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ID PMID Title PublicationDate abstract
28515692 Wu-Tou Decoction in Rheumatoid Arthritis: Integrating Network Pharmacology and In Vivo Pha 2017 Purpose: This study aimed to explore underlying action mechanism of Wu-Tou decoction (WTD) in rheumatoid arthritis (RA) through network pharmacology prediction and experimental verification. Methods: Chemical compounds and human target proteins of WTD as well as RA-related human genes were obtained from TCM Database @ Taiwan, PubChem and GenBank, respectively. Subsequently, molecular networks and canonical pathways presumably involved in the treatment of WTD on RA were generated by ingenuity pathway analysis (IPA) software. Furthermore, experimental validation was carried out with MIP-1β-induced U937 cell model and collagen induced arthritis (CIA) rat model. Results: CCR5 signaling pathway in macrophages was shown to be the top one shared signaling pathway associated with both cell immune response and cytokine signaling. In addition, protein kinase C (PKC) δ and p38 in this pathway were treated as target proteins of WTD in RA. In vitro experiments indicated that WTD inhibited MIP-1β-induced production of TNF-α, MIP-1α, and RANTES as well as phosphorylation of CCR5, PKC δ, and p38 in U937 cells. WTD treatment maintained the inhibitory effects on production of TNF-α and RANTES in MIP-1β-induced U937 cells after CCR5 knockdown. In vivo experiments demonstrated that WTD ameliorated symptoms in CIA rats, decreased the levels of IL-1β, IL-2, IL-6, TNF-α, MIP-1α, MIP-2, RANTES, and IP-10 in serum of CIA rats, as well as mRNA levels of MIP-1α, MIP-2, RANTES, and IP-10 in ankle joints of CIA rats. Furthermore, WTD also lowered the phosphorylation levels of CCR5, PKC δ and p38 in both ankle joints and macrophages in ankle joints from CIA rats. Conclusion: It was demonstrated in this research that WTD played a role in inhibiting inflammatory response in RA which was closely connected with the modulation effect of WTD on CCR5 signaling pathway in macrophages.
28144130 Persistence and costs with subcutaneous TNF-alpha inhibitors in immune-mediated rheumatic 2017 OBJECTIVES: The objectives of this study were to 1) describe and compare treatment persistence with first- and second-line subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), or rheumatoid arthritis (RA) (collectively immune-mediated rheumatic disease) in Sweden and 2) estimate and contrast health care costs in the two groups. METHODS: Patients who initiated their first or second SC-TNFi between May 6 2010 and December 12 2012 were identified from the Prescribed Drug Register. Persistence was estimated using survival analysis. Costs comprised specialized outpatient care, inpatient care, and medication. The persistence analysis was stratified by immune-mediated rheumatic disease diagnosis. RESULTS: A total of 4,903 patients treated with their first and 845 patients treated with their second SC-TNFi were identified. Baseline characteristics differed between the two groups. Therefore, propensity score matching analysis was implemented. Second-line patients were matched to first-line patients, and four cohort pairs (AS, PsA, RA, and all diagnoses combined) were generated. Patients treated with their first SC-TNFi had statistically significant higher persistence than patients treated with their second SC-TNFi in PsA (P=0.036), RA (P=0.048), and all diagnoses combined (P<0.001) but not in AS (P=0.741). Patients who were treated with their second SC-TNFi incurred higher costs than patients treated with their first SC-TNFi. CONCLUSION: Overall, persistence to the first SC-TNFi was higher than persistence to the second SC-TNFi. Furthermore, the second SC-TNFi was associated with higher costs than the first SC-TNFi. Therefore, prescribing the SC-TNFi with the best long-term persistence first may be beneficial.
