Peficitinib inhibits fibroblast-like synoviocyte activation and angiogenic vascular endothelial tube formation via inhibitory effects on PDGF and VEGF signaling in addition to JAK.

PURPOSE: Peficitinib and tofacitinib are known to suppress inflammation in rheumatoid arthritis (RA) by inhibiting Janus kinases (JAKs). However, these effects on tyrosine kinases other than JAKs have not yet been well investigated. We evaluated the effects of peficitinib and tofacitinib on platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) receptor tyrosine kinases (RTKs) and on the activation of fibroblast-like synoviocytes (FLSs) and endothelial cells, main pathological causes of RA. METHODS: Peficitinib and tofacitinib were tested in PDGF and VEGF RTK assays. We then used FLSs derived from RA patient (RA-FLSs) and human umbilical vein endothelial cells (HUVECs) to study the effects of peficitinib and tofacitinib on PDGF- and VEGF-induced signal transduction and on the activation of RA-FLSs and endothelial cell tube formation. FINDINGS: Peficitinib, not tofacitinib, inhibited both PDGF and VEGF RTKs in addition to JAKs in cell-free assay system. Peficitinib and tofacitinib attenuated PDGF- and VEGF-induced intracellular signal transduction pathways in RA-FLSs and HUVECs to varying degrees. Only peficitinib potently inhibited PDGF-induced secretion of interleukin-6, VEGF, and matrix metalloproteinase-3 in RA-FLSs, and endothelial cell tube formation by HUVECs. CONCLUSION: Peficitinib may improve RA through inhibition of PDGF and VEGF signal transduction, in addition to JAK inhibition.

Peficitinib improves bone fragility by recovering bone turnover imbalance in arthritic mice.

Peficitinib, a pan-JAK inhibitor, is known to suppress the activation of fibroblast-like synoviocytes (FLSs) and thereby reduces joint inflammation associated with rheumatoid arthritis (RA). However, the effect on osteoporosis in RA remains to be elucidated. In this study, the effect of peficitinib or etanercept on joint inflammation, and consequently decreased bone mineral density (BMD) was evaluated in mice with collagen-induced arthritis (CIA). Additionally, the effect on RANKL production from osteoblasts differentiated from the mesenchymal stem cells of RA patients was evaluated. Administration of peficitinib for established CIA ameliorated arthritis and improved BMD in the femoral metaphysis, but not in the femoral diaphysis. Conversely, etanercept suppressed an increase in synovial inflammatory markers but did not improve arthritic conditions or the reduction of BMD in either region. All elevated bone formation and bone resorption markers were decreased with peficitinib but only partially decreased with etanercept. Furthermore, production of RANKL by human osteoblasts was suppressed by peficitinib but enhanced by etanercept. Unlike etanercept, peficitinib is thought to increase BMD by ameliorating the high bone turnover associated with RA states, resulting in improvement of bone fragility. Our data provide evidence that peficitinib would be expected to show efficacy for osteoporosis associated with RA.

Region specificity of rheumatoid foot symptoms associated with ultrasound-detected synovitis and joint destruction.

OBJECTIVES: We aimed to clarify the clinical implication of ultrasound (US)-detected foot joint inflammation in tightly controlled patients with rheumatoid arthritis (RA). METHODS: We evaluated bilateral foot joints (second to fifth metatarsophalangeal joints of forefoot; tarsometatarsal, cuneonavicular and midtarsal joints of midfoot) of 430 RA patients for synovitis using Power Doppler (PD) imaging by US. We made a cross-sectional and a 3-year longitudinal analysis about the associations of US-detected synovitis with clinical, laboratory and radiographic data as well as foot-specific outcomes using a self-administered foot evaluation questionnaire (SAFE-Q). RESULTS: The US-detected foot synovitis was seen in 28% of patients. The US-detected synovitis was closely related to 28 joint-disease activity score (DAS28) more in the forefoot than in the midfoot, while related to joint destruction in both. Multiple regression analyses showed significant associations between midfoot PD positivity and SAFE-Q in the remission group. SAFE-Q was worsened after the 3-year interval, but PD positivity at baseline did not contribute to the changes. On the other hand, destruction of the joints with US-detected synovitis significantly progressed in 3 years than with not. CONCLUSIONS: US-detected synovitis on foot joints were related to systemic inflammation, clinical symptoms, and future joint destruction with region specificity.

Severe joint deformity and patient global assessment of disease are associated with discrepancies between sonographic and clinical remission: A cross-sectional study of rheumatoid arthritis patients.

