Inflammatory Rheumatic Disorders Research Articles

Inflammatory Rheumatic Disorders as a Complication of Endocrine Therapy for Breast Cancer

Inflammatory Rheumatic Disorders as a Complication of Endocrine Therapy for Breast Cancer

Dermatologists' and Rheumatologists' Adherence to the Latest Recommendations for Screening of Hydroxychloroquine Retinopathy in Saudi Arabia: A Cross-Sectional Study.

Hydroxychloroquine (HCQ) is used to manage the symptoms of inflammatory rheumatic and dermatologic disorders. However, HCQ retinopathy is aserious side effect becauseeven after the drug is discontinued, irreversible vision loss may occur and may continue to progress.According to the American Academy of Ophthalmology (AAO),the recent recommendation for HCQ dosing is ≤5 mg/kg of real body weight, with baseline ophthalmologic screening during the first year of HCQ treatment and yearly screening after five years of continuous use of HCQ medication, unless the patient is at high risk or symptoms have developed.Nonetheless, this study aims to assess dermatologists' and rheumatologists' adherence in Saudi Arabia to the 2016 AAO HCQ retinal toxicity guidelines. A questionnaire-based cross-sectional study was conducted on dermatologists and rheumatologists in Saudi Arabia. It was conducted between August and September 2022 and questionnaires were sent to dermatologists and rheumatologists via their professional emails or accounts. The collected sample consisted of 635 participants; males and females represented 54% and 46%, respectively; 47.6% were consultants; 50.1% were rheumatologists; and 49.9% were dermatologists. Approximately 28.2% of the participants reported treating one to three patients with HCQ in the previous year. Only 45.4% of the respondents stated that the ideal recommended HCQ dose for reducing the risk of retinopathy is "≤ 5 mg/kg of the real body weight." More than 50% of the respondents stated that systemic lupus erythematosus was the most common disease for which they used HCQ. Additionally, 36.5% of the physicians screened patients during the first year of HCQ treatment. We found significant associations between practice levels and specialty practice-related questions with a p-value of less than 0.05, except for the specialty practice-related question, "What is the most common disease for which you use HCQ?" with a p-value of 0.074. Also, we found significant associations between all demographic variables and screening-related variables with a p-value of less than 0.05, with two exceptions: no significant associations were found between specialty area and the screening-related question, "Do you recommend screening tests for all patients starting treatment with HCQ?" at p = 0.270, and gender and the screening-related question, "When would you recommend screening tests for a patient without risk?" at p = 0.142. Dermatologists and rheumatologists in Saudi Arabia have shown poor adherence to the most recent AAO recommendations. Educating physicians and patients about the AAO guidelines is needed for HCQ to be used in a way that is both effective and safe.

Risk of cardiovascular disease decreases over time in psoriatic arthritis but not in spondylarthritis: meta-analysis of longitudinal studies.

Spondyloarthritis (SpA) and psoriatic arthritis (PsA) represent two frequent inflammatory rheumatic disorders, characterized by an increased burden on quality of life, due to the association of several comorbidities, especially cardiovascular diseases (CVD). The estimated prevalence of CVD ranges from 12-19% and differ between the two diseases, however, its incidence is not completely known. We aimed to systematically review the literature (SLR) and perform a meta-analysis of controlled observational studies to assess the incidence rate of CVD over time, separately in SpA and PsA. We performed a SLR of longitudinal studies with a study period of at least 5 years, including SpA/PsA patients and general population. The main outcome was the occurrence of CVD, including ischemic heart disease, stroke, and death from CV cause. We then performed a random-effect model for meta-analysis. The SLR included 34 articles, mainly focused on the association between SpA/PsA and CVD. Twenty-four articles were then selected for the meta-analysis. The overall incidence of CVD was increased in PsA (HR: 1.28, 95%CI: 1.15-1.43), and in SpA (HR: 1.45, 95%CI: 1.22-1.72) compared with the general population, with consistency across the different types of CVD; Interestingly the incidence tended to decrease over time in PsA, but not in SpA. The SLR and meta-analysis confirmed the increased incidence of CVD in both SpA and PsA patients compared with the general population during the last years, although such increase seems to be less prominent in PsA than in SpA. Future studies are needed to confirm such tendence.

