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31284664 Photosensitizers Used in the Photodynamic Therapy of Rheumatoid Arthritis. 2019 Jul 7 Photodynamic Therapy (PDT) has become one of the most promising treatment against autoimmune diseases, such as rheumatoid arthritis (RA), as well as in the treatment of different types of cancer, since it is a non-invasive method and easy to carry out. The three main ingredients of PDT are light irradiation, oxygen, and a photosensitizer (PS). Light irradiation depends on the type of molecule or compound to be used as a PS. The concentration of O(2) fluctuates according to the medium where the target tissue is located and over time, although it is known that it is possible to provide oxygenated species to the treated area through the PS itself. Finally, each PS has its own characteristics, the efficacy of which depends on multiple factors, such as solubility, administration technique, retention time, stability, excitation wavelength, biocompatibility, and clearance, among others. Therefore, it is essential to have a thorough knowledge of the disease to select the best PS for a specific target, such as RA. In this review we will present the PSs used in the last three decades to treat RA under PDT protocol, as well as insights on the relevant strategies.
31376250 Monotherapy is a relevant option in rheumatoid arthritis treatment: a literature review. 2019 Sep The latest revision of the European League Against Rheumatism (EULAR) recommendations for rheumatoid arthritis (RA) treatment maintains the indication for the combined therapy of biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), namely Jak-inhibitors as tofacitinib and baricitinib, with conventional synthetic DMARDs (csDMARDs). Moreover, the use of bDMARDs and tsDMARDs should be restricted to patients who failed to achieve an adequate response to one or more csDMARDs, in accordance with the current evidence showing the superiority of combination therapy over monotherapy. In patients who cannot use csDMARDs as comedication, IL-6 inhibitors and tsDMARDs should be preferred to other bDMARDs because they are apparently more effective as monotherapy. Registry and real-world data demonstrate that monotherapy is far more commonly used than expected based on treatment recommendations, currently being about 30% of patients with RA on bDMARD monotherapy. We review here the literature on most commonly used DMARDs in monotherapy for RA. Our review points at an increasing evidence of the potential of some bDMARDs and tsDMARDs in monotherapy, which may become a considerable and realistic option in RA patients.
31401534 Genkwanin ameliorates adjuvant-induced arthritis in rats through inhibiting JAK/STAT and N 2019 Oct BACKGROUND: Genkwanin is a flavone isolated from the traditional Chinese herb Daphne genkwa. Our previous work proved that four flavonoids (including genkwanin) isolated from D. genkwa (FFD) significantly improved the symptoms of arthritis in rat models. Recent studies have revealed that genkwanin exhibited anti-inflammatory and immunomodulatory activities, both of which were closely related to the pathology of rheumatoid arthritis (RA). Therefore, studying the anti-RA effects and mechanisms of genkwanin may give us insight into FFD's therapeutic effects on RA. PURPOSE: This study aimed to investigate the anti-rheumatoid arthritis activity of genkwanin on adjuvant-induced arthritis (AIA) model in rats and explore the underlying mechanisms. METHODS: The anti-rheumatoid arthritis activity of genkwanin was evaluated on AIA rat model by determining the paw swelling degrees and arthritis index scores, along with histopathological analysis of joint tissues. The serum cytokine levels were measured by ELISA method, and serum NO levels were measured by Griess method. The expression and phosphorylation levels of proteins in JAK/STAT and NF-κB signaling pathways were determined by western blot analysis and immunohistochemistry analysis. RESULTS: Genkwanin significantly decreased the paw swelling and arthritis index in AIA rats and also decreased the inflammation and bone destruction in joint tissues. The serum TNF-α, IL-6, and NO concentrations were markedly reduced while the IL-10 concentration was markedly increased with the treatment of genkwanin. Genkwanin inhibited the activation of JAK/STAT and NF-κB signaling pathways in synovial tissues of AIA rats. CONCLUSION: Genkwanin exerted anti-rheumatoid arthritis effects on AIA rats through inhibiting the activation of JAK/STAT and NF-κB signaling pathways. The results obtained in this work lead us to suggest that Genkwanin could play a crucial role on the previously demonstrated anti-rheumatoid arthritis activity of flavonoid extract of D. genkwa (namely FFD).
