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Rheumatoid arthritis (RA) is a systemic autoimmune disease driven by highly active autoantibody‐producing B cells. Activation of B cells is maintained within ectopic germinal centres found in affected joints. Fibroblast‐like synoviocytes (FLS) present in inflamed joints support B‐cell survival, activation, and differentiation. CD27+ memory B cells and naive B cells show very different responses to activation, particularly by CD40 ligand (CD40L). We show that FLS‐dependent activation of human B cells is dependent on interleukin‐6 (IL‐6) and CD40L. FLS have been shown to activate both naive and memory B cells. Whether the activating potential of FLS is different for naive and memory B cells has not been investigated. Our results suggest that FLS‐induced activation of B cells is dependent on IL‐6 and CD40L. While FLS are able to induce plasma cell differentiation, isotype switching, and antibody production in memory B cells, the ability of FLS to activate naive B cells is significantly lower. [ABSTRACT FROM AUTHOR]

Background Studies in rheumatoid arthritis synovial fibroblasts (RASF) demonstrated the expression of several transient receptor potential channels (TRP) such as TRPV1, TRPV2, TRPV4, TRPA1 and TRPM8. Upon ligation, these receptors increase intracellular calcium but they have also been linked to modulation of inflammation in several cell types. TNF was shown to increase the expression of TRPA1, the receptor for mustard oil and environmental poisons in SF, but the functional consequences have not been investigated yet. Methods TRPA1 was detected by immunocytochemistry, western blot and cell-based ELISA. Calcium measurements were conducted in a multimode reader. Cell viability was assessed by quantification of lactate dehydrogenase (LDH) in culture supernatants and “RealTime-Glo” luminescent assays. IL-6 and IL-8 production by SF was quantified by ELISA. Proliferation was determined by cell titer blue incorporation. Results After 72 h, mimicking proinflammatory conditions by the innate cytokine TNF up-regulated TRPA1 protein levels in RASF which was accompanied by increased sensitivity to TRPA1 agonists AITC and polygodial. Under unstimulated conditions, polygodial elicited calcium flux only in the highest concentrations used (50 µM and 25 µM). TNF preincubation substantially lowered the activation threshold for polygodial (from 25 µM to 1 µM). In the absence of TNF pre-stimulation, only polygodial in high concentrations was able to reduce viability of synovial fibroblasts as determined by a real-time viability assay. However, following TNF preincubation, stimulation of TRPA1 led to a fast (<30 min) viability loss by necrosis of synovial fibroblasts. TRPA1 activation was also associated with decreased proliferation of RASFs, an effect that was also substantially enhanced by TNF preincubation. On the functional level, IL-6 and IL-8 production was attenuated by the TRPA1 antagonist A967079 but also polygodial, although the latter mediated this effect by reducing cell viability. Conclusion Simulating inflamed conditions by preincubation of synovial fibroblasts with TNF up-regulates and sensitizes TRPA1. Subsequent activation of TRPA1 increases calcium flux and substantially reduces cell viability by inducing necrosis. Since TRPA1 agonists in the lower concentration range only show effects in TNF-stimulated RASF, this cation channel might be an attractive therapeutic target in chronic inflammation to selectively reduce the activity of proinflammatory SF in the joint. [ABSTRACT FROM AUTHOR]

Low levels of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) values are indicative of cartilage degeneration. Patients with early rheumatoid arthritis are known to have low dGEMRIC values due to inflammatory activity. The additional effect of biological disease-modifying antirheumatic drug (bDMARD) and conventional synthetic disease-modifying antirheumatic drug (csDMARD) treatment on cartilage status is still unclear. In this prospective, double-blinded, randomized proof-of-concept clinical trial, patients with early rheumatoid arthritis (disease duration less than 12 months from symptoms onset) were treated with methotrexate + adalimumab (10 patients: 6/4 (f/m)). A control group with methotrexate alone (four patients: 2/2 (f/m)) was used. Cartilage integrity in the metacarpophalangeal joints was compared using dGEMRIC at baseline, 12, and 24 weeks after treatment initiation. A statistically significant increase in dGEMRIC levels was found in the adalimumab group considering the results after 12 and 24 weeks of therapy (p < 0.05) but not in the control group (p: non-significant). After 24 weeks, a tendency towards increased dGEMRIC values under combination therapy was observed, whereas methotrexate alone showed a slight decrease without meeting the criteria of significance (dGEMRIC mean change: +85.8 ms [−156.2–+346.5 ms] vs. 30.75 ms [−273.0–+131.0 ms]; p: non-significant). After 24 weeks of treatment with a combination of methotrexate and adalimumab, a trend indicating improvement in cartilage composition is seen in patients with early rheumatoid arthritis. However, treatment with methotrexate alone showed no change in cartilage composition, as observed in dGEMRIC sequences of metacarpophalangeal joints. [ABSTRACT FROM AUTHOR]

