Search Results (163)

Background and Objectives: Hand joint deformity remains a main cause impairing quality of life in rheumatoid arthritis (RA). This study aimed to investigate the association between biologic and targeted-synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) treatment and the prevalence of hand joint deformity in RA patients. Materials and Methods: This cross-sectional analysis included RA patients recruited between 2019 and 2024. Hand joint deformity was defined as the presence of specific deformity in any of 28 hand joints, including the metacarpophalangeal (MCP) joints I-V, proximal interphalangeal (PIP) joints I-V, and distal interphalangeal (DIP) joints II-V. The key exposure was the use of b/tsDMARDs. Multivariable logistic regression was used to assess the association between b/tsDMARDs treatment and hand joint deformity. Results: A total of 1083 RA patients with a mean age of 52.6 ± 12.4 years and a median disease duration of 5 (2,11) years were included. Hand joint deformity was present in 25.4% (275/1083) of patients. The top three deformed joint locations were PIP V (12.9%, 140/1083), PIP III (11.6%, 126/1083), and PIP IV (10.9%, 118/1083). The top three deformity types were ulnar deviation of MCP II-V (8.0%, 87/1083), boutonniere deformity of II-V fingers (6.8%, 74/1083), and swan neck deformity of II-V fingers (6.7%, 73/1083). In total, 17.4% (188/1083) of patients had received b/tsDMARDs. After 1:1 propensity score matching for age, sex, and disease duration, the prevalence of deformity was significantly lower in patients treated with conventional medicine (csDMARDs and/or GCs) add-on b/tsDMARDs compared to those treated with conventional medicine (27.1% vs. 61.7%, p < 0.001). Multivariable logistic regression analysis showed that b/tsDMARDs use was independently associated with a lower prevalence of hand joint deformity after adjusting for confounding factors (OR = 0.211, 95%CI: 0.129–0.345, p < 0.001). Conclusions: The use of b/tsDMARDs was independently associated with a lower prevalence of hand joint deformity in RA. Full article

Background: Immunomodulatory therapies, including biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) have reshaped the treatment of autoimmune diseases. They alter host defenses, but the current landscape of associated infectious risk is not fully defined. Objective: A scoping review of recent literature was conducted to characterize infectious complications associated with modern immunomodulatory biologic agents, summarize current pathogen patterns, and highlight recommendations for prevention and early recognition in clinical practice. Methods: Following PRISMA-ScR guidelines, a systematic search was performed on Scopus, Science Direct, and PubMed for studies published since 2023. Inclusion criteria focused on adult human subjects, exposure to immunomodulatory therapy, and reported infectious outcomes. Studies focusing exclusively on antineoplastic agents without established use in autoimmune diseases were excluded. After screening 1046 unique records, 16 studies were included in the final review. Findings: High-dose glucocorticoids remain a primary driver of serious infections across autoimmune diseases. Newer agents present mechanism-specific risk profiles. JAK inhibitors are associated with herpes zoster, while TNF-α inhibitors are linked to opportunistic bacterial infections and reactivation of granulomatous infections. B-cell depletion with rituximab correlates with hypogammaglobulinemia and its associated infections, whereas belimumab may offer a lower infection risk in non-renal SLE. Recent post hoc analyses (2023–2025) quantify the elevated risk of herpes zoster with JAK inhibitors compared to TNF inhibitors, particularly in older populations. Conclusions: The infectious risk associated with biologic and targeted DMARDs varies by mechanism. While glucocorticoids remain a primary driver of serious infections, newer data highlights specific vulnerabilities with JAK inhibitors (herpes zoster) and B-cell depletion (hypogammaglobulinemia) that require targeted risk stratification. This review shows the urgent need for individualized risk stratification, targeted prophylaxis (e.g., for Pneumocystis or zoster), and pre-therapy screening to balance therapeutic efficacy with patient safety. Full article

