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ID PMID Title PublicationDate abstract
20533539 Increased prevalence of M694V in patients with ankylosing spondylitis: additional evidence 2010 Oct OBJECTIVE: To assess whether there is a statistically significant difference in the frequency of common MEFV allele variants in patients with ankylosing spondylitis (AS) as compared with control patients with rheumatoid arthritis (RA) and with healthy control subjects. METHODS: Sixty-two patients with AS, 50 healthy control subjects, and 46 patients with RA were assessed for the presence of MEFV variants. Exon 10 was analyzed by direct sequencing. E148Q was analyzed by restriction endonuclease enzyme digestion (REED) or by direct sequencing when REED analysis failed. RESULTS: The allele frequency of all MEFV variants in the AS group was significantly higher than that in the pooled control group of healthy subjects plus RA patients (15.3% versus 6.8%; P = 0.021). M694V was the only variant that was significantly more common in the AS group than in the combined or individual control groups (P = 0.026 for AS patients versus healthy controls, P = 0.046 for AS patients versus RA patient controls, and P = 0.008 for AS patients versus healthy and RA patient control groups). The carriage rate of M694V was also significantly higher in the AS patient group than in the combined control group (odds ratio 7.0, P = 0.014). Neither M694V nor any other MEFV variant showed a correlation with most of the disease-related measures examined. CONCLUSION: We found an increased frequency of MEFV variants in AS patients as compared with healthy controls and with RA patient controls. This was primarily due to the presence of M694V. The roles of other exon 10 variants, as well as the relationship between the variant status and the severity and clinical course of the disease, need to be explored in further studies that include sufficiently large sample sizes.
19531936 Ramipril-induced generalized pustular psoriasis: case report and literature review. 2010 Jan Mrs. M.S. is a 67-year-old African American woman with a history of rheumatoid arthritis and psoriatic arthritis who presented to the emergency room with complaint of new-onset rash, chills, and fatigue after she started taking ramipril (5 mg orally every day) for her hypertension. The rash involved entire upper chest, both arms, palms, and soles and was characterized as exfoliating with scattered small pustules of 1-2 mm in size. Patient was admitted with a differential diagnosis of exfoliative dermatitis versus adverse drug reaction for which her ramipril was stopped. After admission, the patient spiked a temperature of 102 degrees F with chills, the entire workup for which was negative, including blood cultures, chest x-ray, and urine analysis. She underwent skin biopsy to find the cause of her rash. With her given clinical characteristics, she was presumed to have generalized pustular psoriasis (GPP), which was later confirmed by biopsy results. She was treated with methylprednisolone to which she responded dramatically with much improvement in her rash and her fever subsided. The flare of GPP was considered to be secondary to ramipril. After reviewing the published literature, there are no published cases of ramipril-induced GPP. Captopril, a different angiotensin converting enzyme (ACE) inhibitor, is known to cause flare of GPP. We presented this case as apart from being the first reported case of ramipril-induced GPP; clinicians and dermatologist should also be aware of this potentially serious complication of psoriasis when they start ramipril in patients with psoriasis.
19731624 Bone formation versus bone resorption in ankylosing spondylitis. 2009 Ankylosing spondylitis (AS) and other forms of seronegative spondylarthritis (SpA) are characterized by two major processes in joints-the first is chronic inflammation and the second is progressive ankylosis. Both features go hand-in-hand and determine the clinical picture of disease, which is joint pain, progressive stiffness and, in case ofperipheral joint involvement also joint swelling. The interplay between inflammation and ankylosis is best illustrated in AS, where chronic inflammation of the spine leads to progressive stiffness, reduced spinal mobility and kyphosis. AS may thus be considered as a synthesis of inflammatory disease and bone disease.
