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ID PMID Title PublicationDate abstract
25157820 Peptide-siRNA nanocomplexes targeting NF-κB subunit p65 suppress nascent experimental art 2014 Oct The NF-κB signaling pathway is implicated in various inflammatory diseases, including rheumatoid arthritis (RA); therefore, inhibition of this pathway has the potential to ameliorate an array of inflammatory diseases. Given that NF-κB signaling is critical for many immune cell functions, systemic blockade of this pathway may lead to detrimental side effects. siRNAs coupled with a safe and effective delivery nanoplatform may afford the specificity lacking in systemic administration of small-molecule inhibitors. Here we demonstrated that a melittin-derived cationic amphipathic peptide combined with siRNA targeting the p65 subunit of NF-κB (p5RHH-p65) noncovalently self-assemble into stable nanocomplexes that home to the inflamed joints in a murine model of RA. Specifically, administration of p5RHH-p65 siRNA nanocomplexes abrogated inflammatory cytokine expression and cellular influx into the joints, protected against bone erosions, and preserved cartilage integrity. The p5RHH-p65 siRNA nanocomplexes potently suppressed early inflammatory arthritis without affecting p65 expression in off-target organs or eliciting a humoral response after serial injections. These data suggest that this self-assembling, largely nontoxic platform may have broad utility for the specific delivery of siRNA to target and limit inflammatory processes for the treatment of a variety of diseases.
23344687 Antibodies to citrullinated peptides in tuberculosis. 2013 May Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetric polyarthritis, rheumatoid factor (RF) positivity, and bone erosions. Recently, research has been conducted on anti-citrullinated peptide antibodies (ACPAs) to which there are greater sensitivity and specificity than RF. However, these antibodies have also been described in infectious diseases, particularly tuberculosis (TB), placing the high specificity of the test in doubt. The aim of this research was to study the prevalence of ACPAs in TB, RA, and healthy controls. Patients with bacteriologically confirmed pulmonary tuberculosis, RA (ACR criteria), in addition to healthy controls were included. ACPAs were researched by: anti-cyclic citrullinated peptide (CCP), anti-modified citrullinated vimentin (MCV), and RF by ELISA. The study was conducted in 50 TB patients, 50 with RA, and 20 controls. Anti-CCP antibodies were found in 39 (78 %) of the RA patients (median titer, 128 U), whereas anti-MCV antibodies were found in 25 (50 %). Of the patients with TB, two (4 %) had positivity for anti-CCP and anti-MCV and no patient in the control group tested positive for these antibodies. Sensitivity of anti-CCP for RA was 78 % (confidence interval (CI), 63 to 88 %) and specificity was 97 % (CI, 89 to 99 %) while the sensitivity of anti-MCV was 50 % (CI, 35-64 %) and specificity was 97 % (CI, 89 to 99 %). RF was positive in 40 samples (80 %) of RA, in 30 (60 %) of TB, and in 1 (5 %) of the controls. Our findings showed high sensitivity of anti-CCP and high specificity of both anti-CCP and anti-MCV antibodies for RA, even in a population with high incidence of tuberculosis. The higher frequency of positivity of ACPA in TB observed in previous studies may be attributed to methodological factors.
24685910 Risk of solid cancer in patients exposed to anti-tumour necrosis factor therapy: results f 2015 Jun BACKGROUND: Patients with rheumatoid arthritis (RA) have an increased risk of certain solid cancers, in particular lung cancer, compared to the general population. Treatment with tumour necrosis factor (TNF) inhibitors (TNFi) may further enhance this risk. OBJECTIVES: To compare the risk of solid cancer in patients with RA treated with TNFi to that in patients treated with non-biologic (synthetic) disease modifying antirheumatic drugs (sDMARDs). METHODS: Patients with a physician diagnosis of RA enrolled in the British Society for Rheumatology Biologics Register, a national prospective cohort study established in 2001 to monitor the long-term safety of TNFi, were followed via record linkage with the national cancer registries until first solid cancer, death, for 5 years, or until 2011. Rates of solid cancers in 11 767 patients without prior cancer who received TNFi were compared to those in 3249 patients without prior cancer treated with sDMARDs. RESULTS: 427 solid cancers were reported in 52 549 patient-years follow-up for the TNFi group (81 (95% CI 74 to 89) per 10 000 patient-years) and 136 cancers were reported in 11 672 patient-years in the sDMARD cohort (117 (95% CI 98 to 138) per 10 000 patient-years). After adjusting for differences in baseline characteristics there was no difference in risk of solid cancer for TNFi compared to sDMARD treated patients: HR 0.83 (95% CI 0.64 to 1.07). There was no difference in the relative risk of cancer for any of the individual TNFi drugs. CONCLUSIONS: The addition of TNFi to sDMARD does not alter the risk of cancer in RA patients selected for TNFi in the UK.
