Disease-modifying Antirheumatic Drug Therapy Research Articles

Real-world effectiveness of a single conventional disease-modifying anti-rheumatic drug (cDMARD) plus an anti-TNF agent versus multiple cDMARDs in rheumatoid arthritis: a prospective observational study.

The objective of this prospective, observational multicenter study (NCT03264703) was to compare the effectiveness of single conventional disease-modifying anti-rheumatic drug (cDMARD) plus anti-tumor necrosis factor (TNF) therapy versus multiple cDMARD treatments in patients with moderate-to-severe rheumatoid arthritis (RA) following cDMARD failure in the real-world setting in South Korea. At the treating physicians' discretion, patients received single cDMARD plus anti-TNF therapy or multiple cDMARDs. Changes from baseline in disease activity score 28-joint count with erythrocyte sedimentation rate (DAS28-ESR), corticosteroid use, and Korean Health Assessment Questionnaire (KHAQ-20) scores were evaluated at 3, 6, and 12 months. Of 207 enrollees, the final analysis included 45 of 73 cDMARD plus anti-TNF and 91 of 134 multiple-cDMARD recipients. There were no significant between-group differences (BGDs) in ANCOVA-adjusted changes from baseline in DAS28-ESR at 3, 6 (primary endpoint), and 12 months (BGDs -0.18, -0.38, and -0.03, respectively). More cDMARD plus anti-TNF than multiple-cDMARD recipients achieved a >50% reduction from baseline in corticosteroid dosage at 12 months (35.7% vs 14.6%; p=0.007). Changes from baseline in KHAQ-20 scores at 3, 6, and 12 months were significantly better with cDMARD plus anti-TNF therapy than with multiple cDMARDs (BGD -0.18, -0.19, and -0.19 points, respectively; all p≤0.024). In the real-world setting, relative to multiple cDMARDs, single cDMARD plus anti-TNF therapy significantly improved quality-of-life scores and reduced corticosteroid use, with no significant BGD in disease activity, in RA patients in whom previous cDMARD therapy had failed.

Tocilizumab Reduces Depression Risk in Rheumatoid Arthritis Patients: A Systematic Review and Meta-Analysis.

Depression is a possible cause of the increased mental health risks associated with rheumatoid arthritis (RA), including depression-related complications. Biological disease-modifying antirheumatic drug (bDMARDs) therapies have emerged as innovative anti-inflammatory drugs with positive effects on mental well-being. Tocilizumab is a bDMARDs commonly used to treat RA and its influence on depression needs to be studied. It targets interleukin-6 (IL-6) receptors, reducing inflammation, which may also alleviate depressive symptoms due to the role of inflammation in the pathophysiology of depression. Thus, its influence on depression needs to be studied. To assess the strength of the association between exposure to tocilizumab and the rate of development of depression in patients with RA and to evaluate tocilizumab as an exposure and depression as an outcome in these patients, a search was conducted in the MEDLINE, PreMEDLINE, Cochrane, and Scopus databases from January 1980 to April 2024. Inclusion criteria were studies that diagnosed RA according to the latest American College of Rheumatology/European League Against Rheumatism guidelines or a rheumatologist and provided information on tocilizumab exposure and diagnosed depression as an outcome. The present meta-analysis was conducted following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. These studies were assessed for eligibility by the author and an independent assessor. To summarize the findings, the meta-analysis combined the relative risk estimates from each study with raw data counts. Twelve studies in the meta-analysis fulfilled the inclusion criteria. Tocilizumab monotherapy exhibited a promising beneficial effect on the risk of depression, indicated by the decreased risk in RA patients (Relative risk 0.68, 95% CI 0.20, 2.31). Patients with RA on tocilizumab treatment had a lower risk of developing depression compared to those unexposed to tocilizumab treatment. Therefore, future longitudinal studies are needed to confirm the beneficial effect of tocilizumab on depression in the RA population.

Increased NAFLD risk in newly diagnosed patients with RA during the first 4 years of follow-up: a nationwide, population-based cohort study

BackgroundAlthough the non-alcoholic fatty liver disease (NAFLD) is prevalent in the general population, NAFLD risk in newly diagnosed rheumatoid arthritis (RA) has rarely been explored. In this population-based cohort, we...

