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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The Association Between Physician Gender and Career Advancement Among Academic Rheumatologists in the United States.

Arthritis Rheumatol

To determine the potential association between physician gender and academic advancement among US rheumatologists.

We performed a nationwide, cross-sectional study of all rheumatologists practicing in the US in 2014 using a comprehensive database of all licensed physicians. Among academic rheumatologists, we estimated gender differences in faculty rank, adjusting for differences in physician age, years since residency graduation, publications, National Institutes of Health (NIH) grants, registered clinical trials, and appointment at a top 20 medical school using a multivariate logistic regression model. We also estimated gender differences in leadership positions (i.e., division director and fellowship program director).

Among 6,125 total practicing rheumatologists, 941 (15%) had academic faculty appointments in 2014. Women academic rheumatologists (41.4%) were younger and had completed residency more recently than men. Women had fewer total publications, publications on which they were the first or last author, and NIH grants. In fully adjusted analyses, women were less likely to be full or associate professors than men, with an adjusted odds ratio (OR) of 0.78 (95% confidence interval [95% CI] 0.62-0.99]). Women in rheumatology had similar odds as men of being a fellowship program director or division director (adjusted OR 0.99 [95% CI 0.69-1.43] and adjusted OR 0.96 [95% CI 0.66-1.41], respectively).

Among academic rheumatologists, women are less likely than men to be full or associate professors but have similar odds of being fellowship program directors or division directors, when adjusting for several factors known to influence faculty promotion. These differences suggest barriers to academic promotion despite representation in leadership positions within rheumatology divisions.

Risk factors for COVID-19 and rheumatic disease flare in a US cohort of Latino patients.

Arthritis Rheumatol

Latino patients are overrepresented among cases of coronavirus disease 2019 (COVID-19) and are at an increased risk for severe disease. Prevalence of COVID-19 in Latinos with rheumatic diseases are poorly reported. The purpose of this study was to characterize COVID-19 clinical features and outcomes in Latino patients with rheumatic diseases.

This is a retrospective study of Latino patients with rheumatic diseases from an existing observational cohort in the Washington, DC area. Patients seen between April 1 to October 15, 2020 were analyzed in this study. We reviewed demographics, body mass index (BMI), comorbidities, and immunomodulatory therapies. An exploratory Classification and Regression Tree (CART) analysis along with logistic regression (LR) analyses were performed to identify risk factors for COVID-19 and rheumatic disease flare.

Out of 178 patients, 32 (18%) were identified with COVID-19 and the incidence rate of infection was found to be three-fold higher than the general Latino population. No patients required ICU level care. CART analysis and multivariable LR analysis identified BMI>30.35 as a risk factor for COVID-19 [P=0.004, OR=3.37, 95%CI (1.5-7.7)]. COVID-19 positivity was a risk factor for rheumatic disease flare [P=0.02, OR=4.57, 95%CI (1.2-17.4)].

Latino patients with rheumatic diseases had a higher rate of COVID-19 compared with the general Latino population. Obesity was identified as a risk factor for COVID-19 and COVID-19 itself was found to be a risk factor for rheumatic disease flare. Latino patients with risk factors should be followed closely, especially post-COVID-19 in anticipation of disease flare.

eQTL analysis in systemic sclerosis identifies new candidate genes associated with multiple aspects of disease pathology.

Arthritis Rheumatol

To identify the genetic variants that affect gene expression (expression quantitative trait loci, eQTLs) in systemic sclerosis (SSc) to investigate their role in the pathogenesis of the disease.

We performed an eQTL analysis using whole blood sequencing data of 333 SSc patients and 524 controls and integrated them with SSc GWAS data. We integrated our findings from modelling of expression, differential expression analysis and transcription factor binding site (TFBS) enrichment with key clinical features of SSc.

