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ID PMID Title PublicationDate abstract
25994093 Comparative efficacy and safety of tofacitinib, with or without methotrexate, in patients 2015 Dec This study aimed to assess the relative efficacy and safety of tofacitinib 5 and 10 mg twice daily, or in combination with methotrexate (MTX), in patients with active RA. Randomized controlled trials (RCTs) examining the efficacy and safety of tofacitinib in patients with active RA were included in this network meta-analysis. We performed a Bayesian network meta-analysis to combine the direct and indirect evidence from the RCTs. Ten RCTs including 4867 patients met the inclusion criteria. There were 21 pairwise comparisons including 11 direct comparisons of seven interventions. The ACR20 response rate was significantly higher in the tofacitinib 10 mg + MTX group than in the placebo and MTX groups (OR 7.56, 95 % credible interval (CrI) 3.07-21.16; OR 3.67, 95 % CrI 2.60-5.71, respectively). Ranking probabilities based on the surface under the cumulative ranking curve (SUCRA) indicated that tofacitinib 10 mg + MTX had the highest probability of being the best treatment for achieving the ACR20 response rate (SUCRA = 0.9254), followed by tofacitinib 5 mg + MTX (SUCRA = 0.7156), adalimumab 40 mg + MTX (SUCRA = 0.6097), tofacitinib 10 mg (SUCRA = 0.5984), tofacitinib 5 mg (SUCRA = 0.4749), MTX (SUCRA = 0.1674), and placebo (SUCRA = 0.0086). In contrast, the safety based on the number of withdrawals due to adverse events did not differ significantly among the seven interventions. Tofacitinib, at dosages 5 and 10 mg twice daily, in combination with MTX, was the most efficacious intervention for active RA and was not associated with a significant risk for withdrawals due to adverse events.
26912605 Coronary microvascular dysfunction in chronic inflammatory rheumatoid diseases. 2016 Jun 14 Chronic inflammatory rheumatoid diseases (CIRD) such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis are an important risk factor for the development of ischaemic heart disease and a source of high cardiovascular morbidity and mortality. In patients affected by CIRD, inflammation can affect coronary microvascular function and contribute to the development of myocardial ischemia and cardiovascular events, even in the absence of obstructive epicardial coronary artery disease. Understanding the molecular aspects that underlie the development of coronary microvascular dysfunction (CMD) in CIRD is of fundamental importance to identify specific therapeutic targets. In this article, we review the pathogenic mechanisms leading to CMD in CIRD, including the controversial results obtained with the use of different therapeutic strategies. We also propose that a practical diagnostic algorithm as the identification of CMD in patients with CIRD may lead to effective measures to prevent the development of angina pectoris and reduce the risk of rapid disease progression.
27074795 Change from subcutaneous to intravenous abatacept and back in patients with rheumatoid art 2016 Apr 14 BACKGROUND: Vacation can present a major problem to patients with rheumatoid arthritis (RA) treated with weekly subcutaneous biologics, including subcutaneous (SC) abatacept. Therefore, the replacement of four SC doses of abatacept by a single dose of intravenous (IV) abatacept may present an acceptable alternative to cover a 4-week interval needed for vacations. In the study presented, we analyzed the efficacy and safety of this intervention followed by a switch back to SC abatacept after 4 weeks. METHOD: This open-label, prospective, single-arm, 24-week trial recruited patients with established RA in low disease activity (LDA) or in remission on treatment with SC abatacept for at least 3 months to receive a single dose of IV abatacept (baseline) followed by a break of 4 weeks and then continuation of weekly SC abatacept from day 28 on. Disease-modifying anti-rheumatic drug (DMARD)-inadequate or biologic-inadequate responders (or both) were included. RESULTS: The baseline characteristics of the 49 patients (per protocol) were typical for a cohort of RA patients with established disease (mean disease duration of 8.31 years) in LDA under treatment with synthetic DMARDs and a biologic. Two patients (one flare and one patient decision) dropped out of the study. The proportions of patients with disease activity score in 28 joints (DAS-28) of not more than 3.2 at day 28 were 93.9 % (95 % confidence interval (CI) 83.5-97.9) and 93.6 % (95 % CI 82.8-97.8) at the end of the study (day 168). The average DAS-28 values were 1.74 (standard deviation (SD) ± 0.72) at baseline, 2.03 (SD ± 1.03) at day 28, and 1.96 (SD ± 0.92) at the end of the study (day 168). Pre-exposure to IV abatacept and having failed methotrexate or anti-tumor necrosis factor (anti-TNF) did not influence the average DAS-28 or the proportion of patients maintaining LDA over time. The average health assessment questionnaire disability index (HAQ-DI) was stable throughout the study. Adverse events (AEs) occurred in 75 % of subjects. Four serious AEs were described during the study. None of them was related to the investigational product, and all serious AEs could be resolved during hospitalization. CONCLUSION: This prospective, open-label study of abatacept shows for the first time that switching from weekly SC to IV abatacept and back after 4 weeks is an effective and safe way to bridge vacations in RA patients in LDA or remission. (NCT1846975, registered April 19, 2013.).
