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ID PMID Title PublicationDate abstract
22337160 Use of health insurance claim patterns to identify patients using nonsteroidal anti-inflam 2012 Jun PURPOSE: To determine healthcare claim patterns associated using nonsteroidal anti-inflammatory drugs (NSAIDs) for rheumatoid arthritis (RA). METHODS: The CADEUS study randomly identified NSAID users within the French health insurance database. One-year claims data were extracted, and NSAID indication was obtained from prescribers. Logistic regression was used in a development sample to identify claim patterns predictive of RA and models applied to a validation sample. Analyses were stratified on the dispensation of immunosuppressive agents or specific antirheumatism treatment, and the area under the receiver operating characteristic curve was used to estimate discriminant power. RESULTS: NSAID indication was provided for 26,259 of the 45,217 patients included in the CADEUS cohort; it was RA for 956 patients. Two models were constructed using the development sample (n = 13,143), stratifying on the dispensation of an immunosuppressive agent or specific antirheumatism treatment. Discriminant power was high for both models (AUC > 0.80) and was not statistically different from that found when applied to the validation sample (n = 13,116). CONCLUSIONS: The models derived from this study may help to identify patients prescribed NSAIDs who are likely to have RA in claims databases without medical data such as treatment indication.
21285161 Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modi 2011 Jun OBJECTIVE: To develop a fibromyalgia (FM) survey questionnaire for epidemiologic and clinical studies using a modification of the 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia (ACR 2010). We also created a new FM symptom scale to further characterize FM severity. METHODS: The ACR 2010 consists of 2 scales, the Widespread Pain Index (WPI) and the Symptom Severity (SS) scale. We modified these ACR 2010 criteria by eliminating the physician's estimate of the extent of somatic symptoms and substituting the sum of 3 specific self-reported symptoms. We also created a 0-31 FM Symptom scale (FS) by adding the WPI to the modified SS scale. We administered the questionnaire to 729 patients previously diagnosed with FM, 845 with osteoarthritis (OA) or with other noninflammatory rheumatic conditions, 439 with systemic lupus erythematosus (SLE), and 5210 with rheumatoid arthritis (RA). RESULTS: The modified ACR 2010 criteria were satisfied by 60% with a prior diagnosis of FM, 21.1% with RA, 16.8% with OA, and 36.7% with SLE. The criteria properly identified diagnostic groups based on FM severity variables. An FS score ≥ 13 best separated criteria+ and criteria- patients, classifying 93.0% correctly, with a sensitivity of 96.6% and a specificity of 91.8% in the study population. CONCLUSION: A modification to the ACR 2010 criteria will allow their use in epidemiologic and clinical studies without the requirement for an examiner. The criteria are simple to use and administer, but they are not to be used for self-diagnosis. The FS may have wide utility beyond the bounds of FM, including substitution for widespread pain in epidemiological studies.
21345288 Lack of association between RETN rs1862513 polymorphism and cardiovascular disease in rheu 2011 Jan OBJECTIVES: To assess the influence of the RETN rs1862513 polymorphism in the risk of cardiovascular (CV) disease and subclinical atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: Six hundred and sixty-eight patients fulfilling the 1987 American College of Rheumatology classification criteria for RA, seen at the rheumatology outpatient clinics of Hospital Xeral-Calde, Lugo, and Hospital San Carlos, Madrid, Spain, were studied. Patients were genotyped for the RETN rs1862513 polymorphism using predesigned TaqMan single nucleotide polymorphism genotyping assay. Also, HLA-DRB1 genotyping was performed using molecular based methods. Carotid intima-media thickness (IMT), flow-mediated endothelium-dependent and endothelium independent vasodilatation, used as surrogate markers of subclinical atherosclerosis, were measured in a subgroup of patients. RESULTS: No significant differences in the genotypic or in the allelic distribution between RA patients with or without CV disease were found. In this regard, we only observed a slight increased frequency of homozygous and heterozygous for the minor allele G (CG+GG genotypes) among patients who experienced CV events compared to those without CV events (53.04% vs. 52.62%, p=0.94). A higher frequency of classic CV risk factors was observed among the carriers of the minor allele G. However, in the adjusted logistic regression model no association between the RETN variant and CV disease was found (p=0.50). Also, when surrogate markers of subclinical atherosclerosis were assessed, in the adjusted ANCOVA model only a trend towards a higher carotid IMT was found among allele G carriers (p=0.06). CONCLUSIONS: RETN rs1862513 polymorphism does not seem to be a genetic risk factor for both clinically evident CV disease and subclinical atherosclerosis in patients with RA.
