Immune-mediated Rheumatic Diseases Research Articles

Репродуктивная функция у женщин с иммуновоспалительными ревматическими заболеваниями

Репродуктивная функция у женщин с иммуновоспалительными ревматическими заболеваниями

Treat to Target in Rheumatology: A Historical Account on Occasion of the 10th Anniversary.

Chronic immune-mediated rheumatic diseases are characterized by inflammatory signs and symptoms, damage to joints, or spine and physical disability. In all these diseases the adverse outcomes are related to the degree of the inflammatory response and the duration of the high inflammatory situation. A state in which inflammation is minimized or eliminated is the therapeutic goal, but the time to reach such a state is also essential. Repeated treatment adaptations in the course of regular clinical assessments of disease activity are essential until the desired, predefined state is achieved. This approach constitutes the treat-to-target concept.

Considerations for Optimal Trial Design for Rheumatoid Arthritis Prevention Studies

The field of rheumatology has made major contributions to medicine through the identification of cellular and molecular targets and with the development of therapies for the treatment of an impressive range of immune-mediated rheumatic diseases. In recent years new milestones have been achieved. These include the recognition of an “at risk” state, defined by distinct clusters of characteristics, including disease-specific autoantibodies in serum and symptom complexes that include inflammatory joint pain. Studies seeking to prevent high-risk individuals from progressing to a state of clinically apparent arthritis have been initiated. Here, exploiting the current evidence base, an experimental framework to inform trial design is described, taking into consideration study patient phenotypes and highlighting the impact of risk stratification and the options available for therapeutic intervention according to the different phases of the preclinical syndrome. Pragmatic primary end points and suggestions for a set of risk-focused trial outcome measures are proposed, including both clinical assessments and patient-reported outcome measures. Rheumatoid arthritis prevention studies provide an important experimental framework for generating deeper insights into risk stratification and for refining trial design in the future. To this end, a research agenda is suggested, together with some considerations for imaging and for biological sampling. This commentary concludes with some of the operational issues that arise from such studies and addresses some of the challenges associated with recruitment and retention of the at-risk trial participant.

Real-world treatment persistence of golimumab in the management of immune-mediated rheumatic diseases in Europe: a systematic literature review

ObjectivesTo summarise real-world data from studies reporting golimumab persistence in European immune-mediated rheumatic disease (IMRD) populations and to report pooled estimates.DesignSystematic literature review.Data sourcesRelevant literature was identified through searching Medline...

Usefulness of complex bacteriological and serological analysis in patients with spondyloarthritis.

Spondyloarthritis (SpA) is a group of associated chronic systemic inflammatory immune-mediated rheumatic diseases affecting axial and peripheral joints and entheses. The aim of the present study was to identify what parameters are useful to determine in order to better understand the correlation between the disease activity/severity and the microbiological results/immune status against intestinal and/or urogenital pathogens. Microorganisms known to trigger SpA, including Klebsiella spp., Yersinia spp., Salmonella spp., Campylobacter spp. and Chlamydia spp., were analyzed in various specimens (stool, urine, synovial fluid and serum) collected from 27 randomly selected SpA patients and 26 healthy controls using a combined direct and indirect approach relying on conventional culture technique and nucleic acid-based assays together with serological testing by ELISA. Although Escherichia coli derived from phylogroup A prevailed in the gut microflora of the patients and controls, differences were observed regarding the representatives of the other phylogroups with a higher prevalence of E.coli members of phylogenetic group B1 in the stool specimens of patients. Antibodies against the targeted species were detected in SpA patients and controls, and the serological profiles of the former were more diverse and complex. In conclusion, the detection of anti-bacterial antibodies combined with other specific laboratory investigations should be more extensively used to monitor SpA patients in association with their symptoms and in order to determine and administer more effective therapeutics.

