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Background: Psoriatic arthritis is a chronic inflammatory condition associated with psoriasis, which affects joints. The coexistence of vasculitis, an inflammation of blood vessels, with psoriatic arthritis is rare, highlighting a complex interplay between autoimmune diseases that affect both joints and vascular structures. Case presentation: We report on a 56-year-old male with a long-standing history of psoriasis and psoriatic arthritis, who presented with new-onset skin lesions and neurological symptoms. Clinical evaluations confirmed the presence of leukocytoclastic vasculitis and asymmetric sensory motor axonal neuropathy. The absence of positive results from various standard tests led to a challenging diagnostic process, ultimately pointing towards vasculitis associated with psoriatic arthritis. The patient was treated with corticosteroids and immunosuppressive therapy, leading to partial symptom improvement. Conclusions: This case underlines the complex and often overlapping nature of autoimmune conditions, particularly the occurrence of vasculitis in patients with psoriatic arthritis, which is rare. It stresses the importance of considering vasculitis in patients with psoriatic arthritis who present with unexplained skin lesions and neurological symptoms. This case adds to the spectrum of psoriatic disease manifestations and suggests a need for further research to explore the underlying mechanisms and improve management strategies. [ABSTRACT FROM AUTHOR]

This document is a letter published in the journal Clinical Rheumatology. It discusses the use of methotrexate (MTX) and tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). The letter presents the results of a survey conducted among rheumatologists regarding their practices and opinions on the use of these medications in RA-ILD. The survey found that many rheumatologists would perform pulmonary screening prior to initiating MTX or TNFi, but most would not repeat screening. The majority of respondents would avoid MTX in patients with a documented history of ILD or hypersensitivity pneumonitis (HP). The letter also mentions the release of new guidelines by the American College of Rheumatology (ACR) for the management of systemic autoimmune rheumatic disease-associated ILD, which may impact clinical practice. The authors acknowledge the limitations of the survey and suggest further exploration of these practice trends in light of the new guidelines. [Extracted from the article]

Objectives: To evaluate the survival of different biologic or targeted-synthetic disease-modifying antirheumatic drugs (b/tsDMARD) administered after fulfilling difficult-to-treat rheumatoid arthritis (D2TRA) criteria, and to assess factors related to treatment discontinuation. Methods: Retrospective study including D2TRA patients. Drug retention of the b/tsDMARD administered after fulfilling D2TRA was assessed by Kaplan–Meier plots and the log-rank test. Cox hazard models were used to identify factors affecting treatment discontinuation. Results: Of the 122 patients included, 75 maintained active treatment (61.5%) with a subsequent line after D2T compared to 47 (38.5%) who discontinued and required more successive lines of b/tsDMARDs. The median survival of the treatments was 78.3(7.6) months and the treatment after D2T with the better rate of survival was rituximab, followed by JAKi and IL6Ri, while worse survival rates were associated with abatacept and TNFi. Significant differences were noted among b/tsDMARDs (log-rank p < 0.01) and to evaluate these differences, a Cox regression was performed, taking each b/tsDMARD as a reference and comparing it with the others. DAS28 values 6-months after initiation of treatment were higher in those patients who discontinued treatment [4.4(1.2) vs 3.5(1.3), p = 0.01]. The multivariate cox regression model revealed that treatment choice after D2T [HR = 1.26(95%CI 1.06–1.05)] and lower DAS28 values at 6 months [HR = 1.49(95%CI 1.16–1.52)] were independent risk factors associated with treatment discontinuation. Conclusions: Once patients met the D2TRA criteria, the subsequent line of b/tsDMARDs with the best survival rates were rituximab, JAKi and IL6Ri. Moreover, DAS28 at 6-months of treatment after D2T was an independent risk factor for drug discontinuation. Key Points • Rituximab, IL6Ri and JAKi have better retention rates in patients after fulfilling D2TRA criteria • Clinical disease activity in the first six months after fulfillment of D2TRA criteria is an independent risk factor of subsequent treatment survival [ABSTRACT FROM AUTHOR]

The article examines the relationship between biologic treatments for psoriasis and the risk of developing depression, based on a retrospective analysis of U.S. administrative claims data. Topics include the reduced incidence of depression among patients using biologics compared to conventional treatments, the relative risk reduction associated with different classes of biologics, and the implications of these findings for future treatment strategies.

Data on COVID-19 re-infections in patients with systemic rheumatic diseases (SRDs) are lacking. We aimed to describe the course and outcomes of COVID-19 re-infections in these patients versus controls. In this single-center retrospective study, we included 167 consecutive SRD patients with at least one COVID-19 re-infection (mean age 47.3 years, females 70.7%). SRD patients were compared in terms of patient-perceived COVID-19 re-infection severity and hospitalizations/deaths with 167 age/sex-matched non-SRD controls. Logistic regression analysis was performed to assess potential milder re-infection versus primary infection severity, adjusting for study group, demographics (age, sex), vaccination status, body mass index, smoking, and comorbidities. 23 and 7 out of 167 re-infected SRD patients experienced two and three re-infections, respectively, which were comparable to the re-infection rates in controls (two: 32; and three: 2) who also had comparable COVID-19 vaccination history (89% and 95% vaccinated, respectively). In the initial infection, patients with SRDs were hospitalized (7.2% versus 1.8%, p = 0.017), and had received antiviral treatment (16.1% versus 4.7%, p < 0.001) more frequently than controls. However, hospitalizations (1.8% vs 0.6%) and antiviral treatment (7.8% vs 3.5%) did not differ (p > 0.05) between patients and controls at the first re-infection, as well as during the second and third re-infection; no deaths were recorded. Perceived severity of re-infections was also comparable between patients and controls (p = 0.847) and among those on biologic DMARDs or not (p = 0.482). In multivariable analysis, neither SRDs presence nor demographics or comorbidities were associated with COVID-19 re-infection severity. COVID-19 re-infection severity (patient-perceived/hospitalizations/deaths) did not differ between SRDs and controls. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a worldwide public health problem. Interventions to delay or prevent the onset of RA have attracted much attention in recent years, and researchers are now exploring various prevention strategies. At present, there is still no unified consensus for RA prevention, but targeting therapeutic windows and implementing interventions for at-risk individuals are extremely important. Due to the limited number of clinical trials on pharmacologic interventions, further studies are needed to explore and establish optimal intervention regimens and effective measures to prevent progression to RA. In this review, we introduce the RA disease process and risk factors, and present research on the use of both Western and Chinese medicine from clinical perspectives regarding RA prevention. Furthermore, we describe several complete and ongoing clinical studies on the use of Chinese herbal formulae for the prevention of RA. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease which can induce progressive disability if not properly treated early. Over the last 20 years, the improvement of knowledge on the pathogenesis of the disease has made available several drugs targeting key elements of the pathogenetic process, which now represent the preferred treatment option after the failure of first-line therapy with conventional drugs such as methotrexate (MTX). To this category of targeted drugs belong anti-cytokine or cell-targeted biological agents and more recently also Janus kinase inhibitors (JAKis). In the absence to date of specific biomarkers to guide the therapeutic choice in the context of true precision medicine, the choice of the first targeted drug after MTX failure is guided by treatment cost (especially after the marketing of biosimilar products) and by the clinical characteristics of the patient (age, sex, comorbidities and compliance) and the disease (presence or absence of autoantibodies and systemic or extra-articular manifestations), which may influence the efficacy and safety profile of the available products. This viewpoint focuses on the decision-making process underlying the personalized approach to RA therapy and will analyse the evidence in the literature supporting the choice of individual products and in particular the differential choice between biological drugs and JAKis. [ABSTRACT FROM AUTHOR]

Background: To assess the association between various systemic lupus erythematosus (SLE) disease manifestations, SLE disease activity index 2000 (SLEDAI-2K), systemic lupus international collaborating clinics/American College of Rheumatology Damage Index (SLICC/ACR- SDI) and serum levels of Slit2 in SLE patients. Results: The mean age of SLE patients was 31.12 ± 8.68 years while the age at onset was 26.05 ± 7.60 years. Female: male was 9 vs 1. The mean serum levels of Slit2 in SLE patients were significantly higher than the controls (0.55 ± 0.25 vs 0.42 ± 0.15) (P = 0.013). There was no significant difference in Slit2 levels between patients with active vs inactive SLE (P = 0.353) or between patients with and without lupus nephritis (P = 0.900). An insignificant difference in Slit2 levels was found among SLE patients using SDI (P = 0.982). No significant correlations were observed between the serum Slit2 and SLE patients' demographics, laboratory data, SLEDAI-2K, and SDI except for a positive correlation with platelets and a negative correlation with serum albumin. ROC curve analysis showed that at a cutoff value of 0.44, the area under the curve was 0.677 (95% CI 0.538–0.816, P = 0.013) with a sensitivity of 74%, specificity of 56%, and accuracy of 68%. Conclusion: While we observed elevated serum Slit2 levels in SLE patients, there was no significant correlation observed between serum Slit2 levels and SLE clinical manifestations, disease activity, or damage index. Trial registration: NCT05105217. Registered 3 November 2021 [ABSTRACT FROM AUTHOR]

Introduction: With an increasing number of biologic/targeted synthetic disease-modifying antirheumatic drug options available for the treatment of active ankylosing spondylitis (AS), also known as radiographic axial spondyloarthritis, it is of clinical interest to determine the comparative efficacy of these advanced therapies among populations with differing prior advanced therapy exposure. This study aimed to assess the comparative efficacy of approved advanced therapies for AS in tumor necrosis factor inhibitor (TNFi)-naïve and, separately, in TNFi inadequate responder/intolerant (-IR) populations. Methods: A systematic literature review was conducted to identify randomized clinical trials for TNFis, interleukin-17A inhibitors, and Janus kinase inhibitors used as advanced therapies for active AS. Clinical efficacy was considered by the Ankylosing Spondylitis Disease Activity Score low disease activity (ASDAS LDA) criteria, defined as ASDAS score less than 2.1, among approved therapies. Comparative efficacy in the TNFi-naïve population was assessed utilizing network meta-analysis, while comparative efficacy in the TNFi-IR population was assessed utilizing matching-adjusted indirect comparison. Odds ratios were calculated, from which absolute rates and numbers needed to treat were calculated. Safety in the form of trial-reported and placebo-adjusted rates of discontinuation due to adverse events (AEs) was reviewed. Results: Among the TNFi-naïve population, the estimated ASDAS LDA rate between week 12 and 16 was highest for patients treated with upadacitinib (52.8%) and lowest for patients treated with placebo (11.6%). Among the TNFi-IR population, the estimated ASDAS LDA rate was 41.3% for patients treated with upadacitinib and 17.5% for patients treated with ixekizumab. The trial-reported and placebo-adjusted rates of discontinuation due to AEs were generally low across included advanced therapies. Conclusions: Relative to other assessed therapies, upadacitinib demonstrated greater clinical efficacy per ASDAS LDA in the treatment of active AS in both TNFi-naïve and TNFi-IR populations. Head-to-head and real-world data comparisons are warranted to both validate these findings and aid medical decision makers. [ABSTRACT FROM AUTHOR]

