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ID PMID Title PublicationDate abstract
21533614 [Physical exposure by travelling]. 2011 Jun Approximately 40 million Germans travel abroad every year. Air travel is the most frequently used mean of transportation followed by the automobile. During airplane flights rheumatic patients are subjected to numerous physical, biological and climatic factors which can cause stress and adverse effects on general health. Therefore, preventive strategies are helpful to protect against health damage, provided that there is general fitness for air travel. The present article focuses on physical and biological stress as well as psychological aspects during air travel and reviews prophylactic measures.
23259656 Pragmatic and scientific advantages of MDHAQ/ RAPID3 completion by all patients at all vis 2012 The patient history often provides the most important information in diagnosis and management of rheumatoid arthritis (RA) and other rheumatic diseases. A multidimensional health assessment questionnaire (MDHAQ)-with templates to score RAPID3 (routine assessment the patient index data), an index of three patient self-report measures, physical function, pain, and patient global estimate-pro- vides a "scientific" patient history. MDHAQ/RAPID3 scores meet criteria for the scientific method seen for laboratory tests: standard format, quantitative data, protocol for col- lection, and recognition of prognostic implications of levels for management decisions. Extensive evidence supports a scientific rationale for MDHAQ/RAPID3 scores, which are as efficient as joint counts, laboratory tests, DAS28, and CDAI to distinguish active from control treatments in clinical trials and correlated significantly with DAS28 and CDAI scores in clinical trials and usual clinical care, including categories for high, moderate, low severity, and remission. Pragmatic advantages of MDHAQ/RAPID3 include that the patient does almost all the work and prepares for the encounter to focus on concerns to discuss with the doctor. MDHAQ/RAPID3 improves doctor-patient communication and saves time for the doctor with a 10 to 15 second overview of medical history data that otherwise would require 10 to 15 minutes of conversation. RAPID3 is scored in 5 seconds, compared to almost 2 minutes for a CDAI or DAS28, and can be used effectively for treat-to-target in RA. MDHAQ/ RAPID3 is informative in all rheumatic diseases, including systemic lupus erythematosus, osteoarthritis, ankylosing spondylitis, psoriatic arthritis, fibromyalgia, gout, and others. All rheumatologists may include MDHAQ/RAPID3 in all patients in the infrastructure of clinical care.
22766000 Risk of malignancy including non-melanoma skin cancers with anti-tumor necrosis factor the 2012 Sep OBJECTIVES: To assess the risk of malignancy in patients with rheumatoid arthritis (RA) receiving tumour necrosis factor (TNF) antagonists through a meta-analysis of data from registry studies and systematic review of long-term extension (LTE) studies. METHODS: We systematically reviewed the literature up to January 2010 in the Embase and Medline databases, as well as abstracts from the 2008 and 2009 annual meetings of the EULAR and the ACR. The Mantel-Haenszel method was used to provide a common odds ratio (OR). Statistical heterogeneity was assessed by the chi-square Q test (χ²). Standardised incidence ratio (SIR) was extracted for post-marketing studies and registries. RESULTS: The literature search identified 634 articles and 110 abstracts, of which 12 and 5, respectively, were selected for analysis. We could perform a meta-analysis of data from 4 and 3 registries for risk of total malignancy and non-melanoma skin cancers (NMSC), respectively. The pooled OR for total malignancy and for NMSC was 0.81 [95% confidence interval (CI) 0.71-0.94] and 0.79 [0.62-1.02] in TNF antagonist group versus DMARD group, respectively. There was no significant heterogeneity. Among 4 LTE studies and 4 registries, no significant increase in the incidence of total malignancy was noted versus the general population. The only signal may be an increased risk of non-melanoma skin cancers. CONCLUSIONS: Our meta-analysis of data from registries and systematic review of LTE studies did not reveal an increased risk of total malignancy in RA patients receiving anti-TNF therapy.
