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ID PMID Title PublicationDate abstract
29191572 Th17 cells in primary Sjögren's syndrome: Pathogenicity and plasticity. 2018 Feb Th17 cells play an important physiological role at mucosal barriers, and are involved in inflammatory responses to pathogens. Th17 cells and their signature cytokine IL-17 are also present in salivary gland lesions of primary Sjögren's syndrome (pSS) patients and can be elevated in their peripheral blood. In pSS patients, clear correlations between increased Th17 cell activity and symptoms of the disease have not been found, but Th17 cells may contribute to disease progression, for example by supporting autoreactive B cell responses. In mouse models of pSS, Th17 cells play an important role in pathogenesis, particularly at disease onset, when there is a disturbed balance between T effector and T regulatory cells. Studying the pathogenicity of Th17 cells in humans is complicated due to the plasticity of this cell subset, allowing them to obtain different effector functions depending on the local environment. Th17 cells can develop towards Th17.1 cells, producing both IL-17 and IFN-γ, or even towards Th1-like cells producing IFN-γ in the absence of IL-17. These effector subsets may be more pathogenic than bona fide Th17 cells. Co-expression of IFN-γ by Th17 cells has been shown to promote chronic inflammation in several autoimmune diseases and may also contribute to pSS pathogenesis. In line with the noticeable role of IL-17 in pSS mouse models, interference with Th17 cell generation, recruitment or effector functions (e.g. IL-17 inhibition) can prevent or ameliorate disease in these models. Therapies targeting Th17 cells or IL-17 have not been tested so far in pSS patients, although treatment with rituximab seems to lower local and systemic IL-17 protein levels, and to a lesser extent also chemokine receptor-defined Th17 cells. In this review we discuss current knowledge of pathogenicity and plasticity of Th17 cells in human pSS and murine models of pSS. We postulate that plasticity towards Th17.1 cells in pSS may enhance pathogenicity of Th17 cells at the main target sites of the disease, i.e. salivary and lacrimal glands.
26634781 Subjective and objective voice evaluation in Sjögren's syndrome. 2017 Apr Objective The aim of this study is to assess the subjective and objective aspects of voice in Sjögren's syndrome. Methods The study enrolled 10 women with Sjögren's syndrome and 12 healthy women. Maximum phonation time, fundamental frequency, jitter, shimmer, and noise-to-harmonics ratio were determined during acoustic voice analysis. The Stroboscopy Evaluation Rating Form was used for the laryngostroboscopic evaluation. A subjective evaluation was performed using the Turkish version of Voice Handicap Index-10. Results The mean age of the Sjögren's syndrome and control groups was 46 ± 13.89 and 41.27 ± 6.99 years, respectively, and did not differ (P = 0.131). In the laryngostroboscopic evaluation, the smoothness and straightness of vocal folds, regularity, and glottal closure differed significantly. In the acoustic and aerodynamic analyses, none of the parameters differed statistically, while the Sjögren's syndrome group had significantly higher Voice Handicap Index-10 scores than the controls. Conclusion Sjögren's syndrome affects the voice and voice quality.
28197771 Granulomatous interstitial nephritis associated with Primary Sjögren's syndrome. 2017 Jun Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by lymphocytic and plasmacytic infiltration of the exocrine glands. Tubulointerstitial nephritis (TIN) is the most common type of renal involvement in pSS. However, clinically significant renal involvement is uncommon. Granulomatous interstitial nephritis (GIN) is a rare histopathological entity characterized by the presence of granulomas against a background of interstitial inflammation. GIN is not a typical and commonly seen form of TIN in pSS. Herein, we report on a patient who was concurrently diagnosed with pSS and GIN and was treated successfully with rituximab (RTX). pSS should be considered in the differential diagnosis of GIN, and RTX may be a good option in the treatment of this patient group.