20401725 Association analysis of TNFR2, VDR, A2M, GSTT1, GSTM1, and ACE genes with rheumatoid arthr 2011 Oct Genetic associations of TNFR2, VDR (Bsm I and Fok I), A2M, GSTT(1), GSTM(1) and ACE in South Asian and Caucasian patients with rheumatoid arthritis (RA) were assessed in this study. DNA samples from South Asians (134 cases, 149 controls) and Caucasians (137 cases, 150 controls) from the East Midlands of the United Kingdom were genotyped for seven polymorphisms. All cases were rheumatoid-factor positive. Significant genetic associations were observed with TNFR2 R-R (OR = 3.16, CI 1.20-9.26, P < 0.05), A2M 1-1 (OR = 2.09, CI 1.21-3.64, P < 0.05) and GST T(1)null (OR = 1.97, CI 1.07-3.68, P < 0.05) among Caucasian patients. In South Asians, VDR Bsm I B-B genotype (OR = 2.08, CI 1.23-3.52, P < 0.05), A2M 2-2 genotype (OR = 3.99, CI 1.19-17.18, P < 0.05), and GST T(1)null genotype (OR = 2.81, CI 1.40-5.77, P < 0.002) genotypes were associated with RA. In the majority of cases, recessive and multiplicative modes of inheritance explained the observed associations. This study demonstrates that ethnicity affects the genetic associations in RA.
22539481 Quality assurance study of the use of preventative therapies in glucocorticoid-induced ost 2012 Sep OBJECTIVE: To characterize steroid use and compliance with glucocorticoid-induced osteoporosis (GIOP) guidelines within a large early inflammatory arthritis cohort. METHODS: Using the Canadian Early Arthritis Cohort (CATCH) database, patients with inflammatory arthritis on glucocorticoids (oral, IA and i.m.) were identified. Consecutive steroid exposure was defined as using glucocorticoids for two consecutive clinic visits (at least 90 days apart). The primary outcome was the proportion of patients receiving calcium, vitamin D and a bisphosphonate among patients treated with consecutive oral glucocorticoids. RESULTS: Six hundred and fifty-five patients were in the CATCH database, where 273 patients were identified as glucocorticoid users, of whom 48% were on oral prednisone, 38% received i.m. or IA and 13% both. The median oral daily dose of prednisone was 5 mg (interquartile range 2.5-10). Consecutive users (CUs, n = 78) compared with non-consecutive users (NUs, n = 532) showed that CUs were older (56 vs 50 years, P = 0.001); females were fewer (63% vs 74%, P = 0.04), but a similar proportion were RF positive (51% in CU vs 56% in NU, P = 0.73). For the primary outcome, rates of prophylaxis for users of consecutive oral steroids were as follows: 53% were treated with calcium, 47% with vitamin D and 25% were on a bisphosphonate. For users of oral prednisone at doses ≥7.5 mg/day, rates of prophylaxis were as follows: 64% were treated with calcium, 57% with vitamin D and 21% were on a bisphosphonate. CONCLUSION: Glucocorticoid therapy is frequently used in early inflammatory arthritis. The use of calcium, vitamin D or a bisphosphonate was low among chronic glucocorticoid users and illustrates the need for more diligence in patients receiving glucocorticoids to prevent GIOP.