22589255 Treatment with biologic agents improves the prognosis of patients with rheumatoid arthriti 2012 Jul OBJECTIVE: Reactive amyloid A (AA) amyloidosis is a serious and life-threatening systemic complication of rheumatoid arthritis (RA). We evaluated the safety of therapy with anti-tumor necrosis factor and anti-interleukin 6 biologic agents in RA patients with reactive AA amyloidosis, together with prognosis and hemodialysis (HD)-free survival, in comparison with patients with AA amyloidosis without such therapy. METHODS: One hundred thirty-three patients with an established diagnosis of reactive AA amyloidosis participated in the study. Clinical data were assessed from patient records at the time of amyloid detection and administration of biologics. Survival was calculated from the date when amyloid was first demonstrated histologically or the date when biologic therapy was started until the time of death or to the end of 2010 for surviving patients. Patients who had started HD were selected for inclusion only after the presence of amyloid was demonstrated. RESULTS: Fifty-three patients were treated with biologic agents (biologic group) and 80 were not (nonbiologic group). Survival rate was significantly higher in the biologic group than in the nonbiologic group. Nine patients in the biologics group and 33 in the nonbiologic group started HD. Biologic therapy had a tendency for reduced risk of initiation of HD without any statistical significance. CONCLUSION: Patients with amyloidosis have a higher mortality rate, but the use of biologic agents can reduce risk of death. The use of biologics may not significantly influence the HD-free survival rate.
21784728 Association of variants in MMEL1 and CTLA4 with rheumatoid arthritis in the Han Chinese po 2011 Oct BACKGROUND: The genome-wide association study era has made great progress in identifying susceptibility genes and genetic loci for rheumatoid arthritis (RA) in populations of White European ancestry. However, few studies have tried to dissect disease aetiopathogenesis in other ethnic populations. OBJECTIVE: To investigate these associations in the Han Chinese population. METHODS: Haplotypes from the HapMap database Chinese population were used to select tag-single-nucleotide polymorphisms (SNPs) (r(2)=0.8) across 19 distinct RA genomic regions. A two phase case-control association study was performed, with 169 SNPs genotyped in phase I (n=571 cases, n=880 controls), and 64 SNPs achieving p<0.2 in the first phase being genotyped in phase II (n=464 cases, n=822 controls). Association statistics were calculated using permutation tests both unadjusted and adjusted for the number of markers studied. RESULTS: Robust association was detected for MMEL1 and CTLA4, and modest association was identified for another six loci: PADI4, STAT4, PRDM1, CDK6, TRAF1-C5 and KIF5A-PIP4K2C. All three markers genotyped in MMEL1 demonstrated association, with peak signal for rs3890745 (p=2.6 × 10(-5) unadjusted, p=0.003 adjusted, OR=0.79). For CTLA4, significance was detected for three of five variants showing association, with peak association for marker rs12992492 (p=4.3 × 10(-5) unadjusted, p=0.0021 adjusted, OR=0.77). Lack of association of common variants in PTPN22 with RA in Han Chinese was confirmed. CONCLUSION: This study identifies MMEL1 and CTLA4 as RA susceptibility genes, provides suggestive evidence of association for a further six loci in the Han Chinese population and confirms lack of PTPN22 association in Asian populations. It also confirms the value of multiethnic population studies to help dissect disease aetiopathogenesis.
21274978 Measuring bone erosion and edema in rheumatoid arthritis: a comparison of manual segmentat 2011 Feb PURPOSE: To investigate the reliability, feasibility, and validity of a computer-assisted manual segmentation (outlining) technique for measuring magnetic resonance imaging (MRI) bone erosion and edema at the wrist in rheumatoid arthritis (RA). MATERIALS AND METHODS: The 3T MRI scans were obtained in 22 RA patients (<2 years). Bone erosion and edema volumes were scored by two readers using outlining and were compared with RAMRIS scores. RESULTS: Using outlining, intraobserver reliability for erosions and edema was high: intraclass correlation coefficients (ICCs) = 0.994 (0.991, 0.997) and 0.996 (0.994, 0.998), respectively (Reader 1). Interobserver reliability was high for bone erosion (ICC [90% confidence interval, CI] = 0.80 [0.64, 0.92]) and comparable to RAMRIS scoring (ICC 0.78 [0.64, 0.92]), but was only moderate for bone edema (0.46 [0.00, 0.96]), compared with RAMRIS (ICC = 0.84 [0.73, 0.94]). The methods were highly correlated for erosion scores, r = 0.90, 0.82 (Readers 1 and 2) and moderately correlated for edema, r = 0.57, 0.87. CONCLUSION: Segmentation (outlining) can be used to measure the volume of MRI bone erosion and edema at the wrist in RA patients. When compared with RAMRIS scoring, outlining had similar reliability for quantifying erosions but reliability was lower for bone edema, possibly reflecting difficulty delineating the borders of affected bone.
