Rheumatoid arthritis (RA) is a chronic progressive disease, affecting an estimated 1% of the population worldwide. Although the optimal care of RA patients requires various modalities, pharmacotherapy remains the cornerstone of treatment for RA. Clinical studies in patients with RA have broadened understanding of its pathogenesis and have fundamentally changed the therapeutic approach to this disease in the last 10 years. It has become clear that early suppression of RA disease activity is important in preventing progressive joint destruction and functional decline. There has been a complete remodeling of the traditional "therapeutic pyramid" by rheumatologists, who now treat RA earlier and more aggressively than ever before, using combinations of classic disease-modifying antirheumatic drugs or new drugs. Although a cure remains elusive, remission is an approachable goal.
Antirheumatic Agents* ; Arthritis, Rheumatoid ; Drug Therapy ; Humans ; Joints

OBJECTIVE: To study the proportion of cervical spine instability in treatment-naive rheumatoid arthritis (RA) patients, to investigate the associated neck symptoms, and to analyze the clinical characteristics in treatment-naive RA patients and treated RA patients. METHODS: RA patients who underwent cervical spine X-ray imaging from the Department of Rheumatology and Immunology of Peking University Third Hospital and Peking University Shenzhen Hospital from August 2015 to October 2019 and had clinical records of medication administration were included. Clinical and laboratory data including cervical symptoms and X-ray imaging data of cervical spine were collected. The constituent ratio of cervical spine instability in treatment-naive RA patients was statistically analyzed. The clinical data and laboratory data were analyzed by t-test, u-test and chi square to explore the clinical characteristics of the treatment-naive RA patients with cervical instability. RESULTS: Of the 408 RA patients, 105 patients were treatment-naive. Of the 105 treatment-naive patients, 82.9% (87/105) were female, with an average age of (52±14) years, the median duration of the disease was 24 months, the shortest history was 2 weeks, and the longest history was 30 years. 28.6% (30/105) of the treatment-naive RA patients showed cervical spine instability. The prevalence of cervical instability was 13.6% in the treatment-naive RA patients with disease duration less than 24 months. Among them, there were no significant differences in neck symptoms between cervical spine instability group and none cervical spine instability group. The patients with cervical spine instability had a longer duration of disease [60 (18, 180) months vs.16 (8, 51) months], a higher proportion of peripheral joint deformity (63.3%vs.21.3%), and a lower hemoglobin [(106.90±21.61) g/L vs. (115.77±14.69) g/L]. There was no significant difference in the occurrence of cervical instability in the treatment-naive RA patients compared with treated RA patients. Among the RA patients with cervical instability, there was no statistically significant difference in the composition of each type between the patients with treatment-naive RA and patients with treated RA, except for a shorter duration of disease [120.0 (72.0, 240.0) months vs. 60.0 (27.0, 167.5) months]. CONCLUSION 28.6% of treatment-naive RA patients showed cervical spine instability. Cervical instability was also common in RA patients with a duration less than 24 months. There was no significant correlation between cervical instability and neck symptoms. Patients with cervical spine instability had a long-term disease, a higher proportion of peripheral joint deformity and a lower hemoglobin. Controlling the condition of RA early may help to control the progression of cervical involvement in patients with RA.
Adult ; Aged ; Arthritis, Rheumatoid/drug therapy* ; Female ; Humans ; Middle Aged

Wantong Jingu Tablet (WJT), a mixture of traditional Chinese medicine, was reported to relieve the symptoms of rheumatoid arthritis (RA), but its pharmacological mechanism was not completely understood. The aim of this study was to investigate the therapeutic mechanisms of WJT for RA in vivo. The effects of WJT on joint pathology, as well as the levels of Bax, Bcl-2, caspase-3, cleaved-caspase-3, ERK1/2, pERK1/2, TNF-α, IL-1β, and IL-6 were measured using collagen-induced arthritis (CIA) rats. The intestinal flora composition and the metabolites alteration were analyzed by 16S rDNA sequencing and metabolomics method, respectively. We found that WJT ameliorated the severity of the CIA rats which might be mediated by inducing apoptosis, inactivating the MEK/ERK signals and reducing the production of pro-inflammatory cytokines. WJT, in part, relieved the gut microbiota dysbiosis, especially bacterial phylum Bacteroidetes, Tenericutes and Deferribacteres, as well as bacterial genus Vibrio, Macrococcus and Vagococcus. 3'-N-debenzoyl-2'-deoxytaxol, tubulysin B, and magnoline were significantly associated with the specific genera. We identified serotonin, glutathione disulfide, N-acetylneuraminic acid, naphthalene and thromboxane B2 as targeted molecules via metabolomics. Our findings contributed to the understanding of RA pathogenesis, and WJT played essential roles in gut microbiota health and metabolite modulation in the CIA rats.
Animals ; Arthritis, Experimental/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Dysbiosis ; Metabolomics ; Rats ; Tablets

Rheumatoid arthritis(RA) is a widely prevalent autoimmune inflammatory disease that severely affects patients' quality of life. Currently, conventional formulations against RA have several limitations, such as nonspecificity, poor efficacy, large drug dosages, frequent administration, and systemic side effects. Nanotechnology-based drug delivery systems have emerged as a promising stra-tegy for the diagnosis and treatment of RA since nanotechnology can overcome the limitations of traditional treatments and simplify the complexity of the disease. These systems enable targeted delivery of anti-inflammatory drugs to the inflamed areas through active and passive targeting, achieving specificity to the joints, overcoming the need for increased dosage and administration frequency, and reducing associated adverse reactions. This article aimed to review nanocarrier-based drug delivery systems in the field of RA and elucidate how nanosystems can be utilized to deliver therapeutic drugs to inflamed joints for controlling RA progression. By discussing the current issues and challenges faced by nanodrug delivery systems and highlighting the urgent need for solutions, this article offers theoretical support for further research on nanotechnology-based co-delivery systems in the future.
Humans ; Quality of Life ; Drug Delivery Systems ; Arthritis, Rheumatoid/drug therapy* ; Autoimmune Diseases/drug therapy* ; Nanotechnology