27567538 Oxidative stress modulates the cytokine response of differentiated Th17 and Th1 cells. 2016 Oct Reactive oxygen species (ROS) signaling is critical in T helper (Th) cell differentiation; however its role in differentiated Th cell functions is unclear. In this study, we investigated the role of oxidative stress on the effector functions of in vitro differentiated mouse Th17 and Th1 cells or CD4(+) T cells from patients with Rheumatoid Arthritis using pro-oxidants plumbagin (PB) and hydrogen peroxide. We found that in mouse Th cells, non-toxic concentration of pro-oxidants inhibited reactivation induced expression of IL-17A in Th17 and IFN-γ in Th1 cells by reducing the expression of their respective TFs, RORγt and T-bet. Interestingly, in both the subsets, PB increased the expression of IL-4 by enhancing reactivation induced ERK1/2 phosphorylation. We further investigated the cytokine modulatory effect of PB on CD4(+) T cells isolated from PBMCs of patients with Rheumatoid Arthritis, a well-known Th17 and or Th1 mediated disease. In human CD4(+) T cells from Rheumatoid Arthritis patients, PB reduced the frequencies of IL-17A(+) (Th17), IFN(-)γ(+) (Th1) and IL-17A(+)/IFN(-)γ(+) (Th17/1) cells and also inhibited the production of pro-inflammatory cytokines TNF-α and IL-6. N-Acetyl Cysteine (NAC) an antioxidant completely reversed PB mediated cytokine modulatory effects in both mouse and human cells indicating a direct role for ROS. Together our data suggest that oxidative microenvironment can alter cytokine response of terminally differentiated cells and thus altering intracellular ROS could be a potential way to target Th17 and Th1 cells in autoimmune disorders.
27626929 The Rheumatoid Arthritis Risk Variant CCR6DNP Regulates CCR6 via PARP-1. 2016 Sep Understanding the implications of genome-wide association studies (GWAS) for disease biology requires both identification of causal variants and definition of how these variants alter gene function. The non-coding triallelic dinucleotide polymorphism CCR6DNP is associated with risk for rheumatoid arthritis, and is considered likely causal because allelic variation correlates with expression of the chemokine receptor CCR6. Using transcription activator-like effector nuclease (TALEN) gene editing, we confirmed that CCR6DNP regulates CCR6. To identify the associated transcription factor, we applied a novel assay, Flanking Restriction Enhanced Pulldown (FREP), to identify specific association of poly (ADP-ribose) polymerase 1 (PARP-1) with CCR6DNP consistent with the established allelic risk hierarchy. Correspondingly, manipulation of PARP-1 expression or activity impaired CCR6 expression in several lineages. These findings show that CCR6DNP is a causal variant through which PARP-1 regulates CCR6, and introduce a highly efficient approach to interrogate non-coding genetic polymorphisms associated with human disease.