Objectives. To assess the quality of health care for RA patients in the general population of Germany. Methods. A three-stage population survey was conducted to identify individuals with RA using a health care access panel (18–79 years; n = 70 112). A 20-item postal screening questionnaire of musculoskeletal symptoms and diagnoses was followed by a detailed questionnaire for those who indicated the possibility of having RA. Respondents who fulfilled the modified ACR decision tree, who reported an RA diagnosis, care by a rheumatologist or the use of DMARDs were asked to participate in a clinical examination by rheumatologists who diagnosed the participants and rated the adequacy of treatment. Results. RA could not be ruled out in 1177 cases, of which 643 agreed to participate in the clinical examination, which was finally attended by 317 participants. Attendees did not differ with regard to any health or treatment measure from those who did not attend. Forty-one RA patients were detected. Of them, 93% had seen a rheumatologist at least once and 63% within the last 12 months. A total of 73% had received DMARD therapy at some time and 59% were currently receiving it. An unmet need for DMARDs was discovered in 29% of the RA attendees. It pertained almost exclusively to the seronegative cases of which 29% had a need to start and 17% to increase a DMARD therapy according to the opinion of the examining rheumatologist. Conclusion. Health care for RA patients has improved significantly since the last German RA survey in 1989. However, DMARD prescription still does not meet clinical recommendations, specifically in RF-negative patients. Since seronegative RA is a treatable disease, this group should not be overlooked. [ABSTRACT FROM AUTHOR]

Objective. To compare the 24-month course of health-related quality of life (HRQoL) in patients with longstanding RA treated with a conventional synthetic (cs) or a first, second or third biologic (b) DMARD in daily rheumatological care. Methods. Patients enrolled in the German biologics register RABBIT who were observed over at least 12 months were stratified according to the nth bDMARD started at enrolment. HRQoL was captured by the SF36 health survey. Within strata of sequential bDMARD therapy, we examined patients' HRQoL at baseline and at follow-ups in comparison with the general population, the 24-month course of HRQoL of different bDMARDs and the proportion of patients exceeding the minimal detectable improvement of physical and mental health sum scores. Results. All patients reported remarkably lower scores of physical and mental health than the general population at baseline and month 12. In each stratum of sequential bDMARD therapy, patients improved significantly by month 12 and remained stable until month 24. The improvement of HRQoL was not attributable to a particular bDMARD. The following proportions of patients exceeded the minimal detectable improvement of at least 17.85 Physical Component Scale scores or 22.18 Mental Component Scale score points: csDMARD (n = 1113) 31.1%/22.3%, first bDMARD (n = 1352) 39.9%/29.7%, second bDMARD (n = 730) 37.3%/26.2% and third bDMARD (n = 680) 34.2%/30.9%. Conclusion. Lasting improvement of both physical and mental health is achievable even for severely affected RA patients with a history of more than one bDMARD failure. Nevertheless, impairment of HRQoL in RA patients is enormous compared with the general population. [ABSTRACT FROM AUTHOR]

