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1.
BMJ Open ; 11(9): e049850, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489286

RESUMO

INTRODUCTION: Inflammatory arthritis (IA) conditions, including rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis, are characterised by inflammatory infiltration of the joints. Biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), respectively, reduce the effects of proinflammatory cytokines and immune cells to ameliorate disease. However, immunosuppression can be associated with high rates of serious adverse events (SAEs), including serious infections, and maybe an increased risk of malignancies and cardiovascular events. Currently, there is no empirical evidence on the extent to which contextual factors and risk of bias (RoB) domains may modify these harm signals in randomised trials. METHODS AND ANALYSIS: We will search MEDLINE (via PubMed) for systematic reviews published since April 2015 and all Cochrane reviews. From these reviews, randomised trials will be eligible if they include patients with an IA condition with at least one group randomly allocated to bDMARD and/or tsDMARD treatments. A predefined form will be used for extracting data on population characteristics (eg, baseline characteristics or eligibility criteria, such as medication background) and specific harm outcome measures, such as number of withdrawals, numbers of patients discontinuing due to adverse events and number of patients having SAEs. RoB in individual trials will be assessed using a modified Cochrane RoB tool. We will estimate the potentially causal harm effects related to the experimental intervention compared with control comparator as risk ratios, and heterogeneity across randomised comparisons will be assessed statistically and evaluated as inconsistency using the I2 Index. Our metaregression analyses will designate population and trial characteristics and each RoB domain as independent variables, whereas the three harm domains will serve as dependent variables. ETHICS AND DISSEMINATION: Ethics approval is not required for this study. Results will be disseminated through publication in international peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42020171124.


Assuntos
Antirreumáticos , Artrite Psoriásica , Artrite Reumatoide , Espondilartrite , Antirreumáticos/efeitos adversos , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Humanos , Espondilartrite/tratamento farmacológico , Revisões Sistemáticas como Assunto
2.
RMD Open ; 7(3)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34470830

RESUMO

OBJECTIVES: To study the characteristics of B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin lymphoma complicating rheumatoid arthritis (RA) and to identify RA-related factors associated with their occurrence. METHODS: A multicentre case-control study was performed in France. Cases were patients with RA fulfilling ACR-EULAR 2010 criteria in whom B-cell NHL or Hodgkin lymphoma developed after the diagnosis of RA. For each case, 2 controls were assigned at random from the ESPOIR cohort and were matched on age at lymphoma diagnosis (cases)/age at the 10-year follow-up visit in the cohort (controls). Case and control characteristics were compared to identify parameters associated with the occurrence of lymphoma. RESULTS: 54 cases were included and matched to 108 controls. Lymphomas were mostly diffuse large B-cell lymphoma (DLBCL, n=27, 50.0%). On immunochemistry, 4 of 27 (14.8%) lymphoma cases were positive for Epstein-Barr virus. On univariate analysis, factors associated with the occurrence of lymphoma were male sex (OR 3.3, 95% CI 1.7 to 6.7), positivity for ACPA (OR 5.1, 95% CI 2.0 to 15.7) and rheumatoid factor (OR 3.9, 95% CI 1.6 to 12.2), and erosions on radiographs (OR 3.8, 95% CI 1.7 to 8.3) and DAS28 (OR 2.0, 95% CI 1.5 to 2.7), both at the time of matching. Methotrexate, TNF blockers and a number of previous biologics were not associated with the occurrence of lymphoma. On multivariable analysis, erosions and DAS28 remained significantly associated with increased risk of lymphoma. CONCLUSION: Lymphomas complicating RA are mostly DLBCL. Risk of lymphoma in patients with RA was increased with markers of disease activity and severity, which supports the paradigm of a continuum between autoimmunity and lymphomagenesis in RA.


Assuntos
Artrite Reumatoide , Infecções por Vírus Epstein-Barr , Linfoma , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Estudos de Casos e Controles , Herpesvirus Humano 4 , Humanos , Masculino
3.
Rev Med Chil ; 149(2): 295-303, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34479278

