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ID PMID Title PublicationDate abstract
31595721 Biotransformation of cladribine using a stabilized biocatalyst in calcium alginate beads. 2020 Mar Cladribine is a nucleoside analogue widely used in the pharmaceutical industry for the treatment of several neoplasms, including hairy-cell leukemia among others. This compound has also shown efficacy in the treatment of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. In this work, a green bioprocess for cladribine biosynthesis using immobilized Arthrobacter oxydans was developed. The microorganism was stabilized by entrapment immobilization in the natural matrix alginate. Different reaction parameters were optimized obtaining a biocatalyst able to achieve cladribine bioconversion values close to 85% after 1 hr, the shortest reaction times reported so far. The developed bioprocess was successfully scaled-up reaching a productivity of 138 mg L(-1) hr(-1) . Also, the biocatalyst was stable for 5 months in storage and in 96 hr at operational conditions.
31454534 Emerging role of innate B1 cells in the pathophysiology of autoimmune and neuroimmune dise 2019 Oct B1 lymphocytes may be subdivided by CD5 and CD11b/Mac1 expression into B1a, with the CD5 and CD11b/Mac1 phenotype, and B1b, which present as CD19(hi)CD5(lo)CD11b(hi). B1b cells share many surface and functional characteristics with marginal zone B cells but differ in distribution and B cell receptor (BCR) signalling pathways. They are normally concentrated in the peritoneum, pleural cavities, spleen and bone marrow and function as efficient phagocytes and antigen-presenting cells (APCs). While peritoneal B1b cells are relatively anergic, they may be activated by high cytokine levels, notably IL-10, IL-5 and IL-21, CD40 signalling and high doses of Toll-like receptor (TLR) ligands in the context of pathogen invasion; TLR ligation is also necessary. Their anti-inflammatory effects include: secretion of natural IgM by splenic and bone marrow B1b cell subsets as an early response to pathogen invasion; tissue homeostasis and enabling the immunologically silent clearance of neoplastic and apoptotic cells; inhibition of pro-inflammatory cytokines and increased production of TGF-β1, PGE(2) and GcMAF by activated macrophages and dendritic cells; and, in the case of peritoneal B1 lymphocytes, acting as ultimate Breg precurors. Pro-inflammatory B1b properties may result from: abnormal trafficking; acting as APCs; and acting as a source of innate-response activator cells. Functional impairment or deficits in Bregs occur in multiple sclerosis, systemic lupus erythematosus and rheumatoid arthritis. Details are given of potential pathogenic roles of IgM and B1b lymphocytes in these autoimmune disorders and in deficit-schizophrenia, and how these changes relate to inflammatory and oxidative and nitrosative stress.
31452932 The opioid epidemic: helping rheumatologists prevent a crisis. 2019 An endemic increase in the number of deaths attributable to prescribed opioids is found in all developed countries. In 2016 in the USA, more than 46 people died each day from overdoses involving prescription opioids. European data show that the number of patients receiving strong opioids is increasing. In addition, there is an upsurge in hospitalisations for opioid intoxication, opioid abuse and deaths in some European countries. This class of analgesic is increasingly used in many rheumatological pathologies. Cohort studies, in various chronic non-cancer pain (CNCP) (osteoarthritis, chronic low back pain, rheumatoid arthritis, etc), show that between 2% and 8% of patients are treated with strong opioids. In order to help rheumatologists prescribe strong opioids under optimal conditions and to prevent the risk of death, abuse and misuse, recommendations have recently been published (in France in 2016, the recommendations of the French Society of Study and Treatment of Pain, in 2017, the European recommendations of the European Federation of IASP Chapters and the American Society of International Pain Physicians). They agree on the same general principles: opioids may be of interest in situations of CNCP, but their prescription must follow essential rules. It is necessary to make an accurate assessment of the pain and its origin, to formulate therapeutic objectives (pain, function and/or quality of life), to evaluate beforehand the risk of abuse and to get a specialised opinion beyond a certain dose or duration of prescription.
