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In the autoimmune disease rheumatoid arthritis (RA), inflammatory cytokines drive synovial hyperplasia which leads to progressive destruction of cartilage and bone. Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine that activates human RA synovial fibroblasts (RASFs) to produce chemokines that recruit inflammatory cells to the joint, and adhesion molecules that contribute to destructive synovial pannus formation. TNF-α triggers production of additional inflammatory cytokines including interleukin-6 (IL-6), which further activates RASFs through its trans-signaling mechanism. TNF inhibitors are now commonly used to treat RA and other autoimmune diseases, but prolonged systemic inhibition of TNF-α increases the risk of infection and malignancy, underscoring the need for alternate therapeutic approaches. Extracellular sulfatase-1 (Sulf-1) and sulfatase-2 (Sulf-2) are known to play key roles in growth factor and cytokine signaling, especially in musculoskeletal tissues. However, these enzymes have not been examined in the context of RA or in TNF-α signaling. Our studies demonstrate that extracellular sulfatases, especially Sulf-2, are highly upregulated in synovial tissues and serum of RA patients and the TNF-α transgenic mouse model of RA. Our in vitro experiments in human RASFs show that transient knockdown of Sulf-2 significantly modulates TNF-α inflammatory pathways, based on analysis of differentially expressed genes (DEGs). This work focuses primarily on Sulf-2 loss-of-function studies which demonstrate potentially therapeutic dampening effects on known inflammatory targets in RA pathogenesis. We show that knockdown of Sulf-2 limits TNF-α signaling through PKCδ and JNK pathways, significantly reducing nuclear translocation of inflammatory transcription factors NF-κB and AP-1. In addition, pharmacologic inhibition of Sulf-2 using the small molecule inhibitor OKN-007 abrogates TNF-α-induced adhesion molecules (ICAM-1, VCAM-1, cadherin-11) and inflammatory chemokines (CCL2, CCL5, CXCL5, CXCL10 and CXCL11). Interestingly, our studies show that stimulation of RASFs with IL-6 and its soluble receptor induces expression of Sulf-2, and that knockdown of Sulf-2 inhibits IL-6-induced JAK1 and downstream production of inflammatory mediators. These findings reveal novel molecular mechanisms by which Sulf-2 contributes to inflammatory cytokine signaling in RASFs, which may lead to new therapeutic approaches aimed at the site of joint destruction with reduced risks from systemic immunosuppression.

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, affecting 0.5% to 1% of the population. It could ultimately result in joint destruction, functional decline, work disability, and enhanced mortality. Cyclic citrullinated peptide antibodies (CCP Abs) are useful biomarkers for the early detection and diagnosis of RA. In this study, we used plant viral-based expression vectors that produce rapidly large quantities of CCP-specific monoclonal antibodies. Heavy and light chain genes of a CCP monoclonal antibody (CCP mAb) were cloned from the hybridoma cell (12G1) and introduced into two separate plant viral-based expression vectors, TMV and PVX. A cyclic citrullinated peptide monoclonal antibody was produced in Nicotiana benthamiana through an Agrobacterium-mediated transient expression system. The expression of CCP mAb in tobacco plants was confirmed by dot blot, western blot analysis, and enzyme-linked immunosorbent assays (ELISA). It was shown that tobacco plants could accumulate CCP mAbs up to 0.35% of total soluble protein. Accumulated CCP mAb from infiltrated leaves was purified by protein G affinity chromatography. Immunoblot assays and ELISA showed plant-produced CCP mAbs successfully bound to a synthetic CCP peptide antigen. This system provides a fast strategy for the production of pharmaceutical CCP mAbs in tobacco plants.

The aim of the present study is to assess the knowledge and attitudes towards periodontal health among rheumatologists and rheumatoid arthritis (RA) patients. Two questionnaires comprising questions on demographics, knowledge, and attitudes towards periodontal health were created via Qualtrics survey software. A link to the survey was sent via email to rheumatologists registered under the Australian Rheumatology Association (ARA) practising in Western Australia, and a separate survey was distributed to patients via Arthritis and Osteoporosis WA social media pages. Seven and 76 responses were received from rheumatologists and RA patients, respectively. Statistically significant results (p < 0.05) were found between the length of RA diagnosis and signs of periodontal disease, as well as the type of RA diagnosis and knowledge levels. Employed and retired participants attended the dentist more regularly, and a higher percentage believed that maintaining good oral hygiene is important for overall health. A significant correlation was found between patients who thought improving oral hygiene would impact their RA and whether they received periodontal treatment. No significant differences were found for rheumatologists; however, younger practitioners more frequently asked about their patients’ oral health and performed oral exams. There is a deficit in knowledge about the relationship between periodontal disease and RA among both rheumatoid patients and rheumatologists. The high prevalence of periodontitis and the two-way relationship between RA and periodontal disease would benefit from improved knowledge in relation to their association and could have significant benefits in their clinical and public health implications.

Background: Effects of anti-citrullinated polypeptide antibodies (ACPA) on the bone mineral density (BMD) reduction and incidence of major osteoporotic fractures (MOF) in patients with rheumatoid arthritis (RA) were evaluated using a retrospective longitudinal case-control study. Methods: Patients with RA who were examined using dual-energy X-ray absorptiometry and simultaneously treated for more than 5 years were recruited. BMD absolute value and Z-scores at initial measurements (baseline) and changes of these values from baseline were assessed, and associations between BMD and candidate risk factors including ACPA positivity and serum titer levels were statistically evaluated. Additional statistical evaluations of ACPA positivity in regard to the incidence of MOF were tested. Results: A total of 222 patients were included. Higher ACPA titers correlated significantly with lower BMD and Z-scores at baseline using a multivariate model (p < 0.05). ACPA positivity correlated significantly with lower values and an annual decrease in the Z-score in total hip at follow-up using a univariate model (p < 0.05), whereas no significant correlation was found using a multivariate model. Z-scores in the ACPA-positive group were significantly lower than those of the ACPA-negative group (p < 0.05). However, ACPA-positivity demonstrated no higher risk for incident MOF. Conclusions: The presence of ACPA is a potential risk of BMD loss however weak.

Introduction Rheumatoid arthritis (RA) is associated with significant morbidity and economic burden. This study aimed to compare baseline characteristics and patterns of anti-inflammatory drug use and disease-modifying anti-rheumatic drug (DMARD) use among patients with RA in Southern Italy versus the United States. Method Using Caserta Local Health Unit (Italy) and Optum’s de-identified Clinformatics® Data Mart (United States) claims databases, patients with ≥ 2 diagnosis codes for RA during the study period (Caserta: 2010–2018; Optum: 2010–2019) were identified. Baseline patient characteristics, as well as proportion of RA patients untreated/treated with NSAIDs/glucocorticoids/conventional DMARDs (csDMARDs)/biological/targeted synthetic DMARDs (b/tsDMARDs) during the first year of follow-up, and the proportion of RA patients with ≥ 1 switch/add-on between the first and the second year of follow-up, were calculated. These analyses were then stratified by age group ( Results A total of 9227 RA patients from Caserta and 195,951 from Optum databases were identified (two-thirds were females). During the first year of follow-up, 45.9% RA patients from Optum versus 79.9% from Caserta were exclusively treated with NSAIDs/glucocorticoids; 17.2% versus 11.3% from Optum and Caserta, respectively, were treated with csDMARDs, mostly methotrexate or hydroxychloroquine in both cohorts. Compared to 0.6% of RA patients from Caserta, 3.2% of the Optum cohort received ≥ 1 b/tsDMARD dispensing. Moreover, 61,655 (33.7%) patients from Optum cohort remained untreated compared to 748 (8.3%) patients from the Caserta cohort. The subgroup analyses stratified by age showed that 42,989 (39.8%) of elderly RA patients were untreated compared to 18,666 (24.9%) young adult RA patients in Optum during the first year of follow-up. Moreover, a higher proportion of young adult RA patients was treated with b/tsDMARDs, with and without csDMARDs, compared to elderly RA patients (Optum: 6.4%; Optum≥65: 1.0%; P-value : 0.8%; Caserta≥65: 0.1%; P-value : 7.8%; Optum≥65: 1.8%; Caserta: 3.2%; Caserta≥65: 0.6%). Conclusions Most of RA patients, with heterogeneous baseline characteristics in Optum and Caserta cohorts, were treated with anti-inflammatory/csDMARDs rather than bDMARDs/tsDMARDs during the first year post-diagnosis, especially in elderly RA patients, suggesting a need for better understanding and dealing with barriers in the use of these agents for RA patients. Key Points • Substantial heterogeneity in baseline characteristics and access to bDMARD or tsDMARD drugs between RA patients from the United States and Italy exists. • Most of RA patients seem to be treated with anti-inflammatory/csDMARD drugs rather than bDMARD/tsDMARD drugs during the first year post-diagnosis. • RA treatment escalation is less frequent in old RA patients than in young adult RA patients. • An appropriate use of DMARDs should be considered to achieve RA disease remission or low disease activity.

