Are changes in bone mineral density different between groups of early rheumatoid arthritis patients treated according to a tight control strategy with or without prednisone if osteoporosis prophylaxis is applied?

UNLABELLED: Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead to bone loss in early rheumatoid arthritis (RA) patients receiving preventive treatment for osteoporosis. A small increase in lumbar bone mineral density (BMD) during the first year of treatment was recorded, regardless of use of glucocorticoids. INTRODUCTION: This study aims to describe effects on BMD of treatment according to EULAR guidelines with a methotrexate-based tight control strategy including 10 mg prednisone daily versus the same strategy without prednisone in early RA patients who received preventive therapy for osteoporosis. METHODS: Early RA patients were included in the CAMERA-II trial: a randomized, placebo-controlled, double-blind 2-year trial, in which effects of addition of 10 mg prednisone daily to a methotrexate-based tight control strategy were studied. All patients received calcium, vitamin D and bisphosphonates. Disease activity was assessed every 4 weeks. Radiographs of hands and feet and dual-energy X-ray absorptiometry of lumbar spine and left hip were performed at baseline and after 1 and 2 years of treatment. RESULTS: BMD increased significantly over time in both treatment groups at the lumbar spine with a mean of 2.6% during the first year (p<0.001), but not at the hip; at none of the time points did BMD differ significantly between the prednisone and placebo group. Higher age and lower weight at baseline and higher disease activity scores during the trial, but not glucocorticoid therapy, were associated with lower BMD at both the lumbar spine and the hip in mixed-model analyses. CONCLUSION: Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead to bone loss in early RA patients on bisphosphonates. A small increase in lumbar BMD during the first year of treatment was found, regardless of use of glucocorticoids.

Lack of understanding in fibromyalgia and rheumatoid arthritis: the Illness Invalidation Inventory (3*I).

BACKGROUND: Patients with rheumatic diseases may face 'discounting' (denying and patronising) or 'lack of understanding' because of having symptoms without external clinical signs, but instruments to assess such invalidation experiences are lacking. OBJECTIVES: To develop and evaluate the Illness Invalidation Inventory (3*I), to compare invalidation experiences of two groups of patients who differ in visual signs and laboratory findings-rheumatoid arthritis (RA) and fibromyalgia-and to examine the association of invalidation with health status. METHODS: A questionnaire (eight items with respect to five sources: spouse, family, medical professionals, work environment and social services) was constructed. It was completed by 142 patients with RA and 167 patients with fibromyalgia. RESULTS: Principal axis factoring with oblimin rotation yielded two factors with high internal consistency (α>0.70): 'discounting' (five items) and 'lack of understanding' (three items). Patients with fibromyalgia experienced significantly more discounting and lack of understanding from their family, medical professionals, colleagues and social services than did patients with RA. Both patient groups experienced more invalidation from social services, colleagues and family than from medical professionals and spouses. More discounting and lack of understanding correlated with poorer mental well-being and social functioning in both patient groups. Discounting correlated with more physical disability and pain in patients with RA. CONCLUSIONS: The 3*I is a brief, reliable instrument for assessing patients' perceptions of invalidation from different sources, which differ between patient groups and are associated with health status. Future validation research should clarify the clinical impact of invalidation on treatment adherence and outcome.

Smokers and non smokers with rheumatoid arthritis have similar clinical status: data from the multinational QUEST-RA database.

OBJECTIVES: To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. METHODS: The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, pain, and patient global estimate, as well as DAS28, rheumatoid factor (RF), nodules, erosions and number of DMARDs were recorded. Smoking status was assessed by self-report as 'never smoked', 'currently smoking' and 'former smokers'. Patient groups with different smoking status were compared for demographic and RA measures. RESULTS: Among the 7,307 patients with smoking data available, status as 'never smoked,' 'current smoker' and 'former smoker' were reported by 65%, 15% and 20%. Ever smokers were more likely to be RF-positive (OR 1.32;1.17-1.48, p<0.001). Rheumatoid nodules were more frequent in ever smokers (OR 1.41;1.24-1.59, p<0.001). The percentage of patients with erosive arthritis and extra-articular disease was similar in all smoking categories. Mean DAS28 was 4.4 (SD 1.6) in non-smokers vs. 4.0 (SD 1.6) in those who had ever smoked. However, when adjusted by age, sex, disease duration, and country gross domestic product, only ESR remained significantly different among Core Data Set measures (mean 31.7mm in non-smokers vs. 26.8mm in ever smoked category). CONCLUSIONS: RA patients who had ever smoked were more likely to have RF and nodules, but values for other clinical status measures were similar in all smoking categories (never smoked, current smokers and former smokers).

