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ID PMID Title PublicationDate abstract
28298563 Utility of Dose Frequency Adjustment in Tocilizumab Administration for Rheumatoid Arthriti 2017 May OBJECTIVE: To assess the utility of dose frequency adjustment of tocilizumab (TCZ) in rheumatoid arthritis (RA). METHODS: Patients who received TCZ at 3-week (n = 24) or 5-week (n = 61) interval were evaluated. RESULTS: Disease Activity Score at 28 joints based on erythrocyte sedimentation rate in the 3-week group significantly improved after 3 administrations at 3-week intervals (from 4.2 to 2.7, p = 0.001). Forty-five of the patients in the 5-week group (74%) successfully continued 5-week interval administration without disease exacerbation. Lower C-reactive protein level at TCZ initiation and shorter duration to remission achievement were key to successful dose frequency reduction. CONCLUSION: Adjusting the dose frequency of intravenous TCZ is a useful strategy.
28091549 Urinary proteomics can define distinct diagnostic inflammatory arthritis subgroups. 2017 Jan 16 Current diagnostic tests applied to inflammatory arthritis lack the necessary specificity to appropriately categorise patients. There is a need for novel approaches to classify patients with these conditions. Herein we explored whether urinary proteomic biomarkers specific for different forms of arthritis (rheumatoid arthritis (RA), psoriatic arthritis (PsA), osteoarthritis (OA)) or chronic inflammatory conditions (inflammatory bowel disease (IBD)) can be identified. Fifty subjects per group with RA, PsA, OA or IBD and 50 healthy controls were included in the study. Two-thirds of these populations were randomly selected to serve as a training set, while the remaining one-third was reserved for validation. Sequential comparison of one group to the other four enabled identification of multiple urinary peptides significantly associated with discrete pathological conditions. Classifiers for the five groups were developed and subsequently tested blind in the validation test set. Upon unblinding, the classifiers demonstrated excellent performance, with an area under the curve between 0.90 and 0.97 per group. Identification of the peptide markers pointed to dysregulation of collagen synthesis and inflammation, but also novel inflammatory markers. We conclude that urinary peptide signatures can reliably differentiate between chronic arthropathies and inflammatory conditions with discrete pathogenesis.
29174794 Survivin improves the early recognition of rheumatoid arthritis among patients with arthra 2018 Jun OBJECTIVES: The aim of this study was to validate the use of survivin for preclinical recognition of rheumatoid arthritis (RA) among patients with unexplained arthralgia. METHODS: Serum levels of survivin and the arthritis-specific autoantibodies RF and ACPA were measured in total of 5046 patients with musculoskeletal complains during 12 consecutive months in Gothenburg and in Umeå. Among them, 303 arthralgia patients were identified and prospectively followed. RESULTS: After 48 months, 12.2% of the arthralgia patients developed RA. Most of RA cases had high serum survivin, which increased the relative risk for RA (RR = 5.90, p = 3 × 10(-7)). Combination of survivin with autoantibodies was present in only 4.6% of the arthralgia patients and increased further the risk of RA and shortened time to RA development. Presence of any single autoantibody in the survivin-negative patients was associated with a minor risk for RA and had RA-free survival similar to the reference group. CONCLUSION: This study shows that measurement of survivin in serum improves estimation of RA risk and prospectively predicts RA development in patients with arthralgia. Survivin may indicate a phase preceding autoantibody production.