Introduction: Biologic therapies are licensed for both psoriasis (PsO) and psoriatic arthritis (PsA) with some electronic medical record data suggest that IL (Interleukin)-23 blockers might be more protective in PsA prevention than TNF blockers; however, the findings have been inconsistent. Higher Psoriasis Area and Severity Index (PASI) scores have also been linked to an increased PsA risk. To clarify these unresolved issues we investigated biologic agents, methotrexate, phototherapy, and topical therapy for PsA prevention in patients with psoriasis. Methods: This retrospective cohort study analyzed data from 58,671 patients with psoriasis from the Israeli Meuhedet Health Services Organization database was evaluated for incident PsA. Patients were categorized on the basis of treatment: group 1, topical therapy; group 2, phototherapy; group 3, conventional disease-modifying antirheumatic drugs (cDMARDs; methotrexate); group 4, biologic DMARDs which was also stratified according to biologic class. Results: The PsA incidence rate was lower in the biologic agents' group versus the methotrexate group (HR 0.46 [95% CI 0.35–0.62]). The incidence rates per 100 person-years varied across biologic treatment groups, with the anti‑IL‑12/23 or anti‑IL‑23p19 group at 4.57, the anti-IL-17 group at 4.35, and the TNF inhibitor group at 2.55. No differences were found between various biological agents in terms of preventing PsA. The phototherapy group exhibited a higher PsA development rate than the topical therapy group (HR 1.85 [95% CI 1.65–2.07]). Conclusion: Biological agents are more effective than methotrexate in reducing incident PsA in patients with psoriasis. This lower rate of PsA on topical therapy compared to phototherapy supports the importance of psoriasis severity as a risk factor. [ABSTRACT FROM AUTHOR]

This letter to the editor discusses a comparative study that examined the differences between paradoxical psoriasis (PP) and classical psoriasis. The study found that PP patients had a higher frequency of accompanying autoimmune/inflammatory diseases and were exposed to a higher number of biological agents. Additionally, PP patients had less frequent trunk and extremity involvement compared to classical psoriasis patients. The study suggests that PP patients may require different treatment approaches due to these differences. Another finding of the study was that PP patients had lower need for biological treatment and faster response times to treatment compared to classical psoriasis patients. The study suggests that these differences may be due to variations in the underlying causes of PP and classical psoriasis. The study emphasizes the importance of considering concurrent autoimmune/inflammatory diseases and previous use of biologics when making treatment decisions for PP. [Extracted from the article]

The short-term use of glucocorticoids (GCs) in combination with methotrexate was recommended for the initial treatment of rheumatoid arthritis by the European League Against Rheumatism. A randomized controlled trial (GLORIA) showed that treatment of older patients with low-dose GCs in combination with disease-modifying anti-rheumatic drugs was more efficacious than disease-modifying anti-rheumatic drugs plus placebo in terms of disease activity control and prevention of joint destruction. Glucocorticoid-related adverse events were likely to increase relative to placebo, with no increase in serious adverse events and fractures over 2 years. Observational studies showed an increased risk of serious infections, cardiovascular events, and fractures associated with long-term continuation of GCs in older patients, but the adverse events may be associated not only with GC toxicity but also with poor disease control of rheumatoid arthritis. In the GLORIA study, low-dose GCs during 2 years could be tapered off safely, but many patients had a flare of disease activity after discontinuation of GCs. In the two representative large Japanese registries (IORRA and NinJa), the proportion of patients using GCs and non-tumor necrosis factor inhibitors increased with increasing age at disease onset, with a decreasing trend in methotrexate use. The proportion of patients in remission with GC treatment also increased with increasing age at onset. These suggested that it is not easy to discontinue GCs in older patients. If GCs cannot be terminated in the short term, it may be acceptable to use GCs to control disease activity for up to 2 years. [ABSTRACT FROM AUTHOR]

Background: While the variety of biologics (b) and targeted synthetic (ts) disease-modifying anti-rheumatic drugs (DMARDs) available for patients with psoriatic arthritis (PsA) has proved to be efficacious in randomized clinical trials, there is a growing importance to understand the benefits and potential drawbacks of these different therapies in real-world settings, which includes bio-experienced and older patients as well. Objective: To evaluate the real-world adherence, drug survival, and discontinuation risk of bDMARDs and tsDMARDs among patients with PsA, comprising both younger and older patients. Methods: A retrospective study using a computerized database. Treatment-naïve and treatment-experiencedpatients with PsA, younger and older than 60 years, who initiated treatment with bDMARDs [TNF-α inhibitors (TNF-αis), IL-17 inhibitors (IL-17is), IL-12/23 inhibitors (IL-12/23i)] or tsDMARDs (the PDE-4 inhibitor apremilast) during 2015–2018 were included. Adherence was assessed using the proportion of days covered (PDC) method. Time to discontinuation was analyzed using Kaplan–Meier estimates. Risk of discontinuation was estimated by Cox proportional hazard model. Results: We identified 427 eligible patients (22.2 % were older than 60 years), utilizing 673 treatment lines. The proportion of adherent patients (PDC ≥ 0.8) was similar (62.1–66.5%) across all lines of therapy and across different biologics (70.0–72.0%), while apremilast showed the lowest, in both treatment-naïve and experienced settings (43.6% and 25.5%, respectively). The Kaplan–Meier analysis showed that in the treatment-naïve TNF-αis had higher drug survival compared with apremilast (P = 0.032). Apremilast also had the lowest drug survival in the treatment-experienced group (P < 0.0001). Kaplan–Meier analysis by age groups showed similar drug survival rates in older (≥ 60 years) and younger (age < 60 years) patients, regardless of treatment-experience status. The multivariable model showed that apremilast had increased risk for discontinuation compared with TNF-αis. Conclusion: Adherence, drug survival and risk for discontinuation were similar for all included bDMARDs, regardless of treatment experience status, while apremilast showed lower rates and increased risk. Adherence and discontinuation rate were similar in older and younger patients. With the variety of drug modes of action available for patients with PsA, these findings may assist caregivers in selecting the appropriate treatment. [ABSTRACT FROM AUTHOR]

Biological disease-modifying antirheumatic drugs (bDMARDs) can have different effects on various clinical manifestations of ankylosing spondylitis (AS). Data on the effects of interleukin 17 inhibitors (IL17-i) on uveitis in AS continue to accumulate. Objective: to evaluate the effect of IL17-i therapy on the course of uveitis in AS. The study involved 73 patients with AS (New York criteria, 1984), who received IL17-i (57—secukinumab (SEC), 22—netakimab (NTK)) for at least 1 year. The average age of patients at the time of inclusion in the study was 41.93 ± 8.95 years, the average duration of AS was 10.75 ± 6.22 years. There were 40 men (56.7%) and 33 women (43.3%) among the patients. HLA-B27 was detected in 62/73 (85%), coxitis in 58 (79%), enthesitis in 63 (86.3%), peripheral arthritis in 57 (78%), psoriasis in 7 (9.5%), and inflammatory bowel disease (IBD) in 3 (4.1%) patients; in 6 (8.2%) patients, the disease started before the age of 16; 19 (26%) patients had at least one episode of uveitis during the course of the disease. The rates of uveitis was estimated by comparing the number of incidences per 100 patient-years before the start of bDMARDs therapy and during IL17-i using. The incidence rate of uveitis before the start of bDMARDs therapy for all patients was 8.3 per 100 pt-years (95% CI 0.065–0.107), during IL17-i therapy— 9.2 per 100 pt-years (95% CI 0.06–0.15), p = 0.72. The incidence rate of uveitis among patients who used SEC was 10.1 per 100 pt-years (95% CI 0.079–0.13) before the start of bDMARDs therapy and 9.4 per 100 pt-years (95% CI 0.05-0.15), p = 0.74 during SEC therapy. The incidence rate of uveitis among patients who used NTK was 4.8 per 100 pt-years (95% CI 0.028–0.08) before the start of bDMARDs therapy and 7.1 per 100 pt-years (95% CI 0.019–022), p = 0.3 during the NTK therapy. For patients with a history of uveitis, the incidence rate of uveitis was 22.5 per 100 pt-years (95% CI 0.18–0.28) before the start of therapy with bDMARDs and 29.1 per 100 pt-years (95% CI 0.18–0.43), p = 0.29 during IL17-i therapy. Occurrences of uveitis were observed in 4 of 57 patients (7%) during SEC therapy and in 1 of 25 (4%) patients during the NTK therapy. One case of new-onset uveitis was recorded during the using of SEC. There were no significant differences in the incidence rates of uveitis during IL17-i therapy compared with non-biological therapy. IL17-i therapy have not demonstrated a significant effect on the course of uveitis in AS in the study group. [ABSTRACT FROM AUTHOR]

Relapsing polychondritis (RP) is a systemic immune mediated disease characterized by recurrent episodes of inflammation in various cartilage-rich areas. RP may cause extensive tissue destruction and is associated with significant morbidity and mortality. In this multicenter study, we considered the remission status and long-term outcomes of RP in patients who were followed-up in six referral rheumatology centers in Iran. Outcomes of disease was assessed by remission status and RP induced damage. A total of 29 patients with RP were examined for enrollment in the study, and 26 patients with a minimum follow-up period of 6 months were included in the RP outcome analysis. Median time to control of symptoms and sustained remission were 5 and 23 weeks, respectively. Prednisolone was discontinued in 8 (30.8%) patients and medication-free remission was achieved in 7 (23.1%) patients. Regarding the disease course, 34.6% of patients had a relapsing–remitting course, 42.3% had a monophasic course, and 23.1% had an always-active course. Despite extensive treatment with immunosuppressive medications, RP induced damage was developed in 21 (80.8%) patients. Ear deformity and osteoporosis were the most common RP induced damage. Long-term remission and medications-free remission in RP is accessible. However, RP related damage occur in majority of patients. [ABSTRACT FROM AUTHOR]

