Chronic Rheumatic Disorders Research Articles

Ixekizumab in the treatment of psoriatic arthritis.

Psoriatic arthritis (PsA) is a heterogeneous chronic rheumatic disorder with numerous phenotypic facets. A better in deep understanding of the pathophysiologic mechanisms leading to psoriasis and PsA has contributed to the introduction of novel therapeutic agents. IL-17 is at the heart and a critical factor in the onset of PsA. Ixekizumab, a high-affinity monoclonal antibody against IL-17 A, has been approved by the US FDA in March 2016 for baseline psoriasis and Dec 2017 for PsA; by the EMA in April 2016 and January 2018, respectively. This article reviews the published data relating to ixekizumab efficacy and safety in the PsA treatment.

The NZB/WF1 mouse model for Sjögren's syndrome: A historical perspective and lessons learned.

Sjögren's syndrome (SS) is a chronic rheumatic autoimmune disorder affecting multiple organ systems. The clinical findings in SS patients show considerable heterogeneity and overlap with other autoimmune diseases. In addition, the autoimmune response in SS initiates several years before the appearance of clinical symptoms. Thus, understanding the pathogenic mechanisms involved in the disease process have been a challenge. Several animal model systems of SS-like disease have been developed to overcome these issues. The New Zealand Black (NZB) x New Zealand White (NZW) F1 (NZB/WF1) mouse represents the first spontaneous mouse model of SS. In this review, we provide a historical perspective and detailed description of this mouse model focusing on exocrine gland histopathology, autoantibody populations, and glandular dysfunction. Considering that NZB/WF1 mice also develop a systemic lupus erythematosus (SLE)-like disease, this mouse model mimics the clinical presentation of polyautoimmunity seen in a sizable subset of SS patients. It is plausible that such patients will require distinct therapeutic interventions necessary to treat both SLE and SS. Therefore, the NZB/WF1 mouse is a powerful tool to decipher pathogenic mechanisms involved in SS related polyautoimmunity and develop appropriate therapeutic strategies.

Efficacy of physical activities on children with juvenile idiopathic arthritis: a randomized controlled trial

BackgroundJuvenile idiopathic arthritis (JIA) is one of the serious chronic rheumatic disorders in children and adolescents which results in less physical activities and restlessness hours than their peer. The study aims to assess the efficacy of physical fitness training exercises on aerobic capacity and muscular strength of children with JIA. Sixty-five children with JIA were included in the study, out of a total of 70 children who were screened for eligibility. Children were randomized to a control group (n = 32) who received hot packs, transcutaneous electrical nerve stimulation (TENS), and strengthening exercises, or a study group (n = 33) who received a physical fitness training program (hydrotherapy pool exercises, bicycle ergometer, and treadmill apparatus) in addition to what had been given to the control group. Both groups were engaged in a training program for 12 consecutive weeks for three times per week. Evaluation was done pre- and post-interventions included: peak oxygen uptake (Vo2 peak) during an incremental treadmill test and muscle strength assessed by isokinetic dynamometer.ResultsThe current study showed that there were significant differences between pre- and post-interventions in both groups (P < 0.05). Comparing the two groups, there were statistically significant differences between children in both groups in favor of the study group (P < 0.05).ConclusionsPhysical fitness exercise training resulted in improved aerobic capacity and muscle strength of children with JIA. The obtained results suggested that children with arthritis could participate in formal exercise testing and structural physical fitness program.Trial registrationPACTR, PACTR201907504136763. Registered on May 21, 2019. Retrospectively registered, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID = 8150.

