Disease-modifying Antirheumatic Drug Therapy Research Articles

Childhood-Onset Non-Infectious Uveitis in the “Biologic Era”. Results From Spanish Multicenter Multidisciplinary Real-World Clinical Settings

ABSTRACT Objective To characterize and describe clinical experience with childhood-onset non-infectious uveitis. Study Design A multicenter retrospective multidisciplinary national web-based registry of 507 patients from 21 hospitals was analyzed. Cases were grouped as immune disease-associated (IMDu), idiopathic (IDIu) or ophthalmologically distinct. Characteristics of juvenile idiopathic arthritis-associated (non-HLA-B27-related) uveitis (JIAu), IDIu, and pars planitis (PP) were compared. Results IMDu (62.3%) and JIAu (51.9%) predominated in young females; and IDIu (22.7%) and PP (13.6%) in older children, without sex imbalance. Ocular complications occurred in 45.3% of cases (posterior synechiae [28%], cataracts [16%], band keratopathy [14%], ocular hypertension [11%] and cystoid macular edema [10%]) and were associated with synthetic (86%) and biologic (65%) disease-modifying antirheumatic drug (DMARD) use. Subgroups were significantly associated (p < 0.05) with different characteristics. JIAu was typically anterior (98%), insidious (75%), in ANA-positive (69%), young females (82%) with fewer complications (31%), better visual outcomes, and later use of uveitis-effective biologics. In contrast, IDIu was characteristically anterior (87%) or panuveitic (12.1%), with acute onset (60%) and more complications at onset (59%: synechiae [31%] and cataracts [9.6%]) and less DMARD use, while PP is intermediate, and was mostly bilateral (72.5%), persistent (86.5%) and chronic (86.8%), with more complications (70%; mainly posterior segment and cataracts at last visit), impaired visual acuity at onset, and greater systemic (81.2%), subtenon (29.1%) and intravitreal (10.1%) steroid use. Conclusion Prognosis of childhood uveitis has improved in the “biologic era,” particularly in JIAu. Early referral and DMARD therapy may reduce steroid use and improve outcomes, especially in PP and IDIu.

Silajathu Rasayana in Management of Rheumatoid Arthritis

Rheumatoid Arthritis is a systemic autoimmune disease characterized by inflammatory arthritis and extra-articular involvement. Considering the pathophysiology, clinical features, and extra-articular manifestations it can be correlated to Vataraktha in Ayurveda. In this case, a 24-year-old female patient who was diagnosed with Juvenile Rheumatoid Arthritis at the age of 15 and was under Disease-modifying anti-rheumatic drug therapy for several years, complaints of pain and swelling over symmetrical joints of upper and lower limbs along with morning stiffness, and evident boutonniere deformity. She also had pain in her left hip for 4 years. Ayurvedic treatment was initiated with a primary focus on Amapachana, Shodhana, and Rasayana therapies. Patient assessment was conducted using a Visual analog scale, DAS28 score, HAQ-DI score, and Ama assessment tool on the 0th and 69th day. DAS 28 score improved from 7.73 to 3.19, and HAQ-DI score improved from 1.63 to 0.88. The visual analog scale was improved from 8 to 4. Following 69 days of treatment incorporated with Ayurvedic treatment procedures coupled with Rasayana therapy, demonstrated a notable amelioration of symptoms, an enhancement in the overall quality of life, and an improvement in laboratory parameters.

Factors determining resistance to conventional disease-modifying anti-rheumatic drug treatment in oligoarticular juvenile idiopathic arthritis.