RESUMO

Rheumatoid meningitis (RM) is a rare complication of rheumatoid arthritis (RA). RM mimics many other conditions such as subdural empyema, unsteady gait, focal brain dysfunction, stroke, relapsing-remitting motor signs, headache, neuropsychiatric disorders, seizures, parkinsonism, and meningeal tumors. RM is considered a disease with poor prognosis. However, cases reported in the last decade show a good outcome. We report two cases with a favorable outcome. A 48-year-old man with a three-year history of RA admitted for headache, sensory disturbances, and speech difficulties. Brain magnetic resonance imaging (MRI) showed a left parietal subdural laminar lesion with restricted diffusion and a small left superior frontal acute infarction. A subdural empyema was originally suspected, and antimicrobials were prescribed. A follow-up MRI did not show progression of the subdural lesion and the patient was discharged 14 days after admission without focal deficits. A 44-year-old female patient with two years of seronegative RA was admitted for severe headache, confusion, nausea and vomiting. Brain MRI showed subtle supra and infratentorial leptomeningeal involvement and a left cerebellar acute infarct. A meningoencephalitis due to etanercept was initially thought and treated with dexamethasone. The patient was discharged but had to be admitted again and a new MRI showed a progression of the leptomeningeal involvement. She worsened and required endotracheal intubation. Cyclophosphamide was started and the patient became asymptomatic three months later. We propose that treatment should not be delayed waiting a biopsy when a diagnosis of RM is made and after a cerebrospinal fluid infection has been ruled out.


Assuntos
Artrite Reumatoide , Meningite , Adulto , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Encéfalo , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Convulsões
4.
BMC Musculoskelet Disord ; 22(1): 792, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34525992

RESUMO

BACKGROUND: Persistent monoarthritis in otherwise well-controlled rheumatoid arthritis presents a therapeutic challenge. Intra-articular (IA) steroids are a mainstay of treatment, though some have queried whether IA disease modifying anti-rheumatic drugs (DMARD) and biologics can be used in those who fail steroid injections. METHODS: A systematic literature review was conducted using four medical databases to identify randomized, controlled trials assessing IA therapies in RA patients. Included studies underwent Cochrane Risk of Bias 2 assessment for quality. RESULTS: Twelve studies were included, 6 of which examined intra-articular (IA) TNF inhibitors (TNFi), and 6 studies evaluating IA methotrexate. Of those evaluating IA TNFi, one study reported statistical improvement in TNFi therapy when compared with placebo. The remaining 5 studies compared IA TNFi therapy with steroid injections. IA TNFi had statistically improved symptom scores and clinical assessments comparable with IA steroid treatments. In the 6 studies evaluating IA methotrexate, the addition of methotrexate to steroid intra-articular therapy was not found to be beneficial, and singular methotrexate injection was not superior to the control arms (saline or triamcinolone). Risk-of-bias (ROB) assessment with the Revised Cochrane ROB tool indicated that 2 of 6 TNFi studies were at some risk or high risk for bias, compared with 5 out of 6 methotrexate studies. CONCLUSION: For persistent monoarthritis in rheumatoid arthritis, IA methotrexate was not found to have clinical utility. Intra-articular TNFi therapy appears to have equal efficacy to IA steroids, though the optimal dose and frequency of injections is yet unknown.


Assuntos
Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Humanos , Metotrexato/uso terapêutico , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa
5.
Arthritis Res Ther ; 23(1): 228, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465391

RESUMO

OBJECTIVES: The aim of this study was to compare the clinical effectiveness of tofacitinib and abatacept and clarify the impact of the HLA-DRB1 shared epitope (SE) on responses to these treatments in patients with rheumatoid arthritis (RA). METHODS: After adjustments by propensity score matching, 70 out of 161 patients receiving tofacitinib and 70 out of 131 receiving abatacept were extracted. The clinical effectiveness of both drugs over 24 weeks and the impact of the copy numbers of SE on effectiveness outcomes were investigated. RESULTS: The percentage of patients in remission in the 28-joint count disease activity score using the erythrocyte sedimentation rate (DAS28-ESR) did not significantly differ between patients receiving tofacitinib and abatacept at week 24 (32% vs 37%, p = 0.359). The mean change at week 4 in DAS28-ESR from baseline was significantly greater in patients receiving tofacitinib than in those receiving abatacept (- 1.516 vs - 0.827, p = 0.0003). The percentage of patients in remission at week 4 was 30% with tofacitinib and 15% with abatacept (p = 0.016). When patients were stratified by the copy numbers of SE alleles, differences in these numbers did not affect DAS28-ESR scores of patients receiving tofacitinib. However, among patients receiving abatacept, DAS28-ESR scores were significantly lower in patients carrying 2 copies of SE alleles than in those carrying 0 copies at each time point throughout the 24-week period. Furthermore, the percentage of patients in remission with DAS28-ESR at week 24 was not affected by the copy numbers of SE alleles in patients receiving tofacitinib (p = 0.947), whereas it significantly increased as the copy numbers became higher in patients receiving abatacept (p = 0.00309). Multivariable logistic regression analyses showed a correlation between the presence of SE and DAS28-ESR remission in patients receiving abatacept (OR = 25.881, 95% CI = 3.140-213.351, p = 0.0025), but not in those receiving tofacitinib (OR = 1.473, 95% CI = 0.291-7.446, p = 0.639). CONCLUSIONS: Although the clinical effectiveness of tofacitinib and abatacept was similar at week 24, tofacitinib was superior to abatacept for changes from baseline in DAS28-ESR and the achievement of remission at week 4. SE positivity was associated with the achievement of DAS28-ESR remission by week 24 in patients receiving abatacept, but not in those receiving tofacitinib.


