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ID PMID Title PublicationDate abstract
15098376 [Rofecoxib: its efficacy in rheumatoid arthritis and acute pain]. 2003 Cyclooxygenase-II (cox-II) selective inhibitors and other non-steroidal anti-inflammatory drugs (NSAIDs) are indicated for pain and stiffness in inflammatory rheumatoid arthritis. Rofecoxib have been shown to be associated with a reduced incidence of gastric erosions on endoscopy compared to standard NSAIDs in patients with arthritis. Many studies in acute pain management have been performed with rofecoxib. The dental pain model is a typical study design of severe acute pain. Onset of pain relief occurred within 45 minutes in single-dose studies of rofecoxib 50 mg in postoperative dental pain. Rofecoxib consistently demonstrated analgesic efficacy in a variety of moderate to severe pain models.
15146414 Ribozymes that inhibit the production of matrix metalloproteinase 1 reduce the invasivenes 2004 May OBJECTIVE: To investigate whether retroviral gene transfer of ribozymes targeting matrix metalloproteinase 1 (MMP-1) inhibits the production of MMP-1 in rheumatoid arthritis synovial fibroblasts (RASFs) and reduces the invasiveness of these cells in vivo. METHODS: MMP-1-specific ribozymes (RzMMP-1) were designed and cloned into the pLNSX retroviral vector. Cleavage of MMP-1 was determined in vitro, and the most effective ribozyme was selected for further investigation. RASFs were transduced with replication-deficient viruses carrying RzMMP-1 or with empty viruses (mock). Quantitative polymerase chain reaction with cleavage site-spanning fluorescent probes was used to measure the levels of MMP-1, MMP-9, and MMP-13 messenger RNA. In addition, protein levels of MMP-1 in cell culture supernatants were determined by enzyme linked immunosorbent assay. The effects of stimulation with lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFalpha) on the production of MMP-1 were assessed accordingly. The invasiveness of RzMMP-1-transduced, mock-transduced, and untransduced RASFs was analyzed in the SCID mouse in vivo model of RA. RESULTS: Transduction of RASFs with RzMMP-1 significantly decreased the production of MMP-1 in RASFs without affecting other MMPs, such as MMP-9 and MMP-13. RzMMP-1 not only reduced the spontaneous production of MMP-1, but also prevented the LPS- and TNFalpha-induced increase in MMP-1 production. Inhibition of MMP-1 was maintained for at least 2 months and was accompanied by a significant reduction of the invasiveness of RASFs in the SCID mouse model of RA. CONCLUSION: Intracellular expression of ribozymes constitutes a feasible tool for inhibiting the production of matrix-degrading enzymes. Inhibition of MMP-1 alone results in a significant reduction of cartilage invasion by RASFs.
12687534 Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patien 2003 Apr OBJECTIVE: To evaluate the safety of anakinra (a recombinant human interleukin-1 receptor antagonist) in a large population of patients with rheumatoid arthritis (RA), typical of those seen in clinical practice. METHODS: A total of 1,414 patients were randomly assigned to treatment with 100 mg of anakinra or placebo, administered daily by subcutaneous injection. Background medications included disease-modifying antirheumatic drugs, corticosteroids, and nonsteroidal antiinflammatory drugs, alone or in combination. The primary end point was safety, which was evaluated by adverse events (including infections), discontinuation from study due to adverse events, and death. RESULTS: Safety was evaluated in 1,399 patients (1,116 in the anakinra group and 283 in the placebo group; 15 patients were randomized but did not receive any study drug) during the initial 6-month, double-blind, placebo-controlled phase of this long-term safety study. Baseline demographics, disease characteristics, and concomitant medications were similar between the 2 groups. The study group included patients with numerous comorbid conditions and a wide range of RA disease activity. Serious adverse events occurred at a similar rate in the anakinra group and the placebo group (7.7% and 7.8%, respectively). Serious infectious episodes were observed more frequently in the anakinra group (2.1% versus 0.4% in the placebo group). The rate of withdrawal due to adverse events was 13.4% in the anakinra group and 9.2% in the placebo group. CONCLUSION: Results from this large, placebo-controlled safety study demonstrate that anakinra is safe and well tolerated in a diverse population of patients with RA, including those with comorbid conditions and those using multiple combinations of concomitant therapies. Although the frequency of serious infection was slightly higher in the anakinra group, no infection was attributed to opportunistic microorganisms or resulted in death.