21979468 Inflammatory synovial fluid microenvironment drives primary human chondrocytes to actively 2012 Jun The role of human chondrocytes in the pathogenesis of cartilage degradation in rheumatic joint diseases has presently gained increasing interest. An active chondrocyte participation in local inflammation may play a role in the initiation and progression of inflammatory joint diseases and in a disruption of cartilage repair mechanisms resulting in cartilage degradation. In the present study, we hypothesized that inflammatory synovial fluid triggers human chondrocytes to actively take part in inflammatory processes in rheumatic joint diseases. Primary human chondrocytes were incubated in synovial fluids gained from patients with rheumatoid arthritis, psoriasis arthritis and reactive arthritis. The detection of vital cell numbers was determined by using Casy Cell Counter System. Apoptosis was measured by Annexin-V and 7AAD staining. Cytokine and chemokine secretion was determined by a multiplex suspension array. Detection of vital cells showed a highly significant decrease in chondrocyte numbers. Flow cytometry demonstrated a significant increase in apoptotic chondrocytes after the incubation. An active secretion of cytokines such as MCP-1 and MIF by chondrocytes was observed. The inflammatory synovial fluid microenvironment mediates apoptosis and cell death of chondrocytes. Moreover, in terms of cytokine secretion, it also induces an active participation of chondrocytes in ongoing inflammation.
22875828 Selective activation of adenosine A2A receptors on immune cells by a CD73-dependent prodru 2012 Aug 8 Adenosine A(2A) receptor (A(2A)R) agonists are both highly effective anti-inflammatory agents and potent vasodilators. To separate these two activities, we have synthesized phosphorylated A(2A)R agonists (prodrugs) that require the presence of ecto-5'-nucleotidase (CD73) to become activated. In the model of collagen-induced arthritis, 2-(cyclohexylethylthio)adenosine 5'-monophosphate (chet-AMP), but not 2-(cyclohexylethylthio)adenosine (chet-adenosine), potently reduced inflammation as assessed by fluorine-19 ((19)F) magnetic resonance imaging and by histology. The prodrug effect was blunted by inhibition of CD73 and A(2A)R. The selectivity of drug action is due to profound up-regulation of CD73 and adenosine A(2A)R expression in neutrophils and inflammatory monocytes as found in recovered cells from the synovial fluid of arthritic mice. Plasma chet-adenosine was in the subnanomolar range when chet-AMP was applied, whereas concentrations required for vasodilation were about 100 times higher. Thus, chet-AMP is a potent immunosuppressant with negligible vasodilatory activity. These data suggest that phosphorylated A(2A)R agonists may serve as a promising new group of drugs for targeted immunotherapy of inflammation.
22319617 Hydroxyl radical modification of collagen type II increases its arthritogenicity and immun 2012 BACKGROUND: The oxidation of proteins by endogenously generated free radicals causes structural modifications in the molecules that lead to generation of neo-antigenic epitopes that have implications in various autoimmune disorders, including rheumatoid arthritis (RA). Collagen induced arthritis (CIA) in rodents (rats and mice) is an accepted experimental model for RA. METHODOLOGY/PRINCIPAL FINDINGS: Hydroxyl radicals were generated by the Fenton reaction. Collagen type II (CII) was modified by •OH radical (CII-OH) and analysed by ultraviolet-visible (UV-VIS), fluorescence and circular dichroism (CD) spectroscopy. The immunogenicity of native and modified CII was checked in female Lewis rats and specificity of the induced antibodies was ascertained by enzyme linked immunosorbent assay (ELISA). The extent of CIA was evaluated by visual inspection. We also estimated the oxidative and inflammatory markers in the sera of immunized rats. A slight change in the triple helical structure of CII as well as fragmentation was observed after hydroxyl radical modification. The modified CII was found to be highly arthritogenic and immunogenic as compared to the native form. The CII-OH immunized rats exhibited increased oxidative stress and inflammation as compared to the CII immunized rats in the control group. CONCLUSIONS/SIGNIFICANCE: Neo-antigenic epitopes were generated on (•)OH modified CII which rendered it highly immunogenic and arthritogenic as compared to the unmodified form. Since the rodent CIA model shares many features with human RA, these results illuminate the role of free radicals in human RA.