What benefit–risk trade-offs are acceptable to rheumatoid arthritis patients during treatment selection? Evidence from a multicountry choice experiment

ObjectiveUnderstanding preferences of patients with rheumatoid arthritis (RA) can facilitate tailored patient-centric care. This study elicited trade-offs that patients with RA were willing to make during treatment selection.MethodsPatients with RA...

Effect of Combined Neuromuscular Electrical Stimulation and Disease-Modifying Antirheumatic Drug Therapy Versus Disease-Modifying Antirheumatic Drug Therapy Alone on Enhancing Gait and Reducing Fall Risks in Patients with Rheumatoid Arthritis and Peripheral Neuropathy

Background: Rheumatoid Arthritis (RA) with Peripheral Neuropathy (PN) significantly impacts gait and balance, posing challenges in patient management. While Disease-Modifying Antirheumatic Drug (DMARD) therapy is effective for RA, it may not fully address these functional impairments. Neuromuscular Electrical Stimulation (NMES) has been proposed as a complementary therapy to improve these outcomes. Objective: This study aimed to assess the effectiveness of combining NMES with DMARD therapy versus DMARD therapy alone in enhancing gait and reducing fall risks among RA patients with PN. Methods: In a randomized controlled trial, 66 RA patients with PN were allocated to either Group A (NMES + DMARD, n=33) or Group B (DMARD only, n=33). Baseline demographics (age, gender, BMI, RA duration) and clinical outcomes (stride length, gait speed, cadence, etc.) were measured. Assessments were conducted at the study’s onset and after an 8-week intervention period, with data analyzed using independent t-tests. Results: Baseline data revealed no significant differences between the groups. Post-intervention, Group A exhibited marked improvements: stride length reduced to 58.26 cm (± 5.0) compared to Group B’s 69.1 cm (± 5.2, p=0.036), gait speed decreased to 0.77 m/s (± 5.1) against Group B’s 0.94 m/s (± 5.2, p=0.020), and cadence lowered to 81.43 steps/min (± 4.5) versus Group B’s 97.06 steps/min (± 4.7, p=0.029). Significant improvements were also seen in step width, double support time, and balance scales in Group A. However, biochemical markers did not show significant differences post-intervention. Conclusion: The integration of NMES with DMARD therapy resulted in significant improvements in gait and balance parameters compared to DMARD therapy alone in RA patients with PN. These findings suggest that NMES could be an effective adjunct to DMARDs in managing functional impairments in this population.

Effectiveness of a fourth dose of COVID-19 mRNA vaccine in patients with systemic autoimmune rheumatic diseases using disease-modifying antirheumatic drugs: an emulated target trial

Patients with systemic autoimmune rheumatic diseases using disease-modifying antirheumatic drugs (DMARDs) might have blunted responses to COVID-19 vaccines. The initial mRNA vaccine series is defined as three doses for this population and a fourth booster dose is recommended. The effectiveness of the fourth dose in patients with systemic autoimmune rheumatic diseases using DMARDs is not well established. We aimed to assess the effectiveness of receiving versus not receiving a fourth dose of COVID-19 mRNA vaccine using a target trial framework, in a cohort of patients with systemic autoimmune rheumatic diseases receiving DMARD therapy. We conducted an emulated target trial using observational data from the Mass General Brigham health-care system to compare receiving versus not receiving a fourth mRNA vaccine dose. Analysed patients had systemic autoimmune rheumatic diseases, were prescribed DMARDs, and were eligible for a fourth dose of BNT162b2 or mRNA-1273 vaccines between Jan 16 and June 11, 2022. To account for temporal changes, the study period was divided into 1-week intervals. Fourth-dose-exposed patients were included in a 1-week interval if they received a fourth mRNA dose in that interval; fourth-dose-unexposed patients were eligible for but had not received the fourth dose of the vaccine. The primary outcome was a SARS-CoV-2 infection; the secondary outcome was severe SARS-CoV-2 infection (ie, admission to hospital or death within -3 to +14 days of a positive test). We assessed the effectiveness of the fourth dose using time-stratified, overlap propensity score-weighted Cox regression models. We included 4305 patients, 3126 of whom received a fourth dose of vaccine and 1179 who had not. The median follow-up time was 135 days (IQR 112-154) among patients who had received a fourth dose and 65 days (30-156) among patients who had not received a fourth dose. After overlap weighting in both groups, 1863 (72·7%) of 2563 participants were women, 700 (27·3%) were men, and 2242 (87·5%) were White. Rheumatoid arthritis was present in 1392 (54·3%) of 2563 participants; the most frequent treatments were conventional synthetic DMARDs (1489 [58·1%]) or biological DMARDs (1007 [39·3%]). SARS-CoV-2 infection risk was lower among patients receiving versus not receiving a fourth dose of vaccine (HR 0·59 [95% CI 0·47-0·74]). A fourth dose reduced the risk of admission to hospital or death within -3 to +14 days of SARS-CoV-2 infection (0·35 [0·14-0·85]). In this emulated target trial, a fourth dose of COVID-19 mRNA vaccine reduced the risk of SARS-CoV-2 infection and severe COVID-19 among patients with systemic autoimmune rheumatic diseases using DMARDs during the Omicron era. Patients with systemic autoimmune rheumatic diseases should be encouraged to remain up-to-date with COVID-19 vaccinations. The National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Abstract 6 — Are Disease-Modifying Antirheumatic Drugs: for Rheumatoid Arthritis Associated with a Lower Risk of Dementia? A Systematic Review with Meta-Analysis

