Canonical (CD74/CD44) and Non-Canonical (CXCR2, 4 and 7) MIF Receptors Are Differentially Expressed in Rheumatoid Arthritis Patients Evaluated by DAS28-ESR

Macrophage migration inhibitory factor (MIF) significantly contributes to rheumatoid arthritis (RA) pathogenesis. We aimed to evaluate the canonical (CD74/CD44) and non-canonical MIF receptors (CXCR2,4 and 7) expression and sCD74 to establish their association with RA clinical activity according to DAS28-ESR. Methodology: 101 RA patients with different clinical activities (remission (n = 27), low (n = 16), moderate (n = 35) and high (n = 23)) and 9 control subjects (CS) were included. Expression was evaluated by flow cytometry and levels of soluble CD74 (sCD74) by ELISA. Data analysis was performed with FlowJov10.0, STATAv12.0, and GraphPad Prism v7.0. Results: According to disease activity, CXCR7 expression (percentage of expression and mean fluorescence intensity (MFI)) was higher in granulocytes from patients in remission, while the expression of CXCR4 was higher in patients with high disease activity (p < 0.05). The expression of CD74 was higher in B cells (p < 0.05) and monocytes (p < 0.01) from patients in remission. Regarding sCD74 levels these were higher in patients with high disease activity when compared to those in remission (p <0.05). Conclusions: The results support the need for further study of the role of sCD74 as a soluble MIF decoy receptor, sequestering it to negatively regulate MIF signaling though its membrane receptors. The expression patterns of CXCR4 and CXCR7 show that the latter is a scavenger-type receptor that prevents endocytosis and even degradation of CXCR4 under inflammatory conditions.

Platelet-To-Lymphocyte Ratio Can Be Used As Marker To Predict Activity And Severity In Moderate And High Disease Activity of Rheumatoid Arthritis: A Retrospective Study

Objective: This study aimed to study and evaluate the value of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) as markers to predict the disease activity and severity in patients with rheumatoid arthritis (RA).Methods: A total of 139 inpatients with RA were divided into two groups: moderate activity group (3.2<DAS28-CRP score<5.1) and high activity group (≥5.1). The correlation of routine hematological indices with DAS28 and joint ultrasound score (gray-scale ultrasound score, GS-US; power Doppler ultrasound score, PD-US; total ultrasound score, T-US) were analyzed by Pearson's correlation and logistic regression analyses. Receiver operating characteristics (ROC) analysis was performed to compare the efficacy of blood indices, ESR, or CRP in reflecting the disease activity and severity of RA.Results: The values of PLR, NLR, PD-US, and T-US were significantly different between moderate and high disease activity groups (p<0.001), and PLR was significantly correlated with PD-US and DAS28. Logistic regression analyses showed that PLR was an independent risk factor for disease activity by DAS 28 and joint damage severity by PD-US and T-US. ROC analysis showed that the efficacy of using PLR alone to evaluate the disease activity and joint severity of RA was similar to that of using combined CRP and ESR. The best cut-off value of PLR for predicting high disease activity and high joint severity was determined as 236.6.Conclusions: PLR can be used as a marker to predict activity and severity in patients with moderate and high RA disease activity.

Comparison of clinical manifestations of rheumatoid arthritis in patients with moderate or high disease activity depending on the presence or absence of symptoms of neuropathic pain