This study aims to identify factors influencing the alleviation of knee joint symptoms in patients with rheumatoid arthritis treated with biologic or target synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Among 2321 patients who started b/tsDMARDs between 2010 and 2023, we focused on 295 patients who had knee swelling or tenderness at the initiation of b/tsDMARDs and continued b/tsDMARDs at least 3 months, with recorded knee symptoms 6 months later. Symptom relief after 6 months was 78.2% for interleukin 6 (IL-6) inhibitors, 68.6% for Janus kinase (JAK) inhibitors, 65.8% for tumor necrosis factor (TNF) inhibitors, and 57.6% for cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA4-Ig). The initial use of b/tsDMARDs and the use of IL-6 inhibitors in comparison to CTLA4-Ig emerged as a significant factor associated with the improvement of knee joint symptoms. Among 141 patients who underwent knee radiography at baseline and two years later, the deterioration in knee joint radiographs was 7.7% for IL-6 inhibitors, 6.3% for JAK inhibitors, 21.9% for TNF inhibitors, and 25.9% for CTLA4-Ig. The use of IL-6 inhibitors was a significant factor associated with the improvement of knee joint symptoms and the inhibition of joint destruction compared to CTLA4-Ig. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to develop low-cost models using machine learning approaches predicting the achievement of Clinical Disease Activity Index (CDAI) remission 6 months after initiation of tumor necrosis factor inhibitors (TNFi) as primary biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) for rheumatoid arthritis (RA). Methods: Data of patients with RA initiating TNFi as first b/tsDMARD after unsuccessful methotrexate treatment were collected from the FIRST registry (August 2003 to October 2022). Baseline characteristics and 6-month CDAI were collected. The analysis used various machine learning approaches including logistic regression with stepwise variable selection, decision tree, support vector machine, and lasso logistic regression (Lasso), with 48 factors accessible in routine clinical practice for the prediction model. Robustness was ensured by k-fold cross validation. Results: Among the approaches tested, Lasso showed the advantages in predicting CDAI remission: with a mean area under the curve 0.704, sensitivity 61.7%, and specificity 69.9%. Predicted TNFi responders achieved CDAI remission at an average rate of 53.2%, while only 26.4% of predicted TNFi non-responders achieved remission. Encouragingly, the models generated relied solely on patient-reported outcomes and quantitative parameters, excluding subjective physician input. Conclusions: While external cohort validation is warranted for broader applicability, this study highlights the potential for a low-cost predictive model to predict CDAI remission following TNFi treatment. The approach of the study using only baseline data and 6-month CDAI measures, suggests the feasibility of establishing regional cohorts to generate low-cost models tailored to specific regions or institutions. This may facilitate the application of regional/in-house precision medicine strategies in RA management. Plain Language Summary: This study aims to enhance the management of rheumatoid arthritis by predicting the likelihood of achieving the treatment target—Clinical Disease Activity Index remission within 6 months of initiating tumor necrosis factor inhibitors. In rheumatoid arthritis, the goal is often Clinical Disease Activity Index remission, and the standard approach involves using medications like methotrexate and biologic/targeted synthetic disease-modifying antirheumatic drugs. However, not all patients respond to these treatments, leading to a trial-and-error process of changing medications. Tumor necrosis factor inhibitors are commonly used as the initial biologic/targeted synthetic disease-modifying antirheumatic drugs for patients who do not respond adequately to methotrexate; however, tumor necrosis factor inhibitor treatment may not achieve effective outcomes for all patients. The study, using a cohort of patients with rheumatoid arthritis treated with tumor necrosis factor inhibitor, has developed a model predicting Clinical Disease Activity Index remission with tumor necrosis factor inhibitors. The models use only standard clinical parameters, therefore no special examination or additional cost is required for the predictions. This approach holds the potential to improve rheumatoid arthritis management by reducing the need for trial-and-error approaches and facilitating more personalized and effective treatment strategies. While further validation is necessary, the study also suggests that creating cost-effective models tailored to specific regions or institutions is possible. [ABSTRACT FROM AUTHOR]

Introduction: Real-world studies describing biosimilar initiation or switching in patients with rheumatoid arthritis (RA) are limited. The aim of this study was to assess treatment patterns and effectiveness of real-world patients with RA initiating infliximab biosimilar IFX-dyyb (CT-P13; Inflectra®) in the USA. Methods: This observational study evaluated patients with RA from the CorEvitas RA Registry who initiated IFX-dyyb and had Clinical Disease Activity Index (CDAI) recorded at baseline and 6 months. The primary outcome was reaching low disease activity (LDA; CDAI ≤ 10) at 6 months in patients with moderate or high disease activity (CDAI > 10) at baseline. Secondary outcomes were change at 6 months in CDAI and certain patient-reported outcomes (PROs). Patient data were stratified by prior treatment: biologic/targeted synthetic disease-modifying antirheumatic drug (tsDMARD)-naïve, reference infliximab (IFX-REF) or IFX biosimilar, or a non-IFX biologic or tsDMARD. Results: Of 318 patients initiating IFX-dyyb, 176 had baseline and 6-month CDAI scores; 73 (41%) switched from IFX, 61 (35%) switched from another non-IFX/biologic/tsDMARD, 32 (18%) were naïve to biologics/tsDMARDs, and 10 (6%) switched from an IFX biosimilar. Among patients with moderate or high disease activity at baseline, 32.9% (95% CI 22.9, 42.9) achieved LDA at 6 months. Mean 6-month change from baseline in CDAI was − 1.8 (95% CI − 3.3, − 0.3) overall; − 4.7 (− 7.6, − 1.7) in patients who switched from a non-IFX biologic/tsDMARD, − 4.1 (− 7.8, − 0.3) in biologic/tsDMARD-naïve patients, and 1.1 (− 0.4, 2.6) in patients who switched from IFX-REF/IFX biosimilar. Other clinical outcomes/PROs improved at 6 months. Of the IFX-dyyb initiators, 68% remained on IFX-dyyb at 6 months. Conclusion: In this real-world population of patients with RA initiating IFX-dyyb, the majority switched from IFX-REF or a non-IFX biologic/tsDMARD. CDAI remained stable in patients switching from IFX-REF/IFX biosimilar and improved in patients switching from a non-IFX biologic/tsDMARD and in biologic/tsDMARD-naïve patients. Plain Language Summary: Infliximab is an effective treatment for rheumatoid arthritis (RA). Biosimilars—biologic drugs designed to be very similar to the originator products—are now available that may be more affordable with matching efficacy and safety. IFX-dyyb is a US Food and Drug Administration-approved infliximab biosimilar but little is known about its use in real-world clinical practice in patients with RA in the USA. This study used data from a large observational registry to look at treatment patterns and effectiveness of IFX-dyyb in adults with RA. One hundred and seventy-six patients were included who had data available at both baseline and at 6 months. Most patients (47%) switched to IFX-dyyb from the originator infliximab or another infliximab biosimilar; 35% switched from another RA treatment, and 18% were new to treatment. Six months after starting IFX-dyyb, 68% of patients were still receiving treatment. A measure of clinical disease activity remained stable in patients who switched from originator infliximab or another biosimilar, while this measure improved in patients switching to IFX-dyyb from other treatments or starting treatment for the first time. Other clinical measures and patient-reported outcomes such as pain and fatigue also improved over 6 months with IFX-dyyb. This real-world study of patients with RA initiating IFX-dyyb in the USA adds to our knowledge of the use of biosimilars in this patient population. [ABSTRACT FROM AUTHOR]

Introduction: Long-term therapeutic options providing durable response and tolerability are needed for psoriatic arthritis (PsA). The ongoing KEEPsAKE 2 trial is evaluating risankizumab treatment in patients with active PsA who previously had inadequate response/intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) and/or 1–2 biologic DMARDs (bDMARD-IR). Herein, we report results through 100 weeks of treatment. Methods: KEEPsAKE 2 is a global phase 3 trial. Patients with active PsA were randomized 1:1 to double-blind subcutaneous risankizumab 150 mg or placebo (weeks 0, 4, and 16). At week 24, all patients received open-label risankizumab every 12 weeks until end of study. Efficacy endpoints included achieving ≥ 20% improvement in PsA symptoms using American College of Rheumatology criteria (ACR20), attaining minimal disease activity (MDA; meeting ≥ 5/7 criteria of low disease activity and extent), and improving in other measures. Results: At the cutoff date, 345/443 (77.9%) patients were ongoing in the study. ACR20 was achieved in 57.1% and 52.5% of the continuous risankizumab and placebo/risankizumab cohorts, respectively, at week 100 and in 60.0% and 55.8%, respectively, at week 52. In week 52 responders, maintenance of ACR20 at week 100 was achieved in 74.8% (continuous risankizumab) and 78.7% (placebo/risankizumab) of patients. In the continuous risankizumab and placebo/risankizumab cohorts, respectively, MDA was achieved by 33.0% and 33.3% of patients at week 100 and by 27.2% and 33.8% at week 52. Among MDA responders at week 52, maintenance of MDA response was achieved by 83.6% and 73.0% of the continuous risankizumab and placebo/risankizumab cohorts, respectively. Risankizumab was well tolerated through week 100. Conclusions: Risankizumab demonstrated durable efficacy and tolerability through 100 weeks; most patients who achieved ACR20 and MDA responses at week 52 maintained this achievement through week 100. There were no new safety signals in patients who had csDMARD-IR and bDMARD-IR. Trial Registration: ClinicalTrials.gov NCT03671148. Plain Language Summary: Risankizumab, a biologic disease-modifying antirheumatic drug, helps control the body's immune system to reduce symptoms of psoriatic arthritis (a disease that inflames the joints of people who have the skin condition psoriasis). The ongoing KEEPsAKE 2 study is evaluating how well risankizumab works and how safe it is for treating adult patients with active psoriatic arthritis who previously experienced inadequate response to one or more specific types of disease-modifying anti-arthritis drugs. Patients were randomly assigned to receive either risankizumab or an inactive drug; after 24 weeks, all patients received risankizumab. At study week 100, 57% of patients who were assigned to receive continuous risankizumab since the start of the study experienced a 20% or more improvement in a measure of psoriatic arthritis symptoms using criteria established by the American College of Rheumatology (ACR20); a similar proportion of patients achieved a 20% improvement at both weeks 24 and 52. Similarly, 56% and 53% of patients who switched from inactive drug to risankizumab achieved ACR20 at weeks 52 and 100 (more than before switching to risankizumab at week 24). Minimal disease activity (MDA) was evaluated by assessing joint and skin symptoms, affected body surface area, pain, and physical function. At week 100, 33% of patients achieved MDA (both groups), which was similar to week 52. Most patients who achieved ACR20 or MDA at week 52 maintained responses at week 100. Improvements with risankizumab were seen in several other measures of treatment outcomes through week 100. Risankizumab was generally safe through 100 weeks. [ABSTRACT FROM AUTHOR]