Background Dysregulation of several inflammatory cytokines including tumor necrosis factor (TNF) in dementia patients has also been identified as a key factor in the pathogenesis of rheumatoid arthritis (RA). We aimed to investigate the association of disease-modifying anti-rheumatic drugs (DMARDs) therapy for RA with risk of incident dementia. Methods Electronic database searches of PubMed, EMBASE and Cochrane Library were performed. Observational studies that assessed the association of dementia with DMARDs in RA were included. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were used as summary statistic. The certainty of evidence using the GRADE system. Results Fourteen studies involving 940,442 patients with RA were included. Pooled RR for developing dementia was 0.76 (95%CI 0.72-0.80) in patients taking biological DMARDs overall versus those taking conventional synthetic DMARDs, with 24% for TNF inhibitors (RR 0.76, 95%CI 0.71-0.82), 24% for non-TNF biologics (RR 0.76, 95%CI 0.70-0.83), separately. There was a significant subgroup effect among different types of TNF inhibitors (RR 0.58, 0.65, 0.80 for etanercept, adalimumab, infliximab, respectively; P-value between groups=0.002). However, compared with nonusers of DMARDs or investigative treatment, no significant effect on dementia incidence was observed in those receiving conventional synthetic DMARDs overall (RR 0.84, 95%CI 0.59-1.20), methotrexate (RR 0.78, 95%CI 0.54-1.12), hydroxychloroquine (RR 0.95, 95%CI 0.63-1.44), except for sulfasalazine (RR 1.27, 95%CI 1.06-1.50). Conclusions Biological DMARDs for RA are associated with decreased dementia risk, while protective effect is not observed in conventional synthetic DMARDs. Controlled clinical trials on TNF inhibitors is necessary to test their neuroprotective potentials.

Elderly-Onset Rheumatoid Arthritis: Characteristics and Treatment Options.

Elderly-onset rheumatoid arthritis (EORA) is a distinct clinical entity defined as the onset of rheumatoid arthritis (RA) in individuals aged over 60 years. EORA presents unique clinical features, including a more equitable distribution of sexes, a potential predilection for male involvement, a higher incidence of acute onset characterized by constitutional symptoms, a propensity for systemic manifestations, elevated sedimentation rates at disease onset, a reduced occurrence of rheumatoid factor positivity, increased titers of anti-citrullinated protein antibodies, a preference for involvement of large joints, elevated disease activity, the presence of bone erosions, and heightened patient disability. RA is recognized to consist of three partially overlapping subsets. One subset mirrors the classical RA clinical presentation, while the remaining subsets exhibit either a polymyalgia rheumatica-like phenotype or present with remitting seronegative symmetrical synovitis accompanied by pitting edema syndrome. In the initial stages of EORA management, non-steroidal anti-inflammatory drugs (NSAIDs) are not typically the first-line treatment choice, because seniors are much more prone to develop side effects due to NSAIDs, and the use of NSAIDs is in reality contraindicated to the majority of seniors due to comorbidities. Disease-modifying antirheumatic drugs (DMARDs), frequently methotrexate, are introduced immediately after the diagnosis is made. In cases where elderly patients demonstrate resistance to conventional DMARD therapy, the introduction of biological or targeted synthetic DMARDs becomes a viable treatment option. EORA presents a unique clinical profile, necessitating tailored treatment strategies. Our study emphasizes the challenges of NSAID use in seniors, highlighting the imperative shift toward DMARDs such as methotrexate. Future research should explore personalized DMARD approaches based on disease activity, comorbidities, and safety considerations, aiming to optimize treatment outcomes and minimize glucocorticoid reliance, thereby enhancing the quality of care for EORA patients.