30767391 Efficacious transition from reference infliximab to biosimilar infliximab in clinical prac 2019 May OBJECTIVES: To evaluate the transition from reference infliximab Remicade to biosimilar Remsima in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA). METHODS: Patients were informed through a letter about the transition to a biosimilar and were subsequently contacted for possible additional questions and whether they agreed upon the transition. Once agreed, Remsima was administered at the same dosage and interval as previous treatment with Remicade. Data on the transition were analyzed in January 2018. The primary outcome was the percentage of patients continuing treatment with Remsima and secondary outcome was the change in disease activity measured with the Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR). In addition, the reasons for discontinuation with infliximab or restarting Remicade were recorded. RESULTS: In total 47 patients were approached, 45 patients switched from Remicade to Remsima, two patients disagreed upon transition and continued Remicade. At the end of the follow-up period of 2 years, 39 patients (87%) continued with Remsima, three patients (7%) restarted Remicade due to inefficacy according to the patient (this was not objectified by the rheumatologist) 2 (4%) patients switched to another biological due to lack of effect and in one patient (2%) infliximab was stopped because of lung malignancy. Furthermore, the DAS28-ESR remained comparable before and after the switch, with a mean (SD) of 2.34 (±1.02) and 2.31 (±1.11) respectively. CONCLUSION: In our population, 87% of patients continued Remsima during the follow-up period of approximately 2 years. Three patients restarted Remicade, while retaining stable DAS28-ESR.
31333666 IL-6 Mediated Transcriptional Programming of Naïve CD4+ T Cells in Early Rheumatoid Arthr 2019 Objective: We have previously shown that increased circulating interleukin-6 (IL-6) results in enhanced CD4+ T cell signaling via signal transduction and activator of transcription-3 (STAT3) in early rheumatoid arthritis (RA). We tested the hypothesis that transcriptional "imprinting" of T-cells by this mechanism skews downstream effector responses, reinforcing immune dysregulation at a critical, but targetable, disease phase. Methods: We modeled naïve CD4+ T cell exposure to pathophysiological concentrations of IL-6 in vitro, assessing the dynamic transcriptional and functional consequences for downstream effector cells utilizing microarray and flow cytometry. Fresh blood from treatment-naïve early arthritis patients was phenotyped in parallel for comparison. Results: T cell sensitivity to IL-6 was most marked in the naïve subset, and related to gp130 rather than IL-6R expression. Exposure of healthy naïve CD4+ T cells to IL-6 induced the same STAT3 target genes as previously seen to discriminate RA patients from disease controls. After TCR stimulation IL-6 pre-exposed cells exhibited enhanced proliferative capacity, activation, and a propensity toward Th1 differentiation, compared to non-exposed cells. An entirely analogous phenotype was observed in early RA compared to control CD4+ T cells. Conclusions: Sustained IL-6 exposure at a critical point in the natural history of RA "primes" the adaptive immune system to respond aberrantly to TCR stimulation, potentiating disease induction with implications for the optimal timing of targeted therapy.
30742363 Complex Relationships of Smoking, HLA-DRB1 Genes, and Serologic Profiles in Patients With 2019 Sep OBJECTIVE: Smoking is associated with an increased risk of rheumatoid arthritis (RA) in subsets of patients defined according to the presence or absence of anti-citrullinated protein antibodies (ACPAs) and rheumatoid factors (RFs). Moreover, an interaction between smoking and the HLA-DRB1 shared epitope (SE) has been demonstrated to be a risk factor for seropositive RA. The aim of this study was to investigate the interplay between smoking and the HLA-DRB1 SE with regard to risk of RA in different patient subsets based on ACPA and RF status. METHODS: Incident cases of RA (3,645 cases, 5,883 matched controls) were divided into 4 subgroups based on the presence or absence of RF and anti-cyclic citrullinated peptide 2 (anti-CCP2) antibodies. The influence of smoking on the risk of disease was determined in each RA subgroup, using logistic regression models with calculation of odds ratios and 95% confidence intervals (95% CIs). The potential interaction between smoking and HLA-DRB1 SE genes was evaluated by calculating the attributable proportion due to interaction (AP). RESULTS: In the RF+/anti-CCP2+ subset of RA patients, both smoking and the presence of the HLA-DRB1 SE conferred independent disease risks, and there was a strong interaction between the 2 risk factors (AP 0.4, 95% CI 0.3, 0.5). In the RF-/anti-CCP2+ patient subset, the HLA-DRB1 SE conferred an increased risk of RA, whereas the independent influence of smoking was limited. However, there was a significant interaction between the HLA-DRB1 SE and smoking (AP 0.2, 95% CI 0.02, 0.5). In the RF+/anti-CCP2- patient subset, there was an increased risk of disease among smokers, which was only marginally affected by the presence of the HLA-DRB1 SE, and no interaction between the 2 factors was observed (AP 0.002, 95% CI -0.3, 0.3). In the RF-/anti-CCP2- patient subset, neither smoking nor the presence of the HLA-DRB1 SE conferred an increased risk of RA. CONCLUSION: These findings demonstrate different effects of smoking and HLA-DRB1 in the 4 serologically defined RA subsets.
