ACR open rheumatology最新文献

Objective: Idiopathic inflammatory myopathies (IIMs) are a group of heterogeneous, systemic autoimmune diseases characterized by specific clinical features and, frequently, skeletal muscle inflammation. Specific subtypes of IIMs can be characterized by myositis-specific autoantibodies and are associated with distinct clinical phenotypes. Here, we focus on anti-melanoma differentiation-associated protein 5 (MDA5)-positive myositis and anti-signal recognition particle (SRP)-positive myositis, both of which exhibit seasonality but lack known environmental triggers.

Methods: We employed Phage ImmunoPrecipitation Sequencing to profile serum antibodies against the human proteome, the human virome, and a comprehensive enterovirus library. We analyzed sera from 57 patients with anti-MDA5 autoantibodies and 57 patients with anti-SRP autoantibodies, as well as 57 healthy controls. All groups were matched for age, sex, and race.

Results: Our autoantibody profiling results define specific immunogenic regions within the MDA5 and SRP autoantigens. We also discovered that in MDA5 sera, versus SRP sera, there was an elevated antibody response to the viral capsid protein 1 (VP1) of enterovirus B, which was accompanied by a decreased antibody response to rhinovirus A.

Conclusion: Considering the role of MDA5 as a sensor of picornaviral infections and a mediator of inflammatory signaling, our data suggest a novel etiologic link between enterovirus infection and anti-MDA5 dermatomyositis.

Objective: Autoimmune retinopathy and hydroxychloroquine (HCQ)-related retinal toxicity share many similarities, raising the possibility autoimmunity plays a role in HCQ retinopathy. The objective of this study is to determine whether patients diagnosed with HCQ retinal toxicity are more likely to have circulating antiretinal autoantibodies (AAbs) compared to controls.

Methods: We tested plasma samples for the presence of anti-retinal AAbs by immunoblotting in 270 patients with systemic lupus erythematosus (SLE) receiving HCQ. We then evaluated for the presence of HCQ retinal toxicity and other baseline risk factors for HCQ toxicity through chart review. Frequency of specific anti-retinal AAbs in patients with HCQ retinal toxicity was compared to those with no retinal toxicity via multivariate logistic regression.

Results: Patients with HCQ retinal toxicity had a higher likelihood of testing positive for anti-arrestin AAbs (60.7% vs 30.6%, P = 0.001) and anti-pyruvate kinase M2 AAbs (46.4% vs 28.1%, P = 0.05). Patients with HCQ eye toxicity also had a higher number of total anti-retinal AAbs (mean 3.0 ± 2.40 vs 2.04 ± 1.7, P = 0.01). In multivariate analysis accounting for risk factors associated for HCQ eye toxicity, the presence of anti-arrestin antibodies was associated with a 3.2-fold increase in the odds of developing HCQ eye toxicity.

Conclusion: Anti-retinal AAbs were more common in patients with SLE with HCQ retinal toxicity. When controlling for risk factors associated with HCQ toxicity, anti-arrestin AAbs were associated with increased odds for the development of eye toxicity, suggesting a potential role for anti-retinal AAbs as a biomarker of HCQ eye toxicity.

Objective: The objective of this study was to assess the burden of gout flares and examine associated patient characteristics and outcomes in a sample of US adults.

Methods: Data were collected via an online survey of US adults ≥18 years using a random stratified sampling framework. Participants with gout completed questions about treatments, serum urate (SU) levels, severity, satisfaction with control, and gout flares. All participants completed the Veterans RAND 12-Item Health Survey, the Generalized Anxiety Disorder 7-Item Scale, and the Patient Health Questionnaire 9-Item Scale. Data were summarized using descriptive statistics. Multivariable-adjusted logistic regression analyses examined factors predictive of reporting gout flares to a physician.