19455337 The effect of infliximab on antiviral antibody profiles in patients with rheumatoid arthri 2010 Jan The duration of humoral immunity in patients treated with immunosuppressive drugs is poorly defined. The objective of the study was to investigate the effect of infliximab on the levels of antiviral antibodies against poliomyelitis, rubella and measles in rheumatoid arthritis (RA) patients. Fifty-two consecutive RA patients being treated with 3 mg/kg infliximab were prospectively studied. The antiviral antibody profiles for measles, rubella and three serotypes of poliomyelitis were tested on the day of the first infusion of infliximab and 6 months later. The study group comprised 36 women and 16 men (mean age 54 years, range 33-81) with a mean disease duration of 15 +/- 9 years. Forty-two (81%) patients were being treated with methotrexate and 22 (42%) were receiving prednisone. All patients had baseline protective levels of antibodies against measles and the three strains of polio, while 48 (92%) patients had protective antibodies against rubella. No significant change in the levels of antiviral antibodies was observed after 6 months of treatment with infliximab: from 3.67 at baseline to 3.87 IU/ml for measles, 169.50-197.0 IU/ml for rubella. No change was noticed for the geometric mean concentrations of antibodies against strains of poliomyelitis: 366-478 IU/ml for the Mahoney polio strain, 906-845 IU/ml for the MEF strain and 175-196 IU/ml for the Sauket strain. Patients with longstanding RA conserve long-term immunity to common viruses despite the use of immunosuppressive drugs. Levels of antiviral antibodies against measles, rubella and polio remain stable under treatment with infliximab.
19292917 Analysis of TNFAIP3, a feedback inhibitor of nuclear factor-kappaB and the neighbor interg 2009 INTRODUCTION: Genome-wide association studies of rheumatoid arthritis (RA) have identified an association of the disease with a 6q23 region devoid of genes. TNFAIP3, an RA candidate gene, flanks this region, and polymorphisms in both the TNFAIP3 gene and the intergenic region are associated with systemic lupus erythematosus. We hypothesized that there is a similar association with RA, including polymorphisms in TNFAIP3 and the intergenic region. METHODS: To test this hypothesis, we selected tag-single nucleotide polymorphisms (SNPs) in both loci. They were analyzed in 1,651 patients with RA and 1,619 control individuals of Spanish ancestry. RESULTS: Weak evidence of association was found both in the 6q23 intergenic region and in the TNFAIP3 locus. The rs582757 SNP and a common haplotype in the TNFAIP3 locus exhibited association with RA. In the intergenic region, two SNPs were associated, namely rs609438 and rs13207033. The latter was only associated in patients with anti-citrullinated peptide antibodies. Overall, statistical association was best explained by the interdependent contribution of SNPs from the two loci TNFAIP3 and the 6q23 intergenic region. CONCLUSIONS: Our data are consistent with the hypothesis that several RA genetic factors exist in the 6q23 region, including polymorphisms in the TNFAIP3 gene, like that previously described for systemic lupus erythematosus.
19416802 Which subgroup of patients with rheumatoid arthritis benefits from switching to rituximab 2010 Feb BACKGROUND: Patients with rheumatoid arthritis (RA) with an inadequate response to TNF antagonists (aTNFs) may switch to an alternative aTNF or start treatment from a different class of drugs, such as rituximab (RTX). It remains unclear in which clinical settings these therapeutic strategies offer most benefit. OBJECTIVE: To analyse the effectiveness of RTX versus alternative aTNFs on RA disease activity in different subgroups of patients. METHODS: A prospective cohort study of patients with RA who discontinued at least one aTNF and subsequently received either RTX or an alternative aTNF, nested within the Swiss RA registry (SCQM-RA) was carried out. The primary outcome, longitudinal improvement in 28-joint count Disease Activity Score (DAS28), was analysed using multivariate regression models for longitudinal data and adjusted for potential confounders. RESULTS: Of the 318 patients with RA included; 155 received RTX and 163 received an alternative aTNF. The relative benefit of RTX varied with the type of prior aTNF failure: when the motive for switching was ineffectiveness to previous aTNFs, the longitudinal improvement in DAS28 was significantly better with RTX than with an alternative aTNF (p = 0.03; at 6 months, -1.34 (95% CI -1.54 to -1.15) vs -0.93 (95% CI -1.28 to -0.59), respectively). When the motive for switching was other causes, the longitudinal improvement in DAS28 was similar for RTX and alternative aTNFs (p = 0.40). These results were not significantly modified by the number of previous aTNF failures, the type of aTNF switches, or the presence of co-treatment with a disease-modifying antirheumatic drug. CONCLUSION: This observational study suggests that in patients with RA who have stopped a previous aTNF treatment because of ineffectiveness changing to RTX is more effective than switching to an alternative aTNF.
