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Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring in clinical practice: the spanish cohort of the COMORA study.
Balsa, A, Lojo-Oliveira, L, Alperi-López, M, García-Manrique, M, Ordóñez-Cañizares, C, Pérez, L, Ruiz-Esquide, V, Corrales, A, Narváez, J, Rey-Rey, J, et al
Reumatologia clinica. 2019;(2):102-108
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Abstract
OBJECTIVES To describe the prevalence of comorbidities in patients with RA in Spain and discuss their management and implications using data from the Spanish cohort of the multinational study on COMOrbidities in Rheumatoid Arthritis (COMORA). METHODS This is a national sub-analysis of the COMORA study. We studied the demographics and disease characteristics of 200 adults patients diagnosed with RA (1987 ACR), and routine practices for screening and preventing the following selected comorbidities: cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and depression. RESULTS Patients had a mean age of 58 years and a mean RA duration of 10 years. Mean DAS28 score was 3.3 and approximately 25% of patients were in remission (DAS28 <2.6). Forty-four (22%) patients had ≥1 comorbidity, the most frequent being depression (27%) and obesity (26%). A history of myocardial infarction or stroke was observed in 5% and 1% of patients, respectively, and any solid tumor in 6%. Having a Framingham Risk Score >20% (51%), hypercholesterolemia (46%) or hypertension (41%) and smoking (25%) were the most common CV risk factors. For prostate, colon and skin cancers, only 9%, 10% and 18% of patients, respectively, were optimally monitored. Infections were also inadequately managed, with 7% and 17% of patients vaccinated against influenza and pneumococcal, respectively, as was osteoporosis, with 47% of patients supplemented with vitamin D and 56% with a bone densitometry performed. CONCLUSIONS In Spain, the prevalence of comorbidities and CV risk factors in RA patients with established and advanced disease is relatively high, and their management in clinical daily practice remains suboptimal.
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Peficitinib: First Global Approval.
Markham, A, Keam, SJ
Drugs. 2019;(8):887-891
Abstract
Peficitinib [Smyraf® (Astellas Pharma)] is a Janus kinase (JAK)1, JAK2, JAK3 and tyrosine kinase (Tyk)2 (pan-JAK) inhibitor recently approved in Japan for the treatment of rheumatoid arthritis. Inhibition of JAK suppresses the activation of cytokine signalling pathways involved in inflammation and joint destruction in rheumatoid arthritis. Peficitinib has been shown to significantly improve ACR20 and other measures of disease severity and to reduce the mean modified total Sharp score change from baseline in clinical trials. This article summarizes the milestones in the development of peficitinib leading to this first approval as a treatment for rheumatoid arthritis in patients who have an inadequate response to conventional therapies.
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Folate Supplementation for Methotrexate Therapy in Patients With Rheumatoid Arthritis: A Systematic Review.
Liu, L, Liu, S, Wang, C, Guan, W, Zhang, Y, Hu, W, Zhang, L, He, Y, Lu, J, Li, T, et al
Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases. 2019;(5):197-202
Abstract
OBJECTIVE To review the evidence for benefits and harms of folate (folic acid or folinic acid) supplementation on methotrexate (MTX) treatment for rheumatoid arthritis (RA), to assess whether or not folate supplementation would reduce MTX toxicity or reduce MTX benefits, and to decide whether a higher MTX dosage is essential. METHODS We performed a sensitive search strategy and searched systematically the Medline, Embase, Web of Science and Cochrane Library databases from inception to 2 June 2016. Abstracts from major rheumatology meetings and major trial registers were also searched to retrieve all randomized controlled trials that interested us. RESULTS Seven studies with 709 patients were included. No significant heterogeneity was found between these trials. For RA patients treated with MTX, those supplied with folate were less likely to have elevated transaminase (odds ratio [OR] 0.15; 95% confidence interval [95% CI] 0.10, 0.23 [p < 0.00001]) and gastrointestinal side-effects such as nausea and vomiting (OR 0.71; 95% CI 0.51, 0.99 [p = 0.04]). Folate appeared to promote compliance to MTX as it reduced patient withdrawal compared to placebo (OR 0.29; 95% CI 0.21, 0.42 [p < 0.00001]). There was no statistical difference for mouth sores between folate and placebo (OR 0.83; 95% CI 0.57, 1.22 [p = 0.35]). As the markers of disease activity in those trials were not consistent, it was impossible to decide whether folate supplementation reduced MTX efficacy. Besides, we compared high-dose folate (≥25 mg per week) and low-dose folate (≤10 mg per week) on MTX efficacy, finding no statistical difference (OR 2.07; 95% CI 0.81, 5.30 [p = 0.13]), nor on MTX toxicity (OR 1.56; 95% CI 0.80,3.04 [p = 0.19]). CONCLUSION Folate supplementation can reduce the incidence of hepatotoxicity and gastrointestinal side-effects of MTX in patients with RA. It can also reduce patient withdrawal from MTX treatment. Although it tended to reduce mouth sores, it had no statistical significance. No significant difference was found between high-dose folate and low-dose folate on MTX efficacy or toxicity.