Our study was designed to investigate the reasons for starting the conventional disease-modifying anti-rheumatic drugs (DMARDs) and the variables that impact the response to DMARD treatment in oligoarticular juvenile idiopathic arthritis (JIA) patients. Oligoarticular JIA patients (n = 187) were categorized into two groups: Group A consisted of patients who achieved remission with DMARD, and Group B comprised those who did not respond to DMARD therapy. DMARDs were initiated for various reasons: 68 (36.4%) due to active disease despite nonsteroidal anti-inflammatory drugs (± intra-articular corticosteroid) treatment, 59 (31.6%) due to uveitis, 49 (26.2%) due to extended oligoarticular JIA, and 11 (5.9%) due to inflammatory bowel disease. One hundred twenty-three patients (65.8%) achieved remission with DMARDs (Group A), while 64 patients (34.2%) did not respond to DMARD therapy (Group B). In Group B, patients had higher C-reactive protein (CRP) levels as well as higher Juvenile Idiopathic Arthritis Disease Activity Scores-71 (JADAS-71) at diagnosis (both p < 0.001). Moreover, extended oligoarticular JIA subtype (p = 0.017) and involvement of small joints at diagnosis (p = 0.043) were more prevalent among these patients. Group A exhibited a higher frequency of antinuclear antibody positivity (p = 0.014). Elevated CRP levels (> 1.1mg/dL) (OR 1.308, 95% CI 1.203-3.574; p < 0.001) and high JADAS-71 at diagnosis (> 15.8) (OR 1.659, 95% CI 1.179-2.941; p < 0.001) were associated with DMARD resistance. Elevated CRP and high JADAS-71 at diagnosis were the main factors associated with DMARD resistance in oligoarticular JIA. Prospective long-term studies may help verify the role of these factors associated with DMARD resistance in oligoarticular JIA. Key Points • Conventional DMARDs were most commonly started due to active disease despite NSAID (± intra-articular corticosteroids). • Remission was achieved with DMARD in 65.8% of oligoarticular JIA patients. • Elevated CRP and high JADAS-71 at diagnosis were associated with DMARD resistance.

P062 Trust performance in managing inflammatory arthritis over time in England and Wales: a latent class analysis approach

Abstract Background/Aims To evaluate trust-level performance in time to initiation of disease-modifying antirheumatic drug (DMARD) therapy in patients with early inflammatory arthritis (EIA), with identification of change in performance trajectories over time and investigation of trust characteristics associated with this change. Methods We included 130 trusts from the UK contributing to the National Early Inflammatory Arthritis Audit (NEIAA) from 2018 to 2020. The primary outcome was days from referral to initiation of DMARD therapy in patients with EIA. Latent class growth mixture models were applied to identify distinct groups of trusts with similar trajectories of performance change over time. We used mixed-effects linear and multinomial logistic regression models to evaluate the association between delay in treatment and trust-level characteristics. Results The mean (SD) time to DMARD initiation was 53 (18) days, with an average 0.3-day decrease with each month over time. Four latent trajectories were identified in our cohort, with over 77% of individual trusts showing ongoing improvements in decreasing treatment waiting times. Prior to separating by latent class, time to DMARD initiation was shorter in trusts with higher rheumatology staffing, a local EIA treatment pathway and those with access to musculoskeletal ultrasound. Trusts with more nurses in the rheumatology department were less likely to be in the worse performance group (OR = 0.69 [95%CI 0.49, 0.93]). Conclusion In this cohort study, we observed a reduction in treatment waiting time over time. Trusts with better staffed and improved EIA clinical structure are likely to initiate definitive treatment earlier in patients with EIA. Disclosure Z. Yang: None. N. Arumalla: None. M.D. Russell: Honoraria; Lilly, Menarini, Galapagos. Grants/research support; NIHR. Other; Pfizer, Janssen, Biogen, and UCB. K. Bechman: Honoraria; Menarini, Galapagos. Grants/research support; NIHR,Versus Arthritis and Pfizer Global Medical Grants for Quality Improvement in Rheumatology Practice. Other; UCB. E. Alveyn: Other; UCB. S. Gallagher: None. E. Price: None. S. Norton: None. J. Galloway: Honoraria; AbbVie, Biovitrum, BMS, Celgene, Chugai, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UCB.

Classification of rheumatoid arthritis: is it time to revise the criteria?