21128990 Eternacept for the treatment of patients with rheumatoid arthritis and concurrent intersti 2012 Feb WHAT IS KNOWN AND OBJECTIVE: Tumour necrosis factor-α (TNF-α)-blocking agents are increasingly used in the management of refractory rheumatoid arthritis (RA). Although effective, they are associated with rare but potentially fatal adverse effects, including interstitial lung disease (ILD). In patients with pre-existing ILD, eternacept (ETN) monotherapy is often regarded as a suitable choice. Other anti-TNF-α blockers such as infliximab and adalimumab, are used in combination therapy with methotrexate (MTX) in most of the cases. We report on a case of fatal exacerbation of ILD in a patient given ETN monotherapy and review the literature on ETN-associated ILD. METHODS: We report on a case of a 75-year-old male with RA who developed severe ILD after the introduction of ETN, and we undertook a literature search to identify other reports of similar cases. We then critically assessed those reports. RESULTS AND DISCUSSION: In addition to our case, 11 other patients have been reported to have developed ILD in association with the use of ETN. Six patients had pre-existing ILD. Although four patients received MTX, eight patients developed severe ILD without MTX. Ten patients recovered after termination of ETN, although two patients died. WHAT IS NEW AND CONCLUSION: Although ETN is often regarded as safe for patients with ILD, our case and the literature reports suggest that caution is still required.
22349619 Rituximab-it was the best of times, it was the worst of times. 2012 Sep B cell depletion (BCD) has become established in the treatment of patients with rheumatoid arthritis (RA) vasculitis and systemic lupus erythematosus (SLE). However, although successfully confirmed to be useful in major large scale trials in RA and vasculitis, two SLE trials did not meet their endpoints. Given the widespread use of BCD in SLE it seems likely that it will continue to be used though better designed trials (which work) would help resolve on-going problems with regulatory and funding agencies.
21359557 [Genetics of rheumatoid arthritis]. 2011 Apr Genetic influences on susceptibility to and clinical course of rheumatoid arthritis have been known for a long time, but have so far eluded systematic, genome-wide analysis. In recent years, the availability of new typing techniques and international consortia with large patient cohorts has generated a wealth of new information on the genetic basis of this autoimmune disease. Newly described associations between immunologically relevant gene polymorphisms and RA susceptibility have already been replicated with great statistical power, and are currently incorporated into new, pathogenetically relevant functional pathways. The resulting new concepts identify cell populations of great potential relevance for the pathogenesis of the disease, and ultimately might lead to new diagnostic and therapeutic approaches in RA.