25982034 Chronic diseases, medical history and familial cancer, and risk of leukemia and non-Hodgki 2015 Jul PURPOSE: This investigation was aimed at evaluating the association between chronic diseases, medical history and familial cancer, and the risk of developing hematological malignancies. METHODS: Data were drawn from a population-based case-control study carried out to assess the risk of non-Hodgkin's lymphoma and leukemia in an adult population exposed to environmental air pollution in Northern Italy. Each case was classified according to the WHO ICD-O-3 classification. Statistical analyses were performed by multivariable unconditional logistic regression in 573 interviewed subjects (199 lymphoid cases, 95 myeloid cases, and 279 healthy controls). RESULTS: Lymphoid malignancies were associated with a history of gastroduodenal ulcer (OR 2.1, 95 % CI 1.2-3.6), rheumatoid arthritis (OR 4.4, 95 % CI 1.3-19.0), anemia (OR 3.3, 95 % CI 1.2-9.3), cholecystectomy (OR 2.9, 95 % CI 1.0-8.0), heavy diagnostic X-ray exposure (OR 2.1, 95 % CI 1.3-3.7), and a familial risk of non-Hodgkin's lymphoma (OR 10.1, 95 % CI 1.3-458). Myeloid malignancies were associated with non-neoplastic thyroid diseases (OR 6.2, 95 % CI 1.7-35.6) and anemia (OR 6.8, 95 % CI 2.0-23.1). Subgroup analysis highlighted an excess risk of MALT in patients with gastroduodenal ulcer (OR 5.3, 95 % CI 1.04-23.7) and of AML in patients with rheumatoid arthritis (OR 6.9, 95 % CI 1.2-38.1), and of MDS in subjects exposed to heavy diagnostic X-ray (OR 3.4, 95 % CI 1.03-11.2) when the analysis was restricted to irradiation of pelvis, abdomen, or thorax. CONCLUSIONS: Most observed associations confirm results from previous studies. The higher risk of lymphoid malignancies among patients with a history of cholecystectomy needs further investigations.
27098820 Multifactorial intervention to prevent cardiovascular disease in patients with early rheum 2016 Apr 20 INTRODUCTION: Cardiovascular morbidity is a major burden in patients with rheumatoid arthritis (RA). In this study, we compare the effect of a targeted, intensified, multifactorial intervention with that of conventional treatment of modifiable risk factors for cardiovascular disease (CVD) in patients with early RA fulfilling the 2010 American College of Rheumatology European League Against Rheumatism (ACR/EULAR) criteria. METHODS AND ANALYSIS: The study is a prospective, randomised, open label trial with blinded end point assessment and balanced randomisation (1:1) conducted in 10 outpatient clinics in Denmark. The primary end point after 5 years of follow-up is a composite of death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke and cardiac revascularisation. Secondary outcomes are: the proportion of patients achieving low-density lipoprotein cholesterol <2.5 mmol/L, glycated haemoglobin <48 mmol/mol, blood pressure <140/90 mm  Hg for patients without diabetes and <130/80 mm Hg for patients with diabetes and normoalbuminuria (urinary albumin creatinine ratio <30 mg/g) after 1 year of follow-up and the proportion of patients in each treatment group achieving low RA disease activity after 1 year, defined as a disease activity score C-reactive protein (DAS28-CRP) <3.2 and a DAS28-CRP score <2.6 after 12, 24 and 60 months. Furthermore, all hospitalisations for acute and elective reasons will be adjudicated by the event committee after 12, 24 and 60 months. Three hundred treatment-naive patients with early RA will be randomly assigned (1:1) to receive either conventional treatment administered and monitored by their general practitioner according to national guidelines (control group) or a stepwise implementation administered and monitored in a quarterly rheumatological nurse-administered set-up of behaviour modification and pharmacological therapy targeting (1) hyperlipidaemia, (2) hypertension, (3) hyperglycaemia and (4) microalbuminuria (intervention group). ETHICS AND DISSEMINATION: This protocol is approved by the local ethics committee (DK-S-2014007) and The Danish Health and Medicines Authority. Dissemination will occur through presentations at National and International conferences and publications in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02246257.
