Search Results (55)

Background/Objectives: Response to TNF inhibitors in RA remains heterogeneous and reliable predictors of treatment response are still lacking. Biomarker-based stratification may improve therapeutic decision-making and aligns with the emerging paradigm of precision medicine. Methods: We conducted a prospective observational study including 64 biologic-naïve patients with active RA being inadequately controlled by csDMARDs. All patients initiated anti-TNF therapy and were followed for 12 months. Clinical response was assessed at 6 and 12 months using EULAR response criteria based on DAS28-CRP. Baseline serum levels of classical biomarkers (RF type IgM, RF type IgA, anti-CCP) and additional biomarkers (anti-MCV,14-3-3η protein, COMP) were evaluated. Logistic regression analyses were performed to identify predictors of treatment response. Results: At 6 months, 7 patients were classified as non-responders, 38 as moderate responders, and 19 as good responders Lower baseline levels of RF isotypes, anti-CCP antibodies, 14-3-3η protein, and COMP were associated with favorable clinical response at 6 months. Baseline anti-CCP and 14-3-3η protein levels emerged as significant predictors in univariate analysis. Multivariate logistic regression yielded a predictive model incorporating anti-CCP, 14-3-3η protein, and COMP, achieving an overall prediction accuracy of 89.1%. At 12 months, baseline RF isotypes remained associated with treatment response, whereas the predictive value of other biomarkers diminished. Longitudinal analysis demonstrated significant reductions mainly for classical autoantibody levels under anti-TNF α inhibitors. Conclusions: A combined serum biomarker panel may support early prediction of response to anti-TNF therapy in RA. These findings highlight the potential of integrated biomarker-based stratification to optimize therapeutic decisions and support the implementation of precision medicine approaches in RA. Full article

Background: Central sensitization (CS) has been held responsible for both persistent pain and high disease activity scores in Spondyloarthritis (SpA). The Central Sensitization Inventory (CSI) is a questionnaire used to determine CS frequency: a score of at least 40 is associated with a high likelihood of CS. Objectives: To investigate the prevalence of CS in our cohort and its association with clinical characteristics of patients and their quality of life. Methods: Adult patients with a diagnosis of Psoriatic Arthritis (PsA) or Axial Spondyloarthritis (AxSpA) who were also classifiable according to ClASsification criteria for Psoriatic Arthritis (CASPAR) and Assessment of SpondyloArthritis international Society (ASAS) criteria respectively, and regularly followed at the SpA outpatient clinic of our Unit were consecutively enrolled from April to November 2023. Their epidemiologic, clinical and clinimetric data were collected, as well as patient-reported outcome measures (PROMs) [CSI, Health Assessment Questionnaire (HAQ), FACIT-Fatigue (FACIT-F), SHORT-FORM 36 (SF-36), and Hospital Anxiety and Depression Scale (HADS)]. Considering the definition of “difficult-to-treat” rheumatoid arthritis, we defined as “multi-failure” those patients who were treated with more than two biologic disease-modifying anti-rheumatic drugs (bDMARDs) with different mechanisms of action. Intergroup comparisons were assessed by using Chi-square, t-test and ANOVA. p-values < 0.05 were considered significant. Results: A total of 100 patients were enrolled, 46 male (46.0%) and 54 female (54.0%), with a mean age of 59.4 ± 9.8 years and a mean disease duration of 14.8 ± 10.1 years; 79 patients (79%) had a diagnosis of PsA and 21 (21%) of AS. Forty-two patients (42.0%) had a CSI score ≥ 40. Significant correlations were found between a CSI score ≥ 40 and female sex (p = 0.004), the occurrence of enthesitis (p = 0.05), DAPSA-CRP (p = 0.02) and ASDAS scores (p = 0.03), a multi-failure condition (p = 0.01), fibromyalgia (FM) (p = 0.004), thyroid disease (p = 0.016) and obesity (p = 0.047). Regarding PROMs, significant correlations were found between CSI and values of HADS (both anxiety and depression), FACIT-F, HAQ and all the domains of SF-36 (p-value < 0.0001). Conclusions: Our data confirmed that more than 40% of SpA patients had CSI values ≥ 40 and underlined how CS could widely impair their disease burden. A routinary evaluation of CS and a multifactorial biopsychosocial perspective in the diagnosis and management of chronic pain in patients with SpA could help rheumatologists in improving their quality of care. Full article

