after 5 years. Autoantibodies (rheumatoid factor (RF), anti-nuclear antibodies (ANA), antibodies against cyclic citrullinated peptides (ACPA)) and genetic markers (human leukocyte antibody (HLA)-shared epitope, protein tyrosine phosphatase nonreceptor type 22 (PTPN22)) were analyzed at inclusion. Data were stratified as young (YORA) and late (LORA) onset RA, defined as being below/above median age (58 years) at onset.RESULTS: LORA was associated with lower frequency of ACPA (P <0.05) and carriage of PTPN22-T variant (P <0.01), but with greater disease activity at inclusion measured as ESR (P < 0.001), CRP (P <0.01) and accumulated disease activity (area under the curve for DAS28) at 6 (P <0.01), 12 (P <0.01) and 24 months (P <0.05), and a higher HAQ score (P <0.01) compared with YORA. At baseline and 24 months, LORA was more often associated with erosions (P <0.01 for both) and a higher Larsen score (P <0.001 for both). LORA was more often treated with corticosteroids (P <0.01), less often with methotrexate (P <0.001) and biologics (P <0.001). YORA was more often associated with early DMARD treatment (P <0.001). Multiple regression analyses supported our findings regarding impact of age on chosen treatment.CONCLUSION: YORA patients were more frequently ACPA-positive. LORA was more often associated with erosions, higher Larsen scores, disease activity and HAQ at baseline. Nevertheless, YORA was treated earlier with DMARDs, whilst LORA was more often treated with corticosteroids and with less DMARDs in early disease. This could have implications for development of co-morbidities.
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| 3. |
- Innala, Lena, et al.
(författare)
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Cardiovascular events in early rheumatoid arthritis (RA) are a result of inflammatory burden and traditional risk factors : a five year prospective study
- 2011
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 13:4, s. R131-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Co-morbidity and mortality due to cardiovascular disease (CVD) are increased in patients with rheumatoid arthritis (RA). Most published studies in this field are retrospective or cross sectional. We investigated the presence of traditional and disease related risk factors for CVD at the onset of RA and during the first 5 years following diagnosis. We also evaluated their potential for predicting a new cardiovascular event (CVE) during the 5 year follow-up period and the modulatory effect of pharmacological treatment.Methods All patients from the four northern-most counties of Sweden with early RA are since December 1995 consecutively recruited at diagnsosis (T0) into a large survey on the progress of the disease. Information regarding cardiovascular co-morbidity and related predictors was collected from clinical records and supplemented with questionnaires. By April 2008, 700 patients had been included of whom 442 patients had reached the 5-year follow-up (T5).Result Among the 442 patients who reached T5 during the follow-up period, treatment for hypertension increased from 24.5 to 37.4% ( p<0.001)), diagnosis of diabetes mellitus (DM) from 7.1 to 9.5%(p<0.01) whilst smoking decreased from 29.8 to 22.4 % ( p<0.001) and the BMI from 26.3 to 25.8( p<0.05) , respectively. By T5, 48 patients had suffered a new CVE of which 12 were fatal. A total of 23 patients died during the follow-up period. Age at disease onset, male sex, a previous CVE, DM, treatment for hypertension, triglyceride level, cumulative disease activity (AUC DAS28), extra-articular disease, corticosteroid use, shorter duration of treatment with DMARDs and use of COX-2 inhibitors increased the hazard rate for a new CVE. A raised ESR at inclusion and AUC DAS28 at 6 months increased the hazard rate of CVE independently whilst DMARD treatment was protective in multiple Cox extended models adjusted for sex and CV risk factors. The risk of a CVE due to inflammation was potentiated by traditional CV risk factors.Conclusion The occurrence of new CV events in very early RA was explained by traditional CV risk factors and was potentiated by high disease activity. Treatment with DMARDs decreased the risk. The results may have implications for cardio-protective strategies in RA.