20390115 [Health-related quality of life in patients with rheumatoid arthritis: assessment by a Ita 2010 Jan The research carried out by Censis Foundation, in collaboration with SIR (Italian Society of Rheumatology) and ANMAR (National association of rheumatic patients) involved 646 patients, diagnosed with rheumatoid arthritis (RA) by a rheumatologist according to ACR criteria. The patients were recruited through a representative sample of 300 general practitioners (GP). A cross-sectional survey was conducted to study the current status of health-related quality of life (HRQL) of patients using a revised Italian version of a revised version of the Arthritis Impact Measurement Scales 2 (AIMS2). The AIMS2 was administered to the 646 patients with (RA) attending arthritis clinics at various hospitals across the country. Self-report functional disability scores were calculated for all 12 specific scales, summary components, and overall impact measures. The AIMS2 has been validated for the Italian language. Ranging from 0 (perfect health) to 10 (poor health), the mean scores of the AIMS2 showed an important impact of the disease on the 4 components of the health status of these patients: walking and bending, mean score = 5.1; nervous tension = 5.0, arthritis pain = 5.0, and social activity = 4.6. Among other dimensions, the impact of RA was moderate for mood, work, hand and finger function and mobility (mean score: 3.7, 3.7, 3.5 and 3.4, respectively) and low for household tasks, arm function, self-care tasks and family support (3.0, 2.9, 2.5 and 2.1, respectively). There was a tendency for the scores of younger patients to be better than those of olders patients. In conclusion, RA have a clearly detrimental effect on the HRQL in both physical and mental components. Prevention and management of physical disability should be seriously planned in consideration of the changes in these conditions in RA patients. Use of the AIMS2 makes it easier and less costly to collect data and reduces the burden on RA patients.
19594416 TNF alpha inhibition as treatment modality for certain rheumatologic and gastrointestinal 2009 Sep With the development of biologicals that specifically target tumor necrosis factor (TNF)alpha, our therapeutic approach to inflammatory diseases has dramatically changed. There are currently three anti-TNFalpha drugs available: etanercept, infliximab, and adalimumab. Etanercept is a recombinant fusion protein that can be used alone or in combination with other medications for conditions such as rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, psoriasis, and ankylosing spondylitis. Infliximab, a chimeric humanized monoclonal antibody and adalimumab, a fully human monoclonal antibody are approved for the treatment of rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, and moderate to severe Crohn's disease. Infliximab is also approved for ulcerative colitis. Another anti-TNFalpha drug, certolizumab pegol, was declined approval as treatment option for active Crohn's disease due to a lack of sufficient efficacy. Phase III studies for the treatment of rheumatoid arthritis patients are still pending. It is the goal of this review article to summarize various therapeutic indications, underlying studies, safety, and use during pregnancy, as well as future directions for anti-TNF therapies.
20440529 Etanercept can induce resolution of renal deterioration in patients with amyloid A amyloid 2010 Dec The benefit of biological therapies in rheumatoid arthritis (RA) treatment is well known, but their role in amyloid A (AA) amyloidosis secondary to RA is unclear. The aim of this study was to clarify the clinical benefit of etanercept in RA patients with AA amyloidosis. We treated 14 RA patients who had serum amyloid A protein (SAA) 1.3 allele, with biopsy-confirmed AA amyloidosis with etanercept and investigated the efficacy of etanercept treatment, focusing on renal function retrospectively. The AA amyloidosis improved and stabilized after 89.1 ± 27.2 weeks. Proteinuria decreased from 2.24 ± 0.81 to 0.57 ± 0.41 g/day (P < 0.01) and SAA fell from 250 ± 129 to 26 ± 15 μg/ml (P < 0.01), respectively. Diarrhea secondary to gastrointestinal AA amyloidosis was less. Overall, the serum creatinine levels did not benefit with treatment, but in those with a creatinine values <2.0 mg/dl the creatinine level continued to fall (P = 0.021). Serum albumin increased following 96 weeks of etanercept treatment (P = 0.003). Etanercept treatment led to clinical improvement in proteinuria and serum albumin levels accompanied by a fall in SAA levels.