12746892 Meta-analysis of four rheumatoid arthritis genome-wide linkage studies: confirmation of a 2003 May OBJECTIVE: Susceptibility to rheumatoid arthritis (RA) is likely to involve several genes of weak effect, and consequently, individual studies may have insufficient power to detect linkage. Four major RA genome-wide linkage studies have been carried out, but apart from the well-established HLA susceptibility locus, none of the reported significant regions of linkage has been replicated. We applied a genome-search meta-analysis to 4 RA genome searches to assess linkage across studies, using published results. METHODS: For each study, 120 genomic bins of approximately 30 cM were defined and ranked according to the maximum evidence for linkage within each bin. Ranks were summed across studies and each bin was assessed empirically by the magnitude of summed rank, using a permutation test. A high summed rank indicated a region in which evidence for linkage was consistent across several studies. RESULTS: In addition to the HLA locus (P < 0.00002), the strongest evidence for an RA susceptibility locus was found on chromosome 16 (P = 0.004). This locus was not identified as statistically significant in any of the 4 individual RA genome searches. In total, 12 regions achieved a significant (P < 0.05) summed rank, compared with the 6 bins expected by random chance. Four of these regions (on chromosomes 6p, 16cen, 6q, and 12p) reached a significance value of P < 0.01, suggesting that a subset of these regions contains RA susceptibility loci. CONCLUSION: Using a meta-analysis approach, we have identified existing and novel putative RA susceptibility loci. These results can provide a basis for further positional and functional candidate-gene studies, and may prove useful in other complex rheumatic diseases.
15605213 [Clinical trial for differentiation between corticoid-induced osteoporosis and periarticul 2004 Dec PURPOSE: To investigate a new bone densitometric technology based on digital radiogrammetry (DXR) with respect to its ability to measure severity-dependent variations of bone mineral density (BMD) in patients with rheumatoid arthritis and to differentiate between corticoid-induced and periarticular bone mineral density loss. PATIENTS AND METHODS: A total of 153 randomly selected patients suffering from verified rheumatoid arthritis underwent digitally performed plain radiographs of the non-dominant hand and also measurements of dual-energy X-ray absorptiometry (DXA) regarding total femur and lumbar spine in 102 patients and peripheral quantitative computed tomography (pQCT) regarding the distal radius in 51 patients. Using DXR the radiographs of the non-dominant hand were analyzed for cortical bone mineral density calculation. The severity was classified in the DXA group using the Ratingen score. Furthermore, both study populations were divided into patients with and without corticoid therapy. RESULTS: Correlations between BMD determined by DXR and by DXA (R=0.44 for lumbar spine and R=0.61 for total femur) versus pQCT (0.46
15678789 Validity of rheumatoid arthritis diagnoses in the Danish National Patient Registry. 2004 Discharge diagnoses following hospital admissions in Denmark are recorded in the Danish National Patient Registry (NPR). Such routine hospitalization records may serve as useful research tools in epidemiological studies. The aim of the study was to provide measures of the validity and completeness of rheumatoid arthritis (RA) diagnoses recorded in the NPR. We identified medical records for 217 patients recorded as having RA in the NPR between 1977 and 2001. Using two definitions of RA (clinically confirmed RA and fulfilment of the American College of Rheumatology (ACR) 1987 diagnostic criteria for RA), a rheumatologist assessed the proportion of RA diagnoses recorded in the NPR that could be confirmed by scrutiny of the original medical records. The completeness of RA diagnoses in the NPR was estimated by a two-sample capture-recapture method. Overall, 59% of the 217 RA diagnoses in the NPR were confirmed by information in the medical records. However, major differences were seen according to characteristics of the underlying hospital registrations. Generally, RA diagnoses were most often confirmed for patients registered as inpatients and for patients with more than one hospital registration with RA. Specifically, only 42% of patients with one RA registration from a rheumatology department were confirmed as having RA. In contrast, 91% of patients treated at a rheumatology department and having three or more hospital registrations with RA were confirmed as having RA. The completeness of the NPR with respect to RA satisfying the ACR 1987 classification criteria was estimated to 26%. Our conclusion is that with careful attention to the limitations in the data, discharge diagnoses for patients with records of RA in the Danish NPR can be used for epidemiological research purposes; however, our findings prompt general carefulness when using non-audited registries for research in RA.