29154979 Small fiber neuropathy: Diagnosis, causes, and treatment. 2018 Oct Small fiber neuropathy, which affects the sensory Aδ and C fibers, is now a major diagnostic and therapeutic challenge. Nearly 7% of the general population have chronic neuropathic pain responsible for severe quality-of-life impairments. Awareness must therefore be raised among clinicians of the somatosensory and autonomic symptoms that can reveal small fiber neuropathy, appropriate diagnostic investigations, most common causes, and best treatment options for each patient profile. To help achieve this goal, the present review article discusses the clinical presentation of neuropathic pain and paresthesia and/or autonomic dysfunction due to involvement of nerves supplying exocrine glands and smooth muscle; normal findings from standard electrophysiological investigations; most informative diagnostic tests (epidermal nerve fiber density in a skin biopsy, laser-evoked potentials, heat- and cold-detection thresholds, electrochemical skin conductance); main causes, which consist chiefly of metabolic diseases (diabetes mellitus, glucose intolerance), dysimmunity syndromes (Sjögren's syndrome, sarcoidosis, monoclonal gammopathy), and genetic abnormalities (familial amyloidosis due to a transthyretin mutation, Fabry disease, sodium channel diseases); and the available symptomatic and etiological treatments.
28159359 Clinical characteristics and survival of pulmonary arterial hypertension associated with t 2017 Jun 1 OBJECTIVE: Pulmonary arterial hypertension (PAH) is a major cause of death in connective tissue disease patients. This study investigated the clinical characteristics and survival of CTD-PAH in Chinese patients. METHODS: This cohort study enrolled 190 consecutive PAH patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), or primary Sjögren's syndrome (pSS) who visited our referral center between May 2006 and December 2014. Baseline demographics, clinical features, laboratory results, and hemodynamic assessments were analyzed. Cox proportional hazards regression analysis was used to identify independent factors associated with increased risk of mortality. RESULTS: The PAH patients were more likely to have SLE (58.4%) as the underlying CTD than SSc (26.3%) or pSS (15.3%). Mean age was 37.8±10.4years, and patients with SLE were youngest at the time of PAH diagnosis. The most prevalent autoantibody was anti-U1RNP antibody (55.8%). The three groups did not differ significantly regarding World Health Organization functional class or hemodynamic results. The overall 1-, 3-, and 5-year survival rates were 87.1%, 79.1%, and 62.9%, respectively. The 3-year survival rate of 81.3% for those with SLE-PAH was significantly better than that for patients with SSc-PAH (63.6%, P<0.05). Independent predictors of mortality were 6-minute walk distance (6MWD) ≤380m (HR 3.222, 95% CI 1.485-6.987, P=0.003) and underlying CTD (HR 1.684; 95CI% 1.082-2.622, P=0.021). CONCLUSION: Independent predictors of mortality for CTD-PAH were 6MWD <380m and SSc as the underlying CTD. Increased awareness of pSS-PAH is needed because of its worse prognosis compared to SLE-PAH.
28270185 Cigarette smoking and the risk of primary Sjögren's syndrome: a nested case control study 2017 Mar 7 BACKGROUND: Smoking is reported to affect the risk of a number of chronic disorders, including rheumatic diseases. Previous cross-sectional studies have shown a lower frequency of smoking in patients with primary Sjögren's syndrome (pSS). The aim of this study was to investigate the impact of smoking and socioeconomic status on the risk of subsequent diagnosis of pSS in a nested case-control study. METHOD: Participants in two large population-based health surveys who were later diagnosed with pSS were identified through linkage with the Malmö Sjögren's Syndrome Register. Matched controls were obtained from the health surveys. RESULTS: Sixty-three patients with pSS with pre-diagnostic data from the health surveys were identified. Current smoking was associated with a significantly lower risk of later being diagnosed with pSS (odds ratio (OR) 0.3; 95% CI 0.1-0.6). Furthermore, former smoking was associated with an increased risk of subsequent pSS diagnosis (OR 4.0; 95% CI 1.8-8.8) compared to never smoking. Similar results were found in a sub-analysis of patients with reported symptom onset after inclusion in the health surveys. Socioeconomic status and levels of formal education had no significant impact on the risk of later being diagnosed with pSS. CONCLUSION: In this nested case-control study, current smoking was associated with a reduced risk of subsequent diagnosis of pSS. In addition, former smoking was associated with an increased risk. Whether this reflects a biological effect of cigarette smoking or other mechanisms should be further investigated in future studies.