We detected 49,123 validated cis-eQTLs from 4,539 SSc associated SNPs (pGWAS <10-5 ) and 565 of 1.436 genes with an SSc eQTL within 1 Mb distance to the gene. We developed a strategy to prioritize disease-associated genes based on their expression variance explained by SSc eQTLs (r2 >0.05). As a result, 233 candidates were identified, 134 (58%) of them associated with hallmarks of SSc and 105 (45%) of them differentially expressed in blood cells, skin, or lung tissue of SSc patients. TFBS analysis revealed enriched motifs of 24 TFs (5%) among SSc eQTLs, five of which were found to be differentially regulated in blood cells (ELF1 and MGA), skin (KLF4 and ID4), and lungs (TBX4) of SSc patients. Ten candidate genes (4%) can be targeted by approved medications for immune-mediated diseases, of which only two have been tested in clinical trials in patients with SSc.

The data of the present study provides a new layer of the molecular complexity of SSc, contributing to a better understanding of the pathogenesis of the disease.

Contribution of a European-Prevalent Variant near CD83 and an East Asian-Prevalent Variant near IL17RB to Herpes Zoster Risk in Tofacitinib Treatment: Results of Genome-Wide Association Study Meta-Analyses.

Arthritis Rheumatol

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), psoriatic arthritis, and ulcerative colitis, and has been previously investigated for psoriasis (PsO). Genome-wide association studies (GWAS) were performed to identify genetic factors associated with increased risk/faster onset of herpes zoster (HZ) upon tofacitinib treatment, and potential mechanisms of the varying HZ rate across ethnicities.

In an ethnicity-/indication-specific and trans-ethnic trans-indication meta-analysis of GWAS in subjects from RA and PsO phase II, III, and long-term extension tofacitinib studies, 8 million genetic variants on time to HZ and HZ event (case versus control) were evaluated via Cox and logistic regression, respectively.

5,246 subjects were included (RA: 3,168; PsO: 2,078). Adjusting for age, baseline absolute lymphocyte count, genetically-defined ethnicity, and concomitant methotrexate use (RA only), 4 loci were significantly associated with faster HZ onset in Europeans (P < 5×10-8 ), including a single-nucleotide polymorphism (SNP) near CD83 (risk allele in Europeans ~2%, East Asian ~0.1%). In the trans-ethnic trans-population meta-analysis, the CD83 SNP remained significant, and 4 additional significant loci were identified, among which a SNP near IL17RB was associated with faster HZ onset (meta-analysis hazard ratio [95% confidence interval] 3.6 [2.40, 5.44], P = 7.6×10-10 ; risk allele in East Asian subjects ~12%, European subjects <0.2%).

Genetic analysis of tofacitinib-treated RA and PsO subjects identified multiple loci associated with increased HZ risk. European or East Asian population-specific prevalent variants near immune-relevant genes of CD83 and IL17RB, respectively, may contribute to HZ risk in tofacitinib-treated subjects.

The Relationship between Patient-Reported Readiness for Total Knee Arthroplasty and Likelihood of a Good Outcome at One Year.

Arthritis Care Res

To determine the relationship between patients' pre-operative readiness for total knee arthroplasty (TKA) and surgical outcome at one-year.

This prospective cohort study recruited knee osteoarthritis (OA) patients aged 30+ years referred for TKA at two hip/knee surgery centers in Alberta, Canada. Those who received primary, unilateral TKA completed questionnaires pre-TKA to assess WOMAC-pain, KOOS-physical function, Perceived Arthritis Coping Efficacy, General Self-Efficacy, PHQ-8, BMI, comorbidities and TKA readiness (Patient Acceptable Symptom State; willingness to undergo TKA), and one-year post-TKA to assess outcomes. A good TKA outcome was defined as improved knee symptoms (OARSI-OMERACT responder criteria) AND overall satisfaction with results. Poisson regression with robust error estimation was used to estimate relative risk of a good outcome for exposures, before and after controlling for covariates.

Of 1,272 TKA recipients assessed at one year, 1,053 with data for our outcome were included (mean age 66.9 years (SD 8.8); 58.6% female). Most (87.8%) were definitely willing to undergo TKA and had 'unacceptable' knee symptoms (79.7%). 78.1% achieved a good TKA outcome. Controlling for pre-TKA OA-related disability, arthritis coping efficacy, comorbid hip symptoms and depressed mood, definite willingness to undergo TKA and unacceptable knee symptoms were associated with greater likelihood of a good TKA outcome (adjusted RRs 1.18, 95% CI 1.04-1.35, and 1.14, 95% CI 1.02-1.27, respectively).

