Rheumatoid Arthritis Joint Research Articles

Use of TNF Inhibitors in Rheumatoid Arthritis and Implications for the Periodontal Status: For the Benefit of Both?

The inflammatory diseases rheumatoid arthritis (RA) and periodontitis show similarities in misbalances of cytokine levels, such as tumor necrosis factor-α (TNF-α). RA has been treated for two decades with TNF inhibitors which are effective by blocking TNF’s destructive action. Since RA and periodontitis show similarities in high levels of TNF, the periodontal status of RA patients may improve with the use of anti-TNF therapy. To assess this, a systematic review with special emphasis on duration of therapy was performed to evaluate the effect of anti-TNF-α treatment on the periodontal status of RA patients. Overall, studies showed an improvement in periodontal health with anti-TNF therapy. When analyzed over time (6 weeks to 9 months), it became apparent that initial improvements concerned bleeding on probing (BOP) and gingival index (GI) after therapy duration of 6 weeks. Periodontitis parameters that improved after prolonged treatment were: probing pocket depth (PPD) after 3 months and clinical attachment level (CAL) after 6 months. In conclusion, this systematic review reveals that anti-TNF treatment is therefore not only beneficial for rheumatic joints but also for the gums of rheumatoid arthritis patients. We propose that the sequential tissue recovery due to anti-TNF therapy progresses as follows: 1. block of diapedesis by lowering vessel permeability, 2 fewer leukocytes in the inflamed tissue, and 3. reduced proteolytic activity and subsequent repair of collagen fiber functionality and normalization of osteoclast activity. Clinically, this could lead to a decrease in bleeding on probing and ultimately in an improved clinical attachment level.

Quantitative Assessment of the Mandibular Condyle in Patients With Rheumatoid Arthritis Using Diffusion-Weighted Imaging

The purpose of this study was to quantitatively assess the mandibular condyle in patients with rheumatoid arthritis (RA) using the apparent diffusion coefficient (ADC) on diffusion-weighted imaging (DWI). Thirty-one patients with RA and temporomandibular joint (TMJ) pain who underwent magnetic resonance imaging (MRI) examination of the TMJs at our hospital between August 2006 and March 2020 were included in this study. Twenty-one patients with normal TMJs who underwent MRI examination at our hospital between August 2006 and March 2020 were included as controls. The MRI findings were compared between the 2 groups. The mean ADC values of the mandibular condyle in patients with RA were 1.20±0.17×10-3mm2/second. The mean ADC values of the mandibular condyle in patients with RA were significantly greater than the controls (P<.01). Receiver operating characteristic curve analysis revealed a cutoff of 0.89 for the ADC values of the mandibular condyle in patients with RA. The receiver operating characteristic curve analysis revealed areas under the curve for maximum ADC values of 0.98. Our study found that the ADC on DWI could be used for the quantitative assessment of the mandibular condyle in patients with RA, which indicated that the ADC on DWI could be useful for predicting RA.

Chronological effects of non-steroidal anti-inflammatory drug therapy on oxidative stress and antioxidant status in patients with rheumatoid arthritis

Non-steroidal anti-inflammatory drugs (NSAIDs) are effective in reducing pain and inflammation in rheumatoid arthritis and other joint- and muscle-associated diseases. However, the extensive, long-term, and over the counter administration of NSAIDs may cause various side effects in the patients. In the present study, the chronological effect of NSAIDs on oxidative stress and antioxidant status in patients with rheumatoid arthritis was studied. The study included 100 female individuals categorized in four major groups: (1) control group consisting of age- and gender-matched healthy individuals, (2) NRA-NSAID individuals taking NSAIDs without any history of RA, (3) RA individuals with a history of RA but not taking NSAIDs, and (4) RA-NSAID individuals with chronic RA and taking NSAIDs for a long period. The sera of the participants were analyzed for the oxidative stress and antioxidant status. The RA-NSAID group showed the significantly highest oxidative stress, in terms of malondialdehyde content and lipid-reducing ability as determined in thiocyanate and hemoglobin-induced linoleic acid systems. However, the free radical scavenging ability of the RA-NSAID group, against 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, superoxide, and 2,2-azino-bis-tetrazolium sulfate radicals, was found to be lower than those of the other study groups. The regression analysis of the experimental data showed a significant positive relationship between duration of NSAID intake and malondialdehyde production, lipid-reducing ability, and metal chelating ability in the RA-NSAID patients. The free radical scavenging abilities of the RA-NSAID group were negatively correlated with the duration of NSAID intake. The prolonged use of NSAIDs significantly increased the oxidative stress and decrease the antioxidant potential of both the RA patients and NRA individuals. The study provides awareness to the public particularly the RA patients regarding the risk of oxidative stress-associated abnormalities caused by the frequent and prolonged use of NSAIDs for temporary relief from pain. Key Points • The study presents the effects of long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) on antioxidant status of patients with rheumatoid arthritis. • The continuous administration of NSAIDs has been found to significantly increase the oxidative stress of the patients with rheumatoid arthritis as well as the individuals with no signs of rheumatoid arthritis. • The prolonged NSAID therapy also decreased the antioxidant potential of the patients with rheumatoid arthritis as well as the individuals with no signs of rheumatoid arthritis. • The study would be a significant and valuable contribution to the literature for the awareness regarding the use of NSAIDs.