Objective: to study the effect of neuropathic pain symptoms (SNP) on the clinical manifestations of rheumatoid arthritis (RA) in patients with moderate or high disease activity.Patients and methods. The 1st (main) group included 58 RA patients (84.5% of women, age 53.0±11.9 years), in whom SNP were identified using the DN4 (≥4) and PainDETECT (≥13) questionnaires. The 2nd (control) group included 43 patients with RA (79.1% women, age 48.8±14.4 years) who did not have SNP (DN4 ≤4 and PainDETECT ≤13). All patients received disease-modifying antirheumatic drugs (mainly methotrexate and leflunomide), 20% – biologic disease-modifying antirheumatic drugs. We compared groups 1 and 2 for RA activity (DAS28, CDAI, SDAI), pain intensity on a visual analogue scale (VAS, 0–100 mm), functional impairment (HAQ), patient global assessment (PGA, VAS), number of painful and swollen joints, quality of life (EQ-5D), signs of anxiety and depression (HADS), CRP level.Results and discussion. The RA activity in patients of the 1st and 2nd groups did not differ statistically significantly. Patients of the 1st group showed significantly higher indicators of the severity of pain, PGA and anxiety than patients of the control group: 71.0±12.5 and 54.7±17.5 mm, respectively (p<0.001); 61.0±13.1 and 53.7±15.3 mm (p=0.045); 62.1 and 28.6% (HADS ≥7; p<0.001), respectively.Conclusion. SNP are associated with higher rates of pain intensity, PGA, and anxiety in RA patients with moderate to high disease activity.

Clinical utility of quantitative analysis of bone scintigraphy in detecting clinically active joint and high disease activity in patients with rheumatoid arthritis

Background The purpose of this study was to investigate the efficiency of quantitative parameters of bone scintigraphy in detecting clinically active joint and high disease activity in patients with rheumatoid arthritis. Methods We retrospectively enrolled 65 patients with rheumatoid arthritis who underwent bone scintigraphy for diagnostic work-up. Quantitative analysis of bone scintigraphy images was conducted using an in-house software, and joint uptake ratio of 28 joints was measured for the calculation of the disease activity score of 28 joints using erythrocyte sedimentation rate (DAS28-ESR). The relationship between joint uptake ratio and clinical findings and the efficiency of joint uptake ratio in detecting clinically active joint and high disease activity were assessed. Results Clinically active joint (tender and/or swollen joints) showed significantly higher joint uptake ratio than did other non-affected joints (p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of joint uptake ratio for identifying clinically active joint were 78.7%, 52.0%, 32.9%, and 89.1%, respectively, and those of the summed joint uptake ratio for detecting high disease activity were 92.9%, 66.8%, 43.3%, and 97.1%, respectively; the joint uptake ratio showed high detection ability, especially for active joints of the elbow, wrist, and metacarpo-phalangeal joint areas. The summed joint uptake ratio of 28 joints showed a significantly strong positive correlation with DAS28-ESR (p < 0.001; correlation coefficient, 0.725). Conclusion Quantitative parameters of bone scintigraphy showed high sensitivity and NPV for detecting clinically active joint and high disease activity in patients with rheumatoid arthritis.

Platelet-to-lymphocyte Ratio can be used as Marker to Predict Activity and Severity in Moderate and High Disease Activity of Rheumatoid Arthritis: A Retrospective Study

Objective: This study aimed to study and evaluate the value of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) as markers to predict the disease activity and severity in patients with rheumatoid arthritis (RA).Methods: A total of 139 inpatients with RA were divided into two groups: moderate activity group (3.2<DAS28-CRP score<5.1) and high activity group (≥5.1). The correlation of routine hematological indices with DAS28 and joint ultrasound score (gray-scale ultrasound score, GS-US; power Doppler ultrasound score, PD-US; total ultrasound score, T-US) were analyzed by Pearson's correlation and logistic regression analyses. Receiver operating characteristics (ROC) analysis was performed to compare the efficacy of blood indices, ESR, or CRP in reflecting the disease activity and severity of RA.Results: The values of PLR, NLR, PD-US, and T-US were significantly different between moderate and high disease activity groups (p<0.001), and PLR was significantly correlated with PD-US and DAS28. Logistic regression analyses showed that PLR was an independent risk factor for disease activity by DAS 28 and joint damage severity by PD-US and T-US. ROC analysis showed that the efficacy of using PLR alone to evaluate the disease activity and joint severity of RA was similar to that of using combined CRP and ESR. The best cut-off value of PLR for predicting high disease activity and high joint severity was determined as 236.6.Conclusions: PLR can be used as a marker to predict activity and severity in patients with moderate and high RA disease activity.