30884802 Immunopathogenic Mechanisms and Novel Immune-Modulated Therapies in Rheumatoid Arthritis. 2019 Mar 16 Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease of unknown etiology. It is characterized by the presence of rheumatoid factor and anticitrullinated peptide antibodies. The orchestra of the inflammatory process among various immune cells, cytokines, chemokines, proteases, matrix metalloproteinases (MMPs), and reactive oxidative stress play critical immunopathologic roles in the inflammatory cascade of the joint environment, leading to clinical impairment and RA. With the growing understanding of the immunopathogenic mechanisms, increasingly novel marked and potential biologic agents have merged for the treatment of RA in recent years. In this review, we focus on the current understanding of pathogenic mechanisms, highlight novel biologic disease-modifying antirheumatic drugs (DMRADs), targeted synthetic DMRADs, and immune-modulating agents, and identify the applicable immune-mediated therapeutic strategies of the near future. In conclusion, new therapeutic approaches are emerging through a better understanding of the immunopathophysiology of RA, which is improving disease outcomes better than ever.
30917075 Economic Evaluation of Anticyclic Citrullinated Peptide Positivity in Rheumatoid Arthritis 2019 Apr BACKGROUND: Anticyclic citrullinated peptide (anti-CCP) positivity may be a strong predictor of joint erosion and a potential biomarker for guiding treatment decisions for rheumatoid arthritis (RA). However, limited studies are currently available on the effect of anti-CCP positivity on health care utilization and/or medical costs of RA patients. OBJECTIVE: To investigate short-term and long-term direct health care expenditures associated with anti-CCP positivity in newly diagnosed RA patients. METHODS: A retrospective cohort study was conducted in adult RA patients within a U.S. integrated health care delivery system (January 1, 2007-June 30, 2015). Patients were required to have 2 RA diagnoses and treatment with a conventional or biologic disease-modifying antirheumatic drug (DMARD) within 12 months. The first RA diagnosis date was labeled as the index date, and patients were followed until they left the health plan, died, or reached the end of the study period. Patient demographics, anti-CCP results, comorbid conditions, and health care resource utilization during baseline (12 months before the index date) and follow-up periods were collected. Nationally recognized direct medical costs were assigned to health care utilization to calculate health care costs in 2015 U.S. dollars. The baseline differences between anti-CCP positivity and negativity and differences in censoring during follow-up were addressed using propensity scores. The mean differences in costs were estimated using recycled prediction methods. RESULTS: 2,448 newly diagnosed RA patients were identified and followed for a median of 3.7 years (range = 1-8 years). At baseline, 65.8% of patients were anti-CCP positive. Anti-CCP-positive patients had fewer comorbid conditions at baseline. During the first 12 months of follow-up, median (interquartile range) total health care expenditures for anti-CCP-positive and anti-CCP-negative patients were $6,200 ($3,563-$13,260) and $7,022 ($3,885-$12,995), respectively. After adjusting for baseline differences, total incremental mean cost associated with anti-CCP positivity during the first 12 months was estimated to be $2,163 per patient (P = 0.001). The annual incremental costs in anti-CCP-positive patients became progressively larger over time, from $2,163 during the first year to $5,062 during the fourth year. Anti-CCP positivity was associated with higher prescription, laboratory testing, and rheumatologist utilization. A higher percentage of anti-CCP-positive patients received 1 or more biologic DMARDs (11.6% for anti-CCP-positive vs. 5.7% for anti-CCP negative; P < 0.001) compared with anti-CCP-negative patients during the 12-month follow-up, which resulted in $2,499 in incremental prescription costs (P < 0.001). Total additional burden associated with anti-CCP positivity during the first 4 years was estimated to be $14,089 per patient. CONCLUSIONS: In newly diagnosed RA patients, higher economic burden associated with