Among TKA recipients for knee OA, patients' psychological readiness and willingness for TKA were associated greater likelihood of a good outcome. Incorporation of these factors in TKA decision-making may enhance patient outcomes and appropriate use of TKA.

In vivo Compositional Changes in the Articular Cartilage of the Patellofemoral Joint following Anterior Cruciate Ligament Reconstruction.

Arthritis Care Res

To compare T1ρ relaxation times of the medial and lateral regions of the patella and femoral trochlea at 6 and 12 months post-anterior cruciate ligament reconstruction (ACLR) on the ACLR and contralateral limb. Greater T1ρ relaxation times are associated with a lesser proteoglycan density of articular cartilage.

Twenty individuals (11 males, 9 females; age=22±3.9yrs; mass=76.11±13.48kg; height=178.32±12.32) who underwent a previous unilateral ACLR using a patellar tendon autograft. Magnetic resonance images from both limbs were acquired at 6 and 12 months post-ACLR. Voxel by voxel T1ρ relaxation times were calculated using a five-image sequence. The medial and lateral regions of the femoral trochlea and patellar articular cartilage were manually segmented on both limbs. Separate limb (ACLR and contralateral limb) by time (6-months and 12-months) ANOVAs were performed for each region (P<0.05).

For the medial patella and lateral trochlea, T1ρ relaxation times increased in both limbs between 6 and 12-months post-ACLR (medial patella: P=0.012; lateral trochlea: P=0.043). For the lateral patella, T1ρ relaxation times were significantly greater on the contralateral limb compared to the ACLR limb (P=0.001). The T1ρ relaxation times of the medial trochlea on the ACLR limb were significantly greater at 6 (P=0.005) and 12-months (P<0.001) compared to the contralateral limb. T1ρ relaxation times of the medial trochlea significantly increased from 6 to 12-months on the ACLR limb (P=0.003).

Changes in T1ρ relaxation times occur within the first 12 months following ACLR in specific regions of the patellofemoral joint on the ACLR and contralateral limb.

Real-world 6 and 12-month Drug Retention, Remission and Response Rates of Secukinumab in 2,017 Psoriatic Arthritis patients in 13 European Countries.

Arthritis Care Res

There is a lack of real-life studies on IL-17 inhibition in psoriatic arthritis (PsA). We assessed real-life 6-/12-month effectiveness (i.e. retention, remission, low-disease-activity [LDA] and response rates) of the IL-17 inhibitor secukinumab in PsA patients overall, and across 1) number of prior biologic/targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (b/tsDMARDs), 2) years since diagnosis, and 3) European registries.

Thirteen quality registries in rheumatology participating in the European Spondyloarthritis Research Collaboration Network provided longitudinal, observational data collected as part of routine care, for secondary use. Data were pooled and analysed with Kaplan-Meier plots, log-rank tests, Cox regression, and multiple linear and logistic regression analyses.

A total of 2,017 PsA patients started treatment with secukinumab between 2015 and 2018. Overall secukinumab retention rates were 86%/76% after 6/12 months. Crude (LUNDEX adjusted) 6-month remission/LDA (LDA including remission) rates for DAPSA28, DAS28-CRP and SDAI were 13%/46% (11%/39%), 36%/55% (30%/46%) and 13%/56% (11%/47%), and 12-month rates 11%/46% (7%/31%), 39%/56% (26%/38%) and 16%/62% (10%/41%), respectively. CDAI remission/LDA rates were similar to the SDAI rates. Six-month ACR20/50/70 responses were 34%/19%/11% (29%/16%/9%); 12-month: 37%/21%/11% (24%/14%/7%). Secukinumab effectiveness was significantly better for b/tsDMARD naïve patients, similar across time since diagnosis (<2/2-4/>4 years) and varied significantly across the European registries.

In this large real-world study on secukinumab treatment in PsA, 6- and 12-month effectiveness was comparable to previous observational studies of TNFi. Retention, remission, LDA and response rates were significantly better for b/tsDMARD naïve patients, independent of time since diagnosis and varied significantly across the European countries.