BackgroundLymphocyte activation gene-3 (LAG-3) inhibits T cell activation and interferes with the immune response by binding to MHC-II. As antigen presentation is central in rheumatoid arthritis (RA) pathogenesis, we studied aspects of LAG-3 as a serological marker and mediator in the pathogenesis of RA. Since Galectin-3 (Gal-3) is described as an additional binding partner for LAG-3, we also aimed to study the functional importance of this interaction.MethodsPlasma levels of soluble (s) LAG-3 were measured in early RA patients (eRA, n = 99) at baseline and after 12 months on a treat-to-target protocol, in self-reportedly healthy controls (HC, n = 32), and in paired plasma and synovial fluid (SF) from chronic RA patients (cRA, n = 38). Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were examined for LAG-3 expression by flow cytometry. The binding and functional outcomes of LAG-3 and Gal-3 interaction were assessed with surface plasmon resonance (SPR) and in cell cultures using rh-LAG3, an antagonistic LAG-3 antibody and a Gal-3 inhibitor.ResultsBaseline sLAG-3 in the plasma was increased in eRA compared to HC and remained significantly elevated throughout 12 months of treatment. A high level of sLAG-3 at baseline was associated with the presence of IgM-RF and anti-CCP as well as radiographic progression. In cRA, sLAG-3 was significantly increased in SF compared with plasma, and LAG-3 was primarily expressed by activated T cells in SFMCs compared to PBMCs. Adding recombinant human LAG-3 to RA cell cultures resulted in decreased cytokine secretion, whereas blocking LAG-3 with an antagonistic antibody resulted in increased cytokine secretion. By SPR, we found a dose-dependent binding between LAG-3 and Gal-3. However, inhibiting Gal-3 in cultures did not further change cytokine production.ConclusionssLAG-3 in the plasma and synovial fluid is increased in both early and chronic RA patients, particularly in the inflamed joint. High levels of sLAG-3 are associated with autoantibody seropositivity and radiographic progression in eRA, and LAG-3 plays a biologically active role in cRA by decreasing inflammatory cytokine production. This functional outcome is not affected by Gal-3 interference. Our results suggest that LAG-3 is a faceted regulator of inflammation in early and chronic RA.

Background Traditional dogma regarding management of rheumatoid arthritis (RA) patients with trigger digit symptoms holds that A1 pulley release should be avoided. Surgical release was thought to further destabilize the metacarpophalangeal joint. Biologic disease modifying anti-rheumatic drugs (DMARDs) have limited the development of hand deformities. Despite advances in RA treatment, many textbooks continue to discourage release of the A1 pulley in RA patients. The aim of this study was to determine if this belief is consistent with current trends in surgical management of trigger digits in patients with RA. Methods Active Members of the American Society for Surgery of the Hand (ASSH) were surveyed on their training and current practices as related to RA patients with trigger digits. Results Five hundred three surveys were completed (16% response rate). During training, 55% of ASSH Members were taught to avoid releasing the A1 pulley in RA patients. Seventy-one percent of respondents currently release the A1 pulley in RA patients with no preexisting deformities, no tenosynovial thickening, or if tenosynovectomy and flexor digitorum superficialis slip excision fail to relieve triggering. Forty percent reported that their practice has evolved toward more frequent release of the A1 pulley in RA patients. Conclusion The majority of ASSH Active Members were taught during training to avoid surgical release of the A1 pulley in RA patients to prevent acceleration of finger deformities. Indications and contraindications for A1 pulley release are evolving along with the improved natural history of RA associated with the use of biologic DMARDs.

Background. Rheumatoid arthritis (RA) and periodontitis (PD) are chronic diseases that are associated with connective tissue and bone destruction, which affects the quality of life of the people suffering from these conditions. The identification of social conditions and the determinants of RA and PD would permit the elaboration of policies and strategies based on social reality. Objectives. The aim of the present study was to identify the relationship between oral health-related quality of life (OHRQoL) and the indicators of general health and oral health in patients with RA. Material and methods. A cross-sectional study involving 59 patients with RA was conducted between 2019 and 2020. Demographic, general health, periodontal, and oral health parameters were collected. In addition, the Oral Health Impact Profile-14 (OHIP-14) questionnaire was administered to each patient. A description of the OHIP-14 dimensions according to different variables was performed. The relationship between OHRQoL and general/oral health indicators was analyzed with logistic and linear regression analyses. Results. The highest OHIP-14 scores were found in people that were 60 years of age and over, single, had low educational achievements, a low socioeconomic status, were unemployed, and had no health affiliation. In the adjusted model, the prevalence of the impact on OHRQoL was 1.34 (1.10–5.29) times greater in those with erosive RA than in those without, and 2.22 (1.16–29.50) times greater in those who self-reported morning stiffness. Regarding the stage of PD, those with stage IV had a prevalence of the impact on the OHRQoL of 70%, an average extent of 3.4 ±4.5 and a severity score of 11.5 ±22.0, with statistically significant differences. Conclusions. The dimensions with the greatest impact on the OHRQoL of patients were physical pain, discomfort and psychological disability. The type of RA and the severity of PD are indicators of worse scores on the OHRQoL scale. This study was funded with a grant (CODI 2015-6263) from the University of Antioquia, Medellín, Colombia.

Patients with arthralgias who could be at risk of progressing to rheumatoid arthritis (RA) represent a clinical challenge. Recommendations for their management and treatment are lacking. The purpose of the present study was to determine how Argentinean rheumatologists deal with these patients. We developed an anonymous ad hoc survey which was sent to 522 Argentinean rheumatologists. The RA study group of our Argentinean Rheumatology National Society assisted in forwarding the surveys to its members via the internet (e-mail or WhatsApp). The findings of the collected data are presented as descriptive statistics. The questionnaires were completed by 255 rheumatologists (overall response rate of 48.9%), and 97.6% confirmed that their practices had received medical consultations to rule out RA in patients with arthralgias. Ultrasound (US) was the method of first choice (93.7%) as part of the evaluation of these patients. For those in whom US power Doppler signal was present in at least one joint, 93.7% of the participants would start treatment and methotrexate was the first choice (58.1%). In patients with tenosynovitis but no synovitis on US, most rheumatologists would start treatment (89.4%), being NSAIDs the drug of first choice (52.3%). Argentinean rheumatologists evaluate patients with imminent RA and treat them based on their clinical judgment and findings from the US evaluation of affected joints; the drug of first choice for these patients among these rheumatologists was methotrexate. Despite published data of recent clinical trials, recommendations for the management and treatment of these patients are necessary.

Introduction: One target of rheumatoid arthritis (RA) treatment is to achieve early sustained remission; over the long term, patients in sustained remission have less structural joint damage and physical disability. We evaluated Simplified Disease Activity Index (SDAI) remission with abatacept + methotrexate versus abatacept placebo + methotrexate and impact of de-escalation (DE) in anti-citrullinated protein antibody (ACPA)-positive patients with early RA. Methods: The phase IIIb, randomized, AVERT-2 two-stage study (NCT02504268) evaluated weekly abatacept + methotrexate versus abatacept placebo + methotrexate. Primary endpoint: SDAI remission (& LE; 3.3) at week 24. Pre-planned exploratory endpoint: maintenance of remission in patients with sustained remission (weeks 40 and 52) who, from week 56 for 48 weeks (DE period), (1) continued combination abatacept + methotrexate, (2) tapered abatacept to every other week (EOW) + methotrexate for 24 weeks with subsequent abatacept withdrawal (abatacept placebo + methotrexate), or (3) withdrew methotrexate (abatacept monotherapy). Results: Primary study endpoint was not met: 21.3% (48/225) of patients in the combination and 16.0% (24/150) in the abatacept placebo + methotrexate arm achieved SDAI remission at week 24 (p = 0.2359). There were numerical differences favoring combination therapy in clinical assessments, patient-reported outcomes (PROs) and week 52 radiographic non-progression. After week 56, 147 patients in sustained remission with abatacept + methotrexate were randomized (combination, n = 50; DE/withdrawal, n = 50; abatacept monotherapy, n = 47) and entered DE. At DE week 48, SDAI remission (74%) and PRO improvements were mostly maintained with continued combination therapy; lower remission rates were observed with abatacept placebo + methotrexate (48.0%) and with abatacept monotherapy (57.4%). Before withdrawal, de-escalating to abatacept EOW + methotrexate preserved remission. Conclusions: The stringent primary endpoint was not met. However, in patients achieving sustained SDAI remission, numerically more maintained remission with continued abatacept + methotrexate versus abatacept monotherapy or withdrawal.

