Rheumatoid Arthritis: Mowinckel P

Heiberg MS, Rødevand E, Mikkelsen K, Kaufmann C, Didriksen A, Mowinckel P, Kvien TK. · Department of Rheumatology, Diakonhjemmet Hospital, Box 23 Vinderen, N-0319 Oslo, Norway. · Ann Rheum Dis. · Pubmed #16679432 No free full text.

Abstract: OBJECTIVES: To compare the effectiveness of adalimumab monotherapy and adalimumab and methotrexate (MTX) combination therapy in patients with established rheumatoid arthritis. METHODS: Data from an ongoing longitudinal observational study in Norway were used to compare response to treatment with two different adalimumab regimens (monotherapy, n = 84; combination with MTX, n = 99). Patients were assessed with measures of disease activity, health status and utility scores. Within-group changes were analysed from baseline to follow-up at 3 and 6 months and the changes were compared between groups after adjustment for the propensity score. The groups were also compared for the proportions of patients achieving European League Against Rheumatism (EULAR) good response, Disease Activity Score (DAS)28 remission and treatment terminations. RESULTS: The improvement from baseline was significant for all measures in the adalimumab and MTX group, but only for DAS28, joint counts, two Short-form Health Survey with 36 questions (SF-36) dimensions and patient's and investigator's global assessment in the monotherapy group. All between-group differences were numerically in favour of combination therapy and significant for C reactive protein, joint counts, DAS28, Modified Health Assessment Questionnaire, investigator's global assessment, four SF-36 dimensions and Short Form 6D at 6 months. More patients in the combination therapy group reached EULAR good response (p<0.001) and remission (p = 0.07). At 6 months, 80.8% of the patients in the combination therapy group and 59.5% in the monotherapy group remained on treatment (p = 0.002). More withdrawals in the monotherapy group were due to adverse events. CONCLUSIONS: Our results were consistent across several categories of end points and suggest that adalimumab combined with MTX is effective in patients with rheumatoid arthritis treated in daily clinical practice and is superior to adalimumab monotherapy.

Heiberg MS, Nordvåg BY, Mikkelsen K, Rødevand E, Kaufmann C, Mowinckel P, Kvien TK. · Diakonhjemmet Hospital, Oslo, Norway. · Arthritis Rheum. · Pubmed #16052584 links to  free full text

Abstract: OBJECTIVE: To compare the effectiveness of tumor necrosis factor (TNF)-blocking agents (etanercept and infliximab) in patients with rheumatoid arthritis (RA) and patients with ankylosing spondylitis (AS). METHODS: Data from an ongoing longitudinal, observational study in Norway were used to assess changes in health-related quality of life (HRQOL) in patients with RA (n = 291) and AS (n = 62). Patients received anti-TNF therapy, and changes in scores on the Short Form 36 (SF-36), SF-6D, modified Health Assessment Questionnaire, and visual analog scales for patients' assessments of pain, fatigue, and global status from baseline to followup examinations at 3 and 6 months were compared. Data were adjusted for age, sex, and baseline values and are presented as crude estimates as well as standardized response means. RESULTS: Both groups had improvements in all measures at 3 and 6 months. At 3 months, the changes were significantly better in the AS group compared with the RA group for all measures except the SF-36 social functioning scores. At 6 months, all changes were numerically greater in the AS group. Differences were significant for the SF-36 role emotional scores and were borderline significant for the SF-36 physical functioning, role physical, and vitality scores and for the SF-6D scores. CONCLUSION: In this real-life setting, patients with AS experienced improvement in HRQOL that was comparable to, and sometimes greater than, that observed in RA patients. These results support the idea that patients with AS should have the same access to TNF-blocking agents as patients with RA.

Christie A, Hagen KB, Mowinckel P, Dagfinrud H. · National Resource Centre for Rehabilitation in Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · J Shoulder Elbow Surg. · Pubmed #19095181 No free full text.

Abstract: The aim of this study was to explore the methodological properties in 6 commonly used shoulder disability measures (Dash, Spadi, Oxford, the Constant score, Shoulder Function Assessment Scale, Bostrom's shoulder movement impairment scale) in patients with inflammatory or degenerative diseases referred for shoulder surgery. One-hundred and six patients completed the measures preoperatively. Fifty-five (51.9%) were not able to carry out the assessment of the strength component of the Constant score. Pearson correlation coefficients between the measures varied between 0.22 and 0.87. The lowest correlation coefficients were found between performance-based and self-report measures. All measures, except the Dash, were able to differentiate significantly between patients who were more and less severely affected. Performance-based measures differentiated better (effect size, 0.68- 0.87) than self-report measures (effect size, 0.21-0.61) between the 2 patient groups. Performance-based and self-report assessments provide complementary information about shoulder status and should not be used interchangeably.

Paus AC, Steen H, Røislien J, Mowinckel P, Teigland J. · Orthopaedic Department, Rikshospitalet University Hospital, Oslo, Norway. · Spine (Phila Pa 1976). · Pubmed #18784629 No free full text.