28328075 Role of amino acids in rheumatoid arthritis studied by metabolomics. 2019 Jan BACKGROUND: Rheumatoid arthritis (RA) is a complex, chronic autoimmune disease characterized by various inflammatory symptoms, including joint swelling, joint pain, and both structural and functional joint damage. The most commonly used animal model for studying RA is mice with collagen-induced arthritis (CIA); the wide use of this model is due primarily to many similarities with RA in human patients. Metabolomics is used increasingly in biological studies for diagnosing disease and for predicting and evaluating drug interventions, as a large number of disease-associated metabolites can be analyzed and interpreted from a biological perspective. AIM: To profile free amino acids and their biogenic metabolites in CIA mice plasma. METHOD: Ultra-high-performance liquid chromatography/tandem mass spectrometry coupled with multiple reaction monitoring (MRM) was used for metabolomics study. RESULTS: Profile of 45 amine metabolites, including free amino acids and their biogenic metabolites in plasma was obtained from CIA mice. We found that the plasma levels of 20 amine metabolites were significantly decreased in the CIA group. CONCLUSION: The results suggest that a disordered amine response is linked to RA-associated muscle wasting and energy expenditure.
29911088 Rheumatic hand's clinical, functional and imagiological correlations following metacarpoph 2018 Mar OBJECTIVE: Evaluation of rheumatoid hand-associated metacarpophalangeal joint silicone arthroplasty most often relies on functional scores alone. This study aimed to understand the correlation between perceived and observed function, strength, and alignment. METHODS: Cross-sectional study including all 11 women (15 hands) submitted to second to fifth metacarpophalangeal joint arthroplasty due to rheumatoid arthritis involvement for a time period of seven years. Measurements relied on the Michigan Hand Outcomes Questionnaire, Lafayette Purdue Pegboard, pinch and grip strength, and analysis of a lateral "OK-sign" X-ray view. Correlation analysis used Spearman's coefficient, assuming statistical significance for p-values < 0.05. RESULTS: Objective function was strongly correlated with all other variables (p < 0.05), while perceived function failed to correlate with articular alignment in both measurements (p = 0.240 and p = 0.354). Strength and alignment were also strongly correlated (p < 0.05). CONCLUSIONS: Most measurements strongly correlate with each other, with emphasis on objective dexterity measurement.
28166793 Cytotoxic T cells modulate inflammation and endogenous opioid analgesia in chronic arthrit 2017 Feb 6 BACKGROUND: This study examined the development of chronic pain, a cardinal symptom of rheumatoid arthritis (RA), in mice with antigen- and collagen-induced arthritis (ACIA). Since the role of CD8(+) T cells in arthritis is controversial, we investigated the consequences of CD8-depletion on arthritis development and opioid modulation of pain in this novel model of chronic autoimmune arthritis. METHODS: Disease severity in control and CD8-depleted animals was determined by histological assessment of knee-joint sections and measurement of autoantibody formation. Pain was evaluated by measuring mechanical allodynia and thermal hyperalgesia in von Frey and Hargreaves tests, respectively. The production and release of endogenous opioids and inflammatory cytokines was assessed in immunoassays. RESULTS: In ACIA, mice display persistent mechanical allodynia and thermal hyperalgesia for more than 2 months after induction of arthritis. The blockade of peripheral opioid receptors with naloxone-methiodide (NLXM) transiently increased thermal hyperalgesia, indicating that endogenous opioid peptides were released in the arthritic joint to inhibit pain. CD8(+) T cell depletion did not affect autoantibody formation or severity of joint inflammation, but serum levels of the pro-inflammatory cytokines TNFα and IL-17 were increased. The release of opioid peptides from explanted arthritic knee cells and the NLXM effect were significantly reduced in the absence of CD8(+) T cells. CONCLUSIONS: We have successfully modeled the development of chronic pain, a hallmark of RA, in ACIA. Furthermore, we detected a yet unknown protective role of CD8(+) T cells in chronic ACIA since pro-inflammatory cytokines rose and opioid peptide release decreased in the absence of these cells.
28631705 [Vaccination in rheumatology: Evolution of views on the problem]. 2017 The problem of coinfections that are due to both a rheumatic disease (RD) itself and the need to use immunosuppressive drugs deserves apparent attention in modern rheumatology. Coinfections substantially affect morbidity and mortality rates, especially in diffuse connective tissue diseases. The data available in the literature on the above subject matter suggest that vaccination is a powerful method for prevention of infectious diseases that are the most important problem for patients with RD.
