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ID PMID Title PublicationDate abstract
32281878 Recent developments and strategies for the discovery of TACE inhibitors. 2020 Jul INTRODUCTION: TNF-α plays a central role in certain autoimmune diseases as well as in inflammation. The current strategy for excluding TNF-α from circulation is to selectively inhibit TNF-α converting enzyme (TACE), an enzyme that cleaves mTNF-α to active TNF-α. Various TACE inhibitors have been discovered by using different strategies to control inflammatory diseases, cancer, and cardiac hypertrophy. AREAS COVERED: The present article summarizes the design and discovery of novel TACE inhibitors that have been reported in the literature since 2012 onwards. It also includes some reports concerning the new role that TACE plays in cancer and cardiac hypertrophy. EXPERT OPINION: So far, undertaken studies that have looked to design and develop small TACE inhibitors have been discouraging due to the failure of any TACE inhibitors to hit the market. However, some of the latest developments, such as with tartrate-based inhibitors, has given hope to the potentiality of a viable novel selective TACE inhibitor therapeutic in the future. Indeed, some of the novel peptidomimetics and monoclonal antibodies have great potential to pave the way for an effective and safe therapy by selectively inhibiting TACE enzyme.
32607016 A Case of Rhupus with Rowell Syndrome. 2020 We report a case of 30-year-old female who presented initially with hair loss, photosensitive malar rash, morning stiffness and synovitis. She was diagnosed with Rhupus syndrome based on clinical and laboratory findings. Few months after starting hydroxychloroquine, esomeprazole and azathioprine, and failing methotrexate (because of erosive pill-induced esophagitis), she presented with generalized maculopapular dusky reddish rash in her body, back and extremities. Her anti-double stranded-DNA, anti-nuclear antibody, anti-Ro/SSA and anti-La/SSB were positive. Anti-cyclic citrullinated peptide antibody was moderately positive. She had low complements: C3 and C4. Herpes simplex IgM and mycoplasma tested negative. Skin biopsy from right arm showed evidence of erythema multiform. She met the criteria for the diagnosis of Rowell syndrome. We managed her with hydroxychloroquine, prednisolone, mycophenolate mofetil and topical agents and discontinued esomeprazole. We also review the management of Rowell syndrome in the literature.
31834407 The use of real-world data to address questions of patient safety. 2020 Jan 1 Pharmacovigilance registries of biologics were established to evaluate the risk of adverse events that may be missed in trials due to shorter durations and homogeneous samples. This review will present the strengths and weaknesses of registry data in addressing patient safety issues. Since their inception, scope has broadened because registries represent a relatively inexpensive approach to answering many clinical questions, both research and non-research focused. They achieve high statistical power, allow direct comparability, and offer a level of detail about adverse events not possible with trial data. Registries have been central in clarifying the risk of infection and malignancy with anti-TNF therapy, despite the limitations of selection and channelling bias, incomplete case capture, unmeasured confounding, and the inability to infer causality. Routinely collected data from electronic health records and national audits offer alternative real-world resources, further assisting patients and clinicians in understanding the risks of biologic therapy choices.
32132244 Microbiota-Propelled T Helper 17 Cells in Inflammatory Diseases and Cancer. 2020 May 20 Technologies allowing genetic sequencing of the human microbiome are opening new realms to discovery. The host microbiota substantially impacts immune responses both in immune-mediated inflammatory diseases (IMIDs) and in tumors affecting tissues beyond skin and mucosae. However, a mechanistic link between host microbiota and cancer or IMIDs has not been well established. Here, we propose T helper 17 (T(H)17) lymphocytes as the connecting factor between host microbiota and rheumatoid or psoriatic arthritides, multiple sclerosis, breast or ovarian cancer, and multiple myeloma. We theorize that similar mechanisms favor the expansion of gut-borne T(H)17 cells and their deployment at the site of inflammation in extraborder IMIDs and tumors, where T(H)17 cells are driving forces. Thus, from a pathogenic standpoint, tumors may share mechanistic routes with IMIDs. A review of similarities and divergences in microbiota-T(H)17 cell interactions in IMIDs and cancer sheds light on previously ignored pathways in either one of the two groups of pathologies and identifies novel therapeutic avenues.