Facet joint involvement in the inflammatory rheumatic disease

Background: The involvement of facet joints (FJ) in patients with inflammatory rheumatic disorders remains underexplored. This review aims to look at FJ disease from a rheumatologist’s perspective, with the emphasis given to the clinical presentations and patterns of FJ engagement in axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), rheumatoid arthritis (RA), and crystal-related arthropathies, and discussion of challenges in studying FJ in rheumatic disease.Methods: A systematic PubMed search using the pertinent keywords was performed, relevant articles extracted, and the acquired data critically assessed, interpreted, and organized according to the authors’ experience and judgment.Results: FJ involvement is common in patients with radiographic axSpA, occurs throughout the spine, but is more frequently seen in the thoracic segment. The existing data suggests that the FJ are primarily affected by the disease process, while altered spine biomechanics due to the presence of syndesmophytes at the same vertebral level contributes to the FJ fusion. Predominant involvement of FJ of the cervical spinal segment has been suggested in PsA; however, prevalence and clinical significance of FJ involvement in PsA is still markedly underexplored. RA-related FJ disease of the cervical spine in patients with poorly controlled RA is not uncommon and can be related to significant morbidity, while the burden of FJ involvement in the thoracic and lumbar spinal segments in RA is also underexplored. FJ disease is possible in the course of crystal-related arthropathies, but the high level of suspicion is a prerequisite for the timely diagnosis.Conclusions: The involvement of FJ in the course of inflammatory rheumatic disease is not uncommon. Prospective studies are needed to understand the epidemiology and significance of FJ disease in inflammatory rheumatic conditions.

Prevalence of temporomandibular disorders in juvenile idiopathic arthritis evaluated with diagnostic criteria for temporomandibular disorders: A systematic review with meta-analysis.

Juvenile idiopathic arthritis (JIA) is a very common systemic inflammatory rheumatic disorder affecting the musculoskeletal system in children below 16 years of age. Joint inflammation and tissue destruction is the prime characteristic of the disease. Along with the systemic involvement in the long joints, several studies are mentioning the increased association of temporomandibular disorders (TMDs) in JIA. This current systematic review intends to find the prevalence rate of TMD in JIA-affected individuals as compared to healthy controls. We have searched in PubMed, Scopus and Ovid SP for articles published between the timeframe 1 January 1990 and 1 June 2023. All the searched articles were subjected to the Population, Exposure, Comparison, and Outcome model (PECO) based on which inclusion or exclusion is carried out. Participants (P) are children below 18 years of age, Exposure (E) is children or adolescents with a diagnosis of JIA, Comparator is age and gender-matched healthy controls who has no JIA or any systemic disorder, Outcome (O) is the prevalence of TMD. Only the studies that evaluated TMD using diagnostic criteria for evaluation of TMD (DC/TMD) were included in the analysis. We have set the exclusion to the following reasons- diagnostic sensitivity studies, case reports, and systematic reviews. The software Review Manager Version 5.4 (Cochrane Collaboration) was used to perform the pooled analysis. We measured the risk ratio (RR) between the two groups (JIA and no JIA) for the outcome TMD. The pooled total included subjects were 366 in this review with an established diagnosis of JIA as evaluated by DC/TMD. The overall effect of the pooled data suggests that there is a significant difference in the TMD prevalence in the JIA group when compared to the control, results suggest that TMD is more prevalent in the JIA group RR 3.86; 95% CI [2.59, 5.76]. Overall, based on the data we can suggest a positive relationship between JIA and TMD, hence presence of JIA can be a risk factor for the development of TMD. The sensitivity of DC/TMD is low when compared to magnetic resonance imaging.

Recommendations for assessing the risk of cardiovascular disease and venous thromboembolism before the initiation of targeted therapies for chronic inflammatory rheumatic diseases.

Patients with rheumatoid arthritis (RA) and other chronic inflammatory rheumatic disorders have increased risk of cardiovascular disease (CVD) and venous thromboembolism (VTE) compared with the general population. Moreover, recent data have raised concerns around a possible increased risk of major CV events (MACE) and VTE in patients treated with JAK inhibitors (JAKi). In October 2022, the PRAC has recommended measures to minimize the risk of serious side effects, including CV conditions and VTE, associated with all approved in chronic inflammatory diseases. To provide an adequate and feasible strategy to evaluate, at the individual level, the risk of CVD and VTE in patients with chronic inflammatory rheumatic diseases. A multidisciplinary steering committee comprised 11 members including rheumatologists, a cardiologist, a hematologist expert in thrombophilia and fellows. Systematic literature searches were performed and evidence was categorized according to standard guidelines. The evidence was discussed and summarized by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk of MACE and VTE in patients with chronic inflammatory rheumatic diseases compared with the general population. Second, the rheumatologist has a central role in the evaluation of the risk of CVD and VTE in patient with chronic inflammatory rheumatic diseases. Third, the risk of MACE and VTE should be regularly assessed in patients with chronic inflammatory rheumatic diseases, particularly before initiating targeted therapies. Eleven recommendations were defined to prevent potentially life-threatening complications of CVD and VTE in patients with chronic inflammatory rheumatic diseases, providing practical assessment of CVD and VTE before considering the prescription of targeted therapies, and especially JAKi. These practical recommendations based on expert opinion and scientific evidence provide consensus for the prevention and the assessment of CVD and VTE.

