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ABSTRACT: OBJECTIVE: To identify predictors of sick leave and disability pension in patients with early rheumatoid arthritis (RA). METHODS: Individuals aged 19-59 years diagnosed with early RA (≤12 months symptom duration) were identified in the Swedish Rheumatology Quality Register (1999-2007; n=3029). We retrieved days of sick leave and disability pension from the Swedish Social Insurance Agency and baseline predictors of total work days lost during 3 years after RA diagnosis were investigated using linear regression. Due to effect modification by baseline work ability (defined as work days lost the month before diagnosis), analyses were stratified into three categories: full=0 work days lost the month before diagnosis; partial=1-29 work days lost; and none=30 work days lost. RESULTS: 71% of patients with full baseline work ability still had full work ability after 3 years compared with 36% (p<0.001) and 18% (p<0.001) of those with partial and no work ability at baseline, respectively. Elevated baseline levels of HAQ and DAS28, higher age, lower education level and unemployment were associated with more work days lost during 3 years in all strata of baseline work ability (all p<0.05). In a separate analysis, more objective variables (ESR, CRP and swollen joints) were not. Generally, the largest regression coefficients were seen for patients with partial baseline work ability. CONCLUSIONS: Work ability at RA diagnosis was the most important predictor of 3-year sick leave and disability pension. Taking this into account, HAQ, DAS28, age and education level were also significant predictors, whereas ESR and CRP were not.
Annals of the rheumatic diseases 03/2013; · 8.11 Impact Factor
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ABSTRACT: INTRODUCTION: The aim of this study is to explore the persistence of antibody response 1.5 years after vaccination using 7-valent pneumococcal conjugate vaccine in patients with rheumatoid arthritis (RA) or spondylarthropathy (SpA) treated with different anti-rheumatic drugs. METHODS: Of 505 patients initially recruited, data on current anti-rheumatic treatment and blood samples were obtained from 398 (79%) subjects after mean (SD; range) 1.4 (0.5; 1-2) years. Antibody levels against pneumococcal serotypes 23F and 6B were analyzed using ELISA. Original treatment groups were: 1. RA on methotrexate (MTX); 2. RA on anti-TNF monotherapy; 3. RA on anti-TNF+MTX; 4. SpA on anti-TNF monotherapy; 5. SpA on anti-TNF+MTX; and 6. SpA on NSAID/analgesics. Geometric mean levels (GML; 95% CI) and proportion (%) of patients with putative protective antibody levels [greater than or equal to]1 mg/L for both serotypes calculated in different treatment groups were compared to results 4-6 weeks after vaccination. Patients remaining on initial treatment were included in the analysis. Possible predictors of persistence of protective antibody response were analysed using logistic regression analysis. RESULTS: Of 398 patients participating in 1.5 year follow up, 302 patients (RA=163 and SpA=139) had unchanged medication. Compared to post-vaccination levels at 1.5 year GML for each serotype were significantly lower in all groups (p between 0.035 and <0.001; paired sample T-test) as were proportion of patients with protective antibody levels for both serotypes (p<0.001; Chi2 test). Higher prevaccination antibody levels for both serotype 23 F and 6B was associated with better persistence of protective antibodies (p<0.001). Compared to patients with protective antibody levels at 1.5 years those not having protective antibody levels were older, more often women, had longer disease duration, and higher HAQ and DAS, and lower proportion of initial responders to both serotypes. Concomitant anti-TNF treatment and MTX were identified as negative predictors of persistence of protective antibodies among RA patients (p=0.024 and p=0.065, respectively). Only age[greater than or equal to] 65 years (p=0.017) and not anti-rheumatic treatment was found to be a negative predictor of protective antibodies in patients with SpA. CONCLUSIONS: After initial increase, 1.5 years after pneumococcal vaccination with 7-valent conjugate vaccine, postvaccination antibody levels decreased significantly reaching levels prior to vaccination in this cohort of patients with established arthritis treated with different anti-rheumatic drugs. MTX and anti-TNF treatment predicted low persistence of protective immunity among patients with RA. In order to booster antibody response early revaccination with conjugate vaccine might be needed in patients receiving potent immunosuppressive remedies. Trial registration number: EudraCT EU 2007-006539-29 and NCT00828997.