Radiation synovectomy with (90)Yttrium, (186)Rhenium and (169)Erbium: a systematic literature review with meta-analyses.

OBJECTIVE: To perform a systemic review and meta-analysis on the effectiveness of radiosynoviorthesis (RSO). METHODS: A search of medical databases was conducted. Criteria for inclusion: articles in English, minimum follow-up of 6 months, specification of joint disease, reported outcome of at least 5 RSOs. The studies were scored for quality by the Oxford Centre of Evidenced-based Medicine Levels of Evidence, from 1 to 4. RESULTS: Twenty-one (21) studies were included (3 quality 1b, 5 2b and 13 4), analysing 169Erbium/186Rhenium-RSO used predominantly in small joints and 49 (1 quality 1b, 10 2b and 38 4) on 90Yttrium-RSO used predominantly in knee joints. The reported success rates of 169Erbium/186Rhenium-RSO ranged from 69-100% at 6 months, and from 54-100% at > or =12 months; for 90Yttrium they were 24-100% and 29-94%, res-pectively. Studies comparing the effect of RSO with that of glucocorticoid (GC) or saline injection alone were pooled. At 6 months, the pooled odds ratio favouring RSO of the knee with Yttrium over control is 4 (confidence interval (CI) 95% 1.2-14), p=0.02, but at 12 months the ratio was 1.7 (CI95% 0.69-4), p=0.26. For RSO of small joints with Erbium/Rhenium compared to controls, the pooled odds ratio at 6 months is 2 (CI95% 0.66-6), p=0.22 and at 12 months 2 (CI95% 1.09-3.5), p=0.03. CONCLUSION: Reported success rates of RSO are high, but differences in effect with GC injection are less evident, although there is marked heterogeneity in study design of the (small number of) comparative studies.

[The anticitrulline antibody test: unsuitable for screening for rheumatoid arthritis]. / De anticitrullinetest: niet geschikt voor screening op reumatoïde artritis.

In a recent study involving 691 patients, for whom general practitioners had ordered a rheumatoid factor test in 2004, the serum samples had simultaneously been analysed for antibodies against citrullinated fibrinogen. Two years later, 28 of 616 individuals of the original sample met the classification criteria for rheumatoid arthritis. In 8 of these 28 patients (29%), the rheumatoid factor test had been positive in 2004 and the anti-citrullinated fibrinogen test in 7 (25%) of the 28. The pre-test probability for rheumatoid arthritis was thus 5% and the post-test probability in case of a positive test for anti-citrullinated fibrinogen antibodies 37%. The pre-test probability for not having rheumatoid arthritis was 95% and the post-test probability in case of a negative test for anti-citrullinated fibrinogen antibodies 96%. In a patient sample with a low probability or incidence of rheumatoid arthritis, screening with these tests only moderately increases the chance of having rheumatoid arthritis in case of a positive test and adds virtually nothing to exclude rheumatoid arthritis.

[Seronegative spondylarthropathy: variable manifestations, common characteristics]. / Seronegatieve spondylartropathie: variabele verschijningsvormen, gemeenschappelijke kenmerken.

A 38-year-old man and a 35-year-old woman had a 5 and 15 year history, respectively, of oligoarthritis, enthesitis, tendinitis, bursitis, and uveitis, all of varying severity. The diagnosis of these various features and symptoms, which were initially hard to classify, was undifferentiated spondylarthropathy, a member of the family of HLA-B27-associated seronegative spondylarthropathies. The arthritis of peripheral joints of the woman responded to a conventional disease-modifying antirheumatic drug (methotrexaat), but she eventually developed typical ankylosing spondylitis. The spondylarthropathy of the male patient remained undifferentiated and was refractory to conventional disease-modifying antirheumatic drugs, but it responded very well to the TNFalpha-blocking agent adalimumab. Spondylarthropathy includes several chronic, slowly progressive, inflammatory diseases. The treatment of spondylarthropathy comprises life-style advice, physical therapy, non-steroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and local glucocorticoid injections. Conventional disease-modifying antirheumatic drugs fail to inhibit axial inflammation in spondylarthropathy, in contrast to TNFalpha-blocking agents. Early treatment of patients with severe spondylarthropathy with TNFalpha-blocking agents may prevent structural damage and functional disability.