28546530 Quotidian High Spiking Fevers in Adult Still's Disease. 2017 May 26 BACKGROUND Adult Still's disease (ASD) is a rare systemic inflammatory condition, which commonly presents with the triad of quotidian fevers, rash, and non-specific rheumatologic symptoms such as myalgia and arthralgia. The etiology and pathogenesis are poorly understood and both the clinical presentation and laboratory data are typically nonspecific. As such, the presentation is often confused with infection, other autoimmune processes, and malignancy. CASE REPORT We present a case of a 29-year-old Hispanic female who presented with fever, sore throat, myalgia, and shortness of breath. Initially diagnosed with suspected pneumonia, extensive workup led to the final diagnosis of ASD due to the persistence of her symptoms, which met Yamaguchi Criteria, as well as exclusion of other possible etiologies. CONCLUSIONS ASD is a rare systemic inflammatory condition and its nonspecific presentation often leads to diagnostic delay and disease complications. We discuss the incidence, etiology, pathology, diagnosis, and standards in management of ASD. This case emphasizes the need for high clinical suspicion of ASD, and early exclusion of other etiologies, especially with failure of first-line treatment, to limit patient suffering and complications.
27191226 Pregnancy and primary Sjögren's syndrome: management and outcomes in a multicentre retros 2017 Jan OBJECTIVES: Primary Sjögren's syndrome (pSS) is one of the most common autoimmune diseases, mainly affecting women during the fourth decade of life. During pregnancy, the presence of anti-Ro/SSa and anti-La/SSb antibodies increases the risk of congenital heart block (CHB). Foetal and pregnancy outcomes in pregnant women with pSS compared with the general population are difficult to evaluate because of confounding factors including age and body mass index (BMI). METHOD: The aim of this case-control study was to analyse the impact of pSS in pregnant women on foetal and pregnancy outcomes. RESULTS: We enrolled 19 women with pSS (54 pregnancies) matched by age and BMI to 216 controls. Patients with pSS delivered significantly earlier (38 weeks + 3 days vs. 39 weeks + 2 days) and experienced more spontaneous abortions [< 22 weeks of gestation (WG)] than the controls [n = 16/54 (30.0%) vs. n = 1/216 (0.4%); p < 0.00001]. Preterm delivery (≤ 37(+6) WG) was significantly higher in the pSS group than in the control group (29% vs. 12%, p = 0.04). pSS activity significantly affected the birthweight percentile, which was lower in pregnancies occurring after the diagnosis of pSS than in those occurring before (32.43 ± 21.57 vs. 60.46 ± 27.37; p = 0.008). No case of CHB was observed. CONCLUSIONS: pSS is responsible for an increased risk of spontaneous abortion. The duration of pregnancy is lower in patients with than without pSS, with more premature deliveries. Pregnancies that occur after the onset of the disease result in lower birthweight percentile children than when pSS is not clinically overt.
28188909 Extensive preclinical evaluation of an infliximab biosimilar candidate. 2017 May 1 Infliximab is therapeutic monoclonal antibody (mAb) against TNF-α employed in the treatment of immunoinflammatory diseases. The development of biosimilar mAbs is a global strategy to increase drug accessibility and reduce therapy-associated costs. Herein we compared key physicochemical characteristics and biological activities produced by infliximab and infliximab-Probiomed in order to identify functionally relevant differences between the mAbs. Binding of infliximab-Probiomed to TNF-α was specific and had kinetics comparable to that of the reference product. Both mAbs had highly similar neutralizing efficacy in HUVEC cell cultures stimulated with TNF-α. In vitro induction of CDC and ADCC were also similar between the evaluated products. In vivo comparability was assessed using a transgenic mouse model of arthritis that expresses human TNF-α in a 13-week multiple-administration study. Infliximab and infliximab-Probiomed showed comparable efficacy, safety, and pharmacokinetic profiles. Our results indicate that infliximab-Probiomed has highly similar activities to infliximab in preclinical models, warranting a clinical evaluation of its biosimilarity.