Применение ритуксимаба и других анти-В-клеточных препаратов при иммуновоспалительных ревматических заболеваниях

Применение ритуксимаба и других анти-В-клеточных препаратов при иммуновоспалительных ревматических заболеваниях

Prescribing patterns and safety of biologics in immune-mediated rheumatic diseases: Karnataka biologics cohort study group experience

Introduction: Biologics are widely used in Autoimmune rheumatologic diseases (AIRDs), however the need to capture real life data which monitors indications, adverse reactions cannot be over emphasized. Methods: This is a cross-sectional ambidirectional multi-center study conducted over 8 months from January 2016 to August 2016, across 12 tertiary care rheumatology centers in Karnataka, India conducted by members of the Karnataka Rheumatology Association. Results: The most common biologic prescribed is tumour necrosis factor antagonist etanercept. Commonest indication for biologics being Spondyloarthropathy group of disorders. The most common cause for stopping biologics is clinical improvement. Only 4.8% of patents discontinued biologics due to ADRs. Conclusion: The prescribing patterns, mode of use, prebiologics screening methods, and adverse event profile are similar across centres. Pre-screening for latent tuberculosis (TB) is consistent across centres, and TB prophylaxis appears to be effective in preventing its reactivation.

Cognitive disorders in Behçet's disease

To study the prevalence of cognitive disorders (CD) and clinical/pathogenetic correlations of CD in patients with Behçet's Disease (BD). One hundred and six BD patients were enrolled in the study. The majority of patients were natives of the North Caucasus (51.9%). Mean age was 33.3±0.98 years, mean illness duration 148.5±10.4 months. All the patients met the criteria of the International Study Group for BD (1990) classification. The disease activity was assessed by scoring system BDCAF. A diagnosis of a mental disorder (MD) was established by the psychiatrist in accordance with the ICD-10 using a semi-structured interview. The Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HAM-A), a pathopsychological method 'Pictograms', clinical/psychological methods for assessment of cognitive functions (memory, attention concentration, logic thinking) were administered. Brain MRI was done in 44 (41.5%) BD patients. The study was conducted in the frames of the interdisciplinary program 'Stress factors and mental disorders in immune-mediated inflammatory rheumatic diseases'. CD of mild to moderate severity were diagnosed in 82 (77.4%) and anxiety-depressive disorders in 81 (76.4%) of BD patients. The patients with CD were older compared to patients without cognitive disorders (34.3±1.07 vs 29.0±2.14, p=0.006). Patients with CD were most often (84.1% vs 50.0%, p=0.001) diagnosed with anxiety-depressive disorder (anxiety, chronic/recurrent depression). MADRS scores were higher (16.1±0.74 vs 12.2±1.06, p=0.005) though did not exceed the moderate level. The impact of chronic psychosocial stressors was detected more often in CD patients. MRI results showed that the frequency of chronic multifocal, predominantly subcortical, changes in the white matter was higher in CD patients. CD are characteristic of most patients with BD. They are associated with the age, anxiety-depressive disorders, chronic stressors and minor brain multifocal subcortical parenchymal MRI lesions.

Main Oral Manifestations in Immune-Mediated and Inflammatory Rheumatic Diseases.

Oral manifestations are frequent in patients with rheumatic diseases. The aim of this review is to offer readers practical advice concerning the onset, diagnosis and treatment of the main oral manifestations encountered in rheumatological and dental clinics. Signs and symptoms such as oral hyposalivation, xerostomia, temporomandibular joint disorders, periodontal disease, and dysphagia may be the first expression of a number of rheumatic diseases. Some of these manifestations are aspecific and very frequent, such as oral aphthosis, which can be the first manifestation in patients with systemic lupus erythematosus; some are potentially dangerous, such as jaw claudication during the course of giant cell arteritis; and some are very rare but peculiar, such as strawberry-like gingivitis in patients with granulomatosis with polyangiitis. Other oral manifestations are due to adverse reactions to disease-modifying anti-rheumatic drugs. Oral alterations in rheumatic diseases are frequently overlooked in clinical practice, but their prompt recognition not only allows the local lesions to be appropriately treated, but also makes it possible to identify an underlying systemic disease.

Second-line treatment persistence and costs among patients with immune-mediated rheumatic diseases treated with subcutaneous TNF-alpha inhibitors.

