The immune profile of patients with rheumatoid arthritis during immunosuppresive therapy

The aim of the work is to make a complex investigation of the efficiency of biological agents or/and conventional DMARD therapy presenting the evolution of the biomarkers from the pretreatment stage up to 24 weeks of therapy and establishing weather the is a correlation between these biomarkers. A number of 26 patients from 3 clinics in Bucharest (Romania), diagnosed with RA according to ACR criteria, were evaluated prospectively during 24 weeks of therapy with DMARD or/and biological agents. We evaluated IL-1, IL-6, IL-8, IL-17, TNF-alfa, TGF-beta, tDPD, MMP-3, COMP, ICAM1,CD40L, RF IgG, IgA, IgM, CCP, AKA at 0, 6 and 24 weeks of treatment. In this study were included patients who are over 18, are for the first time on this therapy or after 6 months of break and are not on corticosteroids. The entire group of patients was divided in subgroups A (patients under DMARD therapy), and subgroup В (patients under DMARD and biological agents). The RF IgG in the group unde biological agents and DMARD had a much significant decrease (p=0,0028), and after 24 weeks the mean value was in normal limits. DAS28 was more decreased in group В (group В DAS28=0,008, group A DAS28=0,015); CRP was statistically significant decreased in the entire group of patients(X2=5,991), sig=0,013. TNF-alfa was significantly decreased in the entire group of patients (x2=5,991), sig—0,013. ICAM 1 in the group В presented variations which were statistically significant (p=0,021). In the group A CD40L presented variations which were statistically significant (p=0,017). In the group A were significantly decreased MMP3 (p=0,049) and COMP (p=0,015), tDPD was modified in the entire group of patients (x2-5,991), sig=0,013. The parameters which are statistically significant modified during 24 weeks of therapy in the entire group of patients are: CRP, DAS28, TNF-alfa, tDPD. IL-1, IL-17, TGF-beta, ICAM1 had a biphase evolution, with an increase in values at 6 weeks and a decrease at 24 weeks. The TNF-alfa blockers produce a decrease of this cytokine and also a secondary decrease of IL-1 and IL-6 with an increase of TGF-beta. The decrease of MMP3 and tDPD in the group of patients treated with DMARD and biological agents shows that together these agents are more efficient in stopping the bone resorption and cartilage destruction. There is a correlation between rheumatoid factor and markers of inflammation included in DAS28. Low values of IL-17 where correlated with low values of AKA and CCP, and IL-8 in high values was correlated with tDPD. Biological agents along with conventional DMARD therapy are more efficient in control of inflammation and extraarticular complications evidenced through the important dicease in DAS28 and RF

A Pilot Study of the Association of Tumor Necrosis Factor Alpha Polymorphisms with Psoriatic Arthritis in the Romanian Population

Tumor necrosis factor alpha (TNF-alpha) is an important pro-inflammatory cytokine implicated in the pathogenesis of psoriatic arthritis. We have performed a case-control association study of three TNF-alpha gene polymorphisms in a group of Romanian psoriatic arthritis patients versus ethnically matched controls. A second group of patients with undifferentiated spondyloarthritis was used in order to look for similarities in the genetic background of the two rheumatic disorders. The −857C/T polymorphism was associated with susceptibility to psoriatic arthritis in our population at the individual level (p = 0.03, OR 1.65, 95% CI 1.05–2.57) and in combined haplotypes with the −238G/A and −308G/A SNPs. Regarding the investigated polymorphisms and derived haplotypes, no potential association was found with the susceptibility to undifferentiated spondyloarthritis in Romanian patients

A report on the adverse events of special interest from the Romanian Registry of Rheumatic Diseases in patients treated with biologic and targeted synthetic disease-modifying anti-rheumatic drugs during 2022

Background. The evolution of the therapeutic arsenal in inflammatory rheumatic diseases has dramatically improved their evolution and prognosis. On the other hand, the information of the safety data, especially for conditions that may appear in a longer time of exposure, are not reflected by clinical trials, due to their limited time design. Patient registries are a valuable source of safety data applicable to real-world (unselected) patients. The evaluation of these data completes the evidence from the various development programs, with the aim of more concrete knowledge of each therapeutic class (therapeutic agent). Aim. The present report descriptively presents the adverse events (AE) of special interest, recorded by the Romanian Registry of Rheumatic Diseases (RRBR), during 2022, in relation to the dynamics of the recent years. Methods. The observational study included all AEs reported in the RRBR in 2022, their severity class, the relationship with exposure to the therapeutic agent. Results. For a cohort of 10676 patients who were exposed to at least one course of treatment, with data in the RRBR during 2022, there were 669 AEs reported: 432 reports for patients with rheumatoid arthritis (RA), 195 records for patients with ankylosing spondylitis (AS) and 42 reports for patients with psoriatic arthritis (PsA). The most common AEs were infections, especially in RA patients. Of all AEs, 94 (14%) were serious AEs, the majority reported in the RA group (16%). A number of 15 MACE, 13 solid malignancy and 19 deaths were reported in the last year. Conclusion. The distribution of EA by disease, the dominance in RA, as well as the distribution by therapeutic groups is in accordance with scientific data, with the exception of breast cancer, which is more frequently reported in RRBR. EA are underreported in the destinated section in the RRBR, an aspect that gives a limit of this report. This represents an unmet need in terms of safety data reporting, that calls for increased knowledge of EA reporting requirements