Efficacy and safety of a single switch from etanercept originator to etanercept biosimilar in a cohort of inflammatory arthritis

AntiTNF-α biosimilars are broadly available for the treatment of inflammatory arthritis. There are a lot of data concerning the maintenance of clinical efficacy after switching from originators to biosimilars; therefore, such a transition is increasingly encouraged both in the US and Europe. However, there are reports about flares and adverse events (AE) as a non-medical switch remains controversial due to ethical and clinical implications (efficacy, safety, tolerability). The aim of our work was to evaluate the disease activity trend after switching from etanercept originator (oETA-Enbrel) to its biosimilar (bETA-SP4/Benepali) in a cohort of patients in Turin, Piedmont, Italy. In this area, the switch to biosimilars is stalwartly encouraged. We switched 87 patients who were in a clinical state of stability from oETA to bETA: 48 patients were affected by Rheumatoid Arthritis (RA),26 by Psoriatic Arthritis (PsA) and 13 by Ankylosing Spondylitis (AS).We evaluated VAS-pain, Global-Health, CRP, number of swollen and tender joints, Disease Activity Score on 28 joints (DAS28) for RA, Disease Activity in Psoriatic Arthritis (DAPSA) for PsA, Health Assessment Questionnaire (HAQ) and Health Assessment Questionnaire for the spondyloarthropathies (HAQ-S),Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS patients. 11/85 patients (12.6%) stopped treatment after switching to biosimilar etanercept. No difference was found between oETA and bETA in terms of efficacy. However, some arthritis flare and AE were reported. Our data regarding maintenance of efficacy and percentage of discontinuation were in line with the existing literature.

Pathology of bone epiphyses and frequency of various damage degree cases in patients with rheumatoid arthritis complicated by knee joint frontal deformities

Aim: based on several semi-quantitative morphometric indices, which represent pathological changes in femoral and tibial condyles, to determine pathological changes occurrence frequencies of damaged knee joints, complicated by frontal deformations. Materials and methods. Resected femoral and tibial condyles, obtained during knee replacement in 38 patients with rheumatoid arthritis and deformations of knee joints in frontal plane, served as material of current study. The following research methods were used: clinical examination, histological with semi-quantitative morphometric indices determination; statistical with determination of mean parameters, frequency of occurrence of cases with different gradations of indicators expression and their differences. Results. Groups of rheumatoid arthritis patients with lesions of knee joints complicated by deformities in frontal plane of different forms (valgus – varus), had significant differences by several clinical and clinical-visual indices. Pathological changes of epiphyses which are reflected by such morphometric parameters as “pannus structure and inflammation”, “inflammatory activity in subchondral spongiosa” and “stage of dystrophic-destructive changes of the joint surface” with different frequency and severity occur in the tissues of all rheumatoid arthritis patients with knee injuries, complicated by frontal deformations. In condyles from bones of one type, that form knee joint, compared in varus and valgus deformities, occurrence frequency of varying severity cases of separate morphometric indices varies in condyles according to different degree of compression. In condyles from bones of one type, which form knee joint, compared in different bones (femur and tibia) in cases of valgus deformity there was higher occurrence frequency of cases with more expressed indicator of “pannus structure and inflammation” in tibial condyles, in cases of varus deformity – in femoral condyles (independent of degree of compression). Conclusions. Results of study showed that degree of both clinical and morphometric indices of tibia and femur condyles condition in patients with rheumatoid arthritis and knee joint frontal deformities has no constant, unambiguous tendencies, and occurrence frequencies of cases with high and low degrees vary in wide limits.