Background: Juvenile idiopathic arthritis-associated uveitis (JIA-U) is a rare condition, and assessment of the efficacy of disease-modifying antirheumatic drugs, synthetic (sDMARD) or biological (bDMARD), in randomized trials is hindered by this fact. Methods: In this prospective longitudinal study, we observed 38 children aged 1.3 to 15.2 years, with 69 eyes affected with JIA-U for 1970 overall eye examinations (6–59, median 16) irregularly scattered across 4.4–87.6 months (median 21.6) of follow-up, with on- and off-periods of DMARD use and use of topical treatments. Results: With adjustment for several time-invariant and time-varying covariates, periods of exposure to sDMARD vs. no DMARD exposure were associated with peak benefits of 15–20% lower probability of having more severe anterior chamber (AC) inflammation and a similar relative reduction in the daily use of topical corticosteroids (TCS). Periods of bDMARD exposure or of bDMARD + sDMARD exposure vs. no DMARD use were associated with peak benefits of an around 50% reduction in the probability of having more severe AC inflammation, and peak benefits of an around 60–65% reduction in TCS use. Conclusions: The observations regarding bDMARD (only) or bDMARD + sDMARD exposure are in agreement with the extent of benefits suggested for adalimumab vs. placebo (+background sDMARD) in the only existing randomized trial in this setting evaluating AC inflammation and TCS use. Full article

Background: Tumor necrosis factor-α (TNFα) inhibitors have significantly improved outcomes in children with non-systemic juvenile idiopathic arthritis (JIA), achieving long-term clinical remission for many patients. However, the optimal strategy for TNF-α inhibitor withdrawal remains unknown, whether through abrupt discontinuation, gradual dose reduction, or interval extension. Objective: We aim to identify patient-, disease-, and treatment-related predictors of successful TNF-α inhibitor withdrawal in children with non-systemic JIA. Methods: In this prospective, randomized, open-label, single-center study, 76 children with non-systemic JIA in stable remission for ≥24 months on etanercept or adalimumab were enrolled. At the time of TNF-α inhibitor discontinuation, all patients underwent a comprehensive evaluation, including a clinical examination, laboratory tests (serum calprotectin [S100 proteins] and high-sensitivity C-reactive protein [hsCRP]), and advanced joint imaging (musculoskeletal ultrasound and magnetic resonance imaging [MRI]) to assess subclinical disease activity. Patients were randomized (1:1:1, sealed-envelope allocation) to one of three predefined tapering strategies: (I) abrupt discontinuation; (II) extension of dosing intervals (etanercept 0.8 mg/kg every 2 weeks; adalimumab 24 mg/m² every 4 weeks); or (III) gradual dose reduction (etanercept 0.4 mg/kg weekly; adalimumab 12 mg/m² every 2 weeks). Follow-up visits were scheduled at 3, 6, 9, 12, and 18 months to monitor for disease relapse. Results: Higher baseline Childhood Health Assessment Questionnaire (CHAQ) scores (≥2), elevated serum calprotectin [S100 proteins] and hsCRP levels at withdrawal, imaging evidence of subclinical synovitis, and a history of uveitis were all significantly associated with increased risk of flare. No significant associations were found for other clinical or demographic characteristics. Conclusions: Early significant clinical response, absence of subclinical disease activity, and concomitant low-dose methotrexate therapy were key predictors of sustained drug-free remission. These findings may inform personalized strategies for biologic tapering in pediatric JIA. Full article

Background/Objectives: Serum calprotectin is a promising biomarker of inflammation in rheumatoid arthritis (RA), yet real-world longitudinal comparisons across different targeted therapies remain limited. We aimed to evaluate the dynamics and remission-predictive ability of serum calprotectin and C-reactive protein (CRP) in RA patients treated with adalimumab, upadacitinib, or tocilizumab. Methods: In this retrospective cohort study, patients with RA initiating one of the above therapies were included. Serum calprotectin and CRP were measured at baseline, month 3, and month 6. Disease activity was assessed by DAS28 and Clinical Disease Activity Index (CDAI). Linear mixed-effects models adjusted for cumulative prednisone dose were used to assess biomarker trends over time. ROC curve analyses based on CDAI remission (≤2.8) evaluated the discriminative performance of calprotectin and CRP, stratified by treatment subgroups. Results: Sixty patients were enrolled (20 receiving tocilizumab, 20 adalimumab and 20 upadacitinib). Significant reductions in serum calprotectin, CRP, and DAS28 were observed over time (p < 0.001 for all), independent of treatment group. In the overall cohort including baseline, CRP outperformed calprotectin (AUC 0.739 vs. 0.636; p = 0.044). Among patients treated with adalimumab or upadacitinib, calprotectin significantly outperformed CRP (AUC 0.929 vs. 0.857; p = 0.049). In the tocilizumab group, both biomarkers showed similar AUCs (p = 0.888). Conclusions: Serum calprotectin declined significantly after treatment initiation and outperformed CRP in identifying remission under TNFα and JAK inhibition. It also retained a good performance under IL-6 blockade. These findings support its role as a treatment-sensitive biomarker suggesting a complementary role alongside CRP in RA monitoring, particularly in settings where CRP reliability is pharmacologically suppressed. Full article