Introduction: Guselkumab is an interleukin-23 (IL-23) inhibitor licensed for the treatment of psoriatic arthritis (PsA). This study aimed to evaluate the 6-month effectiveness of guselkumab in patients with PsA in a "real-life" multicentre patient cohort. We also estimated the drug retention rate (DRR) of gusulkumab, also assessing the impact of comorbidities and patient clinical characteristics, in a collective 18-month prospective follow-up. Methods: Between December 2021 and September 2023, consecutive patients with PsA were evaluated if treated at least for 6 months with guselkumab in a prospective multicentre study to evaluate the effectiveness of the drug by means of disease activity index for psoriatic arthritis (DAPSA) and cumulative DRR. Results: A total of 111 patients with PsA were evaluated and treated with guselkumab (age 56.8 ± 9.9, male sex 20.7%). These patients were mainly characterised by active and long-standing PsA with median disease duration of 6.0 (7.0) years (55.9% disease duration ≥ 5 years), 55.0% showed comorbidities, 78.4% of patients were previously treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs), and 60.4% concomitantly with conventional synthetic DMARDs (csDMARDs). After 6 months, a significant reduction of DAPSA was observed (β − 15.47, p = 0.001, 95% CI − 23.15 to − 9.79) with 39.6% of patients achieving a DAPSA ≤ 14. At the end of cumulative follow-up, 71.2% of patients were still treated with guselkumab whereas 24.3% discontinued the drug because of inefficacy. An 18-month DRR of guselkumab of 66.7% was estimated with a mean time of administration of 9.8 ± 4.1 months. The results of the DRR were stratified according to patient clinical characteristics. The DRR of guselkumab appeared to be not influenced by long disease duration, comorbidities, obesity, concomitant csDMARDs, and previous bDMARDs. Conclusion: The "real-life" 6-month effectiveness of guselkumab was shown in patients with PsA, mainly characterised by active long-standing disease, previously treated with bDMARDs, and with comorbidities. Furthermore, a good DRR of guselkumab was estimated in the cumulative 18 months of follow-up and appeared to be not influenced by long disease duration, comorbidities, obesity, and previous bDMARDs. [ABSTRACT FROM AUTHOR]

Introduction: Patients with psoriatic arthritis (PsA) require treatment providing durable long-term efficacy in different disease domains as well as safety. We present 100-week efficacy and safety results of risankizumab in patients with active PsA and previous inadequate response/intolerance to ≥ 1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR). Methods: KEEPsAKE 1 (NCT03675308) is a global phase 3 study, including a 24-week, double-blind, placebo-controlled and ongoing open-label extension periods. Patients were randomized 1:1 to receive risankizumab 150 mg or placebo at baseline and weeks 4 and 16. After week 24, all patients received open-label risankizumab every 12 weeks thereafter. Patients were evaluated through 100 weeks. Endpoints included achieving ≥ 20% reduction in American College of Rheumatology criteria for symptoms of rheumatoid arthritis (ACR20), minimal disease activity (MDA; defined as ≥ 5/7 criteria of low disease activity and extent), and other measures. Results: Overall, 828/964 (85.9%) patients completed week 100. For patients receiving continuous risankizumab, 57.3%, 70.6%, and 64.3% achieved ACR20 at weeks 24, 52, and 100, respectively. For the placebo/risankizumab cohort, 33.5% achieved ACR20 at week 24 but increased after switching to active treatment at weeks 52 (63.7%) and 100 (62.1%). In ACR20 responders at week 52, 81.2% of both treatment cohorts maintained response at week 100. MDA was achieved by 25.0%, 38.3%, and 38.2% of the continuous risankizumab cohort at weeks 24, 52, and 100. In the placebo/risankizumab cohort, 10.2% achieved MDA at week 24, increasing at weeks 52 (28.0%) and 100 (35.2%). MDA response was maintained at week 100 in week 52 responders in the continuous risankizumab (75.5%) and placebo/risankizumab cohorts (78.2%). Similar trends were observed for other efficacy measures. Risankizumab was generally well tolerated through 100 weeks. Conclusions: For patients with active PsA who are csDMARD-IR, risankizumab demonstrated durable long-term efficacy and was generally well tolerated, with a consistent long-term safety profile. Trial Registration: ClinicalTrials.gov identifier, NCT03675308. Plain Language Summary: Psoriatic arthritis (PsA) often affects individuals with the skin condition psoriasis. A biologic disease-modifying antirheumatic drug can help control inflammation and regulate the immune system to ease symptoms and slow progression of PsA. The ongoing KEEPsAKE 1 study is evaluating the efficacy and safety of risankizumab in patients with active PsA who previously have not had success with ≥ 1 conventional disease-modifying antirheumatic drug. Patients were initially treated with risankizumab 150 mg (continuous risankizumab group) or inactive drug (inactive drug/risankizumab group). After 24 weeks, all received risankizumab for the rest of the study. At week 100, 64% (continuous risankizumab group) and 62% (inactive drug/risankizumab group) of patients had ≥ 20% improvement in PsA symptoms (measured using American College of Rheumatology [ACR20] criteria). Both groups showed similar percentages at week 52 and improvement from week 24. In patients who achieved ACR20 at week 52, 81% maintained their ACR20 response at week 100. Minimal disease activity was defined as a combination of joint and skin symptoms, affected body surface area, pain, and physical functioning. At week 100, 38% of the continuous risankizumab group and 35% of the inactive drug/risankizumab group achieved minimal disease activity. Percentages were similar at week 52 and higher than week 24 in both groups. In patients who achieved minimal disease activity at week 52, 81% maintained response at week 100. All other measures of treatment responses showed similar patterns from the start of risankizumab through week 100. Risankizumab was considered generally safe by the treating physicians. [ABSTRACT FROM AUTHOR]

Introduction : Rheumatoid arthritis (RA) is usually treated with disease modifying antirheumatic drugs (DMARDs), including biological DMARDs (bDMARDs) and more recently, Janus kinase inhibitors (JAKi). Randomized trials suggest similar infection risks for JAKi and bDMARDs, but real-world data are scarce. Methods: From a nationally representative prescription database, adult RA patients starting a new JAKi or bDMARD between August 1st, 2018, and January 31st, 2021, were included. Prescriptions of antibiotic, antiviral or antifungal medication were used as proxy for infections. Infection incidence rates (IR) were compared between JAKi and bDMARDs and infection risks were estimated using multilevel Poisson regression adjusted for follow-up time and potential confounders and stratified for age < 65 and ≥ 65 years. Results: In 14,989 patients, we identified 20,050 treatment episodes with either JAKi or bDMARDs. The infection IR was significantly higher in JAKi (48/100 patient years) compared bDMARDs (35/100 patient years, adjusted incidence rate ratio (IRR) 1.22, 95% CI 1.12-1.33). More herpes zoster infections were seen in JAKi compared to bDMARDs (adjusted IRR 2.65, 95% CI 1.94-3.60). No significant differences in infection IRs were found comparing JAKi baricitinib and tofacitinib. In older patients, infection IRs were higher, but IRRs were similar between age groups. Conclusion: In comparison to bDMARDs, JAKi are associated with a slightly higher infection risk and a higher risk of herpes zoster specifically. In older patients, infection IRs are higher but similar infection risks for JAKi and bDMARDs are observed. No differences in infection risk between tofacitinib and baricitinib were found. Key Points • Compared to bDMARDs, JAKi are associated with a slightly higher infection risk for all ages • An increased risk of herpes zoster in patients who use JAK inhibitors was confirmed • No significant differences in infection incidence were found between tofacitinib and baricitinib [ABSTRACT FROM AUTHOR]

Objective: To describe the trends in remission rates among RA patients in the OPAL dataset, spanning from 2009 to 2022, and provide insights into the effectiveness of evolving RA management approaches in real-world clinical settings. Methods: Patients with a physician diagnosis of RA and at least 3 visits between 1 January 2009 and December 2022 were identified in the OPAL dataset, an aggregated collection of data extracted from the electronic medical records of patients managed by 117 Australian rheumatologists. Demographics, disease history, prescribed medications and proportions of patients in Disease Activity Score 28-joint count C-reactive protein (DAS28CRP)) categories (remission, low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)) were described. Results: A large population (n = 48,388) of eligible patients with RA were identified in the OPAL dataset. A consistent and substantial improvement in DAS28CRP remission rates were found in (i) all patients, (ii) patients managed on conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and (iii) patients treated with biological or targeted synthetic (b/ts)DMARD therapy, increasing from approximately 50% in 2009 to over 70% by 2022. The increase in DAS28CRP remission was accompanied by reduced proportions of patients in MDA and HDA states. Conclusion: This study highlights a consistent improvement in disease activity and rising remission rates among Australian RA patients within the OPAL dataset, offering the potential for enhanced patient outcomes and reduced disease burden. Key Points • The treat-to-target (T2T) approach, with the treatment goal of remission or, as an alternative, a state of LDA, has been widely adopted for the management of RA in Australia. • This study demonstrates an encouraging trend of improved disease activity over time, with remission rates of Australian patients with RA steadily increasing year on year. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the demographic and clinical characteristics of the groups with and without bDMARDs added to the treatment of persistent oligoarticular juvenile idiopathic arthritis (JIA) patients on methotrexate (MTX) and also to determine the predictors of adding bDMARDs to treatment. This study included 86 oligoarticular JIA patients on MTX. Patients were divided into two groups receiving MTX (n = 69) and MTX plus bDMARD (n = 17). Predictors of adding bDMARDs were investigated by comparing demographic, clinical features and laboratory findings. Gender, age at diagnosis, time elapsed from the onset of symptoms to diagnosis, and disease duration, the number and distribution of affected joint at the time of diagnosis were similar in both groups. The mean JADAS10 at the time of diagnosis were 18.8 ± 4.2 and 19.5 ± 6.4 in the MTX and MTX plus bDMARDs groups, respectively (p = 0.68). JADAS10 at 3rd and 6th month were significantly higher in patients on MTX plus bDMARDs (p = 0.001, p = 0.004, respectively). In multivariate analysis, the risk of adding bDMARD was shown to increase 1.24-fold (p = 0.004, 95% CI: 1.07–1.43) for each point increase on the JADAS 10 at 3rd months. The number (p = 0.64) or type (p = 0.18) of joint involvement at disease onset were not predictors of adding a bDMARD. Conclusion: JADAS10 indicating ongoing severe disease activity at 3rd and 6th months rather than baseline JADAS10 is associated with the addition of bDMARDs. What is Known: • Oligoarticular JIA patients have the best outcomes among JIA categories and respond favorably to first-line therapies such as non-steroidal anti-inflammatory drugs and intraarticular corticosteroid injections. • Clinically inactive disease rates have increased with the widespread use of biological agents in oligoarticular JIA patients who have not responded to initial therapies. What is New: • Approximately one-fifth of patients with persistent oligoarticular JIA on methotrexate may require the addition of a biological disease modifying anti-rheumatic drug during follow-up. • The JADAS10 calculated at 3 and 6 months is a valuable tool to identify patients who should be added biological disease modifying anti-rheumatic drugs in persistent oligoarticular JIA. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) stands as an autoimmune disorder characterized by chronic joint inflammation, resulting in profound physiological alterations within the body. Affecting approximately 0.4–1.3% of the global population, this condition poses significant challenges as current therapeutic approaches primarily offer symptomatic relief, with the prospect of complete recovery remaining elusive. This review delves into the contemporary advancements in understanding the pathophysiology, diagnosis, and the therapeutic potential of herbal medicine in managing RA. Notably, early diagnosis during the initial stages emerges as the pivotal determinant for successful recovery post-treatment. Utilizing tools such as Magnetic Resonance Imaging (MRI), anti-citrullinated peptide antibody markers, and radiography proves crucial in pinpointing the diagnosis of RA with precision. Unveiling the intricate pathophysiological mechanisms of RA has paved the way for innovative therapeutic interventions, incorporating plant extracts and isolated phytoconstituents. In the realm of pharmacological therapy for RA, specific disease-modifying antirheumatic drugs have showcased commendable efficacy. However, this conventional approach is not without its drawbacks, as it is often associated with various side effects. The integration of methodological strategies, encompassing both pharmacological and plant-based herbal therapies, presents a promising avenue for achieving substantive recovery. This integrated approach not only addresses the symptoms but also strives to tackle the underlying causes of RA, fostering a more comprehensive and sustainable path towards healing. [ABSTRACT FROM AUTHOR]