31369928 Identification of the chemical components and metabolites of tripterygium glycoside tablet 2019 Sep 1 Tripterygium glycosides tablets (TGT) contain the main extract of tripterygium and are widely used clinically to treat autoimmune diseases such as rheumatoid arthritis and nephrotic syndrome. However, TGT can lead to liver and renal failure in clinic. The exposed components and their metabolites of TGT in vivo were rarely researched. In this study, the components and metabolites of TGT in mice liver, kidney and plasma were profiled by high performance liquid chromatography coupled with tandem quadrupole time-of-flight mass spectrometry (HPLC-Q/TOFMS) after TGT was orally administered to mice. The components and metabolites were detected and identified based on their retention time, accurate mass data of quasi-molecular ion, characteristic fragment ions, and the fragmentation rules. Finally, 48 prototype components, including 25 diterpenoids, 11 triterpenoids and 12 alkaloids, were detected in mice, as well as 99 metabolites, undergoing hydroxylation, dehydrogenation, ester bond hydrolysis of Phase I metabolism, and glutathione, glucuronic acid binding of Phase II metabolism. The components and metabolites in mice were compared between single- and multiple- low dose groups and between high and low dose groups. Furthermore, a total of 21 components and 35 metabolites were predicted to have potential toxic risk by software. The results would provide material basis to clarify the clinical efficacy and toxicity of TGT.
31309173 Impact of prophylactic TNF blockade in the dual PD-1 and CTLA-4 immunotherapy efficacy and 2019 Jun 27 The TNF blockade therapy is currently a well-established treatment option for a variety of autoimmune diseases such as rheumatoid arthritis (RA), psoriasis or Crohn's disease, given the proinflammatory role of TNF in the course of these diseases. Importantly, TNF neutralization is also used for the treatment of corticosteroid-refractory immune-related adverse events (irAEs) induced by the combined anti-PD-1 and anti-CTLA-4 immunotherapy. The manifestation of these toxicities is an important limiting factor for the successful implementation of the inhibitory checkpoint blockade therapy (ICB), restraining its anti-tumor efficacy. In our recent study (Perez-Ruiz et al., Nature 569(7756): 428-432.), we analyzed the potential impact of prophylactic TNF neutralization therapy in the anti-PD1/CTLA-4 efficacy. Through several mouse models, we demonstrated that TNF neutralization ameliorated ICB-exacerbated colitis in addition to improving ICB-dependent anti-tumor efficacy. Similar results were obtained after prophylactic TNF blockade in graft vs host xenografted mouse models with human immune cells, which showed a reduction in colitis and hepatitis. Importantly, there was a preservation of the immunotherapeutic control of xenografted tumors after ICB treatment. Moreover, TNF and TNF-dependent gene expression is upregulated in the colon mucosa from patients affected by colitis as a side effect of ipilimumab and nivolumab. Our results, thus, provide evidence of the successful combination of prophylactic TNF neutralization with ICB therapy strategy to ameliorate toxicities, while keeping or even ameliorating anti-tumor efficacy. The prophylactic TNF blockade strategy is clinically feasible since excellent TNF inhibitors have been approved for the treatment of autoimmunity and are used for the immune-related serious adverse events in immunotherapy.
31247719 Determination of Real Time in Vivo Drug Receptor Occupancy for a Covalent Binding Drug as 2019 Jul 2 We report a novel immunocapture (IC)-LC-MS/MS methodology to directly measure real time in vivo receptor occupancy (RO) for a covalent binding drug in blood lysate. A small molecule quencher was added immediately after sample collection to convert the free receptor to a quencher-bound receptor (QB-R) which was measured with the drug-bound receptor (DB-R) simultaneously by LC-MS/MS after immunocapture enrichment, followed by trypsin digestion. Addition of the quencher is necessary to prevent the free receptor from ex vivo binding with the drug. The real time RO was calculated based on the concentrations of DB-R and the free receptor (which is now QB-R) that were obtained from each sample. This strategy has been successfully applied to the measurement of the RO for Bruton's tyrosine kinase (BTK) in the blood lysate of monkeys after dosing with branebrutinib (BMS-986195), a covalent BTK inhibitor being evaluated to treat rheumatoid arthritis. A custom-made quencher, which is more reactive to BTK than branebrutinib, was added in excess amount to bind with all available free BTK to form quencher-bound BTK (QB-BTK) during blood sample collection. To measure a wide range of % BTK RO, including those of <5% or >95%, the required LLOQ at 0.125 nM for QB-BTK and 0.250 nM for drug-bound BTK (DB-BTK) in blood lysate were successfully achieved by using this IC-LC-MS/MS strategy. This proof-of-concept assay demonstrated its suitability with high throughput for real time in vivo BTK RO measurement as a pharmacodynamic (PD) biomarker for clinical drug development.