anti-CCP positivity was mainly driven by prescription costs. DISCLOSURES: This research and manuscript were funded by Bristol-Myers Squibb (BMS). Alemao and Connolly are employees and shareholders of BMS and participated in the design of the study, interpretation of the data, review/revision of the manuscript, and approval of the final version of the manuscript. An and Cheetham received a grant from BMS for this research. At the time of this study, An was employed by Western University of Health Sciences, and Cheetham was employed by Kaiser Permanente Southern California. Bider-Canfield, Kang, and Lin have nothing to disclose. Some study results were presented as a poster at the American College of Rheumatology Annual Meeting; November 5, 2017; San Diego, CA, and at the International Society for Pharmacoeconomics and Outcomes Research Meeting; May 19, 2018; Baltimore, MD.
31760330 Assessment of Aortic Stiffness in Patients with Rheumatoid Arthritis Using Pulse Wave Velo 2019 Oct BACKGROUNDS: Rheumatoid arthritis (RA) is a systemic autoimmune disease that confers one of the strongest risks for cardiovascular disease (CVD) morbidity and mortality than in general population. Pulse wave velocity (PWV) and augmentation index (AIx) are composite measures of arterial stiffness (AS) and associated with CV risk. AIM OF THE STUDY: The aim of this study was to systemically review the evidence regarding the relationship between PWV, AIx and RA, as well as underlying influential factors. METHODS: Eligible literatures were searched in PubMed, EMBASE and The Cochrane Library published up to February 28, 2019 in English. The pooled weight mean difference (WMD) with its 95% confidence interval (CI) was calculated using random-effect model analysis. RESULTS: A total of 38 studies were finally incorporated in the meta-analysis. The results indicated that, compared to controls, RA patients had significantly increased levels of carotid-femoral (cf)-PWV (WMD = 1.10 m/s, 95% CI: 0.84-1.35), brachial-ankle (ba)-PWV (WMD = 0.20 m/s, 95% CI: 0.12-0.28), cartoid-radial (cr)-PWV (WMD = 0.51 m/s, 95% CI: 0.23-0.79), AIx (WMD = 4.79%, 95% CI: 1.34-8.24) and AIx normalized to a 75 beats/minute heart rate (AIx@75) (WMD = 5.78%, 95% CI: 3.82-7.74) (all p <0.001). Meta-regression and subgroup analysis demonstrated significant association of cf-PWV with age, disease duration and erythrocyte sedimentation rate (ESR) in RA. CONCLUSIONS: Overall, there is increased PWV level in patients with RA, and this alteration is associated with age, disease duration and ESR.
31016369 [Depressive symptoms in early rheumatoid arthritis : Within the rheumatism network ADAPTHE 2019 Sep BACKGROUND AND OBJECTIVE: For patients with established rheumatoid arthritis and also early arthritis an increased prevalence of depression has been described. For a better understanding of depression in early arthritis patients, depression prevalences of a German early arthritis cohort were examined, with a focus on disease activity, anti-CCP status, disease duration and functional capacity over a period of 2 years. MATERIAL AND METHODS: The evaluation was based on the early arthritis cohort ADAPTHERA from Rhineland-Palatinate. The inclusion criterion was a symptom duration before diagnosis of a maximum of 1 year. Data from the disease activity score 28 (DAS28), the Health Assessment Questionnaire (HAQ, functional status), the WHO-5 Well-Being Index (WHO-5, well-being and depressive symptoms) and the Patient Health Questionnaire-9 (PHQ-9, depressive symptoms) were collected. RESULTS: At the beginning, 43.5% of patients had depressive symptoms (WHO-5 > 28). After the 2 year follow-up the percentage of patients with depressive symptoms had reduced to 20.8%. Correlations with disease activity according to DAS28 and the function of HAQ could be confirmed. There was no correlation between depressive symptoms and anti-CCP status (p = 0.431) or duration from symptom onset to diagnosis (p = 0.671). CONCLUSION: Screening of early arthritis patients for the presence of depressive symptoms is of essential importance. Patients seem to be at high risk of developing depressive symptoms especially at the beginning of the disease and when showing high disability and poor results on disease activity score (DAS28 and visual analog scale).