25246639 Profound reduction in hospital admissions and musculoskeletal surgical procedures for rheu 2015 Apr OBJECTIVES: The aims of this study were to audit the annual national incidence of inpatient days and musculoskeletal surgical procedures (MSKSPs) for RA patients and to establish concurrent changes in clinical rheumatology practice from 1995 to 2010. METHODS: Hospital inpatient enquiry systems were evaluated for 57 hospitals from 1995 to 2010. National annual TNF inhibitor (TNFi) and MTX prescriptions were analysed. Trends were analysed by logistic regression and correlations by Spearman's rho. RESULTS: Fifty-four thousand eight hundred and six RA inpatient records were reviewed from 1995 to 2010 [70% female, mean age 66 years (s.d. 16)]. RA inpatient days decreased from 53 671 in 1995 to 29 000 in 2010 (r(2) = 0.8, P < 0.0001). Inpatient MSKSPs for RA patients decreased from a peak of 370 in 1996 to 188 in 2010 (r(2) = 0.7, P < 0.0001). Knee and hip replacements for the general population annually increased over the past 15 years, yet there was a significant decrease in the annual ratio of hip arthroplasties and knee arthroplasties for RA patients compared with those done for the general population from 1995 to 2010 (r(2) = 0.6, P < 0.001 and r(2) = 0.8, P < 0.01, respectively). Annual national TNFi prescriptions increased from 2389 units in 2000 to 116 747 in 2010. Concurrently MTX prescriptions increased nationally from 3300 in 2001 to 9600 in 2010. During the same period there was an increase in rheumatologists from 15 to 40 and in orthopaedic surgeons from 64 to 88. CONCLUSION: Elective MSKSPs for RA patients have almost halved over the past 15 years, despite an increase in hip and knee arthroplasties for the general population, along with an almost halving of inpatient days for RA patients.
27872288 MIF allele-dependent regulation of the MIF coreceptor CD44 and role in rheumatoid arthriti 2016 Dec 6 Fibroblast-like synoviocytes mediate joint destruction in rheumatoid arthritis and exhibit sustained proinflammatory and invasive properties. CD44 is a polymorphic transmembrane protein with defined roles in matrix interaction and tumor invasion that is also a signaling coreceptor for macrophage migration inhibitory factor (MIF), which engages cell surface CD74. High-expression MIF alleles (rs5844572) are associated with rheumatoid joint erosion, but whether MIF signaling through the CD74/CD44 receptor complex promotes upstream autoimmune responses or contributes directly to synovial joint destruction is unknown. We report here the functional regulation of CD44 by an autocrine pathway in synovial fibroblasts that is driven by high-expression MIF alleles to up-regulate an inflammatory and invasive phenotype. MIF increases CD44 expression, promotes its recruitment into a functional signal transduction complex, and stimulates alternative exon splicing, leading to expression of the CD44v3-v6 isoforms associated with oncogenic invasion. CD44 recruitment into the MIF receptor complex, downstream MAPK and RhoA signaling, and invasive phenotype require MIF and CD74 and are reduced by MIF pathway antagonists. These data support a functional role for high-MIF expression alleles and the two-component CD74/CD44 MIF receptor in rheumatoid arthritis and suggest that pharmacologic inhibition of this pathway may offer a specific means to interfere with progressive joint destruction.
28530055 [PULMONARY FIBROSIS INDUCED BY ANTI־TNF-Αlpha TREATMENT]. 2016 Oct INTRODUCTION: TNFα-targeted therapies have emerged as a new class of drugs in the treatment of various inflammatory diseases, including psoriasis. With the increasing use and longer follow-up periods of TNFα targeted therapies, a spectrum of immunological adverse events have been described, ranging from asymptomatic immunological alterations to life-threatening systemic diseases such as pulmonary fibrosis. We present a case of a 66 year old man diagnosed with psoriasis who developed pulmonary fibrosis three years after initiation of Etanercept (Enbrel) for his skin disease. CONCLUSIONS: We presented a rare case of a patient who developed pulmonary fibrosis, possibly triggered by anti-TNFα treatment. We suggest that adverse effects related to anti-TNFα should be evaluated carefully, considering pulmonary fibrosis as a possible side effect, especially among patients with risk factors for its development. DISCUSSION: There are growing numbers of reports of the paradoxical induction of pulmonary interstitial disease due to TNFα blockers, yet most of them are uncontrolled studies in patients with rheumatoid arthritis or other autoimmune diseases that can involve the lungs. Therefore, definitive conclusions are not possible at this stage. Recent studies described the poor prognosis of pulmonary fibrosis secondary to anti-TNFα therapy, with the mortality rate of up to 60% among patients with previous pulmonary disease. Coexisting or previous therapy with Methotrexate had stronger association with the development of drug-induced pulmonary fibrosis.