Background: Reports on treatment patterns of biologic disease-modifying antirheumatic drugs (bDMARDs)/Janus kinase inhibitors (JAKi) for rheumatoid arthritis (RA) in clinical practice are still sparse in Japan, especially in combination with conventional synthetic DMARDs (csDMARDs). Objectives: The aim of this study was to investigate treatment patterns of bDMARD/JAKi in the treatment of RA in real-world clinical practice in Japan. Method: A retrospective cohort study was conducted using the Japanese Medical Data Vision health claims database. The inclusion criteria required a recorded diagnosis of RA, defined by ICD-10 codes, in patients aged 18 years and older on the index date. We analyzed 39,903 RA patients treated with DMARDs from 2008 to 2020. Results: Among analyzed subjects, 10,196 patients (25.6%) were prescribed bDMARDs/JAKi in combination with csDMARDs, and 3067 patients (7.7%) were prescribed these drugs without csDMARDs. Among the bDMARDs/JAKi, tumor necrosis factor inhibitors (TNFi) were the most commonly prescribed DMARD overall, and also the most common first-line therapy, accounting for 60.0% or 45.5% of patients prescribed these drugs in combination with or without csDMARDs, respectively. Switching, temporary discontinuation (restarting with the same agents), and discontinuation of bDMARDs/JAKi were observed in 3150 (30.9%), 1379 (13.5%), and 2025 (19.9%) patients with csDMARDs, and in 849 (27.7%), 513 (16.7%), and 833 (27.2%) patients without csDMARDs, respectively. Conclusions: Real-world treatment trajectories of bDMARDs/JAKi with and without csDMARDs was analyzed in RA patients in Japan between 2008 and 2020. TNFi were the predominant first-line therapy, and likely to be switched to different classes. Understanding the current treatment patterns, including discontinuation, is important to find an optimal treatment strategy for RA patients. [ABSTRACT FROM AUTHOR]

Background: Disease-modifying anti-rheumatic drugs (DMARDs), since their introduction in 1990, have revolutionized the management of rheumatoid arthritis. Newer DMARDs have recently been approved, influencing treatment patterns and clinical guidelines. Objective: To update the current prescribing patterns of DMARDs in the pharmacotherapy of rheumatoid arthritis (RA) to include the pandemic era. Methods: This was a retrospective cross-sectional multi-year study. Using Optum's Clinformatics® Data Mart Database, we summarized trends in the prevalence of DMARD use in the USA from 2016 to 2021 by year for adult patients ≥ 18 years old with at least one medical RA claim and one pharmacy/medical claim of a DMARD medication. Trends included type of DMARD, class of DMARD (conventional (csDMARDs), biologics [tumor necrosis factor (TNFi) and Non-TNFi), and Janus kinase inhibitors (JAKs)], and triple therapy [methotrexate (MTX), hydroxychloroquine (HCQ), sulfasalazine (SUL)] used. Results: The total sample from 2016 to 2021 was 670,679 commercially insured patients. The average age was 63.7 years (SD 13.6), and 76.7% were female and 70% were White. csDMARDs remain the most prescribed (ranging from 77.2 to 79.2%). Although JAKs were the least prescribed DMARD class, their proportion more than doubled from 2016 (1.5%) to 2021 (4%). MTX utilization declined from 40% in 2016 to 34% in 2021. In contrast, HCQ use increased during the pandemic era from < 25% in 2018 to 30% in 2021. Although there is evidence of the therapeutic benefit of triple therapy, its use was very low (~ 1%) compared to biologics only (~ 17%) or biologics+MTX (~ 10%). Conclusion: About half of patients with RA were on DMARDs. As expected, csDMARDs were highly used consistently. The COVID-19 pandemic might have influenced the use of HCQ and infusion DMARDs. Triple therapy use remains low. [ABSTRACT FROM AUTHOR]

Monocyte-derived macrophages play a key pathogenic role in inflammatory diseases. In the case of rheumatoid arthritis (RA), the presence of specific synovial tissue-infiltrating macrophage subsets is associated with either active disease or inflammation resolution. JAK inhibitors (JAKi) are the first targeted synthetic disease-modifying antirheumatic drugs (tsDMARD) approved for treatment of RA with comparable efficacy to biologics. However, the effects of JAKi on macrophage specification and differentiation are currently unknown. We have analyzed the transcriptional and functional effects of JAKi on human peripheral blood monocyte subsets from RA patients and on the differentiation of monocyte-derived macrophages promoted by granulocyte-macrophage colony-stimulating factor (GM-CSF), a factor that drives the development and pathogenesis of RA. We now report that JAKi Upadacitinib restores the balance of peripheral blood monocyte subsets in RA patients and skewed macrophages towards the acquisition of an anti-inflammatory transcriptional and functional profile in a dose-dependent manner. Upadacitinib-treated macrophages showed a strong positive enrichment of the genes that define synovial macrophages associated to homeostasis/inflammation resolution. Specifically, Upadacitinib-treated macrophages exhibited significantly elevated expression of MAFB and MAFB-regulated genes, elevated inhibitory phosphorylation of GSK3β, and higher phagocytic activity and showed an anti-inflammatory cytokine profile upon activation by pathogenic stimuli. These outcomes were also shared by macrophages exposed to other JAKi (baricitinib, tofacitinib), but not in the presence of the TYK2 inhibitor deucravacitinib. As a whole, our results indicate that JAKi promote macrophage re-programming towards the acquisition of a more anti-inflammatory/pro-resolution profile, an effect that correlates with the ability of JAKi to enhance MAFB expression. [ABSTRACT FROM AUTHOR]

Although several biological disease-modifying antirheumatic drugs (bDMARDs), including interleukin (IL)-17A inhibitors, are approved for psoriatic arthritis, the treatment of this disease remains suboptimal. Bimekizumab (Bimzelx®), a dual IL-17A and IL-17F inhibitor, is approved in the EU, Great Britain and Japan for the treatment of psoriatic arthritis. In pivotal phase 3 clinical trials in patients who were bDMARD-naïve or previously had an inadequate response or intolerance to tumour necrosis factor (TNF) α inhibitors, bimekizumab improved the signs and symptoms of psoriatic arthritis across a range of joint, skin, radiographic and patient-reported outcomes compared with placebo, including the proportion of patients achieving a ≥ 50% response in the American College of Rheumatology criteria. Phase 2 clinical trial data have shown that responses are maintained up to 3 years. Bimekizumab was generally well tolerated in patients with psoriatic arthritis, with a safety profile consistent with that in other approved indications. The most common adverse events included nasopharyngitis, upper respiratory tract infection, oral candidiasis, headache and diarrhoea. In conclusion, bimekizumab extends the treatment options available to patients with psoriatic arthritis. Plain Language Summary: Psoriatic arthritis is a chronic, painful, inflammatory condition that can involve peripheral and axial joints, skin and nails, and can lead to structural joint damage. Several disease-modifying antirheumatic drugs (DMARDs), including biologicals (bDMARDs) that target various inflammatory cytokines, are approved for psoriatic arthritis. However, many patients do not respond or lose response to these treatments. Bimekizumab (Bimzelx®), an inhibitor of both interleukin (IL)-17A and IL-17F, is approved for the treatment of psoriatic arthritis in the EU, Great Britain and Japan. In clinical trials, bimekizumab improved the signs and symptoms of psoriatic arthritis across key disease domains compared with placebo, including the proportion of patients achieving ≥ 50% response in the American College of Rheumatology criteria. Bimekizumab was efficacious whether patients were naïve to bDMARDs or previously had an inadequate response to or did not tolerate tumour necrosis factor (TNF) α inhibitors. Clinical responses were sustained long-term (up to 3 years). Bimekizumab was generally well tolerated, with the most common adverse events being infections (such as nasopharyngitis, upper respiratory tract infection and oral candidiasis), headache and diarrhoea. In conclusion, bimekizumab extends the treatment options available to patients with psoriatic arthritis. [ABSTRACT FROM AUTHOR]

Rare diseases (RD) affect a small number of people compared to the general population and are mostly genetic in origin. The first clinical signs often appear at birth or in childhood, and patients endure high levels of pain and progressive loss of autonomy frequently associated with short life expectancy. Until recently, the low prevalence of RD and the gatekeeping delay in their diagnosis have long hampered research. The era of nucleic acid (NA)-based therapies has revolutionized the landscape of RD treatment and new hopes arise with the perspectives of disease-modifying drugs development as some NA-based therapies are now entering the clinical stage. Herein, we review NA-based drugs that were approved and are currently under investigation for the treatment of RD. We also discuss the recent structural improvements of NA-based therapeutics and delivery system, which overcome the main limitations in their market expansion and the current approaches that are developed to address the endosomal escape issue. We finally open the discussion on the ethical and societal issues that raise this new technology in terms of regulatory approval and sustainability of production. Nucleic acids-based drugs aim to fix the genetic problem at its source and emerge as a promising new class of drugs. Recent advances in this field enabled their approval for the treatment of orphan genetic diseases for which no cure was available. [ABSTRACT FROM AUTHOR]