Shared and Distinct Gut Microbiota in Spondyloarthritis, Acute Anterior Uveitis, and Crohn's Disease.

Spondyloarthritis (SpA) is a group of immune-mediated diseases highly concomitant with nonmusculoskeletal inflammatory disorders, such as acute anterior uveitis (AAU) and Crohn's disease (CD). The gut microbiome represents a promising avenue to elucidate shared and distinct underlying pathophysiology. We performed 16S ribosomal RNA sequencing on stool samples of 277 patients (72 CD, 103 AAU, and 102 SpA) included in the German Spondyloarthritis Inception Cohort and 62 back pain controls without any inflammatory disorder. Discriminatory statistical methods were used to disentangle microbial disease signals from one another and a wide range of potential confounders. Patients were naive to or had not received treatment with biological disease-modifying antirheumatic drugs (DMARDs) for >3 months before enrollment, providing a better approximation of a true baseline disease signal. We identified a shared, immune-mediated disease signal represented by low abundances of Lachnospiraceae taxa relative to controls, most notably Fusicatenibacter, which was most abundant in controls receiving nonsteroidal antiinflammatory drug monotherapy and implied to partially mediate higher serum C-reactive protein. Patients with SpA showed an enrichment of Collinsella, whereas human leukocyte antigen (HLA)-B27+ individuals displayed enriched Faecalibacterium. CD patients had higher abundances of a Ruminococcus taxon, and previous conventional/synthetic DMARD therapy was associated with increased Akkermansia. Our work supports the existence of a common gut dysbiosis in SpA and related inflammatory pathologies. We reveal shared and disease-specific microbial associations and suggest potential mediators of disease activity. Validation studies are needed to clarify the role of Fusicatenibacter in gut-joint inflammation, and metagenomic resolution is needed to understand the relationship between Faecalibacterium commensals and HLA-B27.

Trends in Total Elbow Arthroplasty in Patients with Rheumatoid Arthritis Receiving Disease-Modifying Antirheumatic Drug Therapy based on Payer Status.

Total elbow arthroplasty (TEA) is often utilized to manage advanced arthropathies of the elbow secondary to inflammatory conditions such as rheumatoid arthritis (RA). Recent literature has shown that utilization of TEA is decreasing in patients with RA, part of which can be attributed to early medical management involving disease-modifying antirheumatic drugs (DMARDs). However, there is a significant economic barrier to accessing DMARD therapy. The purpose of this study was to compare the utilization of TEA between patients with and without DMARD therapy from 2010-2020. A retrospective cohort analysis was performed using a national insurance claim database to investigate the trends of patients with RA undergoing TEA from 2010-2020. Patients who underwent TEA and had a diagnosis of RA were identified using Current Procedural Terminology (CPT) and International Classification of Disease (ICD) 9 and ICD-10 codes between 2010- 2020. These patients were then stratified into two cohorts: those with DMARDs prescription claims and those without. A linear regression, CAGR analysis, and chi-square analysis were conducted to compare trends and demographic variables, including insurance type, between cohorts. Additionally, a multivariable logistic regression was subsequently performed to observe odds ratios (OR) and 95% confidence intervals (%). From 2010-2020 there has been no significant change in the incidence of TEA in RA patients without DMARD prescriptions, while there has been a statistically significant decreasing rate of TEA observed in RA patients with DMARD prescription claims. The analysis showed there was a CAGR of - 4%. For patients with a diagnosis of RA and DMARDs prescription claims, the highest incidence of undergoing TEA was seen in the age group of 60-69 while patients with a diagnosis of RA and no DMARDs prescription claims, had the highest incidence of undergoing TEA in the age group of 70-79. The incidence of patients undergoing TEA with a diagnosis of RA and DMARD prescription claims has shown a statistically significant decrease from 2010 to 2020, while no significant difference was observed for patients without DMARD prescription claims. There were no statistically significant differences in the insurance plans between cohorts.