BASELINE INFLAMMATORY MARKERS AND DISEASE ACTIVITY INDICES PREDICT TAPERING OF BIOLOGIC AGENTS IN ANKYLOSING SPONDYLITIS

Rationale. Clinicians need to have evidence-based information regarding the feasibility of tapering biologics in ankylosing spondylitis (AS). Objective. The study aims to identify significant predictors of tapering in clinical practice. Methods and results. AS patients on their first tumor necrosis factor alpha inhibitor (iTNFα) were enrolled between 2015-2017 and followed until the end of the observation or until tapering or switch of their iTNFα. Binary logistic regression was used to predict tapering (“0” for “non-tapering”, meaning switches and original posology; “1” for “tapering”), significant if p < 0.05. Of the 120 included patients, 50.8% had adalimumab, 21.7% etanercept, 4.2% golimumab and 23.3% infliximab. During follow-up, 40.8% tapered their initial iTNFα, 40.8% remained on its original posology, 16.7% switched it and 1.7% were lost. Judging by odds ratios (OR), inflammatory markers (e.g. odds ratio ORCRP = 0.936, p = 0.014) and activity scores (ORBASDAI = 0.565, p = 0.005) significantly reduced the chance for tapering. Compared to patients on the original posology, patients on tapering had a significantly lower prevalence of uveitis ever (6.8% compared to 11.0%, p = 0.008, post-hoc χ2 test). Discussion. In a real life setting, no more than half of AS patients treated with TNFα inhibitors can undergo tapering. High baseline inflammatory markers and disease activity indices significantly lower the chance of tapering. From a therapeutic point of view, a non-responsive disease phenotype of AS can be hypothesized and it includes extra-spinal manifestations such as uveitis

Is there an early ultrasonographic pattern in salivary glands in both primary and secondary Sjögren syndrome?

Background. Sjögren syndrome (SS) is a systemic chronic inflammatory disorder characterized by lymphocytic infiltrates in exocrine organs. Ultrasonography (US) demonstrates specificity and sensibility in major salivary glands (SG) evaluation. Recent data confirm US might be used as primary evaluation technique for its ability to show structural alterations of parenchyma (1). Objective. To assess the gray scale (GS) parenchymal inhomogeneity of major SG in patients with established primary and secondary SS and correlate with clinical and biological data. Methods. Consecutive patients with SS were recruited and SG US was performed. Inhomogeneity of glandular parenchyma was quantified binary on each gland. ESSDAI and ESSPRI scores were calculated. Statistics was performed with SPSS. Results. Twenty one (42.85% primary SS, 90.47% female) consecutive patients were included. Mean age was 53.66+/-12.99 years and disease duration 5.33+/-3.74 years. Antibody SSA/SSB presence was found in 85.7% (18/21). ESSDAI mean was 8.67+/-8.9 (0-29), ESSPRI 10.13+/-5.59(0-20). There were no differences regarding ESSDAI and ESSPRI in the two groups (primary and secondary SS). Right parotid gland showed alterations in 71.4% patients (77% with primary SS, 66% with secondary SS). Frequently inhomogeneity was found in all major SG (33%, 22% left and right submandibular, 77%, 44.4% left and right parotid glands) in primary SS. Both submandibular glands were symmetrically involved (p<0.02). Duration of disease was negatively correlated to inhomogeneity of right parotid gland (p<0.02). Conclusion. Inhomogeneity in major SG in GS US was found in the majority of patients with primary and secondary SS. The symmetrical involvement of submandibular glands was significant. The inhomogeneity appears in the early period of diagnosis. No major differences were found between two groups