Introduction: Randomized controlled trials have demonstrated tofacitinib efficacy for psoriatic arthritis (PsA); however, real-world effectiveness data are limited. This real-world analysis assessed baseline demographics/disease characteristics and tofacitinib effectiveness in patients with PsA in the CorEvitas PsA/Spondyloarthritis Registry. Methods: This study (NCT05195814) included patients with PsA initiating tofacitinib from December 2017–December 2021, as monotherapy or with oral small molecules (methotrexate/leflunomide/sulfasalazine/apremilast), pre-existing use, or initiated concurrently. Outcomes: mean change from baseline in disease activity/patient-reported outcomes, proportion of patients achieving low disease activity (LDA)/remission at 6 ± 3 months, and discontinuation rates. Results: Of 222 patients with PsA who initiated tofacitinib (60.8% as monotherapy), 123 patients had 6 ± 3 months of follow-up. At initiation, 59.7% were female, 92.3% were White, mean age was 56.3 years, PsA duration since diagnosis was 8.2 years, and 25.7% were biologic disease-modifying antirheumatic drug (bDMARD)-naïve. Improvements to 6 ± 3 months were observed with tofacitinib for Clinical Disease Activity Index for PsA (cDAPSA), DAPSA, PsA Disease Activity Score (PASDAS), Clinical Disease Activity Index, body surface area (BSA), tender/swollen joint count, patient fatigue, pain, Patient Global Skin Assessment, and Health Assessment Questionnaire-Disability Index. At 6 ± 3 months, 25.0%/7.8% of patients treated with tofacitinib achieved cDAPSA-defined LDA/remission, 18.2% achieved minimal disease activity, 30.8% had PASDAS ≤ 3.2, 42.9%/29.4% had resolved enthesitis/dactylitis, and 22.5% achieved BSA = 0%. Tofacitinib discontinuation occurred in 51.2% of patients (51.6% of monotherapy initiators) at/prior to 6 ± 3 months (27.6%/23.6%), 57.1% of whom switched to tumor necrosis factor/interleukin-17 inhibitors. Reasons for discontinuation were not reported in 85.3%/79.3% of patients who discontinued at/prior to 6 ± 3 months. Conclusions: This real-world US cohort analysis described patients with PsA newly initiating tofacitinib; most were bDMARD-experienced or receiving monotherapy treatment. In patients who remained on therapy (48.8%), tofacitinib was effective across multiple PsA domains at 6 ± 3 months. Limitations included small patient numbers at follow-up and potential selection bias. Trial Registration: ClinicalTrials.gov identifier, NCT05195814. [ABSTRACT FROM AUTHOR]

Scleritis, an inflammatory disease of the eye affecting scleral tissue, presents unique challenges in the older adult population. Unlike their younger counterparts, older individuals manifest a distinct spectrum of the disease with different underlying etiologies, co-morbidities, altered immune function, and an increased risk of systemic side effects from medication choices. Addressing these complexities necessitates a comprehensive and multidisciplinary approach. Treatment of choice will depend on any underlying cause but generally involves non-steroidal anti-inflammatory drugs, systemic or local corticosteroids, and potentially disease-modifying anti-rheumatic drugs. Utilization of these therapeutic agents in older adults warrants careful consideration because of their potential side-effect profiles. This article critically examines the specific concerns for the use of these drugs in older patients and reviews the existing literature on their use in this specific cohort. [ABSTRACT FROM AUTHOR]

The categorization of axial spondyloarthritis (axSpA) into radiographic (r-axSpA) and non-radiographic (nr-axSpA) subtypes is important in clinical trials but may be of less value in clinical practice. This exploratory cross-sectional, multi-center study evaluated patients with axSpA under routine care at German clinical rheumatology sites (RHADAR real-world database), with a focus on imaging data used for diagnostic classifications. Our analyses included 371 patients with axSpA. The mean (standard deviation [SD]) age was 50.9 (14.0) years, disease duration was 16.4 (13.5) years, and 39.6% were female. Based on the rheumatologist's final assessment, almost half of patients had definite r-axSpA (n = 179; 48.2%), 53 (14.3%) had suspected r-axSpA, 112 (30.2%) had non-radiographic-axSpA (nr-axSpA), and 27 (7.3%) had undefined axSpA. Patients assessed with definite or suspected r-axSpA were more likely to be treated with disease-modifying antirheumatic drugs (DMARDs) (62.0% and 64.2%, respectively) compared with nr-axSpA or undefined axSpA patients (37.5% and 48.1%, respectively). Almost all patients (348/371; 93.8%) had sacroiliac joint imaging data (radiographs or magnetic resonance imaging) documented in their charts, but only 216 (58.2%) had conventional radiographs required for formal diagnosis of r-axSpA by modified New York criteria. Follow-up radiographic imaging in nr-axSpA patients was uncommon (23/216 [25.0%]) but confirmed r-axSpA in 9/23 patients (39.1%). In conclusion, radiographs were available for slightly more than half of axSpA patients. Follow-up imaging was infrequent during rheumatology care in Germany but confirmed r-axSpA in ~ 40% of patients originally considered to have nr-axSpA. The distinction between r-axSpA and nr-axSpA may be ill-defined in routine clinical practice. [ABSTRACT FROM AUTHOR]

To evaluate the drug persistence in patients with rheumatic and musculoskeletal diseases (RMDs) during the current economic crisis in Lebanon and to estimate predictors of persistence. A nationwide multicentric cross-sectional study using an online questionnaire was conducted in Lebanon with patients with chronic inflammatory rheumatic diseases (CIRDs) and non-inflammatory RMDs controls between July and October 2022. Disease-modifying antirheumatic drugs (DMARDs) were categorized as conventional synthetic (cs), biological (b), subcutaneous (SC) or intravenous (IV), and targeted synthetic (ts). Persistence was defined as "number of tablets or injections taken during the past month versus prescribed". The percentage of patients who discontinued or changed treatment due to cost or non-availability was reported. Factors associated with persistence were identified using multivariable linear regression. The study included 317 patients with RMDs (286 CIRDs); mean age 49.5 years, 68% females, 58% reporting currently low economic level. Persistence at one month was low for tsDMARDs (36%) and bDMARDs (SC55%, IV63%), and acceptable for csDMARDs (88%). A persistence ≥80% was found in 23.3% of patients on tsDMARDs, 42.9% on SC bDMARDs, 45.0% on IV bDMARDs, and 74.7% on csDMARDs. During the past 6 months, 55.8% of CIRD patients discontinued or changed treatment due to non-availability (45.3%) or cost (21.2%). Persistence was positively associated with finding alternative sources such as buying abroad (36%), depending on friends or families abroad (20%), charities (10%), and negatively associated with unemployment and low financial status. Persistence was significantly compromised for essential antirheumatic drugs and was mostly driven by treatment unavailability and cost. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis (RA). Methods: Tumor necrosis factor (TNF)- α -induced fibroblast-like synoviocytes (FLS) was exposed to additional isorhamnetin (10, 20 and 40 µ mol/L). Overexpression vectors for matrix metalloproteinase-2 (MMP2) or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS function. RA-FLS viability, migration, and invasion were evaluated. Moreover, a collagen-induced arthritis (CIA) rat model was established. Rats were randomly divided to sham, CIA, low-, medium-, and high-dosage groups using a random number table (n=5 in each group) and administed with normal saline or additional isorhamnetin [2, 10, and 20 mg/(kg·day)] for 4 weeks, respectively. Arthritis index was calculated and synovial tissue inflammation was determined in CIA rats. The levels of MMP2, MMP9, TNF-α, interleukin-6 (IL-6), and IL-1 β, as well as the phosphorylation levels of SRC, extracellular regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding (CREB), were detected in RA-FLS and synovial tissue. Molecular docking was also used to analyze the binding of isorhamnetin to SRC. Results: In in vitro studies, isorhamnetin inhibited RA-FLS viability, migration and invasion (P<0.05). Isorhamnetin downregulated the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 β in RA-FLS (P<0.05). The overexpression of either MMP2 or MMP9 reversed isorhamnetin-inhibited RA-FLS migration and invasion, as well as the levels of TNF-α, IL-6, and IL-1 β (P<0.05). Furthermore, isorhamnetin bound to SRC and reduced the phosphorylation of SRC, ERK, and CREB (P<0.05). SRC overexpression reversed the inhibitory effect of isorhamnetin on RA-FLS viability, migration and invasion, as well as the negative regulation of MMP2 and MMP9 (P<0.05). In in vivo studies, isorhamnetin decreased arthritis index scores (P<0.05) and alleviated synovial inflammation. Isorhamnetin reduced the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 β, as well as the phosphorylation of SRC, ERK, and CREB in synovial tissue (P<0.05). Notably, the inhibitory effect of isorhamnetin was more pronounced at higher concentrations (P<0.05). Conclusion: Isorhamnetin exhibited anti-RA effects through modulating SRC/ERK/CREB and MMP2/MMP9 signaling pathways, suggesting that isorhamnetin may be a potential therapeutic agent for RA. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the presence of peripheral spondyloarthritis and investigate the clinical characteristics of patients with concurrent peripheral spondyloarthritis in those presenting with refractory plantar fasciitis and Achilles tendinopathy by conducting human leukocyte antigen B-27 (HLA-B27) testing. Methods: This retrospective study aimed to investigate patients who complained of persistent pain and significant limitations in daily activities due to their respective foot pain, despite receiving conservative treatment for over one year under the diagnosis of plantar fasciitis or insertional Achilles tendinopathy. The study included 63 patients who underwent HLA-B27 testing. The patients were classified into two groups based on the presence or absence of HLA-B27 positivity. The Mann–Whitney U test assessed significant relationships between continuous variables, and the chi-square test was used to compare categorical variables. Results: Among the 63 included patients, HLA-B27 positivity was confirmed in 11 patients (17.5%), which was significantly associated with a lower average age (22.8 years versus 31.7 years, P = 0.01) and a substantially lower proportion of females compared to HLA-B27-negative patients (9.1% vs. 25.0%, P = 0.001). Ten of the 11 patients initiated treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) combined with oral steroids as the first-line medication after being diagnosed as HLA-B27 positive. Six patients experienced pain relief with the first-line medication (60%). Four patients who did not achieve pain control with the first-line medication received tumour necrosis factor-alpha inhibitors as the second-line medication. Two patients experienced pain relief, while two experienced reduced but persistent pain. Conclusions: Among the patients with "refractory" plantar fasciitis and insertional Achilles tendinopathy, 17.5% were diagnosed with peripheral spondyloarthritis. Patients diagnosed with peripheral spondyloarthritis had a higher proportion of men and relatively younger mean age compared to those without the diagnosis. Approximately 70% of these patients achieved symptom improvement in foot and ankle joints by taking conventional synthetic DMARDs, TNF-α inhibitors, or both appropriate for spondyloarthritis. [ABSTRACT FROM AUTHOR]

Approximately 1% of all patients with Sjögren's syndrome (SS) are children. Unlike the adult form, in which sicca syndrome is the main presentation, in children, the most common clinical finding is recurrent enlargement of the salivary glands. In pediatric SS, extraglandular manifestations represent a significant feature and, among these, kidney manifestations are relevant. Kidney involvement is observed in 5–20.5% of children with SS, most frequently tubulointerstitial nephritis. This injury can lead to serious phenotypes, including distal kidney tubular acidosis with the development of severe hypokalemia, which can lead to ECG abnormalities, weakness, and hypokalemic periodic paralysis. Kidney implications in pediatric SS also include nephrolithiasis, nephrocalcinosis, and various types of glomerular damage, which often require immunosuppressive therapies. Laboratory findings are usually comparable to adults, including hyperglobulinemia and high rates of antinuclear antibodies (ANA, 63.6–96.2%), and anti-Ro/SSA (36.4–84.6%). The current classification criteria for SS are inaccurate for the pediatric population, and more specific criteria are needed to improve the diagnostic rate. Due to the rarity of the disease, strong recommendations for treatment are lacking, and several therapeutic strategies have been reported, mostly based on glucocorticoids and disease-modifying antirheumatic drugs, with different outcomes. The aim of this paper is to provide an overview of the kidney implications of pediatric SS based on the latest evidence of the medical literature. [ABSTRACT FROM AUTHOR]