20695769 Potent antirheumatic activity of a new DNA vaccine targeted to B7-2/CD28 costimulatory sig 2011 Jan Rheumatoid arthritis is a proinflammatory autoimmune disease attributed to failure of both CD4(+)CD25(+) regulatory T (Tr) and CD8(+)CD28(-) suppressor T (Ts) cells to control autoreactive CD4(+)CD28(+) Th1 (Th1) and autoantibody-producing B cells. Here we show a single intramuscular injection of our novel targeted DNA vaccine encoding Pseudomonas exotoxin A and costimulatory molecule B7-2 without autoantigens in a collagen-induced arthritis model simultaneously increased Tr and Ts cells and selectively decreased autoreactive Th1 cells. The vaccine induced a shift from Th1 to Th2 and Th3 cellular and cytokine profiles and a decrease in CD4(+)/CD8(+) cell ratios. Importantly, the vaccine showed potent antirheumatic activity by clinical and other examinations such as X-ray, histopathology, and anti-type II collagen IgG levels and was comparable to methotrexate, the current "gold standard" treatment. As an effective stimulator of both Tr and Ts cells and a specific suppressor of autoreactive Th1 cells, this vaccine is a promising therapeutic approach for rheumatoid arthritis.
18534538 Rotational kinematics of a modern fixed-bearing posterior stabilized total knee arthroplas 2009 Jun The purpose of this study was to evaluate the rotational kinematics of a fixed-bearing posteriorly stabilized total knee design in moderate and deep flexion. Three-dimensional kinematics analyses were conducted on 20 knees in 4 weight-bearing positions using 3-dimensional shape-matching techniques. Average maximum skeletal flexion was 138 degrees . Internal tibial rotation was demonstrated in 19 of 20 knees. The average internal tibial rotation in midflexed lunge was 5.5 degrees (-3.8 degrees to 14.1 degrees ) and in maximum flexion kneeling was 4.0 degrees (-3.1 degrees to 10.6 degrees ). Separation of articular surfaces was not identified. In this study, patients with this device demonstrated patterns of rotation similar to those previously reported for both the normal knee and rotating platform designs.
19594033 [Preliminary clinical outcome of domestic posterior-stabilized total knee arthroplasty]. 2009 Jun OBJECTIVE: Total knee arthroplasty (TKA) has been widely used in China. More and more attentions are paid to the development of knee prosthesis that fit for the anatomy of Chinese knee. This study is to summarize the surgical techniques and clinical outcome of domestic posterior-stabilized total knee arthroplasty. METHODS: Fifty-one patients including 19 males and 32 females underwent TKA by using TC-Dynamic from Jan. 2003 to Dec. 2004 were reviewed. The average age at the time of operation was (76.4 +/- 4.1) years (range, 71 to 84 years). Thirty-seven patients suffered from osteoarthritis and 14 patients were rheumatism arthritis. The courses of the disease ranged from 5 to 40 years and the symptoms were pain and limitation of motion. The knee rating score system (HSS) as well as X-rays of the lower extremity was used to evaluate the clinical results. RESULTS: All patients were followed up at the 3rd month after TKA and the duration of follow-up of 32 patients ranged from 48 to 61 months. The HSS scores before TKA was (53.3 +/- 6.7) (40 to 59) points. At the 3rd month and 48th month of follow-up, the HSS scores were (86.1 +/- 7.7) (63 to 95) and (83.5 +/- 8.1) (60 to 95) points respectively. The stress X-rays showed preoperative varus deformities from 9 degrees to 30 degrees with the average of (21.0 +/- 5.8) degrees and normal alignment of the lower extremities postoperative. There were no complications related to TC-Dynamic prosthesis and other complications such as infection, prosthetic loosening and dislocation of patella. CONCLUSION: There is a good mid-term clinical result of TC-Dynamic knee system, which is designed according to anatomical characteristic of Chinese knee joint. More attention should be paid to this knee system about the long term follow-up.
21794777 [Consensus on the Use of Rituximab in Rheumatoid Arthritis. A document with evidence-based 2011 Jan INTRODUCTION: Rituximab has been employed successfully for the treatment of Rheumatoid Arthritis (RA). However, its particular mechanism of action, as well as a lack of concrete guidelines for its management have generated doubts on its use. OBJECTIVE: To establish recommendations that facilitates the use of rituximab in common clinical practice. METHODS: In a first Delphi round, 9 expert rheumatologists got together to develop questions on those subjects generating most doubts on the efficacy and safety of the drug. These were adapted to perform a systematic review of the evidence, which was presented in a second meeting. Nominal groups were formed to respond to each question and give a recommendation. These recommendations were presented in a second Delphi round to a larger group of experts in rheumatology. Once again recommendations were discussed, modified and voted upon. Once approved, a vote on the degree of agreement for each recommendation was carried out. RESULTS: 17 recommendations were established, 10 regarding efficacy and 7 safety. All of the efficacy recommendations except 3 presented a good or moderate degree of evidence. Among the safety recommendations, 3 had a good or moderate degree of evidence while in the rest it was indirect, scarce or non-existent and a product of expert recommendation. The degree of agreement between experts was elevated for most of the recommendations. CONCLUSIONS: These recommendations attempt to clear doubts on the use of rituximab and establish guidelines for its use in daily practice. Efficacy recommendations have a high degree of evidence, allowing the clinician to be guided in therapeutic decisions. Safety recommendations have a lower degree of evidence.