23970326 Large ulceration of the oropharynx induced by methotrexate-associated lymphoproliferative 2013 We present a case of a 67-year-old Japanese man with a serious oropharyngeal ulceration that at first seemed to be destructive malignant lymphoma or oropharyngeal carcinoma. We suspected methotrexate (MTX)-associated lymphoproliferative disorder (LPD) induced by MTX treatment for rheumatoid arthritis (RA). About 3 weeks after simple discontinuation of MTX, complete regression of the disease was observed, confirming our diagnosis.
23794171 Abatacept: a review of its use in the management of rheumatoid arthritis. 2013 Jul The biological disease-modifying antirheumatic drug abatacept (Orencia) has a novel mechanism of action; its activity is mediated via the selective modulation of T cell co-stimulation. This article reviews the clinical efficacy and tolerability of intravenous and subcutaneous abatacept in patients with rheumatoid arthritis (RA) and intravenous abatacept in patients with juvenile idiopathic arthritis (JIA), as well as summarizing its pharmacological properties. In patients with RA, the beneficial effects of intravenous or subcutaneous abatacept on signs and symptoms, disease activity, the progression of structural damage, physical function and/or health-related quality of life were seen in a number of well-designed trials, including in methotrexate-naive patients with early RA and poor prognostic factors and in patients with established RA and an inadequate response to either methotrexate or anti-tumour necrosis factor therapy. Subcutaneous abatacept plus methotrexate was also noninferior to subcutaneous adalimumab plus methotrexate in patients with active RA who were naive to biological therapy and had an inadequate response to methotrexate. In paediatric patients with JIA, intravenous abatacept improved signs and symptoms and delayed the time to flare. Abatacept was generally well tolerated in RA and JIA and was associated with low rates of immunogenicity. In conclusion, abatacept is an important option for use in the treatment of RA and JIA.
25483258 Demographic and clinical features of systemic sclerosis patients with anti-RNA polymerase 2015 Feb Anti-RNA polymerase III antibody (RNAP) is primarily detected in diffuse cutaneous type systemic sclerosis (dcSSc) patients and strongly associated with renal crisis. Additionally, there has been increasing evidence that cancer in SSc patients is associated with RNAP. The aim of this study was to examine the demographic and clinical features of SSc patients with RNAP. Among 246 SSc patients, 5.7% were positive for RNAP, 20.7% were positive for anti-topoisomerase I antibody (Topo I) alone and 39.4% were positive for anticentromere antibody (ACA) alone. The modified Rodnan total skin score (mRTSS) in SSc patients with RNAP (19.1 ± 2.6) was significantly higher than those in SSc patients with Topo I (11.5 ± 1.1) and patients with ACA (4.4 ± 0.4). Furthermore, among SSc patients with RNAP, the levels of RNAP were positively correlated with mRTSS. Renal crisis is also significantly more prevalent in SSc patients with RNAP than patients without RNAP. Male sex, dcSSc subtype, digital vasculopathy, including digital ulcers and acro-osteolysis, interstitial lung disease and rheumatoid arthritis complications were prevalent in SSc patients with RNAP and patients with Topo-I. Primary biliary cirrhosis and Sjögren's syndrome were more in SSc patients with RNAP and patients with ACA compared with patients with Topo 1. No significant difference in the frequency of complications, including Raynaud's phenomenon, pulmonary artery hypertension and malignancy was observed between the three groups. Thus, measurement of RNAP in SSc patients is useful for the diagnosis and risk stratification of severe manifestation, such as renal crisis and severe skin sclerosis.