21698477 [Shoulder arthroplasty for primary synovial diseases]. 2011 Jul Shoulder arthroplasty has become an essential component of the standard surgical repertoire for the treatment of severe primary and secondary glenohumeral arthritis and has been shown to provide reliable long-term pain relief with satisfactory functional results. In most cases, in particular in patients with rheumatoid arthritis (RA), the indications for arthroplasty are primarily based on pain, which often includes severe pain at rest. Despite poor bone stock and impaired soft tissue quality in RA which frequently results in massive, irreparable rotator cuff tears, shoulder arthroplasty has been shown to be an effective means of improving shoulder function. Several different types of prostheses are now available for different indications determined by age, functional demand, etiology and structural deficits. For optimal outcome, the most suitable type of prosthesis needs to be selected by an experienced shoulder surgeon who is familiar with the entire spectrum of treatment options.
23092552 A bispecific antibody against IL-1β and IL-17A is beneficial for experimental rheumatoid 2012 Dec IL-1β is a pivotal cytokine and plays an important role in rheumatoid arthritis (RA). More recently, the biological therapy targeting this cytokine has been impressively effective for many RA patients, however, it remains insufficient in some patients. One of the reasons for these failures may be due to multiple cytokines involved in the disease process. In the present study, we constructed a single-chain bispecific antibody (scBsAb1/17) against both human IL-1β and human IL-17A which is the mediator for several key cytokines involved in the RA process such as TNF- and IL-6. A number of in vitro assays demonstrated that scBsAb1/17 simultaneously bound to both targets with a similar antigen-binding affinity as an individual single-chain antibody molecule (anti-IL-1β scFv or anti-IL-17A scFv). Mice with collagen-induced arthritis (CIA) were administrated with either scBsAb1/17 or individual single chain antibody alone, and we noticed that treatment with scBsAb1/17 significantly ameliorated clinical signs and alleviated histological lesion of CIA mice compared to treatments with anti-IL-1β scFv or anti-IL-17A scFv alone. Production of CII-specific antibodies in scBsAb1/17-treated CIA mice was substantially lower than that of single-chain antibody-treated CIA mice. In addition, scBsAb1/17 was more potent in the inhibition of collagen-specific proliferation of splenocytes and mRNA expression of TNF-, IL-6, IL-2, IL-1β and IFN-γ in the spleens of CIA mice compared to a single-chain antibody alone. These results suggest that scBsAb1/17 appears more beneficial in CIA mice than monovalent single-chain antibody molecules.
21253739 The outcomes and cost-effectiveness of intraarticular injection of the rheumatoid knee. 2012 Feb Although intraarticular injections are important to the management of rheumatoid arthritis, there are few studies regarding the cost-effectiveness of alternative injection techniques. This randomized controlled study addressed the cost-effectiveness of two different low-cost, anatomic landmark palpation-directed intraarticular injection techniques. Ninety-six symptomatic rheumatoid knees were randomized to two different low-cost, palpation-guided intraarticular injection techniques utilizing (1) a conventional syringe or (2) a mechanical syringe, the RPD (the reciprocating procedure device). Three milliliters of 1% lidocaine were used to anesthetize the synovial membrane, followed by arthrocentesis and hydrodissection, and injection of 80 mg of triamcinolone acetonide utilizing the one-needle two-syringe technique. Baseline pain, procedural pain, aspirated fluid volume, pain at outcome (2 weeks and 6 months), responders, reinjection rates, cost/patient/year, and cost/responder/year were determined. Pain was measured with the 10 cm Visual Analogue Pain Scale (VAS). Both techniques significantly reduced pain scores at outcome from baseline (P < 0.001). The mechanical syringe technique resulted in a greater volume of aspirated fluid (P < 0.01), a 38% reduction in procedural pain (P < 0.001), a 24% reduction in pain scores at outcome (P < 0.03), an increase in the responder rate (P < 0.025), 33% increase in the time to next injection (P < 0.001), 23% ($35 US) reduction in cost/patient/year for a patient treated in a physician office (P < 0.001), 24% reduction ($26 US) in cost/patient/year for a hospital outpatient (P < 0.001), and 51% ($151 US) reduction in cost/responder/year (P < 0.001). The outcomes and cost-effectiveness of intraarticular injection of the rheumatoid knee can be improved significantly with low-cost alternations in technique.