T-cell leukemia translocation-associated gene (TCTA) protein is expressed ubiquitously in normal human tissues, but its function is not completely understood. We have demonstrated that TCTA protein is essential for human osteoclastogenesis induced by NF-kB ligand (RANKL), inhibits the proliferation of both small-cell lung carcinoma and fibroblast-like synoviocytes in rheumatoid arthritis (RA), and may act as a coupling factor in bone metabolism. In the current study, we constructed a high sensitivity sandwich ELISA system and measured the concentration of soluble TCTA protein-derived products (sTDP), which include an inhibitor of human osteoclastogenesis, in the peripheral blood from two groups of untreated patients with early-onset RA and normal volunteers (NV). In the first group, the concentration of sTDP was significantly higher in the 4 RA patients than in the 3 NV (p=0.0339). The level of C-reactive protein(CRP) in serum was not correlated with the concentrations of sTDP in the RA patients. We confirmed these results by analyzing the second group, which was comprised of 22 untreated patients with early-onset RA and 5 NV. In conclusion, sTDP levels were elevated in untreated patients with early-onset RA independent of inflammation. These findings suggest that sTDP play an important role in the pathogenesis of RA by inhibiting both osteoclastogenesis and the proliferation of fibroblast-like synoviocytes.

Introduction: The efficacy of sarilumab and upadacitinib, in combination with disease-modifying antirheumatic drugs (DMARDs), was demonstrated in phase 3 clinical trials of patients with rheumatoid arthritis (RA) refractive to previous biologic DMARDs. In the absence of head-to-head clinical trials, the matching-adjusted indirect comparison (MAIC) and simulated treatment comparison (STC) estimate the relative efficacy of sarilumab and upadacitinib in patients with RA who had an inadequate response to previous biologic DMARDs. Methods:Patient-level data for sarilumab were obtained from the TARGET trial (NCT01709578) and published aggregate data for upadacitinib were obtained from the SELECT-BEYOND trial (NCT02706847). For the MAIC, individual patient data from the TARGET trial were assigned weights such that weighted mean baseline characteristics of the treatment effect modifiers matched those from SELECT-BEYOND. For the STC, the TARGET patient-level data and mean baseline values from SELECT-BEYOND were used to simulate sarilumab treatment effects for a SELECT-BEYOND population. Endpoints evaluated included the American College of Rheumatology (ACR) response criteria ACR20/50/70, Disease Activity Score-28 for Rheumatoid Arthritis with C-reactive protein (DAS28-CRP) < 3.2, DAS28-CRP < 2.6, Simple Disease Activity Index (SDAI) < 3.3, and Clinical Disease Activity Index (CDAI) < 2.8 at 12 weeks. Results: The analysis included 365 patients from TARGET and aggregated data of 333 patients from SELECT-BEYOND. Matching for potential treatment effect baseline modifiers (i.e., age, oral glucocorticoid use, tender joint count of 68 counts, swollen joint count of 66 counts, serum CRP level, and patient global assessment of disease activity) resulted in a reduction of the effective sample size of TARGET population to 166. Following MAIC and STC analysis, the odds of achieving all aforementioned clinical outcomes versus placebo at week 12 were similar for sarilumab and upadacitinib. Conclusion: In the MAIC and STC analyses from TARGET and SELECT-BEYOND trials, the efficacy of sarilumab and upadacitinib were comparable.

Medication-related osteonecrosis of the jaw (MRONJ) is a side effect in patients taking bone-modifying agents (BMAs), which are highly beneficial for treating osteoporosis and cancer. Bisphosphonates are prescribed to treat secondary osteoporosis in patients with rheumatoid arthritis (RA). We recently encountered two unusual cases of intraoral ONJ in RA patients who had not been treated with a BMA and did not have features of methotrexate- associated lymphoproliferative disorder. Their ONJ stage II bone exposures were treated by conservative therapy, providing good prognoses. These cases indicate that ONJ can occur in RA patients not treated with bisphosphonates. Several risk factors are discussed.

This study compared rheumatoid arthritis (RA) post-menopausal women with pathological involvement of the lower limb joints and age-matched post-menopausal women without RA regarding the dynamic joint stiffness (DJS) of knee during the stance phase of gait. Eighteen RA women and eighteen age-matched women were selected. Gait assessed through a three-dimensional motion analysis system synchronized with a force plate. Subjects walked barefoot at self-selected speed, and 14 valid trials were collected (comprising 7 left and 7 right foot-steps on force plate). The “moment of force—angle” plot of knee in sagittal plane was determined. The stance phase was split into three sub-phases: first knee flexion sub-phase (1st KFS); knee extension sub-phase (KES); second knee flexion sub-phase (2nd KFS). A linear model represented each sub-phase and DJS calculated by the slope. Model fitting was assessed through the coefficient of determination (R2). R2 values for both groups were higher than 0.8 during 1st KFS and KES but not during 2nd KFS. RA women yielded a higher DJS value during 2nd KFS (p < 0.01). Concerning the other sub-phases, no differences were observed between groups. The findings suggested the splitting methodology used could be modelled by a linear “moment of force—angle” relationship, namely, during 1st KFS and KES. During 2nd KFS, RA women yielded a stiffer behavior.

Gold was considered as universal remedies for diseases like inflammation, infections, etc in 19th century. Later in 20th century Robert Koch discovered Gold complex Potassiumdicyanidoaurate(I) showing activity against Mycobacterium tuberculosis, later the treatment was proved to be ineffective subsequently. Further in 1985 Auranofin (Gold salt) was introduced for the treatment of Rheumatoid Arthritis, which had to be taken orally and believed to be the major discovery till injectable gold came into existence. The function of drugs based on gold is majorly related to Rheumatoid arthritis but engrossment has bent towards the adequacy of Gold compounds for anti cancer activities. The review article summarizes the current research on Gold complexes and their biological activities against cancer as well as in case of RA.

Objectives: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. Methods: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. Results: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). Conclusions: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression.

Introduction: Drug-free remission (DFR) and its maintenance have been defined as the most desirable outcome for rheumatoid arthritis (RA) patients. DFR is linked to resolution of arthritis-related symptoms and restoration of normal functioning. However, there is currently no consensus if an optimal strategy, upon the initiation of treatment to the proper drugs withdrawal, is enough to induce it, or whether it is a predetermined condition related to patients' intrinsic characteristics. Areas covered: This review focuses on two key concepts around DFR. First, we analyze patients' intrinsic factors that may increase the chance of DFR, regardless of therapeutic choices. Second, we discuss on the evidence that it can be induced thanks to adequate, extrinsic disease management. Finally, we provide a glimpse into consequences of drugs discontinuation .Expert opinion: The early initiation of DMARD and the subsequent strict monitoring and drug adjustments are of primary importance to allow patients to achieve DFR, irrespective of initial treatment strategy. Once remission is obtained and maintained, it is possible to gradually taper and discontinue drugs with no dramatic consequences on the disease course. Among those who stop medication, ACPA-negative patients more often maintain the remission. Thus, DFR might depend on a combination of intrinsic and extrinsic factors.