Vitamin D3 receptor polymorphisms regulate T cells and T cell-dependent inflammatory diseases

It has proven difficult to identify the underlying genes in complex autoimmune diseases. Here, we use forward genetics to identify polymorphisms in the vitamin D receptor gene (Vdr) promoter, controlling Vdr expression and T cell activation. We isolated these polymorphisms in a congenic mouse line, allowing us to study the immunomodulatory properties of VDR in a physiological context. Congenic mice overexpressed VDR selectively in T cells, and thus did not suffer from calcemic effects. VDR overexpression resulted in an enhanced antigen-specific T cell response and more severe autoimmune phenotypes. In contrast, vitamin D3-deficiency inhibited T cell responses and protected mice from developing autoimmune arthritis. Our observations are likely translatable to humans, as Vdr is overexpressed in rheumatic joints. Genetic control of VDR availability codetermines the proinflammatory behavior of T cells, suggesting that increased presence of VDR at the site of inflammation might limit the antiinflammatory properties of its ligand.

Ethnobotanical Survey of Important Wild Medicinal Plants of Tehsil Gojra, District Toba Tek Singh, Punjab, Pakistan

Abstract Background: Almost every region of the world is stacked with a large number of medicinal plants. Medicinal plants are the major source to cure many diseases among the peoples of the world. There are still many areas in the world which have not been explored for its flora. Pakistan is also a rich with variety of flora but still there are some areas which need to be studied. This study was conducted to enlist the wild ethnomedicinally important plant species and traditional medicinal knowledge of Gojra, district Toba Tek Singh, Punjab, Pakistan. Methods: Field surveys were arranged to enlist the important medicinal plants and traditional knowledge from the local community through questionnaire and group discussion during 2019-2020. Data collected through questionnaire was consist of plant local name, medicinal use, method of use and part used. Results: There were more than 100 plant species including cultivated and wild but only 47 wild plants species were ethnomedicinally important as reported by local respondents that were placed in 20 families. It was noted that leaves had highest percentage (54%) of its use in various prescriptions. Acacia modesta Wall. (Fabaceae) was the most common tree used in teeth pain and gastritis with 0.73 UV (Use Value) and 0.075 RFC (Relative Frequency of Citation) values. Achyranthes aspera L. (Amaranthaceae) showed 0.85 UV and 0.088 RFC values and was used to cure fever, asthma and cough. For stomach, gastric and urinary disorders, Chenopodium album L. (Amaranthaceae) was used with 0.78 UV and 0.156 RFC values. Cichorium intybus L. (Asteraceae) has much importance in summer season as it is commonly used to reduce thirst in hot weather conditions. Its UV was 0.74 and RFC was 0.132. Leaves, fruits and barks of Dalbergia sissoo DC. (Fabaceae) was used to control nosebleed, gonorrhoea, stop vomiting and skin disorder. It has 0.72 UV and 0.075 RFC values. Eucalyptus globulus Labill. (Myrtaceae) was used to treat common cold, respiratory infections and asthma. Its leaves were used to provide steam to the asthma patients. It showed 0.76 UV and 0.08 RFC values. Ricinus communis L. (Euphorbiaceae) was a common weed in the area with 0.74 UV and 0.19 RFC values. Its seeds and leaves were useful to treat rheumatic pain, joint pain and constipation. Acacia modesta showed the highest Fidelity Level (FL) value that was 87% and used in teeth and gastric problems. Conclusions: It was concluded that there are many useful wild plants in Tehsil Gojra, district Toba Tek Singh, Punjab, Pakistan that are used in traditional medicines to cure many diseases. These plants also showed pharmacological importance that can be utilized to develop medicines. Keywords : Gojra, ethnobotany, flora, survey

Mass-spectrometric identification of carbamylated proteins present in the joints of rheumatoid arthritis patients and controls