19446156 Differences in annual medication costs and rates of dosage increase between tumor necrosis 2009 Apr BACKGROUND: Tumor necrosis factor (TNF) antagonists are commonly used to treat rheumatoid arthritis (RA). Differences in the dosage and mode of administration of these agents may result in differential rates of dosage adjustment and costs of care. OBJECTIVE: This study compared dosing patterns and annual costs associated with the use of the subcutaneous TNF antagonists adalimumab and etanercept, and the intravenous TNF antagonist infliximab. METHODS: A large managed care database (PharMetrics) was used to identify patients with RA who newly initiated TNF-antagonist therapy with adalimumab, etanercept, or infliximab on or after January 1, 2003, and had at least 6 months of continuous health plan enrollment before initiation of therapy and 12 months of continuous enrollment after initiation. The patients were followed over 12 months of enrollment. Annual pharmacy, inpatient, and outpatient costs were estimated based on plan reimbursements and were compared between cohorts. The average daily dosage (ADD) between prescription refills was used to compare the percentages of patients with greater-than-expected dosing (GTED), defined as 2 consecutive increases in ADD relative to the patient's established maintenance dosage. RESULTS: A total of 2382 patients (568 adalimumab, 1181 etanercept, 633 infliximab) were included in the analysis. Significantly more patients had GTED with infliximab compared with adalimumab and etanercept (32.1%, 8.5%, and 4.7%, respectively; both comparisons, P < 0.05). For patients with a dosage increase, the mean time to the first GTED was significantly shorter for infliximab compared with adalimu-mab and etanercept (154.5, 173.3, and 167.9 days; both, P < 0.05). The mean annual costs of anti-TNF therapy, adjusted for baseline differences, were significantly greater for infliximab compared with adalimumab and etanercept ($15,617, $12,200, and $12,146; both, P < 0.05). There were also significant differences between infliximab relative to adalimumab and etanercept in total RA-related medication costs ($16,280, $12,989, and $12,794; P < 0.05) and total pharmacy costs ($17,854, $14,805, and $14,398; P < 0.05). CONCLUSION: Patients initiating TNF-antagonist treatment for RA with infliximab incurred annual medication costs that were nearly 30% greater than costs in those initiating therapy with adalimumab or etanercept, in part because of the significantly greater rate of GTED in infliximab recipients.
20726965 Tests for compositional epistasis under single interaction-parameter models. 2011 Jan Compositional epistasis is said to be present when the effect of a genetic factor at one locus is masked by a variant at another locus. Although such compositional epistasis is not equivalent to the presence of an interaction in a statistical model, non-standard tests can sometimes be used to detect compositional epistasis. In this paper we consider empirical tests for compositional epistasis under models for the joint effect of two genetic factors which place no restrictions on the main effects of each factor but constrain the interactive effects of the two factors so as to be captured by a single parameter in the model. We describe the implications of these tests for cohort, case-control, case-only and family-based study designs and we illustrate the methods using an example of gene-gene interaction already reported in the literature.
19553874 Recent research in stress, coping and women's health. 2009 Mar PURPOSE OF REVIEW: To highlight recent publications in the area of stress and coping, with specific reference to women's physical health status. RECENT FINDINGS: The transactional model of stress and coping continues to be the mainstay of research in this area. Several longitudinal studies have demonstrated that stress appraisal and resultant coping responses affect health outcome and health-related quality of life in women. In addition to problem-focused coping, women often use distraction methods, seeking social support and faith or religious coping. Psychological interventions in chronic medical conditions need to move beyond education and incorporate more cognitive behavioral components, at the same time addressing women's specific needs. SUMMARY: Coping behaviors in response to the negative threat appraisal of a chronic or severe medical illness serve to reduce psychological distress. However, it is still not clear how they impact at the physiological level. In addition, coping responses, which enhance positive effects and promote health-related quality of life, merit greater attention from researchers. There is a need for more gender comparative research to improve health outcomes in men and women.