Classification criteria have been developed for rheumatoid arthritis (RA) and other rheumatic diseases in order to gather a homogeneous patient population for clinical studies and facilitate the timely implementation of therapeutic measures. Although classification criteria are not intended to be used for diagnosis, they are frequently used to support the diagnostic process in clinical practice, including clinical decision-making. The 2010 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria for RA are capable of identifying the majority of symptomatic patients with RA already in the earliest stages of the disease who are not yet showing radiographic changes. These patients will also profit from the early implementation of therapy with disease-modifying antirheumatic drugs (DMARDs). However, the risk of misclassification is higher as compared with the former 1987 ACR criteria, which were considerably less sensitive to the recognition of patients with early RA. Of note, the presence of rheumatoid factors (RFs) and anticitrullinated protein antibodies (ACPAs) has been attributed equal weight in the 2010 ACR/EULAR criteria and may contribute up to 50% of the score needed for being classified as RA. However, while ACPAs have been proven to be the most specific serological markers of RA, the specificity of RF is moderate, especially at lower titres. This may lead to the misclassification of RF-positive patients and, consequently, the unjustified implementation of DMARD therapy. Therefore, issues arise on how comprehensive the criteria should be and whether they should be updated and adapted to findings from the past two decades that might increase both their specificity and sensitivity.

Risk perception, well-being, depression and anxiety in children and adolescents with rheumatic diseases during the COVID-19 pandemic - results from the prospective multicenter KICK-COVID study in Germany

ObjectiveTo investigate the psychosocial burden in children and adolescents with juvenile rheumatic diseases during the COVID-19 pandemic.MethodsAs part of the multicentre observational KICK-COVID study linked to the National Pediatric Rheumatology Database, adolescents < 21 years and parents of children < 12 years with rheumatic diseases answered questions on perceptions of health risk (PHR) due to SARS-CoV2, stress, well-being (WHO-5) and symptoms of depression (PHQ-9) and anxiety (GAD-7). Data were collected at routine visits from June to December 2021 and assessed for association with demographic and clinical parameters, treatment and patient-reported outcomes by multivariable regression analyses.ResultsData from 1356 individuals (69% female, 50% adolescents) were included. Median PHR on a numeric rating scale (NRS, 0–10) was 4 (IQR 2–6), median perceived stress was 3 (IQR 1–6). Adolescents reported a worse well-being with a significantly lower median WHO-5-score (60, IQR 40–76) than parents reported for their children < 12 years (80, IQR 68–84). Moderate to severe symptoms of depression and anxiety were reported by 14.3% and 12.3% of the adolescents, respectively. PHR was significantly higher in patients with systemic lupus erythematosus, methotrexate or biologic disease-modifying anti-rheumatic drug therapy than in patients without these characteristics, whereas lower WHO-5 or higher PHQ-9 or GAD-7 scores were only associated with poorer patient-reported health status and physical functioning.ConclusionThe perception of health risk due to SARS-CoV2 infection was not paralleled by an impairment of mental health, which were, however, significantly correlated with self-rated health status and functional capacity, highlighting the importance of patient-reported outcome assessment.Trial registrationGerman Clinical Trials Register (DRKS), no. DRKS00027974. Registered on 27th of January 2022.

Effects of tapering conventional synthetic disease-modifying antirheumatic drugs to drug-free remission versus stable treatment in rheumatoid arthritis (ARCTIC REWIND): 3-year results from an open-label, randomised controlled, non-inferiority trial