Assuntos
Antirreumáticos , Artrite Reumatoide , Abatacepte/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Epitopos , Cadeias HLA-DRB1 , Humanos , Piperidinas , Pirimidinas , Resultado do Tratamento
6.
Ann Palliat Med ; 10(7): 7298-7328, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34353032

RESUMO

BACKGROUND: In China, along with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), some herbal formulae for clearing damp-heat are widely applied in treating rheumatoid arthritis (RA). We aimed to summarize and compare the clinical effects of 4 guideline-recommended formulae, including Baihuguizhi decoction, Dangguiniantong decoction, Simiao pill, and Xuanbi decoction. METHODS: PubMed, Cochrane Library, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technique Journals (CQVIP), WanFang, and SinoMed (CBM) databases were searched for randomized controlled trials from inception to July 2020 evaluating the efficacy and safety of these recommended herbal formulae combined with 1 csDMARD versus csDMARD alone in RA patients. A pairwise meta-analysis was conducted in RevMan 5.3 software, and a Bayesian network meta-analysis (NMA) was performed with Stata 14.0, R 4.0.2, GeMTC 0.14.3, and JAGS 4.3.0 software. Cochrane Handbook 5.1.0 was used to assess the risk of bias. Publication bias was evaluated using Egger's test, the trim-fill adjustment, and funnel plots. Trial sequential analysis (TSA) was performed to validate the overall results. The rank probability of interventions was calculated and clustered by the surface under the cumulative ranking curve (SUCRA). Pharmacologic actions of formulae were explored through the network pharmacology approach. RESULTS: A total of 15 studies, including 1,079 individuals, were identified. Simiao pill + csDMARD [SMPPD, odds ratio (OR) =6.62, 95% confidence interval (CI): 2.88 to 16.84] was superior to csDMARDs alone in clinical efficiency, and was more able to reduce C-reactive protein and erythrocyte sedimentation rate levels [mean difference (MD) =-7.91, 95% CI: -17.41 to -1.25; MD =-9.31, 95% CI: -14.48 to -5.56 respectively]. Although publication bias was observed (P=0.033), the trim-fill method indicated that the pooled values kept stable. Fewer adverse events (AEs) were shown with SMPPD (6.45%). TSA confirmed the results of efficacy rate at SMPPD. Network pharmacology included 5 common components and 66 common targets among 4 formulae in treating RA, involving regulating immunity and relieving inflammation. DISCUSSION: SMPPD might be a preferable complementary therapy for RA. However, considering the limitations of this study, recommendations for clinical practice should be validated by the results of further well-designed studies.


Assuntos
Artrite Reumatoide , Temperatura Alta , Artrite Reumatoide/tratamento farmacológico , Teorema de Bayes , Humanos , Metanálise em Rede , Prescrições
7.
Am J Dent ; 34(4): 211-214, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34370914

RESUMO

PURPOSE: To assess the prevalence of periapical abscesses in patients with rheumatoid arthritis, and to evaluate the effect of commonly used antirheumatic medications on such prevalence. METHODS: Integrated data of hospital patients was used. Data from the corresponding diagnosis codes for rheumatoid arthritis and periapical abscess was retrieved by searching the appropriate query in the database. The odd ratio (OR) of periapical abscesses, its association with rheumatoid arthritis and intake of three commonly prescribed antirheumatic medications were calculated and analyzed statistically. RESULTS: The prevalence of periapical abscesses in patients with rheumatoid arthritis was 1.53% as compared to 0.51% in the general patient population of the hospital. The OR was 2.60 and the difference was statistically significant (P< 0.0001). In patients treated with either Methotrexate, Sulfasalazine, or Etanercept, the ORs were 2.88, 3.1, and 1.07, respectively. The differences between Methotrexate and Sulfasalazine were statistically significant (P< 0.0001). The OR for prevalence of periapical abscesses in patients treated with Etanercept was significantly lower than that of patients treated with either Methotrexate or Sulfasalazine (P< 0.005). CLINICAL SIGNIFICANCE: Oral healthcare providers should be aware of the possible association between rheumatoid arthritis and occurrence of periapical abscesses. Patients with rheumatoid arthritis, mainly women, may exhibit higher prevalence of periapical abscesses. Treatment with TNF alpha inhibitors may lower the prevalence of periapical abscesses in such patients.