21981664 The use of chimeric vimentin citrullinated peptides for the diagnosis of rheumatoid arthri 2011 Nov 10 Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and, in many cases, destruction of the joints. To prevent progressive and irreversible structural damage, early diagnosis of RA is of paramount importance. The present study addresses the search of new RA citrullinated antigens that could supplement or complement diagnostic/prognostic existing tests. With this aim, the epitope anticitrullinated vimentin antibody response was mapped using synthetic peptides. To improve the sensitivity/specificity balance, a vimentin peptide that was selected, and its cyclic analogue, were combined with fibrin- and filaggrin-related peptides to render chimeric peptides. Our findings highlight the putative application of these chimeric peptides for the design of RA diagnosis systems and imply that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs. Each of the target molecules reported here (fibrin, vimentin, filaggrin) has a specific utility in the identification of a particular subset of RA patients.
21248215 Cemented versus cementless total hip replacements in patients fifty-five years of age or o 2011 Jan 19 BACKGROUND: results obtained from single-center studies indicate that a cemented total hip replacement is the treatment of choice for the management of patients over fifty-five years of age with rheumatoid arthritis. The aim of this study was to analyze population-based survival rates for cemented and cementless total hip replacements in patients aged fifty-five years or over with rheumatoid arthritis in Finland. METHODS: between 1980 and 2006, a total of 6000 primary total hip replacements performed for the management of rheumatoid arthritis in patients who were fifty-five years of age or older were entered in the Finnish Arthroplasty Registry. 4019 of them fulfilled our inclusion criteria and were subjected to analysis. The implants were classified into one of three possible groups: (1) a cementless group (a noncemented proximally porous-coated stem and a noncemented porous-coated press-fit cup), (2) a cemented group 1 (a cemented, loaded-taper stem combined with a cemented, all-polyethylene cup), or (3) a cemented group 2 (a cemented, composite-beam stem with a cemented, all-polyethylene cup). RESULTS: cementless stems and cups, analyzed separately, had a significantly lower risk of revision for aseptic loosening than cemented implants in patients who were fifty-five years of age or older with rheumatoid arthritis. The fifteen-year survival rate of cementless total hip replacements (80%) was comparable with the rates of the cemented groups (86% in cemented group 1 and 79% in cemented group 2) when revisions for any reason were used as the end point. CONCLUSIONS: cementless and cemented total hip replacements produced comparable long-term results in patients who were fifty-five years of age or older with rheumatoid arthritis. LEVEL OF EVIDENCE: therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.
23092579 Legionella pneumophila serotype 1 pneumonia in patient receiving adalimumab. 2012 Nov We describe a case of severe pneumonia caused by Legionella pneumophila serotype 1 in a woman receiving the tumor necrosis factor-α antagonist to treat rheumatoid arthritis. As use of tumor necrosis factor-α inhibitors increase, clinicians should consider their possible association with legionellosis.