OBJECTIVE: Although recent clinical trials showed that ultrasound (US) remission is not required to achieve good outcomes at the group level, it currently remains unclear whether the prognosis of individual patients in clinical remission, but not US remission, i.e. those with subclinical sonographic synovitis (SSS), is favorable. However, it is no longer acceptable to perform US on all patients in order to identify those with SSS. Therefore, the present study was initiated to elucidate the conditions under which SSS is frequently detected. METHODS: In total, 563 consecutive RA patients were recruited. Bilateral 2-5 MCP, wrist, ankle, and 2-5 MTP joints were scanned by US, and Gray scale and Power Doppler (PD) images were scored semi-quantitatively. Clinical data were obtained by physicians who were blind to US results. Changes in the modified Total Sharp Score (mTSS) of tocilizumab (TCZ) users were calculated. RESULTS: A total of 402 patients were included. SSS was more frequently detected in patients with more severe joint deformity, even if they were in remission. In contrast, a high Patient Global Assessment of Disease (PtGA) did not reflect SSS. Furthermore, the relationship between PtGA and PD scores was weak. Although the frequency of SSS was high in TCZ user, the presence of SSS in TCZ users not always results in the progression of mTSS. CONCLUSIONS: While remission is overestimated in patients with severe joint deformity, underestimations may occur in those who do not fulfill remission criteria because of a high PtGA.

In vitro pharmacological effects of peficitinib on lymphocyte activation: a potential treatment for systemic sclerosis with JAK inhibitors.

OBJECTIVES: Peficitinib, a novel Janus kinase (JAK) inhibitor, demonstrated promising results in treating RA in phase 3 clinical trials. This in vitro study was undertaken to characterize the pharmacological properties of peficitinib and investigate the involvement of JAK and signal transducer and activator of transcription (STAT) pathways in the pathological processes of SSc, which is also an autoimmune disease. METHODS: Phosphorylation levels of STAT molecules were assessed in peripheral blood mononuclear cells collected from patients with RA or SSc and healthy subjects, and in skin specimens obtained from 19 patients with SSc. In vitro inhibition of STAT phosphorylation and cytokine/chemokine production by peficitinib, tofacitinib and baricitinib were also characterized. RESULTS: Higher spontaneous STAT1 or STAT3 phosphorylation was observed in peripheral T-cells and monocytes from patients with RA and SSc compared with healthy subjects. In skin sections from patients with SSc, phosphorylated STAT3-positive cells were found in almost all cases, irrespective of disease subtype or patient characteristics. Conversely, phosphorylated STAT1-positive cells were observed only in samples from untreated patients with diffuse disease of short duration. Peficitinib inhibited STAT phosphorylation induced by various cytokines, with comparable efficacy to tofacitinib and baricitinib. Peficitinib also suppressed cytokine and chemokine production by peripheral blood mononuclear cells and skin fibroblasts. CONCLUSION: Our results suggest that JAK/STAT pathways are constitutively activated in SSc and RA, and that the JAK inhibitor may represent a novel therapeutic option for SSc.

Feasibility of patient-oriented ultrasound joint selection: Cross-sectional observational study on rheumatoid arthritis.

Objective: Ultrasonography (US) is a useful tool for evaluating the activity of rheumatoid arthritis (RA) patients. As the systemic evaluation of many joints is time-consuming, a method to evaluate this activity with a smaller number of joints is needed. The aim of this study was to clarify whether the number of joints assessed may be reduced using patient-oriented joint selection.Methods: A total of 492 RA patients were recruited at Kyoto University Hospital. Bilateral metacarpophalangeal (MCP), (proximal) interphalangeal (PIP/IP), and wrist joints were evaluated by US. Gray scale and power Doppler imaging findings were scored by a 0-3 semi-quantitative method. Clinical assessments were performed by physicians who were blind to US results, and a questionnaire on subjective symptoms was collected from each patient.Results: The correlation between the US score of all 22 joints (US22) and patient-oriented painful joints (PtUS) or physician-oriented tender and/or swollen joints were moderate (Spearman's ρ = 0.435) and weak (ρ = 0.383), respectively. These correlations were weaker than that between the total US score of 5 preselected joints (unilateral 2MCP, 3MCP, 2PIP, 3PIP, and the wrist) and US22 (ρ = 0.813). However, when focusing on patients whose painful joints were 5 and more, the correlation between PtUS and US22 was markedly stronger (ρ = 0.757).Conclusion: Patient-oriented joint selection reflected actual joint inflammation to some extent. However, excessive reductions in the number of joints assessed need to be avoided even if patients do not have arthralgia because of the potential for underestimations.