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The structure, specificity and function of anti-citrullinated protein antibodies.
Ge, C, Holmdahl, R
Nature reviews. Rheumatology. 2019;(8):503-508
Abstract
In this Perspectives article, we outline a proposed model for understanding the specificity and function of anti-citrullinated protein antibodies (ACPAs). We suggest that ACPAs vary in specificity between two extremes: some are 'promiscuous' in that they are highly specific for the citrulline side chain, but cross-react with a range of citrullinated peptides, whereas others are 'private' in that their recognition of citrulline as well as proximal amino acid side chains enables protein-specific interactions. Promiscuous ACPAs tend to dominate in the sera both before and after the onset of rheumatoid arthritis, but their functional role has not been clarified. No firm evidence exists that these ACPAs are pathogenic. By contrast, private ACPAs encompass antibodies that specifically recognize citrullinated epitopes on joint proteins or that cross-react with joint proteins, thereby opening up the possibility that these private ACPAs are arthritogenic. These joint-reactive antibodies are more likely to target joints by binding to joint tissues and to promote the formation of local immune complexes leading to bone erosions, pain and arthritis.
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Cardiovascular safety of tocilizumab: A systematic review and network meta-analysis.
Castagné, B, Viprey, M, Martin, J, Schott, AM, Cucherat, M, Soubrier, M
PloS one. 2019;(8):e0220178
Abstract
OBJECTIVES Our objective was to compare the cardiovascular safety of tocilizumab and other biological disease-modifying antirheumatic drugs (bDMARD) in rheumatoid arthritis using a network meta-analysis (NMA). METHODS A systematic literature search through May 2018 identified randomized controlled trials (RCT) or observational studies (cohort only) reporting cardiovascular outcomes of tocilizumab (TCZ) and/or abatacept (ABA) and/or rituximab (RTX) and/or tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis patients. The composite primary outcome was the rate of major adverse cardiovascular outcomes (MACE, myocardial infarction (MI), peripheral artery disease (PAD) and cardiac heart failure (CHF)). RESULTS 19 studies were included in the NMA, including 11 RCTs and 8 cohort studies. We found less events with RTX (5.41 [1.70;17.26]. We found no difference between TCZ and other treatments. Concerning MI, we found no difference between TCZ and csDMARD (4.23 [0.22;80.64]), no difference between TCZ and TNFi (2.00 [0.18;21.84]). There was no difference between TCZ and csDMARD (1.51[0.02;103.50] and between TCZ and TNFi (1.00 [0.06;15.85]) for stroke event. With cohorts and RCT NMA, we found no difference between TCZ and other treatments for MACE (0.66 [0.42;1.03] with ABA, 1.04 [0.60;1.81] with RTX, 0.78[0.53;1.16] and 0.91 [0.54;1.51] with csDMARD), but the risk of myocardial infarction was lower with TCZ compared to ABA (0.67 [0.47;0.97]). We lacked data to compare TCZ and other bDMARD for stoke and MI. Not enough data was available to perform a NMA for CHF and PAD. CONCLUSIONS Despite an increase in cholesterol levels, TCZ has safe cardiovascular outcomes compared to other bDMARD.