22562983 Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate resp 2013 Jan OBJECTIVE: In patients with active rheumatoid arthritis (RA) despite methotrexate, to compare the efficacy of adding tocilizumab to that of switching to tocilizumab monotherapy. METHODS: Double-blind, 2-year study in which adults with active RA (DAS28 >4.4) despite methotrexate were randomly assigned either to continue methotrexate with the addition of tocilizumab (MTX+TCZ) 8 mg/kg every 4 weeks or switch to tocilizumab and placebo (TCZ+PBO). The primary endpoint was the DAS28-erythrocyte sedimentation rate (ESR) remission rate at week 24. Secondary objectives included other symptomatic outcomes, quality of life and progression of structural damage. RESULTS: Of 556 randomly assigned patients, 512 (92%) completed 24 weeks. DAS28-ESR remission rates were 40.4% for TCZ+MTX and 34.8% for TCZ+PBO (p=0.19); American College of Rheumatology 20/50/70/90 rates were 71.5%/45.5%/24.5%/5.8% (TCZ+MTX) and 70.3%/40.2%/25.4%/5.1% (TCZ+PBO; differences not significant). A significant difference between groups was seen for low DAS28 (61.7% vs 51.4%). Radiographic progression was small and not different between groups (Genant-Sharp score progression ≤ smallest detectable change in 91% (TCZ+MTX) and 87% (TCZ+PBO)). Rates per 100 patient-years of serious adverse events and serious infections were 21 and six, respectively, for TCZ+MTX and 18 and six, respectively, for TCZ+PBO. Alanine aminotransferase elevations greater than threefold the upper limit of normal occurred in 7.8% and 1.2% of TCZ+MTX and TCZ+PBO patients, respectively. CONCLUSION: No clinically relevant superiority of the TCZ+MTX add-on strategy over the switch to tocilizumab monotherapy strategy was observed. The combination was more commonly associated with transaminase increases. Meaningful clinical and radiographic responses were achieved with both strategies, suggesting that tocilizumab monotherapy might be a valuable treatment strategy in suitable RA patients.
21874795 [Utility of musculoskeletal ultrasonography in rheumatic diseases]. 2011 Jul Musculoskeletal ultrasonography (MSUS) possessing grey-scale and Doppler mode has become an established imaging modality for the diagnosis and follow up of patients with rheumatic diseases. Among rheumatic diseases, rheumatoid arthritis (RA) has been recognized as a good disorder to examine the joint inflammation as known synovitis. Early diagnosis and therapeutic intervention have given good outcomes to patients with RA. The 2010 RA classification criteria was reported and early arthritis patients has been diagnosed as RA, although the diagnostic and discriminative abilities of the 2010 criteria are not well known in Japanese. In the new criteria, synovitis is detected as joint swelling or tenderness on physical examination. Now we have expected if MSUS were used for detection of true synovitis, because we have confirmed that sensitivity of synovitis detection by MSUS was superior to that by physical examination.
21298362 Why TNF-α inhibition is not sufficient to avoid juxta-articular erosions in chronic arthr 2012 Feb There is an emerging interest in the role of anti-TNF-α therapy in reducing bone damage in chronic arthritis with special regard to rheumatoid arthritis. Accumulation of osteoclasts in rheumatoid synovial tissues, and their activation due to osteoclastogenic cytokines and chemokines at cartilage erosion sites suggest that they may advantageously be considered as therapeutic targets. Given that the primary role of TNF-α in osteoclastogenesis, the inhibition of TNF-α represents an important strategy for reducing bone damage in rheumatoid arthritis. In point of fact, there is evidence that treatment with anti-TNF-α agents may avoid or reduce bone damage in rheumatoid arthritis, even if further studies are required to provide a biological explanation and a link for the observation of the advantageous effects of TNF-α inhibitors on the progression of bone damage in chronic arthritis. The existence of factors involved in osteoclast activation, including IL-1, IL-6, IL-7, IL-11, IL-17, M-CSF, TGF-β, MIP-1α, MIP-1β, IP-10, MIG, and OSCAR, indicates that TNF-α is only a single player in the great molecular cauldron of osteoclastogenesis. The presence of mediators behind the TNF-α and RANK-RANKL complex that may be independent in inducing osteoclastogenesis, such as NFATc1, suggests that the anti-TNF-α therapy will not provide a complete reduction of bone damage in chronic arthritis.