23606682 A non-inferiority trial of an attenuated combination strategy ('COBRA-light') compared to 2014 Jun BACKGROUND: Early, intensive treatment of rheumatoid arthritis (RA) with the combination of (initially high dose) prednisolone, methotrexate and sulfasalazine (COBRA therapy) considerably lowers disease activity and suppresses radiological progression, but is infrequently prescribed in daily practice. Attenuating the COBRA regimen might lessen concerns about side effects, but the efficacy of such strategies is unknown. OBJECTIVE: To compare the 'COBRA-light' strategy with only two drugs, comprising a lower dose of prednisolone (starting at 30 mg/day, tapered to 7.5 mg/day in 9 weeks) and methotrexate (escalated to 25 mg/week in 9 weeks) to COBRA therapy (prednisolone 60 mg/day, tapered to 7.5 mg/day in 6 weeks, methotrexate 7.5 mg/week and sulfasalazine 2 g/day). METHOD: An open, randomised controlled, non-inferiority trial in 164 patients with early active RA, all treated according to a treat to target strategy. RESULTS: At baseline patients had moderately active disease: mean (SD) 44-joint disease activity score (DAS44) 4.13 (0.81) for COBRA and 3.95 (0.9) for COBRA-light. After 6 months, DAS44 significantly decreased in both groups (-2.50 (1.21) for COBRA and -2.18 (1.10) for COBRA-light). The adjusted difference in DAS44 improvement between the groups, 0.21 (95% CI -0.11 to 0.53), was smaller than the predefined clinically relevant difference of 0.5. Minimal disease activity (DAS44 <1.6) was reached in almost half of patients in both groups (49% and 41% in COBRA and COBRA-light, respectively). CONCLUSIONS: At 6 months COBRA-light therapy is most likely non-inferior to COBRA therapy. CLINICAL TRIAL REGISTRATION NUMBER: 55552928.
24315820 Interaction between TGF-β1 (869C/T) polymorphism and biochemical risk factor for predicti 2014 Feb 25 OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease. Transforming growth factor-β1 (TGF-β1) may be a promising candidate gene for susceptibility and severity in RA. We aimed to determine whether TGF-β1 polymorphism is associated with susceptibility to RA and progression of joint destruction, as well as to identify the interaction between TGF-β1 polymorphism and biochemical risk factor. METHODS: A total of 160 RA patients and 168 healthy unrelated controls were tested for the TGF-β1 (869C/T) polymorphism using polymerase chain reaction. RESULTS: The TGF-β1 T allele was associated with susceptibility to RA. Within the RA group, TGF-β1 T allele carriers had a significant increased risk to develop osteoporosis (OR=4.4, 95% CI=-2. 4-8.1, P<0.001), as well as more likely to develop bone erosion (OR=1.7, 95% CI=0. 99-2.7, P=0. 034). Better prediction was achieved when the TGF-β1 TT genotype was used in combination with either elevated, rheumatoid factor (RF) or C-reactive protein (CRP) (OR=6.8, 3.7 respectively). Also, they increased the risk to develop bone erosion in patients with rheumatoid arthritis (OR=3.3, 9.8, P=0.017, 0.001 respectively). CONCLUSION: Our results suggest that TGF-β1 TT genotype may determine the development of osteoporosis and bone erosion in RA. Also, our results points to a synergism between TGF-β1 TT genotype and elevated serum RF or elevated CRP that lead to the development of osteoporosis and bone erosion in patients with rheumatoid arthritis.