Assuntos
Antirreumáticos , Artrite Reumatoide , Abscesso Periapical , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Estudos Transversais , Feminino , Humanos , Abscesso Periapical/tratamento farmacológico , Prevalência , Resultado do Tratamento
8.
BMJ Open ; 11(8): e047713, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344678

RESUMO

OBJECTIVE: To evaluate the ability of fluorescence optical imaging (FOI) Xiralite in the discrimination between rheumatoid arthritis (RA) patients with and without need of rituximab (RTX) retherapy-in comparison to clinical, laboratory and musculoskeletal ultrasound parameters. PATIENTS AND METHODS: Patients with established RA were prospectively followed over 1 year by Disease Activity Score 28, patient's global disease activity (visual analogue scale 0-100 mm), C reactive protein and erythrocyte sedimentation rate, ultrasound seven joint (US7) score and FOI in phases 1-3 and automatically generated PrimaVista mode (PVM) at baseline (before RTX) and after 3, 6 and 12 months. The need for RTX retherapy was decided by the treating rheumatologist-blinded to imaging data. RESULTS: 31 patients (female 77.4%, mean age 60.1±11.4, mean disease duration 14.9±7.1 years) were included. Fourteen (45.2%) patients received RTX retherapy within 12 months. In the group with RTX retherapy, FOI in PVM mode was the only parameter that presented significant increase over time (ß: 0.40, 95% CI: 0.08 to 0.71, p=0.013)-compared with the group without retherapy. In the prediction model via ROC analysis, FOI in PVM reached the highest values of all imaging, clinical and laboratory parameters which was associated with retherapy over 1 year with an area under the curve (AUC) of 0.78 (OR: 0.84, 95% CI: 0.72 to 0.98, p=0.031). US7 GS synovitis score revealed similar association with an AUC of 0.73 (p=0.049). CONCLUSION: US7 GS synovitis score and FOI in PVM are able to discriminate between patients with and without need for RTX retherapy better than clinical and laboratory parameters.


Assuntos
Antirreumáticos , Artrite Reumatoide , Sinovite , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Imagem Óptica , Rituximab/uso terapêutico
9.
J Biomed Nanotechnol ; 17(7): 1293-1304, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34446133

RESUMO

De novo designed lipidated methotrexate was synthesized and self-assembled into microbubbles for targeted rheumatoid arthritis theranostic treatment. Controlled lipidatedmethotrexate delivery was achieved by ultrasound-targetedmicrobubble destruction technique. Methotrexate was dissociated inflammatory microenvironment of synovial cavity, owing to representive low pH and enriched leucocyte esterase. We first manipulated methotrexate controlled release with RAW 264.7 cell line in vitro and further verified with rheumatoid arthritis rabbits in vivo. Results showed that lipidated methotrexate microbubbles precisely affected infection focus and significantly enhanced rheumatoid arthritis curative effect comparing with dissociative methotrexate. This study indicates that lipidated methotrexate microbubbles might be considered as a promising rheumatoid arthritis theranostics medicine.


Assuntos
Antirreumáticos , Artrite Reumatoide , Animais , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Metotrexato , Microbolhas , Medicina de Precisão , Coelhos , Ultrassom
10.
S D Med ; 74(7): 304-305, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34449990

RESUMO

Methotrexate is often prescribed for the treatment of autoimmune conditions. There are many well-known side effects of methotrexate, a lesser known side effect is methotrexate-induced cutaneous ulceration. Only eight cases have been reported in the literature. Here we report a ninth case report of methotrexate-induced cutaneous ulceration in a 73-year-old female who had recently had her methotrexate dose increased for her seronegative rheumatoid arthritis. She presented to the emergency department with painful ulcerative nodules on her hands. In addition, laboratory evaluation found her to be pancytopenic. Methotrexate was discontinued and patient was given a dose of leucovorin. Within a couple weeks of methotrexate discontinuation, the ulcers resolved. Our case in addition to a review of the literature suggests that methotrexate-induced cutaneous ulceration may be an indication of life-threatening pancytopenia.