28446208 Calgizzarin (S100A11): a novel inflammatory mediator associated with disease activity of r 2017 Apr 26 BACKGROUND: Calgizzarin (S100A11) is a member of the S100 protein family that acts in different tumors by regulating a number of biologic functions. Recent data suggest its association with low-grade inflammation in osteoarthritis (OA). The aim of our study is to compare S100A11 expression in the synovial tissues, synovial fluid and serum of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to characterize the potential association between S100A11 and disease activity. METHODS: S100A11 protein expression was detected in synovial tissue from patients with RA (n = 6) and patients with OA (n = 6) by immunohistochemistry and immunofluorescence. Serum and synovial fluid S100A11 levels were measured by ELISA in patients with RA (n = 40) and patients with OA (n = 34). Disease activity scores in 28 joints based on C-reactive protein (DAS28-CRP) were used to assess disease activity. Cytokine content in peripheral blood mononuclear cells (PBMCs), synovial fibroblasts (SFs) and synovial fluid was analysed by ELISA, western blotting or cytometric bead array. RESULTS: S100A11 expression was significantly up-regulated in the synovial lining and sublining layers (p < 0.01) and vessels (p < 0.05) of patients with RA compared to patients with OA, and was associated with fibroblasts and T cells. S100A11 was significantly increased in synovial fluid (p < 0.0001) but not in serum (p = 0.158) from patients with RA compared to patients with OA when adjusted for age and sex. Synovial fluid S100A11 correlated with DAS28 (r = 0.350, p = 0.027), serum CRP (r = 0.463, p = 0.003), synovial fluid leukocyte count (r = 0.677, p < 0.001), anti-cyclic citrullinated peptide antibodies (anti-CCP) (r = 0.424, p = 0.006) and IL-6 (r = 0.578, p = 0.002) and IL-8 (r = 0.740, p < 0.001) in synovial fluid from patients with RA. PBMCs and SFs isolated from patients with RA synthesized and spontaneously secreted higher levels of S100A11 in comparison with PBMCs and SFs from patients with OA (p = 0.011 and 0.03, respectively). S100A11 stimulated the production of the pro-inflammatory cytokine IL-6 by PBMCs (p < 0.05) and SFs (p < 0.01). CONCLUSIONS: Our data provide the first evidence of S100A11 up-regulation and its association with inflammation and disease activity in patients with RA.
27984139 Fc fragments of immunoglobulin G are an inductor of regulatory rheumatoid factor and a pro 2017 Feb We recently identified rheumatoid factor, the production of which neither predicts nor exacerbates experimental autoimmune disease, but the opposite, namely it is associated with autoimmune disease resistance and remission. We have named it regulatory rheumatoid factor (regRF). The aim of this study was to determine whether rat Fc fragments and human Fc fragments are an antigen for regRF, and to determine the conditions for obtaining them. The presence of an antigenic determinant for regRF on IgG fragments was inferred from the fragments' ability to inhibit the agglutination caused by regRF and to induce regRF production in vivo. It was found that antigenic determinants for both human regRF and rat regRF are absent from native IgG and can be induced in the hinge region of Fc fragments of homologous IgG by papain digestion. The rat Fc fragments are susceptible to spontaneous reconfiguration, which results in loss of the antigenic determinants for regRF. Reconfiguration can be observed by SDS-PAGE. Immunization of arthritic rats with Fc fragments of rat IgG that carry antigenic determinants for rat regRF reduces the symptoms of collagen-induced arthritis. The Fc fragments can be viewed as the basis for a therapeutic vaccine to suppress autoimmune responses.