33212423 X-ray phase imaging reaching clinical uses. 2020 Nov X-ray phase imaging that uses the phenomena of X-ray refraction and scattering to generate image contrast has the potential to overcome the drawback of conventional X-ray radiography in observing biological soft tissues. After its dawn at synchrotron radiation facilities 30 years ago, the development of X-ray phase imaging is expanding to hospitals by grating-based phase-imaging approaches available with a conventional X-ray tube. In this review, after introducing the physical advantages and methodological details of X-ray phase imaging, recent trials of instrumentation in hospitals for diagnoses of rheumatoid arthritis and chronic obstructive pulmonary disease are introduced.
33214827 Hydrogen Peroxide Inducible JAK3 Covalent Inhibitor: Prodrug for the Treatment of RA with 2020 Nov 12 Selective inhibition of Janus kinases (JAKs) is an arising strategy in drug discovery. Covalent inhibitors targeting a unique cysteine in JAK3 exhibit ultraselectivity among JAK family members. However, safety and tissue specific concerns still remain. A prodrug of a known JAK3 covalent inhibitor sensitive to H(2)O(2) was designed and synthesized and its therapeutic effect was evaluated in the CIA (collagen-induced arthritis) mice model of RA (rheumatoid arthritis). The prodrug strategy relied on the introduction of a hydrogen peroxide-sensitive borate trigger group to avoid random covalent binding to thiol functionalities in biomacromolecules. The results show that the prodrug can be activated and released under pathophysiological concentration of H(2)O(2). In addition, the prodrug demonstrated stability to the physiological environment. In comparison to the parent compound, the prodrug showed a similar therapeutic effect in the CIA model but notably exhibited lower toxicity and a larger therapeutic window.
32922504 Manual Therapy (Postisometric Relaxation and Joint Mobilization) in Knee Pain and Function 2020 OBJECTIVES: The purpose of this study was to evaluate the impact of manual therapy on the management of rheumatoid arthritis (RA) patients with knee pain. MATERIALS AND METHODS: This was a small, randomized clinical pilot study. Subjects were 46 patients with diagnosed RA, randomly assigned to the manual therapy group (postisometric relaxation and joint mobilization) or control group (standard exercise). Subjects in each group had 10 sessions of interventions, once a day with one day break after the sixth day. Outcomes included the pain intensity of knee, Knee Society Score, Oxford Knee Score, and Health Assessment Questionnaire. RESULTS: There were no statistically significant differences between groups, except for the pain intensity of the knee. CONCLUSIONS: This study suggests that manual therapy (postisometric relaxation and joint mobilization) may have clinical benefits for treating knee pain and function in rheumatoid patients. Further extended studies are expected to determine the effectiveness of manual therapy in RA patients with knee pain.
33032999 Burden and trajectory of multimorbidity in rheumatoid arthritis: a matched cohort study fr 2020 Oct 8 OBJECTIVES: To compare the onset and trajectory of multimorbidity between individuals with and without rheumatoid arthritis (RA). METHODS: A matched, retrospective cohort study was completed in a large, US commercial insurance database (MarketScan) from 2006 to 2015. Using validated algorithms, patients with RA (overall and incident) were age-matched and sex-matched to patients without RA. Diagnostic codes for 44 preidentified chronic conditions were selected to determine the presence (≥2 conditions) and burden (count) of multimorbidity. Cross-sectional comparisons were completed using the overall RA cohort and conditional logistic and negative binomial regression models. Trajectories of multimorbidity were assessed within the incident RA subcohort using generalised estimating equations. RESULTS: The overall cohort (n=277 782) and incident subcohort (n=61 124) were female predominant (76.5%, 74.1%) with a mean age of 55.6 years and 54.5 years, respectively. The cross-sectional prevalence (OR 2.29, 95% CI 2.25 to 2.34) and burden (ratio of conditions 1.68, 95% CI 1.66 to 1.70) of multimorbidity were significantly higher in RA than non-RA in the overall cohort. Within the incident RA cohort, patients with RA had more chronic conditions than non-RA (β 1.13, 95% CI 1.10 to 1.17), and the rate of accruing chronic conditions was significantly higher in RA compared with non-RA (RA × follow-up year, β 0.21, 95% CI 0.20 to 0.21, p<0.001). Results were similar when including the pre-RA period and in several sensitivity analyses. CONCLUSIONS: Multimorbidity is highly prevalent in RA and progresses more rapidly in patients with RA than in patients without RA during and immediately following RA onset. Therefore, multimorbidity should be aggressively identified and targeted early in the RA disease course.