30943143 Methods for type I interferon detection and their relevance for clinical utility and impro 2019 Nov Type I interferons (IFN) are a class of inducible and protective cytokines best known for immune defence against viruses and intracellular bacteria. Inappropriate stimulation or defective negative regulation of type I IFN expression however can lead to persistent type I IFN activity with detrimental effects. This is particularly relevant for a class of monogenic autoinflammatory diseases ("type I interferonopathies"), along with many other complex rheumatic diseases such as systemic lupus erythematosus (SLE), dermatomyositis (DM), systemic sclerosis (SSc), rheumatoid arthritis (RA) and Sjögren's syndrome (SS). Direct detection of type I interferon protein in biologic samples has proved challenging, thus indirect methods are often used to infer the presence of type I IFN via quantification of antiviral activity and/or induced expression of IFN-responsive genes. While some of these methods have been used to inform clinical care, none have proven feasible for everyday clinical practice. However, with new technologies emerging, this may soon change. This review provides a brief summary of the available methods to gauge the presence of type I IFN and their application for the improved understanding, diagnosis and monitoring of type I interferonopathies and other rheumatic diseases.
30793700 Reducing arthritis fatigue impact: two-year randomised controlled trial of cognitive behav 2019 Apr OBJECTIVES: To see if a group course delivered by rheumatology teams using cognitive-behavioural approaches, plus usual care, reduced RA fatigue impact more than usual care alone. METHODS: Multicentre, 2-year randomised controlled trial in RA adults (fatigue severity>6/10, no recent major medication changes). RAFT (Reducing Arthritis Fatigue: clinical Teams using CB approaches) comprises seven sessions, codelivered by pairs of trained rheumatology occupational therapists/nurses. Usual care was Arthritis Research UK fatigue booklet. Primary 26-week outcome fatigue impact (Bristol RA Fatigue Effect Numerical Rating Scale, BRAF-NRS 0-10). Intention-to-treat regression analysis adjusted for baseline scores and centre. RESULTS: 308/333 randomised patients completed 26 week data (156/175 RAFT, 152/158 Control). Mean baseline variables were similar. At 26 weeks, the adjusted difference between arms for fatigue impact change favoured RAFT (BRAF-NRS Effect -0.59, 95% CI -1.11 to -0.06), BRAF Multidimensional Questionnaire (MDQ) Total -3.42 (95% CI -6.44 to -0.39), Living with Fatigue -1.19 (95% CI -2.17 to -0.21), Emotional Fatigue -0.91 (95% CI -1.58 to -0.23); RA Self-Efficacy (RASE, +3.05, 95% CI 0.43 to 5.66) (14 secondary outcomes unchanged). Effects persisted at 2 years: BRAF-NRS Effect -0.49 (95% CI -0.83 to -0.14), BRAF MDQ Total -2.98 (95% CI -5.39 to -0.57), Living with Fatigue -0.93 (95% CI -1.75 to -0.10), Emotional Fatigue -0.90 (95% CI -1.44, to -0.37); BRAF-NRS Coping +0.42 (95% CI 0.08 to 0.77) (relevance of fatigue impact improvement uncertain). RAFT satisfaction: 89% scored > 8/10 vs 54% controls rating usual care booklet (p<0.0001). CONCLUSION: Multiple RA fatigue impacts can be improved for 2 years by rheumatology teams delivering a group programme using cognitive behavioural approaches. TRIAL REGISTRATION NUMBER: ISRCTN52709998.
