| 1. |
- Jacobsson, Lennart, et al.
(author)
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Sociodemographic and disease-related factors are associated with patient-reported anxiety and depression in spondyloarthritis patients in the Swedish SpAScania cohort
- 2014
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In: Clinical Rheumatology. - London : Springer Science and Business Media LLC. - 0770-3198 .- 1434-9949. ; 33:11, s. 1649-1656
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Journal article (peer-reviewed)abstract
- Anxiety and depression are common among patients with rheumatic diseases. This study aims to explore which factors are associated with self-reported anxiety and depression in a well-defined cohort of spondyloarthritis (SpA) patients. In 2009, 3,711 patients from the SpAScania cohort were sent a postal questionnaire to assess health-related quality of life (HRQoL) and physical and mental functioning. The Hospital Anxiety and Depression Scale measured anxiety (HADS-A) and depression (HADS-D), subscales 0-21, best-worst. HADS a parts per thousand yen8 indicates possible cases of anxiety or depression. One-way ANOVA (p < 0.05) tested for differences among the SpA subtypes in HADS scores. Linear regression analysis adjusted for age, gender, and disease duration was used to test for associations between HADS and independent variables. In total, 2,167 (58 %) patients (52 % females, mean age 55.4 years) returned the questionnaire. In total, 683 (32 %) cases were classified as "possible anxiety" and 305 (14 %) as "possible depression" cases with mean (SD) HADS-A 5.9 (4.3) and HADS-D 4.4 (3.6). There were no differences among the SpA subtypes in HADS-A and HADS-D. HADS-A and HADS-D were associated with lower education, lower physical activity (HADS-D only), chronic pain problems, more fatigue, lower general health, lower HRQoL, lower level of functioning, higher disease activity, and lower self-efficacy. Associations with anxiety and/or depression appear multifactorial in patients with SpA including both personal and disease-related factors. Since these comorbidities are increased in SpA and treatable, they should be screened for in clinical practice, possibly with instruments like the HADS.
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| 2. |
- Amkreutz, J. A. M. P., et al.
(author)
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Association Between Bone Mineral Density and Autoantibodies in Patients With Rheumatoid Arthritis
- 2021
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In: Arthritis and Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 73:6, s. 921-930
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Journal article (peer-reviewed)abstract
- Objective: Autoantibodies, such as anti–citrullinated protein antibodies (ACPAs), have been described as inducing bone loss in rheumatoid arthritis (RA), which can also be reflected by bone mineral density (BMD). We therefore examined the association between osteoporosis and autoantibodies in two independent RA cohorts. Methods: Dual x-ray absorptiometry (DXA) of the lumbar spine and left hip was performed in 408 Dutch patients with early RA during 5 years of follow-up and in 198 Swedish patients with early RA during 10 years of follow-up. The longitudinal effect of ACPAs and other autoantibodies on several BMD measures was assessed using generalized estimating equations. Results: In the Dutch cohort, significantly lower BMD at baseline was observed in ACPA-positive patients compared to ACPA-negative patients, with an estimated marginal mean BMD in the left hip of 0.92 g/cm2 (95% confidence interval [95% CI] 0.91–0.93) versus 0.95 g/cm2 (95% CI 0.93–0.97) (P = 0.01). In line with this, significantly lower Z scores at baseline were noted in the ACPA-positive group compared to the ACPA-negative group (estimated marginal mean Z score in the left hip of 0.18 [95% CI 0.08–0.29] versus 0.48 [95% CI 0.33–0.63]) (P < 0.01). However, despite clear differences at baseline, ACPA positivity was not associated with greater decrease in absolute BMD or Z scores over time. Furthermore, there was no association between BMD and higher levels of ACPAs or other autoantibodies (rheumatoid factor and anti–carbamylated protein antibodies). In the Swedish cohort, ACPA-positive patients tended to have a higher prevalence of osteopenia at baseline (P = 0.04), but again, ACPA positivity was not associated with an increased prevalence of osteopenia or osteoporosis over time. Conclusion: The presence of ACPAs is associated with significantly lower BMD at baseline, but not with greater BMD loss over time in treated RA patients. These results suggest that ACPAs alone do not appear to contribute to bone loss after disease onset when disease activity is well-managed. © 2020 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
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| 3. |
- Askling, Johan, et al.