29276236 Janus Kinase Inhibitors for the Treatment of Rheumatoid Arthritis. 2017 Nov Rheumatoid arthritis (RA) is a disease where the immune system attacks the linings of the joints, resulting in joint pain, stiffness, swelling, and destruction. Although many products are available for the treatment of RA, limitations such as adverse reactions and tolerance greatly affect adherence. Many of the current biologic disease-modifying antirheumatic drugs on the market are injectables, leaving a void to be filled for a product that can be taken orally. The most advanced of these approaches, the Janus kinase (JAK) inhibitors, are oral drugs that have not only made a breakthrough in RA, but also other skin conditions.
29209946 Usability and Patient Preference Phase 3 Study of the Sarilumab Pen in Patients with Activ 2018 Jun INTRODUCTION: Sarilumab is a human monoclonal antibody that blocks the interleukin-6 receptor alpha (IL-6Rα). The phase 3 SARIL-RA-EASY study (EASY) assessed the robustness of an autoinjector (pen) for administering sarilumab when used by adults with active moderate-to-severe rheumatoid arthritis (RA) who are candidates for anti-IL-6R therapy in an unsupervised real-world setting. METHODS: EASY was a 12-week, multicenter, randomized, open-label, parallel-group usability study of the sarilumab pen and prefilled syringe. Patients were randomized 1:1:1:1 to sarilumab 150 or 200 mg every 2 weeks (q2w) administered via pen or syringe, plus background disease-modifying antirheumatic drugs. Patients reported their ability to remove the pen cap and initiate and complete injections; negative responses were defined as product technical complaints (PTCs). The primary endpoint was the number of validated product technical failures (PTFs; PTC with a validated technical cause). This study was not powered to demonstrate bioequivalence or differences in efficacy among groups. RESULTS: A total of 217 patients were randomized. There were 600 successful injections with the sarilumab pen in 108 patients and no pen-associated PTFs. One PTC was observed (the pen was mistakenly activated before injection). At week 12, 88% of patients indicated the pen was "easy" to use, and 98% reported they were "satisfied" with the pen. Proportions of patients achieving an American College of Rheumatology 20/50/70 response and a 28-joint disease activity score by C-reactive protein < 2.6 were similar at each dose between the pen and syringe groups, as were the pharmacokinetics. There were no clinically meaningful differences in adverse events (AEs), serious AEs, and AEs leading to discontinuation in the pen and syringe groups. The most common treatment-emergent AEs were infections and neutropenia. CONCLUSION: This study demonstrated the ease of use and robustness of the sarilumab pen when used by patients with RA in an unsupervised setting. Pharmacokinetics, safety, and efficacy were generally similar for the pen and syringe groups (NCT02057250). FUNDING: Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. TRIAL REGISTRATION: Clinicaltrials.gov identifier, NCT02057250.
28831751 Discontinuation of Biologic Therapy in Rheumatoid Arthritis: Analysis from the Corrona RA 2017 Dec INTRODUCTION: Despite the availability of multiple effective therapies, discontinuation/switching of treatment is common for many patients with rheumatoid arthritis (RA). This study was designed to examine initiation of biologic disease-modifying anti-rheumatic drugs (bDMARDs) within the Consortium of Rheumatology Researchers of North America (Corrona) RA Registry, and characterize reasons for discontinuation. METHODS: Inclusion criteria were: Corrona-registered adults (≥18 years) with RA (2002-2011); age of RA onset: ≥16 years; ≥6 months' follow-up after initiation of first/subsequent bDMARD. Patients receiving both tumor necrosis factor antagonists and non-TNF antagonists were included. Treatment discontinuation was defined as first report of stopping initial therapy or initiation of new bDMARD at/between visits, using a follow-up physician questionnaire. RESULTS: Overall, 6209 patients met inclusion criteria and 80.7% received TNF antagonists. Median time to discontinuation/change of therapy was 25.1 months (26.5 months with TNF antagonists vs. 20.5 months with non-TNF antagonists; log-rank p < 0.0001); 82.2, 67.3, and 51.1% of patients remained on therapy at 6, 12, and 24 months, respectively. Reasons for discontinuation were captured for 49.2% of patients, including: loss of efficacy (35.8%); physician preference (27.8%); safety (20.1%); patient preference (17.9%); and no access to treatment (9.0%). Baseline factors with greatest correlation to discontinuation were modified Health Assessment Questionnaire scores, patient-reported anxiety/depression, initiation of bDMARD treatment in 2007-2010 versus 2002-2003, and Clinical Disease Activity Index scores. CONCLUSIONS: Almost one-third of patients in the US discontinue currently available bDMARD therapies for RA by 12 months and almost half by 24 months, most commonly due to loss of efficacy. FUNDING: Corrona LLC and MedImmune.