ULTRASONOGRAPHIC SALIVARY GLAND RESPONSE TO RITUXIMAB IN SECONDARY SJÖ GREN’S SYNDROME

B cell hyper-reactivity implied in the pathogenesis of Sjö gren’s syndrome (SS) justifies the therapy that involves B cell depletion. Ultrasound of salivary glands demonstrated alterations during disease progression. Objective. To evaluate changes in salivary gland parenchyma with ultrasound after rituximab treatment in patients’ with secondary SS (sSS). Methods. 7 patients evaluated at baseline (under treatment with rituximab) and after 6 months, underwent ultrasonography of major salivary gland (submandibular and parotid). Clinical data as dryness, pain and diseases activity evaluated with ESSDAI were registered. Salivary gland ultrasound (SGUS) was performed to asses echogenity (using a semiquantitative score from 0-4, with improvement defined as an at least 1 point decrease), size of gland and glandular borders. Results. Of 7 patients, 14% had clinically detectable bilateral parotid tumefaction at baseline. 6 patients (85.71%) showed ultrasonographic alterations at baseline. Parotid parenchyma echostructure improved in 42.85% of patients versus 14.28% in control group (p=0.05). At the submandibular glands, both submandibular glands showed changes in 28.57% of patients, while control group showed no changes. 42.85% patients showed parotid tumefaction which changed in 66.6% of patients at 6 months. Conclusion. Ultrasonography showed improvement in salivary gland echostructure in secondary Sjogren Syndrome with rituximab

GENERAL CHARACTERISTICS AND FAMILIAL AGGREGATION IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which deposit within tissues and fix complement leading to systemic inflammation (1). Is a heterogeneous disease with a continuum of disease activity. Some patients can have predominant skin and joint involvement, whereas others can present with organ-threatening diseases such as nephritis, cardiac involvement or even neurologic manifestations. Relatives of patients with SLE appear to be at higher risk of SLE and other autoimmune diseases, but estimates of individual familial risks are largely unavailable or unreliable (2,3)

Calcinosis in Rheumatic Disease Is Still an Unmet Need: A Retrospective Single-Center Study

Patients with immune-mediated rheumatic disease-related calcinosis comprise a subgroup at risk of encountering a more severe clinical outcome. Early assessment is pivotal for preventing overall disease progression, as calcinosis is commonly overlooked until several years into the disease and is considered as a ‘non-lethal’ manifestation. This single-center retrospective study explored the prevalence, clinical associations, and impact on survival of subcutaneous calcinosis in 86 patients with immune-mediated rheumatic diseases (IMRD). Calcinosis predominantly appeared in individuals with longstanding disease, particularly systemic sclerosis (SSc), constituting 74% of cases. Smaller calcinosis lesions (≤1 cm) were associated with interstitial lung disease, musculoskeletal involvement, and digital ulcerations, while larger lesions (≥4 cm) were associated with malignancy, severe peripheral artery disease, and systemic arterial hypertension. The SSc calcinosis subgroup exhibited a higher mean adjusted European Scleroderma Study Group Activity Index score than those without. However, survival rates did not significantly differ between the two groups. Diltiazem was the most commonly used treatment, and while bisphosphonates reduced complications related to calcinosis, complete resolution was not achieved. The findings underscore current limitations in diagnosing, monitoring, and treating calcinosis, emphasizing the need for further research and improved therapeutic strategies to improve patient care and outcomes

EVIDENCE FOR FAMILIAL AGGREGATION IN SIBLINGS WITH AUTOIMMUNE RHEUMATIC DISEASES

Autoimmune rheumatic disorders have a multifactorial determinism, caused by various environmental factors acting on the individual’s genetic susceptibility, destabilizing the systems which regulate the immune response. Epidemiological and genetic investigations are very important to demonstrate the contribution of genetic factors to the development of these autoimmune diseases. The contribution of genetic factors in causing autoimmune diseases has been demonstrated by familial aggregation. Moreover, it was also quantified by determining heritability, expressing the proportion of genetic factors in the etiology. It is now clear that common genes underlie multiple autoimmune disorders

THE ROLE OF NAILFOLD CAPILLAROSCOPY IN MONITORING LUNG INVOLVEMENT IN SYSTEMIC SCLEROSIS

The usefulness of capillaroscopy in the follow-up of scleroderma patients and the possible prognostic role for the appearance of visceral involvement is suggested by many authors but still under debate.The aim of this study was to assess the role of monitoring capillaroscopic abnormalities (qualitative and semiquantitative) in relation with parameters of interstitial lung involvement and pulmonary arterial hypertension(PAH). A strong correlation was identified between initial capillaroscopy scores and FVC (r=-.47, p=0.002), DLCO (r=- .51, p< 0.001) and sPAP (r=0.34, p<0.001). Active and late capillaroscopic pattern were correlated with diagnosis of lung fibrosis (χ2=14, p=0.007) and PAH at follow-up examinations (χ2=14,2, p=0.007). Progression of capillaroscopic pattern at follow-up evaluations was not correlated with significant worsening of lung volumes, DLCO, sPAP. Instead, progression of microangiopathy evolution score (>1) was asociated with worsening of FVC (r=0.32,p<0.001), DLCO(r=0.21,p=0.02) and new diagnosis of lung fibrosis on HRCT (r=0,19,p=0.035). Semiquantitative scoring, rather then qualitative capillaroscopic assessment can have a predictive role for new involvement or worsening of previous lung involvement (especially interstitial lung disease) in scleroderma patients, confirming the putative role of capillaroscopy as biomarker in SSc