Assuntos
Antirreumáticos , Artrite Reumatoide , Úlcera Cutânea , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Metotrexato/efeitos adversos , Úlcera Cutânea/induzido quimicamente , Úlcera Cutânea/tratamento farmacológico , Úlcera
11.
In Vivo ; 35(5): 2559-2567, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410943

RESUMO

BACKGROUND/AIM: Chloride intracellular channel protein 1 (CLIC1) activates inflammasomes in rheumatoid (RA) and psoriatic (PsA) arthritis. We studied CLIC1 expression in RA and PsA patients' skin with vasculitis and its variability depending on the therapy used. MATERIALS AND METHODS: CLIC1 immunoexpression was evaluated in the vascular (CLIC1-V) and stromal (CLIC1-S) compartments of the RA and PsA skin biopsies of patients treated with methotrexate (MTX), leflunomid (LFN), corticotherapy (CT), or biological therapies. RESULTS: MTX significantly reduced CLIC1-S expression (p=0.016), whereas LFN decreased CLIC1-V (p<0.001). LFN therapy duration also correlated with CLIC1-V (p<0.001). CT decreased CLIC1-S expression (p=0.006). CLIC1-S expression persisted in skin biopsies despite of erythrocyte sedimentation rate (ESR, p=0.018) and C reactive protein (CRP, p=0.0026) normalisation. For PsA, CLIC1-S expression significantly related to MTX (p<0.022). Both CLIC1-S (p<0.001) and CLIC1-V (p=0.007) decreased by biological therapies in RA. CONCLUSION: CLIC1 expression is strongly influenced by the therapy used. Our data strongly support the extensive evaluation of CLIC1 in RA as a potential marker of inflammation and tool to predict therapy response.


Assuntos
Artrite Psoriásica , Artrite Reumatoide , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/genética , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Biópsia , Canais de Cloreto , Humanos , Metotrexato , Pele
12.
Epidemiol Mikrobiol Imunol ; 70(2): 83-90, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34412483

RESUMO

AIM: This study aims to determine the prevalence of latent tuberculosis infection (LTBI) in patients with moderate to severe rheumatoid arthritis (RA) who receive conventional and anti-cytokine therapy, to identify possible risk factors for tuberculosis (TB) and to evaluate the prophylactic treatment in positively screened patients. PATIENT AND METHODS: We conducted an observational, retrospective study in patients with RA, who underwent LTBI screening (chest X-ray, tuberculin skin test and interferon gamma release assay test - IGRA test). RESULTS: Out of 124 patients included, 7.25% of patients were diagnosed with LTBI during the treatment with conventional synthetic anti-rheumatic drugs in combination with glucocorticoids before initiation of anti-cytokine therapy. Another 21.77% were diagnosed during treatment with biologics or Janus kinase inhibitors. We confirmed the highest incidence of LTBI in TNF-treated group (66.66% LTBI positive patients), but also found positive screening in patients treated with other modalities. The mean LTBI detection time since the initiation of anti-cytokine therapy was 39.5 months (12-134 months). Active TB with clinical manifestation has occurred in one patient. Statistical analysis did not show an association between risk of LTBI and age, sex or treatment modality. CONCLUSION: The results of this study confirm the necessity of LTBI screening and long-term monitoring in RA patients treated with any kind of anti-cytokine therapy. The currently used national recommendations are sufficiently sensitive to identify TB in these patients. There remains a question of screening and prophylactic antituberculosis therapy in patients treated with conventional synthetic anti-rheumatic drugs in combination with glucocorticoids.


Assuntos
Artrite Reumatoide , Tuberculose Latente , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Humanos , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Estudos Retrospectivos , Eslováquia/epidemiologia , Fator de Necrose Tumoral alfa
13.
Biomaterials ; 276: 121063, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34391020

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease associated with synovitis and cartilage destruction. Ultrasound (US)-driven sonodynamic therapy (SDT) possess a good application prospect in RA therapy because of its non-invasiveness and strong tissue penetration capabilities, which can kill activated synovial inflammatory cells. Nevertheless, the tiny accumulation of sonosensitizers in the joints and the hypoxic synovial microenvironment severely limit the therapeutic effect of SDT. Hence, we developed a sonosensitizer spafloxacin (SPX) doped and human serum albumin (HSA) loaded concave-cubic rhodium (Rh) nanozyme (Rh/SPX-HSA) to realize mutual-reinforcing SDT during ultrasonic activation. On the one hand, SPX would cause mitochondrial dysfunction by inducing excessive reactive oxygen species (ROS) production, thus suppressing fibroblast-like synoviocyte (FLS) under US conditions. On the other hand, concave-cubic rhodium was utilized as a nanozyme with endogenous peroxidase (POD) and catalase (CAT)-like enzyme activities, which not only relieved the hypoxia of the joint to resist angiogenesis, but also enormously ascended the SDT efficacy by rising 1O2 levels. Interestingly, the activity of nanozymes was also improved by the ultrasonic cavitation effect, thereby realizing mutual-reinforcing SDT. Overall, our strategy provided Rh-based to achieve effective SDT under hypoxic microenvironment, which offered a promising prospect for highly efficient treatment of RA.