29288368 Single nucleotide polymorphism of Methyl-CpG-binding protein 2 gene associates with juveni 2018 Feb Methyl-CpG-binding protein 2 (MeCP2) is a transcription suppressor or activator, acting through binding to methylated DNA. Numerous investigations have established a role for methylation aberrancies in the pathogenesis of autoimmune disorders. Single nucleotide polymorphisms (SNPs) in MECP2 gene have been implicated with susceptibility to rheumatoid arthritis (RA). Here, the plausible association of MECP2 gene polymorphisms was evaluated with juvenile idiopathic arthritis (JIA) predisposition in Iranian pediatric patients. In this case-control association study, 49 JIA patients and 398 age-, sex-, and ethnicity-matched healthy individuals were included. Genotyping of all samples for MECP2 gene rs1734787, rs1734791, rs1734792, and rs17435 polymorphisms was conducted by real-time allelic discrimination PCR technique. Except the AT genotype of rs17435 SNP, none of the alleles and genotypes of other positions were distributed significantly between JIA cases and controls. AT genotype was less frequent in JIA cases and was found to be protective genotype of JIA proneness (OR = 0.42; CI, 0.19-0.90; P = 0.028). Among the haplotypes, CCAA and TTTT were detected to have significant difference between cases and controls (OR = 1.74; CI, 1.01-2.98; P = 0.042 and OR = 1.82; CI, 1.05-3.13; P = 0.028). All positions were in linkage disequilibrium with each other according to D'. MECP2 gene rs17435 polymorphism was associated with JIA predisposition. Considering the involvement of genetic polymorphisms of MECP2 gene in susceptibility to adult-onset RA, this gene might basically play a role in the initiation of arthritis during early stages of life.
28557130 Female sexual pain: Epidemiology and genetic overlap with chronic widespread pain. 2017 Sep BACKGROUND: Increased tender spots and lowered general pain thresholds have been observed in patients with dyspareunia. Based on this, the aim of the study was to compare the co-occurrence of female sexual pain across various pain populations and to further explore the aetiological structure underlying sexual pain by dissecting the genetic and environmental covariation among sexual pain, chronic widespread pain (CWP) and the previously reported psychological correlates of anxiety sensitivity and depression. METHODS: A multivariate twin study including 1489 female twin individuals (246 full MZ pairs, 187 full DZ pairs and 623 whose co-twin did not participate). Main outcomes measures included self-reported diagnosis of osteoarthritis and rheumatoid arthritis, and validated questionnaires for the assessment of sexual pain, CWP, depression and anxiety sensitivity. RESULTS: Sexual pain showed a small but statistically significant correlation with CWP (r = 0.08; p < 0.05), anxiety sensitivity (r = 0.15, p < 0.001) and depression (r = 0.09, p < 0.01). The heritability of sexual pain was found to be 31%. Multivariate variance component analysis revealed a genetic factor common among CWP, depression, anxiety sensitivity and sexual pain, and a second genetic factor shared between anxiety sensitivity and sexual pain only. We further detected genetic and environmental factors unique to sexual pain, explaining 24.01% and 67.24%, respectively, of the phenotypic variance. CONCLUSIONS: Our findings suggest some overlap between sexual pain and CWP and point towards a shared but complex psychophysiological aetiology underlying sexual pain. Results further highlight the influence of specific environmental and contextual stressors in the development and maintenance of sexual pain. SIGNIFICANCE: Sexual pain shares a common genetic aetiology with chronic widespread pain and the frequently reported psychological comorbidities of depression and anxiety. Overall this suggests a complex psychophysiological aetiology underlying chronic pain conditions. The high proportion of variance in sexual pain explained by environmental factors further highlights the importance of specific environmental and contextual stressors in the development and maintenance of the condition.