INFLAMMATION, MENOPAUSE, AND WOMEN’S HEALTH: A RHEUMATOLOGICAL PERSPECTIVE

Inflammatory rheumatic disorders come with their plethora of complications including accelerated ovarian aging and the associated adversities which could be a consequence of disease itself or treatment with immunosuppressants. While aiming for treat-to-target in these patients, its effect on the ovaries takes a backseat.
 This review focusses on this underexplored avenue of effect of inflammation, inflamm-aging and the associated complications that come with early menopause, in the context of autoimmune rheumatic diseases (AIRDs). Some autoimmune diseases like lupus have a major role of estrogen in their causation and tend to be less severe when the onset is after menopause, while in other inflammatory arthritis like rheumatoid arthritis (RA), estrogen may have some anti-inflammatory potential. Inflamm-aging that is associated with the AIRDs also leads to early menopause and premature ovarian insufficiency in some patients, which adds-on to the morbidity and sometimes, mortality.
 With early ovarian aging and precipitous decline in circulating estrogen, there is accelerated reduction in the bone mass and early set-in of osteoporosis. Long-term steroids, on-going inflammation and RA itself are major risk factors. The high risk of detrimental fragility fractures in these patients with a consequential reduction in the quality of life with higher loss of disability adjusted life years (DALY) and poorer functional outcomes, contributes to long-term morbidity. While remission induction and maintenance are a major part of treatment, physicians should exercise a keen eye towards recognizing early menopause and its adversities and inculcate measures for osteo-protection and prevent adding on to the morbidity. Future prospects would include attempts at delaying ovarian aging by targeting mTOR/S6 kinase pathways and preservation of ovarian tissue.

Frequency and severity of sarcopenia in patients with inflammatory and noninflammatory musculoskeletal diseases : Results of a monocentric study in a tertiary care center

Sarcopenia (SP) is defined as the pathological loss of muscle mass and function. This is aclinically relevant problem, especially in geriatric patients, because SP is associated with falls, frailty, loss of function, and increased mortality. People with inflammatory and degenerative rheumatic musculoskeletal disorders (RMD) are also at risk for developing SP; however, there is little research on the prevalence of this health disorder in this patient group using currently available SP criteria. To investigate the prevalence and severity of SP in patients with RMD. A total of 141consecutive patients over 65years of age with rheumatoid arthritis (RA), spondylarthritis (SpA), vasculitis, and noninflammatory musculoskeletal diseases were recruited in across-sectional study at a tertiary care center. The European Working Group on Sarcopenia in Older People (EWGSOP1 and2) definitions of presarcopenia, SP, and severe SP were used to determine the prevalence. Lean mass as aparameter of muscle mass and bone density were measured by dual X‑ray absorptiometry (DXA). Handgrip strength and the short physical performance battery (SPPB) were performed in astandardized manner. Furthermore, the frequency of falls and the presence of frailty were determined. Student'sT-test and the χ2-test were used for statistics. Of the patients included 73% were female, the mean age was73 years and 80% had an inflammatory RMD. According to EWGSOP2, 58.9% of participants probable had SP due to low muscle function. When muscle mass was added for confirmation, the prevalence of SP was 10.6%, 5.6% of whom had severe SP. The prevalence was numerically but not statistically different between inflammatory (11.5%) and noninflammatory RMD (7.1%). The prevalence of SP was highest in patients with RA (9.5%) and vasculitis (24%), and lowest in SpA (4%). Both osteoporosis (40% vs. 18.5%) and falls (15% vs. 8.6%) occurred more frequently in patients with SP than those without SP. This study showed arelatively high prevalence of SP, especially in patients with RA and vasculitis. In patients at risk, measures to detect SP should routinely be performed in astandardized manner in the clinical practice. The high frequency of muscle function deficits in this study population supports the importance of measuring muscle mass in addition to bone density with DXA to confirm SP.

Exploring pain catastrophizing and its associations with low disease activity in rheumatic inflammatory disorders.