Assuntos
Artrite Reumatoide , Ródio , Terapia por Ultrassom , Artrite Reumatoide/tratamento farmacológico , Linhagem Celular Tumoral , Fluoroquinolonas , Humanos , Espécies Reativas de Oxigênio
14.
Arthritis Res Ther ; 23(1): 221, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429152

RESUMO

BACKGROUND: Peficitinib (ASP015K), a novel oral Janus kinase inhibitor, has demonstrated efficacy and safety in the treatment of patients with rheumatoid arthritis (RA). This study evaluated the effect of peficitinib on patient- and physician-reported outcomes in Asian patients with RA and an inadequate response to prior disease-modifying antirheumatic drugs (DMARDs). METHODS: Patients from two randomized, placebo-controlled, double-blind, phase 3 trials (RAJ3 and RAJ4) received once-daily peficitinib 100 mg, peficitinib 150 mg, or placebo, alone or in combination with DMARDs (RAJ3), or in combination with methotrexate (RAJ4). Mean changes in Work Productivity and Activity Impairment (WPAI) questionnaire domain scores from baseline, and percentages of patients achieving minimal clinically important differences (MCIDs) for patient- and physician-reported outcomes (WPAI, Health Assessment Questionnaire - Disability Index [HAQ-DI], and Subject's Global Assessment of Pain [SGAP]), and Physician's Global Assessment of disease activity (PGA) were evaluated at weeks 4, 8, 12, and 12/early termination (ET). RESULTS: Data from 1025 patients were analyzed. At week 12/ET in both studies, patients who received peficitinib 100 mg or 150 mg reported significantly improved WPAI domain scores from baseline (except for absenteeism in RAJ4) compared with placebo (both doses, p<0.05). A higher proportion of peficitinib- versus placebo-treated patients achieved MCID in WPAI, HAQ-DI, SGAP, and PGA in studies RAJ3 and RAJ4. Significant differences with peficitinib versus placebo were evident in both studies as early as week 4 in HAQ-DI (peficitinib 150 mg only), SGAP, and PGA, and week 8 in WPAI loss of work productivity and daily activity impairment. At week 12/ET, significantly higher proportions of patients receiving peficitinib versus placebo achieved MCID in HAQ-DI, SGAP, PGA, and WPAI domains of presenteeism (RAJ3 only), loss of work productivity (RAJ3 only), and daily activity impairment (p<0.05 for all comparisons). CONCLUSIONS: Peficitinib 100 mg or 150 mg administered daily over 12 weeks resulted in clinically meaningful improvements in outcomes that are important to RA patients, including pain, physical function, and work productivity and activity. These observations were reinforced through similar improvements in physicians' rating of disease activity. TRIAL REGISTRATION: RAJ3: ClinicalTrials.gov, NCT02308163 , registered 4 December 2014. RAJ4: ClinicalTrials.gov, NCT02305849 , registered 3 December 2014.


Assuntos
Antirreumáticos , Artrite Reumatoide , Médicos , Adamantano/análogos & derivados , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Método Duplo-Cego , Humanos , Metotrexato/uso terapêutico , Niacinamida/análogos & derivados , Medidas de Resultados Relatados pelo Paciente , Resultado do Tratamento
15.
S D Med ; 74(8): 363-366, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34461001

RESUMO

Methotrexate therapy has evolved over the years to become a fundamental component in the management of rheumatoid arthritis and psoriasis. Liver toxicity remains an ever-present concern when prescribing methotrexate. As such, methotrexate liver toxicity monitoring guidelines have been developed independently by rheumatologists and dermatologists. The main differentiating factor between the dermatology and rheumatology guidelines is risk stratification. Dermatology guidelines are largely based off of the presence or absence of hepatoxicity risk factors (alcohol usage, obesity, type II diabetes, among other) while the rheumatology guidelines do not emphasize this distinction. Thus, the aim of this review is to identify why these screening guidelines differences exist and discuss if the differences in stratification and screening are valid. We will also briefly examine alternatives to the current gold standard hepatoxicity screening test: the liver biopsy.