32318800 A retrospective study on the risk of tuberculosis in patients with rheumatoid arthritis. 2020 Jun Tuberculosis (TB) is an important preventable infection in patients with rheumatoid arthritis (RA). To determine the risk of TB in patients with RA by comparing with those with non-specific back pain (NSBP), and to identify the risk factors in the RA group. Medical data were retrieved from a centralized electronic database. A total of 1099 patients with RA and 2489 patients with NSBP were identified. Clinical data, comorbidities, and use of individual disease-modifying anti-rheumatic drugs (DMARDs) were retrieved. Risks of TB in patients with RA and NSBP were compared by propensity score (PS) adjusted analysis with known or potential risk factors for TB. Risk factors of TB were also determined in patients with RA. There were 14 cases of TB in RA group and 25 cases in NSBP group. Median duration of follow-up were 11.3 (0.1-21.9) years in RA group and 15.4 (0.1-24.4) years in NSBP group. The risk of TB in patients with RA was 2.53 times higher (HR 2.53; 95% CI 1.29, 4.94; p < 0.01) than in patients with NSBP. After excluding patients on DMARDs, the risk became similar (HR 2.72; 95% CI 0.81, 9.14; p = 0.11). Independent risk factors found were etanercept (HR 7.16; 95% CI 1.41, 36.30; p = 0.02), and previous TB infection (HR 25.23; 95% CI 6.99, 91.09; p < 0.001). The risk of extrapulmonary involvement between RA and NSBP groups was similar (HR 1.21; 95% CI 0.22, 6.57; p = 0.83). The risk of TB was increased in patients with RA. Anti-TNF therapy was an identified risk factor.
32025629 Ultrasound detects synovitis in replaced and other surgically operated joints in rheumatoi 2020 BACKGROUND: Joint replacements continue to occur during a rheumatoid arthritis (RA) patient's lifetime despite significant advances in available treatment options. The purpose of this study was to examine and quantify synovitis in surgically operated joints by ultrasound (US) in RA patients starting a new therapeutic agent. METHODS: RA subjects were enrolled in either tocilizumab or tofacitinib open-label, investigator-initiated trials and were assessed by ultrasound. In a subset of RA patients with joint replacements and/or operations of joint areas (OJA; e.g. joint arthroscopies, fusions, and synovectomies), joint-level scores of synovitis were compared between replaced joints, OJAs, and native joints. Joint-level synovitis was measured by grayscale (GSUS (0-3)) and power Doppler (PDUS (0-3)) at baseline and follow-up (3-6 months). McNemar's test or Wilcoxon signed rank test utilized the mixed effects ordinal logistic regression models. RESULTS: Twenty RA patients had a total of 25 replaced joints and 24 OJA. All replaced joints had GSUS> 1 and 92% had PDUS> 1 at baseline, while OJA and native joints had lower evidence of GSUS> 1 (37.5, 38% respectively) and PDUS> 1 (45.8, 62% respectively). GSUS and PDUS semiquantitative scores improved significantly with treatment in replaced joints (p = 0.01, p = 0.007), and native joints (p < 0.001 both), but not OJA. CONCLUSIONS: In RA, joint replacement does not eliminate or prevent ultrasound measured synovitis, where all replaced joints have some evidence of US synovitis. US can also act as a potential marker of response to therapy in replaced joints. Scoring US synovitis in replaced joints should be considered in ultrasound RA clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT01717859 (registered 10/31/2012); ClinicalTrials.gov NCT02321930 (registered 12/22/2014).