(author)
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Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor alpha therapies : does the risk change with the time since start of treatment?
- 2009
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In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:11, s. 3180-3189
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Journal article (peer-reviewed)abstract
- OBJECTIVE:To determine the short-term and medium-term risks of cancer in patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha) therapies that have proven effective in the treatment of chronic inflammatory conditions.METHODS:By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received.RESULTS:During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86-1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed.CONCLUSION:During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed.
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| 4. |
- Askling, Johan, et al.
(author)
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Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden
- 2005
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In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 52:7, s. 1986-1992
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Journal article (peer-reviewed)abstract
- OBJECTIVE:Because treatment with tumor necrosis factor (TNF) antagonists may increase the risk of tuberculosis (TB), and because knowledge of the risk of TB in rheumatoid arthritis (RA) not treated with biologics is scarce and of uncertain generalizability to low-risk populations, this study sought to determine the risk of TB among Swedish patients with RA.METHODS:Using data from Swedish nationwide and population-based registers and data from an ongoing monitoring program of TNF antagonists, the relative risks of TB in patients with RA (versus the general population) and of TB associated with TNF antagonists (versus RA patients not treated with biologics) were determined by comparing the incidence of hospitalization for TB in 3 RA cohorts and 2 general population cohorts from 1999 to 2001. We also reviewed the characteristics of all reported cases of TB in RA patients treated with TNF antagonists in Sweden and calculated the incidence of TB per type of TNF antagonist between 1999 and 2004.RESULTS:During 1999-2001, RA patients who were not treated with TNF antagonists were at increased risk of TB versus the general population (relative risk 2.0, 95% confidence interval [95% CI] 1.2-3.4). RA patients treated with TNF antagonists had a 4-fold increased risk of TB (relative risk 4.0, 95% CI 1.3-12) versus RA patients not treated with TNF antagonists. The reported TB cases during 1999-2004 in RA patients exposed to TNF antagonists (9 infliximab, 4 etanercept, 2 both) were predominantly pulmonary. TB occurred up to 3 years following the start of treatment.CONCLUSION:Irrespective of whether TNF antagonists are administered, Swedish patients with RA are at increased risk of TB. During 1999-2001, TNF antagonists were associated with an increased risk of TB, up to 4-fold in magnitude. This increased risk may persist over time during treatment and is related to both infliximab and etanercept.
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| 5. |
- Askling, Johan, et al.
(author)
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Time-dependent increase in risk of hospitalisation with infection among Swedish RA patients treated with TNF antagonists
- 2007
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 66:10, s. 1339-1344
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Journal article (peer-reviewed)abstract
- OBJECTIVES:The degree to which treatment with tumour necrosis factor (TNF) antagonists may be associated with increased risks for serious infections is unclear. An observational cohort study was performed using prospectively collected data from the Swedish Biologics Register (ARTIS) and other national Swedish registers.METHODS:First, in the ARTIS, all 4167 rheumatoid arthritis (RA) patients starting TNF antagonist treatment between 1999 and 2003 were identified. Secondly, in the Swedish Inpatient Register, all individuals hospitalised for any reason and who also carried a diagnosis of RA, between 1964 and 2003 (n = 44 946 of whom 2692 also occurred in ARTIS), were identified. Thirdly, in the Swedish Inpatient Register, all hospitalisations listing an infection between 1999 and 2003 were identified. By cross-referencing these three data sets, RRs for hospitalisation with infection associated with TNF antagonist treatment were calculated within the cohort of 44 946 RA patients, using Cox regression taking sex, age, geography, co-morbidity and use of inpatient care into account.RESULTS:Among the 4167 patients treated with TNF antagonists, 367 hospitalisations with infections occurred during 7776 person-years. Within the cohort of 44 496 RA patients, the RR for infection associated with TNF antagonists was 1.43 (95% CI 1.18 to 1.73) during the first year of treatment, 1.15 (95% CI 0.88 to 1.51) during the second year of treatment, and 0.82 (95% CI 0.62 to 1.08) for subjects remaining on their first TNF antagonist treatment after 2 years.CONCLUSION:Treatment with TNF antagonists may be associated with a small to moderate increase in risk of hospitalisation with infection, which disappears with increasing treatment duration.