Abstract: STUDY DESIGN: In a prospective cohort study 532 patients with rheumatoid arthritis (RA) and subluxations of the cervical spine were consecutively collected during 1974-1999. OBJECTIVE: The aims of the study were to assess important factors affecting the mortality rate and the timing of surgical intervention. SUMMARY OF BACKGROUND DATA: The average follow-up time from the first visit to death or to the end of the study was 8.5 (SD, 5.7) years. Of the 217 operated patients 144 (66%) died, and of the 315 nonoperated patients 137 (43%) died. METHODS: Patients were selected for operative intervention based on anterior, vertical and subaxial subluxations, pain, and/or cervical neurology. Survival analyses were used for comparisons between patients with RA and the normal population, and between the operated and those treated conservatively. RESULTS: The survival rate for all RA patients was significantly reduced when compared with average survival in Norway (P < 0.001). The operated group had a significantly lower survival rate than the nonoperated group. In patients with severe instability of the cervical spine, the defined selection criteria for surgical intervention were specific. By comparison of calculated propensity scores, the operated and nonoperated groups were too different to be directly comparable. After surgery only 11 patients (5%) experienced residual pain in the neck or neurologic symptoms. None of these patients were alive at the end of the study, signifying that residual pain or neurologic symptoms are poor prognostic signs (P = 0.015). In the operated group, anterior subluxation and vertical settling greater than the lower indication limits did not have a significant influence on the survival rate, but there was a reduced survival for patients with subaxial subluxations. A clear association was found between increased vertical settling and sudden death. CONCLUSION: RA with neck involvement is a progressive and serious condition with reduced lifetime expectancy. Hence, our interpretation is that operative intervention improves local symptoms and most likely changes the condition from worse to better by increasing lifetime expectancy in high risk patients. Since the per- and postoperative complications are few, a changed attitude toward more liberal indications for earlier surgery may reduce the symptoms and the mortality rate even more.

Ringen HO, Dagfinrud H, Mowinckel P, Kvien T. · Department of Surgery, Diakonhjemmet Hospital, Oslo, Norway. · Scand J Rheumatol. · Pubmed #18612925 No free full text.

Abstract: OBJECTIVE: To examine the overall magnitude of change in self-reported physical function over a 10-year period in patients with rheumatoid arthritis (RA), and to compare changes in physical function between the lower and upper limbs. METHODS: Self-reported data on physical function were collected from the patients in the Oslo RA register (ORAR) through mail surveys between 1994 and 2004. The change in overall physical function was measured by the Short Form 36 (SF-36), the Modified Health Assessment Questionnaire (MHAQ), and the Arthritis Impact Measurement Scales (AIMS2). The MHAQ and AIMS2 were used to address activities related to lower and upper limb function. The magnitude of changes was expressed as crude and adjusted changes and standardized response means (SRMs). The analyses were adjusted for age, sex, duration of disease, and number of surgical procedures in the lower and upper limbs. RESULTS: A total of 414 patients [323 (78%) females, mean age 54.9 years and median disease duration 11.6 years] were included in these analyses. The overall physical function measured by AIMS2 physical and MHAQ deteriorated during 10 years. The magnitude of change in physical function was generally worse for activities related to lower limbs (SRM for adjusted changes 0.16-0.27) than upper limbs (SRM 0.06-0.08). During the 10-year follow-up period, 231 patients (56%) underwent orthopaedic surgery because of their RA. Findings were consistent after adjusting for surgical procedures. CONCLUSION: Patient-reported lower limb function deteriorated more than upper limb function over a 10-year period in patients with established RA.

Provan SA, Angel K, Odegård S, Mowinckel P, Atar D, Kvien TK. · Department of Rheumatology, Diakonhjemmet Hospital, Box 23 Vindern, N-0319 Oslo, Norway. · Arthritis Res Ther. · Pubmed #18573197 links to  free full text

Abstract: INTRODUCTION: Disease activity in patients with rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality, of which N-terminal pro-brain natriuretic peptide (NT-proBNP) is a predictor. Our objective was to examine the cross-sectional and longitudinal associations between markers of inflammation, measures of RA disease activity, medication used in the treatment of RA, and NT-proBNP levels (dependent variable). METHODS: Two hundred thirty-eight patients with RA of less than 4 years in duration were followed longitudinally with three comprehensive assessments of clinical and radiographic data over a 10-year period. Serum samples were frozen and later batch-analyzed for NT-proBNP levels and other biomarkers. Bivariate, multivariate, and repeated analyses were performed. RESULTS: C-reactive protein (CRP) levels at baseline were cross-sectionally associated with NT-proBNP levels after adjustment for age and gender (r2 adjusted = 0.23; P < 0.05). At the 10-year follow-up, risk factors for cardiovascular disease were recorded. Duration of RA and CRP levels were independently associated with NT-proBNP in the final model that was adjusted for gender, age, and creatinine levels (r2 adjusted = 0.38; P < 0.001). In the longitudinal analyses, which adjusted for age, gender, and time of follow-up, we found that repeated measures of CRP predicted NT-proBNP levels (P < 0.001). CONCLUSION: CRP levels are linearly associated with levels of NT-proBNP in cross-sectional and longitudinal analyses of patients with RA. The independent associations of NT-proBNP levels and markers of disease activity with clinical cardiovascular endpoints need to be further investigated.