Pain catastrophizing is a maladaptive mechanism associated with the exaggerated experience of pain, increased rumination and feelings of helplessness. The main objective of this study was to explore whether increased pain catastrophizing is independently associated with a lower proportion of low disease activity (LDA) in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondylarthritis (axSpA). Demographics, comorbidities, treatment, disease activity measures and patient-reported outcome data were recorded in RA, PsA and axSpA patients. Pain catastrophizing score (PCS) was assessed using a standardised questionnaire. For each diagnosis, composite disease activity scores with distinct cut-off values for LDA, i.e. DAS28-CRP (RA), DAPSA (PsA) and ASDAS-CRP (axSpA) were calculated and used as the dependent variable in logistic regression reflecting LDA achieved. A total of one thousand two hundred and twenty nine patients were included: 580 with RA, 394 with PsA and 255 with axSpA. In the multivariable analysis, pain catastrophizing was independently associated with LDA rates in axSpA (OR 0.33, 95% CI [0.12, 0.88]) amongst tested groups. In RA (OR 0.90, 95% CI [0.64, 1.28]) and PsA (OR 0.77, 95% CI [0.55, 1.07]), a statistically significant association was not observed. Higher PCS was independently associated with not achieving LDA in axSpA. Our data, however, indicate that pain catastrophizing, which also reflects a patient's personality traits and coping abilities, plays a less important role for the patient than general pain perception.

Phytochemistry, ethnomedicinal uses and pharmacological activity of Diodia scandens; a review of current scientific literature

ABSTRACT Plants are natural sources of readily available phytochemicals which possesses interesting biological activities. The plant Diodia scandens is a creeping and straggling perennial herb commonly dispersed in tropical Africa, tropical Asia and some parts of Cameroon, Congo and Nigeria. It is used traditionally in the treatment of several disease conditions such as snake bites, rheumatic inflammatory disorders, earache, venereal diseases, hypertension and epilepsy. It is also used as an aphrodisiac and in the treatment of uterine inertia and postpartum hemorrhage. Despite its vast traditional uses, a comprehensive information on the plant is still lacking. In this review, we aimed to provide concise information on reported ethnomedicinal uses, phytochemistry, and pharmacological activities of Diodia scandens to support its traditional usage in exploring its therapeutic potentials. Available information about the plant was retrieved from online databases including PubMed and Google Scholar using the search terms ‘Diodia scandens’, ‘ethnomedicinal uses and Diodia scandens’, ‘phytochemistry and Diodia scandens’ and ‘pharmacological activity and Diodia scandens’. The available literatures supported several ethnobotanical claims on the use of D. scandens in traditional medicine. Other claims not yet scientifically verified should be explored to ascertain the veracity of such claims on its therapeutic potentials.

Decidua Stromal Cell (DSCs), As an Alternative Treatment for Acute Inflammatory Diseases