Results: A total of 933 participants met the study criteria for having gout. Those with gout tended to be older (58.3 [SD 13.3] years vs 45.4 [SD 16.1] years; P < 0.001), male (76.3% vs 46.9%; P < 0.001), White (80.5% vs 76.8%; P = 0.01), and married or living with their partner (58.9% vs 52.8%; P < 0.001) compared with those without gout (n = 30,146). The total gout flare burden for those with gout was 6.6 gout flares per year. Nearly 72% of gout flares were either not reported to physicians or pretreated or prevented. Characteristics of those who were less likely to report gout flares included being younger, being less educated, having a lower Charlson Comorbidity Index score, not being diagnosed with gout by their doctor, and not taking a urate-lowering therapy.

Conclusion: This study confirmed that gout flares are common in US adults with gout and found that gout flares are underreported. Reliance on clinical documentation of physician-reported gout flares is insufficient to assess the true patient burden of gout.

Objective: The objective of this study was to determine if baseline adiponectin, leptin, and resistin levels are associated with response to antirheumatic treatment in early rheumatoid arthritis (RA).

Methods: This study included 341 participants of the Nordic Rheumatic Diseases Strategy Trials and Registries trial with untreated early RA, randomized at baseline into four treatment arms: methotrexate combined with (1) prednisolone, (2) certolizumab, (3) abatacept, or (4) tocilizumab. Follow-up was up to 48 weeks. Adipokines were measured in plasma at baseline with enzyme-linked immunosorbent assay. The primary outcome for this report was the difference in remission (Clinical Disease Activity Index [CDAI] ≤2.8) over 48 weeks stratified by median adipokine levels.

Results: At baseline, levels of adiponectin and leptin were not associated with markers of RA activity, whereas participants with higher resistin levels had higher C-reactive protein (CRP) levels, swollen joint count, and Disease Activity Score in 28 joints based on CRP compared to participants with lower resistin. Overall, participants with baseline adipokine levels above the median and those with adipokine levels below the median had similar mean CDAI and changes in CDAI throughout follow-up for up to 48 weeks. Adjusted Cox proportional hazards models did not show any effect of baseline adiponectin, leptin, and resistin levels on the likelihood of achieving CDAI remission (adiponectin: hazard ratio [HR] 1.08, 95% confidence interval [CI] 0.80-1.45, P = 0.62; leptin: HR 0.89, 95% CI 0.64-1.26, P = 0.52; resistin: HR 0.86, 95% CI 0.65-1.13, P = 0.26).

Conclusion: Baseline adiponectin, leptin, and resistin levels are not associated with the likelihood of achieving CDAI remission over 48 weeks of treatment in a large cohort of people with untreated early RA.

Objective: Health literacy is an important social determinant of health, with limited health literacy associated with worse health outcomes. This study examined the associations between limited health literacy with patient-reported outcomes and disease activity/damage among 267 Black women with active systemic lupus erythematosus (SLE) enrolled in the Peer Approaches to Lupus Self-Management (PALS) program.

Methods: The three-item Chew Health Literacy Screening was used to dichotomize those reporting in the "limited" range on any item with outcomes compared via generalized linear models. Baseline surveys and assessments obtained at study entry as part of the PALS study were used. Primary outcomes included disease activity and lupus damage; other secondary outcomes included patient activation, self-efficacy, physician/patient communication, and quality of life.

Results: The study included 267 Black women with SLE. In covariate-adjusted analyses, participants with limited health literacy (88 [33%]) were more likely to have lower patient activation (Patient Activation Measure P < 0.0001), lower self-efficacy (Lupus Self-Efficacy P < 0.0001), higher lupus damage (self-administered Brief Index of Lupus Damage P = .016), higher disease activity (Systemic Lupus Activity Questionnaire symptom severity P = 0.006), and worse physician/patient communication (patient-centered care P < 0.0001) compared to those with adequate health literacy. Those with limited health literacy also reported worse lupus quality of life (P = 0.0004) and greater levels of stress (Perceived Stress Scale-4 P < 0.0001) and were 2.4 times more likely to have probable major depression (Patient Health Questionnaire Depression Scale-8 of ≥10 P = 0.004) and probable anxiety disorder (General Anxiety Disorder-7 of ≥10 P = 0.007) compared to those with adequate health literacy.