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| 6. |
- Klingberg, Eva, et al.
(author)
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Weight loss improves disease activity in patients with psoriatic arthritis and obesity: an interventional study
- 2019
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In: Arthritis Res Ther. - : Springer Science and Business Media LLC. - 1478-6354. ; 21:1
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Journal article (peer-reviewed)abstract
- BackgroundObesity is over-represented in patients with psoriatic arthritis (PsA) and associated with higher disease activity, poorer effect of treatment and increased cardiovascular morbidity. Studies on the effects of weight loss are however needed. This study aimed to prospectively study the effects of weight loss treatment with very low energy diet (VLED) on disease activity in patients with PsA (CASPAR criteria) and obesity (body mass index BMI 33kg/m(2)).MethodsVLED (640kcal/day) was taken during 12-16weeks, depending on pre-treatment BMI. Afterwards, an energy-restricted diet was gradually reintroduced. Weight loss treatment was given within a structured framework for support and medical follow-up.Treatment with conventional synthetic and/or biologic disease-modifying anti-rheumatic drugs was held constant from 3months before, until 6months after baseline.Patients were assessed with BMI, 66/68 joints count, Leeds enthesitis index, psoriasis body surface area (BSA), questionnaires and CRP at baseline, 3 and 6months. Primary outcome was the percentage of patients reaching minimal disease activity (MDA) and secondary outcomes were reaching Psoriatic Arthritis Response Criteria (PsARC) and American College of Rheumatology (ACR) response criteria.ResultsTotally 41/46 patients completed the study, 63% women, median age 54years (IQR 48-62). At baseline increased BMI was associated with higher disease activity and poorer function.The median weight loss was 18.7kg (IQR 14.6-26.5) or 18.6% (IQR 14.7-26.3) of the baseline weight. A majority of the disease activity parameters improved significantly after weight loss, including 68/66 tender/swollen joints count, CRP, BSA, Leeds enthesitis index, HAQ and patient VAS for global health, pain and fatigue. A larger weight loss resulted in more improvement in a dose-response manner. The percentage of patients with MDA increased from 29 to 54%, (p=0.002). PsARC was reached by 46.3%. The ACR 20, 50 and 70 responses were 51.2%, 34.1% and 7.3% respectively.ConclusionsShort-term weight loss treatment with VLED was associated with significant positive effects on disease activity in joints, entheses and skin in patients with PsA and obesity. The study supports the hypothesis of obesity as a promotor of disease activity in PsA.Trial registrationClinicalTrials.gov identifier: NCT02917434, registered on September 21, 2016retrospectively registered
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| 7. |
- Deminger, Anna, 1973, et al.
(author)
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Which measuring site in ankylosing spondylitis is best to detect bone loss and what predicts the decline : results from a 5-year prospective study
- 2017
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In: Arthritis Research & Therapy. - London, United,Kingdom : BioMed Central. - 1478-6362. ; 19
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Journal article (peer-reviewed)abstract
- BACKGROUND: Studies have shown increased prevalence of osteoporosis and increased risk for vertebral fractures in patients with ankylosing spondylitis (AS). Measurements of bone mineral density (BMD) in the lumbar spine anterior-posterior (AP) projection may be difficult to interpret due to the ligamentous calcifications, and the lateral projection might be a better measuring site. Our objectives were to investigate BMD changes after 5 years at different measuring sites in patients with AS and to evaluate disease-related variables and medications as predictors for BMD changes.METHODS: In a longitudinal study, BMD in Swedish AS patients, 50 ± 13 years old, was measured with dual-energy x-ray absorptiometry (DXA) at the hip, the lumbar spine AP and lateral projections, and the total radius at baseline and after 5 years. Patients were assessed with questionnaires, blood samples, and spinal radiographs for grading of AS-related alterations in the spine with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and assessment of vertebral fractures by the Genant score. Multiple linear regression analyses were used to investigate predictors for BMD changes.RESULTS: Of 204 patients included at baseline, 168 (82%) were re-examined after 5 years (92 men and 76 women). BMD decreased significantly at the femoral neck and radius and increased significantly at the lumbar spine, both for AP and lateral projections. Mean C-reactive protein during follow-up predicted a decrease in the femoral neck BMD (change in %, β = -0.15, p = 0.046). Use of bisphosphonates predicted an increase in BMD at all measuring sites (p < 0.001 to 0.013), except for the total radius. Use of tumor necrosis factor inhibitors (TNFi) predicted an increase in AP spinal BMD (β = 3.15, p = 0.012).CONCLUSION: The current study (which has a long follow-up, many measuring sites, and is the first to longitudinally assess the lateral projection of the spine in AS patients) surprisingly showed that lateral projection spinal BMD increased. This study suggests that the best site to assess bone loss in AS patients is the femoral neck and that inflammation has an adverse effect, and the use of bisphosphonates and TNFi has a positive effect, on BMD in AS patients.