Assuntos
Artrite Reumatoide , Doença Hepática Induzida por Substâncias e Drogas , Diabetes Mellitus Tipo 2 , Psoríase , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Consenso , Humanos , Metotrexato/efeitos adversos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico
16.
Artigo em Inglês | MEDLINE | ID: mdl-34444236

RESUMO

Rheumatoid arthritis (RA) flare is related to increased joint damage, disability, and healthcare use. The impact of short-term air pollution exposure on RA disease activity is still a matter of debate. In this cross-sectional study, we investigated whether short-term exposure to particulate matter (PM)10, PM2.5, nitrogen dioxide (NO2), and ozone (O3) affected RA disease activity (DAS28 and SDAI) in 422 consecutive RA residents in Lombardy, North of Italy. Air pollutant concentrations, estimated by Regional Environmental Protection Agency (Lombardy-Italy) at the municipality level, were used to assign short-term exposure from the day of enrolment, back to seven days. Some significant negative associations emerged between RA disease activity, PM10, and NO2, whereas some positive associations were observed for O3. Patients were also stratified according to their ongoing Disease-Modifying anti-Rheumatic Drugs (DMARDs) treatment: no DMARDs (n = 25), conventional synthetic DMARDs (n = 108), and biological or targeted synthetic DMARDs (n = 289). Therapy interaction seemed partially able to influence the relationship between short-term air pollution exposure and RA disease activity (PM2.5 levels and DAS28 at the day of the visit-O3 levels and disease activity scores for the seven days before the evaluation). According to our results, the impact of short-term air pollution exposure (seven days) minimally impacts disease activity. Moreover, our study suggests therapy could alter the response to environmental factors. Further evidence is needed to elucidate determinants of RA flare and its management.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Artrite Reumatoide , Ozônio , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Estudos Transversais , Exposição Ambiental/análise , Humanos , Dióxido de Nitrogênio/análise , Ozônio/análise , Material Particulado/análise
17.
Int J Rheum Dis ; 24(9): 1106-1111, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34375036

RESUMO

Rheumatoid arthritis (RA) is a major health burden in Asia Pacific affecting the quality of life of patients and consuming healthcare resources. According to recent estimates from the World Health Organization-International League Against Rheumatism-Community Oriented Program for Control of Rheumatic Diseases, prevalence is around 0.3%-0.5%. Management guidelines have helped to improve treatment across this diverse region. To gain better insight into current real-world management applications in view of these guidelines, virtual meetings were conducted in mid-2020 to explore perspectives of rheumatologists and patients, as well as discuss the impact of coronavirus disease 2019 on RA management. Patients and rheumatologists from Hong Kong, Malaysia, Singapore, the Philippines, Thailand, India, Pakistan, and Taiwan were included, representing a diverse mix of healthcare systems, wealth, ethnicity and culture. Despite many countries having prospered in recent years, similar challenges in RA diagnosis and treatment were identified. The daily impact and patient experience of RA were also similar across countries, marked by "silent" pain and disability, and universal misunderstanding of the disease. Late diagnosis and treatment, and barriers to access to appropriate treatment, remain problematic. The experience shared by Taiwan offers a glimmer of hope, however, wherein patient advocacy groups have succeeded in being included in policy-making decisions and securing access to advanced treatment. Real-world solutions that pay heed to the unique local needs and diversity of Asia Pacific are required to improve RA management, which will take time. In the interim, help can be sought from the trained, non-rheumatologist community to reduce some of the disease burden.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , COVID-19 , Manejo da Dor/tendências , Padrões de Prática Médica/tendências , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Ásia/epidemiologia , Humanos , Resultado do Tratamento
18.
Front Cell Infect Microbiol ; 11: 670593, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422677

RESUMO

Background: Rheumatoid arthritis (RA) is a long-term autoimmune disorder characterized by chronic inflammation that results in swollen and painful joints and even cartilage and bone damage. The gut microbiota, a novel anti-inflammatory target, is considered an important environmental factor in the development of RA. S-propargyl-cysteine (SPRC), an amino acid analogue, exerts anti-inflammatory, cardioprotective effects, and neuroprotective effects on various diseases. In recent studies, an SPRC treatment exerted anti-inflammatory effects on RA. Meanwhile, gut microbiome dysbiosis in individuals with RA has also been reported by many researchers. However, the relationship between SPRC and gut microbiota in individuals with RA remains unclear. Methods: Thirty male Sprague-Dawley (SD) rats were randomly divided into three groups of 10 each, including the Control, Model, and SPRC groups. Adjuvant-induced arthritis (AIA) rats in SPRC group were treated with SPRC. Measurement of paw volume and serum tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) levels were applied to evaluate the inflammatory status. Fecal samples were collected on the 14th day and 28th day. Gut microbiota were analyzed using 16S ribosomal RNA (rRNA) gene amplicon sequencing. Untargeted metabolomics on plasma samples was applied to investigate the metabolic changes induced by the altered gut microbiota by using derivatization-UHPLC-Q-TOF/MS. Findings: Using 16S rRNA amplicon sequencing, we found that SPRC significantly altered the gut microbiota structure in AIA rats. In particular, Bifidobacterium, a genus of BSH (Bile Salt Hydrolase)-producing microbes, was overrepresented in SPRC-treated AIA rats. Additionally, a subsequent metabolomics analysis indicated that bile acid metabolism was also altered by SPRC treatment. Interestingly, glycochenodeoxycholic acid (GCDCA) and glycocholic acid (GCA), which are formed with the participation of BSH-producing microbes in the intestine, were identified as crucial biomarkers responding to SPRC treatment with significantly lowered levels. Interpretation: A mechanistic link between the gut microbiota and plasma metabolites was revealed in this study, which provides insights into the mechanism of SPRC treatment for RA from the perspective of the gut microbiota.