20847201 Using genetic and clinical data to understand response to disease-modifying anti-rheumatic 2011 Jan The objective of this review is to report on the progress of the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) Registry data collection and summarize previous research in understanding therapeutic response to DMARDs using clinical and genetic data. The BRASS Registry, established in 2003, is a large, single-centre, prospective and observational cohort of 1100 RA patients. Patients with either new-onset or established RA disease are recruited from the practices of rheumatologists. Annual visits collect information on demographics, 28-joint DAS-CRP3 (DAS-28-CRP3), medication use, comorbidities and functional status (Modified Health Assessment Questionnaire, Short Form Health Survey 12). Two published studies have utilized BRASS to examine genetic predictors of treatment response. In a cross-sectional study, examining the association between candidate single nucleotide polymorphisms (SNPs) and disease activity in a subset of 120 RA patients on MTX monotherapy, the minor allele of ATIC rs4673993 was associated with low disease activity (P=0.01, DAS-28-CRP3≤3.2). In an international collaboration, 55 BRASS patients receiving anti-TNF therapy were genotyped for 31 SNPs associated with the risk of RA. With our collaborators, we discovered an SNP at the protein tyrosine phosphatase, receptor type, C (PTPRC) gene locus that was associated with EULAR 'good response'. With accurate data collection and the capacity to run genome-wide association studies and SNP analyses, the BRASS Registry has the ability to determine the contribution of genetic variants to disease onset and to assess their usefulness as biomarkers for treatment response and drug toxicity.
22271322 [Radiological differential diagnosis of rheumatoid arthritis]. 2012 Feb CLINICAL/METHODICAL ISSUE: Establishing an early and reliable diagnosis of rheumatoid arthritis (RA) is of major importance but can be a great clinical challenge leading to direct therapeutic consequences. No single epidemiological, genetic, clinical, serological or radiological test exists which can exclusively diagnose RA. STANDARD RADIOLOGICAL METHODS: In general diagnosis of RA includes a case history, clinical signs, laboratory abnormalities and radiological examinations, viz. conventional radiography of the joints of the hands and feet. PRACTICAL RECOMMENDATIONS: This review summarizes the most important radiological features of RA and the radiological findings of its closest differential diagnoses.
21091275 Ultrasonography shows significant improvement in wrist and ankle tenosynovitis in rheumato 2011 May OBJECTIVE: Tenosynovitis is common in rheumatoid arthritis (RA) but knowledge is limited regarding its response to anti-inflammatory treatment. This study used ultrasonography (US) to examine the distribution and responsiveness of tenosynovitis to anti-tumour necrosis factor (anti-TNF) treatment in RA patients. METHODS: Twenty patients with RA were examined at baseline and 1, 3, 6, and 12 months after starting adalimumab treatment, and grey-scale (GS) and power Doppler (PD) US scoring (semi-quantitative range 0-3) of wrist and ankle tendons was performed in addition to assessment of the 28-joint Disease Activity Score (DAS28), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). RESULTS: The extensor carpi ulnaris (ECU) tendon in the wrists and the closely related tendons tibialis posterior (TB) and flexor digitorum longus (FDL) in the ankles were most often inflamed. Median sum scores for this reduced number of tendons at baseline/12-month follow-up were 5/0.5 for GS (p < 0.001) and 4/0 for PD (p < 0.05), with reductions in the US scores during follow-up as large as those found for sum scores of all tendons. The standardized response means (SRMs) for sum GS or PD scores of the reduced number of tendons were higher (range -0.53 to -0.93) than for the sum scores of all tendons (-0.23 to -0.74), and showed larger responsiveness than CRP (-0.10 to -0.43) and ESR (-0.03 to -0.71). CONCLUSION: Bilateral assessments of ECU, TB, and FDL tendons were as sensitive to change as the sum scores of all tendons, and scoring of this reduced number of tendons is suggested to be included in US scorings for follow-up of RA patients.