OBJECTIVE: To explore the mechanism of METHODS: Healthy male DBA/1 mice were used for CIA modeling. Twenty-five CIA mice with successful modeling and similar arthritis index (AI) scores were randomized equally into model group (CIA), methotrexate (MTX) group, and low-, medium-, and high-dose XWGD groups (0.975, 1.95, and 3.9 g/mL, respectively), with another 5 normal mice as the normal control group. The mice in normal control and CIA groups were given saline once a day, those in MTX group were given 0.1 mg/mL MTX once a week, and those in XWGD groups were treated daily via garage of XWGD containing crude drugs of different doses for 28 consecutive days. The AI score and HE staining were used to evaluate the changes in the joints of the CIA mice. The effect of XWGD on Th1, Th17, MDSC, G-MDSC and M-MDSC cells were evaluated with flow cytometry. RESULTS: Treatment with MTX and different doses of XWGD significantly decreased the AI score of the mice and relieved joint inflammation as compared with the model group ( CONCLUSIONS XWGD can improve joint inflammation in CIA mice by increasing the percentages of G-MDSC cells and decreasing the percentages of M-MDSC, Th1 and Th17 cells, and a high dose of XWGD can produce an equivalent therapeutic effect to methotrexate but with better safety.
Animals ; Arthritis, Experimental/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Male ; Methotrexate ; Mice ; Mice, Inbred DBA ; Th17 Cells

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.
Animals ; Rabbits ; Tumor Necrosis Factor-alpha ; Fluorescence ; Arthritis, Rheumatoid/drug therapy* ; Interleukin-1 ; Arthritis, Experimental/drug therapy*

The idiopathic hypereosinophilic syndrome (HES) is a disorder marked by the sustained overproduction of eosinophils. The disease is characterized by damage of multiple organ including heart, nerve system, skin and lung due to eosinophilic infiltration and the diagnosis is one of exclusion. Rheumatologic manifestations of HES are infrequent. In about 10~40% of rheumatoid arthritis (RA) patients, persistent eosinophilia is observed. That can be due to the RA itself and is often associated with active disease and extra-articular features. Sometimes, it is attributed to the drug therapy, especially gold and penicillamine. We would like to report a 37-year-old female patient with HES who developed seronegative RA 2 years later.
Adult ; Arthritis, Rheumatoid* ; Diagnosis ; Drug Therapy ; Eosinophilia ; Eosinophils ; Female ; Heart ; Humans ; Hypereosinophilic Syndrome* ; Lung ; Penicillamine ; Skin

No abstract available.
Arthritis, Rheumatoid/*drug therapy ; Cross-Cultural Comparison ; Humans ; Korea ; *Medication Adherence ; *Questionnaires

The past decade has greatly enhanced our understanding of rheumatoid arthritis (RA). Not only have new drug therapies become available, but this period has witnessed dramatic changes in treatment strategies as well. Since 1989, when the proposal on reversing the pyramid approach (the step-down bridge concept) was published, the concept of early and aggressive treatment of RA has become the leading paradigm. The theory underlying this approach is based on a bet-ter understanding of the devastating long term consequences of RA in most patients, and the logical tenet that irreversible damage must be prevented before it occurs. Evidence has shown the irreversible joint damage in RA occurs early in the disease, making a "wait and see" approach unacceptable. Thus, it appears logical to begin treatment as soon as a diagnosis of RA is confirmed, to slow disease progression by treatment with disease modifying antirheumatic drugs. This review will address the evidence supporting the benefit and the principles of early treatment, as well as the current update on pharmacological management in early RA.
Antirheumatic Agents ; Arthritis, Rheumatoid* ; Diagnosis ; Disease Progression ; Drug Therapy ; Humans ; Joints ; Logic

INTRODUCTIONUp to 30% of patients with rheumatoid arthritis (RA) respond inadequately to conventional non-biologic disease modifying antirheumatic drugs (nbDMARDs), and may benefit from therapy with biologic DMARDs (bDMARDs). However, the high cost of bDMARDs limits their widespread use. The Chapter of Rheumatologists, College of Physicians, Academy of Medicine, Singapore aims to define clinical eligibility for government-assisted funding of bDMARDs for local RA patients.

MATERIALS AND METHODSEvidence synthesis was performed by reviewing 7 published guidelines on use of biologics for RA. Using the modified RAND/UCLA Appropriateness Method (RAM), rheumatologists rated indications for therapies for different clinical scenarios. Points reflecting the output from the formal group consensus were used to formulate the practice recommendations.

RESULTSTen recommendations including diagnosis of RA, choice of disease activity measure, initiation and continuation of bDMARD and option of first and second-line therapies were formulated. The panellists agreed that a bDMARD is indicated if a patient has (1) active RA with a Disease Activity Score in 28 joints (DAS28) score of ≥3.2, (2) a minimum of 6 swollen and tender joints, and (3) has failed a minimum of 2 nbDMARD combinations of adequate dose regimen for at least 3 months each. To qualify for continued biologic therapy, a patient must have (1) documentation of DAS28 every 3 months and (2) at least a European League Against Rheumatism (EULAR) moderate response by 6 months after commencement of therapy.

CONCLUSIONThe recommendations developed by a formal group consensus method may be useful for clinical practice and guiding funding decisions by relevant authorities in making bDMARDs usage accessible and equitable to eligible patients in Singapore.