Psoriatic arthritis (PsA) is a systemic autoimmune inflammatory disease affecting both the joints and the skin, with the potential involvement of multiple organ systems. A hallmark feature of PsA is enthesitis—inflammation at the sites where tendons and ligaments insert into bone—which arises from a combination of mechanical stress and immune-mediated inflammation. Another defining characteristic of the disease is the paradoxical coexistence of bone erosion and new bone formation, distinguishing it from other inflammatory arthritides. The therapeutic landscape of PsA has evolved considerably over time. Non-steroidal anti-inflammatory drugs (NSAIDs) remain a cornerstone of symptom management, while conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as methotrexate, are widely used to control disease progression. The introduction of biologic agents has revolutionized PsA management, with TNF inhibitors, IL-17 inhibitors, and IL-23 inhibitors demonstrating efficacy across a broad range of clinical manifestations. More recently, targeted synthetic small molecules—including JAK inhibitors and TYK2 inhibitors—have expanded the armamentarium of available therapies. The overarching goals of treatment in PsA include the suppression of the underlying inflammatory process and the prevention of structural joint damage. The impact of each therapeutic option on cutaneous psoriasis is an additional and important consideration that guides individualized treatment options. Full article

Objectives: The long-term effects of rheumatoid arthritis (RA) therapies on bone mineral density (BMD) remain incompletely characterized. We aimed to evaluate BMD trajectories over an 8-year follow-up in patients with RA treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biological DMARDs (bDMARDs) in real-world practice. Methods: Patients were selected from an observational RA cohort established at Nice University Hospital between 2001 and 2016. Participants were classified into two groups according to treatment regimen (csDMARD only or any bDMARD exposure). BMD was assessed by dual-energy X-ray absorptiometry at baseline and after 1, 2, 3, 5, and 8 years at the lumbar spine, femoral neck, and total hip. Longitudinal changes in BMD were analyzed using multivariable linear mixed-effects models adjusted for age, sex, body mass index (BMI), disease duration, seropositivity, glucocorticoid use, anti-osteoporosis treatment, and clinical response. Results: A total of 312 patients were included, of whom 181 received bDMARDs and 131 were treated exclusively with csDMARDs. BMD showed limited change during the first two years in both groups. Beyond two years, modest declines were observed at hip sites at subsequent time points, whereas lumbar spine BMD did not demonstrate significant longitudinal change in pointwise analyses. In mixed-effects models, the treatment group–time interaction was significant for lumbar spine (p = 0.004) and total hip (p = 0.04), but not for the femoral neck (p = 0.34), indicating differential BMD trajectories over time between treatment groups. In the csDMARD group, lumbar spine and total hip BMD decreased by a mean of 0.0006 and 0.0005 g/cm² per month, respectively, whereas no significant slopes were observed in the bDMARD group. Older age was associated with lower BMD, while male sex and higher BMI were associated with higher BMD across sites. Conclusions: In this long-term real-world cohort, BMD remained relatively stable during the first two years of follow-up. Longitudinal analyses suggested a less pronounced decline in lumbar spine and total hip BMD trajectories among bDMARD-treated patients compared with those receiving csDMARD alone, underscoring the need for ongoing bone health monitoring in RA. Full article