31174287 Heart Involvement in Inflammatory Rheumatic Diseases: A Systematic Literature Review. 2019 Jun 6 Introduction: Patients with inflammatory rheumatic diseases have an increased risk of developing cardiovascular manifestations. The high risk of cardiovascular pathology in these patients is not only due to traditional cardiovascular risk factors (age, gender, family history, smoking, sedentary lifestyle, cholesterol), but also to chronic inflammation and autoimmunity. Aim: In this review, we present the mechanisms of cardiovascular comorbidities associated with inflammatory rheumatic diseases, as they have recently been reported by different authors, grouped in electrical abnormalities, valvular, myocardial and pericardial modifications and vascular involvement. Methods: We conducted a systematic search of published literature on the following online databases: EBSCO, ScienceDirect, Scopus and PubMed. Searches were limited to full-text English-language journal articles published between 2010 and 2017 using the following key words: heart, systemic inflammation, autoimmunity, rheumatic diseases and disease activity. After the primary analysis we included 50 scientific articles in this review. Results: The results showed that cardiac manifestations of systemic inflammation can occur frequently with different prevalence in rheumatoid arthritis (RA), systemic lupus erythematosus(SLE), systemic sclerosis(SSc) and ankylosing spondylitis(AS). Rheumatologic diseases can affect the myocardium, cardiac valves, pericardium, conduction system and arterial vasculature. Conclusions: Early detection, adequate management and therapy of specific cardiac involvement are essential in rheumatic disease. Electrocardiographic and echocardiographic evaluation should be performed as routine investigations in patients with inflammatory rheumatic diseases.
30897858 Cysteine Cathepsins and their Extracellular Roles: Shaping the Microenvironment. 2019 Mar 20 : For a long time, cysteine cathepsins were considered primarily as proteases crucial for nonspecific bulk proteolysis in the endolysosomal system. However, this view has dramatically changed, and cathepsins are now considered key players in many important physiological processes, including in diseases like cancer, rheumatoid arthritis, and various inflammatory diseases. Cathepsins are emerging as important players in the extracellular space, and the paradigm is shifting from the degrading enzymes to the enzymes that can also specifically modify extracellular proteins. In pathological conditions, the activity of cathepsins is often dysregulated, resulting in their overexpression and secretion into the extracellular space. This is typically observed in cancer and inflammation, and cathepsins are therefore considered valuable diagnostic and therapeutic targets. In particular, the investigation of limited proteolysis by cathepsins in the extracellular space is opening numerous possibilities for future break-through discoveries. In this review, we highlight the most important findings that establish cysteine cathepsins as important players in the extracellular space and discuss their roles that reach beyond processing and degradation of extracellular matrix (ECM) components. In addition, we discuss the recent developments in cathepsin research and the new possibilities that are opening in translational medicine.
30891043 Prefoldin 5 and Anti-prefoldin 5 Antibodies as Biomarkers for Uveitis in Ankylosing Spondy 2019 Objective: Uveitis is the most common extra-articular manifestation of ankylosing spondylitis (AS), for which no diagnostic biomarkers have been identified. This study was conducted to identify biomarker for uveitis in AS. Methods: To identify autoantibodies associated with uveitis in AS, we performed human protein microarray analysis using sera derived from various autoimmune diseases and ELISA analysis of sera derived from AS and rheumatoid arthritis patients. In the curdlan-induced SKG mice model, ophthalmic examination was performed at week 8 post-immunization and histologic examination of the ocular lesions performed at week 16 post-immunization. Serum levels of target antibodies were assessed at various time-points. To evaluate the functional role of specific autoantibodies, an in vitro apoptosis assay using ARPE-19 cells was performed. Results: Reactivity against prefoldin subunit 5 (PFDN5) was identified in AS with uveitis. Levels of anti-PFDN5 antibodies and PFDN5 in sera from AS with uveitis patients were significantly higher than those in AS without uveitis. At week 8, half of curdlan-treated SKG mice developed anterior uveitis, while all of them developed histologically confirmed uveitis at week 16. The levels of anti-PFDN5 antibodies increased over time in the sera of curdlan-treated SKG mice along with increased expression of PFDN5 and apoptosis in the ocular lesions. Knockdown of PFDN5 in ARPE19 cells resulted in increased apoptosis, suggesting a protective role of PFDN5 against cell death in uveitis. Conclusion: AS patients with uveitis have increased levels of anti-PFDN5 antibodies, and our findings suggest that anti-PFDN5 antibodies could provide a biomarker for uveitis in AS.