29071964 [Effect of Moxibustion on Serum IL-17 and TNF-α Levels in Collagen-induced Arthritis Rats 2017 Apr 25 OBJECTIVE: To observe the influence of moxibustion on serum interleukin -17 (IL-17) and tumor necrosis factor alpha (TNF-α) levels in collagen-induced arthritis (CIA) rats, so as to study its mechanism underlying improvement of rheumatoid arthritis. METHODS: A total of 40 male Wistar rats were used in the present study, and 8 rats were randomly selected as a normal control group. The other 32 rats were modeled. The primary immunity emulsion was made with mixed Type Ⅱ chicken collagen and complete Freund's adjuvant, and 0.3 mL emulsion (containing 0.3 mg collagen) was injected equally into left pelma, tail root and the back. Seven days after the primary immune, the same procedure was conducted to induce the secondary immunity, and the emulsion was made with mixed Type Ⅱ chicken collagen and incomplete Freund's adjuvant. The whole course of mo-deling lasted 21 days. And then 24 CIA rats were randomly divided into model group, medication group and moxibustion group (n=8 in each group). For those of the moxibustion group, suspended moxibustion with 20 mm distance above "Zusanli"(ST 36)and "Kunlun" (BL 60) was performed for 20 min/acupoint, once daily, alternately on left and right hind limbs for 10 consecutive days. For those of the medication group, gavage of methotrexate (0.1 mg/100 g) was administrated once every 5 days, and totally two times. Left ankle joint diameter and body weight were detected, and X-ray of left tarsus was observed in each group before and after modeling or after treatment. Serum levels of IL-17 and TNF-α were determined by ELISA kits. RESULTS: After modeling, the left ankle diameter and serum concentrations of IL-17 and TNF-α increased (P<0.05), and the body weight decreased (P<0.05) in the model group compared to the control group, combined with the tarsus soft tissue swelling, joint space narrowing, bone destruction seen from the tarsal X-ray. After intervention, the ankle diameter, the serum IL-17 and TNF-α levels decreased (P<0.05), and the body weight increased (P<0.05) in both medication and moxibustion groups compared to the model group; meanwhile the tarsus soft tissue swelling and the bone deformity turned to be improved. There were no significant differences between the medication group and the moxibustion group in above mentioned indexes (P>0.05). CONCLUSIONS: Moxi-bustion is effective in CIA rats, and the mechanism may be related to the reduction of serum IL-17 and TNF-α levels.
28134086 The spectrum of early rheumatoid arthritis practice across the globe: results from a multi 2017 May OBJECTIVES: To explore patterns of real-world early RA (ERA) care across countries. METHODS: An online survey was disseminated to practising rheumatologists across Europe and the US, also made accessible on social media between April and May 2015. Survey questions (n=38) assessed the structure and setting of ERA clinics, times to diagnosis and treatment, patient monitoring, guideline use and data recording. RESULTS: A total of 212 rheumatologists from 39 countries (76% European) completed the survey. 62% had an ERA clinic based at a university hospital. Patient referral to rheumatology was mainly (78%) via primary care; 44% had an agreed ERA local referral pathway, 15% a national pathway. Only 16% had dedicated ERA clinics, the majority being practitioners in Northern Europe with access to a local or national referral pathway. Data for research were collected by 42%. Treatment guidelines were followed by the majority, especially rheumatologists practising in Europe. Variations existed in the use of initial DMARDs with treatment decisions reported to be influenced by international/national guidelines in 71%/61%. No significant relationship between country gross national income and the availability of ERA clinics was seen. CONCLUSIONS: This study provides comparative benchmark information regarding the global provision of ERA care. Substantial variations exist in referral and early assessment pathways with guidelines having a most apparent impact in Northern Europe. Provision of an ERA service does not appear to be constrained by cost, with conceptual factors, e.g. clinician engagement, perhaps playing a role. These initial insights could potentially help harmonise ERA management across countries.
27830341 Serum progranulin levels in Hispanic rheumatoid arthritis patients treated with TNF antago 2017 Mar Since progranulin (PGRN) is a natural ligand of TNF receptors, we assessed whether serum PGRN levels predict and/or reflect responsiveness of RA patients to TNF-antagonist therapy. TNF-antagonist-naïve RA patients (N = 35) were started on TNF-antagonist therapy. At baseline and at follow-up visits, DAS28-ESR, DAS28-CRP, and CDAI were calculated, and venous blood was collected for serum PGRN determination. Disease activity and clinical response were based on EULAR criteria. Baseline serum PGRN levels varied considerably and correlated with ESR and CRP. DAS28-ESR, DAS28-CRP, and CDAI were greater in "PGRN-high" than in "PGRN-low". Baseline serum PGRN levels did not predict clinical responsiveness to TNF-antagonist therapy. Nevertheless, changes in serum PGRN levels at 274+ days following initiation of TNF-antagonist therapy correlated with changes in ESR, CRP, DAS28-ESR, DAS28-CRP, and CDAI. At this time, DAS28-ESR, DAS28-CRP, and CDAI in PGRN-high and PGRN-low equalized, but serum PGRN levels remained greater in PGRN-high than in PGRN-low. To our knowledge, the present report is the first prospective study to longitudinally assess changes in serum PGRN levels following initiation of TNF-antagonist therapy. Although pre-treatment serum PGRN levels may not predict clinical responsiveness to TNF-antagonist therapy, changes in serum PGRN levels correlate with changes in disease metrics over time. By inference, administration of PGRN may represent an effective therapeutic option for development in RA patients.