28589079 Role of LIGHT in the pathogenesis of joint destruction in rheumatoid arthritis. 2017 May 20 AIM: To characterise the role of substitutes for receptor-activator nuclear factor kappa-B ligand (RANKL) in rheumatoid arthritis (RA) joint destruction. METHODS: Synovial fluid (SF) macrophages isolated from the knee joint of RA patients were incubated with 25 ng/mL macrophage-colony stimulating factor (M-CSF) and 50 ng/mL LIGHT (lymphotoxin-like, exhibits inducible expression and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes) in the presence and absence of 25 ng/mL RANKL and 100 ng/mL osteoprotegerin (OPG) on glass coverslips and dentine slices. Osteoclastogenesis was assessed by the formation of multinucleated cells (MNCs) expressing tartrate-resistant acid phosphatase (TRAP) on coverslips and the extent of lacunar resorption pit formation on dentine slices. The concentration of LIGHT in RA and osteoarthritis (OA) synovial fluid was measured by an enzyme-linked immunosorbent assay (ELISA) and the expression of LIGHT in RA and OA synovium was determined by immunohistochemistry using an indirect immunoperoxidase technique. RESULTS: In cultures of RA SF macrophages treated with LIGHT and M-CSF, there was significant formation of TRAP + MNCs on coverslips and extensive lacunar resorption pit formation on dentine slices. SF-macrophage-osteoclast differentiation was not inhibited by the addition of OPG, a decoy receptor for RANKL. Resorption pits were smaller and less confluent than in RANKL-treated cultures but the overall percentage area of the dentine slice resorbed was comparable in LIGHT- and RANKL-treated cultures. LIGHT significantly stimulated RANKL-induced lacunar resorption compared with RA SF macrophages treated with either RANKL or LIGHT alone. LIGHT was strongly expressed by synovial lining cells, subintimal macrophages and endothelial cells in RA synovium and the concentration of LIGHT was much higher in RA compared with OA SF. CONCLUSION: LIGHT is highly expressed in RA synovium and SF, stimulates RANKL-independent/dependent osteoclastogenesis from SF macrophages and may contribute to marginal erosion formation.
29901016 Are Illness Perceptions Associated With Disease Activity or Psychological Well-Being in Rh 2017 Dec OBJECTIVES: This study aims to assess the factor structure of the Turkish Revised Illness Perception Questionnaire (IPQ-R) in patients with rheumatoid arthritis (RA) and the relationship of illness perceptions with disease activity and psychological well-being. PATIENTS AND METHODS: One hundred and fifty RA patients (8 males, 142 females; mean age 51.1±12.7 years; range 21 to 81 years) were included in the study. Confirmatory factor analysis was used to test the factor structure of the IPQ-R. Pain was assessed by visual analog scale, disease activity by Disease Activity Score 28, depression by Beck Depression Inventory, global life satisfaction by the Satisfaction with Life Scale, and illness perception by the IPQ-R. RESULTS: Three items (items 12, 18, 19) were deleted because of poor factor loadings. The modified 35-item model showed good reliability and discriminant validity. Beck Depression Inventory scores were correlated with identity, consequences, and emotional representations subscales positively (p<0.001); and with illness coherence subscale negatively (p<0.05). There were positive correlations between Satisfaction with Life Scale scores, and treatment control and illness coherence subscales (p<0.05). Satisfaction with Life Scale scores were negatively correlated with identity, emotional representation, and timeline acute/chronic subscales (p<0.05), and consequences subscale (p<0.001). Disease Activity Score 28 was not correlated with IPQ-R domains (p>0.05). CONCLUSION: The Turkish IPQ-R appears to be a useful clinical assessment tool to evaluate RA-related illness perceptions. RA healthcare should include psychological intervention to strengthen patients' beliefs about their RA regardless of disease activity.