Non-obese visceral adiposity is associated with the risk of atherosclerosis in Japanese patients with rheumatoid arthritis: a cross-sectional study.

Rheumatoid arthritis (RA) patients often have altered body composition including reduced muscle mass and increased fat mass. Some RA patients are likely to increase visceral fat without obesity [Body Mass Index (BMI) ≥ 25]. The objective of the study was to determine the association between obesity and/or visceral adiposity and the risk for atherosclerosis in Japanese RA patients. Obesity was evaluated using the BMI, with visceral adiposity evaluated using the visceral fat area (VFA) and the visceral/subcutaneous fat ratio (V/S ratio), quantified using the dual bioelectrical impedance method. Atherosclerosis was evaluated based on the intima-media thickness (IMT) and Plaque score (PS) of the carotid artery, measured using ultrasonography. Multivariate analysis was performed to determine the factors associated with IMT and PS. IMT and PS were compared among groups of patients sub-classified according to BMI and VFA levels. The V/S ratio was higher in RA patients than healthy controls, after adjustment for age, BMI, and waist circumference. On multivariate analysis, the V/S ratio, but not the BMI, was independently associated with the IMT and PS. Among the sub-classifications for BMI and VFA, non-obese patients with a high visceral adiposity (18.5 ≤ BMI < 25 kg/m2 and VFA ≥ 100 cm2) had the highest IMT (mean IMT, 0.93 ± 0.29 mm; maximum IMT, 1.44 ± 0.71 mm) and PS (1.43 ± 0.61), compared to all other BMI and VFA subgroups. RA patients have increased visceral adiposity, which is associated with a high prevalence of atherosclerotic of plaques. Non-obese RA patients who have visceral adiposity have a specifically higher risk for atherosclerosis.

Effects of the Janus kinase inhibitor CP-690550 (tofacitinib) in a rat model of oxazolone-induced chronic dermatitis.

The effect of CP-690550 (tofacitinib), a new Janus kinase (JAK) inhibitor, was evaluated in chronic allergic dermatitis. Allergic contact dermatitis was induced in rat ears by repeated application of oxazolone. This dermatitis was accompanied by sustained ear swelling and marked epidermal hyperplasia. In the induced ear, a lot of inflammatory cells infiltrated into the dermis site and the amounts of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-22 were elevated. Orally administered CP-690550 significantly suppressed ear swelling as well as epidermal thickening, and the effect at 10 mg/kg was comparable to that of cyclosporin A and etanercept. These results suggest a great potential of CP-690550, a JAK inhibitor, as a treatment for chronic dermatitis featuring epidermal hyperplasia (in the pathogenesis of which IFN-γ, TNF-α and IL-22 play a role) such as psoriasis and chronic atopic dermatitis.

Comparison of the effects of peficitinib and tofacitinib in the adjuvant-induced arthritis rat model.

We investigated and compared the pharmacologic properties of two Janus kinase (JAK) inhibitors, peficitinib and tofacitinib, in an adjuvant-induced arthritis rat model. Repeated administration of peficitinib (3 - 30 mg/kg) or tofacitinib (1 - 10 mg/kg) exhibited a dose-related and significant attenuation of arthritis score, paw swelling, pain threshold, grip strength and histopathologic injuries in the model; peficitinib 10 mg/kg and tofacitinib 3 mg/kg demonstrated comparable efficacy. Equivalent Cmax and AUC0-12h values were observed with peficitinib 10 mg/kg and tofacitinib 3 mg/kg, suggesting that the two drugs may demonstrate comparable efficacy on arthritis-associated symptoms at comparable plasma concentration levels. However, peficitinib 10 mg/kg had greater efficacy than tofacitinib 3 mg/kg on some inflammation- and bone destruction-associated parameters in the paw fluid, including the production of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), receptor activator of nuclear factor kappa-B ligand, and matrix metalloproteinase-3, which are associated with arthritis exacerbation. Peficitinib 10 mg/kg also showed significantly greater inhibitory effects than tofacitinib 3 mg/kg on loss of bone mineral density and synovial thickening score, which might be a result of the VEGF and PDGF receptor kinase inhibitory effects of peficitinib, in addition to JAK inhibition. In conclusion, both tofacitinib and peficitinib potently improved arthritis and associated symptoms in adjuvant-induced arthritis rats; moreover, owing to possible differences in the mechanism of action of the two drugs, peficitinib may have exerted its effects through JAK inhibition and additional unique off-target properties.