28078603 A Comparison of the Anti-Inflammatory Effects of Cis-9, Trans-11 Conjugated Linoleic Acid 2017 Feb Cyclooxygenase (COX)-2 inhibitors, such as celecoxib, for chronic inflammatory disease are associated with adverse health events, while cis-9, trans-11 (c9t11) conjugated linoleic acid (CLA) is anti-inflammatory without adverse events attributed to pure intake. Mechanistically, celecoxib and c9t11 disrupt the arachidonic acid cascade; however, the equivalency of anti-inflammatory effects between these compounds is unknown. Therefore, to test the hypothesis that 0.5% dietary c9t11 reduces inflammation equivalently to a celecoxib dose intended to treat rheumatoid arthritis (RA; 5 mg/kg bw), arthritic mice received diets containing one of the following supplements: 1% corn oil (CO, w/w), 0.5% c9t11 (>91% purity) +0.5% CO, or 1% CO + 0.5, 5, or 50 mg/kg bw celecoxib, and were assessed for changes in arthritic severity over 6 weeks. Overall, arthritic severity in mice fed c9t11 was reduced (34%, P < 0.01) while celecoxib doses (0.5, 5, 50 mg/kg) reduced arthritic severity (16, 56, 48%, respectively) compared to CO-fed arthritic mice. Linear regression of the celecoxib dose-response showed 0.5% c9t11 (570 mg/kg bw) reduced arthritic severity equivalently to 1.5 mg/kg celecoxib. Interleukin-6 (IL-6) was increased in paws of arthritic mice fed CO compared to shams, but was decreased in arthritic groups fed 0.5% c9t11 and 5 mg/kg celecoxib, compared to arthritic mice fed CO (Ps ≤ 0.05). Additionally, paw and plasma IL-10 levels in arthritic mice were decreased by 5 mg/kg celecoxib, but were unaffected by c9t11 compared to CO. Results suggest dietary c9t11 may be an effective adjunct to COX-2 inhibition for treating chronic inflammation.
28007558 Aryl hydrocarbon receptor suppresses the osteogenesis of mesenchymal stem cells in collage 2017 Jan 15 The contributions of aryl hydrocarbon receptor (Ahr) to the pathogenesis of rheumatoid arthritis (RA), particularly bone loss, have not been clearly explored. The imbalance between osteoblasts and osteoclasts is a major reason for bone loss. The dysfunction of osteoblasts, which are derived from mesenchymal stem cells (MSCs), induced bone erosion occurs earlier and is characterized as more insidious. Here, we showed that the nuclear expression and translocation of Ahr were both significantly increased in MSCs from collagen-induced arthritis (CIA) mice. The enhanced Ahr suppressed the mRNA levels of osteoblastic markers including Alkaline phosphatase (Alp) and Runt-related transcription factor 2 (Runx2) in the differentiation of MSCs to osteoblasts in CIA. The 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated activation of Ahr dose-dependently suppressed the expression of osteoblastic markers. In addition, the expression of β-catenin was reduced in CIA MSCs compared with control, and the TCDD-mediated activation of the Ahr significantly inhibited β-catenin expression. The Wnt3a-induced the activation of Wnt/β-catenin pathway partly rescued the osteogenesis decline induced by TCDD. Taken together, these results indicate that activated Ahr plays a negative role in CIA MSCs osteogenesis, possibly by suppressing the expression of β-catenin.
28516237 Rheumatoid factor positivity increases all-cause and cancer mortality: a cohort study. 2017 Jul The aim of this study was to determine whether rheumatoid factor (RF) is associated with mortality from all-cause, cardiovascular disease (CVD), and cancer in the healthy adults. We recruited South Korean health check-up examinees without rheumatoid arthritis (RA). A cohort study was performed in 295,837 participants presumably free of osteoarthritis or RA, and who had undergone health screening between 2002 and 2012 and been followed up to determine the risk of all-cause, CVD, and cancer-specific mortality with respect to the presence or titer of RF. To determine whether the participants were deceased, we used National Death Index death certificates. The prevalence of RF positivity (≥20 IU/mL) was 4.4%. During 1,447,403 person-years of follow-up, 1402 participants died. Comparing subjects negative for RF with those positive for RF, the multivariable adjusted hazard ratio (HR; 95% CI) for all-cause and cancer mortality in subjects with RF-positivity was 1.50 (1.19-1.90) and 1.56 (1.12-2.16), respectively. Also, all-cause and cancer mortality risk was significantly greater in subjects with an RF titer greater than 100 IU/mL than in those with RF-negativity (HR = 2.68, 95% CI = 1.72-4.19; HR = 2.89, 95% CI = 1.58-5.28, respectively) after adjusting for multiple confounders. However, the HR for cardiovascular mortality was not higher in subjects with RF positivity than in those with RF negativity (HR = 0.98, 95% CI = 0.45-2.11). In Korean healthy adults, presumably without RA, RF was associated with a greater risk of all-cause and cancer mortality.