Tapering of disease-modifying antirheumatic drugs (DMARDs) to drug-free remission is an attractive treatment goal for patients with rheumatoid arthritis, although long-term effects of tapering and withdrawal remain unclear. We compared 3-year risks of flare between three conventional synthetic DMARD treatment strategies in patients with rheumatoid arthritis in sustained remission. In this open-label, randomised controlled, non-inferiority trial, we enrolled patients aged 18-80 years with rheumatoid arthritis who had been in sustained remission for at least 1 year on stable conventional synthetic DMARD therapy. Patients from ten hospitals in Norway were randomly assigned (2:1:1) with centre stratification to receive stable conventional synthetic DMARDs, half-dose conventional synthetic DMARDs, or half-dose conventional synthetic DMARDs for 1 year followed by withdrawal of all conventional synthetic DMARDs. The primary endpoint of this part of the study was disease flare over 3 years, analysed as flare-free survival and risk difference in the per-protocol population with a non-inferiority margin of 20%. This trial is registered with ClinicalTrials.gov (NCT01881308) and is completed. Between June 17, 2013, and June 18, 2018, 160 patients were enrolled and randomly assigned to receive stable-dose conventional synthetic DMARDs (n=80), half-dose conventional synthetic DMARDs (n=42), or half-dose conventional synthetic DMARDs tapering to withdrawal (n=38). Four patients did not receive the intervention and 156 patients received the allocated treatment strategy. One patient was excluded due to major protocol violation and 155 patients were included in the per-protocol analysis. 104 (67%) of 156 patients were women and 52 (33%) were men. 139 patients completed 3-years follow-up without major protocol violation; 68 (87%) of 78 patients in the stable-dose group, 36 (88%) of 41 patients in the half-dose group and 35 (95%) of 37 patients in the half-dose tapering to withdrawal group. During the 3-year study period, 80% (95% CI 69-88%) were flare-free in the stable-dose group, compared with 57% (41-71%) in the half-dose group and 38% (22-53%) in the half-dose tapering to withdrawal group. Compared with stable-dose conventional synthetic DMARDs, the risk difference of flare was 23% (95% CI 6-41%, p=0·010) in the half-dose group and 40% (22-58%, p<0·0001) in the half-dose tapering to withdrawal group, non-inferiority was therefore not shown. Adverse events were reported in 65 (83%) of 78 patients in the stable-dose group, 36 (90%) of 40 patients in the half-dose group, and 36 (97%) of 37 patients in the half-dose tapering to withdrawal group. One death occurred in the stable-dose conventional synthetic DMARD group (sudden death considered unlikely related to the study medication). Two conventional synthetic DMARD tapering strategies were associated with significantly lower rates of flare-free survival compared with stable conventional synthetic DMARD treatment, and the data do not support non-inferiority. However, drug-free remission was achiveable for a significant subgroup of patients. This trial provides information on risk and benefits of different treatment strategies important for shared decision making. Research Council of Norway and South-Eastern Norway Regional Health Authority.

Impact of DMARD treatment and systemic inflammation on all-cause mortality in patients with rheumatoid arthritis and interstitial lung disease: a cohort study from the German RABBIT register

ObjectivesTo investigate the impact of disease activity and treatment with disease-modifying antirheumatic drugs (DMARDs) on all-cause mortality in patients with rheumatoid arthritis and prevalent interstitial lung disease (RA-ILD).MethodsPatients with RA-ILD...

Pharmacological Approaches in Rheumatoid Arthritis- An In-depth Analysis of Prescribed Medications

Inflammation, pain, swelling, and stability of the joints are some of the symptoms associated with rheumatoid arthritis (RA). A variety of treatment options are available to manage symptoms and slow the progression of RA, despite the fact that there is no cure. This cross-sectional study, which was conducted in a tertiary care hospital in Kerala, India, aimed to evaluate medication prescribing practices and therapeutic strategies in RA patients. The study included 280 RA patients and data on demographics, medications prescribed, dosage, and mode of administration were collected. The findings revealed that disease-modifying anti-rheumatic drugs (DMARDs) were the cornerstone of RA treatment, with hydroxychloroquine (HCQ), methotrexate (MTX), and sulfasalazine (SAAZ) being the most frequently prescribed DMARDs. Combination DMARD therapy, particularly the triple combination of HCQ + Folitrax + SAAZ, was prevalent among patients. Furthermore, the study highlighted the use of biologic DMARDs, such as rituximab and tofacitinib, albeit at a relatively lower rate due to the outpatient population’s milder disease severity. Supplement therapy, including vitamin D3 and folic acid, was commonly prescribed to address deficiencies and mitigate the side effects of medications like MTX. The prescription patterns also encompassed analgesics, anti-anxiety, and antidepressant medications to manage pain and psychological symptoms associated with RA. Steroids were administered initially to control inflammation, with a focus on minimizing long-term usage. The study underscores the complexity of RA management and the importance of individualized treatment approaches. It highlights the evolving landscape of RA therapeutics, emphasizing the need for clinicians to stay updated on emerging evidence and guidelines. Future research should focus on evaluating the long-term efficacy, safety, and cost-effectiveness of different treatment regimens to optimize patient outcomes in RA management.

Predicting Flare in Patients With Rheumatoid Arthritis in Biologic Induced Remission, on Tapering, and on Stable Therapy.