Arthritis research & therapy 01/2013; 15(1):R1. · 4.27 Impact Factor
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ABSTRACT: To investigate hand bone loss (HBL) measured by digital X-ray radiogrammetry (DXR) in patients with early rheumatoid arthritis (RA) receiving different treatment regimens, and to evaluate if DXR change rates during the first 12 months correlate with radiological damage after 24 months.
From the total SWEFOT trial population, 159 patients had hand radiographs correctly timed and taken with same modality to be analyzed with DXR. All patients started treatment with methotrexate. After 3-4 months, patients with DAS28 > 3.2 were randomized to add sulfasalazine and hydroxychloroquine (triple therapy) or infliximab (MTX + INF). Those with DAS28 ≤3.2 were followed in regular care. Radiographic progression over 24 months was scored according to the Sharp van der Heijde score (SHS) and defined as >5 increase in T-SHS over 24 months. Hand bone mineral density (BMD) was measured by DXR at inclusion and 12 months and a change ≥2.5 mg/cm2/month was used as a cut-off for HBL.
In the MTX responders, triple therapy, and MTX + INF groups, the proportions with HBL were 4.1%, 22.2% and 16.4%, respectively (p = 0.01), and the mean (SD) radiological progression in these groups was 3.91 (6.72), 7.40 (14.63) and 2.72 (4.55) respectively (p = 0.06). Patients with HBL had significantly greater risk for radiographic progression, compared with patients without HBL (odds ratio 3.09, 95% CI =1.20-7.79, p = 0.02).
Non-responders to MTX had a significantly greater risk of HBL than MTX-responders, despite the add-on therapies. Patients with HBL during the 12 months had greater risk of radiographic progression after 24 months. Evaluation of HBL may help to identify patients who are at risk of radiographic progression.
BMC Musculoskeletal Disorders 01/2013; 14:79. · 1.58 Impact Factor
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ABSTRACT: OBJECTIVE: To compare EuroQol 5-Dimensions (EQ-5D) utility and quality-adjusted life-years (QALYs) in patients with early, methotrexate (MTX) refractory rheumatoid arthritis (RA), randomised to addition of infliximab (IFX) or sulfasalazine and hydroxychloroquine (SSZ+HCQ). METHODS: RA-patients with symptoms <1 year were enrolled between 2002 and 2005 at 15 Swedish centres. After 3-4 months of MTX monotherapy, patients with a remaining DAS28>3.2 were randomised to addition of IFX or SSZ+HCQ and followed for 21 months. EQ-5D profiles were collected every 3 months. Between-group comparisons of utility change and accumulated QALYs were performed, using last observation carried forward (LOCF) following protocol breach. Missing data were imputed by linear interpolation or LOCF. Sensitivity analyses applying baseline observation carried forward (BOCF) or restricted to completers were conducted. RESULTS: Of 487 patients initially enrolled, 128 and 130 were randomised to IFX or SSZ+HCQ, respectively. Mean utility in the IFX and SSZ+HCQ groups increased from 0.52 (SD 0.27) and 0.55 (SD 0.27) at randomisation to 0.66 (SD 0.25) and 0.63 (SD 0.27) at 21 months (adjusted mean difference favouring IFX 0.04; 95% CI -0.01, 0.09; p=0.15). Average accumulated QALYs were 1.10 (SD 0.37) and 1.07 (SD 0.42) in the IFX and SSZ+HCQ groups, respectively (adjusted mean difference favouring IFX 0.07; 95%CI -0.01, 0.14; p=0.07). BOCF analysis showed similar results, while differences were reversed, though remained statistically non-significant among completers. Dropout rates in the IFX/SSZ+HCQ groups were 30%/43% (p=0.01). CONCLUSIONS: Comparing addition of IFX or SSZ+HCQ to MTX in active early RA, no statistically significant differences in utility or QALY gain could be detected over 21 months. TRIAL REGISTRATION: Registered in WHO database at the Karolinska University Hospital, number CT20080004.