28855200 Real-world validation of the minimal disease activity index in psoriatic arthritis: an ana 2017 Aug 30 OBJECTIVE: To describe the minimal disease activity (MDA) rate over time in patients with psoriatic arthritis (PsA) receiving antitumour necrosis factor agents, evaluate prognostic factors of MDA achievement and identify the most common unmet criteria among MDA achievers. DESIGN: Biologic Treatment Registry Across Canada (BioTRAC): ongoing, prospective registry of patients initiating treatment for rheumatoid arthritis, ankylosing spondylitis or PsA with infliximab (IFX), golimumab (GLM) or ustekinumab. SETTING: 46 primary-care Canadian rheumatology practices. PARTICIPANTS: 223 patients with PsA receiving IFX (enrolled since 2005) and GLM (enrolled since 2010) with available MDA information at baseline, 6 months and/or 12 months. PRIMARY AND SECONDARY OUTCOME MEASURES: MDA was defined as ≥5 of the following criteria: 28-item tender joint count (TJC28) ≤1, 28-item swollen joint count (SJC28) ≤1, Psoriasis Area and Severity Index (PASI) ≤1 or body surface area≤3, Pain Visual Analogue Scale (VAS) ≤15 mm, patient's global assessment (PtGA) (VAS) ≤20 mm, Health Assessment Questionnaire (HAQ) ≤0.5, tender entheseal points ≤1. Independent prognostic factors of MDA achievement were assessed with multivariate logistic regression. RESULTS: MDA was achieved by 11.7% of patients at baseline, 43.5% at 6 months, 44.8% at 12 months and 48.8% at either 6 or 12 months. Among MDA achievers at 6 months, 75.7% had sustained MDA at 12 months. Lower baseline HAQ (OR=0.210; 95% CI: 0.099 to 0.447) and lower TJC28 (OR=0.880; 95% CI: 0.804 to 0.964), were significant prognostic factors of MDA achievement over 12 months of treatment. The most commonly unmet MDA criteria among MDA achievers was patient reported pain (25%), PtGA (15%) and PASI (12%). CONCLUSIONS: Almost 50% of patients treated with IFX or GLM in routine clinical care achieved MDA within the first year of treatment. Lower baseline HAQ and lower TJC28, were identified as significant prognostic factors of MDA achievement. The most commonly unmet criteria in patients who achieved MDA were pain, PtGA and PASI. TRIAL REGISTRATION NUMBER: BioTRAC (NCT00741793).
28502293 [Wuwei Wentong Chubi Capsule promotes the autophagy in synovial tissue of adjuvant-induced 2017 May Objective To evaluate the effect of Wuwei Wentong Chubi (WWWTCB) Capsule on the PI3K/AKT/mTOR signaling pathway in the synovial tissues of adjuvant-induced arthritis (AA) rats, and investigate its potential pharmacological mechanisms of treating rheumatoid arthritis. Methods Sixty Sprague Dawley (SD) rats were randomly assigned into six groups evenly: normal group, model group, WWWTCB groups at 0.80, 1.60, 3.20 g/kg body mass, and tripterygium glycosides tablet (TPT) group at 40 mg/kg body mass. Except for the normal group, the other five groups were induced into AA models with Complete Freund's Adjuvant (CFA). The WWWTCB or TPT, was administrated from day 12 after injection of CFA by gavage, once a day for 12 days. After that, unaffected ankle-joint tissues from the AA rats were collected for histopathological examination. The mRNA levels of PI3K, AKT, mTOR, p70s6 and beclin1 in the synovial tissue were detected by real-time quantitative PCR. Meanwhile, the protein levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70s6, p-p70s6 and beclin1 were determined by immunofluorescence histochemical staining and/or Western blotting. Results Compared with the model group, WWWTCB (1.60, 3.20 g/kg body mass) groups showed less ankle-joint injury and decreased proliferation of synovial cells in the ankle-joint tissues. In addition, the administration of WWWTCB decreased the mRNA and protein levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70s6 and p-p70s6, while increased the level of beclin1. Conclusion WWWTCB ameliorated AA in rats. The improvement might be closely related to the inhibitory effect of WWWTCB on the PI3K/AKT/mTOR signaling pathway and its promoting effect on the autophagy activity of synovial cells.