The objective of this study was to describe treatment persistence with second-line subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) in patients with immune-mediated rheumatic diseases (IMRDs) in Sweden, and the impact of non-persistence on healthcare costs. This retrospective observational study was based on Swedish national health register data. Adults were identified through filled prescriptions for adalimumab (ADA), etanercept (ETA), certolizumab pegol (CZP) and golimumab (GLM). Persistence was estimated over 3years for propensity score-matched (PSM) cohorts using non-parametric survival analysis. Unadjusted comparisons of costs comprised specialized outpatient care, inpatient care, and medication. In total, N=845 patients were identified and three PSM cohorts were generated (GLM vs. ADA, ETA, and CZP, respectively). GLM exhibited higher persistence than ADA over the study period (p=0.040), and numerically higher persistence than ETA and CZP for 36 and 30months, respectively. Persistent and non-persistent patients had similar mean total cost at 12month pre-treatment ($5185 vs. $5064, p=0.750). During the 12month post-treatment initiation, persistent patients had lower mean total costs ($4377 vs. $6605), corresponding to a cost difference of $2228 (p<0.001). In second-line treatment with SC-TNFis for IMRDs in Sweden, GLM exhibited significantly higher persistence than ADA over the course of the study. Similarly, GLM showed numerically higher persistence than ETA and CZP, which is concurrent with results observed in first-line SC-TNFi treatment. Considering the lower healthcare costs for persistent patients, the choice of second-line SC-TNFi among eligible patients may merit careful consideration given its impact on patients and payers.

Vitamin D supplementation and disease activity in patients with immune-mediated rheumatic diseases: A systematic review and meta-analysis.

Vitamin D serum levels and the presence and activity of rheumatic conditions have been associated. However, many studies are merely observational, and the existent randomized clinical trials were never systematically analyzed. Therefore, this study aims to provide a systematic review and meta-analysis of such a topic. MEDLINE, EMBASE, LILACS, COCHRANE, and CINAHL were explored to identify randomized trials that investigated clinical repercussions of vitamin D (or analogs) supplementation for at least 3 months in rheumatic diseases. Standardized clinical and/or laboratorial outcomes related to disease activity were analyzed according to each disease before and after supplementation. Database searches rendered 668 results; 9 were included-5 on rheumatoid arthritis, 3 on systemic lupus erythematosus, and 1 on systemic sclerosis. Seven of the studies were meta-analyzed. After vitamin D supplementation, rheumatoid arthritis recurrence decreased; however, not significantly (risk difference = -0.10, 95% CI = -0.21, 0.00, P = .05). No statistical significance was observed regarding visual analog scale (mean difference = 2.79, 95% CI = -1.87, 7.44, P = .24) and disease activity score28 (mean difference = -0.31, 95% CI = -0.86, 0.25, P = .28). Regarding systemic lupus erythematosus, anti-dsDNA positivity was significantly reduced (risk difference = -0.10, 95% CI = -0.18, -0.03; P = .005). Vitamin D supplementation reduced anti-dsDNA positivity on systemic lupus erythematosus and could possibly reduce rheumatoid arthritis recurrence, although novel randomized clinical trials are needed to confirm and extend the benefits of this hormone in immune-mediated rheumatic diseases.

Persistence with golimumab in immune-mediated rheumatic diseases: a systematic review of real-world evidence in rheumatoid arthritis, axial spondyloarthritis, and psoriatic arthritis.

PurposeIn immune-mediated rheumatic diseases (IMRDs), persistence to treatment may be used as a surrogate marker for long-term treatment success. In previous comparisons of persistence to tumor necrosis factor α inhibitors (TNFis), a paucity of data for subcutaneous (SC) golimumab was identified. The aim of this study was to conduct a systematic review of persistence to SC golimumab in clinical practice and contextualize these data with five-year persistence estimates from long-term open-label extension (OLE) trials of SC TNFis in IMRDs.Patients and methodsPubMed, Embase, MEDLINE, and conference proceedings from European League Against Rheumatism (EULAR), American College of Rheumatology (ACR), and International Society for Pharmacoeconomics and Outcomes Research (ISPOR) were searched. All studies on patients treated with SC golimumab for IMRD were included if they reported data on the persistence to golimumab.ResultsOf 376 available references identified through the searches, 12 studies with a total of 4,910 patients met the inclusion criteria. Furthermore, nine OLE trials were available. Among the included studies from clinical practice, at six months, one year, two years, and three years, the proportion of patients persistent to treatment ranged from 63% to 91%, 47% to 80%, 40% to 77%, and 32% to 67%, respectively. In the four studies that included comparisons to other biologics, golimumab was either statistically noninferior or statistically superior to other treatments, an observation that was supported by indirect comparisons of unadjusted point estimates of OLE trials.ConclusionThe data reviewed in this study indicate that golimumab may have higher persistence than other TNFis, a notion that is supported by indirect comparisons of persistence data from OLEs of randomized controlled trials (RCTs). Furthermore, the study suggests that persistence may be lower in biologic-experienced compared with biologic-naive patients and higher in axial spondyloarthritis compared with rheumatoid arthritis and psoriatic arthritis.