20483040 Genome-wide analysis of histone H3 lysine 4 trimethylation by ChIP-chip in peripheral bloo 2010 Mar OBJECTIVES: Histone H3 lysine 4 trimethylation(H3K4me3) is an important epigenetic modification and associated with active transcription in multiple organisms. In systemic lupus erythematosus (SLE), global and gene-specific DNA methylation changes have been demonstrated to occur. However, to date, our knowledge about the alterations in the histone lysine methylation in SLE is known little. This study aimed to investigate the variations in H3K4me3 in CpG island regions in the peripheral blood mononuclear cells (PBMCs) of SLE patients and the controls, including rheumatoid arthritis patients and healthy subjects. METHODS: PBMCs were isolated by density gradient centrifugation from 10 active SLE patients, 7 inactive SLE patients, 8 rheumatoid arthritis patients and 8 healthy volunteers. H3K4me3 variations were analysed by using chromatin immunoprecipitation linked to the microarray (ChIP-chip) approach. ChIP-real time PCR was used to validate the microrray results. Expression analysis by qRT-PCR revealed correlations between mRNA and H3K4me3 levels. In addition, DNA methylation status was also further analysed by Methyl-DNA immunoprecipitation-quantitative PCR. RESULTS: Many key relevant candidate genes (such as PTPN22, LRP1B etc.) displaying differential changes in H3K4me3 in SLE versus controls (rheumatoid arthritis patients, healthy subjects) were identified. The results of ChIP-real time PCR were coincided well with those of microarray. Aberrant DNA methylation can also be found on selected randomly positive genes (WDR5, SLC24A3, PTPN22, LRP1B METT10D and CDH13). CONCLUSIONS: Our results first indicate that there are significant alterations of H3K4me3 in PBMCs of SLE patients, and H3K4me3 alterations are associated with the pathogenesis of the SLE. Such novel findings show the significance of H3K4me3 as a potential biomarker or promising target for epigenetic-based lupus therapies.
19790066 Normalization of A2A and A3 adenosine receptor up-regulation in rheumatoid arthritis patie 2009 Oct OBJECTIVE: To investigate A(1), A(2A), A(2B), and A(3) adenosine receptors in lymphocytes and neutrophils from patients with early rheumatoid arthritis (ERA) as well as from RA patients treated with methotrexate (MTX) or anti-tumor necrosis factor alpha (anti-TNFalpha), as compared with those in age-matched healthy controls, and to examine correlations between the status and functionality of adenosine receptors and TNFalpha release and NF-kappaB activation. METHODS: Adenosine receptors were analyzed by saturation binding assays and Western blot analyses. We investigated the potency of typical A(2A) and A(3) agonists in the production of cAMP in control subjects, ERA patients, and RA patients treated with MTX or anti-TNFalpha. In a separate cohort of RA patients, TNFalpha release and NF-kappaB activation were evaluated in plasma and nuclear extracts, respectively. RESULTS: In ERA patients, we found a high density and altered functionality of A(2A) and A(3) receptors. The binding and functional parameters of A(2A) and A(3) receptors normalized after anti-TNFalpha, but not MTX, treatment. TNFalpha release was increased in ERA patients and in MTX-treated RA patients, whereas in anti-TNFalpha-treated RA patients, release was comparable to that in the controls. NF-kappaB activation was elevated in ERA patients and in MTX-treated RA patients. Anti-TNFalpha treatment mediated decreased levels of NF-kappaB activation. CONCLUSION: A(2A) and A(3) receptor up-regulation in ERA patients and in MTX-treated RA patients was associated with high levels of TNFalpha and NF-kappaB activation. Treatment with anti-TNFalpha normalized A(2A) and A(3) receptor expression and functionality. This new evidence of A(2A) and A(3) receptor involvement opens the possibility of exploiting their potential role in human diseases characterized by a marked inflammatory component.