25131613 Thoracic manifestations of connective tissue diseases. 2015 Jan Connective tissue diseases (CTDs) comprise several immunologic systemic disorders, each of which associated with a particular set of clinical manifestations and autoimmune profile. CTDs may cause numerous thoracic abnormalities, which vary in frequency and pattern according to the underlying disorder. The CTDs that most commonly involve the respiratory system are progressive systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren syndrome, polymyositis, dermatomyositis, and mixed connective tissue disease. Pulmonary abnormalities in this group of patients may result from CTD-related lung disease or treatment complications, namely drug toxicity and opportunistic infections. The most important thoracic manifestations of CTDs are interstitial lung disease and pulmonary arterial hypertension, with nonspecific interstitial pneumonia being the most common pattern of interstitial lung disease. High-resolution computed tomography is a valuable tool in the initial evaluation and follow-up of patients with CTDs. As such, general knowledge of the most common high-resolution computed tomographic features of CTD-related lung disease allows the radiologist to contribute to better patient management.
25165034 Cell cycle regulation therapy combined with cytokine blockade enhances antiarthritic effec 2016 Jan OBJECTIVE: Biological disease-modifying antirheumatic drugs (DMARDs) that inhibit aberrant immune reactions in rheumatoid arthritis (RA) cannot induce complete remission in all patients. Combination therapies using two biological DMARDs have failed to exert additive effects and increased serious infections. We have found that cell cycle inhibition of synovial fibroblasts with cyclin-dependent kinase (CDK) inhibitors ameliorated the disease in animal models of RA without attenuating acquired immunity. The objective of this study was to determine whether a clinically well-tolerated selective CDK 4/6 inhibitor (CDKI), palbociclib, is effective and whether combination with cytokine blockers acts additively without enhancing immune suppression. METHODS: The effects of CDKI on haematopoiesis and physical and behavioural findings in mice were evaluated. Mice with collagen-induced arthritis (CIA) were treated with CDKI, etanercept or anti-interleukin (IL)-6 receptor antibody (MR16-1) alone or with a combination of CDKI with etanercept or MR16-1. Their clinical, histological and radiographic scores, serum anti-(type II collagen (CII)) antibody levels and proliferative responses of lymph node cells to CII were determined. RESULTS: Although CDKI induced marginal myelosuppression, it was well tolerated and ameliorated CIA dose-dependently. The combinations of low-dose CDKI and either tumour necrosis factor-α or IL-6 blocker enhanced the antiarthritic effects additively. The addition of CDKI to either cytokine blocker did not affect the levels of anti-CII antibodies and proliferative responses of lymphocytes to CII. CONCLUSIONS: A clinically well-tolerated CDK4/6 inhibitor exerted antiarthritic effects in this mouse model. By combining therapeutic agents targeting immune reaction and synovial proliferation, we have demonstrated for the first time that two molecular targeting treatments act additively and may not increase immune suppression.
24177456 C reactive protein may not be reliable as a marker of severe bacterial infection in patien 2013 Oct 31 This is a case of a 65-year-old man with seropositive erosive rheumatoid arthritis (RA), well controlled on methotrexate, sulfasalazine, low-dose prednisolone and monthly infusions of tocilizumab. He presented with a 3-week history of pain and swelling in his left knee, gradually increasing in severity with an inability to bear weight. He was systemically well with normal vital signs. Examination confirmed an effusion and aspiration was turbid in appearance. C reactive protein (CRP) was normal. He was treated empirically with antibiotics. Synovial fluid and blood cultures confirmed Staphylococcus aureus infection. He completed a 6 weeks course of antibiotics with complete resolution of symptoms. Throughout the treatment his CRP remained normal which is likely to have been the result of prior treatment with tocilizumab.