P25 TB or not TB? An unusual case of inflammatory arthritis in an anti-CCP positive patient

P25 TB or not TB? An unusual case of inflammatory arthritis in an anti-CCP positive patient

Biologic switching patterns among children with non-systemic juvenile idiopathic arthritis

BackgroundIn juvenile idiopathic arthritis (JIA) clinical remission is unattainable in some patients despite modern biologic disease-modifying antirheumatic drugs (bDMARD) therapy and switching bDMARD is required. The best choice of second-line bDMARD remains unclear. This retrospective observational study aims to describe the pattern, timing, frequency, and reasons for bDMARD switching among children diagnosed with non-systemic JIA.MethodsPatients were identified by combining unique personal identification numbers, the International Code of Diagnosis (ICD10) for JIA and biologic therapy. Clinical characteristics were collected retrospectively from the electronic medical records. Included were 200 children diagnosed with non-systemic JIA initiating their first biologic drug between January 1st, 2012, and March 1st, 2021. We compared characteristics of non-switchers vs switchers and early switchers (≤ 6 months) vs late switchers (> 6 months).ResultsThe median age at diagnosis was 7.7 years. We found that 37% switched to a different bDMARD after a median age of 6.3 years after diagnosis. In total, and 17.5% of patients switched at least twice, while 6% switched three or more times. The most common reason for switching was inefficacy (57%) followed by injection/infusion reactions (15%) and uveitis (13%). 77% were late switchers, and switched primarily due to inefficacy. All patients started a tumor necrosis factor inhibitor (TNFi) as initial bDMARD (Etanercept (ETN): 49.5%, other TNFis: 50.5%). The patients who started ETN as first-line bDMARD were more likely to be switchers compared to those who started another TNFi.ConclusionDuring a median 6.3-year follow-up biologic switching was observed in more than one third, primarily due to inefficacy.

Changes in Tumor Necrosis Factor Inhibitor Drug Survival in Patients With Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis Over 15 Years.

To study changes in retention of first biologic disease-modifying antirheumatic drug (DMARD) therapy over a period of 15 years in an inception cohort of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). We assessed patient and disease characteristics and drug survival of patients starting a biologic (tumor necrosis factor inhibitor [TNFi]) therapy between 2004 and 2019 in routine care at the Amsterdam Rheumatology and Immunology Center, Reade, the Netherlands. Starts were classified as early (2004-2008), intermediate (2009-2013), and recent (2014-2018). Kaplan-Meier plots and log-rank tests assessed the overall difference in drug survival between the 3 observation groups and between diagnoses, followed by Cox regression to estimate hazard ratios (HRs). We included 1938 consecutive patients starting TNFi therapy, 63% with RA, 19% with PsA, and 19% with AS; 65% were female. Drug survival decreased significantly over time (overall P < 0.001), mostly caused by decreases in the most recent 4-year period. The HR for drug continuation was 2.04 (95% CI 1.71-2.43, P < 0.001) for the early vs the recent group and 1.92 (95% CI 1.58-2.35, P < 0.001) for the intermediate vs the recent group. Drug survival time was significantly different between diseases (overall P < 0.001), mostly caused by shorter survival in RA. The HR for drug continuation was 0.58 (95% CI 0.47-0.73, P < 0.001) for RA vs PsA and 0.63 (95% CI 0.51-0.78, P < 0.001) for RA vs AS. Patients with RA, PsA, and AS currently initiating biologic (TNFi) therapy discontinue the drug much sooner than those starting shortly after the drugs were introduced. This is most likely because of the availability of alternative novel biologic and targeted synthetic DMARD treatments and treat-to-target protocols enabling and necessitating earlier switching.

