The latest medical research on Rheumatology

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about rheumatology gathered by our medical AI research bot.

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Management of orofacial manifestations of juvenile idiopathic arthritis: Interdisciplinary consensus-based recommendations.

Arthritis Rheumatol

1) To develop consensus-based interdisciplinary recommendations for management of orofacial manifestations of JIA. 2) To create a future research agenda related to management of TMJ arthritis in children with JIA.

The recommendations were developed using online surveying of relevant stakeholders, systematic literature review, evidence-informed generation of recommendations during two consensus-meetings, and Delphi study iterations involving external experts. The process included disciplines involved in the care of orofacial manifestations of JIA: Pediatric rheumatology, radiology, orthodontics, oral and maxillofacial surgery, orofacial pain specialists and pediatric dentistry. Recommendations were accepted if agreement was >80% during a final Delphi study.

Three overarching management principles and 12 recommendations for interdisciplinary management of orofacial manifestations of JIA were outlined. The 12 recommendations pertained to: diagnosis (n=4), treatment of TMJ arthritis (active TMJ inflammation) (n=2), treatment of TMJ dysfunction and symptoms (n=3), treatment of arthritis-related dentofacial deformity (n=2), and other related aspects to JIA (n=1). Additionally, a future interdisciplinary research agenda was developed.

These are the first interdisciplinary recommendations to guide clinical management of TMJ JIA. The 3 overarching principles and 12 recommendations fill an important gap in current clinical practice. They emphasize the importance of an interdisciplinary approach to diagnosis and management of orofacial manifestations of JIA. This article is protected by copyright. All rights reserved.

Hydroxychloroquine and Risk of Long QT Syndrome in Rheumatoid Arthritis: A Veterans Cohort Study with 19-Year Follow-up.

Arthritis Care Res

Recent evidence suggest that hydroxychloroquine use is not associated with higher one-year risk of long QT syndrome (LQTS) in patients with rheumatoid arthritis (RA). Less is known about its long-term risk, the examination of which was the objective of this study.

We conducted a propensity score-matched active-comparator safety study of hydroxychloroquine in 8852 Veterans (mean age, 64±12 years, 14% women, 28% African Americans) with newly-diagnosed RA, in which 4426 patients initiated on hydroxychloroquine and 4426 initiated on another non-biologic disease-modifying antirheumatic drug (DMARD) were balanced on 87 baseline characteristics. The primary outcome was LQTS during 19-year follow-up through December 31, 2019.

Incident LQTS occurred in 4 (0.09%) and 5 (0.11%) patients in hydroxychloroquine and other DMARD groups, respectively, during first two years. Respective 5-year incidences were 17 (0.38%) and 6 (0.14%), representing 11 additional LQTS in hydroxychloroquine group (number needed to harm, 403; 95% CI, 217-1740) and 181% greater relative risk (95% CI, 11%-613%; p=0.030). Although overall 10-year risk remained significant (hazard ratio, 2.17; 95% CI, 1.13-4.18), only 5 extra LQTS occurred in hydroxychloroquine group over the next 5 years (years 6-10) and one over the next 9 years (years 11-19). There was no association with arrhythmia-related hospitalization or all-cause mortality.

Hydroxychloroquine use had no association with LQTS during the first 2 years after initiation of therapy. There was a higher risk thereafter which became significant after 5 years of therapy. However, the 5-year absolute risk was very low, and the absolute risk difference was even lower. Both risks attenuated during longer follow-up. These findings provide evidence for long-term safety of hydroxychloroquine in patients with RA.

Health-Related Quality of Life in Adults with Adolescent- and Adult-onset Systemic Lupus Erythematosus: A Longitudinal Study of a Multiethnic US Cohort (LUMINA LXXXIV).

Arthritis Care Res

The long-term impact of childhood-onset systemic lupus erythematosus on Health-related Quality of Life (HRQoL) in adult SLE patients in comparison to those with adult-onset SLE is unknown. We aim to examine and compare HRQoL trajectories in adults with adolescent- and adult-onset SLE.