Rheumatoid arthritis (RA) is triggered by dysregulated cytokine networks, but the distributional association of conventional synthetic (csDMARDs) and biologic DMARDs (bDMARDs) with circulating mediators has not been fully described. In this study, we aimed to investigate the treatment-associated modulation of TNF-α, IL-17, IL-13, and soluble CTLA-4 (sCTLA-4) in 64 RA patients (untreated, n = 14; csDMARD, n = 32; bDMARD ± csDMARD, n = 18) and 20 controls. ELISA was used to determine the serum levels, and Kruskal–Wallis tests and false discovery rate correction were used to determine the differences between groups, accompanied by DAS28- and CRP-adjusted quantile regression. Group-level analysis demonstrated that the levels of IL-17 were higher in patients treated with csDMARDs and bDMARDs than in the controls (FDR-adjusted p = 0.0009 and <0.0001, respectively), and the levels of IL-13 were higher in patients treated with bDMARDs than in the controls (p = 0.026). However, quantile regression did not reveal consistent treatment-related associations, suggesting that long-term pathway-specific immune responses and context-dependent regulation may be involved. Smoking independently predicted higher IL-13 at lower quantiles (β = 35.5; p < 0.0001), while TNF-α showed treatment-related increases only at the upper quantile in CRP-adjusted models (β = 323.7; p = 0.049). On the other hand, sCTLA-4 had the largest and most significant treatment-based increase (p < 0.0001), regardless of disease activity, and constant effects across mid-quantiles. Taken together, these findings suggest that sCTLA-4 shows therapy-responsive distributional changes, supporting its potential utility as a biomarker of biological efficacy. In contrast, the observed increases in IL-17 and IL-13 reflect ongoing immune activity and possible environmental influences. Distribution-sensitive biomarker profiling provides a nuanced approach to capturing immune response diversity in RA and may enhance precision in monitoring procedures. Full article

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: Cardiovascular implications in systemic lupus erythematosus (SLE) are common and varied, including impacts on the pericardium, myocardium, valves, coronary arteries, and conduction system; all of these could be potential substrates or triggers of cardiac arrhythmias by interfering with disease severity and specific medication. Therefore, this narrative review aimed to assess the cardiac involvement in SLE underlying, mainly, cardiac arrhythmias. Methods: We analyzed studies, published between 2015 and 2025 on PubMed, which explore cardiovascular involvement with a focus on arrhythmias in SLE from the perspectives of epidemiology, underlying mechanisms, diagnostic techniques, and the impact of standard and biologic therapies. Results: The cardiac manifestation of LES (lupus pericarditis, lupus myocarditis, Libman–Sacks endocarditis, coronary artery disease, coronary vasculitis or myocardial fibrosis) represents a substrate for arrhythmia risk. These substrates, in association with other arrhythmias mechanisms considered as triggers or conduction abnormalities, determined arrhythmogenic conditions in these patients. In addition to structural heart disease, arrhythmias in SLE are caused by ongoing inflammation, immune system irregularities, microvascular problems, autonomic imbalance, oxidative stress, and side effects from treatments. Despite this complex background, arrhythmias are often overlooked and not routinely investigated in SLE care. Data that show how disease-modifying drugs may affect arrhythmias are limited and inconsistent, highlighting significant gaps in knowledge. Cardiac arrhythmias are a significant but, as yet, insufficiently underrecognized aspect of SLE, with serious implications for prognosis. Conclusions: Systemic lupus erythematosus causes cardiovascular involvement that is associated with arrhythmias through various and complexes mechanisms, mainly related to direct cardiovascular structural damage, systemic inflammation or specific therapies. Data on arrhythmias secondary to cardiovascular damage in patients with SLE in the literature are limited. Therefore, early detection of electrical issues, regular cardiovascular evaluation in high-risk patients, and careful management of treatment effects are vital. A coordinated, multidisciplinary cardio-rheumatology approach is essential to improving arrhythmia detection, tailoring treatments, and ultimately decreasing cardiovascular complications and deaths in SLE patients. 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: Achieving low disease activity or remission in psoriatic arthritis (PsA) remains difficult. The GRAPPA group recently defined difficult-to-treat (D2T) PsA but did not include a time-based criterion. Objectives: This study aimed to evaluate the prevalence and features of D2T PsA using several operational definitions. Methods: A cross-sectional study at a tertiary center enrolled PsA patients with active disease confirmed by clinical exam and ultrasound. D2T PsA was defined by: (1) failure of ≥1 csDMARD plus ≥2 b/tsDMARDs with different mechanisms of action (GRAPPA definition); (2) ≥2 b/tsDMARDs with different mechanisms of action within 12 months (time-based definition); or (3) failure of >3 b/tsDMARDs with different mechanisms of action (very refractory). Clinical, demographic, radiographic, and ultrasound data were analyzed, and multivariable analyses identified independent associations. Results: Seventy-two patients (54.2% female, median age 56, disease duration 84 months) all had active disease (median DAPSA 17); 68% had comorbidities. Enthesitis, dactylitis, and nail disease were seen in 20.8%, 45.8%, and 41.7%. HLA-B27 positivity was 13.9%. Radiographic erosions and ultrasound paratenonitis were present in 37.5% and 33.3%. GRAPPA D2T criteria were met by 23.6%, linked to longer disease duration, higher activity, HLA-B27, comorbidities, and combined therapy. Time-based D2T (12.5%) showed higher DAPSA and nail involvement, with ultrasound paratenonitis and combined therapy independently associated. Very refractory patients (11.1%) only correlated with combined therapy. Conclusions: Up to one-fourth of PsA patients remain active despite multiple treatments. D2T PsA is associated with disease duration, comorbidities, activity, HLA-B27, combined therapies. Remarkably, patients who fulfilled the <12-month D2T definition were more likely to present with nail involvement and ultrasound-detected paratenonitis. Full article