21149498 Predictors of response to methotrexate in early DMARD naive rheumatoid arthritis: results 2011 Mar OBJECTIVE: To identify predictors of response to methotrexate (MTX) in early rheumatoid arthritis (RA). METHODS: In the SWEFOT trial, patients with RA with symptom duration <1 year started MTX monotherapy (20 mg/weekly) and 405/487 continued until the 3-4- month visit. The primary outcome measure was the DAS28-based European League against Rheumatism (EULAR) response criteria. Multivariate logistic regression was used to study the association between response and the following baseline characteristics: gender, age, symptom duration, cigarette smoking habits, autoantibody status, Health Assessment Questionnaire (HAQ) score, concurrent prednisolone and treatment with non-steroidal anti-inflammatory drugs. Secondary response and remission measures were the American College of Rheumatology and the Simple Disease Activity Index and Clinical Disease Activity Index (SDAI/CDAI)-derived criteria. RESULTS: After 3-4 months of MTX treatment, the frequency of EULAR good/moderate/no response was 34%/41%/25%, respectively. Parameters associated with a decreased likelihood of EULAR response were female gender (adjusted OR (adj OR) 0.50, 95% CI 0.31 to 0.81), symptom duration (adj OR per month increase 0.93, 95% CI 0.88 to 0.99), current smoking (adj OR 0.35, 95% CI 0.20 to 0.63) and higher HAQ (adj OR 0.56, 95% CI 0.40 to 0.80). Parameters associated with an increased likelihood of EULAR response were higher age (adj OR per 10-year increase 1.30, 95% CI 1.11 to 1.51) and prednisolone treatment (adj OR 2.84, 95% CI 1.43 to 5.63). The findings were similar when patients on prednisolone were excluded and other response criteria tested, although current smoking was the only significant predictor using all response criteria, while HAQ was the only significant predictor of all the remission criteria used. A matrix showed up to ninefold differences between subgroups stratified by the main predictors. CONCLUSION: Current smoking, female sex, longer symptom duration and younger age predict a worse response to MTX in patients with new-onset RA. TrialRegNo NCT00764725.
20614469 Tocilizumab for rheumatoid arthritis. 2010 Jul 7 BACKGROUND: Tocilizumab, a new biologic that inhibits interleukin-6, is approved for treatment of rheumatoid arthritis (RA) in Europe, Japan and the US. OBJECTIVES: To assess the efficacy and safety of tocilizumab in patients with RA using the data from published randomized or quasi-randomized controlled trials (RCTs). SEARCH STRATEGY: We performed a search of the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) up to issue 3, 2009; OVID MEDLINE(1966 to 1 October 2009); CINAHL(1982 to 2009); EMBASE (1980 to week 39, 2009); Science Citation Index (Web of Science) (1945 to 2009) and Current Controlled Trials. SELECTION CRITERIA: Tocilizumab alone or in combination with disease-modifying anti-rheumatic drugs (DMARDs) or biologics compared to placebo or other DMARDs or biologics. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted all data including major (ACR50, adverse events, serious adverse events, withdrawals, specific adverse events) and secondary outcomes. We calculated the risk ratio for dichotomous outcomes and mean difference for continuous outcomes. MAIN RESULTS: Eight RCTs were included in this systematic review with 3334 participants; 2233 treated with tocilizumab and 1101 controls. Of the 2233, 1561 were treated with tocilizumab 8 mg/kg every four weeks, which is the approved dose. In patients taking concomitant methotrexate, compared to placebo, tocilizumab-treated patients were four times more likely to achieve ACR50 (absolute %, 38.8% versus 9.6%), 11 times more likely to achieve Disease Activity Score (DAS) remission (absolute %, 30.5% versus 2.7%), 1.8 times more likely to achieve clinically meaningful decrease in Health Assessment Questionnaire (HAQ/mHAQ) scores (absolute %, 60.5% versus 34%), 1.2 times more likely to have any adverse event (absolute %, 74% versus 65%) and 0.6 times less likely to withdraw from therapy for any reason (absolute %, 8.1% versus 14.9%). With the limitation that none of the studies were powered for safety as primary outcome, there were no statistically significant differences in serious adverse effects, or withdrawals due to adverse events. A significant increase in total, HDL and LDL cholesterol and triglyceride level was seen in the tocilizumab treated patients. AUTHORS' CONCLUSIONS: Tocilizumab is beneficial in decreasing RA disease activity and improving function. Tocilizumab treatment was associated with significant increase in cholesterol levels and in total adverse events. Larger safety studies are needed to address these safety concerns.