Patients enrolled in the LUMINA cohort were included. Adolescent-onset SLE were those diagnosed <24 years of age, and adult-onset SLE otherwise. Sociodemographic, clinical, medications, behavioral/psychological and functioning data were obtained. Longitudinal trajectories of the physical component (PCS) and the mental component (MCS) SF-36 summary scores were compared between the groups using a linear mixed model accounting for time-dependent and independent covariates.

470 SLE patients were included (95 adolescent-onset SLE and 375 adult-onset SLE). The mean age at diagnosis was 19.7 years (SD: 2.8) in the adolescent group and 39.3 years (SD: 11.0) in the adult group. Baseline PCS was higher (better physical functioning) in adolescent- when compared to adult-onset SLE (38.9 vs 34.3 respectively, p<0.001); however, the baseline MCS scores was comparable between the groups (41.4 vs 40.5 respectively, p=0.53). The HRQoL improved equally in both groups with no statistically significant difference within and between the groups (last PCS and MCS mean scores: 43.9 and 45.3 in adolescent-onset SLE; 38.1 and 43 in adult-onset SLE respectively).

Adults with adolescent-onset SLE exhibited better physical functioning when compared with the adult SLE group despite more severe disease; noteworthy, HRQoL was below the general US population despite clinically meaningful improvement in HRQoL over time in both groups. This article is protected by copyright. All rights reserved.

Update on the Efficacy and Safety Profile of Voclosporin: An Integrated Analysis of Clinical Trials in Lupus Nephritis.

Arthritis Care Res

This integrated analysis evaluates the efficacy and safety of voclosporin, a novel calcineurin inhibitor, at 23.7 mg twice daily in combination with mycophenolate mofetil (MMF) and oral glucocorticoids in lupus nephritis (LN) using pooled data from two large phase 2 and phase 3 clinical trials. The purpose was to expand the pool of patients for safety analyses and to increase power for efficacy analyses in patient subpopulations.

AURA-LV (phase 2) and AURORA 1 (phase 3) were randomized, placebo-controlled, double-blind trials with similar designs and endpoints comparing voclosporin to control in combination with MMF and oral glucocorticoids for the treatment of LN. The primary efficacy outcome of the integrated analysis was complete renal response (CRR) at approximately 1 year (Week 48 data from AURA-LV and Week 52 from AURORA 1). Safety was assessed throughout the trials.

Overall, 534 patients (voclosporin 268, control 266) were included in the integrated analysis. Significantly more patients achieved a CRR at 1 year in the voclosporin than control group (43.7% vs. 23.3%, OR 2.76; 95% CI 1.88, 4.05 p<0.0001). The incidence of adverse events (AEs) was similar; 91.4% voclosporin and 87.2% control. Most AEs were mild to moderate in severity; the most commonly reported AEs were classified as infections and infestations (62.2% voclosporin, 54.9% control) and gastrointestinal disorders (45.3% voclosporin, 35.3% placebo). No new or unexpected safety signals were detected.

This integrated analysis demonstrates the efficacy and safety of voclosporin in the treatment of LN across the diverse racial and ethnic groups studied. This article is protected by copyright. All rights reserved.

Monitoring and achievement of target serum urate among gout patients receiving long-term urate lowering therapy in the ACR's RISE Registry.

Arthritis Care Res

The American College of Rheumatology's (ACR) 2020 guidelines for the management of gout recommend using a treat-to-target (T2T) approach to lower serum urate (SU). Using the ACR's RISE registry, we examined the use of a T2T approach among gout patients receiving long-term urate lowering therapy and followed longitudinally by rheumatologists.

