Maria L.E. Andersson

Association of obesity with worse disease severity in rheumatoid arthritis as well as with comorbidities: a long-term followup from disease onset.

To determine the association of obesity, defined as a body mass index (BMI) ≥30 or ≥28 kg/m2 or by waist circumference (WC), with disease activity and severity, as well as its relationship to comorbidities in rheumatoid arthritis (RA).

Serum levels of Cartilage Oligomeric Matrix Protein (COMP) increase temporarily after physical exercise in patients with knee osteoarthritis

BackgroundCOMP (Cartilage oligomeric matrix protein) is a matrix protein, which is currently studied as a potential serum marker for cartilage processes in osteoarthritis (OA). The influence of physical exercise on serum COMP is not fully elucidated.The objective of the present study was to monitor serum levels of COMP during a randomised controlled trial of physical exercise vs. standardised rest in individuals with symptomatic and radiographic knee OA.MethodsBlood samples were collected from 58 individuals at predefined time points before and after exercise or rest, one training group and one control group. The physical exercise consisted of a one-hour supervised session twice a week and daily home exercises. In a second supplementary study 7 individuals were subjected to the same exercise program and sampling of blood was performed at fixed intervals before, immediately after, 30 and 60 minutes after the exercise session and then with 60 minutes interval for another five hours after exercise to monitor the short-term changes of serum COMP. COMP was quantified with a sandwich-ELISA (AnaMar Medical, Lund, Sweden).ResultsBefore exercise or rest no significant differences in COMP levels were seen between the groups. After 60 minutes exercise serum COMP levels increased (p < 0.001). After 60 minutes of rest the serum levels decreased (p = 0.003). Median serum COMP values in samples obtained prior to exercise or rest at baseline and after 24 weeks did not change between start and end of the study. In the second study serum COMP was increased immediately after exercise (p = 0.018) and had decreased to baseline levels after 30 minutes.ConclusionSerum COMP levels increased during exercise in individuals with knee OA, whereas levels decreased during rest. The increased serum COMP levels were normalized 30 minutes after exercise session, therefore we suggest that samples of blood for analysis of serum COMP should be drawn after at least 30 minutes rest in a seated position. No increase was seen after a six-week exercise program indicating that any effect of individualized supervised exercise on cartilage turnover is transient.

Natural course of knee osteoarthritis in middle-aged subjects with knee pain: 12-year follow-up using clinical and radiographic criteria

Objective: To explore the natural course of knee osteoarthritis (OA) in a middle-aged population with chronic knee pain. Methods: A population-based sample of 143 subjects (mean age 45 (range 35–54), 44% women) with knee pain (>3 months) at inclusion was studied. Weight-bearing posteroanterior tibiofemoral (TF) radiographs were obtained at baseline and 12 years later, and classified according to Kellgren/Lawrence (K/L). Patellofemoral (PF) OA was determined at 5- and 12-years’ follow-up using a skyline view and a cut-off point of <5 mm joint space width. The ACR clinical criteria were used at baseline. Results: Seventy-six (53%) had no TF OA (K/L 0) at baseline, but 49 had clinical OA. Overall, 65/76 (86%) developed incident TF OA over 12 years (K/L ⩾1): 44/49 (90%) of the subjects with clinical OA and 21/27 (78%) without clinical OA. Progression was found in 65/67 (97%) with TF OA at baseline. Of the 84 with no PF OA at the 5-year examination, 26 (31%) developed PF OA over 7 years. Conclusion: A majority of the subjects with chronic knee pain developed knee OA over 12 years. It is concluded that knee pain is often the first sign of knee OA.

Disease Factors in Early Rheumatoid Arthritis Are Associated with Differential Risks for Cardiovascular Events and Mortality Depending on Age at Onset: A 10-year Observational Cohort Study

Objective. To investigate, within the first 2 years of diagnosis with rheumatoid arthritis (RA), associations between disease-related measures and cardiovascular disease (CVD) and mortality in patients with RA onset before and after 65 years of age. Methods. The study population (n = 741; 67.5% women) was derived from the Better Anti-Rheumatic Pharmaco Therapy (BARFOT) early RA cohort, recruited 1993–1999. The mean age was 55 years (SD 14.7). The outcomes were incident CVD events and all-cause mortality until 2010. Area under the curve (AUC) for disease measures at inclusion, 1 and 2 years, and decrease in measures after 1 year were calculated. Results. In all, 177 CVD events and 151 deaths occurred over 10 years of observation. In adjusted Cox regression analyses, seropositivity for rheumatoid factor (RF) or anticitrullinated protein antibodies (ACPA); white blood (cell) count at diagnosis; and AUC of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and visual analog scale (VAS)-pain were associated with higher CVD risk among patients with disease onset before 65 years of age. Among patients with disease onset after 65 years, larger decreases in CRP, ESR, health assessment questionnaire (HAQ), and use of methotrexate decreased CVD risk, whereas use of glucocorticoids heightened CVD risk. AUC of CRP, ESR, HAQ, and HAQ after 2 years was related to risk of death in both age groups. Seropositivity and AUC for VAS-pain in the younger group and use of glucocorticoids in the elderly were associated with poorer survival. Conclusion. Early treatment of RA may improve longterm outcomes. Presence of RF or ACPA associates with CVD and mortality among RA patients with disease onset before 65 years. Age stratification may improve evaluation of risk for CVD and mortality in early RA.