Introduction: Mesenchymal stromal cells (MSCs) were first explored from the bone marrow in the late 60s and further studies have shown that MSCs are present in several tissues including bone marrow, adipose tissue, umbilical cord, and placenta. Their safety and efficacy were explored in several inflammatory disorders (e.g. acute graft-versus-host disease-aGvHD, Acute respiratory distress syndrome-ARDS) and non-inflammatory diseases (Osteoarthritis and regenerative medicine). We have expanded this cell therapy approach to newer and more efficient stromal cells, derived from human placenta named decidua stroma cells (DSCs). The fetus is protected against the mother's immune system by the placenta and fetal membranes (Fig1). The DSCs play an important role in the feto-maternal tolerance and have been used in Africa for centuries to treat burns. We have cultured stromal cells from fetal membranes and found that they have a better immunosuppressive effect than stromal cells from other origins. DSCs are safe to infuse with no serious side effects. DSCs differ from BM-MSCs in several aspects; they are half the size, more immunosuppressive, need direct contact to show the immunomodulatory effect, have a better expansion capacity, but do not differentiate well to cartilage and bone. We have so far used DSCs to treat patients with ARDS following Covid-19 infection as well as aGVHD and hemorrhagic cystitis (HC) following HCT. In all treated patients we achieved fairly high positive responses in the vast majority of patients. Methods The fetal membranes are dissected from the placenta tissues and undergo enzymatic digestion. DSCs are then isolated and expanded under GMP conditions from healthy donors after caesarian section. The isolated DSCs are characterized by flow cytometry, karyotype analysis. Subsequently DSCs are frozen slowly in fetal bovine serum and stored in liquid nitrogen until use. Optimal dose of DSCs is 1 × 106 /kg body weight. To prevent allergic reactions steroids were administered intravenously before each cell infusion. All DSC infusions were administered intravenously. Results: DSCs were given to ten ARDS patients following Covid-19 infection with pulmonary infiltrate. Eight patients survived and were discharged from ICU, where the blood oxygen level dramatically increased after two DSCs infusions (Behnam et al 2021) (Fig 2). Eleven patients with HC, grade 3-4 were also treated with DSCs after HCT. In 5 patients, HC disappeared within 5 days after DSC infusion. Patients who received DSCs within 3 days after the start of HC had a duration of HC of 5 days and a shorter duration of pain than patients who were given DSCs later (p = 0.02). Nine of the 11 patients (82%) were alive 1 year after HCT (Aronsson-Kurtila et al 2018) . DSCs were also given to 21 patients with severe aGVHD. All patients responded, and one-year survival was 76%. No patient died of GVHD. Cause of death was like those observed in allogeneic HCT patients and no death related to DCS therapy. One-year survival was significantly better than 23% in 22 patients who were treated with BM-MSCs, or 3% for 32 historic controls with conventional therapy (p<0.01) (Ringdén et al 2018). There was no infusion related toxicity. Among more than 200 DSCs infusions we observed only transient reversible infusion reactions in 3 patients. In none of them cell infusion was stopped since no severe side effect was observed ( Sadeghi et al 2019) Conclusion: MSCs from tissues, like BM, adipose, umbilical cord, and placenta tissues, have taken the step from experimental animals to clinical trials. In this abstract, we have presented the use of DSCs as treatment for acute GvHD, HC and ARDS. Further improvements in clinical efficacy by stromal cells therapy may be achieved by optimizing the cell production process. In future, many different types of MSCs products may be used for specific clinical indications. Primary indications for MSCs and DSCs include among others acute GvHD and hemorrhages, e.g. hemorrhagic cystitis and ARDS, but many other indications, e.g. osteogenesis imperfecta, rheumatic inflammatory disorders, cardiovascular diseases, sepsis and septic shock, inflammatory bowel disease, multiple sclerosis, neuroinflammation and other acute inflammatory disorders may join the line of established therapies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Immunometabolic Analysis of Synovial Fluid from Juvenile Idiopathic Arthritis Patients.

Juvenile idiopathic arthritis (JIA) is an inflammatory rheumatic disorder. Polymorphonuclear neutrophils (PMNs) are present in JIA synovial fluid (SF), but with variable frequency. SF PMNs in JIA were previously shown to display high exocytic but low phagocytic and immunoregulatory activities. To further assess whether the degree of SF neutrophilia associated with altered immune responses in JIA, we collected SF and blood from 16 adolescent JIA patients. SF and blood leukocytes were analyzed by flow cytometry. SF and plasma were used for immune mediator quantification and metabolomics. Healthy donor blood T cells were cultured in SF to evaluate its immunoregulatory activities. PMN and T cell frequencies were bimodal in JIA SF, delineating PMN high/T cell low (PMNHigh) and PMN low/T cell high (PMNLow) samples. Proinflammatory mediators were increased in SF compared with plasma across patients, and pro- and anti-inflammatory mediators were further elevated in PMNHigh SF. Compared to blood, SF PMNs showed increased exocytosis and programmed death-1/programmed death ligand-1 expression, and SF PMNs and monocytes/macrophages had increased surface-bound arginase-1. SPADE analysis revealed SF monocyte/macrophage subpopulations coexpressing programmed death-1 and programmed death ligand-1, with higher expression in PMNHigh SF. Healthy donor T cells showed reduced coreceptor expression when stimulated in PMNHigh versus PMNLow SF. However, amino acid metabolites related to the arginase-1 and IDO-1 pathways did not differ between the two groups. Hence, PMN predominance in the SF of a subset of JIA patients is associated with elevated immune mediator concentration and may alter SF monocyte/macrophage phenotype and T cell activation, without altering immunoregulatory amino acids.

High Throughput Genetic Characterisation of Caucasian Patients Affected by Multi-Drug Resistant Rheumatoid or Psoriatic Arthritis.