Proteoglycans and their fragments have potential as diagnostic or theragnostic biomarkers to identify diseases characterized by dysregulated extracellular matrix remodeling, such as juvenile idiopathic arthritis (JIA). Therefore, our study aimed to evaluate the diagnostic utility of plasma proteoglycan profiles, namely, aggrecan, decorin, and biglycan, released from osteoarticular structures into the blood of children with juvenile idiopathic arthritis. These profiles are potential biomarkers of tissue destruction and/or indicators of the efficacy of therapy with the biologic agent etanercept (ETA). This study was conducted on 263 blood samples collected from 25 healthy children and 34 children at various stages of juvenile idiopathic arthritis disease: immediately after diagnosis, following treatment with disease-modifying antirheumatic drugs (DMARD) (methotrexate, sulfasalazine, and prednisone), and during 3, 6, 12, 18, and 24 months of therapy with etanercept. Quantitative levels of aggrecan, biglycan, and decorin were measured using ELISA kits. In children with JIA, plasma aggrecan levels were elevated at diagnosis, decreased after ineffective DMARD therapy, and increased again at 24 months of etanercept treatment despite clinical improvement. By contrast, biglycan levels were similar to those in healthy controls but decreased during etanercept therapy. Decorin levels were initially high in untreated and DMARD-treated patients but returned to normal after 24 months of biologic treatment. After considering these findings and the ROC analysis, we conclude that decorin appears to be a promising biomarker for diagnosing and monitoring etanercept therapy in JIA, and biglycan is a useful biochemical marker for assessing the effectiveness of ETA treatment. Full article

Background: We aimed to investigate the risk for a serious infection in rheumatoid arthritis (RA) patients after tapering the dose of biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Methods: This nested case–control study investigated the risk for a serious infection in RA patients who underwent mandatory b/tsDMARDs dose reduction 2.5 years after starting therapy with a single b/tsDMARD in the National Health Insurance Research Database (NHIRD). Cases were those patients who developed a serious infection afterwards. Matched controls were selected from those patients who did not develop a serious infection. We used unconditional logistic regression to analyze the odds ratios (ORs) of b/tsDMARDs dose reduction and discontinuation between cases and controls. Results: RA patients underwent an average dose reduction of 60%. Among a total of 268 cases and 1072 controls, we did not observe a lower risk for a serious infection in those patients who tapered or discontinued b/tsDMARDs. However, those patients who had discontinued b/tsDMARDs had a higher risk for a serious infection when compared with those who had not and had reduced their b/stDMARDs dose reduction below the average (i.e., ≤60%), with an adjusted OR of 1.48 (95%CI: 1.05, 2.09). Conclusions: Dose reduction in b/tsDMARDs in RA patients might not be associated with a lower risk for serious infection. Discontinuation of b/tsDMARDs, however, was likely associated with a higher risk for serious infection. Full article