Background: Ankylosing spondylitis (AS) is a chronic autoinflammatory rheumatic disease mainly affecting the sacroiliac joints and spine, causing altered bone remodeling. Pro-inflammatory cytokines such as TNF-α and IL-17 contribute to bone loss by modulating pathways including Wnt/β-catenin, which is inhibited by proteins like Dickkopf-1 (DKK-1) and sclerostin (SOST). Bone morphogenetic protein-6 (BMP-6) promotes osteoblast differentiation and bone formation. This study evaluated the association between serum levels of DKK-1, SOST, BMP-6, and bone mineral density (BMD) in AS patients treated with anti-TNF agents and conventional synthetic DMARDs (csDMARDs). Methods: A cross-sectional study included 76 AS patients diagnosed by modified New York criteria and 30 healthy donors matched by age and sex. BMD at the lumbar spine and hips was assessed by DXA in all participants. Disease activity (BASDAI) and functional index (BASFI) were measured in AS patients. Serum levels of DKK-1, SOST, BMP-6, TNF-α, and IL-17 were quantified by ELISA in both groups. AS patients were divided into two treatment groups: combined anti-TNFα and csDMARD therapy (n = 38), and only csDMARDs (n = 38). Results: Bone mineral density showed no significant statistical differences between the spine (p = 0.930) and hips (p = 0.876) in AS patients compared to healthy controls. The activity (BASDAI) and functionality (BASFI) scores were similar in both treatment groups (p = 0.161 and p = 0.271, respectively). No significant differences were found in serum levels of DKK-1 (p = 0.815), SOST (p = 0.771), BMP-6 (p = 0.451), or IL-17 (p = 0.335) between combined anti-TNFα and csDMARD therapy versus monotherapy with csDMARD. Conclusions: The combination of anti-TNF bDMARD therapy and csDMARD therapy is not significantly associated with serum levels of DKK-1, SOST, BMP-6, and BMD compared to those treated with csDMARD monotherapy in patients with AS. This study provides novel and clinically relevant evidence on how anti-TNF bDMARDs and csDMARDs differentially affect bone turnover biomarkers and bone health in patients with AS, contributing to a better understanding of therapeutic strategies and guiding future research and clinical decision-making. Full article

Background: Rheumatoid arthritis is the most prevalent systemic inflammatory disease, mainly affecting the synovial tissue of small and large joints, also associated with significant extra-articular manifestations. Throughout the progression of the disease, cardiac structures may be affected, including the conducting system, myocardium, endocardium, coronary arteries, and valves, potentially resulting in a higher incidence of cardiac arrhythmias. Methods: We performed a narrative review of the most recent studies that highlight the epidemiology, pathophysiology, diagnosis, and management of arrhythmias occurring in patients with rheumatoid arthritis. Furthermore, we examined the impact of disease-modifying antirheumatic drugs (DMARDs)—including conventional synthetic (csDMARDs), biologic (bDMARDs), and targeted synthetic agents (tsDMARDs)—on cardiac electrophysiology. Results: Cardiac immune cells may influence arrhythmogenesis through non-canonical and inflammatory mechanisms by modifying myocardial tissue architecture or by interacting with cardiomyocytes, potentially altering their electrical function. Conclusions: This review emphasizes the essential role of a multidisciplinary approach integrating rheumatology and cardiology expertise in the screening and management of arrhythmias in patients with rheumatoid arthritis. Full article