25701260 Primary laryngeal cryptococcosis resembling laryngeal carcinoma. 2015 Aug A case of an 82-year-old female with primary laryngeal cryptococcosis who had undergone long-term corticosteroid therapy for chronic obstructive pulmonary disease and rheumatoid arthritis is reported. She complained hoarseness with swallowing pain and irritability of the larynx for over a month. Endoscopic examination revealed a white, exudative irregular region on right arytenoid that mimicked a laryngeal carcinoma. Histological examination showed pseudoepitheliomatous hyperplasia and severe submucosal inflammation with ovoid budding yeasts by Grocott's stain. A serological study indicated a high titer of cryptococcal antigen. After treating with oral fluconazole for 3 months, her primary lesion of larynx turned to be clear. We implicate a long-term use of steroids as the significant risk factor in developing cryptococcosis of the larynx.
26764105 Physicochemical characterization and in vivo evaluation of triamcinolone acetonide-loaded 2016 Apr 1 The current study was aimed to investigate the anti-inflammatory effect of triamcinolone acetonide-loaded hydroxyapatite (TA-loaded HAp) nanocomposites in the arthritic rat model. The HAp nanocomposites were synthesized through a chemical precipitation method and the drug was subsequently incorporated into the nanocomposites using an impregnation method. The physicochemical properties as well as cytotoxicity of the prepared nanoformulation were examined as well. To evaluate the therapeutic efficacy of the prepared nanoformulation, the various parameters such as paw volume, haematological parameters and histological studies were assessed in the arthritic rats. The nanocomposites with the particle size of 70.45 nm, pore size of 2.71 nm and drug loading of 41.94% were obtained in this study. The specific surface area (aBET) as well as the volume of nitrogen adsorbed on one gram of HAp to complete the monolayer adsorption (Vm) were decreased after the drug loading process. The prepared nanoformulation revealed the slower drug release profile compared to the pure drug. Furthermore, the obtained data from MTT assay showed that the TA-loaded nanocomposites had a lower cytotoxic effect on NIH-3T3 and CAOV-4 cell lines as compared to the pure drug. Furthermore, TA-loaded HAp nanocomposites demonstrated favorable effects on the paw volume as well as the haematological and histopathological abnormalities in the adjuvant-induced arthritic rats. Therefore, TA-loaded HAp nanocomposites are potentially suggested for treatment of rheumatoid arthritis after further required evaluations.
25349443 Is serum procalcitonin measurement a useful addition to a rheumatologist's repertoire? A r 2015 Feb Early differentiation between infection and aseptic inflammation is difficult and is a challenge often faced in the rheumatology practice. Procalcitonin (PCT) is a biomarker that is preferentially induced in patients with bacterial infections, and a growing body of evidence supports its use for improving diagnosis of bacterial infections and guiding antibiotic therapy. In this article, we review the evidence for the use of PCT measurement in rheumatology practice. Several studies have examined the use of PCT to assist in the differentiation between septic and non-septic arthritis in patients with an inflamed joint and found it to be a sensitive and specific marker of infection. A number of studies in patients with diverse inflammatory rheumatic diseases have provided useful information regarding the usefulness of PCT in these patients. In summary, PCT when used in the appropriate clinical setting can be a useful adjunct to currently available laboratory infection markers, though further studies are warranted. Furthermore, PCT results should be interpreted in parallel with the clinical assessment.
26796771 Content validity of global measures for at-work productivity in patients with rheumatic di 2016 Aug OBJECTIVES: To identify from a patient's perspective, difficulties and differences in the comprehension of five global presenteeism measures in patients with inflammatory arthritis and OA across seven countries. METHODS: Seventy patients with a diagnosis of inflammatory arthritis or OA in paid employment were recruited from seven countries across Europe and Canada. Patients were randomly allocated to be cognitively debriefed on 3/5 global measures [Work Productivity Scale - Rheumatoid Arthritis, Work Productivity and Activity Impairment Questionnaire (WPAI), Work Ability Index, Quality and Quantity questionnaire, and WHO Health and Work Performance Questionnaire (HPQ)], with the WPAI debriefed in all patients as a standard measure of comparison between countries and patients. NVivo was used to code the data into four themes: construct and anchor, time recall, reference frame, and attribution. RESULTS: Discrepancies were found in the interpretation of the word performance (HPQ) between countries, with Romania and Sweden relating performance to sports rather than work. Seventy percent of patients considered that a 7-day recall (WPAI) can accurately represent how their disease affects work productivity. The compared to normal reference (Quality and Quantity questionnaire) was reportedly too ambiguous, and the comparison with colleagues (HPQ), made many feel uncomfortable. Overall, 29% of patients said the WPAI was the most relevant to them, making it the most favoured measure. CONCLUSION: Overall, patients across countries agree that the construct of work productivity in the last 7 days can accurately reflect the impact of disease while at work. Some current constructs to assess at-work productivity are not interchangeable between languages.