25175678 Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis an 2014 Aug 30 INTRODUCTION: Activation of the inflammasome has been implicated in the pathology of various autoinflammatory and autoimmune diseases. While the NLRP3 inflammasome has been linked to arthritis progression, little is known about its synovial regulation or contribution to joint histopathology. Regulators of inflammation activation, such as interleukin (IL)-10, may have the potential to limit the inflammasome-driven arthritic disease course and associated structural damage. Hence, we used IL-10-deficient (IL-10KO) mice to assess NLRP3 inflammasome-driven arthritic pathology. METHODS: Antigen-induced arthritis (AIA) was established in IL-10KO mice and wild-type controls. Using histological and radiographic approaches together with quantitative real-time PCR of synovial mRNA studies, we explored the regulation of inflammasome components. These were combined with selective blocking agents and ex vivo investigative studies in osteoclast differentiation assays. RESULTS: In AIA, IL-10KO mice display severe disease with increased histological and radiographic joint scores. Here, focal bone erosions were associated with increased tartrate-resistant acid phosphatase (TRAP)-positive cells and a localized expression of IL-1β. When compared to controls, IL-10KO synovium showed increased expression of Il1b, Il33 and NLRP3 inflammasome components. Synovial Nlrp3 and Casp1 expression further correlated with Acp5 (encoding TRAP), while neutralization of IL-10 receptor signaling in control mice caused increased expression of Nlrp3 and Casp1. In ex vivo osteoclast differentiation assays, addition of exogenous IL-10 or selective blockade of the NLRP3 inflammasome inhibited osteoclastogenesis. CONCLUSIONS: These data provide a link between IL-10, synovial regulation of the NLRP3 inflammasome and the degree of bone erosions observed in inflammatory arthritis.
25744772 Predictors of mortality in patients with rheumatoid arthritis in Lithuania: Data from a co 2015 BACKGROUND AND OBJECTIVE: Increased mortality and shorter survival among rheumatoid arthritis (RA) patients are recognized but not fully explained. This cohort study aimed to identify predictors of mortality among RA patients at a tertiary clinical setting. MATERIALS AND METHODS: Patients with RA were recruited during 1998-2003 and followed up until April 1, 2012, or death whichever happened first. Baseline variables included sociodemographic and disease characteristics, and comorbidities. Cox regression and hazard risk (HR) were computed to estimate risks for mortality. RESULTS: One hundred ninety-one patients were included into the study, 186 patients were eligible for the analysis and of these 131 patients (70.4%) completed the entire period of followed-up while 55 patients (29.6%) died. The average follow up period was equivalent to 9.24 year per person. A Cox regression model identified four major factors having an impact on survival. History of a stroke at baseline was identified as a major factor (HR=5.33; 95% CI, 2.13-13.32). Statistically significant risk factors were also age over 50 years (HR=4.59; 95% CI, 2.04-10.30); education less than 11 years (HR=3.3; 95% CI, 1.72-6.33) and angina pectoris (HR=1.98; 95% CI, 1.03-3.80). CONCLUSIONS: Higher age, lower education and cardiovascular comorbidities were identified as predictors of mortality in this prospective cohort study while disease-related variables were not independent predictors of mortality.
23636220 Enrichment of vitamin D response elements in RA-associated loci supports a role for vitami 2013 Jul The aim of this study was to explore the role of vitamin D in rheumatoid arthritis (RA) pathogenesis by investigating the enrichment of vitamin D response elements (VDREs) in confirmed RA susceptibility loci and testing variants associated with vitamin D levels for association with RA. Bioinformatically, VDRE genomic positions were overlaid with non-HLA (human leukocyte antigen)-confirmed RA susceptibility regions. The number of VDREs at RA loci was compared to a randomly selected set of genomic loci to calculate an average relative risk (RR). Single-nucleotide polymorphisms (SNPs) in the DHCR7/NADSYN1 (nicotinamide adenine dinucleotide synthase 1) and CYP2R1 loci, previously associated with circulating vitamin D levels, were tested in UK RA cases (n=3870) and controls (n=8430). Significant enrichment of VDREs was seen at RA loci (P=9.23 × 10(-8)) when regions were defined either by gene (RR 5.50) or position (RR 5.86). SNPs in the DHCR7/NADSYN1 locus showed evidence of positive association with RA, rs4944076 (P=0.008, odds ratio (OR) 1.14, 95% confidence interval (CI) 1.03-1.24). The significant enrichment of VDREs at RA-associated loci and the modest association of variants in loci-controlling levels of circulating vitamin D supports the hypothesis that vitamin D has a role in the development of RA.
