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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Risk prediction modeling based on a combination of initial serum biomarkers in myositis-associated interstitial lung disease.Arthritis Rheumatol
To establish predictive models for mortality in patients with polymyositis/dermatomyositis (PM/DM)-associated interstitial lung disease (ILD) using a combination of initial serum biomarkers.
A multicenter JAMI cohort database of 497 incident cases of PM/DM-ILD was used as a derivation cohort, and 111 cases were additionally collected as a validation cohort. Risks for predicting all-cause mortality were identified by univariate and multivariable Cox regression analyses using candidate serum biomarkers as explanatory variables. The predictive models for mortality were generated in patients with and without anti-melanoma differentiation-associated gene 5 (MDA5) antibody, using a combination of risk factors. Cumulative survival rates were assessed using Kaplan-Meier analysis, and were compared between the subgroups with Breslow test.
In a derivation cohort, C-reactive protein (CRP) and Krebs von den Lungen-6 (KL-6) were identified as independent risk factors for mortality in both anti-MDA5-positive and negative patients. We then developed a prediction model termed MCK (MDA5, CRP, and KL-6) model, identifying patients at low (<15%), moderate (15-50%), or high risk (≥50%) of mortality, based on the number of risk factors. The MCK model successfully differentiated cumulative survival rates in anti-MDA5-positive patients (P < 0.01 between low and moderate risk and P = 0.03 between moderate and high risk) and in anti-MDA5-negative patients (P < 0.001 between low and moderate risk). Utility of the MCK model was replicated in the validation cohort.
The evidence-based risk prediction model using CRP and KL-6 combined with anti-MDA5 antibody might be useful for predicting prognosis in patients with PM/DM-ILD.
Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines.Nature Reviews Rheumatology
Knee osteoarthritis (OA) is a heterogeneous disease associated with substantial effects on quality of life, and its clinical management is difficul...
Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme.Annals of the Rheumatic Diseases
This integrated analysis presents the safety profile of upadacitinib, a Janus kinase inhibitor, at 15 mg and 30 mg once daily in patients with moderately to severely active rheumatoid arthritis (RA).
Treatment-emergent adverse events (TEAEs) and laboratory data from five randomised, placebo- or active-controlled phase III trials of upadacitinib for patients with RA were analysed and summarised. Exposure-adjusted event rates are shown for placebo (three trials; 12/14 weeks), methotrexate (two trials; mean exposure: 36 weeks), adalimumab (one trial; mean exposure: 42 weeks), upadacitinib 15 mg (five trials; mean exposure: 53 weeks) and upadacitinib 30 mg (four trials; mean exposure: 59 weeks).
3834 patients received one or more doses of upadacitinib 15 mg (n=2630) or 30 mg (n=1204), for a total of 4020.1 patient-years of exposure. Upper respiratory tract infection, nasopharyngitis and urinary tract infection were the most commonly reported TEAEs with upadacitinib. Rates of serious infection were similar between upadacitinib 15 mg and adalimumab but higher compared with methotrexate. Rates of herpes zoster and creatine phosphokinase (CPK) elevations were higher in both upadacitinib groups versus methotrexate and adalimumab, and rates of gastrointestinal perforations were higher with upadacitinib 30 mg. Rates of deaths, malignancies, adjudicated major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs) were similar across treatment groups.
In the phase III clinical programme for RA, patients receiving upadacitinib had an increased risk of herpes zoster and CPK elevation versus adalimumab. Rates of malignancies, MACEs and VTEs were similar among patients receiving upadacitinib, methotrexate or adalimumab.
SELECT-EARLY: NCT02706873; SELECT-NEXT: NCT02675426; SELECT-COMPARE: NCT02629159; SELECT-MONOTHERAPY: NCT02706951; SELECT-BEYOND: NCT02706847.
Axial involvement in patients with early peripheral spondyloarthritis: a prospective MRI study of sacroiliac joints and spine.Annals of the Rheumatic Diseases
To assess axial involvement on MRI in early peripheral spondyloarthritis (pSpA) and to evaluate whether axial inflammation predicts relapse on treatment withdrawal.