Weekly versus daily leflunomide

Among the most common chronic conditions needing chronic drug therapy are chronic rheumatic diseases, diabetes mellitus,hypertension, depression, psychosis, inflammatory bowel diseases, multiple sclerosis, coronary vascular disease, dyslipidemiaand also chronic rheumatic disorders are among. Most researchers and pharmaceutical companies are constantly trying todevelop new drugs with more specific measures based on the pathophysiology of the disease in question. Finding an idealapproach in practice guidelines with minimum adverse drug effects is optimum. Post-drug effects deal with the biological effectsof a medicine lasting longer than expected from its pharmacological half-life. This could be more evident in many drugs,including hydroxychloroquine, methotrexate, leflunomide, dexamethasone, fluoxetine, and other lipid lowering drugs. Thiseffect not only maintains the therapeutic effect of the drugs, but also reduces the side effects. Leflunomide is animmunomodulatory antirheumatic and disease-modifying drug that is used to treat rheumatoid arthritis as well as otherinflammatory arthritis (namely psoriatic arthritis) by inhibiting the synthesis of pyrimidine. Due to the metabolite of leflunomidein the body and the long half-life of this drug, it is possible to prescribe this drug on a weekly basis. Study results have indicatedthat weekly administration of leflunomide has advantages over daily administration, such as the same therapeutic effect, easeof administration, lower cost of treatment, fewer side effects of medication, and more patient compliance. Thus, based on theresults, it can be recommended that leflunomide be administered weekly.

Recommendations for the assessment and optimization of adherence to disease-modifying drugs in chronic inflammatory rheumatic diseases: A process based on literature reviews and expert consensus.

Adherence to treatment is a key issue in chronic inflammatory rheumatic diseases (CIRDs). To develop recommendations to facilitate in daily practice, the management of non-adherence to disease-modifying drugs in patients with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, connective tissue diseases or other CIRDs. The process comprised (a) systematic literature reviews of methods (including questionnaires) to measure non-adherence, risk factors for non-adherence and efficacy of targeted interventions; (b) development of recommendations through consensus of 104 rheumatologist and nurse experts; (c) assessment of agreement and ease of applicability (1-5 where 5 is highest) by the 104 experts. (a) Overall, 274 publications were analysed. (b) The consensus process led to 5 overarching principles and 10 recommendations regarding adherence. Key points include that adherence should be assessed at each outpatient visit, at least using an open question; questionnaires and hydroxychloroquine blood level assessments may also be useful. Risk factors associated to non-adherence were listed. Patient information and education, and patient/physician shared decision, are key to optimize adherence. Other techniques such as formalized education sessions, motivational interviewing and cognitive behavioral therapy may be useful. All health professionals can get involved and e-health may be a support. (c) The agreement with the recommendations was high (range of means, 3.9-4.5) but ease of applicability was lower (2.7-4.4). Using an evidence-based approach followed by expert consensus, this initiative should improve the assessment and optimization of adherence in chronic inflammatory rheumatic disorders.

Methods to improve medication adherence in patients with chronic inflammatory rheumatic diseases: a systematic literature review

ObjectiveLack of adherence to treatment is frequent in chronic inflammatory rheumatic diseases and is associated with poorer outcomes. The objective of this study was to describe and evaluate interventions that...

Tropical Arthritogenic Alphaviruses

Tropical alphaviruses have special tropism for bone and joint tissue. Patients can develop chronic rheumatic disorders similar to rheumatoid arthritis and ankylosing spondylitis. The prototype is Chikungunya virus, although other lesser known viruses in our environment such as Sindbis, Ross River, Mayaro, O’nyong nyong and Barmah Forest viruses have the potential to be sped through vectors and cause chronic rheumatic disease.International population movements have increased the numbers of patients diagnosed with these tropical viruses in areas in which they are not endemic. Since they can leave persistent symptoms and affect the quality of life of the patients, it is important that we be aware of them. Changes in ecosystems have favored the expansion of competent mosquitoes, making fears of local transmission in southern Europe a reality.The objective of this review is to provide a clinical approach to the different arthritogenic tropical alphaviruses, especially those in which chronic rheumatic disease is more frequent.