Assuntos
Artrite Reumatoide , Microbioma Gastrointestinal , Animais , Artrite Reumatoide/tratamento farmacológico , Ácidos e Sais Biliares , Cisteína , Masculino , RNA Ribossômico 16S/genética , Ratos , Ratos Sprague-Dawley
19.
Medicine (Baltimore) ; 100(32): e26843, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397890

RESUMO

INTRODUCTION: Secondary amyloidosis is a rare complication of rheumatoid arthritis (RA) that is histologically characterized by the deposition of amyloid fibrils in target organs, such as the kidneys and gastrointestinal tract. Controlling the inflammatory response is essential to prevent organ dysfunction in amyloid A (AA) amyloidosis secondary to RA, and no clear treatment strategy exists. PATIENT CONCERNS AND DIAGNOSIS: A 66-year-old woman with RA, who had been treated with disease-modifying anti-rheumatic drugs for 1 year, presented with recurrent abdominal pain and prolonged diarrhea. Endoscopy showed chronic inflammation, and colon tissue histology confirmed AA amyloidosis. INTERVENTIONS AND OUTCOMES: After tocilizumab therapy was begun, her diarrhea and abdominal pain subsided, and articular symptoms improved. Biologic drugs for RA have been used in patients with secondary AA amyloidosis, including tumor necrosis factor and Janus kinase inhibitors, interleukin 6 blockers, and a T cell modulator. Here, we systematically review existing case reports and compare the outcomes of RA-related AA amyloidosis after treatment with various drugs. CONCLUSION: The data indicate that biologic drugs like tocilizumab might be treatments of choice for AA amyloidosis secondary to RA.


Assuntos
Amiloidose , Anticorpos Monoclonais Humanizados/administração & dosagem , Artrite Reumatoide , Terapia Biológica/métodos , Colo , Proteína Amiloide A Sérica/análise , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Idoso , Amiloidose/etiologia , Amiloidose/imunologia , Amiloidose/fisiopatologia , Amiloidose/terapia , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Produtos Biológicos/administração & dosagem , Colo/imunologia , Colo/patologia , Diarreia/diagnóstico , Diarreia/etiologia , Feminino , Humanos , Interleucina-6/antagonistas & inibidores , Resultado do Tratamento
20.
Int J Mol Sci ; 22(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34445661

RESUMO

Exogenous adenosine and its metabolite inosine exert anti-inflammatory effects in synoviocytes of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. We analyzed whether these cells are able to synthesize adenosine/inosine and which adenosine receptors (ARs) contribute to anti-inflammatory effects. The functionality of synthesizing enzymes and ARs was tested using agonists/antagonists. Both OA and RA cells expressed CD39 (converts ATP to AMP), CD73 (converts AMP to adenosine), ADA (converts adenosine to inosine), ENT1/2 (adenosine transporters), all AR subtypes (A1, A2A, A2B and A3) and synthesized predominantly adenosine. The CD73 inhibitor AMPCP significantly increased IL-6 and decreased IL-10 in both cell types, while TNF only increased in RA cells. The ADA inhibitor DAA significantly reduced IL-6 and induced IL-10 in both OA and RA cells. The A2AAR agonist CGS 21680 significantly inhibited IL-6 and induced TNF and IL-10 only in RA, while the A2BAR agonist BAY 60-6583 had the same effect in both OA and RA. Taken together, OA and RA synoviocytes express the complete enzymatic machinery to synthesize adenosine/inosine; however, mainly adenosine is responsible for the anti- (IL-6 and IL-10) or pro-inflammatory (TNF) effects mediated by A2A- and A2BAR. Stimulating CD39/CD73 with simultaneous ADA blockage in addition to TNF inhibition might represent a promising therapeutic strategy.


Assuntos
Adenosina/farmacologia , Anti-Inflamatórios/farmacologia , Artrite Reumatoide/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Membrana Sinovial/efeitos dos fármacos , Sinoviócitos/efeitos dos fármacos , Vasodilatadores/farmacologia , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/metabolismo , Osteoartrite/patologia , Sinoviócitos/metabolismo , Sinoviócitos/patologia
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