Fifty-six patients with early, active, newly diagnosed pSpA underwent MRI of the sacroiliac joints (SIJs) and spine prior to golimumab initiation. At sustained clinical remission of pSpA, treatment was withdrawn and a second MRI was performed. Bone marrow oedema (BME) was scored by three readers according to the Spondyloarthritis Research Consortium of Canada (SPARCC) method. Scores were compared with an axial spondyloarthritis cohort (Belgian Arthritis and Spondylitis cohort). Structural lesions were assessed using a similar method. Furthermore, fulfilment of the Assessment of Spondyloarthritis International Society (ASAS) definition of a positive MRI for sacroiliitis was assessed. Spinal images were evaluated for BME and structural lesions using the Canada-Denmark MRI spine scoring system by two readers.
Thirty-six per cent showed SIJ BME at baseline, all fulfilling the ASAS definition of sacroiliitis. No association with back pain was found. Twenty-one per cent displayed SIJ structural lesions. Spinal BME was limited: the median inflammation scores were low and no patients had ≥5 inflammatory corner lesions. On clinical remission, a significant decrease in SIJ SPARCC scores was detected. On clinical remission, no significant differences in SIJ SPARCC scores were noted between patients relapsing and those maintaining remission after treatment discontinuation.
In patients with early pSpA, a surprisingly high prevalence of sacroiliitis on MRI was observed; SPARCC scores decreased significantly on tumour necrosis factor inhibition. Residual inflammation on MRI was not predictive of relapse of peripheral manifestations. No relevant inflammatory spinal involvement was detected. Collectively, our findings suggest a higher inflammatory burden in patients with early pSpA than anticipated.
Precise targeting of miR-141/200c cluster in chondrocytes attenuates osteoarthritis development.Annals of the Rheumatic Diseases
Despite preclinical studies involving miRNA therapeutics conducted in osteoarthritis (OA) over the years, none of these miRNAs have yet translated to clinical applications, owing largely to the lack of efficient intra-articular (IA) delivery systems. Here, we investigated therapeutic efficacy of the chondrocyte-specific aptamer-decorated PEGylated polyamidoamine nanoparticles (NPs)-based miRNAs delivery for OA.
The role of miR-141/200c cluster during skeletal and OA development was examined by miR-141/200cflox/flox mice and Col2a1-CreERT2; miR-141/200cflox/flox mice. Histological analysis was performed in mouse joints and human cartilage specimens. Chondrocyte-specific aptamer-decorated NPs was designed, and its penetration, stability and safety were evaluated. OA progression was assessed by micro-CT analysis, X-ray and Osteoarthritis Research Society International scores after destabilising the medial meniscus surgery with miR-141/200c manipulation by NPs IA injection. Mass spectrometry analysis, molecular docking and molecular dynamics simulations were performed to investigate the interaction between aptamer and receptor.
Increased retention of NPs inside joint space is observed. The NPs are freely and deeply penetrant to mice and human cartilage, and unexpectedly persist in chondrocytes for at least 5 weeks. OA chondrocytes microenviroment improves endo/lysosomal escape of microRNAs (miRNAs). Therapeutically, IA injection of miR-141/200c inhibitors provides strong chondroprotection, whereas ectopic expression of miR-141/200c exacerbates OA. Mechanistically, miR-141/200c promotes OA by targeting SIRT1, which acetylates histone in the promoters of interleukin 6 (IL-6), thereby activating IL-6/STAT3 pathway.
Our findings indicate that this nanocarrier can optimise the transport kinetics of miR-141/200c into chondrocytes, fostering miRNA-specific disease-modifying OA drugs development.
2015 American College of Rheumatology Workforce Study and Demand Projections of Pediatric Rheumatology Workforce, 2015-2030.Arthritis Care Res
Describe the character and composition of the 2015 pediatric rheumatology workforce in the United States (US), evaluate current workforce trends, and project future supply and demand of pediatric rheumatology workforce through 2030.