To evaluate initial glucocorticoid (GC) therapy in patients with rheumatoid arthritis (RA). Six hundred sixty-nine patients with early RA were followed for 2 years in the multicenter 'Course And Prognosis of Early Arthritis' cohort. Treatment was applied according to routine care. Assessments included disease activity (DAS28), disability Hannover Functional Status Questionnaire (FFbH), and treatment details. Mixed models, ANCOVA, and logistic regression models were used for statistical analysis. In total, 518 patients (77 %) received oral GCs at baseline; 20 % received a low dose (<7.5 mg prednisolone/day), 22 % received a moderate (7.5-19 mg), and 35 % received a high dose (≥20 mg). In a multivariate logistic regression analysis, higher DAS28 values (OR 1.3) were associated with the use of higher GC doses at baseline ( p < 0.001). After adjusting for age, sex, and baseline DAS28 and DMARDs, the patients who started with high-dose GCs had a greater improvement in DAS28 (month 3) and FFbH (month 6, p < 0.001 each). At 2 years, the mean DAS28 remission rates and FFbH values were similar. In all GC groups, the mean dose was tapered to 4 mg/day within 6 months. The reported comorbidities were not increased in patients with high-dose GC therapy. Starting treatment with high-dose GCs led to a better clinical response within 3 to 6 months compared to starting patients on lower dosages. Irrespective of the starting approach, rheumatologists tapered GCs down to a low dose within 6 months. With this strategy, clinical outcomes at 2 years did not differ relevantly. [ABSTRACT FROM AUTHOR]

Background: Because of overlapping phenotypical presentations, the diagnostic differentiation of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) remains challenging. Thus, this study aimed to examine the diagnostic value of distinct imaging features obtained by high-resolution 3-T MRI for the diagnostic differentiation. Materials and methods: Seventeen patients with PsA and 28 patients with RA were imaged at high resolution using 3-T MRI scanners and a dedicated 16-channel hand coil. All images were analyzed according to the outcome measures in rheumatology clinical trials' (OMERACT) RAMRIS (Rheumatoid Arthritis Magnetic Resonance Imaging Score) and PsAMRIS (Psoriatic Arthritis Magnetic Resonance Imaging Score) for the presence and intensity of synovitis, flexor tenosynovitis, bone edema, bone erosion, periarticular inflammation, bone proliferation, and joint space narrowing. Next, odds ratios (OR) were calculated to determine the strength of the associations between these imaging features, demographic characteristics, and the outcome RA vs. PsA. Results: PsA could be differentiated from RA by extracapsular inflammatory changes (PsAMRIS sub-score "periarticular inflammation"), with low odds for the presence of RA (OR of 0.06, p < 0.01) at all metacarpophalangeal (MCP) joints. A prediction model informed by the items that were strongest associated with the presence of RA or PsA demonstrated excellent differentiating capability with an area under the curve of 98.1%. Conclusion: High-resolution imaging is beneficial for the identification of relevant imaging features that may assist the clinical differentiation of inflammatory conditions of the hand. At the MCP level, extracapsular inflammatory changes were strongly associated with PsA and may consequently allow the imaging differentiation of PsA and RA. [ABSTRACT FROM AUTHOR]

Background: Remission is arguably the ultimate therapeutic goal in rheumatoid arthritis (RA). Applying modern strategies, clinical remission can be achieved in a substantial number of patients with early RA (ERA). Even in those patients, the number and scope of erosions can increase. We, therefore, investigated the value of MRI for the detection of radiological progression in patients with DAS28 improvement and/or clinical remission of the German Remission-plus cohort.Methods: Data-sets of 80 RA patients (according to 2010 ACR/EULAR criteria) from the Remission-plus study cohort, who fulfilled the following criteria, were retrospectively analysed: availability of two consecutive MRI scans (low-field MRI, follow-up interval 1 year) of the clinically dominant hand and wrist, and the presence of DAS28 (CRP) scores at both time points, which was used to assess disease activity.Results: Seventy-one of the 80 investigated patients presented a numerical improvement of the DAS28 (CRP) after 12 months (DAS28(CRP) T0 average (Ø) 4.96, SD 1.2; DAS28 T4 (12 month) Ø 2.6, SD 1.0), 73% of them also improved in the RAMRIS-Score, while 24% demonstrated an increase despite DAS28 improvement and 3% showed equal values. 48% of patients who improved in the DAS28 reached EULAR remission. 41% of these patients had an increase in the RAMRIS Erosion-subscore after 12 months. When considering EULAR response criteria (non-response (n = 7), moderate response (n = 19), good response (n = 45)), an increase of erosions was found in 71.4% of non-responders, 52.6% of moderate responders, and 31.1% of good responders after 12 months, all compared to baseline.Conclusion: Up to 40% of patients in this study demonstrated a progressive erosive disease detected by MRI despite DAS28 improvement or EULAR remission. Future studies are needed to determine the prognostic clinical impact of disease progression in MRI despite clinical remission, and to investigate if DAS28 remission may be an insufficient therapeutic goal and should be accompanied by MRI remission criteria. [ABSTRACT FROM AUTHOR]