This thesis focused on steps towards Therapeutic Drug Monitoring (TDM) for effective MTX treatment and methods to measure(non)adherence towards MTX and biological DMARDs. We studied pharmacokinetics and –dynamics of red blood cell (RBC)-MTX-PGs, ways to personalise MTX treatment, including a comparison of different cell types in which MTX was measured, and a proposed PKPD model. As a bridge, drug levels of MTX were compared with electronic monitoring of drug intake. Furthermore, adherence to (biological) DMARDs and ways to measure and improve this were revealed. For more information, please see the full summary.

This thesis focused on steps towards Therapeutic Drug Monitoring (TDM) for effective MTX treatment and methods to measure(non)adherence towards MTX and biological DMARDs. We studied pharmacokinetics and –dynamics of red blood cell (RBC)-MTX-PGs, ways to personalise MTX treatment, including a comparison of different cell types in which MTX was measured, and a proposed PKPD model. As a bridge, drug levels of MTX were compared with electronic monitoring of drug intake. Furthermore, adherence to (biological) DMARDs and ways to measure and improve this were revealed. For more information, please see the full summary.

Introduction Dysfunction of the distal radioulnar joint (DRUJ) can be significantly debilitating. The Sauve-Kapandji (S-K) procedure can be indicated to address multiple etiologies of DRUJ dysfunction. The purpose of this study was to review our institution’s results performing the S-K procedure for DRUJ dysfunction in terms of clinical and radiographic outcomes, as well as complications and reoperations. Methods A retrospective review of S-K procedures performed at 2 institutions between 1998 and 2017 with a minimum of 1-year follow-up was performed. Preoperative and postoperative visual analog scale (VAS) pain, grip strength, and wrist range of motion were reviewed. Radiographs were reviewed for DRUJ healing, carpal translation, and radiocarpal degenerative changes. Results The cohort included 35 patients. The mean age was 51 years. The mean follow-up was 49.5 months. The postoperative range of motion was unchanged in regard to pronation, supination, and wrist extension. There was a decrease in wrist flexion from 43 degrees to 34 degrees. Successful union was noted in 100% of the wrists. There was 1 case (2.8%) of progressive ulnar translation and 4 major complications (11.3%). Conclusion The S-K procedure has several theoretical benefits compared to other procedures for DRUJ dysfunction with results of this study demonstrating excellent pain relief, improved postoperative grip strength, retained wrist pronation, supination, and extension, high rate of successful arthrodesis and low rate of major complications. Level of Evidence Level IV

Reumatoidni artritis (RA) jest autoimuna, sistemska bolest koja najčešće zahvaća sinovijalne zglobove. Reumatska oboljenja bolna su za pojedinca, ona dovode do nesposobnosti za rad, smanjuju kvalitetu života i mogu čak dovesti do teškog oblika invaliditeta. Manifestacija reumatoidnog artritisa jest zahvaćenost malih zglobova šaka i stopala, a nakon toga zahvaća i veće zglobove, karakteristična je i jutarnja ukočenost ruku koja traje do 30 minuta. RA može se pojaviti i izvanzglobnim manifestacijama. Pojavnost reumatoidnog artritisa češća je u žena nego u muškaraca, a uzrok reumatoidnog artritisa još uvijek nije poznat. Kod postavljanja dijagnoze prvo se mora uzeti anamneza od pacijenta, a poslije toga vrši se fizikalni pregled. Osim fizikalnog pregleda za postavljanje dijagnoze potrebne su dijagnostičke obrade poput: radiološke obrade koje obuhvaćaju UZV, RTG snimanje, CT, MR, DXA i MSUS te laboratorijski nalazi. Liječenje se provodi farmakoterapijom i fizikalnom terapijom i rehabilitacijom, a glavni cilj liječenja jest smanjenje aktivnosti bolesti ili postizanje remisije te unaprjeđenje kvalitete života. Oboljeli od RA-a trebali bi konzumirati mediteransku prehranu, a ne preporučuju se konzumiranje kave, zaslađenih sokova, alkohola, soli i šećera. Uloga medicinske sestre kod reumatoidnog artritisa jest pacijenta i obitelj educirati o bolesti, uzimanju terapije, mogućim nuspojavama te kako nastaviti sa svakodnevnim životom. Kao što je važna edukacija pacijenta i obitelji, također je bitna i komunikacija između medicinske sestre i pacijenta, a i liječnika. Tako pacijent dobiva povjerenje u zdravstveno osoblje. U radu je opisan prikaz slučaja osobe oboljele od reumatoidnog artritisa, sestrinske dijagnoze, ciljevi i intervencije vezane uz slučaj. Rheumatoid arthritis is an autoimune, systemic disease that most often affects the synovial joints. Rheumatic diseases are painful for the individual, they lead to incapacity for work, reduce the quality of life and can even lead to a severe form of disability. The manifestation of rheumatoid arthritis is the involvement of small joints of the hands and feet, and after that it affects larger joints, is characteristic and morning stiffness of the hands, which lasts up to 30 minutes. RA can also be manifested by extra-articular manifestations. The incidence of rheumatoid arthritis is more common in women than in men, and the cause of rheumatoid arthritis is still unkown. When making a diagnosis, a medical history must first be taken the patient, and after that, a physical examination is carried out. In addition to physical examination, diagnostic treatments such as radiological examination, which include ultrasound, X-ray imaging, CT, MRI, DXA and MSUS, and laboratory findings, are required to make a diagnosis. Treatment is carried out by pharmacotherapy and physical therapy and rehabilitation, and the main goal of treatment is to reduce the activity of the disease or achieve remission and improve the quality of life. People with RA should consume the Mediterranen diet and it is not recommended to consume coffee, sweetened juices, alcohol, salt and sugar. The role of a nurse in rheumatoid arthritis is to educate the patient and family about the disease, taking therapy, possible side effects, how to continue with everyday life. Just as educating the patient and the family is important, communication between the nurse and the patient and the doctor, is also important. This is how the patient gains confidence in the health care staff. The paper describes a case report of a person suffering from rheumatoid arthritis, nursing diagnosis, goals and interventions related to the case.

The problem of comorbidity is widely discussed in the current medical literature. Its role in rheumatic diseases is particularly interesting because of its multifactorial nature and the involvement of a wide range of pathogenetic mechanisms. For many years, researchers around the world have noted correlations between the presence of active autoimmune disorders and the complicated course of cardiovascular diseases. A better understanding of the pathogenetic mechanisms at the current stage of rheumatology allows a new perspective on the relationship between atherosclerosis and rheumatoid arthritis. The definition of multimorbidity developed in recent years and the results of recent scientific research can contribute to a more correct choice of management tactics for patients with a combination of these two diseases.

Background: Multiple sclerosis (MS) is an immune-mediated central nervous system disease whose course is unpredictable. Finding biomarkers that help to better comprehend the disease's pathogenesis is crucial for supporting clinical decision-making. Blood extracellular vesicles (EVs) are membrane-bound particles secreted by all cell types that contain information on the disease's pathological processes. Purpose: To identify the immune and nervous system-derived EV profile from blood that could have a specific role as biomarker in MS and assess its possible correlation with disease state. Results: Higher levels of T cell-derived EVs and smaller size of neuron-derived EVs were associated with clinical relapse. The smaller size of the oligodendrocyte-derived EVs was related with motor and cognitive impairment. The proteomic analysis identified mannose-binding lectin serine protease 1 and complement factor H from immune system cell-derived EVs as autoimmune disease-associated proteins. We observed hepatocyte growth factor-like protein in EVs from T cells and inter-alpha-trypsin inhibitor heavy chain 2 from neurons as white matter injury-related proteins. In patients with MS, a specific protein profile was found in the EVs, higher levels of alpha-1-microglobulin and fibrinogen β chain, lower levels of C1S and gelsolin in the immune system-released vesicles, and Talin-1 overexpression in oligodendrocyte EVs. These specific MS-associated proteins, as well as myelin basic protein in oligodendrocyte EVs, correlated with disease activity in the patients with MS. Conclusion: Neural-derived and immune-derived EVs found in blood appear to be good specific biomarkers in MS for reflecting the disease state. This work was sponsored by a grant from Miguel Servet (CP20/00024 to Laura Otero-Ortega), Miguel Servet (CPII20/00002 to María Gutiérrez-Fernández), a predoctoral fellowship (FI18/00026 to Fernando Laso-García), a Río-Hortega grant (CM22/00065 to Gabriel Torres Iglesias and CM20/00047 to Elisa Alonso-López) and by Research Project (PI21/00918) from the Instituto de Salud Carlos III and co-funded by the European Union and by a grant CA1/RSUE/2021-00753 to Dolores Piniella funded by Ministerio de Universidades, Plan de Recuperación, Transformación y Resiliencia y la Universidad Autónoma de Madrid. Sí