Annals of the rheumatic diseases 11/2012; · 8.11 Impact Factor
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ABSTRACT: OBJECTIVE: The objective was to estimate the cost-effectiveness of TNF-inhibitors for the treatment of rheumatoid arthritis in Swedish clinical practice, both as a first and second biological treatment, with or without the combination of conventional DMARDs. Further sub-group analysis of etanercept treatment was performed. METHODS AND MATERIALS: Patient level data were obtained from three regions of the Swedish Rheumatology Registers. The dataset contained 2,558 patients who had started TNF-inhibitor treatment, 1,049 with etanercept as their first biological treatment. A total of 819 patients had switched to a second TNF-inhibitor, of which 425 to etanercept. A Markov cohort model was used in which health states of disease severity were classified according to HAQ and DAS28. Disease progression and discontinuation rates of TNF-inhibitors were based on the registry and for the comparator on published literature. Mortality, costs and utilities were based on Swedish data. The main analysis had a societal perspective over 20 years and efficacy was measured in quality-adjusted life-years (QALYs). RESULTS: TNF-inhibitor treatment was associated with an increase in QALYs and an incremental cost compared to no biological treatment. The cost per QALY gained with the three TNF-inhibitors ranged from 50,000 to 120,000, with lower estimates for TNF-inhibitors used in combination with MTX and as a first biologic. At a progression of 0.045 for the comparator, most values remain within the accepted range for cost-effectiveness. CONCLUSIONS: These results demonstrate that the cost per QALY for TNF-inhibitors was higher than in previous assessments based on registry data and that the results were sensitive to the HAQ progression of the comparator.
The European Journal of Health Economics 09/2012; · 1.50 Impact Factor
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ABSTRACT: Analysis of the Swedish Farmacotherapy (Swefot) trial at 12 months showed that the addition of an anti-tumour-necrosis-factor agent gave an improved clinical outcome compared with the addition of conventional disease-modifying antirheumatic drugs in patients with methotrexate-refractory early rheumatoid arthritis. Here we report the 2 year follow-up assessment.
In this randomised, non-blinded, parallel-group trial, we enrolled adult patients older than 18 years with rheumatoid arthritis and a symptom duration of less than 1 year from 15 rheumatology units in Sweden between December, 2002 and December, 2006. All patients were started on methotrexate. After 3-4 months, those who failed treatment were randomly assigned (1:1) to group A (conventional treatment; additional sulfasalazine and hydroxychloroquine) or group B (biological treatment; additional infliximab). Randomisation was done with a computer-generated sequence. We analysed clinical outcomes at months 18 and 24 by the response criteria of the American College of Rheumatology and the European League Against Rheumatism, and radiographs of patients' hands and feet at months 12 and 24 using the Van der Heijde modification of the Sharp score. Analysis was by intention to treat. This trial is registered with www.ClinicalTrials.gov, number NCT00764725.
Of 493 screened individuals, we enrolled 487, of whom 258 were randomly allocated to treatment. The proportion of patients in group B who received a EULAR-defined good response was non-significantly greater than it was in group A at 18 months (49 of 128 [38%] vs 38 of 130 [29%]) and at 24 months (49 of 128 [38%] vs 40 of 130 [31%]; p=0·204). After 24 months, radiological disease progression was greater in patients in group A than it was in those in group B (mean 7·23 [SD 12·72] vs 4·00 [10·0]; p=0·009). We recorded three serious adverse events: an extended generalised illness in group A, an extended febrile episode in group B, and a generalised illness in group B.
Additional biological treatment is a valid option for patients who fail initial methotrexate treatment. However, improved clinical outcomes after 12 months and better radiographical results after 24 months should be weighed against the absence of a convincing clinical difference at 24 months and substantially higher costs. Therefore, for many patients who fail initial methotrexate treatment, add-on treatment with disease-modifying antirheumatic drugs is an appropriate treatment option.