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Comparison of combination therapy with methotrexate and sinomenine or leflunomide for active rheumatoid arthritis: A randomized controlled clinical trial.
Huang, RY, Pan, HD, Wu, JQ, Zhou, H, Li, ZG, Qiu, P, Zhou, YY, Chen, XM, Xie, ZX, Xiao, Y, et al
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2019;:403-410
Abstract
BACKGROUND A combination of conventional disease-modifying anti-rheumatic drugs improves the treatment of rheumatoid arthritis but with high side-effects. Methotrexate (MTX) combination therapy that with high therapeutic efficacy and low toxicity is in demand in many countries to replace the use of expensive biological agents. STUDY DESIGN This study was an open-label, 24-week, parallel randomized controlled trial conducted between November 2015 and December 2017. METHODS Patients were randomly assigned at a 3:2 ratio to receive MTX combined with sinomenine (SIN) at a dose of 120 mg twice daily, or leflunomide (LEF) at a dose of 20 mg once daily. Efficacy and safety were assessed at weeks 4, 12 and 24. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology (ACR)50 response and a European League Against Rheumatism (EULAR) good response at week 24. RESULTS A total of 101/120 (84.2%) patients completed 24 weeks of observation. In the intention-to-treat (ITT) analysis, 65.3% of patients treated with MTX + SIN showed improved disease activity as determined by the ACR50 response at week 24 compared to 69.6% of patients treated with MTX + LEF. A similar insignificant pattern was found for the ACR20 and ACR70 responses, as well as the clinical disease activity index, EULAR response, and remission and low disease activity rates between these two treatment groups. The per-protocol analysis showed results consistent with those of the ITT analysis. Notably, significant reductions in gastrointestinal adverse reactions and liver toxicity were found in patients treated with MTX + SIN compared to patients treated with MTX + LEF (p < 0.05). CONCLUSION Considering the balance of efficacy and toxicity, the current study provides evidence that MTX + SIN combination therapy is probably one of the choices for treating patients with active rheumatoid arthritis in addition to MTX + LEF combination therapy.
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[Control of inflammatory bone destruction by targeting the Wnt signaling pathway.].
Soen, S
Clinical calcium. 2019;(3):337-341
Abstract
Bone erosions develop early in the course of rheumatoid arthritis(RA)and are predictive of a worse prognosis. They deteriorate gradually and cause joint damage, resulting in impaired functional capacity and disability. Lately, a considerable number of studies have increased our understanding of the pathogenic mechanisms participating in the development of bone erosions in RA. Osteoclasts are responsible cells and multiple factors have been identified to stimulate their differentiation and function. RANKL(receptor activator of NF-κB ligand)and other cytokines have been known for a long time to enhance osteoclastogenesis, but the role of other pathways has also been revealed recently. Besides to excessive ostaoclastogenesis, impair osteoblast differentiation and function also plays part in bone erosion formation in RA. Inflamed synovial membrane products increased levels of cytokines and antagonists of the canonical Wnt signaling pathway, which inhibit osteoblast differentiation and function. It seems that downregulation of this pathway leads to impaired osteoblast differentiation and activity and consequently, to reduced capacity of bone erosion to repair. Preclinical studies show that these findings could have implications in RA treatment, although more studies are required in this direction.
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Anti-citrullinated protein antibodies and arthritis in Sjögren's syndrome: a systematic review and meta-analysis.