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| 6. |
- Innala, Lena, 1960-
(författare)
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Early rheumatoid arthritis aspects of severity and co-morbidity
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Rheumatoid arthritis (RA) is a systemic progressive destructive joint disease with an increased risk for co-morbidity and premature death if untreated. Cardiovascular disease (CVD) is the main cause of death but also other co-morbid conditions contribute to the patient’s shorter life expectancy. Inflammation is important for the development of CVD, but knowledge of its relationship with other co-morbidities is sparse. Early disease modifying anti rheumatic drugs (DMARDs) can suppress disease activity and improve the long-term outcome. The aim of this thesis was to evaluate prospectively aspects of disease activity and severity in a large cohort of patients with early RA. Predictive and prognostic markers, e.g., antibodies against citrullinated proteins/peptides (ACPAs), occurring in early disease and with implications for disease outcome and co-morbidity were evaluated.Methods Patients with early RA (i.e., symptomatic for ≤12 months) have, since December 1995, been consecutively included in a large survey of prospective and observational studies on the progression of RA and the development of co-omorbidity. Autoantibodies, inflammatory, genetic markers and radiographs have been analyzed. In paper I, 210 RA patients and 102 controls were followed regularly for two years. The predictive value of four different ACPAs in relation to disease activity and radiological progression was evaluated. In Paper II (n = 700) and in Papers III-IV (n =950), patients with early RA from the four northern-most counties of Sweden were followed regularly for 5 years. Data on risk factors and co-morbidity was collected, according to the study protocol, from clinical records and self-reported questionnaires from patients at inclusion into the study cohort and after five years. The predictive value of traditional and potential disease related risk factors for new cardiovascular events (CVE) was evaluated (II). In Paper III, the impact of age at the onset RA, stratified as being young onset RA (<58 years; YORA) and late onset RA (≥58 years; LORA) on disease activity, severity and chosen treatment, was evaluated. In Paper IV, the development of new co-morbidities after RA onset and their relation to inflammatory activity was assessed.Results The presence of anti-mutated citrullinated vimentin (MCV ) antibodies was associated with a more severe disease course, estimated by disease activity score, erythrocyte sedimentation rate (ESR) and swollen joint count after 24 months, compared with anti-CCP2, anti-CCP3, and anti CCP3.1 antibodies. In Paper II, the incidence of a new CVE during 5 years was explained by several of the traditional CV risk factors, and potentiated by a high disease activity. Treatment with DMARDs decreased the risk. In Paper III, LORA patients were associated with greater disease activity/severity at disease onset and over time compared with YORA who were more often ACPA positive. YORA patients were treated earlier with DMARDs, whilst LORA patients were more often treated with corticosteroids and less so with DMARDs early in the course of their disease. In Paper IV, 53%of patients already had one or more co-morbidities already at the onset of RA. After 5 years, 41% of the patients had developed at least one new co-morbidity. ESR at baseline and accumulated disease activity were associated with a new co-morbidity after five years.Conclusion Early RA patients sero-positive for anti- MCV antibodies appeared to have a higher disease activity over time. The occurrence of a new CVE in early RA patients was predicted by traditional risk factors for CVD which were potentiated by a high disease activity. Treatment with DMARDs decreased the risk. Patients with young onset of RA were associated with a higher frequency of ACPA. Late onset of RA was associated with higher disease activity/severity at inclusion and over time. However, LORA patients were more often treated with corticosteroids and less so with DMARDs early in the disease course. Development of a new co-morbidity during the five years following diagnosis was related to ESR.
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- Södergren, Anna, et al.
(författare)
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Atherosclerosis in early rheumatoid arthritis : very early endothelial activation and rapid progression of intima media thickness
- 2010
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 12:4, s. R158-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION : In this study we aimed to investigate whether there are indications of premature atherosclerosis, as measured by endothelial dependent flow-mediated dilation (ED-FMD) and intima media thickness (IMT), in patients with very early RA, and to analyze its relation to biomarkers of endothelial dysfunction, taking inflammation and traditional cardiovascular disease (CVD) risk factors into account. METHODS : Patients from the three northern counties of Sweden diagnosed with early RA are followed in an ongoing prospective study of CVD co-morbidity. Of these, all patients aged ≤60 years were consecutively included in this survey of CVD risk factors (n = 79). Forty-four age and sex matched controls were included. IMT of common carotid artery and ED-FMD of brachial artery were measured using ultrasonography. Blood was drawn for analysis of lipids, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA)-mass, VonWillebrand factor (VWF), soluble intercellular adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM), sE-selectin, sL-selectin and monocyte chemotactic protein-1 (MCP-1). In a subgroup of 27 RA patients and their controls the ultrasound measurements were reanalysed after 18 months. RESULTS : There were no significant differences between RA patients and controls in terms of IMT or ED-FMD at the first evaluation. However after 18 months there was a significant increase in the IMT among the patients with RA (P < 0.05). Patients with RA had higher levels of VWF, sICAM-1 (P < 0.05) and of MCP-1 (P = 0.001) compared with controls. In RA, IMT was related to some of the traditional CVD risk factors, tPA-mass, VWF (P < 0.01) and MCP-1 and inversely to sL-selectin (P < 0.05). In RA, ED-FMD related to sL-selectin (P < 0.01). DAS28 at baseline was related to PAI-1, tPA-mass and inversely to sVCAM-1 (P < 0.05) and sL-selectin (P = 0.001). CONCLUSIONS : We found no signs of atherosclerosis in patients with newly diagnosed RA compared with controls. However, in patients with early RA, IMT and ED-FMD were, to a greater extent than in controls, related to biomarkers known to be associated with endothelial dysfunction and atherosclerosis. After 18 months, IMT had increased significantly in RA patients but not in controls.
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