28255449 DAS28-CRP and DAS28-ESR cut-offs for high disease activity in rheumatoid arthritis are not 2017 BACKGROUND: In most patients with rheumatoid arthritis (RA), Disease Activity Score 28-joint count C reactive protein (DAS28-CRP) is lower than DAS28 erythrocyte sedimentation rate (DAS28-ESR), suggesting that use of the DAS28-ESR cut-off to assess high disease activity (HDA) with DAS28-CRP may underestimate the number of patients with HDA. We determined the DAS28-CRP value corresponding to the validated DAS28-ESR cut-off for HDA. METHODS: Baseline data were pooled from 2 clinical studies evaluating etanercept (ETN) plus methotrexate (MTX) or MTX in early RA; DAS28-CRP and DAS28-ESR were obtained, allowing the determination of the DAS28-CRP HDA value best corresponding to the DAS28-ESR cut-off of >5.1. RESULTS: At baseline, as expected, fewer patients had HDA by DAS28-CRP than DAS28-ESR; DAS28-CRP>5.1 and DAS28-ESR>5.1 had only modest agreement (κ coefficients 0.45-0.54). Mean DAS28-CRP and DAS28-ESR were 5.7 and 6.2, respectively, in the ETN+MTX group (n=571), and 6.0 and 6.5 in the MTX group (n=262). A DAS28-CRP cut-off of 4.6 corresponded to a DAS28-ESR cut-off of 5.1. CONCLUSIONS: We have shown that a DAS28-CRP of 4.6 corresponds to 5.1 for DAS28-ESR. Since this is substantially lower than the DAS28-ESR cut-off of 5.1, using 5.1 as the cut-off for DAS28-CRP underestimates disease activity in RA. TRIAL REGISTRATION NUMBER: NCT00195494; NCT00913458.
27928943 The Physiological/Pathophysiological Significance of Vitamin D in Cancer, Cardiovascular D 2017 BACKGROUND: Vitamin D, a molecular precursor of the potent steroid hormone calcitriol, has crucial functions and roles in physiology and pathophysiology. Tellingly, calcitriol has been shown to regulate various cellular signalling networks and cascades that have crucial role in cancer biology and diagnostics. Mounting lines of evidences from previous clinical and preclinical investigations indicate that the deficiency of vitamin D may contribute to the carcinogenesis risk. Concomitantly, recent reports suggested that significant reduction in the cancer occurrence and progression is more likely to appear after vitamin D supplementation. Furthermore, a pivotal role functioned by vitamin D in cardiovascular physiology indicates that the deficiency of vitamin D is significantly correlated with enhanced prevalence of stroke, hypertension and myocardial infarction. Notably, vitamin D status is more likely to be used as a lifestyle biomarker, since poor and unhealthy lifestyles are correlated with the deficiency of vitamin D, a feature which may result in cardiovascular complications. Moreover, recent reports revealed that the effect of vitamin D is to cover not only cardiovascular system but also skeletal system. OBJECTIVE: Herein, we are highlighting the recent knowledge of vitamin D roles and functions with respect to pathophysiological disorders such as cancer, cardiovascular diseases, rheumatoid arthritis (RA) and debate the potential avails of vitamin D on slowing cancer, cardiovascular disease and RA progression. CONCLUSION: The findings of this review confirm that the importance of vitamin D metabolites or analogues which can provide a helpful platform to target some kinds of cancer, particularly when used in combination with existing therapies. Moreover, the correlation between vitamin D deficiencies with cardiovascular diseases and rheumatoid arthritis (RA) progression might suggest a pivotal role of vitamin D in either initiation or progression of these diseases.