15022310 Use of multispectral magnetic resonance imaging analysis to quantify erosive changes in th 2004 Mar OBJECTIVE: Magnetic resonance imaging (MRI) has been shown to be more sensitive than radiography for detecting bone erosions in rheumatoid arthritis (RA). Semiquantitative scoring based on visual image assessment has been introduced. However, there is considerable interest in true quantitative measures, particularly in the context of clinical trials designed to show differences between treatment groups. This study was undertaken to investigate the use of a new quantitative approach, multispectral (MS) image analysis, for assessing erosive change. METHODS: T1-weighted spin-echo (SE) and fat-suppressed gradient-echo (GE) sequences of metacarpophalangeal joints of the dominant hand were acquired at various time points throughout a 2-year period. MS analysis was applied to all images, resulting in segmentation into a generalized bone and a soft tissue class. Voxel changes from one to the other class identified apparent bone lesion volume change (Delta BLV). MR images were also visually scored for erosions (E score). All analyses were performed separately, on a per-joint basis, for short-term and long-term data sets. RESULTS: Analysis of variance with adjustment for individual effect revealed similar results in the short-term and the long-term studies, using either GE or SE images for visual assessment. Patients with an increase in E score on visual assessment had a significantly higher Delta BLV than those without. CONCLUSION: Temporal MS analysis of MRIs can be used to detect and quantify erosive changes in RA. This semiautomated method may be useful for demonstrating differences between treatment groups in clinical trials.
14687707 Analysis of two T-cell receptor BV gene segment polymorphisms in caucasoid Brazilian patie 2003 Dec 15 Considering the role of T-lymphocytes in rheumatoid arthritis (RA) and a possible involvement of the TCR in the pathology of this disease we analyzed allelic and genotypic frequencies of variants of two TCRBV gene segments (TCRBV3S1 and TCRBV18) in RA. A total of 95 caucasoid South Brazilian RA patients were genotyped for both TCRBV gene segment variants by restriction fragment length polymorphism preceded by PCR (PCR-RFLP) and the obtained frequencies were compared to those from healthy individuals. Allelic frequencies for the TCRBV3S1 gene segment were, respectively, for RA patients and controls, 0.447 and 0.545 (allele 1) and 0.553 and 0.455 (allele 2). Allelic frequencies for the TCRBV18 gene segment were, respectively, for RA patients and controls, 0.824 and 0.806 (allele 1) and 0.176 and 0.194 (allele 2). Neither allelic frequencies nor genotypic frequencies differ among RA and healthy individuals, suggesting that there is not a direct association among the TCRBV allelic variants studied and the development of RA and thus excluding the possibility of use of these gene segment polymorphisms as RA susceptibility markers.
15124937 Cellular and humoral markers of systemic inflammation in acute reactive arthritis and earl 2004 OBJECTIVE: To compare systemic inflammation in reactive arthritis (ReA), rheumatoid arthritis (RA), and sepsis using novel markers of systemic inflammation, and to study whether they are helpful in distinguishing between ReA and RA. METHODS: In 28 patients with acute ReA, 16 patients with early untreated RA, and 25 patients with blood culture-positive sepsis, phagocyte CD 11b expression was measured by flow cytometry, serum procalcitonin (PCT) levels by immunoluminometric assay, and soluble E-selectin (sE-selectin) levels by enzyme-linked immunosorbent assay (ELISA). RESULTS: Neutrophil and monocyte CD11b expression and serum levels of PCT and sE-selectin were higher in patients with sepsis than patients with ReA or RA, or in healthy subjects (all p < 0.01). They were comparable in healthy subjects, ReA, and RA. CONCLUSION: Patients with acute ReA and early RA have normal CD11b expression levels on phagocytes and normal PCT and sE-selectin levels in serum. Elevated levels suggest possible sepsis.