31863640 Quantitative analysis for modified Schall's classification by stimulation test with dynami 2020 Mar OBJECTIVES: To update Schall's classification for Sjögren's syndrome (SS) by the new quantitative stimulation test with dynamic salivary glands scintigraphy (qsDSGS) and to standardize quantitative salivary gland scintigraphy. METHODS: The histopathology, oral, ocular, serological examination and qsDSGS of 268 consecutive patients with suggestive SS were evaluated in this retrospective cohort study. The serological examination included 15 autoantibodies, antinuclear antibodies (ANA) and so on. The diagnostic thresholds of the functional parameters were set by the quantitative method, and the modified Schall's classification is well established and verified. RESULTS: Based on the quantitative analysis of qsDSGS, the peak uptake level (PUL) and stimulation excretion fraction (sEF) of each parotid gland were determined as the key imaging features, which had good diagnostic performance for SS. By the modified Schall's classification, all patients were classified into: Class 1 (normal; n = 44), Class 2 (mild to moderate involvement; n = 130), Class 3 (severe involvement; n = 56) and Class 4 (very severe involvement, non-function; n = 38). Using the threshold PUL ≤ 10 counts per sec/pixel as positivity, the modified Schall's classification could provide better diagnostic performance with 88.4% specificity, 71.3% sensitivity, 96.14% positive predictive value and 43.20% negative predictive value for SS (likelihood ratio 6.15). The trends of serologically positive frequencies against SSA/Ro, anti-SSB/La and ANA were significantly increased with the new classification. CONCLUSION: The modified Schall's classification by the new stimulation test with dynamic scintigraphy is eligible to standardize quantitative salivary gland scintigraphy for SS, and may be more convenient and suitable in daily practice for clinical research and management of SS.
32573420 Interleukin 17E associates with haematologic involvement and autoantibody production in pr 2021 Mar OBJECTIVES: Primary Sjögren's syndrome (pSS) is one of the most prevalent systemic autoimmune diseases characterised by inflammation and tissue damage of exocrine glands, especially salivary or lacrimal gland. IL-17 related immune response is pathogenic with proinflammatory feature in pSS. However, whether IL-17E, an IL-17 family member, is involved in pSS pathogenesis or not, has not been determined. METHODS: Serum levels of IL-17E and IL-17A as comparison in 107 patients with pSS and 42 healthy controls were determined with multiplex cytokine assays. EULAR Sjögren's syndrome disease activity index (ESSDAI) score was calculated. Laboratory parameters were measured by standard laboratory techniques. The inflammatory infiltration of minor labial gland biopsies was graded based on numbers of lymphocyte and quantified by Focus Score (FS). Expression of IL-17E and IL-17A in the biopsy was evaluated with immunohistochemistry. RESULTS: Significantly elevated IL-17E in pSS patients associated with ESSDAI, haematologic disorders and autoantibody production, including anti-nuclear antibodies (ANA), rheumatoid factor (RF) and anti-SSA antibodies were found. Histopathological features showed that expression of IL-17E was found in labial salivary gland and correlated with lymphocytic infiltration. CONCLUSIONS: IL-17E expression in pSS patients was increased and associated with haematologic disorders, autoantibody production and lymphocytic infiltration in salivary gland. This finding indicated that IL-17E is involved in pSS pathogenesis.
33113810 Discovery of Tricyclic Pyranochromenone as Novel Bruton's Tyrosine Kinase Inhibitors with 2020 Oct 25 Bruton's tyrosine kinase (BTK) is an attractive target for treating patients with B cell malignancies and autoimmune diseases. Many BTK inhibitors have been identified; however, like other kinase inhibitors, they lack diversity in their core structures. Therefore, it is important to secure a novel scaffold that occupies the adenine-binding site of BTK. We screened an in-house library of natural products and their analogs via a biochemical assay to identify a novel scaffold for targeting BTK. A pyranochromenone scaffold, derived from a natural active component decursin, was found to be effective at targeting BTK and was selected for further optimization. A series of pyranochromenone analogs was synthesized through the modification of pyranochromenone at the C7 position. Pyranochromenone compounds with an electrophilic warhead exhibited promising BTK inhibitory activity, with IC(50) values in the range of 0.5-0.9 µM. A docking study of the representative compound 8 provided a reasonable explanation for compound activity. Compound 8 demonstrated good selectivity over other associated kinases and decreased the production of proinflammatory cytokines in THP cells. Moreover, compound 8 presented significant in vivo efficacy in a murine model of collagen-induced arthritis.
31326279 TREX1 variants in Sjogren's syndrome related lymphomagenesis. 2020 Aug Genetic variants of the three-prime repair exonuclease 1 (TREX1) -an exonuclease involved in DNA repair and degradation- have been previously found to increase susceptibility to Aicardi Goutieres syndrome, familial chilblain lupus and systemic lupus erythematosus. We aimed to explore whether TREX1 common variants could influence the risk of primary Sjogren's syndrome (SS) and SS-related lymphoma. Three single nucleotide polymorphisms (SNPs) of the TREX1 gene (rs11797, rs3135941 and rs3135945) were evaluated in 229 SS, 89 SS-lymphoma (70 SS-MALT and 19 SS non-MALT) and 240 healthy controls by PCR-based assays. In available 52 peripheral blood and 26 minor salivary gland tissues from our SS cohort, mRNA expression of type I interferon (IFN) related genes and TREX1 was determined by real-time PCR. Significantly decreased prevalence of rs11797 A minor allele was detected in SS patients complicated by non-MALT lymphoma compared to controls (ΟR [95% CI]: 0.4 [0.2-0.9], p-value: 0.02). SS patients carrying the rs11797 AA genotype had increased type I IFN related gene mRNA expression in minor salivary gland tissues. These data support genetically related dampened type I IFN production as an additional mechanism for SS-related lymphomagenesis.