28741973 Characteristics of functional impairment in patients with long-standing rheumatoid arthrit 2018 May OBJECTIVE: To explore the characteristics of functional impairment in patients with established rheumatoid arthritis (RA) based on the range of motion (ROM) of joints in a prospective observational study of RA patients undergoing joint surgery. METHODS: We collected data on demographics, Health Assessment Questionnaire Disability Index (HAQ-DI), and the ROM of large joints including the shoulder, elbow, wrist, hip, knee, and ankle. Associations between the ROM of each joint and disability in the eight HAQ-DI categories were determined using receiver operating characteristic (ROC) and logistic regression analyses. ROM cut-off values of each joint for the absence of disability in each HAQ-DI category were determined using ROC curves. RESULTS: A total of 460 patients were enrolled and analyzed in this study. Based on ROC analysis, the ROM of each joint was significantly associated with disability in each category. After adjusting for disease activity, age, and sex, shoulder abduction had the highest independent impact on disability in activity [cut-off: 139 degrees (OR: 5.26)], elbow flexion-extension in dressing [121 degrees (OR: 2.22)], wrist flexion-extension in reach [86 degrees (OR: 2.71)], hip flexion-extension in walking [126 degrees (OR: 3.42)], and knee flexion-extension in walking [134 degrees (OR: 2.97)]. CONCLUSIONS: Limited ROM of multiple joints was significantly associated with functional impairment in patients with long-standing RA. Motion in daily activity involves multiple joints, and at least two joints were independently involved in disability.
28451872 The relationship between disease activity, quality of life, and personality types in rheum 2017 Jul We hypothesized that clinical outcomes might be influenced by personality type (A, B, C, D) in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). One hundred ninety-four patients (104 with RA, 90 with AS) participated in a questionnaire study. We evaluated health-related quality of life (HRQoL) using the Medical Outcome Study Short-Form 36 (SF-36), personality type A/B with the Jenkins Activity Survey, type C with the State-Trait Anger Expression Inventory Anger-in Scale, type D with the Type D Personality Scale, and disease activity with Disease Activity Score with 28 joints for RA and Bath Ankylosing Spondylitis Disease Activity Index for AS. We used Pearson's correlation coefficient, independent samples t tests, and multivariate analyses of variance. In the RA group, type D personality was significantly correlated with 7/12 SF-36 components. AS patients with type D personality had deficits in all SF-36 subscales. Type D was related with higher disease activity in RA and AS. Both RA and AS type C patients had more active disease forms and negatively affected HRQoL subscales. In the RA group, type A personality did not correlate with HRQoL, but it positively influenced pain visual analog scale scores. In AS patients, type A personality was linked with higher HRQoL and with less active disease. Type C and type D personality types were correlated with decreased HRQoL and higher disease activity in RA and AS patients. Type A personality was associated with less active disease and higher HRQoL in AS patients and with less pain in RA patients.
28700529 Rheumatologists Modestly More Likely to Counsel Smokers in Visits Without Rheumatoid Arthr 2017 Aug BACKGROUND: Among patients with rheumatoid arthritis (RA), smoking increases risk of severe RA and pulmonary and cardiovascular disease. Despite this, little is known about smoking cessation counseling by rheumatologists. OBJECTIVES: We examined predictors of tobacco counseling in RA patients who smoke including the effect of perceived RA control. We hypothesized that patients with controlled RA would receive more counseling according to the competing demands model, which explains that preventive care gaps occur as a result of competing provider, patient, and clinic factors. METHODS: This secondary data analysis involved RA patients with an additional cardiovascular disease risk factor identified in an academic medical center 2004-2011. Trained abstractors assessed documented smoking counseling and rheumatologists' impression of RA control in clinic notes. We used multivariable logistic regression to predict having received smoking cessation counseling, including sociodemographics and comorbidity in models. RESULTS: We abstracted 3396 RA visits, including 360 visits (10%) with active smokers. Perceived controlled RA was present in 31% of visits involving smokers (39% in nonsmokers). Beyond nurse documentation, providers documented smoking status in 39% of visit notes with smokers and smoking cessation counseling in 10%. Visits with controlled versus active RA were less likely to include counseling (odds ratio, 0.3; confidence interval, 0.1-0.97). Counseling was more likely in visits with prevalent cardiovascular, pulmonary, and psychiatric disease, but decreased with obesity. CONCLUSIONS: Smoking cessation counseling was documented in 10% of visits and was less likely when RA was controlled. Given smoking's impact on RA and long-term outcomes, systematic cessation counseling efforts are needed.