27457510 Physical trauma recorded in primary care is associated with the onset of psoriatic arthrit 2017 Mar OBJECTIVES: To evaluate the risk of psoriatic arthritis (PsA) among patients with psoriasis exposed to physical trauma. METHODS: A matched cohort study was performed using data from The Health Improvement Network (THIN). Patients with psoriasis exposed to trauma were randomly matched to up to five unexposed psoriasis controls based on gender, age, duration of psoriasis and the date of entry into THIN. Trauma exposure was stratified into subgroups of joint, bone, nerve and skin trauma. Cox proportional hazard models were used to estimate the HRs for developing PsA. For comparison, an identical analysis was performed in the entire THIN population evaluating rheumatoid arthritis (RA) risk following physical trauma. RESULTS: Patients with psoriasis exposed to trauma (N=15 416) and matched unexposed patients (N=55 230) were followed for a total of 425 120 person-years during which 1010 incident PsA cases were recorded. Adjusting for potential confounders, patients with psoriasis exposed to trauma had an increased risk of PsA compared with controls, with a multivariate HR of 1.32 (95% CI 1.13 to 1.54). In our subset analysis, bone and joint trauma were associated with multivariate HRs of 1.46 (95% CI 1.04 to 2.04) and 1.50 (95% CI 1.19 to 1.90), respectively; while nerve and skin trauma were not associated with a statistically significant increase in risk compared with controls. Patients exposed to trauma in the entire THIN population did not have an increased risk of developing RA: HR 1.04 (95% CI 0.99 to 1.10). CONCLUSIONS: Patients with psoriasis exposed to physical trauma are at an increased risk of developing PsA.
27600829 Sarilumab plus methotrexate improves patient-reported outcomes in patients with active rhe 2016 Sep 6 BACKGROUND: Sarilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-6 receptor complex. In the MOBILITY phase III randomized controlled trial (RCT), sarilumab + methotrexate (MTX) treatment resulted in clinical improvements at 24 weeks that were maintained at 52 weeks in adults with rheumatoid arthritis (RA), who have inadequate response to MTX (MTX-IR). These analyses indicate the effects of sarilumab + MTX versus placebo on patient-reported outcomes (PROs) in this RCT. METHODS: Patients (n = 1197) were randomized to receive placebo, sarilumab 150 or 200 mg subcutaneously + MTX every 2 weeks for 52 weeks; after 16 weeks, patients without ≥20 % improvement from baseline in swollen or tender joint counts on two consecutive assessments were offered open-label treatment. PROs included patient global assessment of disease activity (PtGA), pain, health assessment questionnaire disability index (HAQ-DI), Short Form-36 Health Survey (SF-36), and functional assessment of chronic illness therapy-fatigue (FACIT-F). Changes from baseline at weeks 24 and 52 were analyzed using a mixed model for repeated measures. Post hoc analyses included percentages of patients reporting improvements equal to or greater than minimal clinically important differences (MCID) and normative values in the FACIT-F and SF-36. Pearson correlation between observed PRO scores and clinical measures of disease activity was tested at week 24. RESULTS: Both doses of sarilumab + MTX vs placebo + MTX resulted in improvement from baseline by week 24 in PtGA, pain, HAQ-DI, SF-36 and FACIT-F scores (p < 0.0001) that was clinically meaningful, and persisted until week 52. In post hoc analyses, the percentages of patients with improvement equal to or greater than the MCID across all PROs were greater with sarilumab than placebo (p < 0.05), with differences ranging from 11.6 to 26.2 %, as were those reporting equal to or greater than normative scores. CONCLUSIONS: In this RCT in patients with MTX-IR RA, sarilumab + MTX resulted in sustained improvement in PROs that were clinically meaningful, greater than placebo + MTX, and complement the previously reported clinical efficacy and safety of sarilumab. TRIAL REGISTRATION: ClinicalTrials.gov. NCT01061736 . February 2, 2010.