22729670 Evaluation of content on EQ-5D as compared to disease-specific utility measures. 2013 May PURPOSE: The goal of this study was to appraise the extent of unique content on disease-specific preference-based measures (DSPMs) when contrasted with the EQ-5D using published studies and to inform whether EQ-5D could be inadequate as a utility measure in its content coverage for a given disease-specific application. METHODS: A structured search of published literature was performed using PubMed and EMBASE/Medline database from Jan 1, 1990 to Mar 31, 2011. Articles were eligible for inclusion if algorithms were developed to convert components from disease-specific measures into utility scores. RESULTS: Of 1,029 articles identified, 50 studies satisfied the inclusion criteria. The most frequent conditions where DSPMs were developed included cancer (12 studies), coronary artery disease (4 studies), osteoarthritis, rheumatoid arthritis (3 studies of each), obesity, and stroke (2 studies of each). Most studies involved mapping items or scores from disease-specific non-preference-based measures onto a preference-based measure of health such as the EQ-5D. A substantial number of DSPMs appeared to include unique content not covered by EQ-5D dimensions. CONCLUSIONS: Several conditions were identified as potential areas where the richness of the EQ-5D descriptive system could be enhanced. It is yet unclear whether added dimension(s) would contribute unique explained variance to a utility score. Given the resources required to rigorously develop a utility measure, the need for such measures should be carefully vetted.
24764263 Secreted frizzled-related protein 5 suppresses inflammatory response in rheumatoid arthrit 2014 Sep OBJECTIVE: This study was performed to investigate the effect of secreted frizzled-related protein 5 (Sfrp5), a novel anti-inflammatory adipokine that competes with the frizzled proteins for Wnt binding, on inflammatory response and the c-Jun N-terminal kinase (JNK) signalling pathway in RA. METHODS: Expression of Sfrp5 mRNA in peripheral blood mononuclear cells (PBMCs) and fibroblast-like synoviocytes (FLSs) from patients with RA and OA was determined using real-time quantitative PCR (qPCR). Sfrp5 RNA interference (RNAi) plasmids were transfected to abrogate Sfrp5 expression in RA FLSs, and adenovirus containing the Sfrp5 transcript was delivered into RA FLSs to strengthen Sfrp5 expression. Levels of pro-inflammatory genes and their protein products were determined using real-time qPCR and ELISA in RA FLSs. Production of mitogen-activated protein kinase kinase 7 (MKK-7), JNK and c-Jun were assessed by Western blot analysis. RESULTS: Expression of Sfrp5 mRNA was decreased in PMBCs and FLSs from patients with RA compared with patients with OA. Gene expression and production of IL-1β, IL-6, chemokine ligand 2 (CCL-2), CCL-7, cyclooxygenase 2 and MMP-9 were markedly increased in Sfrp5 RNAi plasmid-transfected RA FLSs, while transfection with adenoviral vectors encoding Sfrp5 induced reductions in those levels. Phosphorylated forms of MKK-7, JNK and c-Jun were increased by Sfrp5 RNAi plasmids and were decreased by adenoviral vectors encoding Sfrp5. CONCLUSION: Sfrp5 suppressed the inflammatory response and down-regulated JNK signalling in RA FLSs. These findings provide evidence for the anti-inflammatory effect of Sfrp5 in RA.
23380997 Shorter disease duration is important for tocilizumab to achieve Boolean remission. 2013 Nov OBJECTIVE: To determine the optimal conditions for inducing rheumatoid arthritis (RA) into disease remission by tocilizumab (TCZ), we analyzed the TCZ therapy carried out in our facility. METHOD: The study group comprised 116 patients with RA who started TCZ therapy at Kobe University Hospital and Konan-Kakogawa Hospital. The clinical response to TCZ was evaluated by the 2011 Boolean definition and the disease activity score of 28 joints erythrocyte sedimentation rate 4 (DAS28-ESR4). RESULTS: After 24 weeks of TCZ therapy, 25.9% of the patients achieved a Boolean-defined disease remission (Boolean remission). DAS28-ESR4 was improved from 5.25 ± 1.15 at week 0 to 2.75 ± 1.34 at week 24 (mean ± SD, P < 0.0001), and 57.8% patients achieved DAS28 remission. Analysis of the relationship between disease duration and remission showed that this odds ratio peaked at 3.0 years. Univariate analyses showed that Boolean remission was associated with baseline ESR levels, Steinbrocker's class and stage, and patient global assessment of disease activity (PGA). Accordingly, we categorized and compared the patient groups referring to the 3.0-year peak. We found significant differences in Steinbrocker's class and stage. CONCLUSION: TCZ therapy leading to Boolean disease remission is optimal when initiated less than 3.0 years after disease onset.