Mowinckel P, Hagen KB, Heiberg T, Kvien TK. · National Resource Centre for Rehabilitation in Rheumatology, Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · J Clin Epidemiol. · Pubmed #18538992 No free full text.

Abstract: OBJECTIVES: To investigate whether repeated measures in patients with rheumatoid arthritis will reduce the between subject variation and if so, to determine the optimal number of measures to effectively reduce the number of participants required in controlled clinical trials. STUDY DESIGN AND SETTING: A prospective observational study. Thirty-eight rheumatoid arthritis patients with a stable disease reported level of joint pain, fatigue and patient global assessment of disease activity on VAS scales as well as the Rheumatoid Arthritis Disease Activity Index (RADAI) daily during a total of 42 days. RESULTS: In all measures, the variation within each individual was substantial over a 42-day period. By increasing the number of measurements from one to five, the standard deviation (SD) decreased from 5.5% (RADAI score) to 11% (Pain VAS) resulting in a reduction in the number of patients needed in a clinical trial from 11% to 22%, respectively. When we used from 6 to 42 individual measurements, the decrease continued but the reduction was of a smaller magnitude. CONCLUSION: The use of up to five repeated measurements per patient will decrease the number of patients required in a two armed clinical trial by as much as 22%.

Heiberg MS, Koldingsnes W, Mikkelsen K, Rødevand E, Kaufmann C, Mowinckel P, Kvien TK. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Arthritis Rheum. · Pubmed #18240258 links to  free full text

Abstract: OBJECTIVE: To compare the 1-year retention rates of anti-tumor necrosis factor alpha (anti-TNFalpha) medications in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) with complementary analyses of the effect on health status. METHODS: Our analyses comprised 847, 172, and 249 anti-TNFalpha treatment courses in patients with RA, PsA, and AS, respectively. Crude drug survival was compared and hazard ratios (HRs) for treatment termination were calculated with adjustments for age, sex, investigator's global assessment, and concomitant methotrexate (MTX). Adjusted changes in health-related quality of life (HRQOL) were compared among the groups. RESULTS: Unadjusted 1-year retention rates were 65.4%, 77.3%, and 77.5% in the RA, PsA, and AS groups, respectively. The adjusted HRs for treatment termination were 0.76 (95% confidence interval [95% CI] 0.53-1.07) for PsA versus RA and 0.66 (95% CI 0.47-0.92) for AS versus RA. High baseline disease activity and female sex were significantly associated with premature treatment termination, whereas concomitant MTX was associated with better drug survival. However, the impact of MTX was apparent for RA and PsA, but not for AS in stratified analyses. The improvements in HRQOL were superior in patients with PsA and AS compared with RA. CONCLUSION: Our results suggest that survival of anti-TNFalpha treatment is superior in AS and PsA patients compared with RA patients. Larger improvements in HRQOL in patients with spondylarthritides may contribute to the differences in drug survival. Concomitant MTX was associated with better retention rates in RA and PsA patients, but not AS patients.

Uhlig T, Heiberg T, Mowinckel P, Kvien TK. · Department of Rheumatology, Diakonhjemmet Hospital, N-0319 Oslo, Norway. · Ann Rheum Dis. · Pubmed #18218667 No free full text.

Abstract: OBJECTIVES: During the last decades major advances have occurred in the treatment of patients with rheumatoid arthritis (RA), and improvements in the burden of the disease have been suggested. We examined whether there was a secular change towards less severe disease from 1994 to 2004 among patients within the representative setting of the Oslo Rheumatoid Arthritis Register (ORAR). METHODS: All living patients in the ORAR received a postal questionnaire in 1994, 1996, 2001 and 2004, including the Modified Health Assessment Questionnaire (MHAQ), SF-36, Arthritis Impact Measurement Scales 2 (AIMS2) and visual analogue scales for the patient global assessment of disease severity, pain and fatigue. A mixed model approach was used for longitudinal analysis adjusting for sex, age, co-morbidity, and for disease duration and DMARD if indicated. RESULTS: The numbers of respondents aged between 20 and 79 years in 1994, 1996, 2001 and 2004 were 931, 1025, 829 and 914 patients with similar demographic characteristics (mean age in 1994 was 60.6 years, mean disease duration 12.6 years, 78% females). Health status in the population with RA was consistently improved in all dimensions of health, and this improvement was statistically significant for the physical dimension, global health and pain over the 10-year period until 2004. Both year of examination and year of disease onset had an effect on measures of longitudinal health status outcome. CONCLUSIONS: Health status in RA improved from 1994 to 2004, probably due to access to better and more aggressive treatments.