Application of Heterogeneity of Treatment Effect Methods: Exploratory Analyses of a Trial of Exercise-Based Interventions for Knee OA.

Arthritis Care Res

To evaluate heterogeneity of treatment effects (HTE) in a trial of exercise-based interventions for knee osteoarthritis (OA).

Participants (n=350) were randomized to standard physical therapy (PT; n=140), Internet-Based Exercise Training (IBET; n=142), or wait list control (WL; n=68). We applied QUalitative INteraction Trees (QUINT), a sequential partitioning method, and Generalized Unbiased Interaction Detection and Estimation (GUIDE), a regression tree approach, to identify subgroups with greater improvements in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score over 4-months. Predictors included 24 demographic, clinical and psychosocial characteristics. We conducted internal validation to estimate optimism (bias) in the range of mean outcome differences among arms.

Both QUINT and GUIDE indicated that for participants with lower body mass index (BMI), IBET was better than PT (improvements of WOMAC ranged from 6.3 to 9.1 points lower) and for those with higher BMI and longer duration of knee OA, PT was better than IBET (WOMAC improvement was 6.3 points). In GUIDE analyses comparing PT or IBET to WL, participants not employed had improvements in WOMAC ranging from 1.8 to 6.8 points lower with PT or IBT vs. WL. From internal validation, there were large corrections to the mean outcome differences among arms; however, after correction some differences remained in the clinically meaningful range.

Results suggest there may be subgroups who experience greater improvement in symptoms from PT or IBET, and this could guide referrals and future trials. However, uncertainty persists for specific treatment effect size estimates and how they apply beyond this study sample.

Arg206Cys substitution in DNASE1L3 causes a defect in DNASE1L3 protein secretion that confers risk of systemic lupus erythematosus.

Annals of the Rheumatic Diseases

To determine if the polymorphism encoding the Arg206Cys substitution in DNASE1L3 explains the association of the DNASE1L3/PXK gene locus with systemic lupus erythematosus (SLE) and to examine the effect of the Arg206Cys sequence change on DNASE1L3 protein function.

Conditional analysis for rs35677470 was performed on cases and controls with European ancestry from the SLE Immunochip study, and genotype and haplotype frequencies were compared. DNASE1L3 protein levels were measured in cells and supernatants of HEK293 cells and monocyte-derived dendritic cells expressing recombinant and endogenous 206Arg and 206Cys protein variants.

Conditional analysis on rs35677470 eliminated the SLE risk association signal for lead single-nucleotide polymorphisms (SNPs) rs180977001 and rs73081554, which are found to tag the same risk haplotype as rs35677470. The modest effect sizes of the SLE risk genotypes (heterozygous risk OR=1.14 and homozygous risk allele OR=1.68) suggest some DNASE1L3 endonuclease enzyme function is retained. An SLE protective signal in PXK (lead SNP rs11130643) remained following conditioning on rs35677470. The DNASE1L3 206Cys risk variant maintained enzymatic activity, but secretion of the artificial and endogenous DNASE1L3 206Cys protein was substantially reduced.

SLE risk association in the DNASE1L3 locus is dependent on the missense SNP rs35677470, which confers a reduction in DNASE1L3 protein secretion but does not eliminate its DNase enzyme function.

10-Year natural course of early hip osteoarthritis in middle-aged persons with hip pain: a CHECK study.

Annals of the Rheumatic Diseases

To explore the natural course of hip osteoarthritis (OA) in a population of first-time presenters with hip complaints.

Data were collected at baseline and after 2, 5, 8 and 10 years on participants from the Cohort Hip and Cohort Knee study with early symptomatic hip OA. Descriptive statistics were used to analyse the natural course of the hip complaints with respect to clinical signs and symptoms, physical functioning and radiographic osteoarthritis (ROA) features.