Objectives: To estimate the prevalence of psoriatic arthritis (PsA) and associated factors in patients with moderate-to-severe psoriasis. Methods: Retrospective, single-center study of a cohort of psoriasis patients in standard follow-up in a dermatology department from July 2008 to January 2024. Patients ≥18 years with moderate-to-severe psoriasis were included and classified into three groups according to the treatment received: group 1, biologics or small molecules with or without conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs); group 2, only csDMARDS; and group 3, non-pharmacological treatments. Demographic and clinical variables were collected. The prevalence of PsA was estimated with its 95% confidence interval (CI). The cumulative incidence of PsA was analyzed across groups, and logistic regression models were built. Results: The study population comprised 308 patients (67.2%, 22.7%, 10% in groups 1, 2, and 3, respectively). Differences between the groups were observed in severity of psoriasis, weight, smoking status, and dyslipidemia (p < 0.05). The prevalence of PsA was 11.7% (95% CI, 8.1–15.3), with most patients in group 1. This group had a higher risk of PsA following diagnosis of psoriasis or initiation of treatment. Belonging to groups 2 and 3 had a smaller effect than belonging to group 1 in the development of PsA; nail involvement and obstructive sleep apnea (OSA) were associated with development of PsA (p < 0.05). Conclusions: The prevalence estimate was lower than previous estimates, probably owing to the increased use of biologics. Nail involvement and OSA were associated with PsA. Full article

Psoriatic arthritis (PsA) is a chronic, immune-mediated inflammatory arthritis associated with psoriasis, affecting joints, entheses, and the axial skeleton. While primary care providers and dermatologists frequently encounter psoriasis (PsO), early recognition of PsA remains critical to preventing irreversible joint damage. This paper is written to provide a comprehensive overview of PsA, beginning with a clinical case that highlights diagnostic and therapeutic challenges. In this review, the epidemiology of PsA will be discussed, emphasizing its prevalence and risk factors among patients with PsO. The discussion extends to the underlying pathogenesis, focusing on genetic predisposition, environmental triggers, and key cytokines, including TNF-α, IL-17, and IL-23, that have become targets for advanced therapeutics. The clinical features of PsA are explored in detail, including peripheral and axial arthritis, enthesitis, dactylitis, and extra-articular manifestations. Diagnostic approaches are discussed, with a focus on the Classification Criteria for Psoriatic Arthritis (CASPAR) and Moll & Wright criteria. Additionally, we examine screening tools designed to facilitate early detection in dermatology clinics. Diagnostic modalities, including imaging and serologic markers, are reviewed. Finally, we explore the evolving landscape of PsA treatment, spanning conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologic agents (bDMARDs), and targeted synthetic DMARDs (tsDMARDs). Given the increasing availability of cytokine-targeted therapies, an interdisciplinary approach between dermatologists and rheumatologists is essential for optimizing outcomes in PsA patients. Patients with PsA are cared for by rheumatologists, dermatologists, and primary care providers who help manage the comorbidities associated with PsA. By bridging primary care, dermatology, and rheumatology in the care of PsA, this paper aims to enhance understanding of PsA for facilitating early identification and timely intervention for improved patient care. Full article

Background/Objectives: Patients with rheumatic diseases have an increased burden of infection owing to biological disease-modifying antirheumatic drug (bDMARD) therapy. Therefore, vaccination is crucial for the prevention of infection in these patients. In this case–control study, we aimed to evaluate vaccine response to hepatitis B, pneumococcus, and measles using antibody titers in patients undergoing biological therapy. Methods: This study included 16 patients aged 5–18 years of age who received bDMARD treatment and 20 healthy controls. Serum samples of the patients were collected at baseline and subsequently on the 3rd and 6th months after bDMARD therapy, and IgG antibodies against pneumococcal capsular polysaccharide antigen (PCP), measles, and hepatitis B were measured. Results: There were no statistically significant differences in mean anti-HBsAg, anti-PCP, and anti-measles antibody titers between the study and control groups. The percentages of patients with anti-HbsAg, anti-PCP, and anti-measles protective antibodies were 68.8% (n = 11/16), 100% (n = 16/16), and 56.25% (n = 9/16), respectively. There were no statistically significant differences in the mean antibody titers at baseline and 3rd month. Only the anti-measles IgG titer level decreased below 200 (mIU/mL) in one patient in the 3rd month and in two patients in the 6th month. Conclusions: Patients with low or declining hepatitis B and measles antibody titers before or during bDMARD treatment may require close monitoring to ensure adequate protection against vaccine-preventable diseases. Regular screening and follow-up are essential in this patient population. Full article