28097375 Hypoxia-Induced Fibroblast Growth Factor 11 Stimulates Osteoclast-Mediated Resorption of B 2017 Apr Over-activation of osteoclasts is directly responsible for pathological bone loss in conditions such as rheumatoid arthritis and cancer metastasis to bone. Hypoxia is a common feature of these conditions, associated with poor prognosis, which also stimulates osteoclast-mediated bone resorption via induction of the hypoxia-inducible transcription factor HIF-1α. Here, we investigate the effects of fibroblast growth factor 11 (FGF11) on osteoclast function. FGF11 is an intracellular FGF that was induced both by hypoxia (2% O(2), p < 0.01) and by inhibition of the HIF-regulating prolyl hydroxylase enzymes (CoCl(2), p < 0.001) in osteoclasts. Isoform-specific siRNA demonstrated that the induction of Fgf11 mRNA expression by hypoxia is HIF-1α-dependent (p < 0.01). Hypoxic stimulation of bone resorption was inhibited in osteoclasts treated with siRNA targeting FGF11 (p < 0.05). This was at least partially due to reduced secretion of an unidentified pro-resorptive factor downstream of FGF11. FGF11 expression within hypoxic, resorbing osteoclasts co-localised with microtubule-associated alpha-tubulin. FGF11 was also abundantly expressed in osteoclasts within the rheumatoid synovium and in giant cell tumour of bone. This study suggests FGF11 as a novel factor driving pathological bone resorption in osteolytic disease and as a potential target for the development of new anti-resorptive therapeutic agents.
32185277 Study of the natural course and specific immunity after herpes zoster in patients with rhe 2017 Sep Herpes zoster is a common infection especially in elderly persons. It is caused by reactivation of varicella zoster virus (VZV) that has remained dormant within dorsal root ganglia after primary infection. Besides patients with immunodeficiency and malignancies, zoster incidence is also higher in patients with rheumatic diseases compared to the general population. Especially in the group of rheumatoid arthritis (RA) patients being treated with biologics, the risk seems to be steady among regimens with different modes of action (1.6-2.4/100 patients-years). RA patients receiving tumor necrosis factor (TNF) inhibitors are at increased risk during the first year of treatment. The aim of the current research protocol is to evaluate the natural course of herpes zoster and the effect of biologic and conventional synthetic disease modifying anti-rheumatic drugs (DMARDs) on the VZV-specific cell mediated immunity in RA patients after herpes zoster infection. We will - prospectively - include RA patients who develop herpes zoster, while being treated with biologics (anti-TNF, tocilizumab, rituximab, abatacept) and a control group comprised of patients with herpes zoster [RA patients under non-biologic therapies (corticosteroids/csDMARDs) and age- and sex-matched healthy controls). Titers of IgG specific antibodies against VZV glycoprotein gp1 and the percentage and absolute number of VZV-specific activated CD4+ T cells (CD4+CD69+IFN-γ+) at the time of rash onset and during follow-up will be measured by ELISA and flow cytometry respectively. This study will contribute to the better understanding of various aspects of immune response to VZV in the modern treatment era with biologic DMARDs.