28214498 Vasculitic and autoimmune wounds. 2017 Mar OBJECTIVE: Chronic wounds are a major cause of morbidity and mortality. Approximately 20% to 23% of nonhealing wounds that are refractory to vascular intervention have other causes, including vasculitis, pyoderma gangrenosum, and other autoimmune diseases. The purpose of this article was to review the literature across medical and surgical specialties with regard to refractory chronic wounds associated with vasculitis and autoimmune diseases and to delineate clinical outcomes of these wounds in response to vascular and other interventions. METHODS: An electronic search encompassing MEDLINE, PubMed, Cochrane Library, and Scopus was completed using the following search terms: rheumatoid arthritis; systemic sclerosis; systemic lupus erythematosus; antineutrophil cytoplasmic antibody-associated vasculitis; mixed connective tissue disease; antiphospholipid syndrome; pyoderma gangrenosum; thromboangiitis obliterans; cryoglobulinemia; hydroxyurea; sickle cell; atrophie blanche; livedoid vasculitis; cholesterol emboli; calciphylaxis; antiphospholipid antibodies; prothrombotic; combined with the terms: chronic wound and leg ulcer. Full-text articles published in English up to March 1, 2016, that investigated the clinical outcomes of chronic wounds associated with autoimmune diseases were included. Review articles and evaluations of management of chronic wounds were also reviewed. Primary outcomes included in the review were amputation, ulcer healing, reduction in wound size, overall survival, and freedom from reintervention. Owing to the heterogeneity of data reporting among articles, qualitative analysis is also reported. RESULTS: Vasculitis and autoimmune diseases play a role in 20% to 23% of patients with chronic lower extremity ulcers. Furthermore, patients with autoimmune disease have a significantly high rate of split thickness skin graft failure (50% compared to 97% in patients without autoimmune disease; P = .0002). The management of leg ulcers associated with autoimmune diseases is discussed. CONCLUSIONS: Autoimmune and vasculitic causes should be considered in patients with chronic wounds who do not respond to appropriate vascular intervention and standard local wound care. A multidisciplinary approach with the involvement of rheumatologists allows investigation for underlying systemic disease and improves clinical outcomes for many of these challenging patients.
27889300 Tofacitinib Versus Biologic Treatments in Patients With Active Rheumatoid Arthritis Who Ha 2016 Dec PURPOSE: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This analysis compared the efficacy and safety of tofacitinib with biologic disease-modifying antirheumatic drugs in patients with RA and a prior inadequate response (IR) to tumor necrosis factor inhibitors (TNFi). METHODS: A systematic literature review identified 5 randomized placebo-controlled trials that evaluated tofacitinib or biologic disease-modifying antirheumatic drugs (bDMARDs) against placebo in patient populations with RA with a prior IR to TNFi. The definition of TNFi-IR varied across studies, and included patients with an IR or who had failed treatment with TNFi for any reason. A network meta-analysis was conducted comparing study data with regard to American College of Rheumatology response rates and Health Assessment Questionnaire-Disability Index improvement at weeks 12 and 24, rates of treatment withdrawal due to all causes; adverse events (AEs) and lack of efficacy; and rates of AEs, serious AEs, and serious infections. FINDINGS: The 5 trials included a total of 2136 patients. Tofacitinib 5 mg twice daily combined with methotrexate was found to have relative risk estimates of American College of Rheumatology responses and change from baseline in Health Assessment Questionnaire-Disability Index score comparable with abatacept, golimumab, rituximab, and tocilizumab combined with conventional synthetic disease-modifying antirheumatic drugs. Withdrawal rates from trials due to all causes and AEs were comparable between treatments, and tofacitinib had a lower rate of withdrawals due to lack of efficacy. Rates of AEs and HAQ-DI were comparable between tofacitinib, other active treatments, and placebo. No serious infections were reported with tofacitinib during the placebo-controlled period (up to week 12) in this study population; rates of serious infection with other active treatments were generally low and similar to placebo. IMPLICATIONS: During a 24-week period, tofacitinib had efficacy and rates of AEs comparable with currently available bDMARDs in the treatment of patients with RA who had a prior IR to TNFi. ClinicalTrials.gov identifiers: ORAL Step, NCT00960440; ATTAIN, NCT00124982; GO-AFTER, NCT00299546; RADIATE, NCT00106522; REFLEX, NCT00462345.