30660786 Integrating Genomics Into Management of Fibrotic Interstitial Lung Disease. 2019 May Fibrotic interstitial lung diseases (ILDs) have a high mortality rate with an unpredictable disease course and clinical features that frequently overlap. Recent data indicate important roles for genomics in the mechanisms underlying susceptibility and progression of pulmonary fibrosis. The impact of these genomic markers on pharmacotherapy and their contribution to outcomes is increasingly recognized. Interstitial lung abnormalities, frequently considered representative of early ILD, have been consistently associated with the MUC5B promoter polymorphism, a common gene variant. Other rare gene variant mutations, including TERT, TERC, SFTPC, and DKC1, may be present in patients with familial interstitial pneumonia and are frequently associated with a usual interstitial pneumonia pattern of fibrosis. The minor allele of the MUC5B rs35705950 genotype is prevalent in several sporadic forms of ILD, including idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis. Gene mutations that characterize familial pulmonary fibrosis may be present in patients with connective tissue disease-related ILD, such as rheumatoid arthritis-ILD. Additionally, shorter telomere lengths and mutations in telomere biology-related genes have been demonstrated in both familial and sporadic ILD, with significant implications for disease progression, lung function, and survival. An improved understanding of the impact of genetic and genomic risk factors on disease progression would better guide personalized therapeutic choices in persons with fibrotic ILD.
30552952 Molecular mechanism involved in cyclophosphamide-induced cardiotoxicity: Old drug with a n 2019 Feb 1 Cyclophosphamide (CP) is an important anticancer drug which belongs to the class of alkylating agent. Cyclophosphamide is mostly used in bone marrow transplantation, rheumatoid arthritis, lupus erythematosus, multiple sclerosis, neuroblastoma and other types of cancer. Dose-related cardiotoxicity is a limiting factor for its use. CP-induced cardiotoxicity ranges from 7 to 28% and mortality ranges from 11 to 43% at the therapeutic dose of 170-180 mg/kg, i.v. CP undergoes hepatic metabolism that results in the production of aldophosphamide. Aldophosphamide decomposes into phosphoramide mustard & acrolein. Phosphoramide is an active neoplastic agent, and acrolein is a toxic metabolite which acts on the myocardium and endothelial cells. This is the first review article that talks about cyclophosphamide-induced cardiotoxicity and the different signaling pathways involved in its pathogenicity. Based on the available literature, CP is accountable for cardiomyocytes energy pool alteration by affecting the heart fatty acid binding proteins (H-FABP). CP has been found associated with cardiomyocytes apoptosis, inflammation, endothelial dysfunction, calcium dysregulation, endoplasmic reticulum damage, and mitochondrial damage. Molecular mechanism of cardiotoxicity has been discussed in detail through crosstalk of Nrf2/ARE, Akt/GSK-3β/NFAT/calcineurin, p53/p38MAPK, NF-kB/TLR-4, and Phospholamban/SERCA-2a signaling pathway. Based on the available literature we support the fact that metabolites of CP are responsible for cardiotoxicity due to depletion of antioxidants/ATP level, altered contractility, damaged endothelium and enhanced pro-inflammatory/pro-apoptotic activities resulting into cardiomyopathy, myocardial infarction, and heart failure. Dose adjustment, elimination/excretion of acrolein and maintenance of endogenous antioxidant pool could be the therapeutic approach to mitigate the toxicities.