12784421 OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Exercise 5: an internatio 2003 Jun Scoring erosions on magnetic resonance imaging (MRI) is one method of estimating damage in patients with rheumatoid arthritis (RA), but it has limitations. The aim of this pilot study was to assess the feasibility and inter-reader reliability of computer assisted erosion volume estimation in patients with RA. Intra-reader and inter-occasion reliability was also assessed, and different slice thicknesses were compared in terms of erosion volume estimation. A 3 mm slice thickness 3D gradient-echo sequence followed by a 1 mm sequence was performed at baseline and repeated within 24 h with metacarpophalangeal (MCP) joints 2 to 5 of the dominant hand included in the field of view. Three readers were instructed to grade MCP 2 and 3 using the OMERACT grading system and then to measure the erosion volume of the same joints using OSIRIS software. The inter-reader reliability of the grading method and the volume method was calculated, as well as the inter-occasion reliability, by comparing results from each reader from baseline to the followup scan. One reader performed repeat volume measurements on 5 patients to assess the intra-reader reliability. Five patients were included in the study. Expressed in terms of intraclass correlation coefficients (ICC), the inter-reader and inter-occasion reliability of the volume method were comparable to the existing OMERACT scoring system, but large systematic differences in volume estimations were found between readers. The intra-reader reliability was excellent. Good correlation was demonstrated between the total erosion scores and the total erosion volumes. For both erosion volumes and erosion scores, 1 mm and 3 mm acquisitions produced variable results between readers, with no clear pattern of underestimation or overestimation for either slice thickness. The volume estimation method was more time consuming, taking roughly 5 times as long as the scoring method. Computerized MRI erosion volume measurements are feasible, with high intra-observer and inter-occasion reliabilities. Despite high ICC, the inter-observer reliability is not sufficient for multicenter use without prior reader training and calibration. The optimal slice thickness was not determined.
11786429 Inflammation, immune reactivity, and angiogenesis in a severe combined immunodeficiency mo 2002 Jan Severe combined immunodeficiency (SCID) mice were engrafted with rheumatoid arthritis (RA) synovium and evaluated to determine whether RA synovial morphology and function were maintained in the RA-SCID grafts. The four major components of RA synovitis, inflammation, immune reactivity, angiogenesis, and synovial hyperplasia persisted in RA-SCID grafts for 12 weeks. Retention of chronic inflammatory infiltrates was demonstrated by histological evaluation and by immunohistology for CD3, CD20, and CD68. Staining for CD68 also revealed that the grafts had undergone reorganization of the tissue, possibly as a result of fibroblast hyperplasia. Immune and inflammatory components were confirmed by the detection of human immunoglobulins and human interleukin-6 in serum samples obtained from grafted animals. Human blood vessels were detected by dense expression of CD31. Small vessels persistently expressed the vitronectin receptor, alpha v beta 3, a marker of angiogenesis. All vessels expressed VAP-1, a marker of activated endothelial cells. Finally, the grafts retained the ability to support immigration by human leukocytes, as demonstrated by the functional capacity to recruit adoptively transferred 5- (and -6)-carboxyfluorescein diacetate succinimidyl ester-labeled T cells. T cells entering the RA-SCID grafts became activated and produced interferon-gamma, as detected by reverse transcriptase-polymerase chain reaction analysis. These studies demonstrate that the RA-SCID model maintains many of the phenotypic and functional features of the inflamed RA synovium.