Background: To evaluate a combined rheumatoid arthritis magnetic resonance imaging score (RAMRIS) for hand and foot (HaF-score) in rheumatoid arthritis (RA). Methods: Magnetic resonance imaging (MRI, 0.2 Tesla) of the dominant hand and foot of 26 ACPA positive RA patients before and 6 months after initiation of methotrexate was obtained. RAMRIS of the hand was complemented by corresponding scoring of the foot (MTP I-V; HaF-score). Disease Activity Score 28 (DAS28) and a tender and swollen joint count (JC) of the joints scored in MRI were recorded. Changes in these scores (Δ) were assessed. Results: ΔHaF-score correlated significantly with ΔDAS28 (r = 0.820, 95%-CI 0.633-0.916). Correlations to ΔDAS28 were best for changes in the synovitis subscore (0.648) and bone marrow edema (0.703). Correlations to ΔDAS28 were significantly better for of the ΔHaF-score than ΔRAMRIS (0.499, 0.139-0.743, p = 0.0368). All patients with at least moderate response (EULAR criteria, n = 11) had continuing disease activity on MRI, including five cases with new erosions, three of them at the feet. Improvements of the hand JC or foot JC were seen in 16 and 15 cases, respectively. However, MRI of the hand or feet improved in only 10 and 9 cases, respectively. No patient fulfilled SDAI remission criteria. Conclusions: The HaF-score identifies patients with continuing disease activity despite clinical response that would have been missed by consideration of the traditional RAMRIS or the DAS28 alone. Response as opposed to remission may be an insufficient goal in RA as all patients showed continuing disease activity, especially at the feet. [ABSTRACT FROM AUTHOR]

To investigate patterns of inflammatory MRI pathologies of the fore- and midfoot in rheumatoid arthritis (RA) and early RA (ERA) and their changes under therapy. In this prospective study, MRI data of the foot of 39 RA patients (29 female, 10 male; age: 54 ± 13 years; disease duration: 35 ± 37 months; baseline DAS28: 3.0 ± 2.0; medication: 29 DMARD, 1 biological, 9 symptomatic or non-specific treatment) were evaluated for synovitis in 314 joints, bone marrow edema and erosions according to RAMRIS criteria in a total of 585 joints. The change in joint pathology intensity was evaluated on follow-up MRI (time of follow-up: 8 ± 4 months) in 25 patients. Inflammation was generally more frequent in the metatarsophalangeal (MTP) joints (221/292; 76 %) than in the proximal metatarsal (47/292; 16 %) and tarsal bones (24/292; 8 %). The overall most frequently involved joints of the foot were MTP 5 (51/292; 18 %) and 1 (49/292; 17 %). Change under therapy was most frequently seen in the MTP 1 joint. Progress of inflammation in the MTP 1 was more frequently found in ERA patients than in patients with established RA (disease duration >12 months) ( p = 0.002). In RA, the MTP joints, primarily MTP 5 and 1, are the predominant sites of inflammatory MRI pathologies of the foot. A change of inflammatory activity under therapy can be most frequently noted in the MTP 1 joint. This information might be helpful to improve effectiveness of MRI-controlled therapy approaches and clinical trials. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To evaluate the utility of sequentially acquired, post hoc fused, magnetic resonance imaging (MRI) and multi-pinhole single photon emission computed tomography (MPH-SPECT) with technetium-99m-labeled disphosphonates (Tc99m-DPD) for the identification of finger joints with later erosive progression in early rheumatoid arthritis (ERA) patients. Methods: Ten consecutive ERA patients prospectively underwent MPH-SPECT and MRI of metacarpophalangeal (MCP) joints prior to and after 6 months methotrexate therapy. Tc99m-DPD uptake was measured at proximal and distal MCP sites using regional analysis. The course of joint pathologies was scored according to the Rheumatoid Arthritis MRI Score (RAMRIS) criteria. Results: The frequency of increased Tc99m-DPD uptake, synovitis and bone marrow edemadecreased under MTX therapy; but the number of bone erosions increased. Joints with progressive and new erosions on follow-up had a higher baseline Tc99m-DPD uptake (2.64±1.23 vs. 1.43±0.91) (p =0.02). Conclusions: Joints with erosive progression are characterized by an early increased Tc99m-DPD uptake, even in absence of MRI bone pathologies. Tc99m-DPD MPH-SPECT might thus be of additional value to morphological MRI for the identification of RA patients with a high risk for erosive progression. [Copyright &y& Elsevier]