29160727 A Review of Perioperative Complications of Outpatient Total Ankle Arthroplasty. 2018 Feb BACKGROUND: Total ankle arthroplasty (TAA) is commonly pursued for patients with painful arthritis. Outpatient TAA are increasingly common and have been shown to decrease costs compared to inpatient surgery. However, there are very few studies examining the safety of outpatient TAA. In this study, we retrospectively reviewed 65 consecutive patients who received outpatient TAA to identify complication rates. METHODS: The medical records of 65 consecutive outpatient TAA from October 2012 to May 2016 with a minimum 6-month follow-up were reviewed. All patients received popliteal and saphenous blocks prior to surgery and were managed with oral pain medication postoperatively. All received a STAR total ankle. Demographics, comorbidities, American Society of Anesthesiologists (ASA) class, and perioperative complications including wound breakdown, infection, revision, and nonrevision surgeries were observed. Mean follow-up was 16.6 ± 9.1 months (range, 6-42 months). RESULTS: There were no readmissions for pain control and 1 patient had a wound infection. The overall complication rate was 15.4%. One ankle (1.5%) had a wound breakdown requiring debridement and flap coverage. This patient thrombosed a popliteal artery stent 1 month postop. The 1 ankle (1.5%) with a wound infection occurred in a patient with diabetes, obesity, hypertension, and rheumatoid arthritis. CONCLUSION: This study demonstrates the safety of outpatient TAA. The combination of regional anesthesia and oral narcotics provided a satisfactory experience with no readmissions for pain control and 1 wound infection. The 1 wound breakdown complication (1.5%) was attributed to arterial occlusion and not outpatient management. LEVEL OF EVIDENCE: Level IV, retrospective case series.
28711138 Genomic Influences on Susceptibility and Severity of Rheumatoid Arthritis. 2017 Aug Genetics in rheumatoid arthritis (RA) has moved from the finding of HLA-shared epitope decades ago toward the understanding of the role of HLA in RA and the findings of ∼100 additional genetic risk variants for disease susceptibility as well as several risk variants for severe disease. These findings increased our understanding of RA abnormality. Still, the mechanisms by which many of the variants exhibit their effect are not yet understood.
27841031 Improving B-cell depletion in systemic lupus erythematosus and rheumatoid arthritis. 2017 Jul Rituximab-based B-cell depletion (BCD) therapy is effective in refractory rheumatoid arthritis (RA) and although used to treat patients with refractory systemic lupus erythematosus (SLE) in routine clinical practice, rituximab failed to meet the primary endpoints in two large randomised controlled trials (RCTs) of non-renal (EXPLORER) and renal (LUNAR) SLE. Areas covered: We review how BCD could be improved to achieve better clinical responses in RA and SLE. Insights into the variability in clinical response to BCD in RA and SLE may help develop new therapeutic strategies. To this end, a literature search was performed using the following terms: rheumatoid arthritis, systemic erythematosus lupus, rituximab and B-cell depletion. Expert commentary: Poor trial design may have, at least partly, contributed to the apparent lack of response to BCD in the two RCTs of patients with SLE. Enhanced B-cell depletion and/or sequential therapy with belimumab may improve clinical response at least in some patients with SLE.