Predictive value of microRNA-132 and its target gene NAG-1 in evaluating therapeutic efficacy of non-steroidal anti-inflammatory drugs treatment in patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a common chronic rheumatic disorder, accompanied by the differential expression of various microRNAs (miRNAs) in patients suffering from the condition, some of which have the potential to serve as novel complementary AS biomarkers. During this study, AS patients were recruited in connection with our investigation into the correlation of microRNA-132 (miR-132) in peripheral blood and its target gene NAG-1 expressions in relation with the clinical efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) treatment in patients with AS. A total of 218 AS patients who had been previously treated with oral diclofenac sodium and were placed into either the response (n = 175) or non-response groups (n = 43) following a 16-week period of therapeutic evaluation. An additional 113 healthy patients were also recruited for the purposes of the study. AS patient peripheral blood samples were obtained at the 0th, 8th, and 16th week, with the corresponding samples of the healthy patients collected at week 0. The expressions of miR-132 and NAG-1 were detected by RT-qPCR and analyzed using a ROC curve for the elucidation of the diagnostic value of peripheral blood miR-132 expressions as well as their predictive value among AS patients undergoing NSAIDs treatment. The targeting relations of miR-132 and NAG-1 were validated by microRNA.org and luciferase assay. Greater levels of peripheral blood miR-132 expression were observed among AS patients prior to treatment, in comparison to the healthy patients in the study. Prior to treatment, the area under the miR-132 ROC curve (AUC) of AS patients was 0.965, with a critical point of 2.605. The sensitivity and specificity of miR-132 were 91.7 and 97.3%, respectively, in regard to the AS diagnostic clinical efficacy. In comparison with the non-response group, the miR-132 expression of patients in the response group exhibited descended levels while the mRNA expression of NAG-1 increased. The ROC results indicated that the AUC of miR-132 was 0.876 with its sensitivity and specificity observed to be 95.3 and 80.0%, respectively. The AUC of NAG-1 was 0.912 with its sensitivity and specificity observed to be 76.6 and 79.1%, respectively. In comparison with the high miR-132 expression group and the low NAG-1 mRNA expression group, significantly improved blood biochemistry indexes, sign indexes, blood indexes, and adverse reaction rate were observed among the low miR-132 expression group and the high NAG-1 mRNA expression group. The microRNA.org and luciferase assay revealed NAG-1 to be a target of miR-132. Based on the results of this study, it was concluded that the expressions of MiR-132 and NAG-1 could serve as biological markers in the prediction of the therapeutic efficiency of NSAID treatment in AS patients.

Immuno-biological Assessments of Temporomandibular Joint Disease in Patients with Immune-mediated Rheumatic Conditions. A cross sectional study of 273 cases

Temporomandibular joint (TMJ) is commonly involved in various immune-mediated rheumatic disorders accounting for significant disability and impaired quality of life. The aim of our study was to assess inflammatory and immune parameters in patients with TMJ arthritis related to rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) and to identify potential relation with severity and dysfunction of TMJ pathology. We performed a cross-sectional study in a cohort of 433 consecutive RA, 32 JIA, 258 AS, and 103 PsA. Only patients presenting with clinically significant TMJ involvement (273) related to their rheumatic condition were included in the final analysis. TMJ involvement is traditionally described in chronic inflammatory rheumatic disorders, particularly in patients with higher levels of inflammation as detected in rheumatoid arthritis and psoriatic arthritis. Disease activity and severity, as well as biological and positive serological assessments (rheumatoid factor, anti-cyclic citrullinated peptide, IL-1) remain significant determinants of the severity of TMJ arthritis.

Suicidal behaviors in patients with rheumatic diseases: a narrative review.