Slatkowsky-Christensen B, Mowinckel P, Loge JH, Kvien TK. · Diakonhjemmet Hospital, Oslo, Norway. · Arthritis Rheum. · Pubmed #18050180 links to  free full text

Abstract: OBJECTIVE: Data on the burden of disease and impact on health-related quality of life (HRQOL) in hand osteoarthritis (OA) are limited. The goal of this study was to compare HRQOL in patients with hand OA with HRQOL in patients with rheumatoid arthritis (RA), healthy controls, and normative data from the general population. METHODS: A total of 190 women with hand OA were compared with 194 women with RA and 144 healthy women of the same age. Health status was measured using the Short Form 36 (SF-36), Short Form 6D (SF-6D), modified Health Assessment Questionnaire (M-HAQ), pain and fatigue visual analog scales, and grip strength. Scores were compared by analysis of variance and a multivariate analysis of covariance, adjusting for age, number of comorbidities, and years of education. Gaps between patients and population subjects were assessed by calculating S scores on all dimensions of the SF-36. RESULTS: Hand OA and RA patients had worse scores on all assessed dimensions of subjective health compared with healthy controls. RA patients showed poorest general health (SF-36), poorest physical function (M-HAQ, SF-36 physical, grip strength), and highest level of fatigue compared with hand OA patients. Hand OA patients reported poorer mental health. Mean utility scores (SF-6D) in hand OA and RA were 0.64 and 0.63, respectively, with a mean difference compared with healthy controls of 0.13 in hand OA and 0.14 in RA patients. S scores confirmed a marked disparity between individuals with a rheumatic diagnosis (hand OA, RA) and population subjects. CONCLUSION: This study illustrates that patients with hand OA experience a broad impact on HRQOL compared with healthy controls. Fatigue and physical function are worse in RA than hand OA.

Heiberg T, Kvien TK, Mowinckel P, Aletaha D, Smolen JS, Hagen KB. · Department of Research and Education, Ullevål University Hospital, N- 0407 Oslo, Norway. · Ann Rheum Dis. · Pubmed #17965118 No free full text.

Abstract: BACKGROUND: Established thresholds for low levels of disease activity need to be examined from a patients' perspective. OBJECTIVE: To identify new cut-off points for patients' perception of satisfactory condition (patient acceptable symptom state (PASS)) in composite indices and patient-reported outcomes, and to examine the agreement between the new PASS cut-off points for composite indices and existing thresholds for remission, low and moderate disease activity. METHODS: Patients with rheumatoid arthritis from a treatment register (n = 1496, 72.1% women, mean (SD) age 53.9 (13.5) years, disease duration 7.6 (9.1) years, 28-joint Disease Activity Score (DAS28) 4.98 (1.36)) responded during follow-up (12, 24 and 52 weeks) to a global dichotomised question on satisfactory condition (PASS). New PASS cut-off points were identified with the 75th centile estimation and receiver operating characteristic analyses for a variety of outcome measures, and cut-off points for composite indices were examined for agreement with the low disease activity threshold (1.625) of the Patient Activity Scale (PAS) and thresholds for remission, low and moderate disease activity in DAS28, Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI). RESULTS: New PASS cut-off points for DAS28, SDAI and CDAI were in the moderate range of disease activity, and the cut-off point was 3.56 for PAS. Agreement between thresholds for disease activity levels and the PASS cut-off points was best for low disease activity (accuracy 64.5-74.6), and better for moderate disease activity (accuracy 61.3-67.2) than for remission (accuracy 30.7-45.8). CONCLUSION: The current PASS concept seems to be in the range of moderate disease activity.

Syversen SW, Gaarder PI, Goll GL, Ødegård S, Haavardsholm EA, Mowinckel P, van der Heijde D, Landewé R, Kvien TK. · Department of Rheumatology, Diakonhjemmet Hospital, PB 23 Vindern, N-0319 Oslo, Norway. · Ann Rheum Dis. · Pubmed #17526555 No free full text.

Abstract: OBJECTIVES: New effective therapies with particularly good effect on joint destruction have highlighted the need for reliable predictors of radiographic progression in rheumatoid arthritis (RA). Our objective was to assess the combined predictive role of a set of laboratory markers with regard to 10-year radiographic progression, and to examine the effect of anti-cyclic citrullinated peptide (anti-CCP) level. METHODS: A cohort of 238 patients with RA was followed longitudinally for 10 years with the collection of clinical data and serum samples. 125 patients with radiographs of the hands available at both baseline and after 10 years were included in this study. Radiographs were scored according to the van der Heijde modified Sharp score. Baseline sera were analysed for C-reactive protein, erythrocyte sedimentation rate (ESR), anti-CCP, IgA rheumatoid factor (RF) and IgM RF. Logistic regression analyses were used to identify predictors of radiographic progression and to examine the effect of anti-CCP level. RESULTS: Anti-CCP (OR 4.0; 95% CI 1.6 to 10.0) was the strongest independent predictor of radiographic progression. Female gender (OR 3.3; 95% CI 1.3 to 7.6), high ESR (OR 3.2; 95% CI 1.2 to 7.6) and a positive IgM RF (OR 3.1; 95% CI 1.2 to 7.9) were also independent predictors. Compared with the anti-CCP-negative patients, patients with low to moderate levels of anti-CCP (OR 2.6; 95% CI 0.9 to 7.2) and patients with high levels of anti-CCP (OR 9.9; 95% CI 2.7 to 36.7) were more likely to develop radiographic progression. CONCLUSIONS: Anti-CCP, IgM RF, ESR and female gender were independent predictors of radiographic progression and could be combined into an algorithm for better prediction. Patients with high levels of anti-CCP were especially prone to radiographic progression, indicating that the anti-CCP level may add prognostic information.