Antibodies targeting post-translationally modified proteins, such as anti-carbamylated protein antibodies (anti-CarP antibodies) are present in the sera of rheumatoid arthritis (RA) patients. These autoantibodies associate with increased risk of RA development and with severity of joint destruction. It is not known which proteins in the RA joint are recognised by anti-CarP antibodies. Therefore, we investigated the presence and identity of carbamylated proteins in the human (inflamed) joint. We obtained synovium, cartilage and synovial fluid from RA joints. Cartilage and synovium were obtained from controls. Samples were processed and used for immunohistochemistry or mass-spectrometric analysis to investigate the presence of carbamylated proteins. Anti-CarP antibody reactivity towards identified carbamylated proteins was tested by ELISA. Immunohistochemistry showed extensive staining of RA and control synovial tissue. Whole proteome analyses of the joint tissues revealed a large number of carbamylated peptidyllysine residues. We identified many carbamylated proteins in cartilage and were also able to detect carbamylation in synovial tissue and synovial fluid. Carbamylation was not exclusive to the RA joint and was also present in the joints of controls. Anti-CarP antibodies in the sera of RA patients were able to recognise the identified carbamylated proteins. We conclude that numerous carbamylated proteins are present in the RA joint. These carbamylated proteins can be recognised by anti-CarP antibodies, substantiating the notion that anti-CarP antibodies may play a role in the pathogenesis of RA.

Incredible health benefits of adusa (Adhatoda vasica)

Adusa is a well-known herbal remedy used in Unani system of medicine for its beneficial effects, especially in bronchitis. The herb containing fresh, dried, ripe leaves of Adhatoda vasica Nees, Family Acanthaceae, is a sub-herbaceous bush which grows and found throughout the year in plains and sub-Himalayan tracts in India, ascending up to 1200 m., flowering occurs during February-March and also at the end of rainy season. Adusa leaves, bark, root bark, fruit and flowers help to remove intestinal parasites. Adusa herb is used in the treatment of cold, cough, bronchitis and asthma. In acute bronchitis especially when the sputum is thick and sticky, it gives unfailing relief. Its action on liquefying the sputum makes it easier for body to expel sputum. It’s dried leaves may be smoked to get relief from asthma. Local application of poultice of adusa leaves is also used with beneficial results over rheumatic joints, inflammatory swellings and fresh wounds. Scabies and other skin diseases may also be treated with a warm decoction of its leaves. In this paper general medicinal uses and pharmacological activities of various parts of this plant have been discussed and reviewed.

Altered Lymphatic Vessel Anatomy and Markedly Diminished Lymph Clearance in Affected Hands of Patients With Active Rheumatoid Arthritis

To assess differences between lymphatic function in the affected hands of rheumatoid arthritis (RA) patients with active synovitis and that of healthy controls, using indocyanine green (ICG) dye and near-infrared (NIR) imaging. NIR imaging of the hands of 8 patients with active RA and 13 healthy controls was performed following web space injection of 0.1 ml of 100 μM ICG. The percentage of ICG retention in the web spaces was determined by NIR imaging at baseline and at 7 days (±1 day) after the initial injections; image analysis provided contraction frequency. ICG+ lymphatic vessel (LV) length and branching architecture were assessed. Retention of ICG in RA hands was higher compared to controls (P < 0.01). The average contraction frequency of ICG+ LVs in RA patients and in controls did not differ (mean ± SD 0.53 ± 0.39 contractions/minute versus 0.51 ± 0.35 contractions/minute). Total ICG+ LV length in RA hands was lower compared to healthy controls (58.3 ± 15.0 cm versus 71.4 ± 16.1 cm; P < 0.001), concomitant with a decrease in the number of ICG+ basilic LVs in the hands of RA patients (P < 0.05). Lymphatic drainage in the hands of RA patients with active disease was reduced compared to controls. This reduction was associated with a decrease in total length of ICG+ LVs on the dorsal surface of the hands, which continued to contract at a similar rate to that observed in controls. These findings provide a plausible mechanism for exacerbation of synovitis and joint damage, specifically the accumulation and retention of inflammatory cells and catabolic factors in RA joints due to impaired efferent lymphatic flow. NIR/ICG imaging of RA hands is feasible and warrants formal investigation as a primary outcome measure for arthritis disease severity and/or persistence in future clinical trials.

The impact of pharmaceutical care on the efficacy and safety of transdermal glucosamine sulfate and capsaicin for joint pain.