Purpose: To prospectively evaluate four non-invasive markers of cartilage quality-T2* mapping, native T1 mapping, dGEMRIC and ΔR1-in healthy volunteers and rheumatoid arthritis (RA) patients. Materials and methods: Cartilage of metacarpophalangeal (MCP) joints II were imaged in 28 consecutive subjects: 12 healthy volunteers [9 women, mean (SD) age 52.67 (9.75) years, range 30-66] and 16 RA patients with MCP II involvement [12 women, mean (SD) age 58.06 (12.88) years, range 35-76]. Sagittal T2* mapping was performed with a multi-echo gradient-echo on a 3 T MRI scanner. For T1 mapping the dual flip angle method was applied prior to native T1 mapping and 40 min after gadolinium application (delayed gadolinium-enhanced MRI of cartilage, dGEMRIC, T1). The difference in the longitudinal relaxation rate induced by gadolinium (ΔR1) was calculated. The area under the receiver operating characteristic curve (AROC) was used to test for differentiation of RA patients from healthy volunteers. Results: dGEMRIC (AUC 0.81) and ΔR1 (AUC 0.75) significantly differentiated RA patients from controls. T2* mapping (AUC 0.66) and native T1 mapping (AUC 0.66) were not significantly different in RA patients compared to controls. Conclusions: The data support the use of dGEMRIC for the assessment of MCP joint cartilage quality in RA. T2* and native T1 mapping are of low diagnostic value. Pre-contrast T1 mapping for the calculation of ΔR1 does not increase the diagnostic value of dGEMRIC. [ABSTRACT FROM AUTHOR]

Objective To assess cartilage glycosaminoglycan content and cartilage thickness in the metacarpophalangeal (MCP) joints of patients with early rheumatoid arthritis (RA) and healthy volunteers. Methods After review board approval and informed consent were obtained, 22 subjects were prospectively enrolled (9 patients with early RA [7 women and 2 men with a mean ± SD age of 49 ± 13 years; range 25-68 years] and 13 healthy volunteers [10 women and 3 men with a mean ± SD age of 51 ± 12 years; range 25-66 years). In a total of 44 MCP joints of the index and middle fingers, measurements of cartilage thickness and delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) index (T1 [msec]) were obtained using the variable flip-angle method and a 3T MR scanner. MRIs were evaluated for bone edema, erosions, and synovitis (using the RA MRI Scoring criteria). Student's t-test was used to test the significance of differences between groups. Results The mean ± SD dGEMRIC index was 497 ± 86 msec in healthy volunteers and was significantly lower in the early RA group (421 ± 76 msec) ( P = 0.042). There was no joint space narrowing seen on standard radiographs. No significant difference was found between cartilage thickness in patients with early RA and that in controls (index finger mean ± SD 1.27 ± 0.23 mm in RA patients versus 1.46 ± 0.34 mm in controls [ P = 0.16] and middle finger 1.26 ± 0.23 mm in RA patients versus 0.97 ± 0.47 mm in controls [ P = 0.10]). No significant correlation was noted between cartilage thickness and dGEMRIC index (R = 0.36, P = 0.88 in RA patients; R = 0.156, P = 0.445 in controls). Conclusion Our findings indicate that cartilage damage is present in the MCP joints of patients with early RA despite the absence of joint space narrowing on standard radiographs and MRI. Cartilage damage in RA can be imaged with dGEMRIC. [ABSTRACT FROM AUTHOR]