Heiberg T, Kvien TK, Dale Ø, Mowinckel P, Aanerud GJ, Songe-Møller AB, Uhlig T, Hagen KB. · Centre for Education and Skill Training, Ulleval University Hospital, Oslo, Norway. · Arthritis Rheum. · Pubmed #17394232 links to  free full text

Abstract: OBJECTIVE: The patient perspective workshops at the Outcome Measures in Rheumatology Clinical Trials have included daily measures of health status (patient diary) and use of electronic tools for data collection in the research agenda. The objective of this study was to compare daily and weekly registrations of self-reported health status measures between personal digital assistant (PDA) and paper-pencil (PP) format regarding scores, variation, and feasibility. METHODS: Thirty-eight patients with stable rheumatoid arthritis recorded their health status during 84 days in a repeated crossover design, using PDA or PP format during four 21-day periods. Visual analog scales (VAS) for pain, fatigue, and global disease and the Rheumatoid Arthritis Disease Activity Index were scored daily; the Short Form 36 and Modified Health Assessment Questionnaire were scored weekly. RESULTS: The average scores and measures of variation of the 4 daily health status measures over 21 days did not differ significantly between PDA and PP formats in either of the 2 crossover periods. The values for the average range between the maximum and minimum values for daily measures were similar between the 2 formats, but showed considerable variation (e.g., range for pain VAS was 19-28 mm over each 21-day period). The time to complete the instruments was similar between the 2 formats. Missing daily data entries were generally low for both periods and somewhat higher for PDA. The majority of patients (82.9%) preferred using PDA. CONCLUSION: Daily assessments with PDA may be efficiently used for frequent data collection because this format performs similarly to the traditional PP format.

Odegård S, Finset A, Mowinckel P, Kvien TK, Uhlig T. · Department of Rheumatology, Diakonhjemmet Hospital, N-0319 Oslo, Norway. · Ann Rheum Dis. · Pubmed #17392351 No free full text.

Abstract: OBJECTIVE: To examine rheumatoid arthritis (RA) with short disease duration over 10 years, and to identify factors that are associated with the course of pain, depression and anxiety. METHODS: A cohort of 238 patients with RA (age 20-70 years, mean disease duration 2.3 years, 68% rheumatoid factor positive) was followed with assessments at baseline and after 1, 2, 5 and 10 years. Self-reported health status was assessed by pain on a 100 mm visual analogue scale, the Arthritis Impact Measurement Scales (AIMS), the 28-item version of General Health Questionnaires, and the Health Assessment Questionnaire. We also examined the erythrocyte sedimentation ratio, grip strength (kg) and radiographic progression of the hands (van der Heijde modified Sharp score). Repeated measures analyses of variance were used to explore the effect of time on measures of outcome among completers, whereas repeated measures analyses using a mixed model were applied to identify factors that were longitudinally associated with pain, depression and anxiety. RESULTS: At the various assessment points 30% had a visual analogue scale pain score of > or =40 mm, 5-13% had an AIMS depression score of > or =4.0 and 20-30% had an AIMS anxiety score of > or =4.0. The perceived level of pain was explained longitudinally by anxiety, disease activity, physical function and female gender, depression by high disease activity and anxiety, whereas anxiety was explained by low disease activity and depression. CONCLUSION: More patients had increased levels of anxiety (20-30%) than increased levels of depression (5-13%). Several factors, including anxiety, but not depression, were associated with the course of pain.

Hammer HB, Odegard S, Fagerhol MK, Landewé R, van der Heijde D, Uhlig T, Mowinckel P, Kvien TK. · Department of Rheumatology, Diakonhjemmet Hospital, Box 23, Vinderen, N-0319 Oslo, Norway. · Ann Rheum Dis. · Pubmed #17234650 No free full text.

Abstract: OBJECTIVE: Calprotectin is a major leucocyte protein, shown to correlate well with laboratory and clinical assessments in several inflammatory rheumatic diseases, and large concentrations of calprotectin have been found in synovial fluid from patients with rheumatoid arthritis (RA). The objective of the present study was to examine correlations between calprotectin and joint damage. METHODS: 145 patients with RA were analysed cross sectionally with laboratory (calprotectin, C reactive protein (CRP), and erythrocyte sedimentation rate (ESR)), clinical (28 joint counts (tender, swollen), physician global VAS, DAS28 and RA Articular Damage score (RAAD)), and radiographic (plain hand radiographs; modified Sharp's method) measurements, on the same day. RESULTS: Calprotectin showed a highly significant correlation with measures of joint damage; modified Sharp score r = 0.43 (p<0.001) and RAAD r = 0.40 (p<0.001). The association with modified Sharp score and RAAD score was maintained after adjustment for CRP, ESR, rheumatoid factor, DAS28, sex, and age in a multiple regression analysis (p = 0.018 and p = 0.04, respectively), while neither CRP nor ESR showed any independent associations. Highly significant correlations (p<0.001) were also found between calprotectin and both laboratory and clinical markers of inflammation. CONCLUSION: Calprotectin was found to significantly and independently explain the variation in the radiological and clinical assessments of joint damage. Longitudinal studies are required to examine whether calprotectin may predict the progression of joint damage in RA.

Uhlig T, Lillemo S, Moe RH, Stamm T, Cieza A, Boonen A, Mowinckel P, Kvien TK, Stucki G. · National Resource Center for Rehabilitation in Rheumatology, Department of Rheumatology, Diakonhjemmet Hospital, Postboks 23 Vinderen, N-0319 Oslo, Norway. · Ann Rheum Dis. · Pubmed #17223659 No free full text.