29072610 Spectrum-Effect Relationships between Fingerprints of Caulophyllum robustum Maxim and Inha 2017 Oct 26 Caulophyllum robustum Maxim (CRM) is a Chinese folk medicine with significant effect on treatment of rheumatoid arthritis (RA). This study was designed to explore the spectrum-effect relationships between high-performance liquid chromatography (HPLC) fingerprints and the anti-inflammatory effects of CRM. Seventeen common peaks were detected by fingerprint similarity evaluation software. Among them, 15 peaks were identified by Liquid Chromatography-Mass Spectrometry (LC-MS). Pharmacodynamics experiments were conducted in collagen-induced arthritis (CIA) mice to obtain the anti-inflammatory effects of different batches of CRM with four pro-inflammation cytokines (TNF-α, IL-β, IL-6, and IL-17) as indicators. These cytokines were suppressed at different levels according to the different batches of CRM treatment. The spectrum-effect relationships between chemical fingerprints and the pro-inflammation effects of CRM were established by multiple linear regression (MLR) and gray relational analysis (GRA). The spectrum-effect relationships revealed that the alkaloids (N-methylcytisine, magnoflorine), saponins (leiyemudanoside C, leiyemudanoside D, leiyemudanoside G, leiyemudanoside B, cauloside H, leonticin D, cauloside G, cauloside D, cauloside B, cauloside C, and cauloside A), sapogenins (oleanolic acid), β-sitosterols, and unknown compounds (X3, X17) together showed anti-inflammatory efficacy. The results also showed that the correlation between saponins and inflammatory factors was significantly closer than that of alkaloids, and saponins linked with less sugar may have higher inhibition effect on pro-inflammatory cytokines in CIA mice. This work provided a general model of the combination of HPLC and anti-inflammatory effects to study the spectrum-effect relationships of CRM, which can be used to discover the active substance and to control the quality of this treatment.
29267302 Efficacy and safety of selective glucocorticoid receptor modulators in comparison to gluco 2017 BACKGROUND: Long-term treatment with glucocorticoids (GCs) plays an important role in the management of arthritis patients, although the efficacy/safety balance is unfavorable. Alternatives with less (severe) adverse effects but with good efficacy are needed. Selective GC receptor modulators (SGRMs) are designed to engage the GC receptor with dissociative characteristics: transactivation of genes, which is mainly responsible for unwanted effects, is less strong while trans-repression of genes, reducing inflammation, is maintained. It is expected that SGRMs thus have a better efficacy/safety balance than GCs. A systematic review providing an overview of the evidence in arthritis is lacking. OBJECTIVE: To systematically review the current literature on efficacy and safety of oral SGRMs in comparison to GCs in arthritis. METHODS: A search was performed in Medline, Embase and the Cochrane Library, from inception dates of databases until May 2017. Experimental studies involving animal arthritis models or human material of arthritis patients, as well as clinical studies in arthritis patients were included, provided they reported original data. All types of arthritis were included. Data was extracted on the SGRM studied and on the GC used as reference standard; the design or setting of the study was extracted as well as the efficacy and safety results. RESULTS: A total of 207 articles was retrieved of which 17 articles were eligible for our analysis. Two studies concerned randomized controlled trials (RCT), five studies were pre-clinical studies using human material, and 10 studies involved pre-clinical animal models (acute and/or chronic arthritis induced in mice or rats). PF-04171327, the only compound investigated in a clinical trial setting, had a better efficacy/safety balance compared to GCs: better clinical anti-inflammatory efficacy and similar safety. CONCLUSION: Studies assessing both efficacy and safety of SGRMs are scarce. There is limited evidence for dissociation of anti-inflammatory and metabolic effects of the SGRMs studied. Development of many SGRMs is haltered in a preclinical phase. One SGRM showed a better clinical efficacy/safety balance.