18F-fluorodeoxyglucose PET (18F-FDG PET) is highly sensitive to inflammatory changes within the synovial tissue in rheumatoid arthritis (RA). However, the highest spatial resolution for soft tissue can be achieved with MRI. Here, we report on the first true hybrid PET-MRI examination of the hand in early RA exploiting the advantages of both modalities. PET-MRI was performed with a prototype of an APD-based magneto-insensitive BrainPET detector (Siemens Healthcare, Erlangen, Germany) operated within a standard 3T MR scanner (MAGNETOM Trio, Siemens). PET images were normalized, random, attenuation and scatter-corrected, iteratively reconstructed and calibrated to yield standardized uptake values (SUV) of 18F-FDG uptake. T1-weighted TSE in coronal as well as sagittal orientation prior to and following Gadolinium administration were acquired. Increased 18F-FDG uptake was present in synovitis and tenovaginitis as identified on contrast-enhanced MRI. The tracer distribution was surrounding the metacarpophalangeal joints II and III. Maximum SUV of 3.1 was noted. In RA, true hybrid 18F-FDG PET-MRI of the hand is technically feasible and bears the potential to directly visualize inflammation. [ABSTRACT FROM AUTHOR]

The article considers the hazard risk of developing or worsening heart failure among patients with rheumatoid arthritis who have been treated with tumor necrosis factor (TNF) alpha inhibitors. According to the authors, three-year heart failure incidence rates among patients with cardiovascular disease was at 2.2 percent, while those without cardiovascular problem at the start of treatment was at 0.4 percent. They conclude that TNF alpha inhibitor treatment is more beneficial than harmful.

Objective: To quantify direct costs of medication and cost of illness (according to functional capacity) for patients with rheumatoid arthritis (RA) in Germany, allowing further use in a health economic evaluation of sequential therapy with disease-modifying antirheumatic drugs (DMARDs) in specialised, i.e. rheumatological, care in Germany.Design and Setting: The analysis was conducted from the societal perspective in Germany using a modelling approach, which was based on secondary analysis of existing data and on data from a sample of 583 patients from the German rheumatological database of 1998. Functional capacity was defined by the Hannover Functional Ability Questionnaire (HFAQ) scores. Costs were calculated from resources utilised and patients' work capacity. Direct costs consisted of outpatient medical services, inpatient treatment, long-term care and rehabilitation treatment. Indirect costs incurred by sick leave and premature retirement were quantified according to the human-capital approach.Main Outcome Measures and Results: Average total direct costs (year 1998-2001 values) per patient per year for continuous treatment with the selected DMARDs comprising costs for drugs, monitoring and treatment of adverse drug reactions (ADRs) were highest for intramuscular gold (sodium aurothiomalate) [euro 2106 (euro 1 approximately equal to $US 0.91; average of the period from 2000 through 2001)] followed by leflunomide (euro 2010), azathioprine (euro 1878), sulfasalazine (euro 1190), oral methotrexate (euro 708), and lowest for the antimalarials chloroquine/hydroxychloroquine (euro 684). There were additional yearly costs for RA-related non-DMARD medication of euro 554 per patient, including management of ADRs. Mean cost of illness (year 1998 values) excluding medication cost amounted to euro 17,868 per RA patient per year. Annual costs increased with increasing disability, i.e. decreasing functional capacity, of RA patients from euro 6029 per patient with more than 94% of functional capacity to euro 28,509 per patient with <20% of functional capacity. In general, there was a predominance of indirect costs in each of the categories of functional capacity, ranging between 74% and 87% of total (direct and indirect) annual costs per RA patient. Annual direct costs increased from euro 811 to euro 7438 per patient with increasing disability. Inpatient treatment was the predominant component of direct costs. Patients in the worst category (<20%) of function experienced hospital costs that were 6.5 times higher than those of patients in the best category (>94%).Conclusions: On the basis of the data presented it can be concluded that the results of this investigation are typical for patients in rheumatological care in Germany and can therefore be used in a health economic analysis of different DMARD sequences aimed at changing disease progression over time. [ABSTRACT FROM AUTHOR]