Conclusion: Black women with SLE and limited health literacy have worse clinical outcomes and represent a particularly vulnerable population with significantly disparate health outcomes. These findings suggest health literacy and complexities of managing SLE may impair clinical care in multiple domains, ultimately contributing to higher disease activity and death/damage, and are important to address in clinical care and future interventions in patients with SLE.

Objective: Overlapping chronic pain syndromes, including fibromyalgia, are heterogeneous and often treatment-resistant entities carrying significant socioeconomic burdens. Individualized treatment approaches from both a somatic and psychological side are necessary to improve patient care. The objective of this study was to identify and visualize patient clusters in refractory musculoskeletal pain syndromes through an extensive set of clinical variables, including immunologic, psychosomatic, wearable, and sleep biomarkers.

Methods: Data were collected during a multimodal pain program involving 202 patients. Seventy-eight percent of the patients fulfilled the criteria for fibromyalgia, 77% had a concomitant psychiatric-mediated disorder, and 22% a concomitant rheumatic immune-mediated disorder. Five patient phenotypes were identified by hierarchical agglomerative clustering as a form of unsupervised learning, and a predictive model for the Brief Pain Inventory (BPI) response was generated. Based on the clustering data, digital personas were created with DALL-E (OpenAI).

Results: The most relevant distinguishing factors among clusters were living alone, body mass index, peripheral joint pain, alexithymia, psychiatric comorbidity, childhood pain, neuroleptic or benzodiazepine medication, and response to virtual reality. Having an immune-mediated disorder was not discriminatory. Three of five clusters responded to the multimodal treatment in terms of pain (BPI intensity), one cluster responded in terms of functional improvement (BPI interference), and one cluster notably responded to the virtual reality intervention. The independent predictive model confirmed strong opioids, trazodone, neuroleptic treatment, and living alone as the most important negative predictive factors for reduced pain after the program.

Conclusion: Our model identified and visualized clinically relevant chronic musculoskeletal pain subtypes and predicted their response to multimodal treatment. Such digital personas and avatars may play a future role in the design of personalized therapeutic modalities and clinical trials.

Objective: The objective of this study was to assess 52-week efficacy and safety of bimekizumab in patients with active psoriatic arthritis (PsA) with or without concomitant methotrexate (+/-MTX) treatment at baseline.

Methods: We conducted a post hoc analysis of patients in BE OPTIMAL (NCT03895203; biologic disease-modifying antirheumatic drug [bDMARD]-naïve), BE COMPLETE (NCT03896581; prior inadequate response or intolerance to tumor necrosis factor inhibitors [TNFi-IR]), and the BE VITAL open-label extension (NCT04009499) study. Patients were randomized to one of the following treatment groups: bimekizumab 160 mg every four weeks, placebo, or a reference drug (adalimumab 40 mg every two weeks; BE OPTIMAL only). From Week 16, placebo-randomized patients received bimekizumab. Missing data were imputed using non-responder imputation, multiple imputation, or worst-category imputation.

Results: Through Week 52, similar proportions of bimekizumab-treated patients achieved American College of Rheumatology 50% (ACR50) response criteria for both +MTX and -MTX (BE OPTIMAL: 54.4% +MTX, 54.7% -MTX; BE COMPLETE: 56.3% +MTX, 48.0% -MTX). Similar proportions of bimekizumab-treated patients achieved complete skin clearance (Psoriasis Area and Severity Index 100% [PASI100] response) and minimal disease activity in both +MTX and -MTX groups. Similar trends were seen in placebo/bimekizumab-treated patients. Through Week 52, the proportion of bimekizumab-treated patients with ≥1 treatment-emergent adverse event were similar between the +MTX and -MTX groups (BE OPTIMAL 325 of 410 [79.3%] vs 230 of 292 [78.8%], BE COMPLETE 105 of 168 [62.5%] vs 138 of 220 [62.7%]). The safety profile was comparable between subgroups and consistent with the prior safety profile of bimekizumab.

Conclusion: Treatment with bimekizumab demonstrated consistent, sustained efficacy to 52 weeks in bDMARD-naïve and TNFi-IR patients with PsA and was well tolerated, irrespective of concomitant MTX.