The universal presence of poor prognostic factors based on EULAR recommendations: A real-world study in 1164 Chinese RA patients

IntroductionPoor prognostic factors (PPFs) have been used in assisting therapeutic decision-making in rheumatoid arthritis (RA). There are no standard lists of PPFs for RA, and whether PPFs can guide RA treatment remains controversial. ObjectivesTo analyze the profile of PPF based on EULAR recommendations in RA patients and explore the necessity of considering these PPFs in adjusting therapy. MethodsPrognostic factors including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), swollen joint count (SJC), early erosions, and response to first conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) therapy in 1164 RA patients were collected. The profile of PPFs was graphically displayed. The correlation between different PPFs was analyzed. ResultsElevated ESR/CRP was presented in 746 (64%) patients, and positive RF/ACPA in 1021 (88%) patients. Two hundred and sixty-eight (23%) patients had≥4 swollen joints. Three hundred (26%) patients had moderate or high disease activity (MDA/HDA) despite csDMARD therapy. Failure of≥2 csDMARDs was found in 30% (224/740) of patients. One hundred and fifty-three out of 459 (33%) patients had early bone erosions, usually coexisted with other PPFs. Ninety-seven percent of RA patients had≥1 PPF. Being MDA/HDA≥3 months was significantly correlated with elevated ESR/CRP or high SJC, however uncorrelated with RF/ACPA positivity or early erosions. ConclusionsPPFs are universally present in RA patients. The reasonability of guiding treatment strategies just based on the presence or absence of PPFs requires further investigation. The categories of PPFs can be simplified and the role of different PPFs combinations in guiding treatment needs to be explored.

Risk of incident cardiovascular events with disease-modifying anti-rheumatic drugs among adults with rheumatoid arthritis: a nested case-control study.

This study examined the risk of cardiovascular disease (CVD) associated with the disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). This nested case-control study used the MarketScan database (2012-2014), involving adult RA patients (aged ≥18 years) initiating either a conventional synthetic (cs) DMARD, biologic DMARD, or targeted synthetic (ts) DMARD between January 1, 2013 and December 31, 2014 (cohort entry) and had no CVD history. Cases were individuals with incident CVD identified using diagnosis codes or procedure codes from medical claims. For each case, 10 age- and sex-matched controls were selected using the incident density sampling with replacement. Prescriptions of DMARDs were measured 90 days before the event date. Conditional logistic regression examined the association of risk of CVD with DMARDs in combination treatment or individual use, with reference to methotrexate (MTX) monotherapy, adjusting for baseline confounders. Subgroup analyses were performed separately in DMARD combination therapy users or individual DMARD users, respectively. In total, 270 cases of incident CVD and 2700 controls were included (mean [standard deviation (SD)] age: 54[1]; 75.6% women). The commonly prescribed DMARD therapies were csDMARD monotherapy (n = 795, 27.04%), followed by tumor necrosis factor inhibitors (TNFi) monotherapy (n = 367, 12.48%), and TNFi in combination with MTX (n = 314, 10.68%). Compared with MTX monotherapy, overall use of DMARD agents was not associated with the differential risk of CVD, including various types of DMARD combination regimens. The findings were similar across subgroup analyses. The study found no differential risk of CVD with DMARDs in combination therapy or monotherapy compared to MTX monotherapy in patients with RA. Key Points • This study evaluated the risk of cardiovascular disease (CVD) associated with the disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). • Findings suggest no differential CVD risk with DMARDs in combination with MTX or used individually compared with MTX monotherapy in patients with early RA. • Further efforts should focus on a better understanding of the mechanism of DMARD combination treatments with MTX in modifying CV risk.

Persistence and Use of Ixekizumab in Patients with Psoriatic Arthritis in Real-World Practice in Spain. The PRO-STIP Study.