[TNF-blocking drugs and infection; recommendations for daily practice]. / TNF-blokkerende geneesmiddelen en infecties; adviezen voor de dagelijkse praktijk.

Anti-tumour necrosis factor (TNF) therapy is associated with an increased risk of infection. There are sparse data and no evidence-based guidelines on how to deal with this problem in daily practice. However, recommendations can be made based on theoretical considerations and by extrapolating from recommendations for other types ofimmunodeficiency. Before starting anti-TNF therapy, screening for tuberculosis and other possible infections is indicated. During therapy, alertness is required to the increased risk of infection, infections with a more serious clinical course or unusual manifestations and opportunistic infections. Flu vaccination during anti-TNF therapy is indicated. Travel vaccinations with live microbial inocula should not be given.

Radiation synovectomy of the upper extremity joints: does leakage from the joint to non-target organs impair its therapeutic effect?

Does leakage impair the therapeutic effect of radiosynoviorthesis (RSO)? Are there differences in leakage between (169)Erbium and (186)Rhenium? At baseline and at 6 and 12 months after RSO, six clinical parameters were scored. Changes in clinical variables over time were summed to a change composite index (CCI), ranging from 0 (no effect) to 12 (maximal effect). CCI >or= 6 was considered successful treatment. Differences in leakage between responders and non-responders, and between (169)Erbium and (186)Rhenium were examined. Regression analyses were performed to explore whether baseline variables predicted leakage. Both at 6 and 12 months response rates were 25 of 36 (69%). Five of 11 (45%) non-responders showed leakage versus 20 of 25 (80%) responders (P=0.06). Mean leakage to lymph nodes was 0.4+/-0.7% versus 2.4+/-0.8% (P=0.04). Median leakage to liver/spleen was 0% versus 0.3% (P=0.4). Only age at the time of injection correlated significantly with leakage to lymph nodes. The (169)Erbium group showed leakage in 1 of 7 (14%) versus 24 of 30 (80%) for the (186)Rhenium group (P=0.002). Mean leakage to lymph nodes was 0.11+/-0.3% versus 2.1+/-2.8% (P=0.001). Median leakage to liver/spleen was 0% versus 0.5% (P=0.006). Leakage to non-target organs does not impair the clinical effect of RSO. Only age predicted leakage to lymph nodes significantly. Other baseline characteristics did not predict leakage. (169)Erbium shows significantly lower leakage to non-target organs than (186)Rhenium in RSO.

The intra-articular distribution of 90yttrium does not influence the clinical outcome of radiation synovectomy of the knee.

OBJECTIVES: To assess the impact of the intra-articular distribution of (90)yttrium-citrate ((90)Y) on the clinical effect of radiosynoviorthesis (RSO) of the knee and on (90)Y leakage from this joint. METHODS: Patients with arthritis of the knee received 185 MBq (90)Y combined with a glucocorticoid, followed by clinical bed rest. Intra-articular (90)Y distribution, measured with a dual-head gamma camera immediately or after 24 hours, was scored as mainly diffuse or mainly focal. Leakage to regional lymph nodes, the liver and spleen was assessed with a dual-head gamma camera after 24 hours. Clinical effect was scored after 6 months by a composite change index (CCI), range 0-12; responders were defined as having a CCI > or =6. RESULTS: Seventy-eight knees of 69 patients, mostly suffering from undifferentiated arthritis (42%) or RA (28%), were treated. (90)Y distribution was mainly diffuse in 54% and mainly focal in 46% with clinical response rates of 40% versus 56%, respectively, p = 0.3. CCI was not correlated with distribution. (90)Y leakage was found only to the liver and the spleen (mean leakage 0.4% and 1.1%, respectively). Leakage was significantly less in case of diffuse intra-articular (90)Y distribution, whereas leakage to the liver was correlated with distribution (r = 0.68, p<0.001). (90)Y leakage was not correlated with CCI. CONCLUSIONS: Intra-articular (90)Y distribution does not influence the clinical effect of RSO of the knee. Although (90)Y leakage from the joint is less if (90)Y distributes diffusely in the joint cavity, leakage does not seem to hamper the clinical effect.