Abstract: BACKGROUND: The comprehensive ICF Core Set for rheumatoid arthritis (RA) is a selection of 96 categories from the International Classification of Functioning, Disability and Health (ICF), representing relevant aspects in the functioning of RA patients. OBJECTIVES: To study the reliability of the ICF Core Set for RA in rheumatological practice, and to explore the metric of the qualifiers' scale. METHODS: 25 RA patients from an outpatient department of rheumatology were interviewed using the ICF Core Set for RA (76% females, mean (SD) age 57.5 (12.5) years, disease duration 15.9 (14.6) years). Interviews were performed independently by both a physiotherapist and an occupational therapist on the same day and again after one week by one of them. The severity of the patients' problems was quantified on a qualifier scale ranging from 0 (no problem) to 4 (complete problem). Analyses of intra-rater and inter-rater agreement, kappa statistics, and Rasch analyses were applied. RESULTS: Mean intra-rater (inter-rater) complete agreement for all categories was seen in 59% (47%) of observations, ranging from 29% (0%) to 96% (80%) for individual categories. Weighted kappa statistics with value > or =0.4 showed reliability in 86% of categories within raters, and in 43% of categories between raters. Improved inter-rater and intra-rater reliability was observed with a reduced number of qualifiers for the categories. CONCLUSIONS: Inter-rater and intra-rater reliability of the ICF Core Set of RA was low to moderate. The metric of the qualifiers' scale may be improved by reducing the number of qualifiers to three for all components.

Kjeken I, Dagfinrud H, Mowinckel P, Uhlig T, Kvien TK, Finset A. · National Resource Centre for Rehabilitation in Rheumatology, Diakonhjemmet Hospital, boks 23 Vinderen, 0319 Oslo, Norway. · Arthritis Rheum. · Pubmed #16739186 links to  free full text

Abstract: OBJECTIVE: To examine levels of received information, involvement in medical decisions, and satisfaction with care, to explore factors related to current involvement in medical decisions, and to assess patients' unmet health care needs related to their disease. METHODS: A total of 1,193 patients with rheumatoid arthritis and ankylosing spondylitis completed self-reported health status questionnaires, including registration of sociodemographic data and questions about rheumatology care. Separate questions addressed information received, involvement in decisions, and satisfaction with care. Aspects of unmet health were assessed by an open-ended question. RESULTS: The majority of patients reported medium to high levels of received information, involvement in medical decisions, and satisfaction with care. High involvement in medical decisions was univariately associated with high levels of perceived information and satisfaction, as well as with lower age and a good health status. In the multivariate analyses, patient satisfaction (odds ratio [OR] 4.21) and a high level of received information (OR 7.85), age (OR 0.99), and >12 years of formal education (OR 1.46) remained as significant predictors to current involvement. Nearly one-third reported a variety of unmet health care needs, and this report was associated with poor health. CONCLUSION: The results indicate a need for a more flexible and patient centered care model, in which patients to a larger degree can decide which services they need and how these services should be delivered.

Odegård S, Finset A, Kvien TK, Mowinckel P, Uhlig T. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Scand J Rheumatol. · Pubmed #16393765 No free full text.

Abstract: OBJECTIVE: To explore the prevalence of work disability (WD) and to identify bio-psychological factors that predicts future WD in rheumatoid arthritis (RA) over a 7-year period. METHODS: Patients were selected from the Oslo RA register. The prevalence of WD was studied cross-sectionally among respondents <67 years (n = 526) in a postal survey. Mean age (SD) was 51.1 (11.9) years, mean disease duration 11.3 (9.4) years, and 49% of patients were RF-positive. The patients studied for predictive factors for WD were respondents in postal surveys both at baseline and at the 7-year follow-up, in work at baseline and still in working age (<67 years) at follow-up (n = 159). Mean age at baseline (SD) was 44.5 (9.7) years, mean disease duration 8.4 (6.6) years, mean years of formal education 12.7 (3.1) years, 48% were RF-positive. Assessments included socio-demographic variables and health status measures (MHAQ, AIMS2, SF-36, fatigue and pain on VAS 0-100 mm, self efficacy, and RAI as a measure for helplessness). RESULTS: Among the 526 respondents at baseline <67 years, the prevalence of WD was 40%. A high level of education was a predictor of reduced risk of work disability [odds ratio (OR) = 0.4, 95% confidence interval (CI) 0.1; 0.9], while female gender (OR 3.0, 95% CI 1.1; 8.0), physical disability (MHAQ-score) (OR = 3.9, 95% CI 1.2; 12.5) and helplessness over median RAI-score (OR = 3.0, 95% CI 1.4; 6.7) were independent predictors of increased risk for new work disability over 7 years. CONCLUSION: Physical disability, increased helplessness, low formal education, and female gender were found to be independent risk factors for new work disability over the 7-year study period.