Diurnal variation in serum levels of cartilage oligomeric matrix protein in patients with knee osteoarthritis or rheumatoid arthritis

Objective: To monitor changes in serum concentrations of cartilage oligomeric matrix protein (COMP) during a 24-h period to determine any diurnal variation, and to estimate the half life of COMP in the circulation in patients with symptomatic knee osteoarthritis and in those with rheumatoid arthritis. Methods: Serum samples were drawn every 4 h (7 samples/patient over 24 h) in 10 patients with knee osteoarthritis and 14 patients with rheumatoid arthritis. Osteoarthritis was defined radiographically and clinically (American College of Rheumatology (ACR) criteria) and rheumatoid arthritis according to the 1987 ACR criteria. Serum COMP was measured by sandwich ELISA. A statistical model for the diurnal variation in the COMP levels was developed using the computer program NONMEM. Results: No considerable changes in COMP levels were observed during the day between 08:00 and 21:00 in either group. A significant decrease in serum COMP was apparent during bed rest at night, reaching the lowest levels between 04:00 and 05:00 (p<0.03 or better v all other time points) in patients with osteoarthritis and in those with rheumatoid arthritis. From the rate of decreasing serum COMP levels, a putative half life of COMP in the circulation was estimated to be 7.4 h. Conclusion: During normal daytime activities, serum COMP levels are constant. The decrease during the night indicates a rapid elimination of COMP once it has reached the circulation. The stable COMP levels during the day suggest that it is not necessary to further standardise the time of serum sampling in clinical practice.

Chronic Widespread Pain in Patients with Rheumatoid Arthritis and the Relation Between Pain and Disease Activity Measures over the First 5 Years

Objective. To study the prevalence of chronic widespread pain (ChWP), chronic regional pain (ChRP), and fibromyalgia in patients with early rheumatoid arthritis (RA) followed for 5 years after inclusion, and to study the effect of pain on measures of disease activity and function. Methods. A questionnaire was sent to 1910 patients participating in the Better Anti-Rheumatic Pharmacotherapy study. The responders (73%) were divided into 3 groups according to the reported pain duration and distribution — patients having no chronic pain (NChP), ChWP, and ChRP. Outcome measures were the 28-joint Disease Activity Score (DAS28), the Health Assessment Questionnaire (HAQ), and C-reactive protein (CRP). Results. Thirty-four percent of respondents reported ChWP, 46% ChRP, and 20% NChP. Patients reporting ChWP were more often women and had more pain and tender joints at inclusion. From 6 months to 5 years of followup, mean DAS28, visual analog scale (VAS) pain, VAS global health, and HAQ were significantly higher in the ChWP group than in the other groups. However, all groups showed a similar pattern in swollen joint count, erythrocyte sedimentation rate (ESR), and CRP. From 12 months the ChWP group was treated with prednisolone to a greater extent than the ChRP group, and it had a rate of treatment with disease-modifying antirheumatic drugs similar to that of the ChRP group. Conclusion. ChWP is a common feature in RA, more associated with high values for variables related to pain such as the DAS28 and HAQ than to indicators of ongoing inflammation such as swollen joint count, ESR, and CRP. Patients with ChWP should be identified so that adequate treatment also of the noninflammatory pain may be instituted.

Early increase in serum-COMP is associated with joint damage progression over the first five years in patients with rheumatoid arthritis

BackgroundCurrently available biomarkers for the early tissue process leading to joint damage in rheumatoid arthritis are insufficient and lack prognostic accuracy, possibly a result of variable activity of the disease over time. This study represents a novel approach to detect an altered activity of the disease process detected as increasing serum-COMP levels over a short time and whether this would correlate with joint damage progression over the first 5 years of disease.MethodsIn all, 349 patients from the Swedish BARFOT early RA study were examined. Serum-COMP was analysed by ELISA at diagnosis and after 3 months. Based on changes in serum-COMP levels, three subgroups of patients were defined: those with unchanged levels (change ≤ 20%) (N=142), decreasing levels (> 20%) (N=173) and increasing levels (> 20%) (N=34). Radiographs of hands and feet were obtained at inclusion, after 1, 2 and 5 years and scored according to Sharp van der Heijde (SHS). Radiographic progression was defined as increase in SHS by ≥5.8.ResultsThe group of patients with increasing COMP levels showed higher median change in total SHS and erosion scores at 1, 2 and 5 year follow-up compared with the groups with stable or decreasing COMP levels. Furthermore, the odds ratio of radiographic progression was 2.8 (95% CI 1.26-6.38) for patients with increasing COMP levels vs. patients with unchanged levels.The group of patients with increasing COMP levels had higher ESR at inclusion but there were no baseline differences between the groups for age, gender, disease duration, disease activity (DAS28), function (HAQ), CRP, nor presence of rheumatoid factor or anti-CCP. Importantly, neither did changes over the 3-month period in DAS28, HAQ, ESR nor CRP differ between the groups and these variables did not correlate to joint damage progression.ConclusionIncreasing serum-COMP levels between diagnosis and the subsequent 3 months in patients with early RA represents a novel indicator of an activated destructive process in the joint and is a promising tool to identify patients with significant joint damage progression during a 5-year period.