21360493 Acquisition of the rheumatoid arthritis HLA shared epitope through microchimerism. 2011 Mar OBJECTIVE: HLA-DRB1 alleles associated with risk of rheumatoid arthritis (RA) encode similar HLA-DRB1 sequences, called the shared epitope (SE). The most common SE sequences are QKRAA and QRRAA. Nevertheless, a substantial number of RA patients lack the SE. Bidirectional fetal-maternal trafficking results in long-term persistence of fetal cells in the mother and maternal cells in her offspring, a process known as microchimerism. This study was undertaken to discover whether RA patients who lack the SE can acquire it through microchimerism. METHODS: We studied a total of 86 female subjects who were genotypically negative for the SE, comprising 52 patients with RA and 34 healthy controls. We developed specific real-time quantitative polymerase chain reaction assays for the SE-encoded sequences QKRAA and QRRAA, and used them to test DNA extracted from peripheral blood mononuclear cells. RESULTS: Microchimerism with the SE was found significantly more often in RA patients than controls (odds ratio 4.1 [95% confidence interval 1.6-10.0], P = 0.003). Concentrations of SE microchimerism were also significantly higher among RA patients than controls (P = 0.002). In separate analyses for SE type, the prevalence of QKRAA microchimerism in RA patients versus healthy controls was 17% versus 3% (9 of 52 versus 1 of 34; P = 0.03) and the prevalence of QRRAA microchimerism was 40% versus 18% (21 of 52 versus 6 of 34; P = 0.04), respectively. Microchimerism concentrations were also higher in RA patients than healthy subjects for QKRAA (P = 0.03) and QRRAA (P = 0.03). CONCLUSION: These results indicate that RA patients who genotypically lack the SE can acquire the SE as persistent microchimerism from fetal-maternal cell exchange, suggesting that SE-encoding microchimerism could be a risk factor for RA.
20062998 Effect of etanercept and entecavil in a patient with rheumatoid arthritis who is a hepatit 2012 Apr In this report, we describe a case of a 48-year-old Japanese woman who is a hepatitis B (HB) carrier with rheumatoid arthritis (RA). She had the following antibody profile: HBs Ag(+), HBs Ab(-), HBe Ag(-), HBe Ab (+), HBc Ab(-) and undetectable HBV-DNA level. She was treated with auranofin, salazosulfapyridine, and bucillamine. Finally, she was treated with D: -penicillamine, but her disease activity remained elevated. Prophylactic treatment of entecavir 0.5 mg daily was started in March 2008 and all disease-modifying anti-rheumatic drugs were stopped. After 2 weeks, etanercept monotherapy was started at 25 mg subcutaneously once a week. Significant improvement in clinical parameters of disease activity and well being was observed. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and HB virus viral load did not change significantly. Serum ALT, AST, and HB virus viral load were followed-up at every 3-month intervals, from initiation of therapy up to 24 months after the start of treatment with etanercept. We have also summarized the course of nine RA patients who received etanercept and were HB carriers or had chronic HB according to our literature search. Based on the results of our study, treatment of these patients with etanercept co-administered with lamivudine or entecavir appears to be safe.
22505694 Incidence of new-onset and flare of preexisting psoriasis during rituximab therapy for rhe 2012 May OBJECTIVE: Psoriasis could be a paradoxical reaction to tumor necrosis factor-α antagonist therapy and it has been reported with rituximab therapy. Our objective was to assess the rates of new-onset and flare of preexisting psoriasis in patients taking rituximab for rheumatoid arthritis (RA). METHODS: The nationwide multicenter prospective AutoImmunity and Rituximab (AIR) registry was set up in 2006 by the French Society for Rheumatology to collect data on patients taking rituximab for joint diseases. We identified patients with RA in the registry who had psoriasis listed as an adverse drug reaction, and we obtained additional information from their physicians if needed. We computed the incidence rates of new-onset and flare of preexisting psoriasis according to the rituximab exposure time. RESULTS: Among the 1927 patients in the registry with RA, 2 had new-onset and 5 had flare of preexisting psoriasis after a median followup of 39.2 weeks. Incidence rates were 1.04/1000 person-years (95% CI 0.13 to 3.8) for new-onset psoriasis and 2.6/1000 person-years (95% CI 0.84 to 6.1) for flare of preexisting psoriasis. Rituximab rechallenge in the 2 new-onset cases and in 2 flare cases was not followed by recurrence or exacerbation of psoriasis. Two of the 5 flare cases developed after discontinuation of methotrexate. CONCLUSION: Despite the small number of cases observed, leading to wide CI, the incidence rates in our study do not support a causative role of rituximab therapy in new-onset or flare of preexisting psoriasis in patients with RA.