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| 8. |
- Haglund, Emma, et al.
(author)
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Work productivity in a population-based cohort of patients with spondyloarthritis
- 2013
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In: Rheumatology. - Oxford : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 52:9, s. 1708-1714
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Journal article (peer-reviewed)abstract
- Objective. To assess work productivity and associated factors in patients with SpA. Methods. This cross-sectional postal survey included 1773 patients with SpA identified in a regional health care register. Items on presenteeism (reduced productivity at work, 0-100%, 0 = no reduction) were answered by 1447 individuals. Absenteeism was defined as register-based sick leave using data from a national register. Disease duration, disease activity (BASDAI), physical function (BASFI), health-related quality of life (EQ-5D), anxiety (HAD-a), depression (HAD-d), self-efficacy [Arthritis Self-efficacy Scale (ASES) pain and symptom], physical activity and education were also measured. Results. Forty-five per cent reported reduced productivity at work with a mean reduction of 20% (95% CI 18, 21) and women reported a higher mean reduction than men (mean 23% vs 17%, P < 0.001). Worse quality of life, disease activity, physical function and anxiety all correlated with reduced productivity (r = 0.52-0.66, P < 0.001), while sick leave did not. Worse outcomes on the EQ-5D (beta-est -9.6, P < 0.001), BASDAI (beta-est 7.8, P < 0.001), BASFI (beta-est 7.3, P < 0.001), ASES pain (beta-est -0.5, P < 0.001) and HAD-d (beta-est 3.4, P < 0.001) were associated with reduced productivity at work in patients with SpA regardless of age, gender and disease subgroup. ASES symptoms, HAD-a and education level < 12 years were associated with reduced productivity but were not significant in all strata for age, gender and disease subgroup. Conclusion. Work productivity was reduced in patients with SpA and more so in women. Worse quality of life, disease activity, physical function, self-efficacy and depression were all associated with reduced productivity at work in patients with SpA.
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| 9. |
- Ostergaard, M., et al.
(author)
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MRI assessment of early response to certolizumab pegol in rheumatoid arthritis: a randomised, double-blind, placebo-controlled phase IIIb study applying MRI at weeks 0, 1, 2, 4, 8 and 16
- 2015
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 74:6, s. 1156-1163
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Journal article (peer-reviewed)abstract
- Objectives To identify the first time point of an MRI-verified response to certolizumab pegol (CZP) therapy in patients with rheumatoid arthritis (RA). Methods Forty-one patients with active RA despite disease-modifying antirheumatic drug therapy were randomised 2:1 to CZP (CZP loading dose 400mg every 2weeksat weeks 0-4; CZP 200mg every 2weeksat weeks 6-16) or placeboCZP (placebo at weeks 0-2; CZP loading dose at weeks 2-6; CZP 200mg every 2weeks at weeks 8-16). Contrast-enhanced MRI of one hand and wrist was acquired at baseline (week 0) and weeks 1, 2, 4, 8 and 16. All six time points were read simultaneously, blinded to time, using the Outcome Measures in Rheumatology Clinical Trials RA MRI scoring system. Primary outcome was change in synovitis score in the CZP group; secondary outcomes were change in bone oedema (osteitis) and erosion scores and clinical outcome measures. Results Forty patients were treated (27 CZP, 13 placeboCZP), and 36 (24 CZP, 12 placeboCZP) completed week 16. In the CZP group, there were significant reductions from baseline synovitis (Hodges-Lehmann estimate of median change, -1.5, p=0.049) and osteitis scores (-2.5, p=0.031) at week 16. Numerical, but statistically insignificant, MRI inflammation reductions were observed at weeks 1-2 in the CZP group. No significant change was seen in bone erosion score. Improvements across all clinical outcomes were seen in the CZP group. Conclusions CZP reduced MRI synovitis and osteitis scores at week 16, despite small sample size and the technical challenge of reading six time points simultaneously. This study provides essential information on optimal MRI timing for subsequent trials.