Rheumatoid and psoriatic arthritis (RA and PsA) are inflammatory rheumatic disorders characterised by a multifactorial etiology. To date, the genetic contributions to the disease onset, severity and drug response are not clearly defined, and despite the development of novel targeted therapies, ~10% of patients still display poor treatment responses. We characterised a selected cohort of eleven non-responder patients aiming to define the genetic contribution to drug resistance. An accurate clinical examination of the patients was coupled with several high-throughput genetic testing, including HLA typing, SNPs-array and Whole Exome Sequencing (WES). The analyses revealed that all the subjects carry very rare HLA phenotypes which contain HLA alleles associated with RA development (e.g., HLA-DRB1*04, DRB1*10:01 and DRB1*01). Additionally, six patients also carry PsA risk alleles (e.g., HLA-B*27:02 and B*38:01). WES analysis and SNPs-array revealed 23 damaging variants with 18 novel “drug-resistance” RA/PsA candidate genes. Eight patients carry likely pathogenic variants within common genes (CYP21A2, DVL1, PRKDC, ORAI1, UGT2B17, MSR1). Furthermore, “private” damaging variants were identified within 12 additional genes (WNT10A, ABCB7, SERPING1, GNRHR, NCAPD3, CLCF1, HACE1, NCAPD2, ESR1, SAMHD1, CYP27A1, CCDC88C). This multistep approach highlighted novel RA/PsA candidate genes and genotype-phenotype correlations potentially useful for clinicians in selecting the best therapeutic strategy.

Inflammatory Arthritis Facilitators and Barriers (IFAB) for physical activity questionnaire: cross-cultural adaptation into Turkish and evaluation of its psychometric properties

Purpose We aimed to conduct the translation and cross-cultural adaptation of the Inflammatory arthritis Facilitators and Barriers (IFAB) questionnaire into Turkish language for patients with axial spondyloarthritis (axSpA) and analyze the psychometric properties of the IFAB-Turkish version (IFAB-Tr). Methods Data from ninety-three patients with axSpA were analyzed who completed the IFAB-Tr, Health Assessment Questionnaire (HAQ), Hospital Anxiety and Depression Scale (HADS) and Bath Ankylosing Spondylitis Functional Index (BASFI). Internal consistency, test-retest reliability, convergent validity, floor and ceiling effect, measurement error were examined. Exploratory factor analysis (EFA) and confirmatory factor analysis were conducted. Results Small modification was needed in the translation and cultural adaptation process. Internal consistency of the IFAB-Tr total score was 0.71 and test-retest reliability was excellent for IFAB-Tr (ICC = 0.90). A moderate negative correlation was found between IFAB-Tr total score and HAQ, HADS, BASFI scores. No floor and ceiling effect was detected. Minimal detectable change was 10.34 points. EFA revealed two factors which accounted for 55% of the variance. Conclusions The IFAB was successfully translated into the Turkish language and seems suitable for evaluating barriers and facilitators for physical activity in rheumatic diseases and could be used in clinical settings before designing a physical activity intervention. IMPLICATIONS FOR REHABILITATION The Turkish version of the Inflammatory arthritis FAcilitators and Barriers (IFAB) is a valid and reliable tool to assess barriers and facilitators to physical activity for patients with axial spondyloarthritis. More work is needed to assess all psychometric properties of the IFAB questionnaire in other inflammatory rheumatic disorders. The Inflammatory arthritis FAcilitators and Barriers questionnaire in Turkish is an easy and quick way to determine potential barriers to physical activity in clinical and research settings.

SARS-CoV-2 Vaccine Response in Patients With Autoimmune Hepatitis

Patients suffering from autoimmune hepatitis, a chronic immune-mediated liver disease with an incidence of 0.9 to 2 per 100,000 population per year in Europe, are considered to have a particularly increased risk for coronavirus disease 2019 (Covid-19)-associated hospitalization and death.1,2 Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination provides an essential tool to reduce morbidity and mortality in this cohort. However, a large multicenter study in China has shown a lower immunogenic response to inactivated whole-virion SARS-CoV-2 vaccines of chronic liver disease patients in comparison with the healthy population.3 Furthermore, reports from inflammatory bowel diseases or rheumatic disorders showed a reduced serologic response in patients taking glucocorticoids or thiopurine.4,5 The decrease in vaccine-induced antibodies over time, as well as the emergence of variants of concern, led to the recommendation of an additional vaccination in immunocompromised patients.

Analytical and clinical evaluation of DiaSorin Liaison® Calprotectin fecal assay adapted for serum samples.