Background Arthritis is a common chronic joint disease. It progressively causes joint pain, stiffness, and disability. Glucosamine sulfate has been shown to be an effective symptom-relieving biological agent. Pharmaceutical care, including patient counseling, is very important to overcome inconsistencies in compliance and adherence. Objective The aim of this study is to evaluate the impact of pharmaceutical care on the efficacy and safety of transdermal glucosamine sulfate and capsaicin (TGC-Plus cream) in the management of chronic joint pain. Settings A rheumatology outpatient clinic, Jordan University Hospital, Amman, Jordan. Methods A cross sectional study with a single treatment group was conducted. One hundred (100) patients diagnosed with either osteoarthritis, rheumatoid arthritis or chronic joint pains were recruited. Patients started on TGC-Plus cream applied twice daily for duration of 12weeks. Patients received pharmaceutical care services during the study duration. Main outcome measure Efficacy and safety of TGC-Plus cream in pain relief and jointfunction improvement (alleviating joint stiffness) the need of alternative analgesics and number of doctor's visits. Results There was a significant reduction of numericalpain score (7 ± 1.40 vs. 3.53 ± 2.13, p < 0.05), with significant reduction in the limitation ofjoint movement (6.18 ± 2.14 vs. 3.47 ± 2.23, p < 0.05) after 12weeks. In addition, the need for analgesics and the number of doctor's visits were significantly reduced (1.99 ± 2.77 vs. 0.71 ± 1.90, p < 0.05), (1.11 ± 1.28 vs. 0.06 ± 0.293, p < 0.05) respectively. Conclusion Pharmacist supervised treatment with the TGC-Plus cream significantly reduces pain and enhances locomotor function in patients with chronic pain who failed to achieve adequate prior pain relief.

Tocilizumab-Conjugated Polymer Nanoparticles for NIR-II Photoacoustic-Imaging-Guided Therapy of Rheumatoid Arthritis.

The progressive debilitating nature of rheumatoid arthritis (RA) combined with its unknown etiology and initial similarity to other inflammatory diseases makes early diagnosis a significant challenge. Early recognition and treatment of RA is essential for achieving effective therapeutic outcome. NIR-II photoacoustic (PA) molecular imaging (PMI) is emerging as a promising new strategy for effective diagnosis and treatment guidance of RA, owing to its high sensitivity and specificity at large penetration depth. Herein, an antirheumatic targeted drug tocilizumab (TCZ) is conjugated to polymer nanoparticles (PNPs) to develop the first NIR-II theranostic nanoplatform, named TCZ-PNPs, for PA-imaging-guided therapy of RA. The TCZ-PNPs are demonstrated to have strong NIR-II extinction coefficient, high photostability and excellent biocompatibility. NIR-II PMI results reveal the excellent targeting abilities of TCZ-PNPs for the effective noninvasive diagnosis of RA joint tissue with a high signal-to noise ratio (SNR) of 35.8 dB in 3D PA tomography images. Remarkably, one-month treatment and PA monitoring using TCZ-PNPs shows RA is significantly suppressed. In addition, the therapeutic evaluation of RA mice by NIR-II PMI is shown to be consistent with clinical micro-CT and histological analysis. The TCZ-PNPs-assisted NIR-II PMI provides a new strategy for RA theranostics, therapeutic monitoring and the beyond.

Variation in the definition of the examination of joints in rheumatoid arthritis: Results of a survey conducted on a group of Colombian rheumatologists