Ixekizumab (IXE) is an IgG4-type monoclonal antibody targeting IL-17A indicated alone or in combination with methotrexate, for the treatment of active psoriatic arthritis (PsA) in adult patients with insufficient response or with intolerance to one or more disease-modifying anti-rheumatic drug (DMARD) therapy. The PRO-STIP study aimed to describe persistence, patient characteristics, treatment patterns, and effectiveness in patients with PsA receiving IXE in a real-world clinical setting in Spain. This was an observational, multicentric, retrospective, longitudinal study in adult PsA patients who started IXE between January 2019 and December 2020, with at least 24weeks of follow-up. A descriptive analysis of patient characteristics and treatment patterns was performed. The primary objective, treatment persistence, was estimated by Kaplan-Meier survival curve. Effectiveness was evaluated by Disease Activity in Psoriatic Arthritis (DAPSA) scores at baseline and at 12 and 24weeks. Eighty-nine patients met the selection criteria (55.1% women and mean age 51.5years). The median time from PsA diagnosis to starting IXE was 7.7years (IQR 3.4-14.6). Prior to IXE, 95.5% patients had been treated with at least one biologic or targeted synthetic DMARD (b/tsDMARD). The observed persistence rates were 95.5%, 84.3% and 68.5% at 24, 48, and 104weeks, respectively. The median persistence was not reached in the study period (mean persistence, 86.9 [95% CI 80.6-93.2] weeks). Twenty-eight (31.5%) patients discontinued IXE, 19 patients (21.3%) due to loss of effectiveness and two patients (2.2%) due to adverse events. In patients receiving treatment and with available effectiveness assessment (n = 24), DAPSA decreased significantly from baseline 23.7 (95% CI 19.5-27.9) to 14.8 (95% CI 10.5-19.2) at 12weeks (p = 0.005) and 14.3 (95% CI 11.1-17.4) at 24weeks (p = 0.004). PsA patients treated with IXE in a real-world setting show high treatment persistence through 104weeks and improvements in disease activity after treatment initiation. This suggests that IXE could be an effective treatment for patients with PsA. Date of registration: 25th May 2021.

Is it possible to discontinue glucocorticoids in rheumatoid arthritis with the use of synthetic disease-modifying antirheumatic drugs?

The aim of the work is to study the possibility of glucocorticoid (GC) discontinuation or their target dose achievement in patients (pts) with rheumatoid arthritis (RA) receiving conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Materials and methods. 270 pts with RA (women – 86.6 %) aged 51.2 ± 0.71 years, with a disease duration of 50.20 ± 3.82 months were examined. Rheumatoid factor was found in 64.8 % of individuals, anti-cyclic citrullinated peptide (ACCP) antibodies – in 66.6 %. DMARD therapy included methotrexate (n = 91), leflunomide (n = 95), sulfasalazine (n = 51), hydroxychloroquine (n = 3) or its combination (n = 126). The SPSS (version 22.0) software was used for the statistical analysis. Results. During the 3-year study, GC was withdrawn in 33 % of pts in the period from 3 to 30 months (mostly in the first 6 moths). Among those who continued to take GC, the target dose (&lt;7.5 mg/d) was achieved only in 32.6 % of pts. Among pts continuously receiving GC, compared with pts who discontinued GC therapy, there were significantly more women (89.5 % vs. 80.8 %), ACCP-positive pts (88.4 % vs. 55.0 %), with higher DAS-ESR values (5.29 ± 0.10 vs. 4.84 ± 0.15) and more pronounced structural changes on the SHS scale (43.40 ± 2.42 vs. 32.40 ± 2.71). According to the logistic regression analysis, female sex (OR 2.39), elderly pts (OR 1.02), ACCP-positivity (OR 3.73), disease activity by DAS-ESR (OR 1.19) and structural joint changes (OR 1.01) were significantly associated with the risk of continuing GC treatment. Only the initial dose of GC ≥7.5 mg/d was associated with the inability to reach the target dose of GC during the entire follow-up period (OR 6.32). Conclusions. Despite of the treatment with conventional synthetic DMARD, only a third of RA pts can withdraw GC, mostly in the first 6 months. For the pts who continue taking GC, the target dose can be achieved in 33 % of them. Independent predictors of the impossibility to withdraw GC are female sex, old age, ACCP-positivity, higher RA activity according to DAS-ESR and more pronounced joint destruction in early stages. An initial GC dose ≥7.5 mg/d is a negative prognostic factor in achieving the target dose.

Aberrant B-cell activation and B-cell subpopulations in rheumatoid arthritis: analysis by clinical activity, autoantibody seropositivity, and treatment.