Included patients had ≥ 1 ICD9/10 diagnosis for gout in 2018 - 2019 and continuous use of ULT for ≥ 12 months. We assessed the proportions of patients (1) with SU monitoring and (2) among those tested, who achieved SU < 6.0 mg/dL during the measurement year. Multi-level logistic regression adjusting for sociodemographics, comorbidities, region, and healthcare utilization was used to determine factors associated with SU monitoring and achievement of target SU.

9,560 patients were included: mean (SD) age was 67.2 (12.7) years, 73.5% were male, 32.3% were non-white. 56% of patients had at least one SU recorded during the measurement year; among patients with at least one SU recorded, 74% achieved the SU target. In multivariate analyses, non-white patients were slightly less likely to be tested or achieve a target SU.

Among gout patients receiving long-term ULT followed longitudinally by rheumatologists, more than half had a documented SU and among those tested, three quarters achieved the recommended SU target. Routine monitoring of SU is a first step toward improving quality of care for patients with gout. This article is protected by copyright. All rights reserved.

Using data-driven approaches to classify and predict healthcare spending in patients with gout using urate-lowering therapy.

Arthritis Care Res

Despite increasing overall healthcare spending over the past several decades, little is known about long-term patterns of spending among US patients with gout. Current approaches to assessing spending typically focus on composite measures or patients agnostic to disease state; in contrast, examining spending using longitudinal measures may better discriminate patients and target interventions to those in need. We used a data-driven approach to classifying and predicting spending patterns in patients with gout.

Using insurance claims data from 2017-2019, we used group-based trajectory modeling to classify patients aged ≥40 years diagnosed with gout and treated with urate-lowering therapy (ULT) by their total healthcare spending over 2 years. We assessed the ability to predict membership in each spending group using logistic and generalized boosted regression with split-sample validation. Models were estimated using different sets of predictors and evaluated using C-statistics.

In 57,980 patients, mean age was 71.0 (SD:10.5) years, and 17,194 (29.7%) were female. The best-fitting model included the following groups: minimal-spending (13.2%), moderate-spending (37.4%), and high-spending (49.4%). The ability to predict groups was high overall (e.g., boosted C-statistics with all predictors: minimal-spending [0.89], moderate-spending [0.78], and high-spending [0.90]). While average adherence was relatively high in the population, for the high-spending group, the most influential predictors were greater gout medication adherence and diabetes diagnosis.

We identified distinct long-term healthcare spending patterns in patients with gout using ULT with high accuracy. Several clinical predictors could be key areas for intervention, such as gout medication use or diabetes.

Diagnostic evaluation of the sacroiliac joints for axial spondyloarthritis: should MRI replace radiography?

Annals of the Rheumatic Diseases

The possibility of detection of structural damage on magnetic resonance imaging (MRI) of sacroiliac joints raises the question of whether MRI can s...

Coexisting autoantibodies against transcription factor Sp4 are associated with decreased cancer risk in patients with dermatomyositis with anti-TIF1γ autoantibodies.

Annals of the Rheumatic Diseases

In dermatomyositis (DM), autoantibodies are associated with unique clinical phenotypes. For example, anti-TIF1γ autoantibodies are associated with an increased risk of cancer. The purpose of this study was to discover novel DM autoantibodies.

Phage ImmunoPrecipitation Sequencing using sera from 43 patients with DM suggested that transcription factor Sp4 is a novel autoantigen; this was confirmed by showing that patient sera immunoprecipitated full-length Sp4 protein. Sera from 371 Johns Hopkins patients with myositis (255 with DM, 28 with antisynthetase syndrome, 40 with immune-mediated necrotising myopathy, 29 with inclusion body myositis and 19 with polymyositis), 80 rheumatological disease controls (25 with Sjogren's syndrome, 25 with systemic lupus erythematosus and 30 with rheumatoid arthritis (RA)) and 200 healthy comparators were screened for anti-SP4 autoantibodies by ELISA. A validation cohort of 46 anti-TIF1γ-positive patient sera from the University of Pittsburgh was also screened for anti-Sp4 autoantibodies.