Swedish Rheumatism Association, Stockholm County, and Schering-Plough/Merck Sharp and Dohme.
The Lancet 03/2012; 379(9827):1712-20. · 38.28 Impact Factor
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ABSTRACT: Cartilage 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.
COMP-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.
COMP-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).
COMP-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.
Arthritis research & therapy 01/2012; 14(1):R15. · 4.27 Impact Factor
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ABSTRACT: To investigate the 2-year clinical and radiological outcomes of patients with early rheumatoid arthritis (RA; symptom duration <1 year) who had initially responded well to methotrexate monotherapy.
In the SWEFOT trial, all 487 patients started methotrexate (target dose 20 mg/week). After 3-4 months, 147 had low disease activity, 28-joint based disease activity score (DAS28) ≤3.2. These patients were not randomly selected but were followed in regular care for 2 years. Clinical outcomes and radiographic progression according to the van der Heijde modified Sharp (SvdH) score were analysed.
The majority of the 147 patients continued on methotrexate monotherapy. After 1 and 2 years, DAS28 remission was achieved in 59.6% and 71.8% and mean observed DAS28 values were 2.53 and 2.25, respectively. Despite the favourable clinical course, a proportion of the patients progressed radiographically with a mean (SD) increase in the SvdH score after 2 years of 3.90 (6.84). There was no significant difference in progression between patients in DAS28 remission versus not in remission (p=0.73). At baseline, approximately half the patients had no radiographic damage, while after 2 years the proportion was approximately 20%.
Most early RA patients who achieve low disease activity after 3-4 months of methotrexate monotherapy continue to have low disease activity during 2 years follow-up, and additional treatment is needed infrequently. Some radiological progression occurs in most patients, and may be marked or severe in some, even despite sustained DAS28 remission. Close monitoring for radiological progression is thus warranted.
Annals of the rheumatic diseases 09/2011; 71(2):186-91. · 8.11 Impact Factor
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ABSTRACT: To study how the choice of national EQ-5D tariff may affect utility and incremental quality-adjusted life-year (QALY) estimates.
South Swedish rheumatoid arthritis patients in an observational study, starting and continuing anti-tumour necrosis factor (TNF) monotherapy (n=54) or anti-TNF plus methotrexate (n=215) for 1 year during May 2002 to April 2009, were included. EQ-5D questionnaires were completed at baseline, 3, 6 and 12 months. Utilities and accumulated QALY were compared using the UK, US and Danish EQ-5D tariffs. Utilities for all 243 possible EQ-5D health states were also compared.
US utilities were generally higher than UK, with Danish falling in between. A substantial 1-year mean utility improvement was seen in both study groups using all tariffs (UK 0.28 vs 0.29; US 0.18 vs 0.19; Danish 0.20 vs 0.22). Adjusting for baseline differences between groups, the incremental QALY gain of combined treatment was 0.09 using the UK tariff, while 0.06 according to both US and Danish tariffs. Inter-tariff disagreement in utility and accumulated QALY varied irregularly across the range of utilities.
Applying different national EQ-5D tariffs to the same data may result in substantially different incremental QALY estimates, crucial knowledge when interpreting cost-utility analyses. Studies using different tariffs cannot be directly compared.
Annals of the rheumatic diseases 08/2011; 70(12):2163-6. · 8.11 Impact Factor
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ABSTRACT: To study the influence of antiinflammatory treatments, including methotrexate (MTX) and tumor necrosis factor (TNF) inhibitors, on antibody response following vaccination using a 7-valent conjugate pneumococcal vaccine in adult patients with established arthritis.