Few studies analyze the role of B-cell subpopulations in rheumatoid arthritis (RA) pathophysiology. Therefore, this study aimed to analyze the differences in B-cell subpopulations and B-cell activation according to disease activity, RA subtype, and absence of disease-modifying antirheumatic drugs (DMARDs) therapy. These subgroups were compared with control subjects (CS). One hundred and thirty-nine subjects were included, of which 114 were RA patients, and 25 were controls. Patients were divided into 99 with seropositive RA, 6 with seronegative RA, and 9 without DMARDs. The patients with seropositive RA were subclassified based on the DAS28 index. A seven-color multicolor flow cytometry panel was used to identify B-cell immunophenotypes and cell activation markers. There were no changes in total B-cell frequencies between RA patients and controls. However, a lower frequency of memory B cells and pre-plasmablasts was observed in seropositive RA compared to controls (P < 0.0001; P = 0.0043, respectively). In contrast, a higher frequency of mature B cells was observed in RA than in controls (P = 0.0002). Among patients with RA, those with moderate activity had a higher percentage of B cells (P = 0.0021). The CD69+ marker was increased (P < 0.0001) in RA compared to controls, while the CD40+ frequency was decreased in patients (P < 0.0001). Transitional, naïve, and double-negative B-cell subpopulations were higher in seronegative RA than in seropositive (P < 0.01). In conclusion, in seropositive and seronegative RA patients, there are alterations in B-cell activation and B-cell subpopulations, independently of clinical activity and DMARDs therapy.

Racial and Ethnic Disparities in Treatment Initiation Among Patients with Newly Diagnosed Psoriatic Arthritis: A Retrospective Medicaid Claims Database Study.

In patients with psoriatic arthritis (PsA), potential differences in care by race/ethnicity have not been well studied. This retrospective, observational cohort analysis utilized the IBM MarketScan® Multi-State Medicaid database. Patients aged ≥ 18years with two or more PsA-related claims between January 1, 2010 and December 31, 2019, and ≥ 12months of continuous enrollment before the first diagnosis of PsA (index date) were included. Outcomes evaluated were the use of disease-modifying antirheumatic drugs (DMARDs) overall and by type (conventional synthetic, biologic, targeted synthetic) within 12months following initial PsA diagnosis, as well as the time to DMARD initiation after initial PsA diagnosis, stratified by race/ethnicity. Multivariate Cox proportional hazards models were used to assess potential associations between patient baseline characteristics and time to DMARD initiation. Among patients with newly diagnosed PsA (N = 3432), the mean age was 44.4years, 69.9% were female, 77.4% were White, and 10.1% were Black. Of the 2993 patients with at least 12months of follow-up, fewer Black patients received any DMARD therapy compared with White patients (68.4 vs. 76.4%, respectively, p = 0.002), and, specifically, a lower percentage of Black patients received biologic DMARDs compared with White patients (33.6 vs. 42.6%, respectively, p = 0.003). After adjusting for baseline characteristics, Black patients had significantly longer time to initiation of any DMARD (HR [95% CI] 0.82 [0.71-0.94]) and biologic DMARD (0.84 [0.71-0.99]) compared with White patients. Other baseline variables such as older age, anxiety, and hepatitis C were also significantly associated with longer time to any DMARD initiation after initial PsA diagnosis. Time to treatment initiation was significantly longer in Black patients compared with White patients with newly diagnosed PsA. These findings suggest care delivery disparities in patients with PsA and highlight the need for future studies to understand factors that drive the observed differences in drug therapy by race/ethnicity.

The association between neutrophil-to-lymphocyte ratio and disease activity in rheumatoid arthritis.

The inflammatory response is responsible for the promotion of pannus development over the joint, which is the primary factor in joint injury in rheumatoid arthritis (RA). More in-depth investigations have been conducted in recent years leading to a greater understanding of RA. Yet, it's difficult to gauge inflammation levels in RA patients. Some people who have RA do not exhibit normal symptoms, which makes it more challenging to make a diagnosis. Typical RA evaluations are subject to a few restrictions. Earlier research demonstrated that some patients continued to experience the progression of bone and joint degeneration even while in clinical remission. This progression was attributed to ongoing synovial inflammation. As a result, performing a precise evaluation of the level of inflammation is of the utmost importance. The neutrophil-to-lymphocyte ratio (NLR) has consistently been one of the most interesting novel non-specific inflammatory indicators. It is a reflection of the equilibrium between lymphocytes and neutrophils, which are inflammatory regulators and inflammatory activators, respectively. A higher NLR is linked to more severe levels of imbalance and inflammation. The aim of this study was to depict the role of NLR in RA progression and to show if NLR could predict the response to disease-modifying antirheumatic drugs (DMARDs) therapy in RA.