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting the joints, with neurogenic inflammation involving the nervous system being a hallmark of the condition. Treatments include medications such as disease-modifying antirheumatic drugs (DMARDs), corticosteroids, and biologics targeting inflammatory pathways. Yet, these treatments are not curative for RA. Heat Shock Proteins (HSPs) are molecular chaperones with immunoregulatory properties; however, their role is not yet fully understood, as these molecules may play a dual, pro- and anti-inflammatory role. In this study, we evaluated the protein expression levels of HSPs 27, 60, 70, and 90 in the synovial membrane and spinal cord of the RA rats’ model to determine their roles during the disease course, both on the neurological and immunological levels. Furthermore, HSP levels have been evaluated in the spinal cord of control and RA rats’ model after high and low doses of ketamine injection. Significant changes in Hsp60, 70, and 90 expression levels were observed only in the spinal cord of RA rats. We demonstrated that blocking N-methyl-D-aspartate receptors with ketamine can modulate spinal cord HSPs expression in RA rats and subsequently impact neurogenic inflammation and adult neurogenesis. This suggests that HSPs may be a promising target for RA treatment due to their complex immunomodulatory effects and potential interactions with the nervous system. Further research is needed to explore their therapeutic potential and develop effective interventions for RA. Full article

Background: Nurses play a central role in the management of inflammatory joint diseases (IJD), of which the success depends on patient adherence to treatment, self-monitoring, timely detection of adverse drug reactions (ADRs), and adopting a healthy lifestyle. This study sought to examine the opinions of patients with IJD regarding the educational and supportive contributions of nurses. Methods: The research is based on a cross-sectional survey of patients with IJD treated with biologic disease-modifying antirheumatic drugs (bDMARDs) in two rheumatology clinics in Plovdiv, Bulgaria, from the beginning of August 2024 to the end of January 2025. The group included patients of three diagnoses: (1) rheumatoid arthritis (RA), (2) psoriatic arthritis (PsA), and (3) axial spondyloarthritis (axSpA). Results: Regardless of the diagnosis, and after adjusting for covariates, patients rated the roles of nurses in disease treatment and management, the acquisition of self-injection skills for bDMARDs, the implementation of a healthy lifestyle, and the maintenance of psychological well-being at the higher end of the 0 to 4 scale. However, the axSpA patients were less affirmative in their responses compared to the RA and PsA patients. In the RA and PsA groups, the working patients were associated with the lowest ratings, followed by retirees with disability. Conclusions: Our findings indicate that nurse-led education in patient self-management skills is greatly appreciated by patients with IJD. Further developments in specialized training programs tailored to the specific needs of different diagnoses and in consideration of patients’ social status will lead to increased patient satisfaction and a better overall quality of life. Full article

Objectives: To examine long-term outcomes and predictors of structural and functional remission in rheumatoid arthritis (RA) after 10-year disease-modifying antirheumatic drug (DMARD) therapy under tight control. Methods: We used real-world cohort data from RA patients who completed 10-year DMARD therapy toward remission or low disease activity based on every-3-month measurements between April 2001 and July 2024. Baseline characteristics, disease control during follow-up, and outcomes after 10 years were examined. Results: Among 204 patients, 76% received biological and/or non-biological targeted DMARDs. Clinical remission, structural remission defined as an increase in modified total Sharp score (mTSS) ≤ 5 per 10 years, and functional remission defined as health assessment questionnaire-disability index (HAQ-DI) ≤ 0.5 were achieved by 68.1%, 73.0%, and 81.4% of patients, respectively. The mean increase (∆) in mTSS was 5.4 for 10 years (∆erosion score, 1.2; ∆joint space narrowing [JSN] score, 4.2), and 28.9% of patients had no structural progression (51% for erosion score and 34.8% for JSN score). Mean HAQ-DI was 0.26. During a 10-year follow-up, 8.8% of patients experienced high or moderate disease activity lasting for ≥12 months and they had a low structural remission rate (11.1%) and functional remission rate (16.6%). According to multivariable logistic regression analysis, baseline mTSS and JNS score (but not erosion score) were strong predictors for structural and functional remission after 10 years. Conclusions: Structural damage progression and functional loss are limited during 10-year tightly controlled DMARD therapy. Compared with bone erosion, JSN appears to be of much higher relevance to structural and functional outcomes. Full article