32928700 Adult-onset Still's disease successfully treated with Chinese herbal medicine: A case repo 2020 Nov Adult-onset Still's disease (AOSD) is a rare but clinically well-known, polygenic, and systemic autoinflammatory disease, which is characterized by spiking fever, evanescent skin rash, arthralgia, and sore throat. The application of non-steroidal anti-inflammatory drugs and glucocorticoids, which are first-line therapies of AOSD, is limited due to their side effects such as liver injury or disorder of blood glucose. Therefore, patients who suffer from systemic diseases in China prefer to seek help from Chinese herbal medicine (CHM), which is an important part of complementary and alternative medicine. In this case, we report a 28-year-old male badminton coach presenting with a 15-day history of fever and skin rash, accompanied by sore throat, fatigue, myalgia and chills. Additionally, hepatosplenomegaly, multiple lymphadenopathies, aminotransferase abnormality, and elevated inflammatory factor levels were observed during hospitalization. Infectious diseases, solid tumors, hematological diseases, and common autoimmune diseases were excluded. Not benefitting from antibiotic therapy, the patient was finally diagnosed with AOSD, after a careful examination, then showed rapid remission after a six-week treatment with CHM granules based on Xiaochaihu Decoction and Yinqiao Powder. After stopping the treatment, there was no relapse within a 15-month follow-up period. To the best of our knowledge, this is the first well-documented case of this successful treatment. The present case report suggests that CHM is a reliable choice for complementary and alternative therapy for AOSD, but confirming the utility of CHM for AOSD requires further support from prospective studies.
32430612 Combination value of biomarkers in discriminating adult onset Still's disease and sepsis. 2021 Feb BACKGROUND: Lymphocyte and plateletcrit (PCT) as proportions of routine complete blood count tests, have been studied as simple biomarkers for inflammatory diseases. The aim of our study was to investigate whether blood routine parameters, especially platelet parameters could be a useful tool to distinguish Adult onset Still's disease (AOSD) from sepsis. METHODS: We retrospectively reviewed 58 patients with AOSD and 55 sepsis patients diagnosed at the First Affiliated Hospital of Nanjing Medical University between January, 2015 to December 2018. Laboratory data including ferritin, blood routine parameters and C‑reactive protein (CRP) level were collected, and the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR) were calculated. RESULTS: The results showed that AOSD patients showed higher ferritin, lymphocyte and PCT (all P < 0.01) and these factors are independent risk factors for predicting AOSD. In receiver operating characteristic (ROC) curve analysis of LY, PCT and ferritin for distinguish of AOSD, the area under the curve (AUC) was 0.676 (0.576-0.777); 0.706 (95% CI = 0.596-0.816); 0.715 (0.617-0.814). Meanwhile, the AUC of the combination of lymphocyte, PCT and ferritin was 0.836 (0.737-0.909) with sensitivity 67.3, specificity 92.3, and the difference was significant. CONCLUSIONS: Thus we suggest that lymphocyte, PCT may be a useful tool to make a distinction between AOSD and sepsis, as supplementary biomarkers to ferritin.