Ødegård S, Landewé R, van der Heijde D, Kvien TK, Mowinckel P, Uhlig T. · Department of Rheumatology, Diakonhjemmet Hospital, N-0319 Oslo, Norway. · Arthritis Rheum. · Pubmed #16385497 links to  free full text

Abstract: OBJECTIVE: To investigate the longitudinal relationship between physical disability, disease activity, and radiographic damage over 10 years in patients with rheumatoid arthritis (RA). METHODS: A cohort of 238 consecutively enrolled RA patients from the European Research on Incapacitating Disease and Social Support study (age range 20-70 years, mean disease duration 2.3 years, 68% rheumatoid factor [RF] positive) was followed up longitudinally for 10 years. Assessments at baseline and at years 1, 2, 5, and 10 comprised review of demographic variables, measurement of disease activity with the erythrocyte sedimentation rate (ESR), functional evaluations using the Health Assessment Questionnaire (HAQ) and grip strength (average value of the right and left hand), and radiographs of the hands scored by the van der Heijde modification of the Sharp method. Marginal modeling by generalized estimating equations was used to study the longitudinal relationship between the ESR and modified Sharp radiographic damage score with respect to explaining the HAQ score and grip strength. Age, sex, RF status, and disease duration were entered as covariates. RESULTS: The HAQ score and grip strength were longitudinally associated with the momentary modified Sharp/van der Heijde score as well as with progression in this score, independent of the ESR. Therefore, an increase of 10 units in the modified Sharp/van der Heijde score will result in a 0.03-unit increase in HAQ score and a 0.95-kg decrease in grip strength, after adjustment for the ESR. CONCLUSION: This 10-year observational study provides evidence that both radiographic damage and disease activity are independent contributors to impaired physical function in RA, both early and late in the disease process.

Kvien TK, Mowinckel P, Heiberg T, Dammann KL, Dale Ø, Aanerud GJ, Alme TN, Uhlig T. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Ann Rheum Dis. · Pubmed #15843456 links to  free full text

Abstract: BACKGROUND: Increasing use of self reported health status in clinical practice and research, as well as patient appreciation of monitoring fluctuations of health over time, suggest a need for more frequent collection of data. Electronic use of health status measures in the follow up of patients is a possible way to achieve this. OBJECTIVE: To compare self reported health status measures in a personal digital assistant (PDA) version and a paper/pencil version for test-retest reliability, agreement between scores, and feasibility. METHODS: 30 patients with stable rheumatoid arthritis (mean age 61.6 years, range 49.8 to 70.0; mean disease duration, 16.7 years; 63% female; 67% rheumatoid factor positive; 46.6% on disease modifying antirheumatic drugs) completed self reported health status measures (pain, fatigue, and global health on visual analogue scales (VAS), rheumatoid arthritis disease activity index, modified health assessment questionnaire, SF-36) in a conventional paper based questionnaire version and on a PDA (HP iPAQ, model h5450). Completion was repeated after five to seven days. RESULTS: Test-retest reliability was similar, as evaluated by the Bland-Altman approach, the coefficient of variation, and intraclass correlation coefficients. The scores showed acceptable agreement, but with a slight tendency to higher scores on VAS with the PDA than the paper/pencil version. No significant differences were seen for measures of feasibility (time to complete, satisfaction score), but 65.5% preferred PDA, 20.7% preferred paper, and 13.8% had no preference. CONCLUSIONS: The clinimetric performance of paper/pencil versions of self reported health status measures was similar to an electronic version, using an inexpensive PDA.

Ørstavik RE, Haugeberg G, Uhlig T, Mowinckel P, Kvien TK, Falch JA, Halse JI. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Ann Rheum Dis. · Pubmed #15249321 links to  free full text

Abstract: BACKGROUND: Quantitative ultrasound (QUS) is a reliable tool for discriminating between subjects with and without vertebral deformities in postmenopausal osteoporosis. Less is known about osteoporosis caused by inflammatory diseases or corticosteroid use. OBJECTIVES: (1). To compare in patients with rheumatoid arthritis the ability of QUS and dual energy x ray absorptiometry (DXA) to discriminate between those with and without vertebral deformities; (2). to explore whether the results are similar in population based controls. METHODS: Standardised lateral radiographs of the spine were obtained from 210 patients with rheumatoid arthritis aged over 50 years and 210 individually matched controls. Vertebral deformities were assessed morphometrically and semiquantitatively. All participants underwent bone measurements by DXA (Lunar Expert) and QUS (Lunar Achilles+). Receiver operating curve (ROC) analysis was used to compare the discriminating ability of BMD and QUS measurements in patients and controls with and without vertebral deformities. Analyses were repeated in patients stratified according to corticosteroid use. RESULTS: For all bone measurements except lumbar spine in the rheumatoid arthritis group, BMD discriminated significantly between the patients with and without vertebral deformities, and the results were similar to those obtained in controls. Among current corticosteroid users, neither QUS nor DXA could discriminate between subjects with and without vertebral deformities. CONCLUSIONS: These findings support QUS as an alternative tool for identifying patients at risk of having vertebral deformities in rheumatoid arthritis, although results should be interpreted with caution in current users of corticosteroids.

Orstavik RE, Haugeberg G, Uhlig T, Mowinckel P, Falch JA, Halse JI, Kvien TK. · Department of Rheumatology, Diakonhjemmet Hospital, Box 23, Vinderen, 0319, Oslo, Norway. · Osteoporos Int. · Pubmed #15197538 No free full text.