31371648 Rheumatoid Arthritis Initiating as Palindromic Rheumatism: A Distinct Clinical Phenotype? 2020 May 1 OBJECTIVE: To analyze the prevalence of preexisting palindromic rheumatism (PR) in patients with established rheumatoid arthritis (RA) and to evaluate whether these patients have a distinctive clinical and serological phenotype. METHODS: Cross-sectional study in patients with established RA. Preexisting PR was determined using a structured protocol and confirmed by retrospective review of medical records. Demographic, clinical, radiological, immunological, and therapeutic features were compared in patients with and without PR. RESULTS: Included were 158 patients with established RA (78% female) with a mean disease duration since RA onset of 5.1 ± 2.7 years. Preexisting PR was recorded in 29 patients (18%). The median time from the onset of PR to progression to RA was 1.2 years. No between-group differences in demographic features, current disease activity, radiographic erosive disease, or disability were observed. Patients with PR had a higher prevalence of smoking (72% vs 40%). Positive rheumatoid factor, anticitrullinated peptide antibodies, and anticarbamylated protein antibodies were numerically higher in patients with PR. No differences in treatment were observed except for greater hydroxychloroquine (HCQ) use in patients with PR (38% vs 6%). Palindromic flares persisted in a significant proportion of patients during the RA course, including patients in clinical remission or receiving biological disease-modifying antirheumatic drugs. CONCLUSION: Eighteen percent of patients with RA had a history compatible with PR previous to RA onset. No specific clinical or serological phenotype was identified in these patients, although higher HCQ use and smoking prevalence were identified. Palindromic flares may persist during the RA disease course despite treatment.
31852367 Platelet indices in patients with chronic inflammatory arthritis: a systematic review and 2020 Oct 2 Correlation between platelet indices and chronic inflammatory arthritis (CIA) remains a moot point today. This meta-analysis aimed to evaluate whether platelet (PLT) count, mean platelet volume (MPV) and platelet distribution width (PDW) associated with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). A systematic literature search was performed in PubMed, EMBASE, and Web of Science up to August 2019. Pooled standardized mean differences (SMD) and 95% confidence interval (CI) were calculated using a random-effect model. As a result, 34 studies were included, encompassing 17 on RA, 12 on AS, 3 on PsA and 2 on both RA and AS. In these studies, PLT count was significantly higher in RA (SMD = 0.55, 95% CI = 0.36-0.73, P < .001), AS (SMD = 0.53, 95% CI = 0.36-0.70, P < .001) and PsA patients (SMD = 1.29, 95% CI = 0.82-1.77, P < .001) than that in healthy subjects, while MPV and PDW presented nonsignificant differences in these intergroup comparisons (P > .05), and similar results were observed in subgroup analyses. The meta-regression analysis demonstrated that there were strong positive correlations between erythrocyte sedimentation rate and PLT count, and weak correlation trend between the disease activity score and PLT count in both RA and AS subjects without statistically significant difference. The sensitivity analysis indicated that these results were not unduly influenced by any single study. In conclusion, this meta-analysis demonstrated that PLT count was elevated in CIA patients and could be suitable for evaluating the disease activity, whereas MPV and PDW were independent of CIA.
31028551 Long-term safety and effectiveness of tocilizumab in patients with rheumatoid arthritis an 2019 Sep OBJECTIVE: To assess the long-term safety, tolerability, and effectiveness of tocilizumab (TCZ) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in clinical practice in patients with moderate to severe rheumatoid arthritis (RA). METHODS: Patients in the 24-week, open-label ACT-SURE study who had at least a moderate EULAR response by week 24 and were from a participating country were eligible for this long-term extension (LTE); the patients continued to receive TCZ 8 mg/kg intravenously every 4 weeks as monotherapy or in combination with ≥ 1 csDMARD for up to an additional 108 weeks. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs). Effectiveness endpoints included Disease Activity Score in 28 joints (DAS28) responses, American College of Rheumatology (ACR) responses, and patient-reported outcomes (PROs). RESULTS: Of the 1102 patients who completed the core 24-week study, 934 participated in the LTE; the median exposure to TCZ was 64.3 weeks. From baseline to the end of the LTE, AEs and SAEs occurred in 90% and 9% of patients, respectively. The overall event rates (95% CI) of AEs and SAEs were 406.5 per 100 patient-years (PY) (395.5, 417.8) and 8.8 per 100 PY (7.3, 10.6), respectively. Mean (SD) improvement in DAS28 was 4.12 (1.18), P < 0.0001. The DAS28 remission rates, ACR response rates, and PRO scores were maintained during the LTE study. CONCLUSION: In clinical practice, TCZ as monotherapy or in combination with csDMARDs was safe, well tolerated, and efficacious in patients with moderate to severe RA.