14608356 An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter 2003 Dec Rheumatoid arthritis is a common inflammatory disease with complex genetic components. We investigated the genetic contribution of the cytokine gene cluster in chromosome 5q31 to susceptibility to rheumatoid arthritis in the Japanese population by case-control linkage disequilibrium (LD) mapping using single nucleotide polymorphisms (SNPs). Here we report that there is significant association between rheumatoid arthritis and the organic cation transporter gene SLC22A4 (P = 0.000034). We show that expression of SLC22A4 is specific to hematological and immunological tissues and that SLC22A4 is also highly expressed in the inflammatory joints of mice with collagen-induced arthritis. A SNP affects the transcriptional efficiency of SLC22A4 in vitro, owing to an allelic difference in affinity to Runt-related transcription factor 1 (RUNX1), a transcriptional regulator in the hematopoietic system. A SNP in RUNX1 is also strongly associated with rheumatoid arthritis (P = 0.00035). Our data indicate that the regulation of SLC22A4 expression by RUNX1 is associated with susceptibility to rheumatoid arthritis, which may represent an example of an epistatic effect of two genes on this disorder.
15103252 Rheumatoid factor revisited. 2004 May PURPOSE OF REVIEW: Initial studies of the pathogenesis of rheumatoid arthritis focused on the role of rheumatoid factor and immune complex-associated vasculitis and synovitis. Subsequent work has delineated T cell responses, the role of cytokines, chemokines, and the aggressive nature of rheumatoid synovitis. Recent findings underscore the importance of humoral immunity in this entity and are the subject of this review. RECENT FINDINGS: By the discovery of anti-cyclic citrullinated peptide, anti-RA33, and anti-GPI antibodies in the human and mouse systems, respectively, the impact of humoral autoimmunity in rheumatoid arthritis regained remarkable interest. This review summarizes recent insights into humoral autoimmunity in rheumatoid arthritis in the context of the generation of rheumatoid factors, including B cell activation via toll-like receptors and genetic predispositions that can trigger the induction of rheumatoid arthritis. The generation of rheumatoid factors that can also be found during host defense against infectious agents and under pathologic conditions, such as rheumatoid arthritis, Sjögren syndrome, and hepatitis C-associated mixed cryoglobulinemia after hepatitis C infection is likely the result of genetic predispositions and the intensity of the (primary) immune reaction. Models of the role of rheumatoid factors in health and disease, including related lymphomagenesis, will be discussed. SUMMARY: In patients with rheumatoid arthritis, the induction of rheumatoid factors can be taken as an indicator of severe disease with a striking involvement of B cell activation. Very recent clinical trials using B cell depletion support the concept that humoral immunity, as evidenced by the production of rheumatoid factors, plays a significant role in the course of the disease.
14579036 [Imaging techniques in rheumatology: scintigraphy in rheumatoid arthritis]. 2003 Oct Bone scintigraphy is an important tool for staging and follow-up in patients with rheumatoid arthritis, and is part of the training for board certified physicians in nuclear medicine in Germany. Bone scintigraphy uses the accumulation of i.v. injected technetium-99m labeled phosphonates imaged with a gamma camera. Different phases can be defined: perfusion phase (0-60 s p. i.), blood pool phase (2-5 min p. i.), and bone (turnover) phase (2-5 h p. i.). The blood pool phase allowes judgement of inflammatory (soft tissue) components of joint disease ("arthritis"), the bone (turnover) phase of longer lasting bone processes ("arthrosis"). The technical details including documentation of the scintigraphic results are presented according to the procedure guidelines of the German Society of Nuclear Medicine (www.nuklearmedizin. de).