IntroductionIn the follow-up of rheumatoid arthritis (RA) patients, the physical examination of the joints in order to determine the number of painful and swollen joints is the cornerstone for determining activity. The objective of this study was to find out the opinion of a group of rheumatologists as regards the examination of joints of patients with RA to define the swollen or painful joint. At the same time an evaluation was made on the variation in the joints examination between the participants. MethodsA questionnaire was administered to a group of rheumatologists in order to determine general issues and examining each of the joints, as well as concepts of definitions of pain and inflammation in the joints. ResultsThe majority of the participants (78%) stated that all aspects were important, such as evaluating passive joint mobilisation, pain to palpation, and spontaneous pain. Passive mobility without having pain or swollen joint tenderness was said to be important by 53.8% of the participants, and 62.6% agreed with observing the pressure exerted by the examiner until the nail bed of the finger started to turn pale. As regards touching the margin of joint to determine swelling, 55% agreed, and 14.3% were not sure. Synovial effusion, fluctuation, and the alteration in the range of motion to define inflammation in the examination of joint were important for 47.2% of the examiners. Almost three-quarters agreed with the temporomandibular, acromioclavicular, sternoclavicular, shoulder and ankle joint technique. It was obvious that few were in accordance with the technique in the hip joint. When asked about more than one technique in some joints such as the MCF (57.1%) and mid tarsal (45%) joints, there was a decrease in the percentage of those who agreed with one of the 2 techniques. DiscussionApparently, there is no standard joint assessment method, since there were different opinions in the techniques proposed. This could be critical since examination of joints is the basis of the clinimetric examination in RA. A significant percentage of the group did not agree or were unsure of some components of the examination. This could lead to a variation in the concepts and a misclassification of patients in order to determine the activity of RA. This would also have an impact on the T2T or treat to target strategy. ConclusionThere was a wide variation in opinions about the concepts related to the examination of joints, such as defining swollen or painful joints in patients suffering RA. This requires a process of standardisation as the best recommended alternative.

Research on Application of Improved Random Forest in Medical Ultrasound Image Classification

Gray-scale ultrasound imaging methods are commonly used to assess synovitis in Rheumatoid Arthritis (RA) in clinical practice. This paper proposed an improved classification algorithm for ultrasound image of metacarpophalangeal joint in Rheumatoid Arthritis(RA). Using several features of gray scale co-occurrence matrix and improved Random Forest method to achieve automatic classification of Rheumatoid Arthritis(RA). Three grading experiments were carried out in the experiment: the first one is for the binary classification of grade 0 (normal) and grade 3 (lesion) ultrasound images of 80 × 50 pixels, 130 × 70 pixels, and 185 × 90 pixels. The second is for the binary classification of grade 0 (normal) and grade 1/2/3 (lesion) ultrasound images of 80 × 50 pixels, 130 × 70 pixels, and 185 × 90 pixels. The third is for four-grade classification of ultrasound images at grade 0(normal), grade 1(mild), grade 2(moderate), and grade 3(severe). Conclusion shows that use the method of combing gray scale co-occurrence matrix and improved Random Forest algorithm can achieve automatic classification of Rheumatoid Arthritis(RA), which has a high Classification Accuracy.

Cell Biology in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease, which affects about 0.33 to 2.65% of the population. In RA Synovium contain various type of immune cell. In which only one cell population cannot cause rheumatoid arthritis that requires more than one cell population. In normal condition, they act as a switch (active or inactive the cell signaling). It controls cell growth, proliferation or metastasizes. In an autoimmune disorder such as rheumatoid arthritis, the immune system mistakenly attacks and destroys the body's cells and tissues. Mostly cells are present in limited numbers in normal human synovium, but in rheumatoid arthritis and other inflammatory joint diseases, this population can expand to constitute 5-20% or more of all synovial cells. Recent investigations in a murine model have demonstrated that cells can have a critical role in the generation of inflammation within the joint.&#x0D; Keyword: Cell Biology in rheumatic arthritis; Dendrite cell; T-cell; Mast cell; Fibroblastic cell; Macrophages cell.

Efficacy and safety of switching from reference adalimumab to SB5 in a real-life cohort of inflammatory rheumatic joint diseases.

SB5 showed comparable efficacy and safety profile in respect to adalimumab originator (ADA) in randomized clinical trials of rheumatoid arthritis (RA) and psoriasis. We aimed to describe the efficacy and safety of SB5 after switching from ADA in RA, axial spondyloarthritis (axSpA), psoriatic arthritis (PsA) and juvenile idiopathic arthritis (JIA) patients. Adult RA, PsA, axSpA, JIA patients treated with ADA for at least 6months, switched to SB5 in stable clinical conditions, were eligible. Data on safety, activity indexes and patient-reported outcomes were collected at baseline, 3 and 6months after switching. Eighty-two patients (19 RA, 28 PsA, 32 axSpA and 3 JIA; 45 females, mean age 54 ± 14years, disease duration 13 ± 7years, ADA duration 6 ± 3years) were enrolled. RA patients showed stable conditions, while PsA patients showed an increase in both HAQ, DAS28(CRP) and DAPSA and axSpA patients an increase in VAS pain, VAS patient disease activity and ASDAS, both at 3months. There were changes in the concomitant medications profile, with regression of activity indexes increases at 6months. Adverse events were reported by 33.7% patients at 3months and 16.6% patients at 6months, mostly disease flares and infectious events. Two patients stopped SB5. Despite temporary changes in the concomitant medication profile for mild disease flares, our real-life data replicate the safety profile of switching from ADA to SB5 in RA, with additional data for its applicability in PsA and axSpA patients, further supporting switching to biosimilars in treating inflammatory rheumatic conditions. Key Points • Switching from adalimumab originator to SB5 is feasible in real life rheumatic inflammatory joint diseases. • Mild disease flares can present after switching from originator adalimumab to SB5, in particular in axial spondyloarthritis and psoriatic arthritis. • Changes in concomitant medications profile allows the control of minor disease flares presenting after switching from adalimumab originator to SB5.