30503332 The impact of the reverse prosthesis on revision shoulder arthroplasty: analysis of a high 2019 Feb BACKGROUND: Since the approval of reverse shoulder arthroplasty (RSA) in 2004, the use of shoulder arthroplasty increased dramatically. Although the success of RSA in the revision setting has been demonstrated, there remains a paucity of studies examining the epidemiology of RSA in revision arthroplasty. This study describes trends of revision arthroplasty during the "era of the reverse," from 2005 through 2016. METHODS: In a multicenter retrospective analysis, we analyzed 274 revision shoulder arthroplasties converted to a RSA (n = 182), anatomic total shoulder arthroplasty (TSA, n = 68), or hemiarthroplasty (n = 24) from 2005 to 2016. Demographics, surgical indications, and types of prosthesis were analyzed. RESULTS: The number of revision arthroplasties increased over 12 years. From 2005 to 2010, TSA (33%) or hemiarthroplasty (16%) were used in similar rates as RSA (51%). From 2011 to 2016, there was a much higher incidence of revision arthroplasty with RSA (78%) compared with TSA (19%) or hemiarthroplasty (3%). Specifically, the number of RSAs increased in 2011 to 2016 compared with 2005 to 2010 in patients aged younger than 60 years, obese patients, patients with indications of glenoid loosening, and those with a diagnosis of diabetes mellitus or rheumatoid arthritis. CONCLUSIONS: The use of RSA for revision arthroplasty increased over the "era of the reverse" and became the majority by 2016. The reverse prosthesis has had expanding indications regarding both patient demographics and pathology. This study demonstrates the reverse prosthesis has had a similar and even more profound effect on revision shoulder arthroplasty than what has previously been well documented in the primary setting.
30819662 Phenotypic variability and disparities in treatment and outcomes of childhood arthritis th 2019 Apr BACKGROUND: To our knowledge, the characteristics and burden of childhood arthritis have never been studied on a worldwide basis. We aimed to investigate, with a cross-sectional study, the prevalence of disease categories, treatment methods, and disease status in patients from across different geographical areas and from countries with diverse wealth status. METHODS: In this multinational, cross-sectional, observational cohort study, we asked international paediatric rheumatologists from specialised centres to enrol children with a diagnosis of juvenile idiopathic arthritis, according to International League of Associations for Rheumatology criteria, who were seen consecutively for a period of 6 months. Each patient underwent retrospective and cross-sectional assessments, including measures of disease activity and damage and questionnaires on the wellbeing and quality of life of the children. We qualitatively compared the collected data across eight geographical areas, and we explored an association between disease activity and damage and a country's gross domestic product (GDP) with a multiple logistic regression analysis. FINDINGS: Between April 4, 2011, and Nov 21, 2016, 9081 patients were enrolled at 130 centres in 49 countries, grouped into eight geographical areas. Systemic arthritis (125 [33·0%] of 379 patients) and enthesitis-related arthritis (113 [29·8%] of 379) were more common in southeast Asia, whereas oligoarthritis was more prevalent in southern Europe (1360 [56·7%] of 2400) and rheumatoid factor-negative polyarthritis was more frequent in North America (165 [31·5%] of 523) than in the other areas. Prevalence of uveitis was highest in northern Europe (161 [19·1%] of 845 patients) and southern Europe (450 [18·8%] of 2400) and lowest in Latin America (54 [6·4%] of 849), Africa and Middle East (71 [5·9%] of 1209), and southeast Asia (19 [5·0%] of 379). Median age at disease onset was lower in southern Europe (3·5 years, IQR 1·9-7·3) than in other regions. Biological, disease-modifying antirheumatic drugs were prescribed more frequently in northern Europe and North America than in other geographical settings. Patients living in countries with lower GDP had greater disease activity and damage than those living in wealthier countries. Damage was associated with referral delay. INTERPRETATION: Our study documents a variability in prevalence of disease phenotypes and disparities in therapeutic choices and outcomes across geographical areas and wealth status of countries. The greater disease burden in lower-resource settings highlights the need for public health efforts aimed at improving equity in access to effective treatments and care for juvenile idiopathic arthritis. FUNDING: IRCCS Istituto Giannina Gaslini.
30824462 'Carpal tunnel syndrome' and 'tennis elbow' as prodromes for granulomatosis with polyangii 2019 Feb 28 A 62-year-old man presented with excruciating joint pains, back stiffness and numbness of his hands and feet. Over the past 18 months, he had experienced similar episodes for which the diagnoses of bilateral carpal tunnel syndrome and lateral epicondylitis had been made. Physical examination revealed polyarticular arthritis affecting the shoulders, wrists and right knee. Palpable purpura overlying the calves and ankles was present. Laboratory tests showed markedly elevated erythrocyte sedimentation rate and C-reactive protein in the setting of negative blood and urine cultures. Rheumatoid factor and antinuclear antibodies were negative. Chest CT demonstrated bilateral pulmonary infiltrates. A punch biopsy of the rash showed leukocytoclastic vasculitis. Anti-proteinase-3 titers returned strongly positive. A diagnosis of granulomatosis with polyangiitis was made. Treatment with high-dose steroids, followed by rituximab resulted in normalisation of inflammatory markers with subsequent resolution of joint pains, rash and pulmonary infiltrates and improvement of neuropathic symptoms.