Patients with rheumatoid arthritis (RA) or spondylarthropathy (SpA) (including psoriatic arthritis) were vaccinated (n = 505). All patients were stratified into 6 prespecified groups based on diagnosis and treatment (RA patients receiving MTX, RA patients receiving anti-TNF agents and MTX, RA patients receiving TNF inhibitors as monotherapy, SpA patients receiving anti-TNF agents and MTX, SpA patients receiving TNF inhibitors as monotherapy, and SpA patients receiving nonsteroidal antiinflammatory drugs [NSAIDs] and/or analgesics). SpA patients receiving only NSAIDs/analgesics served as a control group. All patients received 1 dose (0.5 ml) of vaccine intramuscularly. Levels of IgG antibodies against 23F and 6B serotypes were measured at vaccination and at 4-6 weeks following vaccination, using standardized enzyme-linked immunosorbent assays.
Positive antibody response was defined as an antibody response ratio (ARR) (i.e., ratio of post- to prevaccination antibody levels) of ≥2. The ARR differed significantly between the groups. A better ARR was seen among patients in the control group compared to those in groups treated with MTX or MTX in combination with TNF inhibitors. Among patients treated with TNF inhibitors as monotherapy, ARRs for both serotypes were lower numerically, but were not significantly different, compared to those in controls. Ongoing MTX treatment was predictive of reduced response (odds ratio 0.41 [95% confidence interval 0.24-0.68], P = 0.001). Higher age was associated with impaired positive antibody response. Concomitant prednisolone treatment elicited better positive antibody response in patients with RA.
Treatment with MTX and higher age were predictive of an impaired antibody response to the 7-valent conjugate pneumococcal vaccine in this cohort of patients with chronic arthritis. TNF inhibitors did not significantly affect antibody responses.
Arthritis & Rheumatism 08/2011; 63(12):3723-32. · 7.87 Impact Factor
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ABSTRACT: To explore the cost-effectiveness of early biologic treatment, followed by dose-reduction in the case of remission, of active rheumatoid arthritis (RA), compared with standard treatment with methotrexate (MTX) in Sweden.
Effectiveness (function, disease activity, erosions) in early RA for both alternatives was taken from a clinical trial comparing etanercept (ETA) combined with MTX to MTX alone. Patients discontinuing treatment can switch to another or their first biologic treatment. For patients in remission (Disease Activity Score [DAS28] < 2.6), ETA is reduced to half the dose. Return to full dose occurs when DAS28 reaches ≥ 3.2 again. Costs and utilities by level of functional capacity from an observational study are used. The model is analyzed as a micro-simulation and results are presented from the societal perspective for Sweden, for 10 years; costs (€2008) and effects are discounted at 3 percent. Sensitivity analysis was performed for the perspective, the time horizon, switching, and dose-reduction.
The main analysis conservatively assumes 50 percent switching at discontinuation. The cost per quality-adjusted life-year (QALY) gained with early ETA/MTX treatment is €13,500 (societal perspective, incremental cost of €15,500 and incremental QALYs of 1.15). With 75 percent switching, the cost per QALY gained was €10,400. Over 20 years, the cost per QALY gained was €8,200. Results were further sensitive to the time patients remained on half dose and the perspective. CONCLUSIONS AND POLICY IMPLICATIONS: This study combines clinical trial and clinical practice data to explore cost-effective treatment scenarios in early RA, including the use of biologics. Our results indicate that a situation where a considerable proportion of patients achieve remission, dose-adjustments will increase the cost-effectiveness of treatment.
International Journal of Technology Assessment in Health Care 07/2011; 27(3):193-200. · 1.37 Impact Factor
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ABSTRACT: To study levels of sick leave and disability pension before and after TNF-antagonist therapy in AS patients.
Using the population-based South Swedish Arthritis Treatment Group register, we identified 139 AS patients (aged 18-58 years, 78% men), who between January 2002 and December 2008 started their first treatment with adalimumab, etanercept or infliximab. We linked data to the payment register by the Swedish Social Insurance Agency and calculated the proportion on sick leave in 30-day intervals from 12 months before treatment start until 12 months after. For each AS patient, we randomly selected four subjects from the general population matched for age, sex and area of residence.