29424301 Novel Therapeutic Approaches in Rheumatoid Arthritis: Role of Janus Kinases Inhibitors. 2019 Rheumatoid Arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and hyperplasia, autoantibody production, cartilage and bone destruction and several systemic features. Cardiovascular, pulmonary, psychological, and muscle involvement are the main comorbidities of RA and are responsible for the severity of the disease and long-term prognosis. Pharmacological treatment of rheumatic diseases has evolved remarkably over the past years. In addition, the widespread adoption of treat to target and tight control strategies has led to a substantial improvement of outcomes, so that drug-free remission is nowadays a realistic goal in the treatment of RA. However, despite the availability of multiple therapeutic options, up to 40% of patients do not respond to current treatments, including biologics. Small-molecule therapies offer an alternative to biological therapies for the treatment of inflammatory diseases. In the past 5 years, a number of small-molecule compounds targeting Janus Kinases (JAKs) have been developed. Since JAKs are essential for cell signaling in immune cells, in particular controlling the response to many cytokines, their inhibitors quickly became a promising class of oral therapeutics that proved effective in the treatment of RA. Tofacitinib is the first Janus Kinase (JAK) inhibitor approved for the treatment of RA, followed more recently by baricitinib. Several other JAK inhibitors, are currently being tested in phase II and III trials for the treatment of a different autoimmune diseases. Most of these compounds exhibit an overall acceptable safety profile similar to that of biologic agents, with infections being the most frequent adverse event. Apart from tofacitinib, safety data on other JAK inhibitors are still limited. Long-term follow-up and further research are needed to evaluate the general safety profile and the global risk of malignancy of these small molecules, although no clear association with malignancy has been reported to date. Here, we will review the main characteristics of JAK inhibitors, including details on their molecular targets and on the clinical evidences obtained so far in the treatment of RA.
31067155 Multicenter, observational clinical study of abatacept in Japanese patients with rheumatoi 2019 Mar The aim of this study was to assess abatacept in rheumatoid arthritis (RA) patient. Patients (20 men, 89 women, aged 61.9 ± 10.4 y) who responded inadequately to conventional synthetic disease-modifying anti-rheumatic drug were treated with abatacept for 24-months. Disease activity score in 28 joints (DAS28-CRP) was evaluated. Of 109 patients, 82 (75.2%) were on methotrexate (MTX; mean dosage 9.0 ± 2.7 mg/week); 48 (44.0%) were naive to biologics and 61 (56.0%) had failed biologics. The 1- and 2-year retention rates were 77% and 53%, respectively. At 24-months, the DAS28-CRP remission rates were 54.5% in the biologic-naïve patients, and 28.2% in the biologic-failure patients (p < .01), while the structural remission rates were 83.9% and 73.1%, respectively (p = .461). Abatacept was equally effective in RA patients who were and were not on concomitant MTX. Biologic-naïve was associated with better clinical outcome. Abatacept was effective in patients who showed decreasing anti-CCP antibody titers or serum MMP-3 levels during treatment. Infection was the most frequent adverse effect of abatacept therapy. In conclusion, abatacept is more effective in biologic-naïve than in biologic-failure RA patients with or without concomitant use of MTX. Abatacept is more effective in RA patients with than without decreasing serum MMP-3 or anti-CCP antibody titers during treatment.