Proposal for an Urgency Score as General Referral Strategy to Second- Care Rheumatology

Objectives: To assess the practicability of a questionnaire to routinely discriminate between urgent and non-urgent rheumatology appointments by administrative personnel. Second, to discuss the results in view of current literature on referral strategies of rheumatic patients from primary to secondary care, including those with immune-mediated rheumatic diseases.

Biologic agents in immune-mediated inflammatory rheumatic diseases: current state of the art and clinical practice in Romania

The article describes a wide spectrum of biological agents for treatment of Immune-mediated inflammatory rheumatic diseases in clinical practice in EU. Pharmacological classification, main characteristics of anti-TNF agents and biologics with another modes of action, as well as the most important results of clinical trials are provided. Authors focused on the use of biological agents in clinical practice in emerging market regions such as Central and Eastern Europe, particularly in Romania, were disparity due to economic and social factors provides challenges to achieving optimal monitoring and physician’s decision making. Such very important points as an adoption of «treat to target» recommendations to local practice, consensus guidelines on the criteria for biological treatment, patient education initiatives, the development of a national patients registry, are discussed.

Biologicals in uveitis

Most noninfectious uveitis appears to be autoimmune or autoinflammatory in nature, requiring treatment with immunosuppressive and/or anti-inflammatory drugs. Inflammatory uveitis is a difficult condition to treat. Recently, a new class of drugs obtained by a biological process and therefore defined as biologics has been successfully used in the treatment of immune-mediated rheumatic diseases. These drugs target different proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and IL-6 or immune effector cells including B- and T-lymphocytes. The success in rheumatology of the TNF-α inhibitors adalimumab (ADA) and infliximab (IFX) over the past several years has led to their use in uveitis, in particular in patients with Behcet's disease and for early use in patients with juvenile idiopathic arthritis who have not benefitted from methotrexate. The first experience with anti-TNF inhibitors etanercept, IFX, and ADA gave us excellent results in uveitis. Other newer biologics approved by the United States Food and Drug Administration for rheumatic diseases are emerging treatments for uveitis. These include the anti-CD20 inhibitors rituximab, the anti-TNF inhibitors certolizumab and golimumab, the IL-6 inhibitor tocilizumab, the IL-1 inhibitor anakinra, the cytotoxic T-lymphocyte antigen 4 inhibitor abatacept. Uveitis, a significant cause of ocular morbidity worldwide, is undergoing major changes as biologic therapies have entered into the field. We used PubMed and CrossRef (Google) search engine as the main source of information. In this review, we outline the ideal characteristics of drugs for uveitis and review the data to support the use of current and emerging biological therapies in this context.

Scleroderma Lung Study II—clarity or obfuscation?

Systemic sclerosis (scleroderma) is one of the most recalcitrant of the immune-mediated rheumatic diseases because of its clinical impact and the high mortality associated with the internal organ complications that it causes. 1 Tyndall AJ Bannert B Vonk M et al. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis. 2010; 69: 1809-1815 Crossref PubMed Scopus (857) Google Scholar Lung fibrosis has emerged as a major cause of scleroderma-related death, and with better treatments for pulmonary arterial hypertension, the other main lethal lung manifestation of scleroderma, this looks set to continue. 2 Galiè N Barberà JA Frost AE et al. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med. 2015; 373: 834-844 Crossref PubMed Scopus (732) Google Scholar Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trialTreatment of scleroderma-related interstitial lung disease with mycophenolate mofetil for 2 years or cyclophosphamide for 1 year both resulted in significant improvements in prespecified measures of lung function over the 2 year course of the study. Although mycophenolate mofetil was better tolerated and associated with less toxicity, the hypothesis that it would have greater efficacy at 24 months than cyclophosphamide was not confirmed. These findings support the potential clinical effectiveness of both cyclophosphamide and mycophenolate mofetil for progressive scleroderma-related interstitial lung disease, and the present preference for mycophenolate mofetil because of its better tolerability and toxicity profile. Full-Text PDF

Pharmacoeconomics of Biosimilars: What Is There to Gain from Them?