One to 3 months before treatment, an average of 24% of AS patients were on sick leave. During the first 6 months after treatment start, this fraction dropped to 15%, and further declined to 12% at 12 months (P < 0.001). Comparing AS patients with the general population, the relative risk of being on sick leave 3 months before treatment, treatment start and 12 months after treatment start was 8.0 (95% CI 4.6, 13.9), 9.2 (95% CI 5.4, 15.7) and 4.0 (95% CI 2.1, 6.3), respectively. The decrease in sick leave was not substantially offset by changes in disability pension.
There is a decline in sick leave during the first 12 months after initiation of TNF-antagonist treatment in AS patients not explained by societal factors or secular trends. The proportion of AS patients on disability pension remained unchanged during the observation period.
Rheumatology (Oxford, England) 05/2011; 51(2):243-9. · 4.24 Impact Factor
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ABSTRACT: To identify predictors of response to methotrexate (MTX) in early rheumatoid arthritis (RA).
In the SWEFOT trial, patients with RA with symptom duration <1 year started MTX monotherapy (20 mg/weekly) and 405/487 continued until the 3-4- month visit. The primary outcome measure was the DAS28-based European League against Rheumatism (EULAR) response criteria. Multivariate logistic regression was used to study the association between response and the following baseline characteristics: gender, age, symptom duration, cigarette smoking habits, autoantibody status, Health Assessment Questionnaire (HAQ) score, concurrent prednisolone and treatment with non-steroidal anti-inflammatory drugs. Secondary response and remission measures were the American College of Rheumatology and the Simple Disease Activity Index and Clinical Disease Activity Index (SDAI/CDAI)-derived criteria.
After 3-4 months of MTX treatment, the frequency of EULAR good/moderate/no response was 34%/41%/25%, respectively. Parameters associated with a decreased likelihood of EULAR response were female gender (adjusted OR (adj OR) 0.50, 95% CI 0.31 to 0.81), symptom duration (adj OR per month increase 0.93, 95% CI 0.88 to 0.99), current smoking (adj OR 0.35, 95% CI 0.20 to 0.63) and higher HAQ (adj OR 0.56, 95% CI 0.40 to 0.80). Parameters associated with an increased likelihood of EULAR response were higher age (adj OR per 10-year increase 1.30, 95% CI 1.11 to 1.51) and prednisolone treatment (adj OR 2.84, 95% CI 1.43 to 5.63). The findings were similar when patients on prednisolone were excluded and other response criteria tested, although current smoking was the only significant predictor using all response criteria, while HAQ was the only significant predictor of all the remission criteria used. A matrix showed up to ninefold differences between subgroups stratified by the main predictors.
Current smoking, female sex, longer symptom duration and younger age predict a worse response to MTX in patients with new-onset RA. TrialRegNo NCT00764725.
Annals of the rheumatic diseases 03/2011; 70(3):469-75. · 8.11 Impact Factor
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ABSTRACT: Changes in bone mineral density (BMD) in the hand as evaluated by digital X-ray radiogrammetry (DXR) of the second to fourth metacarpal bones has been suggested to predict future joint damage in patients with rheumatoid arthritis (RA). This study's objective was to investigate whether DXR-BMD loss early in the course of the disease predicts the development of joint damage in RA patients followed for up to 20 years.
A total of 183 patients (115 women and 68 men) with early RA (mean disease duration, 11 months) included from 1985 to 1989 were followed prospectively (the Lund early RA cohort). Clinical and functional measures were assessed yearly. Joint damage was evaluated according to the Larsen score on radiographs of the hands and feet obtained in years 0 to 5 and years 10, 15 and 20. These radiographs were digitized, and BMD of the second to fourth metacarpal bones was evaluated by DXR. Early DXR-BMD change rate (that is, bone loss) per year calculated from the first two radiographs obtained on average 9 months apart (SD ± 4.8) were available for 135 patients. Mean values of the right and left hand were used.