Chronic rheumatic disorders are characterized by inflammation and chronic pain, and both anxiety and depression have been frequently observed in these patients. Depression and chronic pain are recognized as risk factors for the development of suicidal behaviors. Accordingly, the objective of the present review is to provide a comprehensive review of suicidal behaviors associated with rheumatic diseases. Medline and EMBASE were searched for English language publications using key words related with rheumatic diseases, suicide, suicide attempts, and suicidal ideation. 34 records (30 full-length published papers and 4 studies published in abstract form) that included data related to the frequency and/or potential determinants of suicidal behaviors in rheumatic diseases were included in the review. It was found that both suicidal ideation and completed suicide seem to be more frequent in patients experiencing systemic lupus erythematosus, fibromyalgia and arthritis. Major determinants were comorbid depression in fibromyalgia and arthritis, and neuropsychiatric disease in systemic lupus erythematosus. Based on these findings, suicide risk should be assessed in patients suffering from systemic lupus erythematosus, fibromyalgia and/or arthritis.

Ultrasound and follow-up of rheumatoid arthritis

Rheumatoid arthritis (RA) is chronic rheumatic disorder leading to joint inflammation and potential structural damages. This destruction occurs early in the disease outcome leading to the concept of window of opportunity. New diagnosis RA criteria have been proposed to allow an earlier diagnosis and subsequently a better management of the disease. Moreover, tight control of the disease was able to improve the prognosis of RA. For this, rheumatologists need routinely feasible tools and ultrasound (US) appears as the ideal imaging modality. US is superior to clinical exam for the detection of subclinical synovitis. US has a good correlation with clinical findings and markers of inflammation. US persistence of synovitis is associated with higher rate of relapse and more radiographic progression. However, standardization of scoring and settings procedures is necessary before being universally accepted as a marker of disease activity. Finally, US did not improve the tight control strategy and did not replace clinical exam for RA management.

CD4+ T cells in patients with chronic inflammatory rheumatic disorders show distinct levels of exhaustion

CD4+ T cells in patients with chronic inflammatory rheumatic disorders show distinct levels of exhaustion

Downstream activation of NF-κB in the EDA-A1/EDAR signalling in Sjögren's syndrome and its regulation by the ubiquitin-editing enzyme A20.

Sjögren's syndrome (SS) is an autoimmune disease and the second most common chronic systemic rheumatic disorder. Prevalence of primary SS in the general population has been estimated to be approximately 1-3%, whereas secondary SS has been observed in 10-20% of patients with rheumatoid arthritis, systemic lupus erythematosus (SLE) and scleroderma. Despite this, its exact aetiology and pathogenesis are largely unexplored. Nuclear factor-kappa B (NF-κB) signalling mechanisms provide central controls in SS, but how these pathways intersect the pathological features of this disease is unclear. The ubiquitin-editing enzyme A20 (tumour necrosis factor-α-induced protein 3, TNFAIP3) serves as a critical inhibitor on NF-κB signalling. In humans, polymorphisms in the A20 gene or a deregulated expression of A20 are often associated with several inflammatory disorders, including SS. Because A20 controls the ectodysplasin-A1 (EDA-A1)/ectodysplasin receptor (EDAR) signalling negatively, and the deletion of A20 results in excessive EDA1-induced NF-κB signalling, this work investigates the expression levels of EDA-A1 and EDAR in SS human salivary glands epithelial cells (SGEC) and evaluates the hypothesis that SS SGEC-specific deregulation of A20 results in excessive EDA1-induced NF-κB signalling in SS. Our approach, which combines the use of siRNA-mediated gene silencing and quantitative pathway analysis, was used to elucidate the role of the A20 target gene in intracellular EDA-A1/EDAR/NF-κB pathway in SS SGEC, holding significant promise for compound selection in drug discovery.

Reversal of Arthritis by Human Monomeric IgA Through the Receptor-Mediated SH2 Domain-Containing Phosphatase 1 Inhibitory Pathway.