30936146 T-Cell-Specific PTPN2 Deficiency in NOD Mice Accelerates the Development of Type 1 Diabete 2019 Jun Genome-wide association studies have identified PTPN2 as an important non-MHC gene for autoimmunity. Single nucleotide polymorphisms that reduce PTPN2 expression have been linked with the development of various autoimmune disorders, including type 1 diabetes. The tyrosine phosphatase PTPN2 attenuates T-cell receptor and cytokine signaling in T cells to maintain peripheral tolerance, but the extent to which PTPN2 deficiency in T cells might influence type 1 diabetes onset remains unclear. NOD mice develop spontaneous autoimmune type 1 diabetes similar to that seen in humans. In this study, T-cell PTPN2 deficiency in NOD mice markedly accelerated the onset and increased the incidence of type 1 diabetes as well as that of other disorders, including colitis and Sjögren syndrome. Although PTPN2 deficiency in CD8(+) T cells alone was able to drive the destruction of pancreatic β-cells and the onset of diabetes, T-cell-specific PTPN2 deficiency was also accompanied by increased CD4(+) T-helper type 1 differentiation and T-follicular-helper cell polarization and increased the abundance of B cells in pancreatic islets as seen in human type 1 diabetes. These findings causally link PTPN2 deficiency in T cells with the development of type 1 diabetes and associated autoimmune comorbidities.
31081461 Patient Support Program Increased Medication Adherence with Lower Total Health Care Costs 2019 Jul BACKGROUND: The U.S. health care system is currently evolving from a volume-based care to a value-based care approach, which is in part supported by the introduction of patient support programs (PSP). For patients treated with adalimumab (ADA), the addition of a dedicated, trained nurse to the PSP (HUMIRA Complete, rolled out nationally in 2015) provides further emphasis on value-based care. OBJECTIVE: To determine the effectiveness of the HUMIRA Complete PSP, including the Nurse Ambassador component, in a real-world setting for patients receiving ADA across a broad range of approved indications (rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, psoriatic arthritis, ankylosing spondylitis, uveitis, and hidradenitis suppurativa). METHODS: A longitudinal retrospective study was conducted using patient-level data from the HUMIRA Complete PSP data linked to the real-world, patient-level Symphony Health Solutions administrative claims database. Commercially insured patients were included who were aged ≥ 18 years with ≥ 2 diagnoses of an indicated disease who were biologically naive before initiating ADA or who had no claims for synthetic-targeted immune modulator therapy before their earliest ADA claim in the database between January 2015 and February 2017. The first claim had to have occurred in 2015 or later, and continuous medical and drug data coverage were required for ≥ 6 months before and ≥ 12 months after the first ADA claim and index date. PSP patients (with at least an initial and follow-up dedicated nurse call) were matched 1:1 to non-PSP patients based on pharmacy type, indication, and propensity score, estimated with covariates for age, sex, year of first ADA use, and baseline comorbidities. Adherence to ADA was compared using proportion of days covered along with discontinuation of ADA, defined as a gap in treatment greater than the previous days supply with no additional ADA claim, total costs, medical costs, and drug costs (2017 U.S. dollars) over 12 months. Baseline demographic and clinical characteristics were summarized descriptively. Differences between cohorts were assessed using t-tests for adherence and costs and log-rank tests for discontinuation. RESULTS: 2,268 patients (1,134 per group) were included. Baseline characteristics were similar between cohorts after matching. Participation in the PSP was associated with 29.3% higher ADA adherence (64.8% vs. 50.1%; P < 0.0001) and 22.0% lower ADA discontinuation rate (51.4% vs. 65.9%; P < 0.0001). Disease-related medical costs and all-cause medical costs were significantly lower by 35% ($10,162 vs. $15,511; P = 0.005) and 29.2% ($25,074 vs. $35,419; P = 0.0004), respectively, for PSP versus non-PSP patients. Total costs were also lower by 9% ($62,421 vs. $68,706; P = 0.056), and drug costs were 12.2% higher ($37,347 vs. $33,287; P = 0.0016). CONCLUSIONS: This retrospective study demonstrates that participation in the PSP augments value-based care by improving outcomes for patients with chronic diseases by helping them not only manage a complex treatment regimen but also lower annual health care costs. DISCLOSURES: Design, study conduct, and financial support for this study were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the