Mean early DXR-BMD loss during the first year calculated was -0.023 g/cm2 (SD ± 0.025). Patients with marked bone loss, that is, early DXR-BMD loss above the median for the group, had significantly worse progression of joint damage at all examinations during the 20-year period.
Early DXR-BMD progression rate predicted the development of joint damage evaluated according to Larsen score at year 1 and for up to 20 years in this cohort of early RA patients.
Arthritis research & therapy 02/2011; 13(1):R31. · 4.27 Impact Factor
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ABSTRACT: To investigate the effect of tumour necrosis factor (TNF) antagonist treatment of patients with rheumatoid arthritis (RA) on sick leave (SL) and disability pension (DP) in a population-based setting in southern Sweden.
All patients with RA in the South Swedish Arthritis Treatment Group register living in the county of Skåne (population 1.2 million), who started their first treatment with a TNF antagonist between January 2004 and December 2007 and were 18-58 years at treatment start (n = 365), were identified. For each patient with RA, four matched reference subjects from the general population were randomly selected. Data were linked to the Swedish Social Insurance Agency register and the point prevalence of SL and DP as well as days of SL and DP per month were calculated from 360 days before until 360 days after treatment start.
At treatment start 38.6% of the patients with RA were registered for SL. During the first 6 months this share dropped to 28.5% (decrease by 26.2%, p< 0.001). This level remained stable throughout the first treatment year. Comparing patients with RA to the reference group the relative risk of being on SL was 6.6 (95% CI 5.2 to 8.5) at initiation of anti-TNF treatment and 5.2 (95% CI 4.0 to 6.8) 1 year after that. The corresponding figures for DP were 3.4 (95% CI 2.7 to 4.2) and 3.2 (95% CI 2.7 to 3.9).
There was a marked decline in SL during the first 6 months of TNF antagonist treatment in patients with RA in southern Sweden, maintained throughout the first year, which was not offset by a corresponding increase in DP.
Annals of the rheumatic diseases 12/2010; 69(12):2131-6. · 8.11 Impact Factor
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Julia F Simard,
Elizabeth V Arkema,
Anders Sundström, Pierre Geborek,
Tore Saxne,
Eva Baecklund,
Lars Coster,
Christina Dackhammar,
Lennart Jacobsson,
Nils Feltelius,
Staffan Lindblad,
Solbritt Rantapää-Dahlqvist,
Lars Klareskog,
Ronald F van Vollenhoven,
Martin Neovius,
Johan Askling
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ABSTRACT: During the past decade, the position of biologics in the therapeutic armamentarium, the number of approved indications and the number of available biologics have changed. Available data on (long-term) safety might thus pertain to patient populations not comparable with contemporary patients. The aim of this study was to assess the extent to which contemporary patients who start or switch biologic therapies are comparable with those patients who gave rise to the currently available data on effectiveness and safety.
We identified all adult patients with RA (n=9612), PsA (n=1417) and other SpA (n=1652) initiating a first biologic therapy between 1 January 1999 and 31 December 2008, registered in the Swedish Biologics Register (ARTIS), including information on demographics, disease characteristics and 1-year risk of first-line treatment discontinuation.
Over calendar time, measures of disease activity at start declined substantially for all indications, and diminished between first-, second- and third-line therapy starts. One-year risks of first-line therapy discontinuation increased. Switchers to anti-TNF and non-TNF biologics had different comorbidities. Despite <50% drug retention at 5 years, most patients remained exposed to some biologic.
The trends in baseline characteristics and drug retention underscores that any effects of biologics, including comparison between different biologics, must be interpreted in light of the characteristics of the population treated. The observed differences further call for continued vigilance to properly evaluate the safety profiles of biologic treatments as they are currently used. Exposure to multiple biologics presents a challenge for attribution of long-term effects.
Rheumatology (Oxford, England) 11/2010; 50(1):204-13. · 4.24 Impact Factor
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ABSTRACT: To introduce a novel, simple, utility-based outcome measure, the number needed per quality-adjusted life year (QALY) gained (NNQ), and to apply it in clinical practice in anti-tumor necrosis factor (anti-TNF)-treated patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and spondylarthritis (SpA).