The tapering of biologic disease-modifying antirheumatic drug (b-DMARD) therapy for patients with rheumatoid arthritis (RA) in stable remission is frequently undertaken, but specific guidance on how to successfully taper is lacking. The objective of this study is to identify predictors of flare in patients in stable b-DMARD-induced clinical remission, who did or did not follow structured b-DMARD tapering. Patients with RA receiving b-DMARD treatment who had achieved sustained remission according to a Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) <2.6 for ≥6 months were offered tapering. Clinical, ultrasound (US) (total power Doppler [PD]/grayscale abnormalities), CD4+ T cell subsets, and patient-reported outcomes (PROs) were collected at inclusion. The primary endpoint was the occurrence of flare (loss of DAS28-CRP remission) over 12 months. Logistic regression analyses identified predictors of flare. Dichotomization into high/low-risk groups was based on 80% specificity using the area under the receiving operator curve (AUROC). Of 63 patients choosing tapering, 23 (37%) flared compared with 12 of 60 (20%) on stable treatment (P = 0.043). All patients who flared regained remission upon reinstating treatment. In the tapering group, flare was associated with lower regulatory T cell (Treg) (P < 0.0001) and higher CRP levels (P < 0.0001), erythrocyte sedimentation rate (P < 0.035), and inflammation-related cells (IRCs) (P = 0.054); stepwise modeling selected Tregs (odds ratio [OR] = 0.350, P = 0.004), IRCs (OR=1.871, P = 0.007), and CRP level (OR=1.577, P = 0.004) with 81.7% accuracy and AUROC=0.890. In the continued therapy group, modeling retained the tender joint count, total PD, and visual analog scale pain score, with 82.1% accuracy and AUROC=0.899. Most patients in the study were considered low risk of flare (80 of 123 patients [65%]). Only 5 of 37 (13.5%) of the low-risk patients who tapered flared, which was notable compared with the continued therapy group (20% flare). Flare on tapering b-DMARDs was predicted by lower Tregs and elevated inflammation biomarkers (IRCs/CRP level); flare on continued b-DMARDs was associated with raised pain parameters and US inflammation. Knowledge of these biomarkers should improve outcomes by targeted selection for tapering, and by increased monitoring of those on continued therapy predicted to flare.

Association between disease-modifying antirheumatic drugs for rheumatoid arthritis and risk of incident dementia: a systematic review with meta-analysis

BackgroundDysregulation of several inflammatory cytokines including tumour necrosis factor (TNF) in dementia patients has also been identified as a key factor in the pathogenesis of rheumatoid arthritis (RA). We aimed...

Treatment response in rheumatoid arthritis is predicted by the microbiome: a large observational study in UK DMARD-naïve patients.

Disease-modifying antirheumatic drugs (DMARDs) are first line treatment in rheumatoid arthritis (RA). Treatment response to DMARDs is patient-specific, dose efficacy is difficult to predict and long-term results variable. The gut microbiota are known to play a pivotal role in prodromal and early-disease RA, manifested by Prevotella spp. enrichment. The clinical response to therapy may be mediated by microbiota, and large-scale studies assessing the microbiome are few. This study assessed whether microbiome signals were associated with, and predictive of, patient response to DMARD-treatment. Accurate early identification of those who will respond poorly to DMARD therapy would allow selection of alternative treatment (e.g. biologic therapy), and potentially improve patient outcome. A multicentre, longitudinal, observational study of stool- and saliva microbiome was performed in DMARD-naïve, newly diagnosed RA patients during introduction of DMARD treatment. Clinical data and samples were collected at baseline (n = 144) in DMARD-naïve patients and at six weeks (n = 117) and 12 weeks (n = 95) into DMARD-therapy. Samples collected (n = 365 stool, n = 365 saliva) underwent shotgun sequencing. Disease activity measures were collected at each timepoint and minimal clinically important improvement determined. In total, 26 stool microbes were found to decrease in those manifesting a minimal clinically important improvement. Prevotella spp. and Streptococcus spp. were the predominant taxa to decline following six weeks and 12 weeks of DMARDs, respectively. Furthermore, baseline microbiota of DMARD-naïve patients were indicative of future response. DMARDs appear to restore a perturbed microbiome to a eubiotic state. Moreover, microbiome status can be used to predict likelihood of patient response to DMARD.

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.

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.