Anti-Sp4 autoantibodies were present in 27 (10.5%) patients with DM and 1 (3.3%) patient with RA but not in other clinical groups. In patients with DM, 96.3% of anti-Sp4 autoantibodies were detected in those with anti-TIF1γ autoantibodies. Among 26 TIF1γ-positive patients with anti-Sp4 autoantibodies, none (0%) had cancer. In contrast, among 35 TIF1γ-positive patients without anti-Sp4 autoantibodies, 5 (14%, p=0.04) had cancer. In the validation cohort, among 15 TIF1γ-positive patients with anti-Sp4 autoantibodies, 2 (13.3%) had cancer. By comparison, among 31 TIF1γ-positive patients without anti-Sp4 autoantibodies, 21 (67.7%, p<0.001) had cancer.

Anti-Sp4 autoantibodies appear to identify a subgroup of anti-TIF1γ-positive DM patients with lower cancer risk.

The relationship between knee biomechanics and pain in people with knee osteoarthritis: a systematic review and meta-analysis.

Arthritis Care Res

Our primary aim was to determine the cross-sectional relationship between knee biomechanics during gait and pain in people with medial knee osteoarthritis. Our secondary aim was to evaluate differences in knee biomechanics between symptomatic and asymptomatic participants with medial knee osteoarthritis.

Four online databases were searched from inception to July 2021. Eligible studies included people with medial/non-specific knee osteoarthritis and a reported relationship between knee biomechanics during gait and pain, or biomechanics of symptomatic and asymptomatic participants. Two reviewers independently extracted data and evaluated risk of bias. Random-effects meta-analyses were performed where ≥ three studies reported the same biomechanical variable for pooling (knee adduction moment (KAM), KAM impulse, varus thrust and peak knee flexion moment (KFM)).

Forty studies were included. Methodological quality ranged from 4-9/10. Forty-seven unique biomechanical variables were reported. For the KAM, there was no correlation with pain for peak values pooled (early stance and overall) (r=0.00,95%CI:-0.12,0.11, k=16), a small negative correlation for early stance peak alone (r=-0.09,95%CI:-0.18,-0.002, k=12), and a medium positive correlation for the overall peak during stance (r=0.30,95%CI:0.17,0.42, k=4). Meta-regression identified that body mass index moderated the peak KAM-pain relationship (p<0.001). KAM impulse had a small positive correlation with pain (r=0.23,95%CI:0.04,0.40, k=5), and people with varus thrust had 3.84 greater odds of reporting pain compared to people without (95%CI:1.72,8.53, k=3). Meta-analyses for the peak KFM and pain correlation, and secondary aim were non-significant.

Some knee gait biomechanics were associated with pain in this cohort. Longitudinal studies are required to determine causality. This article is protected by copyright. All rights reserved.

Clinical Phenotypes of Patients with Systemic Sclerosis with Distinct Molecular Signatures in Skin.

Arthritis Care Res

Systemic sclerosis (SSc) patients are classified according to degree of skin fibrosis (limited and diffuse cutaneous) and serum autoantibodies. We undertook the present multicenter study to determine if intrinsic subset (IS) classification based upon skin gene expression yields additional valuable clinical information.

SSc patients and healthy participants (HP) were classified as Normal-like, Limited, Fibroproliferative and Inflammatory IS using a previously trained classifier. Clinical data were obtained (serum autoantibodies, pulmonary function testing, modified Rodnan Skin scores [mRSS], and high-resolution chest computed tomography [HRCT]). Statistical analyses were performed to compare patients classified by IS, traditional cutaneous classification, and serum autoantibodies.