Objective: The chronic autoimmune disease affecting the joints that are characterized by a progressive symmetric inflammation of affected joints resulting in cartilage destruction, bone erosion, and disability has been called Rheumatoid arthritis (RA). The aim of this study is to the assessment of FAS and lipid profiles in Iraqi patients with RA. Methods: In the current study, the demographic characteristics of the 90 studied subjects, 45 patients with RA, and 45 control subjects. Results: The result showed statically significance for increased cholesterol, and LDL in the study group (p-value Conclusion: Assessment of both FAS and IL-17A may be given as an appropriate and useful method for diagnosis and following with patients with RA.

ispartof: JOINT BONE SPINE vol:90 issue:4 ispartof: location:France status: published

Physical activity (PA) is a key strategy for improving symptoms in people with rheumatic and musculoskeletal diseases (RMDs). The aim of this study was to investigate and rank the importance of known barriers and facilitators for engaging in PA, from the perspective of people living with RMD. Five hundred thirty-three people with RMD responded to a survey (nine questions) disseminated by the People with Arthritis and Rheumatism (PARE) network of the European Alliance of Associations for Rheumatology (EULAR). The survey required participants to rank — based on their perceived importance — known PA barriers and facilitators from the literature, and specifically RMD symptoms as well as healthcare and community factors that may affect PA participation. Of the participants, 58% reported rheumatoid arthritis as their primary diagnosis, 89% were female, and 59% were between 51 and 70 years of age. Overall, participants reported fatigue (61.4%), pain (53.6%) and painful/swollen joints (50.6%) as the highest ranked barriers for engaging in PA. Conversely, less fatigue (66.8%) and pain (63.6%), and being able to do daily activities more easy (56.3%) were identified as the most important facilitators to PA. Three literature identified PA barriers, i.e., general health (78.8%), fitness (75.3%) and mental health (68.1%), were also ranked as being the most important for PA engagement. Symptoms of RMDs, such as pain and fatigue, seem to be considered the predominant barriers to PA by people with RMD; the same barriers are also the ones that they want to improve through increasing PA, suggesting a bi-directional relationship between these factors.Key Points• Symptoms of rheumatic and musculoskeletal disease (RMD) are the predominant barriers for lack of physical activity engagement.• RMD symptoms are the factors that people with RMDs want to improve when engaging in PA.• The barriers that stop people living with RMDs to do more PA are the ones that can be significantly improved through PA engagement.

AMAÇ: Romatoid artrit (RA) etyopatogenezinde viral enfeksiyonlar çevresel tetikleyici faktörler olarak rol almaktadır. Yeni corona virüs SARS-CoV-2’nin neden olduğu hastalığın (COVİD-19) otoimmüniteyi ve inflamatuar artritleri tetiklediği bildirilmiştir. Çalışmanın amacı, COVİD-19 sonrası RA tanısı alan hastaları klasik RA özellikleriyle karşılaştırmak ve RA gelişimindeki olası mekanizmaları irdelemektir. GEREÇ VE YÖNTEM: Romatoloji polikliniğine başvurarak RA tanısı alan olgular retrospektif olarak çalışmaya dahil edildi. Eklem yakınmaları başlamadan önce COVİD-19 öyküsü olan ve olmayan hastalar olarak iki grup oluşturuldu. Cinsiyet, yaş, komorbidite, çalışma durumu, sigara, aile öyküsü, eklem tutulum paterni, semptom süresi, eritrosit sedimantasyon hızı (ESR) ve C-reaktif protein (CRP), hastalık aktivite skorları (DAS28-ESR), romatoid faktör (RF), anti-siklik sitrülline peptid (anti-CCP) kaydedildi. Normal dağılım göstermeyen veriler için Wilcoxon testi, normal dağılım gösteren veriler için paired-t testi kullanıldı, p, OBJECTİVE: In rheumatoid arthritis (RA) etiopathogenesis, viral infections role as environmental trigger factors. The new corona virus SARS-COV-2 has been reported to trigger the autoimmunity and inflammatory arthritis. The aim of the study is to compare the patients diagnosed as RA after COVİD-19 with regular RA patients and to assess the possible mechanisms in RA development.MATERİALS AND METHODS: Two groups were formed in newly diagnosed RA patients depending on COVİD-19 history before the initiation of joint symptoms. Gender, age, comorbidity, working status, smoking habits, family history, joint involvement pattern, symptom duration, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), disease activity scores (DAS28-ESR), rheumatoid factor (RF), anti-cyclic citrulline peptide (anti-CCP) was recorded. Wilcoxon test was used for data that does not show normal distribution, paired-t test used for data showing normal distribution, p

Background: Cyclooxygenase (COX) and Lipoxygenase (LOX) enzymes catalyze the production of pain mediators like Prostaglandins (PGs) and Leukotrienes (LTs), respectively from arachidonic acid. Introduction: The COX and LOX enzyme modulators are responsible for the major PGs and LTs mediated complications like asthma, osteoarthritis, rheumatoid arthritis, cancer, Alzheimer’s disease, neuropathy and Cardiovascular Syndromes (CVS). Many synthetic Nonsteroidal Anti- Inflammatory Drugs (NSAIDs) used in the treatment have serious side effects like nausea, vomiting, hyperacidity, gastrointestinal ulcers, CVS, etc. Methods: The natural inhibitors of pain mediators have great acceptance worldwide due to fewer side effects on long-term uses. The present review is an extensive study of the advantages of plantbased vs synthetic inhibitors. Results: These natural COX and LOX inhibitors control inflammatory response without causing side-effect-related complicacy. Conclusion: Therefore, the natural COX and LOX inhibitors may be used as alternative medicines for the management of pain and inflammation due to their less toxicity and resistivity.

Objective: In patients with rheumatoid arthritis (RA) with cardiovascular disease risk, it is unknown whether exercises are safe, improve cardiorespiratory fitness and reduce disease-related symptoms and cardiovascular-disease (CVD) risk factors. We aimed to investigate in RA patients with CVD risk: (1) safety of medium to high-intensity aerobic exercises, (2) potential changes of cardiorespiratory fitness and (3) disease activity and CVD risk factors in response to the exercises. Methods: Single-arm pilot-exercise intervention study including 26 consecutive patients (21 women) with > 4% 10-year risk of CVD mortality according to the Dutch Systematic Coronary Risk Evaluation. Aerobic exercises consisted of two supervised-sessions and five home-sessions per week for 12 weeks. Patients were required to exercise at intensities between 65 and 85% of their maximum heart rate. To assess safety, we recorded exercise related adverse events. Before and after the exercises, cardiorespiratory fitness was assessed with a graded maximal oxygen-uptake exercise test, while disease activity was evaluated via the Disease Activity Score-28 (DAS28) using the erythrocyte segmentation rate (ESR). Resting blood pressure, ESR and total cholesterol were assessed as CVD risk factors. Results: Twenty out of 26 patients performed the 12-week exercises without any adverse events. According to patients, withdrawals were unrelated to the exercises. Exercises increased cardiorespiratory fitness (pre: 15.91 vs. post: 18.15 ml.kg−1 min−1, p = 0.003) and decreased DAS28 (pre: 2.86 vs. post: 2.47, p = 0.04). No changes were detected in CVD risk factors. Conclusion: A 12-week exercise intervention seems to be safe and improves cardiorespiratory fitness and disease activity in patients with RA with a high risk for cardiovascular diseases.Key Points1. Rheumatoid arthritis patients with high cardiovascular disease risk were able to perform a maximum exercise test and a 12-week aerobic-based medium-to-high intensity exercise intervention.2. The exercise intervention improved cardiorespiratory fitness and disease activity in rheumatoid arthritis patients with high cardiovascular disease risk.3. Cardiorespiratory fitness levels were still low post-exercise intervention (i.e. 18.15 ml.kg−1min−1 compared to the 20.9 ml.kg−1min−1 baseline mean of the RA patients without CVD risk).