23337970 Gene polymorphisms that can predict response to anti-TNF therapy in patients with psoriasi 2013 Aug Psoriasis (Ps) is a chronic inflammatory disease with an important genetic component. It shares pathophysiological mechanisms with other autoimmune diseases such as psoriatic arthritis (PsA), rheumatoid arthritis (RA) and Crohn's disease (CD). These conditions can be treated using biological drugs such as infliximab, adalimumab and etanercept, which selectively block the proinflammatory cytokine tumor necrosis factor (TNF)-α. Although these agents have greatly improved the prognosis of Ps, PsA, RA and CD, they do not cure the disease and are expensive; in addition, significant proportions of patients do not respond or develop serious adverse effects. Therefore, it is important to investigate biomarkers, such as gene polymorphisms, that can predict which patients will respond best to a specific drug. Some polymorphisms in genes TNF, TNF receptor superfamily 1B (TNFR1B) and TNFα-induced protein 3 gene (TNFAIP3) have been associated with response to anti-TNF therapy in patients with Ps. The present article reviews other polymorphisms that could also play a role in prediction of response to these treatments.
25433041 Predictors of satisfactory improvements in pain for patients with early rheumatoid arthrit 2015 Jun OBJECTIVE: The aim of this study was to identify baseline predictors of achieving patient-perceived satisfactory improvement (PPSI) in pain after 6 months of treat to target in patients with early RA. METHODS: Baseline and 6 month data were used from patients included in the Dutch Rheumatoid Arthritis Monitoring remission induction cohort study. Simple and multivariable logistic regression analyses were used to identify significant predictors of achieving an absolute improvement of 30 mm or a relative improvement of 50% on a visual analogue scale for pain. RESULTS: At 6 months, 125 of 209 patients (59.8%) achieved an absolute PPSI and 130 patients (62.2%) achieved a relative PPSI in pain. Controlling for baseline pain, having symmetrical arthritis was the strongest independent predictor of achieving an absolute [odds ratio (OR) 3.17, P = 0.03] or relative (OR 3.44, P = 0.01) PPSI. Additionally, anti-CCP positivity (OR 2.04, P = 0.04) and having ≤12 tender joints (OR 0.29, P = 0.01) were predictive of achieving a relative PPSI. The total explained variance of baseline predictors was 30% for absolute and 18% for relative improvements, respectively. CONCLUSION: Symmetrical joint involvement, anti-CCP positivity and fewer tender joints at baseline are prognostic signs for achieving satisfactory improvement in pain after 6 months of treat to target in patients with early RA.
24097992 The development of genome-wide association studies and their application to complex diseas 2013 Oct In this review, we explain the motivation for carrying out genome-wide association studies (GWAS), contrasting the achievements of linkage-based experiments for Mendelian traits with the difficulties found when applying that type of experiment to complex diseases. We explain the technical and organizational developments that were required to make GWAS feasible, as well as some of the theoretical concerns that were raised during the design of these studies. We describe the impressive achievements of GWAS in lupus, and compare them with the experiences in three other genetically complex disorders: rheumatoid arthritis, type 1 diabetes and coronary heart disease. GWAS have been successful in identifying many new susceptibility loci for these four diseases, and have provided the motivation for novel immunological work. We conclude by describing preliminary steps that have been taken towards translating the results of GWAS into improvements in patient care, explaining some of the difficulties involved, as well as successes that have already been achieved.