In total, 588 participants were included with hip complaints and 86% completed the 10-year follow-up. The 10-year follow-up showed that 12% (69 participants) underwent hip replacement (HR), an increase of ROA of the hip (Kellgren and Lawrence score≥2) from 19% to 49%, and an increase in clinical hip OA according to the American College of Rheumatology criteria from 27% to 43%. All Western Ontario and McMaster Osteoarthritis Index subscales and physical activity remained on average constant during the 10-year follow-up for those who did not undergo an HR. The use of pain medication increased from 43% at baseline to 50% after 10 years.

One out of nine participants with early hip problems received an HR during the 10-year follow-up. Prevalence of clinical hip OA and hip ROA increased steadily during the 10-year follow-up. Overall, we observed more hip OA, but fewer or stable complaints with respect to clinical signs and symptoms, and physical functioning. So it could be cautiously concluded that after 10 years, first-time presenters with hip complaints either received an HR or their symptoms remained stable.

New EULAR/ACR 2019 SLE Classification Criteria: defining ominosity in SLE.

Annals of the Rheumatic Diseases

To determine the ominosity of the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Systemic Lupus Erythematosus Classification Criteria by determining its predictive role for disease severity in the first 5 years following diagnosis.

867 patients with systemic lupus erythematosus (SLE) from the Toronto Lupus Clinic were included (all first 12 months after SLE diagnosis). The EULAR/ACR criteria score was calculated based on baseline information. To determine disease severity in the first 5 years after diagnosis, adjusted mean SLE Disease Activity Index 2000 (AMS), flares, remission and immunosuppressive treatment were used as outcomes. The Systemic Lupus International Collaborating Clinics (SLICC) registry comprised the validation cohort.

Based on receiver operating characteristic analysis, a EULAR/ACR score of 20 was used as a threshold to compare outcomes between groups. In the first 5 years of disease course, patients with a score of ≥20 had higher AMS scores (p<0.001) and were more likely to ever experience a flare (p<0.001). These patients had lower probabilities of achieving remission and higher requirements for immunosuppressives. Results were confirmed in the SLICC validation cohort. Patients with a score of ≥20 had higher AMS during the first 5 years of disease (5.4 vs 3.1% and ≥20 vs <20 respectively, p≤0.001). The score correlated with AMS (r=0.43, p≤0.001) in the same time frame.

A EULAR/ACR score of ≥20 is an indicator of ominosity in SLE. Patients with a score of ≥20 were characterised by a more active disease course throughout the first 5 years. These criteria provide prognostic information regarding disease severity in the first 5 years following diagnosis.

Filgotinib in combination with methotrexate or as monotherapy versus methotrexate monotherapy in patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: the phase 3, randomised controlled FINCH 3 trial.

Annals of the Rheumatic Diseases

To investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure.

This 52-week, phase 3, multicentre, double-blind clinical trial (NCT02886728) evaluated once-daily oral filgotinib in 1252 patients with RA randomised 2:1:1:2 to filgotinib 200 mg with MTX (FIL200 +MTX), filgotinib 100 mg with MTX (FIL100 +MTX), filgotinib 200 mg monotherapy (FIL200), or MTX. The primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 24.

The primary endpoint was achieved by 81% of patients receiving FIL200+ MTX versus 71% receiving MTX (p<0.001). A significantly greater proportion treated with FIL100+ MTX compared with MTX achieved an ACR20 response (80%, p=0.017) at week 24. Significant improvement in Health Assessment Questionnaire-Disability Index was seen at week 24; least-squares mean change from baseline was -1.0 and -0.94 with FIL200+MTX and FIL100+MTX, respectively, versus -0.81 with MTX (p<0.001, p=0.008, respectively). Significantly higher proportions receiving FIL200+MTX (54%) and FIL100+MTX (43%) achieved DAS28(CRP) <2.6 versus MTX (29%) (p<0.001 for both) at week 24. Hierarchical testing stopped for comparison of ACR20 for FIL200 monotherapy (78%) versus MTX (71%) at week 24 (p=0.058). Adverse event rates through week 52 were comparable between all treatments.

FIL200+MTX and FIL100+MTX both significantly improved signs and symptoms and physical function in patients with active RA and limited or no prior MTX exposure; FIL200 monotherapy did not have a superior ACR20 response rate versus MTX. Filgotinib was well tolerated, with acceptable safety compared with MTX.