Adult-onset Still's disease (AOSD) is a multisystemic complex disorder clinically characterised by episodes of spiking fever, evanescent rash, polyarthritis or diffuse arthralgias; multiorgan involvement may develop according to the hyper-inflammatory extent. The pathogenesis of AOSD is not completely recognised. The central role of macrophage activation, which results in T helper 1 (Th1) cell cytokine activation, is well established. Pro-inflammatory cytokines such as interleukin (IL)-1, IL-6 and IL-18 play a fundamental role in disease onset and progression. The disease may develop in both children and adults with overlapping clinical features, and although several subsets depending on the clinical manifestations and the cytokines expressed have been identified, the dichotomy between systemic juvenile idiopathic arthritis (sJIA) and AOSD nowadays has been overcome, and the pathology is considered a disease continuum between ages. Various therapeutic approaches have been evaluated thus far, and different compounds are under assessment for AOSD treatment. Historically, glucocorticoids have been employed for treating systemic manifestations of Still's disease, while conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) demonstrated efficacy in controlling the articular manifestations. Currently, biological (b) DMARDs are widely employed; IL-1 inhibitors such as anakinra and canakinumab have proven to have high efficacy and an excellent safety profile and the anti-IL-6 tocilizumab is approved for sJIA, with several trials and longitudinal studies confirming its efficacy and safety. Moreover, in the light of the 'window of opportunity', new evidence showed that the earlier these treatments are initiated, the sooner clinical inactivity can be achieved. Other treatment options are being considered since several molecules involved in the disease pathophysiology can be targeted through various mechanisms. This review will provide a broad overview of AOSD pathophysiology, insights into specific organ manifestations and the currently available treatments with the identification of potential therapeutic targets involved in AOSD pathogenesis will be outlined. [ABSTRACT FROM AUTHOR]

Background: Systemic glucocorticoids are commonly used in practice in the treatment of psoriatic arthritis. However, authorities advise against prescribing it, primarily because of the risk of psoriasis flare-ups. The authors aimed to assess the glucocorticoid use in psoriatic arthritis (PsA), factors associated with the use of glucocorticoids and to uncover whether gender has an impact on glucocorticoid use and treatment responses. Disease-modifying antirheumatic drug (DMARD)-naive PsA patients were included in this cross-sectional study. Baseline clinical and demographic characteristics were recorded. After starting DMARD treatment, patients were followed for 2 years. The number of patients who started glucocorticoids, the clinical demographics of these patients, the duration of glucocorticoid administration, and the dose for administration were recorded. Patient outcomes and gender differences were analyzed. Disease activity was measured using the Disease Activity Scale 28 (DAS28-CRP) and the Disease Activity Index for Psoriatic Arthritis (DAPSA). Results: Fifty-five of the 141 patients (39%) received glucocorticoids at the 2-year follow-up. There was no difference between the sexes who are in remission-low disease activity (LDA) on cDMARD monotherapy (p = 0.300). Glucocorticoid usage (p = 0.660), dose (p = 0.054), and duration (p = 0.159) did not differ between male and female patients. Higher glucocorticoid doses were associated with dactylitis, higher CRP levels, higher DAS-28 and DAPSA scores, and longer (> 3 months) glucocorticoid administration. Glucocorticoid duration was longer in patients with higher TJS, SJS, serum CRP, higher DAS-28 and DAPSA scores, and higher glucocorticoid doses. Sustained remission-LDA was achieved in 16 of 55 patients after cessation of glucocorticoids and no sex difference was observed. Conclusion: Systemic glucocorticoids are commonly prescribed in PsA, and when added to treatment even for short periods and in low doses, they help achieve significant disease control. Except for axial involvement, there is no difference in treatment responses between male and female patients, making it unnecessary to make a gender distinction in the treatment algorithm. Given these findings, prospective studies are needed to evaluate glucocorticoids as a bridging treatment in PsA, such as rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Introduction: Clinical guidelines offer little guidance for treatment selection following inadequate response to conventional synthetic disease-modifying antirheumatic drug (csDMARD) in rheumatoid arthritis (RA). A molecular signature response classifier (MSRC) was validated to predict tumor necrosis factor inhibitor (TNFi) inadequate response. The decision impact of MSRC results on biologic and targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) selection was evaluated. Methods: This is an analysis of AIMS, a longitudinal, prospective database of patients with RA tested using the MSRC. This study assessed selection of b/tsDMARDs class after MSRC testing by surveying physicians, the rate of b/tsDMARD prescriptions aligning with MSRC results, and the percentage of physicians utilizing MSRC results for decision-making. Results: Of 1018 participants, 70.7% (720/1018) had treatment selected after receiving MSRC results. In this MSRC-informed cohort, 75.6% (544/720) of patients received a b/tsDMARD aligned with MSRC results, and 84.6% (609/720) of providers reported using MSRC results to guide treatment selection. The most prevalent reason reported (8.2%, 59/720) for not aligning treatment selection with MSRC results from the total cohort was health insurance coverage issues. Conclusion: This study showed that rheumatologists reported using the MSRC test to guide b/tsDMARD selection for patients with RA. In most cases, MSRC test results appeared to influence clinical decision-making according to physician self-report. Wider adoption of precision medicine tools like the MSRC could support rheumatologists and patients in working together to achieve optimal outcomes for RA. [ABSTRACT FROM AUTHOR]

Axial spondyloarthritis (axSpA) is a chronic, inflammatory rheumatic disease that primarily affects the axial skeleton, often inflicting severe pain, diminished mobility, and a compromised quality of life. The advent of Assessment of SpondyloArthritis international Society (ASAS) classification criteria for spondyloarthritis (SpA) have enabled the classification of patients with axSpA in the non-radiographic stage but poorly perform if mistakenly used for diagnostic purposes. Despite notable progress in early diagnosis facilitated by referral strategies and extensive magnetic resonance imaging (MRI) utilization, diagnostic delays persist as a concerning issue. This underscores the urgency to narrow the diagnostic gap and highlights the critical role of early diagnosis in mitigating the long-term structural damage associated with this condition. Research into the impact of non-steroidal anti-inflammatory drugs (NSAIDs) and biologic disease-modifying antirheumatic drugs (bDMARDs) on inflammatory symptoms and radiographic progression has been extensive. A compelling body of evidence suggests that early intervention leads to superior disease outcomes. However, most of these studies have centered on patients with established diseases rather than those in the early stages. Consequently, findings from studies on early pharmacological intervention remain inconclusive, and the potential for modifying the disease trajectory is still debatable. Without precise data from clinical trials, insights from basic science regarding the pathogenic mechanisms might point toward potential targets that warrant early intervention in the disease process. This review underscores the urgency of early diagnosis and intervention in axSpA, highlighting ongoing research gaps and the need for further exploration to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To assess cigarette smoking's effects on efficacy of the preferential Janus kinase (JAK) 1 inhibitor filgotinib and drug persistence in patients with rheumatoid arthritis (RA). Methods: Efficacy in non-smokers, former smokers, and current smokers from phase 3 filgotinib trials was analyzed, including patients with inadequate response (IR) to methotrexate (MTX) or biologic disease-modifying antirheumatic drugs (bDMARDs) or who were MTX-naïve. Proportions achieving Disease Activity Score in 28 joints with C-reactive protein (DAS28[CRP]) ≤ 3.2 were compared using logistic regression. Retrospective claims-based switching data were reviewed. Results: Week 12 (W12) DAS28(CRP) ≤ 3.2 was achieved by 50, 61, and 62% of MTX-IR non-smokers, former smokers, and current smokers taking filgotinib 200 mg (FIL200) + MTX vs. 23, 16, and 32% taking placebo + MTX (p < 0.001, < 0.001, and 0.001) and 50, 34, and 33% taking adalimumab + MTX (p = 0.97, 0.013, and 0.006 vs. FIL200 + MTX). W12 DAS28(CRP) ≤ 3.2 was achieved by 46, 48, and 32% of bDMARD-IR non-smokers, former smokers, and current smokers taking FIL200 + conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) vs. 16, 23, and 5% taking placebo + csDMARD (p < 0.001, 0.077, and 0.051); 57, 58, and 59% of respective MTX-naïve smoking groups achieved W12 DAS28(CRP) ≤ 3.2 with FIL200 + MTX vs. 28, 37, and 18% with MTX (p < 0.001, 0.026, and < 0.001). Claims data showed former/current smokers were likelier than non-smokers to switch from adalimumab to other biologics or JAK inhibitors. Conclusions: Greater proportions of MTX-IR current/former smokers responded to FIL200 + MTX vs. adalimumab + MTX. In non-smoking MTX-IR, bDMARD-IR, and MTX-naïve patients with RA, FIL200 + MTX demonstrated increased response vs. controls. Current/former smokers were likelier to discontinue adalimumab vs. non-smokers in real-world clinical settings. Trial Registration: NCT02889796, NCT02873936, NCT02886728. [ABSTRACT FROM AUTHOR]

Objectives: To compare the current disease activity and remission rates, and their regional variation in patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA) in Finland. Methods: Data of patients' most recent visit in 1/2020–9/2021 were extracted from the Finnish Rheumatology Quality Register. Measures for disease activity and remission included joint counts, DAS28, cDAPSA, CDAI, the Boolean definition, and physician assessment. Regression analyses were applied, adjusted for age and sex. Results: Data of 3598 patients with PsA (51% female, mean age 54 years) and 13,913 patients with RA (72% female, 74% ACPA-positive, mean age 62 years) were included. The median (IQR) DAS28 was 1.9 (1.4, 2.6) in PsA and 2.0 (1.6, 2.7) in RA (p = 0.94); for cDAPSA, the median (IQR) values were 7.7 (3.1, 14) in PsA and 7.7 (3.3, 14) in RA (p < 0.001). In all regions in both diseases, the median DAS28 was ≤ 2.6 and the median cDAPSA < 13. Remission rates included DAS28 < 2.6 in 73% in PsA and 69% in RA (p = 0.17) and Boolean remission in 17% in PsA and 15% in RA (p < 0.001). By other definitions of remission, the rates ranged between 30% and 46%. Methotrexate was currently used by 49% in PsA and 57% in RA (p < 0.001). Self-administered bDMARDs were currently used by 37% in PsA and 21% in RA (p < 0.001). Conclusion: The overall disease activity was low and similar in patients with PsA and RA across the country. Remission rates varied between 15 and 73%, depending on the definition but were similar in PsA and RA. Key Points • The disease activity and clinical picture was similar between patients with PsA and RA, in a cross-sectional setting in 1.2020–9.2021. • A significant majority of patients with PsA had low disease activity or were in remission according to cDAPSA. Majority of patients with RA were in remission according to DAS28. • Patients with PsA and RA used methotrexate similarly. The utilization of bDMARDs was more prevalent in patients with PsA. [ABSTRACT FROM AUTHOR]