Rheumatoid arthritis (RA), one of the most frequent chronic inflammatory rheumatic disorders, is characterized by the presence of autoantibodies and joint infiltration by activated immune cells, leading to cartilage and bone destruction. IgA occurs predominantly as monomers (mIgA) in plasma and regulates many cell responses through interaction with the Fcα receptor type I (FcαRI). FcαRI targeting by anti-FcαRI Fab inhibits activating receptors by inducing an inhibitory immunoreceptor tyrosine-based activation motif (ITAMi) configuration through SH2 domain-containing phosphatase 1 (SHP-1) recruitment. The aim of this study was to investigate the potential utility of mIgA for the treatment of arthritis by acting as an inducer of ITAMi signaling. The effect of plasma-derived human mIgA on inhibition of multiple heterologous receptors was evaluated on FcαRI+ cell transfectants, blood phagocytes from healthy individuals, and synovial cells from RA patients. FcαRI-transgenic mice and wild-type mice treated with mIgA were studied in models of collagen antibody-induced arthritis (CAIA) and collagen-induced arthritis (CIA). The mice were assessed for development of arthritis using an arthritis score, and joint tissue samples were evaluated for the extent of leukocyte infiltration and expression of phosphatase. Treatment with mIgA impaired cell activation in an FcαRI-FcRγ-dependent manner, involving ITAMi signaling. Human mIgA or anti-FcαRI Fab were strongly effective in either preventing or attenuating CAIA or CIA in FcαRI-transgenic mice. Administration of mIgA markedly inhibited the recruitment of leukocytes to the inflamed joints of mice, which was associated with induction of SHP-1 phosphorylation in joint tissue cells. Moreover, mIgA reversed the state of inflammation in the synovial fluid of RA patients by inducing an ITAMi configuration. These results demonstrate a therapeutic potential of human mIgA in experimental arthritis. The findings support future clinical exploration of mIgA for the treatment of RA.

Adherence to recommendations for cervical and breast cancer screening in systemic sclerosis

The aim of the study was to evaluate the adherence of systemic sclerosis (SSc) female patients to cervix and breast cancer screening procedures, as suggested by local guidelines. A cohort of 84 SSc women was asked if they had undergone mammography and Pap test during the previous 2- and 3-year intervals, as indicated according to the Italian recommendations. The results were compared with those collected in patients affected by other chronic rheumatic disorders and in the general population. More than 85% of SSc women declared to comply with an age-related cervix and breast cancer screening schedule. The data were similar to those collected in patients affected by other chronic rheumatic disorders, whereas the subjects belonging to the general population reported to undergo breast cancer screening more frequently. Among SSc women, neither the educational level, nor the lung and skin involvement influenced their cancer screening program compliance. Only a positive history of ischemic digital ulcers seemed to interfere with mammography. Our study reported a very high percentage of SSc female patients who adhered to programs for the early detection of cervical and breast cancer. The significant adherence to guidelines may be due to the schedule adopted by the local health public service, which regularly invites eligible subjects by mail to undergo cancer screening at no charge.

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with ankylosing spondylitis

Objectives. Ankylosing spondylitis (AS) is a chronic multi-systemic inflammatory rheumatic disorder. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with AS, and to assess the relation with inflammation.Methods. Sixty-two patients with AS and 50 controls were included. Tp-e interval and Tp-e/QT ratio were measured from a 12-lead electrocardiogram, and the Tp-e interval corrected for heart rate. The plasma level of high sensitive C-reactive protein (hsCRP) was measured. These parameters were compared between groups.Results. In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in AS patients compared to the controls (31.7 ± 9.6 vs 28.2 ± 7.4 and 35.8 ± 11.5 vs 30.6 ± 7.9 ms, P = 0.03 and P = 0.007, respectively). cTp-e interval and Tp-e/QT ratio were also significantly higher in AS patients (92.1 ± 10.2 vs 75.8 ± 8.4 and 0.22 ± 0.02 vs 0.19 ± 0.02 ms, all P values <0.001). cTp-e interval and Tp-e/QT ratio were significantly correlated with hsCRP (r = 0.63, P < 0.001 and r = 0.49, P < 0.001, respectively).Conclusions. Our study revealed that Tp-e interval and Tp-e/QT ratio were increased in AS patients. These electrocardiographic ventricular repolarization indexes were significantly correlated with the plasma level of hsCRP.