The American College of Rheumatology (ACR) created the Workforce Study Group (WSG) to study the rheumatology workforce. The WSG used primary and secondary data to create a representative workforce model. Pediatric rheumatology supply and demand was projected through 2030 using an integrated data-driven framework to capture a more realistic clinical full-time equivalent (FTE) and produce a better picture of access to care issues in pediatric rheumatology.
The 2015 pediatric workforce was estimated at 287 FTE (300 providers), while the estimated excess demand was 95 (33%). The projected demand will continue to increase to almost 100% (N=230) by 2030 if no changes occur in succession planning, new graduate entrants into the profession, and other factors associated with the workforce.
This study projects that the pediatric rheumatology workforce gap will continue to worsen significantly from the 2015 baseline, and by 2030 the demand for pediatric rheumatologists will be twice the supply. Innovative strategies are needed to increase the workforce supply and to improve access to care.
Combined genetic analysis of juvenile idiopathic arthritis clinical subtypes identifies novel risk loci, target genes and key regulatory mechanisms.Annals of the Rheumatic Diseases
Juvenile idiopathic arthritis (JIA) is the most prevalent form of juvenile rheumatic disease. Our understanding of the genetic risk factors for this disease is limited due to low disease prevalence and extensive clinical heterogeneity. The objective of this research is to identify novel JIA susceptibility variants and link these variants to target genes, which is essential to facilitate the translation of genetic discoveries to clinical benefit.
We performed a genome-wide association study (GWAS) in 3305 patients and 9196 healthy controls, and used a Bayesian model selection approach to systematically investigate specificity and sharing of associated loci across JIA clinical subtypes. Suggestive signals were followed-up for meta-analysis with a previous GWAS (2751 cases/15 886 controls). We tested for enrichment of association signals in a broad range of functional annotations, and integrated statistical fine-mapping and experimental data to identify target genes.
Our analysis provides evidence to support joint analysis of all JIA subtypes with the identification of five novel significant loci. Fine-mapping nominated causal single nucleotide polymorphisms with posterior inclusion probabilities ≥50% in five JIA loci. Enrichment analysis identified RELA and EBF1 as key transcription factors contributing to disease risk. Our integrative approach provided compelling evidence to prioritise target genes at six loci, highlighting mechanistic insights for the disease biology and IL6ST as a potential drug target.
In a large JIA GWAS, we identify five novel risk loci and describe potential function of JIA association signals that will be informative for future experimental works and therapeutic strategies.
Brodalumab in psoriatic arthritis: results from the randomised phase III AMVISION-1 and AMVISION-2 trials.Annals of the Rheumatic Diseases
To compare the efficacy and safety of brodalumab, an interleukin-17 receptor subunit A inhibitor, with placebo, in patients with psoriatic arthritis (PsA).
Adult patients with active PsA and inadequate response to, or intolerance to, conventional treatment were enrolled into two phase III studies (NCT02029495 and NCT02024646) and randomised 1:1:1 to receive subcutaneous brodalumab 140 mg or 210 mg or placebo at weeks 0, 1 and every 2 weeks up to 24 weeks. About 30% of patients had prior use of biologics. The primary endpoint for both studies was the American College of Rheumatology 20 (ACR20) response at week 16.
962 patients were randomised across the studies prior to early termination due to sponsor decision. The primary endpoint was met in both studies. Based on comparable design and eligibility criteria, data from both studies were pooled. Significantly more patients achieved ACR20 at week 16 in both brodalumab treatment groups (45.8% and 47.9% for 140 mg and 210 mg, respectively) versus placebo (20.9%) (p<0.0001). Similar results were observed at week 24. Significantly higher proportions of patients receiving brodalumab achieved ACR50/70, Psoriasis Area and Severity Index 75/90/100 and resolution of dactylitis and enthesitis versus placebo (p<0.01). Adverse event rates were similar across treatments at week 16 (54.4%, 51.6% and 54.5% for placebo, brodalumab 140 mg and 210 mg, respectively). No new safety signals were reported.