11869085 Local overexpression of adeno-viral IL-4 protects cartilage from metallo proteinase-induce 2002 Mar OBJECTIVE: To determine whether IL-4 protects against metalloproteinase-induced cartilage destruction during immune complex mediated arthritis and to elucidate its mechanism. METHODS: Experimental immune complex arthritis (ICA) was raised by injecting lysozyme into the knee joints of mice which previously were given anti-lysozyme antibodies. Three days before ICA induction, mice were injected into the right knee joint with either IL-4 expressing or empty control recombinant human type 5 adenovirus. Joint inflammation and cartilage destruction (PG depletion, erosion) was measured by histology of total knee joints. Aggrecan breakdown in cartilage caused by metalloproteinases (MMPs) was studied by immunolocalization using anti-VDIPEN antibodies. RESULTS: Four days after ICA induction, histological analysis showed comparable exudate and infiltrate in both groups. Depletion of proteoglycans as measured by loss of red staining was also comparable in both groups. IL-4 treatment inhibited MMP-mediated neoepitope expression by 90%. Moreover, cartilage matrix erosion was evident in all animals (10 out of 10 mice) in the control group and significantly diminished (only two out of ten mice) in the IL-4 treated group. Incubation of patellae with APMA, which activates latent MMPs resulted in VDIPEN expression which was not significantly different from control ICA indicating that comparable amounts of latent pro-MMPs are present in IL-4 treated arthritic knee joints. CONCLUSION: This study indicates that during ICA, IL-4 largely prevents MMP-mediated aggrecan breakdown and severe cartilage erosion. IL-4 does not inhibit production of latent MMPs by the chondrocyte but predominantly interferes with its activation.
15228618 Effective use of TNF antagonists. 2004 Tumor necrosis factor (TNF) antagonists are biologic response modifiers that have significantly improved functional outcomes in patients with rheumatoid arthritis (RA). RA is a progressive disease in which structural joint damage can continue to develop even in the face of symptomatic relief. Before the introduction of biologic agents, the management of RA involved the use of disease-modifying antirheumatic drugs (DMARDs) early in the course of disease. This focus on early treatment, combined with the availability of the anti-TNF agents, has contributed to a shift in treatment paradigms favoring the early and timely use of DMARDs with biologic therapies. Improvement in symptom control does not always equate to a reduction in disease progression or disability. With the emergence of structure-related outcome measures as the primary means for assessing the effectiveness of antirheumatic agents, the regular use of X-rays is recommended for the continued monitoring and evaluation of patients. In addition to the control of symptoms and improvement in physical function, a reduction in erosions and joint-space narrowing should be considered among the goals of therapy, leading to a better quality of life. Adherence to therapy is an important element in optimizing outcomes. Durability of therapy with anti-TNF agents as reported from clinical trials can also be achieved in the clinical setting. Concomitant methotrexate therapy might be important in maintaining TNF antagonist therapy in the long term. Overall, the TNF antagonists have led to improvements in clinical and radiographic outcomes in patients with RA, especially those who have failed to show a complete response to methotrexate.
12600798 Validation of the arthritis self-efficacy short-form scale in German fibromyalgia patients 2003 Self-efficacy is assumed to account for significant variance in the treatment outcome of chronic pain patients. The aim of this study was to provide a German version of an approved measure of disease-related self-efficacy in fibromyalgia (FM) patients which assesses treatment outcomes and specific differences compared to other pain patients. The 8-item short-form of the arthritis self-efficacy scale was translated into German (ASES-D) and administered to 148 FM patients and 53 patients with rheumatoid arthritis (RA). In addition, similar cognitive constructs (locus of control, optimism/pessimism, and general self-efficacy) and disease-related variables (pain, functioning, depression, and coping) were assessed. The instrument was further applied to 43 FM patients who underwent interdisciplinary group therapy. Validation methods consisted of correlation, principal component analysis and difference testing between the disease groups. The instrument met good psychometric properties. Evidence for construct validity was provided. Self-efficacy was sensitive to changes and could be used in predicting the treatment outcome in FM patients. The German short-form ASES-D is a further step toward an internationally comparable assessment of disease-related self-efficacy in FM.