Pulmonary accelerated rheumatoid nodules (ARN) represent a rare occurrence within the context of rheumatoid arthritis (RA), with conventional treatment typically involving corticosteroids. In this report, we present a unique case of pulmonary ARN managed with baricitinib, a Janus kinase inhibitor. The patient, a 46-year-old woman diagnosed with RA, initially displayed no evident pulmonary nodules upon pulmonary imaging. Her treatment regimen encompassed corticosteroids, methotrexate, and leflunomide. Nevertheless, a chest computed tomography (CT) scan conducted after a year unveiled the presence of multiple bilateral pulmonary nodules. A thoracoscopic biopsy of these nodules confirmed the presence of rheumatoid nodules. Treatment with baricitinib, a Janus kinase inhibitor or synthetic disease-modifying antirheumatic drug (DMARD), effectively reduced the size of the nodules. Our review of 45 articles on ARN published since 1986 found that nine of them reported 13 cases of pulmonary ARN. These nodules may be caused by certain synthetic and biological DMARDs and often present with respiratory symptoms. CT scans typically reveal multiple solid nodules or ground-glass opacities, some of which may have cavities. Treatment customarily involves discontinuing the suspected drugs and administering corticosteroids. This case suggests that Janus kinase inhibitors may be an effective treatment option for ARN. [ABSTRACT FROM AUTHOR]

Non-medicinal therapies with water, salts, exercise, massage, supportive devices, and electricity have been used for centuries and continue to be of benefit for some people with musculoskeletal disorders. Historical texts refer to the two electuaries mithridatium and theriaca as early therapeutic attempts of man to provide relief of musculoskeletal symptoms and attempt disease cures. For over 200 years, morphine-derived products have been used for musculoskeletal pain. The development of acetyl salicylic acid was a major breakthrough in joint pain management. This was followed by the introduction of nonsteroidal anti-inflammatory agents, paracetamol, and the use of corticosteroids. The gold-based compounds were the initial disease-modifying drugs and have been followed by the highly successful biologics agents. The basic objectives of musculoskeletal pain management include: reduction or elimination of joint pain; improvement or restoration of joint function and mobility; improvement of muscle strength to protect cartilage, ligaments, and joint capsule; prevention and reduction of damage to joint cartilage and supporting structures. [ABSTRACT FROM AUTHOR]

The popularity of esthetic medicine is growing every year, also among patients with autoimmune inflammatory rheumatic diseases (AIRD). The objective of this study was to evaluate the safety of esthetic medicine (AM) procedures in patients with AIRD. A semi-structured, anonymous questionnaire regarding rheumatic and concomitant diseases and AM procedures was distributed among adult patients hospitalized in the rheumatology department or attending outpatient clinic in the National Institute of Geriatrics, Rheumatology, and Rehabilitation, Warsaw. The main outcome was the occurrence of an adverse event. A number of 512 patients took part in the survey and 15 were excluded (AM procedure preceded the diagnosis of AIRD). The study group consisted of 497 patients, of whom 47 had undergone AM procedures. The procedures performed included: tattooing (22 patients), piercing (16 patients), hyaluronic acid (7 patients), botulinum toxin (5 patients) injections, laser procedures (6 patients), plastic surgery (4 patients), mesotherapy (3 patients) and others. The vast majority of patients had these performed during remission or low disease activity. 70.2% of patients received treatment with disease-modifying antirheumatic drugs (DMARDs) during the AM procedure, with TNF-alfa inhibitors being the most common (63.6%). Adverse events occurred in 15% of patients. All were mild and transient site reactions. Most patients would like to repeat the AM procedure in the future. The use of esthetic medicine procedures in patients with AIRD, including those treated with biologic DMARDs, was associated with a risk of mild site reactions. Most of the patients expressed satisfaction with the results of the AM procedure. [ABSTRACT FROM AUTHOR]

The objectives of our study were to assess retention rate, safety, and predictive factors for retention of subcutaneous (SC) TNF inhibitors (TNFi) (adalimumab (ADA), etanercept (ETN), golimumab (GOL), and certolizumab pegol (CZP)) in axial spondyloarthritis (axSpA) depending on the line of treatment in real-life conditions. A multicentre retrospective observational study was conducted including 552 patients fulfilling the ASAS criteria for axSpA followed in the RIC-France register who began SC-TNFi between 01/01/13 and 08/31/2018 for a total of 824 prescriptions. Taking all lines of treatment into account, GOL had a significantly higher retention rate compared with ADA, ETN, and CZP with a mean retention length of 59 months. As first-line bDMARDs, GOL had a significantly higher retention rate compared with ADA and ETN. ETN had the best retention rate when prescribed as at least 3rd bDMARD. Taking all lines of treatment into account, female sex, peripheral disease, BASDAI at initiation, and line of treatment were predictive factors for treatment cessation. Primary inefficiency was the most frequent reason for treatment cessation. In conclusion, GOL showed the highest retention rate in axSpA. Male sex, absence of peripheral disease, and early line of prescription were associated with better SC-TNFi retention in axSpA. [ABSTRACT FROM AUTHOR]

Background: Diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (1H-MRS) can detect the microstructural changes in normal-appearing conventional MRI. So, they may differentiate between multiple sclerosis (MS) cases and cerebral small vessel disease (CSVD). This work aimed to investigate if MRS and DTI are helpful in differentiating between MS and CSVD cases. Methods: The study was conducted on 90 subjects divided into three groups: 30 relapsing–remitting MS patients, 30 patients with MRI showing CSVD, and 30 healthy controls. Diffusion tensor imaging measuring thalamic FA, ADC values, and 1H-MRS were conducted on patients and controls. Results: Thalamic FA values were significantly higher in the RRMS group than in the control and CSVD groups (P < 0.001, for each) but significantly lower in the CSVD group than the control group (P < 0.001). Moreover, thalamic ADC values were significantly higher in the CSVD group than in the control and MS groups (P < 0.001, for each). Also, thalamic NAA values were significantly lower in RRMS and CSVD groups than in controls (P < 0.001 for each). Still, they were significantly lower in the RRMS group than the CSVD group only on the left side (P = 0.004). The thalamic NAA/Cr values were significantly lower in RRMS (P < 0.001 for both sides) and CVSD than in controls (P = 0.044 and 0.036, for RT and LT sides, respectively). Conclusions: Thalamic DTI and 1H-MRS can help detect the microstructural changes in normal-appearing thalami in RRMS and CSVD patients. Moreover, they can help differentiate MS from CSVD patients. [ABSTRACT FROM AUTHOR]

Purpose: SYVN1 is an endoplasmic reticulum (ER)-resident E3 ubiquitin ligase that has an essential function along with SEL1L in rheumatoid arthritis (RA) pathogenesis. This study aimed to investigate the changes in the expression of peripheral blood ncRNAs and SYVN1-SEL1L affected by DMARDs treatment. Methods: Twenty-five newly diagnosed RA patients were randomly assigned to receive conventional DMARDs (csDMARDs) and methylprednisolone for six months. The peripheral blood gene expression of SYVN1 and SEL1L and possible regulatory axes, NEAT1, miR-125a-5p, and miR-19b-3p, were evaluated before and after qRT-PCR. We also compared differences between the patients and healthy controls (HCs), and statistical analyses were performed to determine the correlation between ncRNAs with SYVN1-SEL1L and the clinical parameters of RA. Results: Expression of NEAT1 (P = 0.0001), miR-19b-3p (P = 0.007), miR-125a-5p (P = 0.005), and SYVN1 (P = 0.036) was significantly increased in newly diagnosed patients compared to HCs; also, miR-125a-5p, miR-19b-3p, and SYVN1 were significantly overexpressed after treatment (P = 0.001, P = 0.001, and P = 0.005, respectively). NEAT1 was positively correlated with SYVN1, and miR-125a-5p had a negative correlation with anti-cyclic citrullinated peptides. The ROC curve analysis showed the potential role of selected ncRNAs in RA pathogenesis. Conclusion: The results indicate the ineffectiveness of the csDMARDs in reducing SYVN1 expression. The difference in expression of ncRNAs might be useful markers for monitoring disease activity and determining therapeutic responses in RA patients. Key Points • The expression of NEAT1 is significantly upregulated in RA patients compared to HC subjects. • miR-19b-3p, miR-125a-5p, and SYVN1 are significantly upregulated in RA patients compared to HC subjects. • The expression of miR-19b-3p and miR-125a-5p is significantly increased in RA patients after treatment with DMARDs and methylprednisolone. • NEAT1 is positively correlated with SYVN1. [ABSTRACT FROM AUTHOR]

Introduction: Psoriatic arthritis (PsA) is a chronic, progressive inflammatory joint disease that is associated with higher prevalence of depression. There is limited literature about the impact of depression, particularly regarding the response to therapy. Methods: A retrospective cohort study with PsA patients that started their first biologic disease-modifying antirheumatic drugs (bDMARD) was conducted. In the majority of cases, a cutoff score of ≥ 8 in Hospital Anxiety and Depression Scale (HADS) was used to define cases of depression. In cases where patients did not complete the questionnaire, a previous diagnosis made by a psychiatrist was used to establish the presence of depression. Response to therapy 12 months after the start of bDMARD was evaluated and the switch rate to another bDMARD due to inefficacy was assessed at month 12. Results: A total of 129 patients (66 females, 51.2%; mean age of 47.7 ± 11.0 years and mean disease duration of 10.0 ± 7.7 years) with PsA were included. Thirty-two (24.8%) patients had depression. Patients with depression and peripheral involvement had a significantly lower ACR20/50/70 responses (p = 0.001, p = 0.002, and p = 0.001 respectively) after 12 months of therapy and a significantly worse EULAR response (p = 0.002). Furthermore, patients with depression and axial involvement had a significantly worse response based on ASDAS response criteria (p = 0.031). Switch due to ineffectiveness in the first 12 months was significantly higher in patients with depression (p = 0.002). Conclusion: Depression in PsA is a frequent yet often understudied comorbidity. The causal relationship between depression and PsA is difficult to decrypt and further research is needed. Recognition of depressive symptoms is crucial and a multidisciplinary approach should be provided to individuals with this comorbidity. Key Points • Depression in PsA is a frequent yet often understudied comorbidity. In our study, the prevalence of depression was 24.8%. • Depression in PsA seems to be associated to lower response to therapy and higher discontinuation rates of bDMARD. • Recognition of depressive symptoms is crucial and a multidisciplinary approach should be provided to individuals with this comorbidity. [ABSTRACT FROM AUTHOR]