manuscript; all authors contributed to the development of the publication and maintained control over the final content. Brixner reports consulting fees from AbbVie, AstraZeneca, Becton Dickinson, Millcreek Outcomes Group, Sanofi, and UCB Pharma. Rubin reports consulting fees from AbbVie, Abgenomics, Allergan, Forward Pharma, Genentech/Roche, Janssen Pharmaceuticals, Merck & Co., Napo Pharmaceuticals, Pfizer, Shire, Takeda, and Target Pharmaceuticals and research support from AbbVie, Genentech/Roche, Janssen Pharmaceuticals, Prometheus Laboratories, Shire, and Takeda. Mease reports grant/research support from AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, SUN Pharma, and UCB; consulting fees from AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, SUN Pharma, and UCB; and served on the speakers bureaus for AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, and UCB. Mittal and Ganguli are employees and stockholders of AbbVie. Liu has no financial conflict of interest. Davis is an employee of Medicus Economics, which reports payment from AbbVie to participate in this research. Fendrick reports personal fees from Merck, AstraZeneca, Trizetto, Amgen, Lilly, AbbVie, Johnson & Johnson, and Sanofi; grants from the National Pharmaceutical Council, PhRMA, the Gary and Mary West Health Foundation, the states of New York and Michigan, the Laura and John Arnold Foundation, the Robert Wood Johnson Foundation, and the Agency for Healthcare Research and Quality; and has equity in Zansors, Sempre Health, Wellth, and V-BID Health. Data from this study were presented in part at the Academy of Managed Care & Specialty Pharmacy Annual Meeting; April 25, 2018; Boston, MA.
31773391 Enthesitis and its relationship with disease activity, functional status, and quality of l 2020 Feb Psoriatic arthritis (PsA) is an inflammatory arthritis with distinct phenotypic subtypes. Enthesitis is assigned as a hallmark of the disease, given its significant relations to disease activity and quality of life. Our objective is to evaluate the prevalence of enthesitis and its association with some clinical parameters, particularly quality of life, using data from a national registry. Patients with PsA meeting ClASsification criteria for Psoriatic Arthritis (CASPAR) were enrolled by means of a multi-centre Turkish League Against Rheumatism (TLAR) Network Project. The following information was recorded in web-based case report forms: demographic, clinical and radiographic data; physical examination findings, including tender and swollen joint counts (TJC and SJC); nail and skin involvement; Disease Activity Score-28 for Rheumatoid Arthritis with Erythrocyte Sedimentation Rate (DAS 28-ESR); Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); Maastricht Ankylosing Spondylitis Enthesitis Score (MASES); Psoriasis Area Severity Index (PASI); Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI-s); Health Assessment Questionnaire (HAQ); Bath Ankylosing Spondylitis Functional Index (BASFI); Health Assessment Questionnaire for the spondyloarthropathies (HAQ-s); Psoriatic arthritis quality of Life scale (PsAQoL); Short Form 36 (SF-36); Hospital Anxiety Depression Scale (HADS); Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F); and Fibromyalgia Rapid Screening Tool (FiRST) scores. The patients were divided into two groups, namely with and without enthesitis, based on the triple Likert-type physician-reported statement of 'active enthesitis', 'history of enthesitis' or 'none' in the case report forms. Patients with active enthesitis were compared to others in terms of these clinical parameters. A total of 1130 patients were enrolled in this observational study. Of these patients, 251 (22.2%) had active enthesitis according to the clinical assessment. TJC, HAQ-s, BASDAI, FiRST and PsAQoL were significantly higher whereas the SF-36 scores were lower in patients with enthesitis (p < 0.05). Chronic back pain, dactylitis, and tenosynovitis were more frequent in the enthesopathy group (59.4%/39%, 13.1%/6.5% and 24.7%/3.4%, respectively). Significant positive correlations between the MASES score and the TJC, HAQ, DAS 28-ESR, BASDAI, FiRST and PsAQoL scores, and a negative correlation with the SF-36 score were found. When linear regression analysis was performed, the SF-36 MCS and PCS scores decreased by - 9.740 and - 11.795 units, and the FiRST scores increased by 1.223 units in patients with enthesitis. Enthesitis is an important involvement of PsA with significant relations to quality of life determined with PsAQoL and SF-36 scores. Our study found higher frequency of dactylitis and chronic back pain, and worse quality of life determined with SF-36 and PsAQoL scores in patients with enthesitis.