Molano-González, N, Olivares-Martínez, E, Anaya, JM, Hernández-Molina, G
Scandinavian journal of rheumatology. 2019;(2):157-163
Abstract
OBJECTIVE The presence of anti-citrullinated protein antibodies (ACPAs) in primary Sjögren's syndrome (pSS) ranges from 3% to 9.9%; however, there is no agreement about their clinical significance. Our aim was to systematically review the literature regarding the association of arthritis and ACPAs in pSS and their role in the development of rheumatoid arthritis (RA). METHOD A comprehensive search of MEDLINE, ISI Web of Knowledge, and Cochrane Library from inception until June 2016 was undertaken using the combination of two or three of the keywords: primary Sjögren's syndrome, Sjögren's syndrome, arthritis, synovitis, arthropathy, anti-cyclic citrullinated peptide antibodies, and anti-citrullinated protein antibody - ACPA. No language restriction was used. Studies were included if they: assessed the association of arthritis and ACPAs, had sufficient data to construct a two-by-two table, tested immunoglobulin G ACPA by any method, and included patients with pSS according to a validated set of classification criteria. We used a random effects model and evaluated the heterogeneity and publication bias. RESULTS Ten studies were included (involving 1322 patients). We found a pooled odds ratio of 4.42 (95% confidence interval 1.15-16.94, p = 0.03). The test for heterogeneity was I2 = 0.87. Publication bias was not observed. Based on data from three studies, 33 of 58 pSS patients with ACPAs (57%) developed RA compared with none of 598 pSS patients with negative ACPA (p < 0.000001). CONCLUSION Patients with pSS disclosing ACPAs are prone to arthritis as part of the clinical spectrum of the disease, but are also at risk of developing RA.
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Erythema elevatum diutinum: a case report and review of literature.
Doktor, V, Hadi, A, Hadi, A, Phelps, R, Goodheart, H
International journal of dermatology. 2019;(4):408-415
Abstract
Erythema elevatum diutinum (EED) is a rare cutaneous leukocytoclastic vasculitis thought to be related to increased levels of circulating antibodies. It has been shown to be associated with HIV infection, tuberculosis, as well as various autoimmune diseases. A retrospective review of all cases of EED indexed in PubMed between 1990 and 2014 was performed. Inclusion criteria for articles was availability of full text in English and a biopsy-confirmed diagnosis of EED. All other articles were excluded. Cases were stratified by age and anatomic location of the lesions. Treatment response was coded as "complete," "partial," and "none." A total of 133 cases of EED with 381 lesions detailed in case reports and case series were included. Twenty-one cases were associated with HIV. Of 47 patients with reported paraproteinemias, IgA paraproteinemia was found in 57.45%, IgG paraproteinemia in 29.8%, IgM paraproteinemia in 10.6%, and IgD paraproteinemia in 2.1% of cases. Of 40 (30.1%) patients with reported comorbid autoimmune disease, rheumatoid arthritis was associated with 10 cases. Cancer was found to be associated with 9.77% of cases. Seventy-five patients were treated with dapsone, with 36 (48%) achieving complete treatment response, 24 (32%) achieving partial response, and seven (9.3%) achieving no response. Keeping the clinical associations of EED in mind, especially malignancy, is critical in management of the disease. More structured studies need to take place in order to fully define the mechanisms and strength of these associations.
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[Serum nesfatin-1 as a marker of systemic inflammation in rheumatoid arthritis.].
Kvlividze, TZ, Zavodovsky, BV, Akhverdyan, YR, Polyakova, YV, Sivordova, LE, Yakovlev, AT, Zborovskaya, IA
Klinicheskaia laboratornaia diagnostika. 2019;(1):53-56
Abstract
The purpose of this study was to determine the level of nesfatin-1 (NF-1) in the blood serum of healthy volunteers and patients with rheumatoid arthritis (RA) to establish the threshold for normal values of this parameter and to reveal the relationship between the level of NF-1 and clinical manifestations of RA. We examined 170 people, of which 110 patients with RA and 60 donors who made up the comparison group. The mean level of serum nesfatin-1 in healthy subjects was 31.61 ± 3.17 ng/ml (M ± σ). The level of normal values of nesfatin-1 in healthy individuals, defined as M ± 2σ, was from 25.27 to 37.95 ng/ml. These studies showed the relationship between the concentration of NF-1 and the severity of clinical manifestations of RA. We found that a higher serum level of NF-1 was characteristic of patients with a more severe clinical course of the disease. The data obtained indicate that high level of NF-1 positively correlates with higher concentrations of C-reactive protein and ESR. This data indirectly proves the proinflammatory effect of NF-1 and confirms the hypothesis about the primary role of systemic inflammation in the pathogenesis of RA.