Objective: To determine whether tumor necrosis factor (TNF) blockade improves small airway obstruction in rheumatoid arthritis (RA) patients without apparent respiratory symptoms.Methods: Pulmonary function tests were performed before and one year after TNF blockade therapy in 29 RA patients without apparent respiratory symptoms. As a control, pulmonary function was examined at a one-year interval in 27 RA patients with conventional disease-modifying antirheumatic drugs (DMARDs) alone. Small airway obstruction was diagnosed when one of maximal mid-expiratory flow rate (MMEF), forced expiratory flow at 50% (FEF50) or 75% (FEF75) of the vital capacity was decreased to less than 60%, 55%, or 45% of predicted values, respectively.Results: Small airway obstruction was found in 62.5% of RA patients. No differences were found in age, sex, disease duration, or disease activities. TNF inhibitors dramatically reduced disease activities. However, TNF inhibitors failed to improve small airway obstructions but worsened them.Conclusions: TNF blockade fails to improve small airway obstruction, suggesting that TNF-independent pathways play important roles in the development of small airway obstruction in RA.

Native American (NA) populations have higher rates of rheumatic disease and present with overlapping disease symptoms and nontraditional serologic features, thus presenting an urgent need for better biomarkers in NA diagnostics. This study used a machine learning approach to identify immune signatures that more effectively stratify NA patients with rheumatic disease.Adult NA patients with autoantibody-positive (AAB+) rheumatoid arthritis (RA; n = 28), autoantibody negative (AAB-) RA (n = 18), systemic autoimmune rheumatic disease (n = 28), arthralgia/osteoarthritis (n = 28), or polyarthritis/undifferentiated connective tissue disease (n = 28), and control patients (n = 28) provided serum samples for cytokine, chemokine, and AAB assessment. Random forest clustering and soluble mediator groups were used to identify patients and control patients with similar biologic signatures. The American College of Rheumatology criteria specific for systemic disease and RA identified differences in disease manifestations across clusters.Serum soluble mediators were not homogenous between different NA rheumatic disease diagnostic groups, reflecting the heterogeneity of autoimmune diseases. Clustering by serum biomarkers created 5 analogous immune phenotypes. Soluble mediators and pathways associated with chronic inflammation and involvement of the innate, B cell, T follicular helper cell, and interferon-associated pathways, along with regulatory signatures, distinguished the 5 immune signatures among patients. Select clinical features were associated with individual immune profiles. Patients with low inflammatory and higher regulatory signatures were more likely to have few clinical manifestations, whereas those with T cell pathway involvement had more arthritis.Serum protein signatures distinguished NA patients with rheumatic disease into distinct immune subsets. Following these immune profiles over time may assist with earlier diagnoses and help guide more personalized treatment approaches.

Patient-clinician goal concordance is associated with improved outcomes in certain chronic diseases but not explored in rheumatoid arthritis (RA). We examined goal concordance, correlates of concordance, and the association of concordance with health outcomes.Adult patients with RA seen at least 1 time in the prior 12 months at 1 of 2 rheumatology clinics participated. Patients and their clinicians independently ranked top 3 goals for RA treatment from 8 options before a routine visit. Patients completed postvisit surveys on health, demographic information, health literacy, and adherence. Goal concordance was defined as the patient's number 1 goal being among the clinician's top 3 goals for that patient. Bivariable and multivariable logistic regression models were used to examine correlates of concordance.Patients were 58% female and 16% Spanish-speaking, and 29% had limited health literacy. Among 204 patient-clinician dyads, 20% were goal-discordant. "Have less pain" was selected by both patient and clinician in 81% of dyads, followed by "have fewer problems doing daily activities" by 63%. Otherwise, clinicians prioritized avoiding side effects, whereas patients ranked improved sleep, fatigue, and mood. Longer disease duration was associated with discordance (median 13.3 years, interquartile range [IQR] 5.2-20 among discordant vs. 7 years, IQR 4-14; P = 0.039); higher depressive symptoms were associated with concordance (8.1% vs. 24%; P = 0.04). Goal concordance was associated with higher medication adherence (adjusted odds ratio 2.76 [95% confidence interval 1.01, 7.56]).One in 5 patient-clinician dyads had discordant treatment goals. Goal concordance was associated with higher medication adherence. Studies to improve goal elicitation and communication of patients with RA's priorities are needed.

Objectives: Remission is the ultimate purpose of treatment in rheumatoid arthritis (RA). However, even when the most stringent composite scores are used, structural damages can occur; hence, ultrasonography (US) appears to be the best way to assess real remission. This study aimed to investigate the validity of different RA remission scores using US as a reference. Methods: An analytic diagnostic study, of 30 RA patients in remission (according to the Disease Activity Score in 28 Joints [DAS28]) and a control group with active RA, was conducted between January and October 2018 at Mongi Slim Hospital in Tunis, Tunisia. Among them, patients in remission were identified according to their Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) and the Boolean American College of Rheumatology/European League against Rheumatism activity index (ACR/EULAR) remission scores. The validity of each activity score for remission was calculated by considering the absence of power Doppler (PD) signals as a gold standard. Results: All patients were in remission according to the DAS28, with an average score of 2.03 (1.1–2.6). US examination showed PD signals in 57% of patients. A total of 26 patients were in remission according to the CDAI; a Doppler signal was detected in 58% of those cases. SDAI remission was accomplished in 19 patients, with PD activity in 53% of cases. Of the 14 patients in remission according to the Boolean ACR/EULAR criteria, synovial hyper-vascularisation was found in 64%. Considering true remission as the absence of PD signals, the most sensitive and specific score was the DAS28 (93% and 68%, respectively). Conclusion: Considering remission in RA as the absence of vascularised synovitis, the DAS28 is the most sensitive and most specific score.Keywords: Rheumatoid Arthritis; Ultrasonography; Doppler; Reproducibility of Results; Tunisia.

The risk of osteoporosis in patients with rheumatoid arthritis (RA) is frequently overlooked, and investigating a simple indicator in routine care may be beneficial to motivate osteoporosis examination. The aim of this retrospective, case-controlled study was to identify the correlation between serum albumin concentrations and the prevalence of osteoporosis in postmenopausal patients with RA.This study enrolled 197 patients who underwent dual-energy X-ray absorptiometry of lumbar spine (LS) and proximal femur without osteoporosis treatment [mean age, 67.5 years; disease duration, 12.8 years; Disease Activity Score assessing 28 joints with C-reactive protein, 2.0; prednisolone dose, 4.9 mg/day (usage, 42.6%); and LS T-score, -1.9]. Patients were classified into 2 groups: osteoporosis, defined as ≥ 1 part bone mineral density T-score ≤ -2.5 or history of fragility fracture of the vertebra or proximal femur (121 patients), and non-osteoporosis (76 patients). Groups were then matched by propensity score using clinical backgrounds affecting bone metabolism.In non-matched model, serum albumin concentration was significantly associated with osteoporosis-related factors such as aging, inflammation, physical disability, and glucocorticoid dose. Multivariate logistic regression revealed that serum albumin concentration was independently and significantly associated with osteoporosis risk (odds ratio = 0.22, 95% confidence interval = 0.08, 0.61, p = 0.0033). After propensity score matching, 57 patients for each group showed that in addition to the LS and femoral neck T-scores (p 0.001), serum albumin concentrations (p = 0.01) remained lower in the osteoporosis group compared to non-osteoporosis group. Receiver operating characteristic curve analysis in non-matched model revealed that when cut-off value of serum albumin concentration for indicating osteoporosis was set at 4.2 g/dl, the area under the curve was 0.69, sensitivity 0.74, and specificity 0.58.Low serum albumin concentration was significantly and independently associated with the prevalence of osteoporosis, which may be considered as one of the osteoporosis-related factors in postmenopausal patients with RA.