Cladribine tablets are a cost-effective strategy in high-disease activity relapsing multiple sclerosis patients in Iran

Background: Cladribine tablets are the foremost oral immune-reconstitution therapy for high disease activity relapsing multiple sclerosis (HDA-RMS). We aimed to assess the cost-effectiveness of cladribine tablets compared to natalizumab in patients with HDA-RMS in Iran. Methods: A 5-year cohort-based Markov model was developed with 11 expanded disability status score (EDSS) health states, including patients with HDA-RMS as on and off-treatment. All costs were identified from the literature and expert opinion and were measured in Iranian Rial rates, changed to the 2020 USD rate and were discounted by 7.2%. Quality adjusted life years (QALY), discounted by 3.5%, and life years gained (LYG) were adopted to measure efficacy. The final results were presented as incremental cost-effectiveness ratio that was compared to a national willingness to pay (WTP) threshold of 1 to 3 gross domestic product (GDP) per capita. Deterministic and probabilistic sensitivity analyses (D/PSA) were employed to evaluate uncertainty. Results: Cladribine tablets dominated natalizumab and yielded 6,607 USD cost-saving and 0.003 additional QALYs per patient. LYG was comparable. The main cost component was drug acquisition cost in both arms. DSA indicated the sensitivity of the results to the cost discount rates and also the patients’ body weight; while they were less sensitive to the main clinical variables. PSA indicated that cladribine tablets were cost-effective in Iran, with a probability of 57.5% and 58.6% at lower and higher limits of threshold, respectively. Conclusion: Cladribine tablets yielded higher QALYs and lower costs compared to natalizumab, in patients with HDA-RMS in Iran.

The first experience of using upadacitinib in the treatment of rheumatoid arthritis in real clinical practice (results of the multicenter project “RACURS”)

Upadacitinib (UPA), a JAK inhibitor, is a new therapeutic option that allows patients with insufficient response to therapy with basic anti-inflammatory drugs (DMARDs) or genetically engineered biological drugs (GEBDs) to achieve the goals of therapy for rheumatoid arthritis (RA). Despite the availability of convincing data from international randomized clinical trials, there is insufficient information about the efficacy and safety profile of UPA, the quality of life of patients receiving the drug in real clinical practice.Aim of the study – to assess the efficacy and tolerability of the UPA drug at a dose of 15 mg/day in patients with rheumatoid arthritis with moderate and high disease activity and to assess their quality of life in real clinical practice.Materials and methods. The study included 41 patients with RA with insufficient effect of previous therapy with DMARDs or GEBDs, persisting moderate or high disease activity, who were initiated with UPA therapy in 7 rheumatological centers of the Russian Federation. To assess the activity of the disease, standard indices were used: DAS28- ESR, DAS28-CRP, SDAI, CDAI. Functional ability was assessed according to the HAQ questionnaire, quality of life – according to the EQ-5D questionnaire, the activity of the disease according to the patient’s opinion – according to the RAPID-3 index. The HADS scale was used to identify the states of depression, anxiety and emotional disorder.Results. During the first week of taking the drug, there was a marked decrease in pain from 60 to 30 mm on a visual analogue scale, which lasted until the third month of therapy. There was a statistically significant decrease in morning stiffness, the number of painful and swollen joints, health assessments by the doctor and patient, erythrocyte sedimentation rate and C-reactive protein (p≤0.001). A decrease in disease activity was also noted according to the dynamics of the activity indices DAS28, SDAI, CDAI (p<0.001). The goals of therapy (remission or low disease activity) by the 3rd month of therapy according to the combined indices of activity DAS28-ESR and DAS28-CRP reached 44.8 and 63.4% of patients, respectively, according to the SDAI index – 56.7%, according to the CDAI index – 25.9%. A pronounced improvement in joint function (70% improvement according to the criteria of the American College of Rheumatology) was noted by 33.3% of patients, population indicators of functional state (HAQ≤0.5) had 15.8% of patients. The difference in the HAQ index by the 3rd month of therapy compared to the indicator before treatment was –0.60 points. The quality of life, assessed by patients using the EQ-5D questionnaire, improved in 98.5% of patients, with a 70% improvement noted in more than a third of them (41.7%). The drug was well tolerated, no adverse reactions were registered by the 3rd month of therapy, all patients continued treatment.Conclusions. The first results of the use of UPA in RA patients with insufficient efficacy of previous therapy with DMARDs or GEBDs in real clinical practice indicate its efficacy and safety, an improvement in the functional state and quality of life of patients by the 12th week of the study.