15228615 Do anti-TNF agents have equal efficacy in patients with rheumatoid arthritis? 2004 Tumor necrosis factor (TNF) antagonists have dramatically improved the outcomes of rheumatoid arthritis (RA). Three agents currently available in the USA--infliximab, etanercept, and adalimumab--have been designed to modify the biologic effects of TNF. Infliximab and adalimumab are monoclonal antibodies, and etanercept is a soluble protein. The pharmacokinetic and pharmacodynamic properties of each differs significantly from those of the others. All three agents are effective and safe, and can improve the quality of life in patients with RA. Although no direct comparisons are available, clinical trials provide evidence that can be used to evaluate the comparative efficacy of these agents. Infliximab, in combination with methotrexate, has been shown to relieve the signs and symptoms of RA, decrease total joint score progression, prevent joint erosions and joint-space narrowing, and improve physical function for up to 2 years. Etanercept has been shown to relieve the signs and symptoms of RA, decrease total joint score progression, and slow the rate of joint destruction, and might improve physical function. Etanercept is approved with and without methotrexate for patients who have demonstrated an incomplete response to therapy with methotrexate and other disease-modifying anti-rheumatic drugs (DMARDs), as well as for first-line therapy in early RA, psoriatic arthritis, and juvenile RA. Adalimumab relieves the signs and symptoms of RA with and without methotrexate and other DMARDs, decreases total joint score progression, prevents joint erosions and joint-space narrowing in combination with methotrexate, and might improve physical function. When selecting a TNF antagonist, rheumatologists should weigh evidence and experience with specific agents before a decision is made for use in therapy.
15546895 Patient initiated outpatient follow up in rheumatoid arthritis: six year randomised contro 2005 Jan 22 OBJECTIVES: To determine whether direct access to hospital review initiated by patients with rheumatoid arthritis would result in improved clinical and psychological outcome, reduced overall use of healthcare resources, and greater satisfaction with care than seen in patients receiving regular review initiated by a rheumatologist. DESIGN: Two year randomised controlled trial extended to six years. SETTING: Rheumatology outpatient department in teaching hospital. PARTICIPANTS: 209 consecutive patients with rheumatoid arthritis for over two years; 68 (65%) in the direct access group and 52 (50%) in the control group completed the study (P = 0.04). CLINICAL OUTCOME: pain, disease activity, early morning stiffness, inflammatory indices, disability, grip strength, range of movement in joints, and bone erosion. Psychological status: anxiety, depression, helplessness, self efficacy, satisfaction, and confidence in the system. Number of visits to hospital physician and general practitioner for arthritis. RESULTS: Participants were well matched at baseline. After six years there was only one significant difference between the two groups for the 14 clinical outcomes measured (deterioration in range of movement in elbow was less in direct access patients). There were no significant differences between groups for median change in psychological status. Satisfaction and confidence in the system were significantly higher in the direct access group at two, four, and six years: confidence 9.8 v 8.4, 9.4 v 8.0, 8.7 v 6.9; satisfaction 9.3 v 8.3, 9.3 v 7.7, 8.9 v 7.1 (all P < 0.02). Patients in the direct access group had 38% fewer hospital appointments (median 8 v 13, P < 0.0001). CONCLUSIONS: Over six years, patients with rheumatoid arthritis who initiated their reviews through direct access were clinically and psychologically at least as well as patients having traditional reviews initiated by a physician. They requested fewer appointments, found direct access more acceptable, and had more than a third fewer medical appointments. This radical responsive management could be tested in other chronic diseases.
12048289 Dose titration using the Disease Activity Score (DAS28) in rheumatoid arthritis patients t 2002 Jun OBJECTIVE: Anti-tumour necrosis factor alpha (TNF-alpha) therapy yields high response rates shortly after institution of therapy in patients with rheumatoid arthritis (RA), and on theoretical grounds large differences in the effective dose between patients can be expected. Together with the high costs, these differences warrant new approaches to the way patients are dosed. METHODS: We used the Disease Activity Score (DAS28), a composite disease activity index, to titrate the dose of anti-TNF-alpha (adalimumab, D2E7; Knoll) in 21 patients with low disease activity in an open extension study lasting 40 weeks. The dose of anti-TNF-alpha was reduced stepwise and dosing intervals were kept stable. Disease activity and flares were assessed using the DAS28. Patients who flared received the previous effective dose. RESULTS: Dose reduction was accomplished in 15 patients. The total amount of anti-TNF-alpha given to the patients was reduced by 67%. At the end of the study the mean DAS28 had not changed and no patients dropped out because of persistent worsening of the RA. CONCLUSION: Dose titration of anti-TNF-alpha treatment using the DAS28 is feasible and leads to overall dose reduction while maintaining clinical efficacy. This approach will save costs and possibly prevent long-term side-effects.