BackgroundCalprotectin is a calcium‐binding protein that can be measured in serum, plasma, and feces. Increased serum and plasma calprotectin concentrations have been found in chronic inflammatory rheumatic disorders. An analytical and clinical evaluation of the DiaSorin Liaison® fecal Calprotectin assay using LIAISON® XL was performed.MethodsThe protocol included an analytical and clinical evaluation in which imprecision, the linearity of dilution, differences between serum and plasma samples and method comparison with CalproLab™ ELISA kit were assessed. Serum calprotectin concentrations in active (n = 26) and remission (n = 23) rheumatoid arthritis (RA) patients were compared.ResultsThe intra‐day and inter‐day analytical imprecision CVs ranged from 2.9% to 4.0% and 2.7% to 10.4%, respectively. Correlation between measured and expected values was high (R > 0.99), indicating good linearity. The Wilcoxon signed‐rank test showed that serum and plasma matched samples presented statistically significant differences (p < 0.001) being the highest concentrations of calprotectin observed in serum samples. Deming regression equation was as follows: Diasorin calprotectin (μg/ml) = −0.32 (95% CI: −0.65 ‐ −0.05) +1.58 (95% CI: 1.42–1.79).* Calprolab calprotectin (μg/ml). Significantly higher serum calprotectin levels were found in RA patients with active disease when compared to patients with low disease activity or in clinical remission (mean ± SD) [(3.35 μg/ml ± 1.55) vs. (1.63 μg/ml ± 0.52), p < 0.001] and these levels correlated well with all disease activity indices.ConclusionsThe DiaSorin Liaison® fecal Calprotectin assay adapted for serum samples showed adequate technical performances and the clinical performances were similar to other assays.

Ankylosing Spondylitis: A Risk Factor for Parkinsonism-A Nationwide Population-Based Study.

Ankylosing spondylitis (AS) is an immune-mediated, chronic inflammatory rheumatic disorder. The etiology of Parkinson's disease (PD) is multifactorial; however, inflammation is receiving an increasing amount of attention as an underlying cause of the neurodegenerative process of PD. We performed a nationwide longitudinal, population-based matched cohort study to assess the association with the later development of parkinsonism in Korea. This study was conducted using records from the Health Insurance Review and Assessment Service database. The cumulative incidence rate of PD was estimated. Fine-Gray subdistribution hazard models were used to identify hazards associated with PD development based on the presence of AS. Exposure to anti-inflammatory drugs was measured and analyzed to determine the protective effect of these medications. Additionally, the hazard ratio (HR) for atypical parkinsonism was estimated. The results of the Fine-Gray subdistribution hazard model revealed that the HR for PD development in the AS group was 1.82 (95%confidence interval [CI], 1.38-2.39, p < 0.001). A significant decrease in PD development was observed in patients with AS taking non-steroidal anti-inflammatory drugs (NSAIDs). The HR for atypical parkinsonism in the AS group was 3.86 (95%CI, 1.08-13.78, p < 0.05). We found that AS was associated with an increased risk of PD and atypical parkinsonism. NSAIDs used for AS control have some protective effects against PD. Further studies assessing whether biological treatment mitigates PD risk in patients with high activity are warranted.

Immunogenicity of Rituximab biosimilar GP2013 in chronic inflammatory rheumatic disorders in daily clinical practice

ObjectiveTo study in daily practice the risk of immunogenicity of patients treated with the biosimilar rituximab (RTX) GP2013 used for chronic inflammatory rheumatic disorders. MethodsA prospective monocentric routine care study was carried out between September 2018 and May 2021, including consecutive patients treated with the biosimilar RTX GP2013. Biosamples were taken before each infusion to quantify anti-RTX antibodies (ADAbs) and serum RTX trough levels by ELISA (Lisa Tracker Duo Rituximab, LTR005, Theradiag). Results168 GP2013-treated patients were included (129 who switched from originator RTX and 39 originator RTX naïve). The analysis of 602 samples identified 15 patients (8%) with positive ADAbs including 6 and 9 with transient and persistent ADAbs, respectively. The switch from originator RTX to GP2013 did not increase the risk of immunogenicity, with an incidence rate of 0.8 for 100 patient years. The frequency of persistent ADAs was higher in non-RA patients (5/56, 9% vs. 4/112, 3.5%). Patients with positive persistent ADAbs were more frequently non-caucasian (7/9, 78%, vs. 56/159, 35%, p<0.01) and all had detectable circulating B cells (vs. 40% in ADAb-negative patients, P<0.001). ADAb positivity was not associated with disease activity or RTX discontinuation but patients with ADAb titers >100 ng/mL experienced reduced treatment efficacy or severe infusion-related reaction. ConclusionWithin the study duration, the immunogenicity of GP2013 is a rare event affecting the pharmacodynamics of RTX. Although development of ADAbs had no impact on treatment discontinuation, possible harmful consequences may be observed in patients with high antibody levels.