Despite representing a breakthrough in the treatment of immune-mediated rheumatic diseases, the direct costs of biotechnological therapies represent a burden to healthcare budgets worldwide. Furthermore, several studies demonstrated that socioeconomically constrained countries have poorer access to these therapies and this has consequences on the optimal management of rheumatic patients. Experience with small peptide biosimilars like filgrastim and epoetin confirmed significant cost savings but revealed variable market uptake. In this report, we summarize the available budget impact models and discuss possible determinants of the pharmacoeconomic performance of antirheumatic biosimilar drugs.

Improved serological detection of rheumatoid arthritis: a highly antigenic mimotope of carbonic anhydrase III selected in a murine model by phage display.

IntroductionRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects around 1 % of the human population worldwide. RA diagnosis can be difficult as there is no definitive test for its detection. Therefore, the aim of this study was to identify biomarkers that could be used for RA diagnosis.MethodsSera from a collagen-induced arthritis mouse model were used to select potential biomarkers for RA diagnosis by phage display technology. In silico and in vitro analyses were performed to characterize and validate the selected peptides. Samples were classified into three groups: RA; two other immune-mediated rheumatic diseases (systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS)); and healthy controls (HC). Enzyme-linked immunosorbent assay (ELISA) was carried out to determine antibody levels, and diagnostic parameters were determined by constructing receiver operating characteristic curves. Mass spectrometry and Western blot were performed to identify the putative autoantigen that was mimicked by a highly reactive mimotope.ResultsAfter three rounds of selection, 14 clones were obtained and tested for immunoreactivity analysis against sera from RA and HC groups. The phage-fused peptide with the highest immunoreactivity (M12) was synthesized, and was able to efficiently discriminate RA patients from SLE, AS and HCs (p < 0.0001) by ELISA. The specificity and sensitivity of anti-M12 antibodies for RA diagnosis were 91 % and 84.3 %, respectively. The M12 peptide was identified as one that mimics a predicted antigenic site of the carbonic anhydrase III (CAIII) protein, a ubiquitous biomarker that has been identified in patients with other diseases.ConclusionM12 is the first peptide associated with the CAIII protein that may be used as an antigen for antibody detection to aid in RA diagnosis with high sensitivity and specificity.

MENTAL DISORDERS IN PATIENTS WITH RHEUMATIC DISEASES: DIAGNOSIS AND TREATMENT

The paper considers the prevalence, pattern, and clinical features of mental disorders (MDs) that are characteristic of patients with immune-mediated inflammatory rheumatic diseases (RDs). It discusses in detail risk factors for MDs, their pathogenesis, association with inflammatory activity, and major clinical symptoms of RD. Particular emphasis is placed on the diagnosis and treatment of MDs in patients with RDs in primary health care facilities and at rheumatology hospitals.

The classification and diagnostic criteria of ankylosing spondylitis

Ankylosing spondylitis is the prototype of immune-mediated inflammatory rheumatic diseases grouped under the term spondyloarthritis (SpA). An early diagnosis has now become increasingly important because effective therapies are available and anti-TNF drugs are even more effective if used in early stages of the disease. In ankylosing spondylitis, the 1984 modified New York criteria have been used widely in clinical studies and daily practice but are not applicable in early disease when the characteristic radiographic signs of sacroiliitis are not visible but active sacroiliitis is readily detectable by magnetic resonance imaging (MRI). Thus there has been a need for new classification or diagnostic criteria to identify inflammatory spondyloarthritis at early stage of the disease. This led to the concept of axial SpA to include the entire spectrum of patients with axial disease both, with and without radiographic damage. New classification criteria for the wider group of SpA have been proposed by ASAS (Assessment of Spondylo Arthritis International Society); and the patients are sub-grouped into (1) a predominantly axial disease, termed axial SpA including AS and non-radiographic axial SpA; (2) peripheral SpA. The clinical course and disease process of non-radiographic axial spondyloarthritis remains unclear. However the development of the SpA criteria by ASAS particularly for axial SpA, is an important step for early diagnosis and better management of these patients.