This study aimed to longitudinally evaluate the development of locomotive syndrome (LS) in rheumatoid arthritis (RA) patients during the COVID-19 pandemic using the 25-question Geriatric Locomotive Function Scale (GLFS-25). Subjects were 286 RA patients (female, 70.6%; mean age, 64.2 years) who had GLFS-25 and Clinical Disease Activity Index (CDAI) data available for a 1-year period during the COVID-19 pandemic and who did not have LS at baseline. Associations between subject characteristics and development of LS were determined using logistic regression analysis. Among the 286 patients, 38 (13.3%, LS group) developed LS at 1 year after baseline. In the LS group, scores of the GLFS-25 categories “GLFS-5” and “Social activities” were significantly increased at 1 year relative to baseline. GLFS-5 is a quick 5-item version of the GLFS-25, including questions regarding the difficulty of going up and down stairs, walking briskly, distance able to walk without rest, difficulty carrying objects weighing 2 kg, and ability to carry out load-bearing tasks and housework. A significant correlation was also observed between changes in “Social activities” and that of “GLFS-5.” Multivariable logistic regression analysis revealed that the development of LS was significantly associated with BMI (OR: 1.11 [95% confidence interval (CI): 1.00–1.22]) and CDAI (OR: 1.08 [95%CI: 1.00–1.16]) at baseline. Adequate exercise and tight control of RA disease activity are important for preventing the development of LS in view of restrictions on going out imposed during the COVID-19 pandemic. GLFS-5 is useful for evaluating the physical function of RA patients.

We sought to understand the frequency of contraception documentation for women with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a large US electronic health record (EHR)-based registry and to identify disparities by teratogen prescription and patient race and ethnicity.Contraception documentation from structured data fields within the Rheumatology Informatics System for Effectiveness (RISE) registry was collected for women of childbearing age (18-45 years) in 2018 who had at least 2 visits with International Classification of Diseases, Ninth Revision or Tenth Revision, diagnosis codes for SLE or RA (at any time). Univariate and multivariate analyses compared the frequency of contraception documentation based on patient characteristics including diagnosis, age, race, and teratogenicity of prescribed antirheumatic medications.In 2018, there were 9,826 women of childbearing age with SLE and 19,009 with RA, of whom 9.1% had any contraception documented. Rates of contraceptive documentation were significantly lower for women with SLE (adjusted odds ratio [OR] 0.84 [95% confidence interval (95% CI) 0.76-0.92]). Women of Hispanic ethnicity and Black and Asian race were all less likely than White women to have contraception documentation. Teratogen prescription was associated with higher rates of contraception documentation for women with RA but not SLE (RA adjusted OR 1.31 [95% CI 1.16-1.47]; SLE adjusted OR 1.08 [95% CI 0.91-1.28]).There are large gaps in contraception documentation within the RISE registry that are particularly stark among women of color. Although these data likely underestimate contraception use, they highlight that most rheumatologists do not have a systematic approach to collecting and recording this information in the EHR.

Rheumatoid arthritis (RA) is an autoimmune disease of multifactorial etiology, characterized by a chronic inflammatory reaction of the joints, but can also affect other tissues. Some environmental factors can trigger an immune system response in genetically susceptible individuals, activating the disease. Lower diversity of gut microbiota, and dysbiosis, have been observed in RA patients. In this regard, approaches to decrease inflammation, and to restore the microbiota, have been suggested. These include oral administration of single probiotics, or probiotic mixtures, on their own, or in combination with drugs. Vitamin K (VitK) is one of the many products of the intestinal microbiota. Lower levels of some forms of VitK have been measured in the serum and stools of RA patients and some studies have found an inverse correlation between VitK levels and the clinical severity of the disease. Additionally, some forms of this vitamin, when given orally, have been shown to exert positive effects in decreasing RA activity, and delaying its onset and progress. This review aims at describing the link between the gut microbiota and RA, focusing on the role of VitK and probiotics as possible adjuvant therapies in this disease.

Background: The catabolism of tryptophan (Trp) in the kynurenine (Kyn) pathway is thought to have a critical immunosuppressive effect.Aim of the work: To evaluate plasma Trp and metabolite levels to identify their diagnostic potential in rheumatoid arthritis (RA).Patients and methods: 50 RA patients and 41 control were included in this study. The Trp and Kyn were analyzed and the Kyn\textbackslash{}Trp ratio was calculated to estimate Indolamine 2,3 dioxygenase (IDO) enzyme activity involved in Trp degradation.Results: The 50 patients had a mean age of 58.5 +/- 10.6 years

Purpose: A high cardiovascular risk has been described in patients with rheumatoid arthritis (RA); the effects of different biological agents have also been described in these patients. The aim of the present study is to examine the effects of tumor necrosis factor inhibitors (TNFi) in the lipoprotein profile of RA patients using a broad laboratory assessment including a large number of non-routine tests. Patients and Methods: RA patients treated with and without TNFi (70 patients in each group) were cross-sectionally compared regarding a broad spectrum of lipoprotein parameters including serum levels of total and HDL, LDL and VLDL cholesterol triglycerides, lipoprotein A (LpA), apolipoprotein A1 (Apo A), B100 (Apo B) and paroxonase. For each lipoprotein subfraction (HDL, LDL and VLDL), we assess specific concentrations of cholesterol, triglycerides, phospholipids and proteins and total mass of each one. Additionally, HDL Apo A, LDL and VLDL Apo B concentrations and number of particles of LDL and VLDL were also determined. Exploratory univariate and multivariate analyses of the different variables were performed. Results: Seventy patients in each subset were enrolled. Patients on treatment with TNFi showed a trend to be younger and to have a longer disease duration. Regarding the lipoprotein analyses, borderline significant higher levels of serum Apo A were detected and an independent association with lower HDL mass, LDL triglyceride, VLDL cholesterol, VLDL Apo B, VLDL mass, number of VLDL cholesterol molecules and number of particles of VLDL was clearly observed. Conclusion: TNFi treatment was associated with beneficial atherogenic effects at the lipoprotein level especially centered in the VLDL-related parameters consistent with a reduction of the atherogenic risk. Funding: This study was carried out with the support of Instituto de Salud Carlos III (ISCIII) (grant number PI0810119).

Summary Rheumatoid arthritis (RA) is an autoimmune disease of multifactorial etiology, characterised by a chronic inflammatory reaction of the joints, but can also affect other tissues. Some environmental factors can trigger an immune system response in genetically susceptible individuals, activating the disease. Lower diversity of gut microbiota, and dysbiosis, have been observed in RA patients. In this regard, approaches to decrease inflammation, and to restore the microbiota, have been suggested. These include oral administration of single probiotics, or probiotic mixtures, on their own, or in combination with drugs. Vitamin K (VitK) is one of the many products of the intestinal microbiota. Lower levels of some forms of VitK have been measured in the serum and stools of RA patients and some studies have found an inverse correlation between VitK levels and the clinical severity of the disease. Additionally, some forms of this vitamin, when given orally, have been shown to exert positive effects in decreasing RA activity, and delaying its onset and progress. This review aims at describing the link between the gut microbiota and RA, focusing on the role of VitK and probiotics as possible adjuvant therapies in this disease., This study was supported by the Portuguese Foundation for Science and Technology(FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and FCT within CINTESIS, R&D Unit (reference UIDB/04255/2020)., info:eu-repo/semantics/publishedVersion

Objective To investigate the incidence of and factors associated with SARS-CoV-2 testing and infection in immune mediated inflammatory diseases (IMIDs) versus matched non-IMIDs comparators from the general population. Methods We conducted a population-based, matched cohort study among adult residents from Ontario, Canada, from January to December 2020. We created cohorts for the following IMIDs: rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, ankylosing spondylitis, systemic autoimmune rheumatic diseases, multiple sclerosis (MS), iritis, inflammatory bowel disease (IBD), polymyalgia rheumatica and vasculitis. Each patient was matched with five patients without IMIDs based on socio-demographic factors. We estimated the incidence of SARS-CoV-2 testing and infection in IMIDs and non-IMIDs patients. Multivariable logistic regressions assessed odds of SARS-CoV-2 infection. Results We studied 493,499 patients with IMIDs and 2,466,946 patients without IMIDs. Patients with IMIDs were more likely to have at least one SARS-CoV-2 test, versus patients without IMIDs (27.4% vs. 22.7%), but the proportion testing positive for SARS-CoV-2 was identical (0.9% in both groups). Overall, IMIDs patients had 20% higher odds of being tested for SARS-CoV-2 (odds ratio (OR) 1.20, 95% CI 1.19, 1.21). The odds of SARS-CoV-2 infection varied across IMIDs groups but was not significantly elevated for most IMID groups compared with non-IMIDs. The odds of SARS-CoV-2 infection was lower in IBD and MS and marginally higher in RA and iritis. Conclusions Patients across all IMIDs were more likely to be tested for SARS-CoV-2 versus those without IMIDs. The risk of SARS-CoV-2 infection varied across disease sub-groups.