29139035 Certolizumab Pegol in the Treatment of Psoriasis and Psoriatic Arthritis: Preliminary Real 2017 Dec INTRODUCTION: We present the results of real-life tests conducted in adults affected by psoriatic arthritis (PsA) with mild cutaneous involvement to evaluate the efficacy of certolizumab pegol (CZP), an anti-tumor necrosis factor-alpha agent approved in Europe for the treatment of rheumatoid arthritis and PsA. METHODS: Assessments included an evaluation of the Psoriasis Area and Severity Index (PASI) and the Disease Activity Score computed on 44 joints (DAS-44) correlated to the erythrocyte sedimentation rate (ESR) (DAS44-ESR). A total of 41 patients (16 men, 25 women; mean age 59.8 ± 8 years) completed the study. Of these, 36 patients were affected by both PsA and psoriasis, and five patients were affected only by PsA. A total of 32 patients (group A) completed 3 months of treatment (W12), and 12 patients completed 6 months of treatment (W24) (group B). RESULTS: The clinical efficacy of CZP was consistent on both the cutaneous and rheumatic components of the treatment. The mean PASI score decreased from 4.4 ± 4.7 at baseline (BL) to 2.3 ± 3.7 at W12 (group A), and from 5.1 ± 5.7 at BL to 0.8 ± 1.2 at W24 (group B). The DAS44-ESR decreased from 4.4 ± 0.6 at BL to a mean of 2.2 ± 0.9 at W12 (group A) and from 4.1 ± 0.6 at BL to a mean of 1.9 ± 0.5 at W24 (group B). No adverse events were reported. CONCLUSION: Our results demonstrate that CZP can be used safely and effectively to treat both the cutaneous and joint components of PsA. However, long-term data are needed to confirm our preliminary observations.
29164002 Biological therapy in arthritis patients with hepatitis B or C infection: a multicenter re 2017 Sep OBJECTIVE: Reactivation of viral hepatitis B (HBV) and C (HCV) has been reported in various case reports of patients with arthritis on biological therapy. The objective of this study was to describe the clinical characteristics and outcomes of arthritis patients with HBV or HCV treated with biological therapy. MATERIAL AND METHODS: This is a retrospective case series including all patients above 13 years of age with arthritis patients from four centers in Saudi Arabia with concurrent chronic viral hepatitis infection (HBV or HCV) who received biological agents in the rheumatology clinics during their course of their disease from duration of the disease onset until last outpatient visit up to November 2015. Demographic information, full details about the hepatitis status of each patient, rheumatic disease diagnosis and different therapies used were reviewed. RESULTS: We identified 10 cases each with HBV and HCV on biological therapy. The mean age in the HBV group was 51 (34-85) years and 80% were females. Eight patients had rheumatoid arthritis (RA), one patient had RA/systemic lupus erythematosus, and one had human immunodeficiency virus related-arthritis. Seven were chronic inactive HBsAg carriers and three had chronic active HBV. Nine HBV patients received prophylactic antiviral therapy. Two cases with chronic HBV had reactivation with no elevation of the transaminases.The mean age in the HCV group was 54 (23-79) years and all were female RA patients. Three had detectable hepatitis C virus-ribonuecleic acid (HCV-RNA) before the start of biological therapy. Nine HCV patients received antiviral treatment and seven had a sustained virologic response (SVR) before start of biological treatment. Three patients had detectable HCV-RNA during the course of biological therapy. One of the three was a non-responder and two were relapsers. One of the patients with HCV relapse was started on sofosbuvir plus ribavirin and achieved SVR on follow-up. CONCLUSION: We report the successful use of biological therapy in arthritis patients with hepatitis B infection with antiviral therapy with no detoriation of their viral status. Due to the lack of sufficient prospective studies demonstrating the rate of HCV flare on biological therapy, caution should be exercised and careful monitoring with liver enzymes and viral load is mandated in vulnerable HCV RNA patients. Treatment should be individualized by the rheumatologist in collaboration with the hepatologist to minimize complications.