Clinical Outcomes of Switching from Zoledronic Acid to Denosumab for the Management of Severe Bone Metastasis from Hepatocellular Carcinoma: A Single-Center, Open-Label, Prospective Intervention Trial.

Background: Zoledronic acid reduces the risk of bone metastasis, but denosumab is a better option for treating bone metastases. However, few studies have evaluated the use of denosumab to treat bone metastasis originating from hepatocellular carcinoma. This study aimed to assess the clinical outcomes of switching from zoledronic acid to denosumab for treating bone metastasis in patients with hepatocellular carcinoma. Methods: This prospective study enrolled 10 patients with HCC and bone metastases. The levels of type 1 collagen cross-linked N-telopeptide (NTx) and tumor growth remained abnormal in these patients despite administration of zoledronic acid for over 3 months. We switched from zoledronic acid to 120 mg denosumab every 4 weeks and evaluated the clinical outcomes, including changes in the NTx level, pain level, and activities of daily living, as well as adverse events, after each administration. Results: Urinary NTx clearance was normal in all patients. The average urinary NTx clearance increased from 13.2 to 21.2 nmol BCE/nmol ·â€†Cre (P = 0.54) after the switch to denosumab. Serum NTx levels were abnormal in all cases. The serum NTx level decreased from 142 nmol BCE/L to 126 nmol BCE/L (P = 0.56). The answers to questionnaires on pain and activities of daily living did not change significantly. Some patients showed elevated transaminase levels, but this was not due to the drug switch. Conclusion: Switching to denosumab did not show a significant change of the pain and activity of daily living for the patients with severe bone metastasis from hepatocellular carcinoma, in whom the efficacy of zoledronic acid was limited.

Processed skin surface images acquired by acoustic impedance difference imaging using the ultrasonic interference method: a pilot study.

To clarify the potential of a novel system using the acoustic impedance difference imaging (AIDI) method for diagnosis of skin disorders, we used it on a coin and swine skin. An ultrasound wave with a central frequency of 20 MHz, emitted from a fused quartz rod with a diameter of 1.25 mm, was focused on the surface of the coin and skin samples. The difference in acoustic impedance was determined by the reflection-type interference-based acoustic impedance measurement method. The processed data were produced as greyscale images on which the maximum measured amplitudes were mapped. We applied the method to a coin. Swine skin, burned and covered with an acrylic sheet with a thickness of 0.2 mm (a few times the half-wavelength) to eliminate the undulations of the skin surface, was employed to obtain processed images from which undulation data were excluded. All the processed images obtained corresponded almost exactly with the magnified optical ones. In the processed images of swine skin, a marked difference was found after the burning procedure. The processed images obtained using the AIDI method reflected not only the undulations but also other information such as elasticity. In conclusion, our system using AIDI has the potential to become a useful modality for the diagnosis of skin disorders.

Sonographic findings of Sister Mary Joseph's nodule from ovarian cancer.

Sister Mary Joseph's nodule (SMJN), which is known as a malignant tumor metastasized to the umbilicus, is a rare condition. We report ultrasonic findings of SMJN secondary to ovarian cancer in a 66-year-old woman. The umbilical tumor was observed as a hypoechoic mass with punctate hyperechoic foci. A pathological specimen obtained by needle biopsy confirmed adenocarcinoma with psammoma bodies. A comparison of the ultrasonographic findings with the pathological findings of the resected specimen suggested that the hyperechoic foci corresponded to psammoma bodies. When hyperechoic foci are observed inside SMJN by ultrasonography, adenocarcinoma from ovarian cancer should be included in the differential diagnosis.

Machine learning-based prediction of relapse in rheumatoid arthritis patients using data on ultrasound examination and blood test.