Objective: To estimate the 3-year incremental cost effectiveness and cost utility of introducing leflunomide into sequential therapy, consisting of the most frequently used disease-modifying antirheumatic drugs (DMARDs), for patients with rheumatoid arthritis in specialised, i.e. rheumatological, care in Germany.Design and Setting: The analysis was conducted from the societal perspective in Germany using an existing 3-year simulation model, which was adapted to the German healthcare system after secondary analysis of relevant publications and data. DMARD sequences including leflunomide were compared with those excluding leflunomide. Costs comprised direct costs incurred by treatment and indirect costs incurred by loss of productivity (sick leave and premature retirement) of rheumatoid arthritis patients. Effectiveness parameters were given by response years gained (RYGs) according to the American College of Rheumatology (ACR) criteria for 20%, 50% and 70% improvement (ACR20/50/70RYGs) and by QALYs gained (QALYGs). Costs, effects and QALYs were discounted by 5% per annum. In the base-case analysis, average values of costs, response years and QALYs were applied. Costs were in 1998-2001 values (euro 1 approximately equal to $US 0.91, average of the period from the year 2000 through 2001).Main Outcome Measures and Results: After 3 years, adding leflunomide was less costly and more effective than the strategy excluding leflunomide when total (direct and indirect) costs were considered. There were savings of euro 271,777 and 8.1, 4.3, 5.1 and 4.9 ACR20RYGs, ACR50RYGs, ACR70RYGs and QALYGs per 100 patients, respectively, obtained through adding leflunomide. Focusing on direct costs, adding leflunomide was more costly and more effective compared with excluding leflunomide, with an incremental cost effectiveness of euro 5004 per ACR20RYG, euro 9535 per ACR50RYG, euro 7996 per ACR70RYG, and an incremental cost utility of euro8301 per QALYG, after 3 years. The robustness of the results was shown in comprehensive sensitivity analyses. In the analysis of extremes, different combinations of the limits of cost, effectiveness and utility parameters were investigated. Adding leflunomide to sequential DMARD therapy remained dominant in 79% of the possible cases, i.e. was less costly and more effective than the strategy excluding leflunomide. Focusing on direct costs, adding leflunomide became dominant in 29% and remained more costly and more effective in 50% of possible cases.Conclusions: Our analysis suggests, with its underlying data and assumptions, that having leflunomide as an additional option in a DMARD treatment sequence extends the time patients benefit from DMARD therapy at reasonable additional direct costs. Adding leflunomide may even be cost saving when total (direct and indirect) costs are considered. As data on DMARD effectiveness were extracted from the results of clinical trials, real-world data from observational studies would be needed to corroborate the findings of the present analysis. [ABSTRACT FROM AUTHOR]

Background: Even though cartilage loss is a known feature of psoriatic (PsA) and rheumatoid arthritis (RA), research is sparse on its role in the pathogenesis of PsA, its potential use for disease monitoring and for differentiation from RA. We therefore assessed the use of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) to evaluate biochemical cartilage changes in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints in PsA patients and compared these to RA patients. Materials and Methods: A total of 17 patients with active PsA and 20 patients with active RA were evaluated by high-resolution 3 Tesla dGEMRIC using a dedicated 16-channel hand coil. Images were analyzed by two independent raters for dGEMRIC indices and joint space width (JSW) at MCP and PIP joint levels. Results: No significant differences of dGEMRIC values could be found between both study populations (PsA 472.25 ms, RA 461.11 ms; p = 0.763). In all RA and most PsA patients, PIP joints showed significantly lower dGEMRIC indices than MCP joints (RA: D2: p = 0.009, D3: p = 0.008, D4: p = 0.002, D5: p = 0.002; PsA: D3: p = 0.001, D4: p = 0.004). Most joint spaces had similar widths in both disease entities and no significant differences were found. Conclusions: As evaluated by dGEMRIC, the molecular composition of the MCP and PIP joint cartilage of PsA patients is similar to that of RA patients, demonstrating the scientific and clinical feasibility of compositional magnetic resonance (MR) imaging in these disease entities. Patterns and severity of compositional cartilage degradation of the finger joints may therefore be assessed beyond mere morphology in PsA and RA patients. [ABSTRACT FROM AUTHOR]