The NNQ is the number of patients one has to treat in order to gain 1 QALY. It is calculated as the inverted value of the utility gain (area under the curve) over 1 year in a cohort subjected to an intervention. EuroQol Index utility data from the South Swedish Arthritis Treatment register were used.
Patients with RA (n = 1,001), PsA (n = 241), and SpA (n = 255) were eligible for the study. First, second, and third treatment courses were studied. For RA, NNQ was 4.5, 6.4, and 5.2 for first, second, and third courses, respectively. For PsA and SpA, NNQ was 4.2-4.5, irrespective of treatment order. Treatment groups with <50 patients were not analyzed. During the study period 2002-2007, there were no secular trends of utility gains.
The NNQ is an easily derived and understandable utility-based outcome measure that may be useful for stakeholders and decision makers as well as for clinicians. It was readily applied in this study of TNF blockade across 3 arthritis diagnoses. NNQ varied little over diagnoses and treatment course order, with a possible exception in second treatment course in RA.
Arthritis care & research. 10/2010; 62(10):1399-406.
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ABSTRACT: To gain updated estimates of prevalence and incidence of RA and proportion on biological treatment in southern Sweden.
Inpatient and outpatient health care provided to residents in the southernmost county of Sweden (1.2 million inhabitants) is registered in the Skåne Health Care Register (SHCR). We identified residents aged > or = 20 years who had received a diagnosis of RA at least twice during 2003-08. Valid point prevalence estimates by 31 December 2008 were obtained by linkage to the Swedish population register, and information on biological treatment was obtained from the South Swedish Arthritis Treatment Group register. We also tested our estimates of RA occurrence in a series of sensitivity analyses to investigate the effect of altered case criteria and the uncertainty generated by clinical visits without diagnoses.
The prevalence of RA in adults was estimated to 0.66% (women = 0.94%, men = 0.37%). The prevalence peaked at age 70-79 years (women = 2.1%, men = 1.1%) before dropping in those aged > or = 80 years. Of prevalent cases, 20% had ongoing biological treatment, a percentage that was highest in women aged 40-49 years (36%). The incidence of RA in 2008 was estimated as 50/100,000 (women = 68/100,000, men = 32/100,000).
When compared with a previous report from southern Sweden, the prevalence of RA seems not to have declined in the last decade. The proportion of patients with ongoing biological treatment was slightly higher in women than men. SHCR data are promising additions to other methods to gain frequency estimates of clinically important disease in a timely and cost-efficient manner.
Rheumatology (Oxford, England) 05/2010; 49(8):1563-9. · 4.24 Impact Factor
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Johan Askling,
Ronald F van Vollenhoven,
Fredrik Granath,
Pauline Raaschou,
C Michael Fored,
Eva Baecklund,
Christina Dackhammar,
Nils Feltelius,
Lars Cöster, Pierre Geborek,
Lennart T Jacobsson,
Staffan Lindblad,
Solbritt Rantapää-Dahlqvist,
Tore Saxne,
Lars Klareskog
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ABSTRACT: 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.
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.
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.
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.
Arthritis & Rheumatism 11/2009; 60(11):3180-9. · 7.87 Impact Factor
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ABSTRACT: Absolute treatment efficacy (via number needed to treat) of rheumatoid arthritis for each of the three available anti tumour necrosis factor alpha inhibiting therapies. Our aim was to indirectly compare the long-term efficacy of the available anti-tumour necrosis factor (TNF) therapies in patients with established rheumatoid arthritis. The results indicate that the absolute efficacy associated with use of these anti-TNF therapies is equivalent if applied in equivalent dosages. In standard dosages, infliximab (3 mg/kg/eight weeks) is only half as effective as adalimumab (40 mg/two weeks) and etanercept (25 mg twice weekly).
Ugeskrift for laeger 07/2009; 171(26):2192-4.