28618429 Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear Cells from 2017 BACKGROUND/AIMS: Circular RNAs (circRNAs) compose a large class of RNAs that can be used as biomarkers in clinical blood samples. This study aimed to determine the expression of circRNAs in peripheral blood mononuclear cells (PBMCs) from rheumatoid arthritis (RA) patients to identify novel biomarkers for RA screening. METHODS: We started with a microarray screening of circRNA changes in PBMCs from 5 RA patients and 5 healthy controls. We then confirmed the selected circRNA changes in PBMCs from 30 RA patients and 25 age- and sex-matched controls using the real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Spearman correlation test was performed to assess the correlation of circRNAs and clinical variables. Receiver operating characteristic (ROC) curve was calculated to evaluate the diagnostic value. RESULTS: We identified and verified five circRNAs (092516, 003524, 103047, 104871, 101873) that were significantly elevated in PBMCs from RA patients. Among these RA patients, we detected no significant correlation between the five circRNAs and the disease severity, including disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and health assessment questionnaire (HAQ). Yet, ROC curve analysis suggested that circRNA_104871 has significant value of RA diagnosis (AUC=0.833, P<0.001), followed by circRNA_003524 (AUC = 0.683, P = 0.020), circRNA_101873 (AUC = 0.676, P = 0.026), and circRNA_103047 (AUC = 0.671, P = 0.030). CONCLUSIONS: This study suggests that increased expression of circRNAs circRNA_104871, circRNA_003524, circRNA_101873 and circRNA_103047 in PBMC from RA patients may serve as potential biomarkers for RA patient diagnosis.
28290137 Sarilumab: First Global Approval. 2017 Apr Sarilumab (Kevzara™) is a fully human IgG1 monoclonal antibody that binds specifically to both soluble and membrane-bound interleukin (IL)-6 receptors (sIL-6Rα and mIL-6Rα) and thereby inhibits IL-6-mediated signalling through these receptors. Subcutaneous sarilumab is approved in Canada for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more biological or non-biological disease-modifying anti-rheumatic drugs. It is under regulatory review for use in rheumatoid arthritis in other countries, including in the EU, USA and Japan. Sarilumab is also under phase II investigation for the treatment of juvenile idiopathic arthritis. This article summarizes the milestones in the development of sarilumab leading to its first global approval for the treatment of rheumatoid arthritis.
29109029 Transcriptional profile of human macrophages stimulated by ultra-high molecular weight pol 2018 Jan Osteolysis is a serious postoperative complication of total joint arthroplasty that leads to aseptic loosening and surgical revision. Osteolysis is a chronic destructive process that occurs when host macrophages recognize implant particles and release inflammatory mediators that increase bone-resorbing osteoclastic activity and attenuate bone-formation osteoblastic activity. Although much progress has been made in understanding the molecular responses of macrophages to implant particles, the pathways/signals that initiate osteolysis remain poorly characterized. Transcriptomics and gene-expression profiling of these macrophages may unravel key mechanisms in the pathogenesis of osteolysis and aid the identification of molecular candidates for therapeutic intervention. To this end, we analyzed the transcriptional profiling of macrophages exposed to ultra-high molecular weight polyethylene (UHMWPE) particles, the most common components used in bearing materials of orthopedic implants. Regulated genes in stimulated macrophages were involved in cytokine, chemokine, growth factor and receptor activities. Gene enrichment analysis suggested that stimulated macrophages elicited common gene expression signatures for inflammation and rheumatoid arthritis. Among the regulated genes, tumor necrosis factor superfamily member 15 (TNFSF15) and chemokine ligand 20 (CCL20) were further characterized as molecular targets involved in the pathogenesis of osteolysis. Treatment of monocyte cultures with TNFSF15 and CCL20 resulted in an increase in osteoclastogenesis and bone-resorbing osteoclastic activity, suggesting their potential contribution to loosening between implants and bone tissues. STATEMENT OF SIGNIFICANCE: Implant loosening due to osteolysis is the most common mode of arthroplasty failure and represents a great challenge to orthopedic surgeons and a significant economic burden for patients and healthcare services worldwide. Bone loss secondary to a local inflammatory response initiated by particulate debris from implants is considered the principal feature of the pathogenesis of osteolysis. In the present study, we analyzed the transcriptional profiling of human macrophages exposed to UHMWPE particles and identified a large number of inflammatory genes that were not identified previously in macrophage responses to wear particles. Our data provide a new insight into the molecular pathogenesis of osteolysis and highlights a number of molecular targets with prognostic and therapeutic implications.