Functionally Active Antibodies to the Angiotensin II Type 1-Receptor Measured by a Luminometric Bioassay Do Not Correlate With Clinical Manifestations in Systemic Sclerosis: A Comparison With Antibodies to Vascular Receptors and Topoisomerase I Detected by ELISA.

Objectives1) To detect functionally active antibodies(abs) to the angiotensin II type-1-receptor (AT1R) by a novel luminometric assay. 2) To assess their prevalence in systemic sclerosis (SSc), other collagen disorders, as well as in further chronic inflammatory disorders including autoimmune, toxic and chronic viral diseases. 3) To compare these abs with anti-AT1R antibodies by ELISA as well as with antibodies to endothelin-type-A receptors (ETA1) and to topoisomerase I (topo-I) with respect to their specificity and clinical relevance.MethodsSera from 98 SSc-patients, 110 patients with other chronic inflammatory rheumatic disorders, 97 patients with autoimmune liver diseases, 57 patients with toxic or chronic viral liver diseases and 36 healthy controls were analyzed. A luminometric bioassay was established with Huh-7-cells constitutively expressing the AT1R. Patients’ sera were also tested by commercially available ELISA for anti-AT1R, -ETA1- and by an in-house ELISA for anti–topo-I-abs.ResultsFifty-two percent of the SSc-patients had functionally active anti-AT1R-abs with stimulatory (34%) or inhibitory capacity (18%). They were present also in up to 59% of patients with other rheumatic diseases but only 22% of healthy individuals (sensitivity 52%, specificity 53%). The functionally active antibodies detected by the luminometric assay did not correlate with anti-AT1R-, -ETA1- or -topo-I-abs measured by ELISA, but there was a strong correlation between anti-topo-I-, AT1R-, and -ETA1-ab reactivity measured by ELISA. Sensitivities of 55%, 28% and 47% and specificities of 66%, 87%, and 99% were calculated for these anti-AT1R-, -ETA1-, and anti-topo-I-abs, respectively. Functionally active abs did not correlate with disease severity or any organ manifestation. In contrast, abs to topo-I, AT1R, and ETA1 were associated with digital ulcers, pulmonary- and esophageal manifestation.ConclusionsFunctionally active anti-AT1R-abs can be detected in SSc-patients but do not correlate with disease activity. They are not specific for this disease and occur also in other autoimmune disorders and even viral or toxic diseases. Also, the vascular antibodies detected by ELISA are not SSc-specific but correlated with disease manifestations. In contrast, anti-topo-I-abs were confirmed to be a highly specific biomarker for both, diagnosis and organ manifestations of SSc.

Evidence for the Use of Secukinumab in Patients with Radiographic and Non-radiographic Axial Spondyloarthritis in the Last 5 Years.

Axial spondyloarthritis (axSpA) is an inflammatory rheumatic disorder that causes chronic pain, primarily in the spine and sacroiliac joints. It is characterized by the presence of type 1 major histocompatibility complex HLA-B27 genetic marker, arthritis in peripheral joints, enthesitis and/or dactylitis and extra-articular manifestations. Current guidelines recommend biological therapy when first-line therapy is not sufficiently effective. The finding that the interleukin (IL)-17 axis is vital for the pathogenesis of axSpA propelled the development of secukinumab, a fully human monoclonal antibody directed against IL-17A. The present review provides evidence on the efficacy and safety of secukinumab in the treatment of radiographic and non-radiographic axSpA from nine randomized controlled phase III trials, as well as evidence from real-world observational analyses. The primary endpoint in six clinical trials was the proportion of patients meeting the Assessment of SpondyloArthritis international Society criteria for either 20% or 40% improvement (ASAS20, ASAS40) at week 16. Significantly more patients achieved the primary endpoint with secukinumab compared with placebo in all the studies except MEASURE 4. Both clinical trials and real-world studies showed significant improvements in the secondary endpoints of disease activity, quality of life, and pain and fatigue relative to placebo. The benefits of secukinumab were generally sustained during longer-term (up to 5 years) treatment. Overall, secukinumab was well tolerated with a low frequency of adverse events and treatment persistence was high in the real-world setting. Although indirect comparisons suggest that secukinumab and adalimumab have comparable efficacy and safety, they are being directly compared in the ongoing SURPASS study. During the current coronavirus disease 2019 (COVID-19) pandemic, it is advisable to continue biological therapy in patients who do not have severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection, but interrupt treatment during an infection, reinitiating once the patient has recovered from the infection. In conclusion, secukinumab is a largely safe and effective treatment for radiographic and non-radiographic axSpA.