Introduction. The Italian Committee for Tailored BIOlogic Therapy (ITABIO), in a first report, has reviewed the literature to identify the best strategy for the choice of second-line biologic therapy in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). To verify the application of ITABIO recommendations in real life and how the recommendations perform in maintaining the health status of patients affected by inflammatory arthritis (RA, SpA, PsA), a database has been developed by Pharmaceutical Governance to evaluate the appropriateness of prescriptions. Methods. We have analyzed retrospectively 616 patients, 288 (46.7%) affected by RA, 117 (19%) affected by SpA, and 211 (34.3%) affected by PsA. Age, sex, diagnosis, current treatment, previous treatments with csDMARDs, b-DMARDs, ts-DMARDs, presence of risk factors for cardiovascular (CV) events, liver disease, infections, extra-articular manifestations such as interstitial lung disease (ILD) for RA, enthesitis, dactylitis, uveitis, inflammatory bowel disease for SpA and PsA, neoplasms, diabetes, presence or absence of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) for RA were evaluated. Results. The percentage of treatments with anti-TNF biosimilars was 65.1, 52.4, and 24.3% in SpA (76 patients(pt)), PsA (110 pt), and RA (69 pt), respectively. The percentage of monotherapy was 68% (418 pt) in the three diseases. For RA, 34.2% of patients were difficult to treat (D2T) (98 pt), 54.8% (157 pt) were in monotherapy (tocilizumab-sarilumab-upadacitinib-filgotinib). Abatacept was the most prescribed treatment in RF and ACPA-positive patients and in those with ILD. The anti-IL-17A secukinumab was prescribed in 12% of SpA, of which 71% had enthesitis and dactylitis (14 pt). Ixekizumab was prescribed in 10.4% of PsA patients over 65 years with previous CV events, enthesitis, and dactylitis (21 pt). Apremilast was present in 71% of PsA with previous cancer. Conclusions. The cross-sectional analysis of prescriptions in patients with RA, SpA, and PsA demonstrates how the ITABIO recommendations can guide towards the correct appropriateness of prescription. RA and especially D2T-RA remains the disease with the greatest therapeutic failures, with the highest percentage of monotherapy (anti-IL-6 and Jak-i) and of discontinuation of MTX. Full article