28251584 Improvements in Fatigue in 1536 Patients with Rheumatoid Arthritis and Correlation with Ot 2017 Jun INTRODUCTION: A post hoc analysis of three randomized controlled trials of abatacept in rheumatoid arthritis (RA) was conducted to explore the effect of abatacept on fatigue in RA and its correlation with other outcomes. METHODS: In this analysis of AGREE (early RA) and AIM and ATTAIN (established RA), changes in baseline fatigue (0-100 mm scale), pain, sleep (AIM and ATTAIN only) and Disease Activity Score (DAS) 28 (C-reactive protein; CRP) were calculated at days 29, 85, and 169. Agreement between improvements ≥minimum clinically important differences (MCID) in fatigue and other outcomes were evaluated using agreement statistics (kappa) in each study and at each time point. RESULTS: Of 1536 patients (mean disease duration: 6.2 months [AGREE], 8.5 years [AIM], 12.2 years [ATTAIN]), mean (SE) decreases in fatigue from baseline to day 169 with abatacept were 28.9 (1.7), 25.3 (1.2), and 21.9 (1.6) in AGREE, AIM, and ATTAIN, respectively, with corresponding decreases of 16.0, 13.7, and 13.4 at day 29. Most patients (67.8%; 624/920) reported improvements ≥MCID in fatigue with abatacept at day 169; 79.2% (671/847) and 57.8% (388/671) reported improvements ≥MCID in pain and sleep, respectively; 18.9% (158/836) were in DAS28 (CRP) remission. Agreement between improvement in fatigue and other outcomes was low (kappa range 0.30-0.51 [pain], 0.14-0.26 [sleep], and 0.02-0.12 [DAS28 (CRP) remission]). CONCLUSIONS: Abatacept resulted in rapid improvements in fatigue and pain in patients with RA. However, low agreement between improvements in these outcomes indicates that fatigue and other outcomes including pain and sleep may represent different domains of response. FUNDING: Bristol-Myers Squibb.
30697263 Prevalence and clinical characteristics of rheumatoid arthritis in Poland: a nationwide st 2019 Jan INTRODUCTION: There are no reliable data regarding the prevalence of rheumatoid arthritis (RA) in Poland. MATERIAL AND METHODS: The first stage was a face-to-face survey on a nationwide representative sample of 3000 people, which identified respondents with a physician-confirmed diagnosis of RA. The second stage was a survey of RA patients, which characterized the disease course and treatment. It was evaluated by analysis of a representative group of 1957 RA patients in routine clinical practice. RESULTS: The overall RA prevalence in Poland was 0.9% (95% CI: 0.6-1.2%), 1.06% for women, 0.74% for men. Seventy-eight percent were female, mean age was 56 and mean disease duration 7 years. Younger patients (< 50) remained professionally active in 90% of cases. Thirty percent of patients were diagnosed within 3 months of the first RA symptoms, while for 17% it took more than 1 year. Fifty-six percent of newly diagnosed patients were characterized by high disease activity (DAS-28 > 5.1). Presently, low disease activity (DAS-28 < 3.2) was found in 38.5% of patients. In Poland, 94% of patients have been treated with non-steroid anti-inflammatory drugs, almost 80% with glucocorticoids. Meanwhile, methotrexate, as an anchor drug in Poland, has been used by 80% of patients, biological agents by 2.94% of patients. CONCLUSIONS: This is the first cross-sectional population-based epidemiological study regarding prevalence of RA in the adult Polish population. The results demonstrate a high prevalence, falling within the upper boundary estimates for Europe. Despite ongoing treatment, the majority still have moderate to high disease activity, and the use of biological therapies is low.
29138986 Secukinumab in Active Rheumatoid Arthritis after Anti-TNFα Therapy: A Randomized, Double- 2017 Dec INTRODUCTION: 'REASSURE' (NCT01377012), a phase 3 study, evaluated the efficacy and safety of secukinumab in patients with active rheumatoid arthritis (RA) who had an inadequate response to, or intolerance of, tumor necrosis factor inhibitors (TNF-inhibitors). METHODS: A total of 637 patients were randomized (1:1:1) to receive intravenous secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous secukinumab 150 mg or 75 mg every 4 weeks (starting from week 8) or placebo at the same dosing schedule. The primary endpoint was the American College of Rheumatology 20% improvement criteria (ACR20) at week 24. Other predefined hierarchical endpoints included Health Assessment Questionnaire-Disability Index, van der Heijde modified total Sharp score (vdH-mTSS) at week 24, and major clinical response (MCR; continuous 6 month period of ACR70 response) at 1 year. RESULTS: The primary efficacy endpoint was met with both secukinumab dose groups: ACR20 response rate at week 24 was 35.2% for both secukinumab dose groups (P = 0.0009) vs 19.6% for placebo. The improvements in secondary endpoints were greater in the secukinumab dose groups vs placebo but did not meet statistical significance. The overall safety profile was similar across all treatment groups. CONCLUSION: Secukinumab demonstrated efficacy in reducing disease activity over placebo as measured by ACR20 in patients with active RA who had an inadequate response to TNF-inhibitors. Secukinumab demonstrated a safety profile similar to other biologics currently approved for RA. FUNDING: Novartis Pharma AG. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01377012.