31775834 The effect of pilocarpine on dental caries in patients with primary Sjögren's syndrome: a 2019 Nov 27 BACKGROUND: Primary Sjögren's syndrome (pSS) is associated with dental caries. Pilocarpine, a salivary stimulant, can improve the amount and flow rate of saliva in patients with pSS. This study aimed to assess whether the risk of dental caries decreases with the use of pilocarpine in patients with pSS. METHODS: For this prospective cohort study, we identified pSS patients from the catastrophic illnesses registry of the National Health Insurance Research Database of Taiwan between 2009 and 2013. We divided participants into pilocarpine and non-user groups based on the pilocarpine prescriptions available during the first 3-month follow-up. The primary endpoint was dental caries. The secondary endpoints were periodontitis and oral candidiasis. We compared the risk of these oral manifestations using the Cox proportional hazard model. RESULTS: A total of 4973 patients with new-onset pSS were eligible for analysis. After propensity score matching, we included 1014 patients in the pilocarpine group and 2028 patients in the non-user group. During the mean follow-up of 2.6 years, the number of events was 487 in the pilocarpine group (48.0%) and 1047 in the non-user group (51.6%); however, the difference was not significant (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.82 to 1.06). Furthermore, there was no significant difference between groups regarding risk of periodontitis (HR 0.91, 95% CI 0.81 to 1.03) and oral candidiasis (HR 1.16, 95% CI 0.70 to 1.94). CONCLUSION: Pilocarpine may have no protective effect on dental caries, periodontitis, or oral candidiasis in patients with pSS.
31393368 Refractory adult-onset Still disease treated by tocilizumab combined with methotrexate: A 2019 Aug Some patients have poor response to adult-onset Still disease (AOSD) traditional treatment, which easily recurs during the reduction of prednisone. We observed the efficacy and safety of tocilizumab combined with methotrexate (MTX) in the treatment of refractory AOSD, and to explore the possibility of reducing the dosage of tocilizumab after disease control.A total of 28 refractory AOSD cases who had an inadequate response to corticosteroids combined with at least 1 traditional immunosuppressive agent, and even large-dose prednisone could not relieve their conditions after recurrence, were selected in this study. They were treated with tocilizumab (intravenous 8 mg/kg) combined with MTX (oral 12.5 mg once a week). In detail, tocilizumab was firstly given every 4 weeks and after 6-month remission, it was then given every 8 weeks. Some items including body temperature, skin rash, joint swelling and pain, hepatosplenomegaly, blood routine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum ferritin, and dosage of prednisone were observed before treatment as well as 2, 4, 8, 12, 24, 36, and 48 weeks after treatment. The adverse reactions occurring during the treatment were recorded.The body temperature was normal, the skin rash as well as joint swelling and pain disappeared, and laboratory indexes including CRP, ESR, white blood cell, neutrophilic granulocyte, platelet, hemoglobin, and ferritin were significantly improved after 8-week treatment (all P < .05). The clinical symptoms and laboratory indexes above mentioned were continuously improved 12, 24, 36, and 48 weeks after treatment. The mean dosage of prednisone was reduced from 71.4 ± 20.7 mg/day to 55.0 ± 11.1 mg/day after 2-week treatment, and to 3.3 ± 2.1 mg/day after 48-week treatment (all P < .05). Prednisone was discontinued in 5 cases after 36-week treatment and in 7 cases after 48-week treatment. No serious adverse reactions occurred during the treatment.Tocilizumab can rapidly and markedly improve the clinical symptoms and laboratory indexes and contribute to reduction and discontinuation of prednisone in refractory AOSD. The patients' conditions are stable after reduction or discontinuation of prednisone and the tocilizumab possesses good safety.
31171301 Skin Biopsy in the Context of Systemic Disease. 2019 Nov The skin is the largest and most exposed organ in the human body and the ideal place to look for signs that aid in the early diagnosis of systemic diseases with cutaneous effects. As the concepts that underpin our understanding of many of these diseases have evolved or expanded in recent years, there have also been changes in the criteria we use for early diagnosis, including our approaches to skin biopsy and dermatopathologic evaluation. This review focuses on some of the systemic processes with skin manifestations for which our basic understanding has changed most in recent decades.