22440821 Treatment-specific changes in circulating adipocytokines: a comparison between tumour necr 2012 Sep OBJECTIVE: There is increasing evidence that adipocytokines may exert proinflammatory and destructive effects in rheumatoid arthritis (RA). Hence, the authors investigated the relationship between adipocytokines and several features associated with RA (inflammation, joint destruction and cardiovascular disease), as well as the effect of treatment with a tumour necrosis factor inhibitor or glucocorticoids (GCs) hereupon. METHODS: Serum levels of adiponectin, leptin, resistin, visfatin, vaspin and lipids were determined in a well-defined cohort of patients with RA before and after 16 weeks of adalimumab treatment (adalimumab cohort). The same parameters were analysed in two other cohorts of patients with RA before and after 2 weeks of high-dose prednisolone (high GC cohort) and before and after 22 weeks of treatment with a combination regimen with tapered high-dose prednisolone (COBRA -GC cohort). Radiographs of hands and feet (adalimumab and COBRA-GC cohorts) were assessed at baseline and after treatment. RESULTS: Treatment with adalimumab or GC showed opposing effects on vaspin and visfatin levels. Lipid levels improved after several months of adalimumab or GC treatment; in the adalimumab cohort, this was related to reduced visfatin levels, independent of C reactive protein levels. After long-term adalimumab or GC treatment, resistin levels declined, which was associated with a decrease in inflammation markers. In the adalimumab cohort, baseline resistin levels were predictive of baseline radiological damage, independent of anticitrullinated peptide antibodies status or C reactive protein levels. CONCLUSION: Changes in serum adipocytokine levels were treatment specific, further strengthening the role of visfatin and resistin in several disease manifestations of RA.
22092173 Analysis of a genome-wide association study-linked locus (CCR6) in Asian rheumatoid arthri 2012 Apr A genome-wide association study in Japan identified the C-C chemokine receptor type 6 gene (CCR6) as associated with rheumatoid arthritis (RA). This finding has not been validated in other Asian populations. A case-control study involving 996 subjects, comprising 440 controls and 556 RA patients, was done to determine their anticyclic citrullinated peptide (anti-CCP) antibody status and CCR6 polymorphism (rs3093024) genotype. Three hundred eighty-seven patients were anti-CCP positive and 153 anti-CCP negative. Logistic regression showed that allele A was likely to increase the risk of developing RA among females via a recessive model (odds ratio [OR]=1.55, 95% confidence interval [CI]=1.01, 2.39), whereas the risk effect appeared to be reduced among males via an additive model (OR=0.60, 95% CI=0.42, 0.85). Considering only subjects who are anti-CCP positive, allele A increased RA risk among females via a recessive model (OR=1.68, 95% CI=1.07, 2.64) but decreased the risk among males via an additive model (OR=0.59, 95% CI=0.39, 0.89). We showed that CCR6 polymorphism was a risk factor among females but a protective factor among males. Functional studies are warranted to unravel the pathophysiological relevance of the gene variant and other linked variants with RA.
21628307 Deletion of LCE3C_LCE3B is associated with rheumatoid arthritis and systemic lupus erythem 2011 Sep OBJECTIVES: The deletion of LCE3C_LCE3B confers susceptibility to psoriasis and rheumatoid arthritis (RA) in Caucasians. The aim of this study was to investigate the variant involvement in RA in the Chinese Han population and to further explore its potential role in the susceptibility to systemic lupus erythematosus (SLE). METHODS: LCE3C_LCE3B-del was genotyped in 898 patients with RA and 681 healthy controls. Two single nucleotide polymorphisms (SNPs, rs4112788 and rs4085613) in strong linkage disequilibrium with LCE3C_LCE3B-del were then genotyped in patients with RA (n=1222), SLE (n=870) and healthy controls (n=1031). RESULTS: The deletion of LCE3C_LCE3B and SNPs rs4112788 and rs4085613 showed an association with RA (allele analysis: p=7.72×10(-4), OR 1.28, 95% CI 1.11 to 1.47; p=6.39×10(-4), OR 1.23, 95% CI 1.09 to 1.38; and p=5.38×10(-4), OR 1.23, 95% CI 1.10 to 1.39, respectively). The two SNPs were also significantly associated with SLE (allele analysis: p=7.68×10(-3), OR 1.19, 95% CI 1.05 to 1.36 and p=5.30×10(-3), OR 1.20, 95% CI 1.06 to 1.37). CONCLUSIONS: This study provides evidence for an association between LCE3C_LCE3B-del and RA in non-Caucasian populations, and SNPs rs4112788 and rs4085613 tagging LCE3C_LCE3B-del were novel susceptibility factors for SLE.