The aim of this study was to explore experiences of people with rheumatoid arthritis during and after COVID-19-induced quarantine in terms of physical activity and health status. Rheumatoid arthritis affects multiple facets of the person, both physically and psychologically. Physical activity is considered a safe and effective intervention to improve symptoms and systemic manifestations of rheumatoid arthritis. In the context of the COVID-19, countries like Spain were forced to impose restrictions on mobility, prohibiting outings even to perform physical activity. Structured interviews were conducted and developed using the Tampa Scale for Kinesiophobia-11 questionnaire. Data were analysed using a six-step thematic analysis. The results make it clear that even though the patients declared that physical activity is essential for them to deal with their disease, most of the participants affirmed that they significatively reduced their levels of physical activity during the pandemic. Physical activity should be promoted in people, even in difficult times, to improve disease outcomes, well-being and mental health. Knowing the experiences of these patients enables nursing managers to develop interventions that ensure the delivery of comprehensive nursing care regarding physical activity and health status, in future situations like this pandemic.

To investigate previously identified and novel correlates of acute calcium pyrophosphate (CPP) crystal arthritis among well-characterized cases.In this case-control study, we identified cases of acute CPP crystal arthritis using a validated algorithm (positive predictive value 81%) applied in the Partners HealthCare electronic health record (EHR). Cases were matched to general patient controls on the year of first EHR encounter and index date. Prespecified potential correlates included sex, race, and comorbidities and medications previously associated with CPP deposition/acute CPP crystal arthritis in the literature. We estimated odds ratios (ORs) and 95% confidence intervals using conditional logistic regression models adjusted for demographic characteristics, comorbidities, medications prescribed in the past 90 days, health care utilization, and multimorbidity score.We identified 1,697 cases matched to 6,503 controls. Mean ± SD age was 73.7 ± 11.8 years, 56.7% were female, 80.8% were White, and 10.3% were Black. All prespecified covariates were more common in cases than controls. Osteoarthritis (OR 3.08), male sex (OR 1.35), rheumatoid arthritis (OR 2.09), gout (OR 2.83), proton pump inhibitors (OR 1.94), loop diuretics (OR 1.60), and thiazides (OR 1.46) were significantly associated with acute CPP crystal arthritis after full adjustment. Black race was associated with lower odds for acute CPP crystal arthritis compared to White race (OR 0.47).Using a validated algorithm to identify nearly 1,700 patients with acute CPP crystal arthritis, we confirmed important correlates of this acute manifestation of CPP deposition. This is the first study to report higher odds for acute CPP crystal arthritis among males.

Clinical guidelines for the treatment of rheumatoid arthritis (RA) are based on the use of: nonsteroidal anti-inflammatory drugs (NSAIDs), conventional disease-modifying drugs (csDMARDs), immunosuppressants and biological therapies. Unfortunately, a large number of patients have other chronic diseases in addition to RA, which requires additional multiple use of drugs and often leads to polypharmacy. According to the definition of the World Health Organization (WHO), polypharmacy is defined as the routine use of 5 or more drugs, including prescription of over-the-counter drugs, dietary supplements, and traditional medicines. The aim of the study was to examine the impact of polypharmacy on the functional ability of patients with RA estimated based on the HAQ-DI index. A retrospective study included 131 patients diagnosed with RA. Within the clinical characteristics, attention was focused on the present comorbidities, therapy and the total number of drugs used. The HAQ questionnaire was used to assess health status and functional ability. The obtained data were analyzed and statistically processed using appropriate software and statistical methods. The study involved 29 males and 102 females mean age 60.25 ± 11.21 years. The analysis of the collected clinical data showed the presence of comorbidities in 80.15% of patients. Synthetic disease-modifying drugs were used 88.55%, while 13.74% of patients were on biological therapy. HAQ-DI values < 1.5 were present in 83.21%, while HAQ-DI ≥ 1.5 values were recorded in 16.79% of respondents. Polypharmacy was present in 75.57% of respondents. Potential interactions were more frequent in the group of respondents who can perform normal physical activities without or with mild restrictions (HAQ-DI < 1.5), while the presence of one serious potential interaction was more pronounced in the group of respondents with reduced functional ability (HAQ-DI ≥ 1.5). The results of this study show a high frequency of polypharmacy and consequent potential drug interactions in patients with RA. Accordingly, monitoring of polypharmacy in patients with RA is necessary in order to achieve optimal functional status, disease control, minimize drug interactions and side effects.

To determine whether multimorbidity is associated with treatment changes and achieving target disease activity thresholds in patients with active rheumatoid arthritis (RA).We conducted a retrospective cohort study of adults with active RA within the Rheumatology Informatics System for Effectiveness (RISE) registry. Multimorbidity was measured using RxRisk, a medication-based index of chronic disease. We used multivariable logistic regression models to assess the associations of multimorbidity with the odds of initiating a new disease-modifying antirheumatic drug (DMARD) in active RA, and among those initiating a new DMARD, the odds of achieving low disease activity or remission.We identified 15,626 patients using the Routine Assessment of Patient Index Data 3 (RAPID3) cohort and 5,733 patients using the Clinical Disease Activity Index (CDAI) cohort. All patients had active RA, of which 1,558 (RAPID3) and 834 (CDAI) initiated a new DMARD and had follow-up disease activity measures. Patients were middle aged, female, and predominantly White, and on average received medications from 6 to 7 RxRisk categories. Multimorbidity was not associated with new DMARD initiation in active RA. However, a greater burden of multimorbidity was associated with lower odds of achieving treatment targets (per 1-unit RxRisk: RAPID3 cohort odds ratio [OR] 0.95 [95% confidence interval (95% CI) 0.91, 0.98]; CDAI cohort OR 0.94 [95% CI 0.90, 0.99]). Those with the highest burden of multimorbidity had the lowest odds of achieving target RA disease activity (RAPID3 cohort OR 0.54 [95% CI 0.34, 0.85]; CDAI cohort OR 0.65 [95% CI 0.37, 1.15]).These findings from a large, real-world registry illustrate the potential impact of multimorbidity on treatment response and indicate that a more holistic management approach targeting multimorbidity may be needed to optimize RA disease control in these patients.

Sinomenine (SIN) is commonly used as part of rheumatoid arthritis (RA) therapy in China, but there is still no published evidence of the efficacy of SIN monotherapy. This work investigates the efficacy and safety of SIN in treating RA patients and analyzes the correlation between ornithine level and the alleviation of disease activity in RA patients. In this 24 week, randomized, placebo-controlled, double-blind clinical trial, people with mild to moderate RA were randomly assigned (1:1:1, stratified by hospital) to receive SIN (120 mg, twice daily), methotrexate (MTX) (10 mg per week), or SIN + MTX therapy. The primary outcome was the proportion of patients who achieved a 50% improvement in the American College of Rheumatology (ACR) criteria at week 24 and who showed improvement according to the clinical disease activity index (CDAI). In this prospective subgroup analysis, we also assessed whether the 24 week alterations of disease activity in the treatment group were significantly correlated to the levels of blood ornithine. Of the 135 enrolled participants, 38, 39, and 36 patients were treated with SIN, MTX, and SIN + MTX, respectively. In the SIN-treated group, 52.63% of patients achieved ACR50 after 24 weeks of treatment, which was comparable to the results in the MTX-treated and SIN + MTX-treated groups. Hepatic and gastrointestinal disorders were the main adverse events; however, the ratio of patients suffering from hepatic disorder in the SIN group (1/38) was much lower than that in the MTX (10/39) and SIN + MTX (8/36) groups. A total of 221 serum samples were collected at the four follow-up time points in the three treatments, and the levels of ornithine, citrulline, and arginine were obtained through ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). The serum ornithine level decreased after the 24 week treatment along with a decrease in disease activity, and may reflect therapeutic responses with a sensitivity value of 80%. In conclusion, SIN revealed a comparable efficacy to MTX for treating RA patients, but with fewer side effects. In addition, the serum ornithine level was found for the first time to have a close correlation with the alleviation of RA, which shows the value of this measure as an assessment indicator of drugs in treating RA.