Background: Fibromyalgia syndrome (FS) is one of the most common causes of chronic generalised pain and often complicates the therapeutic management of inflammatory chronic arthritis (ICA), negatively impacting both the real assessment of disease activity and the perception of response. Our study aims to evaluate in a group of patients with ICA, multi-resistant to biologic/target synthetic disease-modifying antirheumatic drugs (b/ts-DMARDs), both the impact of FS on the possibility of achieving low disease activity (LDA) or remission (REM) and the possible improvement in the severity of FS symptoms, after starting b/ts-DMARDs with different a mechanism of action (MoA). Methods: A prospective study was conducted, from January 2023 to December 2024, on patients who fulfil the classification criteria for psoriatic arthritis (PsA) or fulfil the 2010 American College of Rheumatology criteria for RA. Results: Sixty-four Caucasian patients with ICA, of which 47 with FS, were enrolled in the study. At the baseline visit, FS patients had a significantly shorter ICA disease duration, worse fibromyalgia symptom-related indices (such as Fibromyalgia Severity Scale (FSS), Widespread Pain Index (WPI), and Symptom Severity Scale (SSS)) and functional and disability scores (such as health assessment questionnaire (HAQ) and Functional Assessment of Chronic Illness Therapy (FACIT)), and a higher basal value of Disease Activity in Psoriatic Arthritis (DAPSA) score compared to patients without FS. After 6 months of starting b/ts-DMARDs, no differences in severity of arthritis clinimetric indices (disease activity score (DAS) 28 (erythrocyte sedimentation (ESR)) and DAPSA) and Visual Analogue Scale (VAS) pain were found between the patients with FS compared to those without. At the follow-up visit, 36% of the whole group of patients were in LDA (36% ICA patients with FS vs. 35% of ICA patients without FS; p = 0.080), while 17% of patients reached REM (11% ICA with FS vs. 35% ICA without FS patients; p = 0.031). The FS presence appeared to be a factor associated with failure to reach REM (OR 4.5 (95%CI: 1.1–17.8), p = 0.028), but not for achieving LDA (OR 2.7 (95%CI: 0.8–8.9), p = 0.099). The overall retention rate at 6 months was 79%; in particular, 11 patients discontinued treatment with b/ts-DMARD, 69% of whom belonged to the FS group (p = 0.489). Among the group of patients with ICA and FS, patients in LDA/REM presented an important improvement in FSS, SSS, and VAS pain, with the best percentage variation from the baseline of these indices compared to patients who did not achieve the LDA/REM. Of note, sixteen patients with FS at the baseline no longer met the diagnostic criteria for FS after 6 months of follow-up. Conclusions: The presence of FS seems to negatively impact the achievement of REM, but not LDA, in both RA and PsA patients, even in b/ts-DMARDs patients with multi-failure of at least two different MOAs. Only a cluster of patients with FS, presumably those with FS triggered and/or amplified by the chronic joint inflammatory process, appear to improve their perception of FS severity by achieving ICA LDA/REM. However, these findings require further supporting data for more accurate validation. Full article

Immunosenescence refers to the set of immunoendocrinological alterations underlying the progressive decline in innate and adaptive immune function that occurs with aging. It is closely linked to the concept of inflammaging, a state of low-grade chronic systemic inflammation that contributes to age-related diseases. In the elderly, key features of diseases such as rheumatoid arthritis, particularly in its elderly onset form, and senile osteoporosis are characterized by a decline in sex hormones and the immunoregulatory IL-2; an increase in serum autoantibodies and pro-inflammatory mediators such as TNF-α, IL-6; and upregulation of bone-related factors RANKL, DKK1, and sclerostin, including the dysregulation of the IL-33/IL-31 axis. The aim of this review is to examine the key molecular pathways of immunosenescence in osteoimmunology, as well as the potential for therapeutic modulation of inflammaging through biologic and target synthetic disease-modifying antirheumatic drugs, denosumab and romosozumab, with particular attention to their management in elderly patients. Full article