Background/Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory condition that primarily affects the musculoskeletal system and skin. While biologic and targeted synthetic DMARDs have improved treatment, many patients still fail to achieve remission. Combining conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) with biologic (b) DMARDs or targeted synthetic (ts) DMARDs shows no added benefit over monotherapy with IL-17, IL-23 inhibitors, or JAK inhibitors, unlike TNFi, which benefit from csDMARD co-administration. Guselkumab (GUS) and risankizumab (RKZ) target IL-23 with high specificity. RCTs (DISCOVER 1 and 2, COSMOS) have confirmed GUS efficacy regardless of methotrexate (MTX) use, though liver toxicity was higher with MTX. Real-world data on GUS remain limited, with gaps in understanding its long-term effectiveness and drug survival. The aim of this study is to assess the following three points within a multicenter Italian real-life cohort of PsA patients treated with guselkumab (GUS) and followed for 12 months: (1) effectiveness and safety of GUS; (2) drug retention rate (DRR) and reasons for discontinuation; (3) impact of comorbidities on achieving minimal disease activity (MDA). Methods: This study utilized data from the GISEA registry, which includes centers in different parts of Italy (north, center, south, and islands), and included patients aged 18 and older diagnosed with PsA according to the CASPAR criteria. Results: Data on 170 PsA patients treated with GUS were collected. In the first 6 months, a prompt mean percentage improvement in all clinimetric indexes was observed compared to the baseline. At 6-month follow-up, ACR 20 was reached by 60% of patients, ACR 50 by 30%, ACR 70 by 15%, MDA by 28%, and DAPSA < 14 by 50% of patients in the overall group. Significant differences were found in the rate of ACR 50 in the bDMARD-naive group (50%) compared to one bDMARDs non-responder (NR) (8%) (p = 0.021). At 12-month follow-up, a notable gap was observed in the rate of patients reaching MDA between bDMARD-naive (60%) and one bDMARDs NR (22%) (p = 0.035) and between bDMARD-naive (60%) and ≥2 bDMARDs NRs (22%) (p = 0.024). By using multivariate binary logistic analysis, the predictors of reaching MDA at 12-month follow-up were naive bDMARDs (OR: 7.9, 95% CI: 1.3–44.8, p = 0.019) and a higher value of pGA at baseline (OR: 1.1, 95% CI: 1–1.5; p = 0.046). The presence of comorbidities, including fibromyalgia and obesity, did not seem to affect the reaching of MDA. At 12-month follow-up, the GUS retention rate was 76%, with a mean survival time of 10.5 months ± 0.2 (95% CI: 10–10.9). No significant differences in GUS survival time were found among bDMARD-naive, one bDMARDs NR, and ≥2 bDMARDs NR patients (in the latter, regardless of the previous mechanism of action: TNFi or other mechanism), as well as between patients treated with GUS in monotherapy and those treated in combination with csDMARDs. A low rate (17%) of discontinuation was found due to both primary NR and secondary NR. The high safety of GUS was recorded. In fact, discontinuation due to adverse events (all definable as minor) was observed in just 4% of patients. By using COX regression multivariate analysis, the factors associated with higher GUS discontinuation risk were a more severe baseline PASI (HR: 1.05, 95% CI: 1–1.1, p = 0.038) and higher baseline ESR (HR:1.06, 95% CI: 1–1.03, p = 0.05). Conclusions: Good performance of GUS was observed in both biologic-naive patients and those with failure of previous bDMARDs (regardless of the mechanism of action of the previous drug: TNFi or non-TNFi), presenting good persistence in therapy even when used as a third mechanism of action. Its high safety profile allows the use of GUS even in particularly complex patients. Full article

Background: Interstitial lung disease (ILD) is a prominent complication in the course of rheumatoid arthritis (RA), with a prevalence ranging from 5% to 60% and several phenotypes. The existing knowledge on the impact of different pharmacological interventions in individuals with rheumatoid arthritis-related interstitial lung disease (RA-ILD) is inconclusive, and this variable response to treatment highlights the need for a personalized approach to the management of RA-associated ILD. Therefore, we aimed to evaluate the therapeutic effect and safety of different pharmacological agents, including conventional synthetic DMARDs (Cs DMARDs), biologic DMARDs (bDMARDs), targeted synthetic DMARDs (Ts DMARDs), and antifibrotic agents, in patients with RA-ILD. Method: This systematic review and meta-analysis searched for available randomized controlled trials (RCTs) and prospective cohort studies. A search was performed in the PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Eligible studies comprised those involving hospitalized patients diagnosed with RA-ILD, regardless of concomitant medications, who were of adult age (≥18 years); the studies measured the effect of pharmacological interventions, including methotrexate, leflunomide, tumor necrosis factor inhibitors (anti-TNF), abatacept, rituximab, JAK inhibitors, and antifibrotic agents, compared to placebo or other therapies for RA. Results: Out of 446 studies from 2002 to 2024, only 16 were included in this systematic review, including 14 prospective cohort studies and 2 placebo-controlled studies. Unfortunately, no RCTs were found that address our research question. The most relevant studies (n = 4) were performed in different countries (mainly Spain and the UK), with sample sizes varying from 23 to 381 patients (total: 2199 patients). The current study reveals that non-anti-TNF biologics were associated with a decreased risk of radiologic progression, while advanced therapies improved disease-related outcomes in patients requiring oxygen therapy. Methotrexate and other DMARDs were found to have inconsistent effects on ILD progression and mortality. Conclusions: Our review supports the integration of personalized medicine into the management of RA-ILD. By considering patient-specific factors and therapeutic responses, clinicians can better tailor interventions. We confirmed the high methodological quality of the trials, yielding solid evidence for the clinical management of RA-ILD. This review adds to the existing literature by identifying nintedanib as a potential disease-modifying therapy with the potential to slow the progression of lung disease. Full article