A9.1 Macrophage activation syndrome after mycoplasma pneumoniae infection

Introduction Macrophage activation syndrome is a rare and potentially life threatening condition, triggered by various events like bacterial and viral illness and sometimes it can be a complication of childhood...

OPTIMIZATION OF HEALTHCARE FOR CHILDREN WITH RHEUMATIC DISEASES IN EPOCH OF TREATMENT WITH GENETICALLY ENGINEERED BIOLOGICAL AGENTS (BY THE EXAMPLE OF THE REPUBLIC OF BASHKORTOSTAN)

Juvenile arthritis — is the most common chronic rheumatic disorder among children, which causes rapid development of disability, decrease of the quality of life, social and psychological dysadaptation . In the majority of cases the main pathogenetic treatment is methotrexate, however when there is resistance or intolerability of this drug, therapy with genetically engineered biological agents is indicated . Aim : to develop measures of optimization of medical support for children with juvenile arthritis according to analysis of its medical and social as well as economic consequences at regional level . Patients and methods : the epidemiologic study included screening questionnaires of 43 907 children with subsequent examination of those of them with inflammatory swelling of the joints during 1 year. F ormation of regional registry of children with juvenile arthritis has been performed in the Republic of Bashkortostan since 2003, regional component of the federal on-line registry has been functioning since 2011 . The prevalence of juvenile arthritis, its social and economic consequences and the «costs of the disease» were established. In total there were registered 474 patients with juvenile arthritis, among them 62 receive treatment with genetically engineered biological agents . Results : an order of providing the children with juvenile arthritis with medical agents is established — in-patient treatment is performed within the framework of specialized (including high-tech) medical care; genetically engineered biological drugs for out-patient therapy are purchased at the expense of republican state resources in the network of the social support of certain population groups («regional benefit»).

Adherence to medication for chronic disorders during pregnancy: results from a multinational study

For a variety of chronic disorders, low medication adherence during pregnancy may jeopardize maternal as well as foetal health. Little is known about how closely pregnant women follow their chronic pharmacotherapy regimens. To explore the level of adherence to medication for a variety of chronic disorders, namely cardiovascular, rheumatic and bowel disorders, diabetes and epilepsy, during pregnancy and to identify determinants of low adherence during pregnancy. This multinational, cross-sectional, internet-based study was undertaken in 18 countries in Europe, North America and Australia. Data originating from some South American countries were also collected. The study period lasted from 1-October-2011 to 29-February-2012. By using an anonymous on-line questionnaire we collected information about maternal demographics, chronic disorders and related medication use during pregnancy, and women's pregnancy-specific beliefs about medication. Main outcome measure Adherence to medication during pregnancy via the 8-item Morisky Medication Adherence Scale (MMAS-8). A total of 210 pregnant women reported chronic medication use during pregnancy and filled in the MMAS-8. Overall, 36.2 % had low medication adherence. On the basis of the MMAS-8, the rates of low adherence were 55.6 % for medication for rheumatic disorders, 40.0 % for epilepsy, 36.1 % for bowel disorders, 32.9 % for cardiovascular disorders, and 17.1 % for diabetes. A lack of folic acid use, having previous children, and individual pregnancy-specific beliefs about medication were significant determinants of low medication adherence during pregnancy. Many pregnant women had low adherence to their chronic pharmacotherapy regimens during pregnancy. Women's beliefs about medication were a central factor determining low adherence.

THU0454 Thyroid Involvement in Patients with Spondyloarthritis

BackgroundThe association between chronic inflammatory diseases and thyroid dysfunction is well recognized. This fact can be attributed to hormonal factors and the presence of a facilitator genetic terrain. Increased prevalence...