23763224 Rheumatoid pericardial mass producing right ventricle inflow tract restriction: a case rep 2012 Sep Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints affecting multiple organs in the body. Pericardial disease is a relative common systemic manifestation of RA. A small number of cases are described in the literature related to pericardial involvement in RA. We described a case of a 69 year-old-male with chronic RA who presented with progressively worsening shortness of breath at exertion. Previous echocardiogram performed one year ago had normal ejection fraction and no structural abnormalities. Laboratories showed no significant abnormalities. The echocardiogram and MRI performed at the time of evaluation, revealed a mass in the right ventricle free wall pericardia. On the pathology report the pericardial mass resection showed mild chronic inflammation, extensive fibrosis, fat necrosis and branchial cyst surrounded with mild chronic inflammation. After surgical resection the patient improved clinically.
21977818 Evidence-based Chinese medicine for rheumatoid arthritis. 2011 Jun Chinese medicine (CM) has long been adopted for treatment of rheumatoid arthritis (RA). CM approaches RA as it does for other diseases by holistic treatment, focusing on the whole body condition, and giving a variety of applications in accordance with the stage and symptoms of the disease. For seeking the best evidence of CM in making decisions for the care of RA individual patients, a number of clinical studies have been conducted in China to gain credibility with the researchers' unremitting efforts. But the heterogeneity in many of these clinical trials and the low quality of design in some previous studies present an obstacle to the meaningful systematic reviews (SR) and meta-analysis. Some favorable results in improvement of response to biomedicine and reduction of severe adverse reactions of conventional RA therapy should be carefully interpreted and need further research. Fortunately, more appropriate quality assurance and control of CM researches are raised for the implementation of CM in RA therapy to pave the evidence-based way. Guidelines for the diagnosis and treatment of RA recommend evidence to the clinicians. In future, randomized controlled trials (RCT) with smart and flexible design as a good approach to evaluate the effectiveness will be widely used in CM for RA clinical study, with better research methods suitable for certain CM clinical researches. The development of evidence-based CM for RA will be full of challenge and opportunity, but we have full confidence.
21909699 Inhibition of MAP kinase in synovium by treatment with tocilizumab in rheumatoid arthritis 2011 Nov To investigate the histological changes of mitogen-activated protein kinase (MAPK) in synovium with tocilizumab in rheumatoid arthritis (RA), synovial tissue samples were assessed from ten methotrexate (MTX)-treated RA patients for control and ten tocilizumab with MTX-treated RA patients. The synovium was observed using hematoxylin and eosin (H&E) stain and analyzed immunohistochemically for the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), CD4 (T cell), CD20 (B cell), CD68 (macrophage), vascular endothelial growth factor (VEGF), CD29 (β-1 integrin), phospho-p38 MAPK (Tyr180/Tyr182), phospho-p44/42 MAPK [extracellular signal-regulated kinase (ERK) 1/ERK2], and phospho-c-Jun N-terminal kinase (JNK). H&E staining showed that there is a significant difference of cell proliferation; however, there is no change of hypervascularity in the synovium between both groups. An immunohistochemical examination showed that the decrease of CD29 (β-1 integrin) and JNK was found significant, while ERK was increased in the tocilizumab group. CD20, B-lymphocyte, was decreased in the tocilizumab group compared with the MTX group significantly. IL-6 was completely blocked in the patients who received tocilizumab. TNF-α was similarly expressed in the interstitial cells of synovium of patients in both groups. MMP-3 and CD68 were similarly expressed on the surface of synovium. VEGF was less expressed in both groups. These findings indicate that the inhibition of CD20, CD29, and JNK in MAPK may be involved in the efficacy of tocilizumab compared with MTX treatment in RA.