Recent effective therapies enable most rheumatoid arthritis (RA) patients to achieve remission; however, some patients experience relapse. We aimed to predict relapse in RA patients through machine learning (ML) using data on ultrasound (US) examination and blood test. Overall, 210 patients with RA in remission at baseline were dichotomized into remission (n = 150) and relapse (n = 60) based on the disease activity at 2-year follow-up. Three ML classifiers [Logistic Regression, Random Forest, and extreme gradient boosting (XGBoost)] and data on 73 features (14 US examination data, 54 blood test data, and five data on patient information) at baseline were used for predicting relapse. The best performance was obtained using the XGBoost classifier (area under the receiver operator characteristic curve (AUC) = 0.747), compared with Random Forest and Logistic Regression (AUC = 0.719 and 0.701, respectively). In the XGBoost classifier prediction, ten important features, including wrist/metatarsophalangeal superb microvascular imaging scores, were selected using the recursive feature elimination method. The performance was superior to that predicted by researcher-selected features, which are conventional prognostic markers. These results suggest that ML can provide an accurate prediction of relapse in RA patients, and the use of predictive algorithms may facilitate personalized treatment options.

Educational courses for physiological function examination at Jichi Medical University: practical trainings in ultrasonography.

To foster work-ready general physicians, Jichi Medical University has developed various clinical teaching practices since its foundation. The educational courses for clinical laboratory medicine, being one of them, adopt practical trainings in ultrasonography, which is essential in practical medicine today. The aims and the specifics of the trainings adopted in the seminar of ultrasound and the required or the optional subjects of Bedside Learning (BSL) at Jichi Medical University are reported.

Degradation of ultrasound probes caused by disinfection with alcohol.

The aim of this study was to clarify the degree of degradation of ultrasonic probes that results from their disinfection with alcohol. No defect in the ultrasound beams was found in any of the probes, but a significant decrease of the brightness was found after a certain period of use of the linear-type probe. Disinfection with alcohol may degrade ultrasound probes despite its high degree of effectiveness in preventing iatrogenic bacterial transmission.

Inhibitory effects of ultrasound irradiation on Staphylococcus epidermidis biofilm.

PURPOSE: We aimed to investigate whether low-intensity continuous and pulsed wave ultrasound (US) irradiation can inhibit the formation of Staphylococcus epidermidis biofilms, for potential application in the treatment of catheter-related bloodstream infections (CRBSI). METHODS: S. epidermidis biofilms that formed on the bottom surfaces of 6-well plates were irradiated on the bottom surface using the sound cell incubator system for different intervals of time. RESULTS: US irradiation with continuous waves for 24 h notably inhibited biofilm formation (p < 0.01), but the same US irradiation for 12 h had no remarkable effect. Further, double US irradiation with pulsed waves for 20 min inhibited biofilm formation by 33.6%, nearly two-fold more than single US irradiation, which reduced it by 17.9%. CONCLUSION: US irradiation of a lower intensity (ISATA = 6-29 mW/cm2) than used in a previous study and lower than recommended by the Food and Drug Administration shows potential for preventing CRBSI caused by bacterial biofilms.

Positive rate and prognostic significance of the superb microvascular imaging signal in joints of rheumatoid arthritis patients in remission with normal C-reactive protein levels and erythrocyte sedimentation rates.

PURPOSE: This study aimed to evaluate the positive rate and prognostic significance of superb microvascular imaging (SMI) in rheumatoid arthritis (RA) patients in remission with normal C-reactive protein (CRP) levels and erythrocyte sedimentation rates (ESR). METHODS: The study enrolled 112 RA patients, and ultrasound (US) assessment was performed on 28 joints of each patient. RESULTS: The SMI signal-positive rates for each joint were: metacarpophalangeal (MCP) joints: 20.5%, wrist joints: 43.8%, metatarsophalangeal (MTP) joints: 17.0%, and other foot joints: 25.0%. Investigation of the prognostic significance of the SMI signal in each joint revealed that only in the MTP joints was the total score of the SMI signal in the patients with relapse significantly higher than that in the patients with remission (P = 0.01). Comparison of the receiver operating characteristics curves for predicting relapse showed that the area under the curve (AUC) of the MTP joints was the highest (AUC = 0.66) of the investigated joints. The optimal threshold for the total MTP SMI score was 1 (accuracy = 83.3%). Positive/negative data of the SMI signal in the MTP joints were not significantly associated with the values of conventional disease activity markers. CONCLUSION: In RA patients in remission with normal CRP and ESR levels, the percentage of positive SMI signal was highest in the wrist joints. However, the accuracy of the SMI signal for predicting relapse was greatest for the MTP joints, suggesting that US assessment of the MTP joints by SMI is useful for predicting relapse in these patients.

Complete Response for Advanced Hepatocellular Carcinoma by Conversion Surgery Therapy Following a Good Response of Regorafenib Despite Rapid Progressive Disease with Sorafenib.