AB1134 ULTRASOUND FINDINGS IN HAND JOINTS INVOLVEMENT: A COMPARATIVE STUDY BETWEEN PSORIATIC AND RHEUMATOID ARTHRITIS

Background:Psoriasis is a common skin disease that is associated with multiple conditions. The most prevalent coexisting condition is psoriatic arthritis (PsA) which develops in up to 30% of patients with psoriasis and characterized by diverse clinical features often resulting in delayed diagnosis and treatment. [1]Objectives:The aim of this study was to investigate the potential of ultrasound (US) in the differential diagnosis between rheumatoid arthritis (RA) and PsA at the level of small joints of the hand and wrist.Methods:Fifteen patients with PsA of the hands and wrists and 20 age and sex-matched RA patients were examined with musculoskeletal US. Radiocarpal, midcarpal, distal radioulnar, metacarpophalangeal (MCP), proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints and flexor and extensor tendons (in wrist and hand) were examined bilaterally. Synovitis, erosions and tenosynovitis were scored according to semiquantitative method.[2]Results:Among 510 and 680 joints examined in PsA and RA respectively, certain US features such as synovitis and erosions at the DIP were exclusively detected in PsA (p&lt;0.001). Synovitis was frequently present at the radioulnar joints in RA in comparison to PsA patients (52.5% vs 26.7% respectively, p=0.029). Joint effusion was frequently detected at radiocarpal and midcarpal joints in RA in comparison to PsA (p=0.047, 0.039 respectively). Effusion at the 3rdPIP joints was more significantly present in PSA than RA (p=0.037),while erosions were significantly detected at radiocarpal joints in RA in comparison to PsA patients (45%vs 20%respectively,p=0.029).Tenosynovitis was significantly detected at the extensor tendons in RA and at the flexor tendons in PsA patients (p=0.021, 0.022 respectively).Conclusion:There are significant differences in the US findings of the hand and wrist that can help to distinguish between RA and PsA

THU0624-HPR COMPARISON OF WRIST PROPRIOCEPTION, GRIP STRENGTH AND PINCH STRENGTH IN PATIENTS WITH PSORIATIC ARTHRITIS AND RHEUMATOID ARTHRITIS: PRELIMINARY STUDY