25640532 Increasing patients with pulmonary Mycobacterium avium complex disease and associated unde 2015 May This study was conducted to evaluate trends in the isolation of strains of nontuberculous mycobacteria (NTM) and trends in the number of patients with pulmonary Mycobacterium avium complex (MAC) disease. We retrospectively reviewed microbiological results and clinical data to identify patients who were diagnosed with pulmonary MAC disease at Kyoto University Hospital in Japan between 2000 and 2013. NTM were isolated from 6327 of 80,285 samples (7.9%) for mycobacterial culture. The proportion of NTM isolates among all mycobacterial isolates increased from 355 of 792 samples (44.8%) in 2000 to 688 of 847 samples (81.2%) in 2013. MAC was most frequently observed (5436 isolates, 85.9%), followed by Mycobacterium abscessus (175 isolates, 2.8%) and Mycobacterium kansasii (74 isolates, 1.2%). A total of 592 patients with pulmonary MAC disease were identified (age, 66.0 ± 11.5 years; females, 61.1%). Compared with the early cohort (2000-2006, 236 patients), more patients in the late cohort (2007-2013, 356 patients) had an underlying disease (157 [66.5%] vs. 284 [79.8%], P = 0.0003), a Charlson comorbidity index score ≥ 1 (115 [48.7%] vs. 213 [59.8%], P = 0.008), collagen vascular disease (18 [7.6%] vs. 60 [16.9%], P = 0.001), rheumatoid arthritis (11 [4.7%] vs. 41 [11.5%], P = 0.004), and used immunosuppressive drugs (22 [9.3%] vs. 63 [17.7%], P = 0.004). The numbers of patients with lung disease, malignant disease and diabetes mellitus increased; however, their frequencies did not differ. The recovery rate of NTM and patients with pulmonary MAC disease increased, especially in patients with collagen vascular disease or rheumatoid arthritis or who used immunosuppressive drugs.
27255354 Association of Pentraxin 3 with Autoimmune Diseases: A Systematic Review and Meta-Analysis 2016 Apr BACKGROUND AND AIMS: Pentraxin 3 (PTX3) plays an important role in the inflammatory processes. Recently it has been reported to be involved in autoimmune diseases. Many studies have investigated the serum/plasma levels of PTX3 in autoimmune diseases, but the results are contradictory or inconclusive among those findings. The purpose of this meta-analysis was to investigate whether serum/plasma levels of PTX3 were associated with autoimmune diseases by comparing the serum/plasma levels of PTX3 in the autoimmune diseases and healthy controls. METHODS: PubMed, ELSEVIER ScienceDirect and Cochrane Library databases (up to December 26, 2015) were used to obtain all relative published literatures. The study quality was assessed by the Newcastle-Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis. RESULTS: A total of 20 studies including seven studies of systemic lupus erythematosus (SLE), four studies of ankylosing spondylitis (AS), five studies of rheumatoid arthritis (RA), three studies of systemic sclerosis (SSc) and one study of multiple sclerosis (MS) were finally included in the meta-analysis. The results revealed that the serum/plasma levels of PTX3 in autoimmune diseases were significantly higher than in normal controls (SMD = 0.496 ng/mL, 95% CI = 0.107-0.886, p <0.001; I(2) = 91.9, p <0.001). The subgroup analysis showed that the serum/plasma levels of PTX3 in AS and SSc were higher than in healthy controls (pooled SMD = 0.926 ng/mL, 95% CI = 0.174-1.677, p <0.001, I(2) = 77.0, p = 0.013; pooled SMD = 0.546 ng/mL, 95% CI = 0.136-0.957, p <0.001; I(2) = 30.9, p = 0.299, respectively). CONCLUSIONS: Serum/plasma levels of PTX3 in autoimmune diseases were higher than in normal controls.