Clinical effect of radiation synovectomy of the upper extremity joints: a randomised, double-blind, placebo-controlled study.

PURPOSE: To compare the clinical efficacy of radiosynoviorthesis (RSO) with intra-articular radionuclide plus glucocorticoid (GC) injection (group A) with that of placebo plus GC injection (group B) for the treatment of persistent synovitis in joints of the upper extremity. METHODS: At baseline and at 6 and 12 months after intra-articular injection, six clinical parameters were scored. Changes in clinical values over time were summed to provide a change composite index (CCI), ranging from 0 (no effect) to 12 (maximal effect). A CCI > or =6 was considered to indicate successful treatment. Differences in response rate and CCI between groups A and B were examined. Regression analyses were performed to explore whether baseline variables could predict therapeutic effect. RESULTS: Sixty-eight joints in 44 patients were treated. Six months after intra-articular injection, response rates (CCI > or =6) were 69% (25/36) in group A and 29% (9/31) in group B (p=0.001). The mean CCIs +/- standard deviation at 6 months were 6.7+/-3.2 for group A and 3.3+/-3.8 for group B (p=0.001). At 12 months the response rates were 69% (25/36) in group A and 32% (8/25) in group B (p=0.004). The mean CCIs at 12 months were 6.8+/-3.3 for group A and 4.2+/-4.7 for group B (p= 0.046). None of the baseline variables predicted the therapeutic effect. CONCLUSION: RSO (radionuclide plus GC) of upper extremity joints with immobilisation for 72 h shows a significantly better response rate than placebo plus GC in patients with persistent synovitis after at least one failed outpatient intra-articular GC injection.

Action potential simulation (APS) in patients with fibromyalgia syndrome (FMS): a controlled single subject experimental design.

OBJECTIVES: Action potential simulation (APS) is becoming a popular method of pain reduction. Nevertheless, little is known about the efficacy of this relatively new treatment. The aim of this study was to investigate whether APS helps to reduce pain, improves patients' perception of daily functioning and social participation in patients with fibromyalgia syndrome (FMS). MATERIALS AND METHODS: Ten patients with FMS according to the American College of Rheumatology (ACR) criteria entered this double blind crossover single-case study. In a period of 20 weeks, the patients underwent two treatment periods of 4 weeks, one with verum and one with placebo, at random, in a double blind fashion. Outcome measures were evaluated on a weekly basis. Primary outcome measure was pain measured with the Fibromyalgia Impact Questionnaire (FIQ) questions 4 and 5, the number of tender points and the total tender point pain intensity score. Both visual inspection and statistical analysis were done to analyse the data from this single-subject design. RESULTS: Performing visual inspection and statistical analysis, no positive results of the APS treatment were found in this study. Remarkable is the fact that placebo APS had significantly better results than verum APS. CONCLUSIONS: In this single-case study with ten patients (all female), APS was not a helpful method to reduce pain, to improve patients' perception of daily functioning and social participation in patients with FMS.

Joint surgery in the Utrecht Rheumatoid Arthritis Cohort: the effect of treatment strategy.