High Disease Activity Influences the Presence of Vertebral Fractures in Rheumatoid Arthritis

Background: To investigate the prevalence and risk factors for vertebral fractures in patients with rheumatoid arthritis (RA) during an era of tight management.Methods: We retrospectively reviewed 426 RA patients who had visited our outpatient RA clinic between July 2017 and June 2020. Among them, we included 107 patients (19 males and 88 females) who had undergone lateral X-ray of the thoracolumbar spine and dual-energy X-ray absorption spectroscopy for the assessment of osteoporosis. We assessed the disease activity score for 28 joints (DAS28), the history of medication for RA and osteoporosis, the number and location of vertebral fractures, and the bone mineral density (BMD). Two board-certified specialists determined osteoporotic vertebral fractures on a lateral X-ray of the thoracolumbar spine.Results: The mean age, average disease duration, and average DAS28 of the analyzed patients were 67.9 years, 14.9 years, and 2.8, respectively. Vertebral fractures were found in 33 patients (30.8%). In this population, 84.8% of patients with vertebral fractures and 59.5% of those without vertebral fractures were treated for osteoporosis with active vitamin D3, bisphosphonate, and/or denosumab. RA patients with vertebral fractures had significantly higher DAS28 values, a higher rate of patients with a history of glucocorticoid use, and lower BMD in comparison to those than without vertebral fractures (p = 0.009, p = 0.004, and p = 0.01, respectively). Logistic regression analysis showed DAS28 (p = 0.038) and BMD (p = 0.004) were independent factors associated with the presence of vertebral fractures. The ordered logistic regression analysis also showed DAS28 (p = 0.043) and BMD (p = 0.024) were independent factors that explained the number of vertebral fractures.Conclusions: Vertebral fractures were frequently observed in RA patients, even when patients were treated the recommended anti-osteoporotic agents. A high disease activity score and low BMD were associated with the presence and number of vertebral fractures in patients with RA.

Systemic lupus erythematous presenting with hemorrhagic shock caused by gastric penetration of pancreatic pseudocyst: a case report

Background Systemic lupus erythematous that causes various organ damage is rarely associated with pancreatic lesion. To the best of our knowledge, no cases presenting with hemorrhage shock caused by gastric penetration of pancreatic pseudocyst due to lupus pancreatitis have been reported. Herein, we report a case of hemorrhage shock caused by gastric penetration of pancreatic pseudocyst due to lupus pancreatitis. Case presentation A 53-year-old Japanese man with a history of systemic lupus erythematous, pancreatic pseudocyst, and chronic pancreatitis complained of epigastric pain and had hematemesis. He visited our emergency room and was admitted in our hospital. Upper endoscopy showed that hemostasis was obtained; however, computed tomography scan was performed since he was suspected to have gastric penetration into hollow viscera. The computed tomography revealed accumulation of fluid around the pancreas and gastric penetration of pancreatic cyst. Blood test showed increased serum amylase level. These results suggest that the exacerbation of chronic pancreatitis causes the penetration. Surgery was considered; however, we took a wait-and-see approach since hemostasis was obtained. After that, he was in stable condition, although he suffered from fever and accumulation of left pleural effusion was observed by computed tomography. However, he had massive hematemesis and melena 9 days after hospitalization and died in spite of several treatments including blood transfusion. Autopsy revealed that he actually had pleural thickening, which is not caused by accumulation of left pleural effusion but by severe pleural inflammation. We therefore performed additional blood and urinary tests on the same day. The test results showed that he had a high titer of anti-double-stranded deoxyribonucleic acid (DNA) antibody, hypocomplementemia, and erythrocyturia, indicating that he had systemic lupus erythematous with high disease activity considering his fever and pleural inflammation. Conclusions Patients who have systemic lupus erythematous with high disease activity have the potential to develop fatal complications due to pancreatitis, so appropriate treatments are required for such patients.