30529501 Helminth-based therapies for rheumatoid arthritis: A systematic review and meta-analysis. 2019 Jan OBJECTIVE: Proteins from parasitic worms have been posed as novel therapies for rheumatoid arthritis (RA) and other auto-inflammatory diseases. However, with so many potential therapeutics, it is important that drug discovery be based on the specific phyla or species which show the most promising effects. Therefore, the aim of this systematic review and meta-analysis was to evaluate the reported effects of helminthic secretory proteins and derivative therapy on RA in an animal model. METHODS: Medline, Scopus and Web of Science were searched to identify studies evaluating helminthic therapy in the collagen-induced arthritis model of RA. A meta-analysis was undertaken to determine the overall effect of the proteins. Subgroup analyses were also undertaken to investigate individual treatments. RESULTS: Seven articles were included in the analysis. Overall, helminthic therapy significantly reduced arthritis score (SMD -1.193, 95% CI -1.525, -0.860). Subgroup analyses found a significant reduction in arthritis score following treatment with helminth protein ES-62 (SMD -1.186, 95% CI -1.633, -0.738) and phosphorylcholine-based treatment (SMD -0.997, 95% CI -1.423, -0.571). Subgroup analyses found ES-62 treatment significantly decreased IFN-γ levels (SMD -1.611, 95% CI -2.734, -0.487) and significantly increased levels of IL-10 (SMD 0.946, 95% CI 0.127, 1.765). CONCLUSIONS: Therapeutics from parasitic worms are a promising avenue for drug discovery, especially with all included studies reporting a significant improvement in arthritis score. Based on pooled data presented in this study, the nematode Acanthocheilonema viteae seems to be of particular interest for therapeutics.
31492436 Descriptive epidemiology of hip and knee replacement in rheumatoid arthritis: An analysis 2020 Apr OBJECTIVE: To provide descriptive data on rates of total hip replacement (THR) and total knee replacement (TKR) within a large RA cohort and describe variation in risk. METHODS: Incident RA patients (1995 to 2014) were identified from the Clinical Practice Research Datalink (CPRD). First subsequent occurrence of THR and TKR were identified (analysed separately) and incidence rates calculated, stratified by sex, age, BMI, geographic region, and quintiles of the index of multiple deprivation (IMD) score. RESULTS: There were 27,607 RA patients included, with a total of 1,028 THRs (mean age at surgery: 68.4 years) and 1,366 TKRs (mean age at surgery: 67.6 years), at an overall incidence rate per 1,000 person-years (PYs) [95% CI] of 6.38 [6.00-6.78] and 8.57 [8.12-9.04], respectively. TKR incidence was similar by gender but THR rates were higher in females than males. Rates of TKR but not THR rose according to BMI. An increasing trend was observed in rates of both outcomes according to age (although not ≥75) but of decreasing rates according to socio-economic deprivation. There was some evidence for regional variation in TKR. The 10-year cumulative incidence was 5.2% [4.9, 5.6] and 7.0% [6.6, 7.4] for THR and TKR, respectively. CONCLUSION: We provide generalizable estimates of THR and TKR incidence in the UK RA patient population and note variation across several key variables. Increased BMI was associated with a large increase in TKR but not THR incidence. Increased deprivation was associated with a downward trend in rates of THR and TKR.
31388708 Cuff tear arthropathy in the nineteenth century: 'chronic rheumatic arthritis' with 'parti 2019 Oct INTRODUCTION: Cuff tear arthropathy of the shoulder is a common indication for insertion of an increasing number of reverse shoulder arthroplasties. It is widely believed that this condition was unknown to medical practitioners and writers prior to the introduction of the term cuff tear arthropathy by Charles Neer in 1977. PURPOSE: To search nineteenth-century written sources for pathoanatomical and biomechanical descriptions of the typical changes found in cuff tear arthropathy. METHODS: A historical review. Nineteenth-century medical textbooks, reviews, case series, autopsy reports and illustrations were systematically searched and retrieved for relevance. References were hand-searched. Illustrations were reproduced and interpreted. RESULTS: A richly illustrated nineteenth-century literature was identified. The typical changes in cuff tear arthropathy were termed 'chronic rheumatic arthritis' of the shoulder with 'partial luxation upwards' of the humeral head and interpreted within a pathoanatomical and biomechanical framework. Detailed descriptions and illustrations of massive rotator cuff tears, biceps pathology and the osseous changes were identified and presented. CONCLUSION: The pathoanatomical and biomechanical changes later termed cuff tear arthropathy were well understood and nicely described in nineteenth-century medical literature.