OBJECTIVE: To investigate the prevalence and prognostic factors of joint surgery in a large cohort of patients with rheumatoid arthritis, whose treatment, clinical and radiographic data have been assessed at predefined points in time since disease onset. METHODS: Data on surgical interventions were retrospectively obtained from 482 patients with rheumatoid arthritis whose follow-up data for at least 2 years were available, including treatment and response to treatment during the first 2 years. Survival time until the first surgical intervention and until the first major surgical intervention was determined for the total study population by Kaplan-Meier survival curves. Three separate Cox regression analyses were carried out to determine which variables measured at baseline, during the first year and during the first 2 years were predictors for joint surgery. RESULTS: 27% of the patients underwent surgical interventions. Mean survival time until the first surgical intervention was 10.4 years. The percentage of patients with a surgical intervention was 10% lower in the group with response to treatment when compared with the non-response group. Next to a delayed start with disease-modifying antirheumatic drugs, fast radiographic progression during the first year and first 2 years was a predictor of joint surgery in the multivariate regression analyses. CONCLUSION: Treatment with disease-modifying antirheumatic drugs immediately after diagnosis results in less joint surgery when compared with a delayed start. Furthermore, joint surgery is carried out more often in patients who do not respond to treatment.

Pretreatment macrophage infiltration of the synovium predicts the clinical effect of both radiation synovectomy and intra-articular glucocorticoids.

OBJECTIVE: To explore whether pretreatment features of synovial tissue in patients with gonarthritis could predict the clinical effect of radiation synovectomy with yttrium-90 (90Y) and glucocorticoids or with intra-articular glucocorticoids alone. METHODS: A synovial biopsy was carried out blindly 2 weeks before treatment in 66 patients with persistent gonarthritis, who were randomised to treatment either with 90Y and triamcinolone or with placebo and triamcinolone. Immunohistochemistry was used to detect T cells, macrophages, B cells, plasma cells, fibroblast-like synoviocytes, adhesion molecules and pro-inflammatory cytokines. Stained sections were evaluated by digital image analysis. Individual patient improvement was expressed using a composite change index (CCI; range 0-12). Successful treatment was defined as CCI > or = 6 after 6 months. RESULTS: Patients with rheumatoid arthritis, psoriatic arthritis, undifferentiated arthritis and other causes of gonarthritis were included. The overall response rate was 47%. Clinical efficacy in both therapeutic groups was similar and not dependent on diagnosis. No significant differences were noted between baseline microscopic features of synovial tissue inflammation in patients with rheumatoid arthritis and in those with non-rheumatoid arthritis (ie, all diagnoses other than rheumatoid arthritis). The number of macrophages in the synovial sublining was significantly higher in responders than in non-responders (p = 0.002), independent of treatment group and diagnosis. The clinical effect was positively correlated with pretreatment total macrophage numbers (r = 0.28; p = 0.03), sublining macrophage numbers (r = 0.34; p = 0.005) and vascular cell adhesion molecule 1 expression (r = 0.25; p = 0.04). CONCLUSION: The observations support the view that intra-articular treatment either with 90Y and glucocorticoids or with glucocorticoids alone is especially successful in patients with marked synovial inflammation.

Clinical significance of quantitative immunohistology in labial salivary glands for diagnosing Sjogren's syndrome.

OBJECTIVES: Because patients with primary Sjögren's syndrome (pSS) are at risk of developing other autoimmune phenomena and malignant lymphoma, it is important to distinguish pSS from non-Sjögren's (nSS) sicca syndrome. However, this distinction might be difficult because of the lack of a gold standard for pSS. We studied the clinical significance of quantitative immunohistology (QIH) in labial salivary glands for diagnosing pSS. METHODS: In a model mimicking the making of a clinical diagnosis, five experts diagnosed 396 patients as nSS, 'indefinite', pSS or secondary SS (sSS) using 25 clinical parameters. Patients were diagnosed twice, namely without (yielding gold-standard diagnoses) and with knowledge of QIH. The numbers of changes in diagnosis from 'indefinite' to 'definite' (nSS, pSS or sSS) or vice versa were compared. Patient groups with vs without a changed diagnosis in the four gold-standard diagnosis groups were compared regarding objective autoimmune parameters. RESULTS: Sensitivity, specificity, positive and negative predictive value for abnormal QIH in pSS vs nSS were 93, 86, 76 and 96%, respectively. Changes in diagnosis from 'indefinite' to 'definite' (31%) were found more often (P = 0.00) than changes from 'definite' to 'indefinite' (10%). Knowledge of QIH distinguished patient groups within the gold-standard nSS, indefinite and pSS patient group with regard to autoimmune parameters. CONCLUSION: In view of the consequences of distinguishing pSS from nSS, these results point to an additional diagnostic role for QIH in clinical practice.