223 participants (165 SSc [115 dcSSc and 50 lcSSc] and 58 HP) were classified. Inflammatory IS patients had higher mRSS (22.1±9.9, p <0.001) than other IS and dcSSc (19.4±9.4, p= 0.05) despite similar disease duration (median [IQR] months 14.9[19.9] vs 18.4[31.6], p=0.48). In multivariable modeling, no significant association between mRSS and RNA Pol III (p=0.07) or Scl-70 (p=0.09) was found. Radiographic ILD was more prevalent in Fibroproliferative IS compared to other IS (91%, p=0.04) with similar prevalence between lcSSc and dcSSc (67% vs. 76%, p=0.73). Positive Scl-70 antibody was the strongest ILD predictor (p<0.001). Interestingly, all lcSSc/Fibroproliferative patients were demonstrated radiographic ILD.

Classification by IS identifies patients with distinct clinical phenotypes versus traditional cutaneous or autoantibody classification. IS classification identifies subgroups of SSc patients with more radiographic ILD (Fibroproliferative), higher mRSS (Inflammatory) and milder phenotype (Normal-like), and may provide additional clinically useful information to current SSc classification systems. This article is protected by copyright. All rights reserved.

Sleep Disorders among Individuals with Rheumatoid Arthritis.

Arthritis Care Res

Self-reported sleep problems are common in RA with potential negative health implications, yet relatively little research has focused on sleep in RA. We examined the prevalence of obstructive sleep apnea (OSA) risk, restless legs syndrome (RLS) symptoms, and short sleep (SS) in a large RA cohort (n=4200), and factors associated with each.

Data are from FORWARD, The National Databank for Rheumatic Diseases. Validated screening measures assessed OSA risk and RLS symptoms. SS was based on self-reported average sleep time (<6 hours). The Medical Outcomes Study Sleep Problems Index I measured self-reported sleep quality. Multivariable logistic regression models identified independent predictors of sleep disorders and sleep quality and the independent association of OSA risk, RLS symptoms, and SS with self-reported poor sleep quality.

Twenty-one percent (n=899) had OSA diagnosis or risk, 30% (n=1272) had RLS symptoms or diagnosis, and 43% (n=1737) reported SS, and. RA disease activity was associated with each sleep disorder. Abatacept use was associated with lower odds of RLS and SS. Use of conventional DMARDS or abatacept were less frequent in the SS group. No medications were associated with OSA in multivariable analyses. Both RLS and SS were associated with worse perceived sleep quality.

Almost two thirds met criteria for at least one sleep disorder. RA disease activity and pain were significantly associated with each sleep condition. Additional research is needed to identify the causal pathway between sleep disorders and RA disease activity and pain and the long-term consequences of sleep disorders in RA. This article is protected by copyright. All rights reserved.

Perceived Cognitive Function in People with Systemic Sclerosis: Associations with Symptoms and Daily Life Functioning.

Arthritis Care Res

Perceived cognitive dysfunction is prevalent in patients with systemic sclerosis (SSc) but not well-understood. This study aimed to examine potential factors associated with perceived cognitive function and to investigate the contributions of perceived cognitive function and symptoms to functional measures.

A cross-sectional survey was conducted among patients with SSc (N = 106). Participants were mainly female (84%) and White (82%). Perceived cognitive function, symptoms, and functional measures were assessed with PROMIS measures. A multivariable regression was conducted to identify factors associated with perceived cognition. Hierarchical linear regressions examined the unique contributions of perceived cognitive function and symptoms to social participation and physical function.

Fifty-nine (56%) patients with SSc perceived mild to severe cognitive dysfunction. Being on work disability and having more fatigue were both significantly associated with perceived cognitive dysfunction. When examining the contributions of cognition and other symptoms to functional measures, self-reported cognition became nonsignificant after fatigue and pain were entered into the regression model.

Being on work disability and having more fatigue were most highly associated with perceived cognitive dysfunction in patients with SSc. Unlike fatigue and pain, perceived cognitive function was not independently associated with functional measures. Nonetheless, future research should disentangle cognitive function and other symptoms as well as their effects on daily activities in SSc. This article is protected by copyright. All rights reserved.