32683379 Risk factors related to oral candidiasis in patients with primary Sjögren's syndrome. 2020 Sep 1 BACKGROUND: Candidiasis is the most frequent mycotic infection of the oral cavity. The aim of this study was to investigate the presence of clinical oral candidiasis and Candida albicans yeast in a population diagnosed of primary Sjögren's syndrome (pSS) and to study the possible factors associated with this infection. MATERIAL AND METHODS: An observational cross-sectional study was conducted in 61 pSS patients (60 women, 1 man, mean age 57.64±13.52) where patient based information (demographic and medical, tobacco and alcohol consumption history), intraoral parameters (presence of dentures, clinical signs of candidiasis), salivary analytical information (number of Candida albicans as colony-forming units per millilitre (CFU/mL), salivary pH levels, unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) were collected. RESULTS: 13.1% of pSS patients presented oral signs of candidiasis. Denture stomatitis and angular cheilitis were the most common lesions. 87.5% of patients with clinical candidiasis presented reduced pH levels and salivary flow in both UWS and SWS. A significant statistical negative correlation was found between CFU/mL of Candida albicans and levels of UWS and SWS. A negative correlation was found between pH levels and CFU/mL, although not statistically significant. CONCLUSIONS: A reduced salivary flow may predispose pSS patients to Candida albicans overgrowth, which may show with clinical signs. Preventive measures are of great importance to avoid and to treat this condition promptly.
33204558 Bilateral Wrist Tenosynovitis owing to Acute Conversion of Adult T-Cell Leukemia-Lymphoma 2020 Human T-cell leukemia virus type 1- (HTLV-1-) associated arthritis is a relatively common disease. However, tenosynovitis owing to adult T-cell leukemia-lymphoma (ATL) is a rare condition. To the best of our knowledge, there have been no reports of tenosynovitis caused by conversion to acute ATL from one of the other ATL types. We present the case of a 60-year-old woman with rheumatoid arthritis (RA) with bilateral wrist tenosynovitis owing to the conversion to acute ATL from one of the other ATL types. She had swelling around the bilateral wrist joint under well controlled RA inflammation. She had no symptoms, physical findings, or laboratory findings indicative of conversion to acute ATL from one of the other ATL types. She underwent tenosynovectomy on the volar and dorsal sides of the left wrist joint to diagnose the cause of swelling around the bilateral wrist joint. Pathological analysis revealed diffuse proliferation of medium-sized atypical CD4(+) lymphocytes. Interestingly, she was diagnosed with wrist tenosynovitis caused by an acute ATL type. This diagnosis suggested that clinicians must consider ATL in connection with atypical wrist tenosynovitis in HTLV-1-endemic areas.
32631600 Risk of Malignancy in Spondyloarthritis: A Systematic Review. 2020 Aug Systematic inflammatory diseases, including rheumatoid arthritis (RA), are associated with an increased risk of malignancies. However, the pathogenesis of spondyloarthritis (SpA), which includes both ankylosing spondylitis and psoriatic arthritis, is different from RA, and the risk of malignancy and sites involved may also be different. It is important to better understand associations of SpA with site-specific cancers to facilitate appropriate cancer screening. The goal of this review was to examine the association of SpA with malignancy and the potential impact of therapy for SpA on development of malignancy.
32499694 Tanshinone IIA Suppresses Proliferation and Inflammatory Cytokine Production of Synovial F 2020 Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disease in which activated RA fibroblast-1ike synoviocytes (RA-FLSs) are one of the main factors responsible for inducing morbidity. Previous reports have shown that RA-FLSs have proliferative features similar to cancer cells, in addition to causing cartilage erosion that eventually causes joint damage. Thus, new therapeutic strategies and drugs that can effectively contain the abnormal hyperplasia of RA-FLSs and restrain RA development are necessary for the treatment of RA. Tanshinone IIA (Tan IIA), one of the main phytochemicals isolated from Salvia miltiorrhiza Bunge, is capable of promoting RA-FLS apoptosis and inhibiting arthritis in an AIA mouse model. In addition, RA patients treated at our clinic with Tan IIA showed significant improvements in their clinical symptoms. However, the details of the molecular mechanism by which Tan IIA effects RA are unknown. To clarify this mechanism, we evaluated the antiproliferative and inhibitory effects of proinflammatory factor production caused by Tan IIA to RA-FLSs. We demonstrated that Tan IIA can restrict the proliferation, migration, and invasion of RA-FLSs in a time- and dose-dependent manner. Moreover, Tan IIA effectively suppressed the increase in mRNA expression of some matrix metalloproteinases and proinflammatory factors induced by TNF-α in RA-FLSs, resulting in inflammatory reactivity inhibition and blocking the destruction of the knee joint. Through the integration of network pharmacology analyses with the experimental data obtained, it is revealed that the effects of Tan IIA on RA can be attributed to its influence on different signaling pathways, including MAPK, AKT/mTOR, HIF-1, and NF-kB. Taken together, these data suggest that the compound Tan IIA has great therapeutic potential for RA treatment.