A 68-year-old man with hepatocellular carcinoma (HCC) visited his previous hospital due to abdominal pain and was diagnosed with ruptured HCC. Before visiting our hospital, he underwent HCC treatment at his previous hospital, but his tumors did not improve. Although he started treatment with sorafenib, the tumors rapidly grew. Subsequently, regorafenib was given, and the tumors shrank. After 22 months being treated with regorafenib, HCC reoccurred, with a new lung metastasis and a contrast-enhanced nodule on the peritoneal dissemination appearing. He underwent conversion surgery and survived for 4.5 years after his HCC was diagnosed.

Role of JAK-STAT signaling in the pathogenic behavior of fibroblast-like synoviocytes in rheumatoid arthritis: Effect of the novel JAK inhibitor peficitinib.

Rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS) play a crucial role in the pathogenesis of RA. RA-FLS display passive pro-inflammatory responses and self-directed aggressive responses, such as pro-inflammatory mediator production, reduced apoptosis and formation of a thickened synovial lining. Evidence suggests a role for Janus kinase (JAK)-signal transducer and transcriptional activator (STAT) signaling in the passive response but the aggressive behavior of RA-FLS is poorly understood. The pharmacologic effects of the novel JAK inhibitor, peficitinib, on cytokine-induced intracellular signaling and self-directed aggressive behavior of RA-FLS (e.g., increased expression of apoptosis-resistant genes and sodium nitroprusside-induced apoptosis) were investigated and compared with approved JAK inhibitors. RA-FLS assembly to form a lining-like structure and pro-inflammatory mediator production was investigated in three-dimensional (3D)-micromass culture. Peficitinib inhibited STAT3 phosphorylation in RA-FLS following induction by interferon (IFN)-α2b, IFN-γ, interleukin (IL)-6, oncostatin M, and leukemia inhibitory factor in a concentration-related manner, and was comparable to approved JAK inhibitors, tofacitinib and baricitinib. Peficitinib and tofacitinib suppressed autocrine phosphorylation of STAT3 and expression of apoptosis-resistant genes, and promoted cell death. In 3D-micromass culture, peficitinib reduced multi-layered RA-FLS cells to a thin monolayer, an effect less pronounced with tofacitinib. Both compounds attenuated production of vascular endothelial growth factor-A, matrix metalloproteinases, IL-6 and tumor necrosis factor superfamily-11. This study confirmed the pathogenic role of uncontrolled JAK-STAT signaling in the aggressive and passive responses of RA-FLS that are critical for RA progression. The novel JAK inhibitor peficitinib suppressed the pro-inflammatory behavior of RA-FLS, accelerated cell death and abrogated thickening of the synovium.

Prediction of recurrence and remission using superb microvascular imaging in rheumatoid arthritis.

PURPOSE: Ultrasound is commonly used to assess the degree of synovitis in patients with rheumatoid arthritis (RA); however, it is unclear which joints are optimal for evaluating and predicting recurrence and remission. PATIENTS AND METHODS: In 293 RA patients enrolled in the KURAMA cohort, 28 joints were assessed by ultrasound. RESULTS: Results from patients in remission in both 2015 and 2017 (Group 1, n = 152) were compared with those from patients in remission in 2015 and non-remission in 2017 (Group 2, n = 60). The SMI scores for total (3.1 vs. 6.3, P = 0.004), MCP2-5 (1.1 vs. 2.4, P = 0.03), wrist (0.9 vs. 2.1, P = 0.0003), MTP2-5 (0.4 vs. 1.0, P = 0.03), and Lisfranc joints (0.07 vs. 0.25, P = 0.04) were significantly higher for Group 2. When those in non-remission in 2015 and remission in 2017 (Group 3, n = 27) were compared with those in remission in 2015 and non-remission in both 2015 and 2017 (Group 4, n = 54), the GS-SMI combined score (3.0 vs. 5.0, P = 0.04) and SMI score (1.5 vs. 2.9, P = 0.04) for MCP2-5 joints were significantly higher for Group 4. Multivariate logistic regression analysis identified "wrist SMI score ≧ 1" as an independent prognostic factor for recurrence (odds ratio 3.08, P = 0.001) and "MCP2-5 GS-SMI combined score ≦ 4" as an independent prognostic factor for remission (odds ratio 3.25, P = 0.048). CONCLUSION: We identified the optimal joint cut-off scores for predicting recurrence and remission in RA patients. Risk-stratification therapy based on the ultrasound scores may improve outcome and quality of life for patients with RA.