Long-term sustained remission in a cohort study of patients with rheumatoid arthritis: choice of remission criteria.

Objectives Remission is a widely accepted goal for treatment of rheumatoid arthritis (RA) but has to be sustained to arrest joint damage and disability. However, appropriate criteria for the assessment of sustained remission in long-term studies are not established. Therefore, we have compared the disease activity score calculated on 28 joints (DAS28) remission criterion, the Simplified Disease Activity Index less than 3.3 remission criterion (SDAI Cr) and the new Boolean-based set of criteria (Boolean Cr), and assessed the association of these criteria with radiographic and functional outcome. Design Prospective, long-term observational study of patients with early RA. Setting Secondary level of care; six participating centres from southern Sweden; both urban and rural populations. Participants 698 patients were consecutively included in the study and 527 remained at the 8-year follow-up visit. Almost all patients were Caucasians, of which 64% were women. To be included, a patient, 18 years or older, had to fulfil the 1987 American College of Rheumatology criteria for RA and have a disease duration of no more than 1 year. Results Sustained remission was most common by the DAS28 Cr (14%), while 3% met the Boolean Cr and 5% the SDAI Cr, the latter figures increasing to 9% and 8%, respectively, when the patient’s global assessment was excluded. Radiographic joint damage was common but least pronounced in patients in sustained remission by all criteria. Sustained remission was associated with rapid and lasting improvement in function assessed by the Health Assessment questionnaire, irrespective of criteria. Conclusions The DAS28 Cr acquired more patients in sustained remission compared with the other criteria. In spite of that, radiographic damage and disability were not worse than that seen by other criteria and the patients’ perspective was preserved. The DAS28 Cr may therefore still be used in long-term observational studies until more accurate criteria are available.

Is knee osteoarthritis a symmetrical disease? Analysis of a 12 year prospective cohort study

BackgroundThe aim of this study was to document the development of bilateral knee osteoarthritis over a 12 year period using a middle-aged population-based cohort with knee pain at inclusion.MethodsOne hundred and forty three patients aged 35 to 54 were recruited from a population based cohort of 279 subjects who had knee pain at baseline and assessed with clinical and radiographic data, with 5 and 12 year follow up. The data was analysed with regard to the development and progression of uni- and bilateral knee osteoarthritis over 12 years. A definition of KL = 1 was used to define radiographic disease.Results24 of the 30 (80%) patients with unilateral disease at baseline developed bilateral disease after 12 years. At baseline 37 patients (26%) had bilateral disease, whereas that number increased to 65 (52%) at 5 years and 100 (70%) at the 12 year follow up. The most common pattern was medial compartment involvement in both knees. Six patients had lateral compartment disease in one knee and medial in the other whereas only two had lateral compartment disease bilaterally.ConclusionsBilateral knee osteoarthritis is very common with time, as the majority of sufferers will eventually develop radiographic disease in both knees. Clinicians need to be aware of the ‘joint at risk’ and researchers need to remember to account for both knees when assessing the relationship between physical function, pain and structural disease. The other knee should not be used for comparison, even if it appears to be normal at baseline.

Serum COMP-C3b complexes in rheumatic diseases and relation to anti-TNF-α treatment

IntroductionCartilage oligomeric matrix protein (COMP) is found at elevated concentrations in sera of patients with joint diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA). We recently showed that COMP activates complement via the alternative pathway and that COMP-C3b complexes are present in sera of RA patients, but not in healthy controls. We now set out to elaborate on the information provided by this marker in a variety of diseases and larger patient cohorts.MethodsCOMP-C3b levels in sera were measured by using an enzyme-linked immunosorbent assay (ELISA) capturing COMP and detecting C3b. Serum COMP was measured by using ELISA.ResultsCOMP-C3b levels were significantly elevated in patients with RA as well as in systemic lupus erythematosus (SLE), compared with healthy controls. SLE patients with arthritis had significantly higher COMP-C3b levels than did those without. COMP-C3b was furthermore elevated in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, systemic sclerosis, and OA. COMP-C3b did not correlate with COMP in any of the patient groups. COMP-C3b correlated with disease activity in RA, but not in other diseases. COMP-C3b levels in RA patients decreased on treatment with tumor necrosis factor (TNF)-α inhibitors, whereas the levels increased in patients with AS or PsA. The changes of COMP-C3b did not parallel the changes of C-reactive protein (CRP).ConclusionsCOMP-C3b levels are elevated in several rheumatologic diseases and correlate with inflammatory measures in RA. COMP-C3b levels in RA decrease during TNF-α inhibition differently from those of CRP, suggesting that formation of COMP-C3b relates to disease features not reflected by general inflammation measures.