21345295 Identification and quantification of selected inflammatory genes modulated by leflunomide 2011 Jan OBJECTIVES: The present study evaluates the effects of combined leflunomide (LEF) and low dose of prednisone therapy, on selected inflammatory gene expression in peripheral blood mononuclear cells (PBMCs) of early rheumatoid arthritis (ERA) patients by gene microarray analysis and quantitative real time-polymerase chain reaction (qRT-PCR). METHODS: Ten ERA patients (mean age 53 ± 10 years) were assigned as untreated (group 1) or pre-treated (group 2) with prednisone (5 mg/day for 3 months) after informed consent and ethics committee approval. Five sex- and age-matched healthy subjects were used as controls (CNT). RNA was extracted by PBMCs, amplified, labelled and hybridised on inflammation DualChip microarray. The expression ratio of 282 inflammatory genes between CNT and ERA patients, before (T0) and after 12 weeks (T1) of combined therapy was detected. qRT-PCR was performed on 7 selected inflammatory RA-related genes (STAT4, MAPK9, HIF1A, MIF, STAT6, NFKB1, TNFRSF1B). RESULTS: At T0, microarray analysis showed 34 altered genes in both ERA groups when compared to CNT (vs. CNT). Seven RA-related genes, investigated in further details, were found up-regulated in group 1 and down-regulated or unchanged in group 2 vs. CNT. At T1, combined therapy induced the down-regulation of these genes in both groups vs. CNT as also confirmed by qRT-PCR performed on selected genes. CONCLUSIONS: Untreated ERA patients seem characterised by up-regulation of specific genes involved both in the resistance/inhibition to apoptosis and in the stimulation of pro-inflammatory cytokine production by immune inflammatory cells. Combined LEF and low dose of prednisone therapy seems to play synergistic effects on down-regulation of these genes.
22539479 Two-year direct and indirect costs for patients with inflammatory rheumatic joint diseases 2012 Sep OBJECTIVE: The overall aim of this study was to estimate the total costs for patients with RA, AS and psoriatic arthritis (PsA) treated with DMARDs. Specific aims were to compare the costs across diagnoses and over time. METHODS: The main data source was the Norwegian DMARD register (NOR-DMARD) that captures outcomes and resource use among patients starting therapy with synthetic and biologic DMARDs. Costs were estimated for four 6-month periods from the start of a DMARD regimen. We included RA (n=1152), AS (n=186) and PsA (n=374) patients with available 2-year data. Direct costs included pharmaceuticals, imaging examinations, in-hospital and out-hospital care, stays in rehabilitation units and visits to general practitioners, private rheumatologists and physiotherapists. Indirect cost included patients' work absenteeism. Differences in costs across diagnoses were tested by Kruskal-Wallis equality-of-populations rank test and changes in costs between first and fourth 6-month periods were tested by paired t-tests. RESULTS: Total 2-year costs were similar across diagnoses for patients on synthetic treatment (RA/AS/PsA €64,300/63,200/64,500) and on biologic treatment (€121,900/115,319/111,200). The largest cost component was productivity loss. Total costs decreased significantly from the first to the fourth 6-month periods for all diagnoses, and this decrease was influenced by reductions both in direct and indirect costs. CONCLUSION: Total costs were similar across the main inflammatory rheumatic diseases. Biologic DMARD treatment entails considerable drug cost, but the total costs decline during the first 2 years on treatment in both RA, AS and PsA.