29067050 Delayed conventional DMARDs therapy is effective in Rheumatoid Arthritis. 2017 Jul OBJECTIVE: To determine the disease severity in patients with Rheumatoid Arthritis (RA), at baseline and the impact of treatment on disease activity (DA) after six months of disease modifying anti-rheumatic drugs (DMARDs) therapy. METHODS: This prospective study was conducted at the 'Rheumatology Clinic' of Jinnah Postgraduate Medical Centre (JPMC), Karachi, from June 2014 to May 2015. A total of 111 patients, with the diagnosis of RA were included in the study. DA was calculated using 'Clinical Disease Activity Index' (CDAI) score at base line and after 6 months of DMARDs therapy. RESULTS: Out of 111 patients, 17 (15.3%) were male and 94 (84.7%) were female. The mean age was 37.16±11.3 years and the mean duration of joint pain was 3.8±3.6 years (median 2.5 years). The mean Hb was 10.8±1.8 g/dl and the mean ESR at baseline was 59.63±30.9 mm/Hr. The mean initial CDAI score was 18.14±11.69; reflecting moderate to severe disease. Of all of these patients, 32 (28.8%) patients received monotherapy, 78 (70.3%) received dual therapy and 1(0.9%) was given triple DMARDs therapy. The mean ESR was 39.5±27.31 mm/Hr, and mean CDAI was 7.36±7.8 with a median of 6.0 after 6 months of DMARDs treatment. CONCLUSION: The CDAI score and the ESR reflected that majority of our patients were in remission or at low disease activity, after six months of DMARDs therapy. It is possible to control DA in RA, in a low resource health care facility with conventional DMARDs therapy. Continuity of treatment was ensured through motivation, regular supply of drugs and regular follow-up.
28450917 Diagnostic value of high-frequency color Doppler ultrasonography examination in combinatio 2017 Mar We studied the diagnostic value of high-frequency color Doppler ultrasonography (HCDU) examination in combination with anti-cyclic citrullinated peptide (anti-CCP) antibody testing in rheumatoid arthritis (RA) patients with finger joint damage. From January 2015 to December 2015, 80 patients diagnosed with RA with finger joints damage were enrolled in this study. Patients were examined with HCDU. Serum anti-CCP antibody level was tested using ELISA, and results were compared with the healthy control group. Results obtained by ELISA demonstrated that the positive rate of anti-CCP antibodies was 73.8% in the study group, and 10% in the control group. The negative rate was 26.2% in the study group, and 90% in the control group. HCDU examination suggested that the predominantly affected joint by bone erosion of RA with finger joint damage was MCP3 (16.7%), followed by PIP3 (14.1%), MCP2 (13.5%) and PIP2 (12.8%). The slightest affected joint was thumb metacarpophalangeal joint, followed by thumb, little finger metacarpophalangeal joint and proximal interphalangeal joint. The sensitivity of diagnosis of RA with finger joints damage with both HCDU and CCP antibody examination showed a significantly lower level compared with examination with each one of the methods alone, while specificity showed a significantly higher level. Thus, a combination of HCDU examination and anti-CCP antibody testing can be considered useful to improve the early diagnostic rate of RA. HCDU examination is a sensitive, secure, atraumatic and easily-operated diagnostic method for early RA patients with finger joint damage. When combined with anti-CCP antibody testing, it will provide a better chance for RA patients, and give them hope for a better treatment and improved prognosis.