28762476 Use of Early Clinical Trial Data to Support Thorough QT Study Waiver for Upadacitinib and 2018 May Exposure-response analyses of QT data from early-stage clinical studies represent a valuable tool to assess the QT prolongation potential for drugs in development in lieu of standalone thorough QT (TQT) studies. However, demonstrating adequate electrocardiogram assay sensitivity can be challenging in the absence of a positive pharmacological control. Upadacitinib is a Janus kinase 1 inhibitor currently being evaluated in phase III rheumatoid arthritis trials. Exposure-response analyses to evaluate the QT prolongation potential for upadacitinib from phase I trials and the utility of the effect of food on QTcF to demonstrate ECG assay sensitivity are presented. The analyses demonstrated no effect of upadacitinib on QT interval and confirmed the sensitivity of the ECG assay to detect the small QT shortening effect caused by food. Lack of bias from manual ECG adjudication was also demonstrated. These analyses supported requesting a waiver for the regulatory requirement for a dedicated thorough QT study for upadacitinib.
28796299 Complement C3 and fatty liver disease in Rheumatoid arthritis patients: a cross-sectional 2017 Oct BACKGROUND: Recent evidence suggested a potential role of complement fraction C3 as a biomarker of nonalcoholic fatty liver disease (NAFLD) in the general population. Aim of this study was to evaluate the performance of C3 for prediction of NAFLD in RA patients. MATERIALS AND METHODS: For the present study, consecutive RA patients were recruited. NAFLD was diagnosed according to predefined ultrasonographic (US) criteria. For comparison, the hepatic steatosis index (HSI) was calculated. RESULTS: Of 164 consecutive RA patients, 41 (25%) were diagnosed with NAFLD. The NAFLD group had a significant lower proportion of females (P = 0·04), higher BMI (P < 0·0001), C-reactive protein (P = 0·04), complement C3 (P = 0·001) and HSI (P = 0·003). In a logistic regression model, only male sex (OR 2·65, 95% CI: 1·08-6·50, P = 0·03), increasing BMI (OR 1·22, 95% CI: 1·02-1·46, P = 0·03) and complement C3 (OR 5·05, 95% CI: 1·06-23·93, P = 0·04) were associated with higher likelihood of being diagnosed with NAFLD. Finally, we built ROC curves for BMI, complement C3 and their combination for prediction of having NAFLD. The best cut-off for BMI was 28·5 kg/m(2) and yielded a sensitivity of 66% and a specificity of 71%; the best cut-off for complement C3 was 1·23 g/L and yielded a sensitivity of 76% and a specificity of 64% for classification of NAFLD cases. CONCLUSIONS: Our results provide preliminary evidence for a potential role of complement C3 as a surrogate biomarker of NAFLD in RA patients.
28338585 A 16-Year Journey in the Study of Rheumatoid Hand Disease. 2017 Jul Evidence-based medicine is a relatively new concept in hand surgery. A lack of high-level evidence often leads to uncertainty in the effectiveness of various procedures and regional variation in their use. Rheumatoid hand surgery has been plagued by a lack of quality data that has caused controversy between rheumatologists and hand surgeons. Research over the past 16 years has strived to provide data that can be used to provide evidence-based care for rheumatoid arthritis patients. The Silicone Arthroplasty in Rheumatoid Arthritis study is a prospective, long-term cohort study of rheumatoid arthritis patients with severe metacarpophalangeal joint deformity who have elected to undergo or not to undergo metacarpophalangeal joint arthroplasty; the study was funded for 10 years by the National Institutes of Health and has provided invaluable results on the effectiveness of this procedure in terms of outcomes and cost, improving knowledge for both physicians and patients.