Background:Hand articular damage occurs in rheumatoid arthritis (RA) and functional ability deteriorates as the disease progresses. Limitation of hand motion, oedema, pain etc. factors contribute to reduce grip strength, pinch strength and joint position sense; this problems contribute to function and disability. Following RA, affecting grip and pinch strength (1) and joint position sense (2) was reported former research. But there is a little knowledge about disabilitiy of hand functions in psoriatic arthritis (PsA).Objectives:To compare joint position sense, grip strength and pinch strength in patient with PsA and RA.Methods:In our cross sectional study, 23 RA patients [Mean age; 52.7±12.6, Women:20(87.0%)] who were classified according to the ACR 2010 criteria and 19 PsA patients [Mean age 53.5±12.6, Women:14 (%73.7)] who were classified according to the CASPAR criteria were included.It was recorded demographic and clinical data of patients. Wrist position sense was evaluated by goniometric re-position error test (in 30◦ wrist extansion, 3 repeat). Grip strenght was examined using a hand dynamometer (Lafayette Proffessional Hand Dynamometer, USA) and pinch strength (two point, three point, lateral) was evaluated by pinchmeter (Lafayette,USA).Results:Patients were similar in terms of age, gender, disease duration, morning stiffness duration, pain of hand joints, number of tender and swallen joints and disease activity (p&gt;0.05). RA patients had longer disease duration (p=0.004) and lower ESR levels (p=0.046) compared to PsA. Grip and pinch strength were found similar in both dominant and non-dominant side between RA and PsA patients (Table 1). Wrist joint position error was higher in PsA group in non-dominant side (p=0.011).Table 1.Comparison of Groups for Grip and Pinch Strength and Joint Position SenseVariablesRA(n=23)Median(IQR)PsA(n=19)Median(IQR)p*Grip StrengthDominantNon-dominant20(14/25)20(14/25)25(20/29)21(15/26)0.1090.404Pinch StrengthDominant2 Point3 PointLateralNondominant2 Point3 PointLateral3.1(2.2/3.8)3(2.3/4.0)3.4(3.0/4.2)3(1.9/3.7)2.8(2.3/3.8)2.9(2.5/4.0)3(2.2/3.4)3.4(2.5/4.20)3.5(2.6/4.5)3(2.4/3.7)3.1(2.3/4.2)3.2(2.4/4.2)0.8100.4710.8400.7140.7230.561Joint Position ErrorDominantNon-dominant6(5/7)6(3/8)7(5/9)8(6/11)0.2340.011Data have shown as median (interquartile range 25-75) *Mann Whitney-U TestConclusion:Our study showed that patients with PsA had hand impairment as much as RA patients. We think, hand assessment in patients with PsA rehabilitation programme is essential for clinicians. There is need future studies including asymptomatic healthy group to interpret of results in detailed.

Drug screening and identification of key candidate genes and pathways of rheumatoid arthritis.

Rheumatoid arthritis (RA), which normally manifests as a multi-joint inflammatory reaction, is a common immunological disease in clinical practice. However, the pathogenesis of RA has not yet been fully elucidated. Rituximab (RTX) is an effective drug in the treatment of RA, however its therapeutic efficacy and mechanism of action require further investigation. Thus, the present study aimed to screen the candidate key regulatory genes and explain the potential mechanisms of RA. Gene chips of RA and normal joint tissues were analyzed and, gene chips of RTX before and after treatment were investigated. In the present study, strong evidence supporting the pathogenesis of RA and mechanism of action of RTX were also revealed. Differentially expressed genes (DEGs) were analyzed using the limma package of RStudio software. A total of 1,150 DEGs were detected in RA compared with normal joint tissues. The upregulated genes were enriched in ‘interleukin-12 production’, ‘I-κB kinase/NF-κB signaling’, ‘regulation of cytokine production involved in immune response’ and ‘cytokine metabolic process’. Functional enrichment analysis showed that RTX was primarily involved in the inhibition of ‘adaptive immune response’, ‘B cell activation involved in immune response’ and ‘immune effector process’. Subsequently, leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1), a hub gene with high connectivity degree, was selected, and traditional Chinese medicine libraries were molecularly screened according to the structure of the LILRB1 protein. The results indicated that kaempferol 3-O-β-D-glucosyl-(1→2)-β-D-glucoside exhibited the highest docking score. In the present study, the DEGs and their biological functions in RA and the pharmacological mechanism of RTX action were determined. Taken together, the results suggested that LILRB1 may be used as a molecular target for RA treatment, and kaempferol 3-O-β-D-glucosyl-(1→2)-β-D-glucoside may inhibit the pathological process of RA.

Enhanced Pro-apoptotic Effects of Fe(II)-Modified IVIG on Human Neutrophils.

Mild modification of intravenous immunoglobulin (IVIG) has been reported to result in enhanced polyspecificity and leveraged therapeutic effects in animal models of inflammation. Here, we observed that IVIG modification by ferrous ions, heme or low pH exposure, shifted the repertoires of specificities in different directions. Ferrous ions exposed Fe(II)-IVIG, but not heme or low pH exposed IVIG, showed increased pro-apoptotic effects on neutrophil granulocytes that relied on a FAS-dependent mechanism. These effects were also observed in human neutrophils primed by inflammatory mediators or rheumatoid arthritis joint fluid in vitro, or patient neutrophils ex vivo from acute Crohn's disease. These observations indicate that IVIG-mediated effects on cells can be enhanced by IVIG modification, yet specific modification conditions may be required to target specific molecular pathways and eventually to enhance the therapeutic potential.