Abstract: To date, no studies have been published on incident deformities in patients with rheumatoid arthritis (RA). Morphometric X-ray absorptiometry (MXA) is an alternative to conventional X-rays for identifying vertebral deformities. The aim of the present study was to describe the incidence of vertebral deformities in 255 female RA patients measured by MXA, and the relationship between incident deformities and clinical and demographic variables. MXA is still under evaluation for its ability to identify deformities, so we explored four different cut-off thresholds including fixed percentage reduction and the principle of least significant change (LSC). MXA (T4-L4) and BMD (L2-L4 and total hip; Lunar Expert) were performed on 255 patients (mean age 54.3, range 29.2-70.8 years) at baseline and after a mean period of 2.3 years. MXA scans were analyzed pairwise by the same trained technician, and incident deformities calculated applying LSC with a 99.9% and 99.99% confidence limit, and a fixed reduction of 20% and 25% for anterior, middle or posterior heights. Long term precision (%CV) of height measurements for all vertebrae combined (T4-L4) were 4.8, 4.8 and 4.4, respectively. Frequency and distribution of incident deformities varied from 39 deformities in 33 patients (fixed 20% reduction) to 17 deformities in 15 patients (fixed 25% reduction), and quality control analyses revealed a high number of presumed false deformities. Incidence per 100 patient years varied from 2.9 to 6.7 deformities according to method, and was comparable to those obtained from intervention studies in corticosteroid-induced osteoporosis. Patients with incident deformities were significantly older, had lower BMD, higher disability and more often a previous non-vertebral fractures than those without incident deformities Incident deformities by MXA need further evaluation in secondary osteoporosis. It seems, however, that older patients with previous limb fractures and low BMD are especially prone to this complication.

Ørstavik RE, Haugeberg G, Mowinckel P, Høiseth A, Uhlig T, Falch JA, Halse JI, McCloskey E, Kvien TK. · Oslo City Department of Rheumatology, Oslo, Norway. · Arch Intern Med. · Pubmed #14980993 links to  free full text

Abstract: BACKGROUND: Previous studies have shown an increased prevalence of osteoporosis in rheumatoid arthritis (RA), but the extent of osteoporotic fractures is not clarified. The aim of this study was to compare the prevalence of vertebral deformities in a representative, population-based cohort of female patients with RA with that in matched controls, and to examine the relationship between deformities and RA, bone mineral density (BMD), and corticosteroid use. METHODS: Female patients (mean age, 63.0 years; range, 50.7-73.6 years) were recruited from a county register of patients with RA. Population controls were matched for age, sex, and residential area. Participants had thoracolumbar radiographs taken according to a standardized procedure, and BMD was measured at the hip and spine (L2-L4). RESULTS: The overall number of vertebral deformities was substantially higher in the RA group compared with controls (147 vs 51, applying the morphometric criteria), with a highly significant difference between patients and controls regarding the presence of multiple deformities measured morphometrically (11.2% vs 4.8%; odds ratio, 2.60; 95% confidence interval, 1.21-6.04) and moderate or severe deformities measured semiquantitatively (17.3% vs 10.0%; odds ratio, 2.00; 95% confidence interval, 1.11-3.74). In Poisson regression analysis, vertebral deformities were independently associated with RA, BMD, and long-term corticosteroid use. CONCLUSIONS: Vertebral deformities are markedly increased in patients with RA compared with controls, especially regarding severe and multiple deformities. A diagnosis of RA was associated with vertebral deformities independently of BMD and long-term corticosteroid use. These findings have important implications for prevention of established osteoporosis in RA.

Ørstavik RE, Haugeberg G, Uhlig T, Mowinckel P, Falch JA, Halse JI, Kvien TK. · Oslo City Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Ann Rheum Dis. · Pubmed #14722207 links to  free full text

Abstract: OBJECTIVE: To compare the incidence of self reported non-vertebral fractures after RA diagnosis between female patients with RA and control subjects, and to explore possible associations between non-vertebral fractures and bone mineral density (BMD), disease, and demographic factors. METHODS: 249 women (mean age 63.0 years) recruited from a county register of patients with RA and population controls (n = 249) randomly selected after matching for age, sex, and residential area were studied. Data on previous non-vertebral fractures were obtained from a detailed questionnaire, and BMD was measured at the hip and spine. RESULTS: 53 (21.3%) patients with RA had had 67 fractures after RA diagnosis, the corresponding numbers for controls were 50 (20.1%) and 60 (odds ratio (OR) for paired variables for overall fracture history 1.09, 95% CI 0.67 to 1.77). The overall fracture rates per 100 patient-years were 1.62 and 1.45, respectively, but self reported hip fractures were increased in RA (10 v 2, OR 9.0, 95% CI 1.2 to 394.5). Patients with a positive fracture history had longer disease duration, were more likely to have at least one deformed joint, and had lower age and weight adjusted BMD than those with no fracture history. In logistic regression analysis, fracture history was independently related to BMD only. CONCLUSIONS: With the probable exception of hip fractures, non-vertebral fractures do not seem to be a substantial burden in RA. Similar independent relationships between levels of BMD and fracture history were found in patients with RA and in population based controls.