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| 10. |
- Thorstensson, Carina
(author)
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Exercise and Functional Performance in Middle-aged Patients with Knee Osteoarthritis
- 2005
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Doctoral thesis (other academic/artistic)abstract
- The overall purpose of this thesis was to explore the impact of exercise and functional performance on development and treatment of knee osteoarthritis in the middle aged. In this thesis, I have studied a population based cohort of middle-aged subjects (35-54 years, 42 % women) with chronic knee pain at baseline, to evaluate the longitudinal effect of muscle weakness on knee osteoarthritis development, the relationship between muscle function and joint load and the effects of exercise on joint load. I have also studied the effect of exercise on pain and function in another middle-aged cohort (36-65 years, 51 % women) with moderate to severe knee osteoarthritis, and explored their conceptions of exercise as treatment. In the first study, 148 subjects with chronic knee pain underwent radiographic examination and tests of functional performance at baseline. 94 of them had no radiographic signs of knee osteoarthritis. Five years later they had new radiographs taken and 41/94 (44 %) had developed incident knee osteoarthritis. I found that reduced functional performance, assessed by maximum number of one-leg rises from a stool, predicted knee osteoarthritis development. The result was controlled for the previously known risk factors of age, BMI and pain. In the second study, I used 3-dimensional motion analysis to explore the possibility of altering joint load by exercise. The medial compartment joint load (peak adduction moment) during maximum number of one-leg rises was assessed in 13 subjects with early radiographic signs of knee osteoarthritis from the cohort in study one, before and after 8 weeks of exercise. Two subjects were lost to follow up for reasons not related to the knee. The peak adduction moment could be reduced by exercise, and a high maximum number of one-leg rises was associated with lower levels of peak adduction moment. The third study included 61 subjects with moderate to severe radiographic knee osteoarthritis. They were randomized to 6 weeks of intensive exercise or to a control group. The effects of exercise were assessed using questionnaires. No effects were seen on pain or self estimated function, however, the quality of life improved. The individual response to exercise ranged from clinically significant improvement to clinically significant worsening. As an attempt to understand this large inter individual response to exercise, I designed the fourth study, where I interviewed 16 of the 30 patients in the exercise group about their conceptions of exercise as treatment. The interviews were analysed using qualitative methodology, and it was revealed that all patients were aware of the general health benefits of exercise, but had doubts about exercise as treatment of osteoarthritis even if they had perceived pain relief and improvement in physical function from the exercise intervention. The pain experienced during exercise caused the patients to believe that exercise was harmful to their knees, and some of them would prefer not to exercise at all. They thought that exercise should be introduced early during the course of the disease, and all of them expressed the need of continuous encouragement and support to adhere to exercise. From this thesis I conclude that reduced muscle function is a risk factor of knee osteoarthritis development among middle aged subjects with knee pain. Reduced muscle function is associated with increased joint load, which seem to be modifiable by exercise. Initial pain when starting exercise, or occasional pain from exercise, should be treated by combining exercise with pain relief such as analgesics or acupuncture. Pain contributes to the difficulty patients have determining the degree of benefit or damage related to exercise, and thus causes feelings of anxiety and helplessness (paper IV). Pain also seems to interfere with the possibility of achieving increased functional performance (paper II, III, IV).
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