Brodalumab was associated with rapid and significant improvements in signs and symptoms of PsA versus placebo. Brodalumab was well tolerated, with a safety profile consistent with other interleukin-17 inhibitors.
Factors associated with treatment response in patients with idiopathic inflammatory myopathies. A registry-based study.Arthritis Care Res
To identify predictors of response to immunosuppressive therapy after one year, with a focus on autoantibodies, in patients newly diagnosed with idiopathic inflammatory myopathies (IIM) followed longitudinally in an electronic registry.
We assessed the association between autoantibody-defined groups and improvement according to ACR/EULAR 2016 response criteria.
We identified 156 patients; of them, 111 patients (71%) were positive for any autoantibody tested, 90% received glucocorticoid treatment at baseline, and 78% received immunosuppressive drugs at some follow-up point. After one year from the index date, the overall median improvement score was 27.5 (IQR 10-51). No differences were observed in the total improvement score between the autoantibody-defined groups. Sixty-two percent of patients (n = 96) showed a minimal response, 38% (n = 60) achieved a moderate response, and 19% (n=30) achieved a major response. Regarding the different levels of response, DM-specific autoantibodies were associated with a moderate response versus the seronegative group (reference), OR 4.12 (95% CI 1.2-16.5). In addition, dysphagia, time from symptom onset to diagnosis, and initial glucocorticoid dose were significant predictors of response after one year of follow up.
Patients with DM-specific autoantibodies achieved better levels of response compared to other autoantibody-defined groups. Dysphagia, shorter time span from symptom onset to diagnosis and intensive initial immunosuppressive treatment were associated with a higher response rate after one year of pharmacological treatment from the index date, regardless of autoantibody status.
Treatment of Sarcoidosis in U.S. Rheumatology Practices: Data from ACR's Rheumatology Informatics System for Effectiveness (RISE) Registry.Arthritis Care Res
Sarcoidosis is often treated with glucocorticoids, although the use of biologics is growing. Prescribing patterns for biologics for sarcoidosis patients in U.S. rheumatology practices have never been examined. Given that there are no steroid-sparing FDA-approved therapies for sarcoidosis, we sought to characterize the real-world treatment of sarcoidosis and to assess practice-level variation in prescribing patterns.
We conducted an observational study of sarcoidosis patients using data from the Rheumatology Informatics System for Effectiveness (RISE) registry (2014-2018). The RISE registry represents an estimated 32% of the U.S. clinical rheumatology workforce. Adult patients with ≥ 2 codes for sarcoidosis ≥ 30 days apart were included. We examined sarcoidosis-specific medication use at any time during the study period. Data was analyzed at the practice level.
A total of 3276 patients with sarcoidosis from 184 practices were included. 75.1% were women; with mean age 59.0 ± 12.5; 48.3% were White and 27.6% were Black. Overall, 59.3% of patients were prescribed glucocorticoids; 24.7% received prolonged glucocorticoid therapy (≥10 mg/day for 90 days). 12.1% received a biologic or targeted synthetic disease modifying drug (tsDMARD), most commonly TNF inhibitors. There was wide practice-level variation among 31 practices with ≥ 30 sarcoidosis patients: biologic use ranged from 15.6% to 69.2%; infliximab represented the most common biologic prescribed.
In a large sample of U.S. rheumatology practices, 12.1% of patients with sarcoidosis received biologics or tsDMARD. We found high variability in biologic use across practices. The significant use of long-term glucocorticoids suggests unmet therapeutic needs in this patient population.
Hydroxychloroquine: Not a Heart Breaker!Arthritis Care Res
Prior to 2020, there was a lack of general awareness of hydroxychloroquine's (HCQ) and chloroquine's (CQ) potential for cardiac arrhythmias, as rhe...
Reproducibility of the Six-Minute Walk Test in Children and Youth with Juvenile Idiopathic Arthritis.Arthritis Care Res
While the six-minute walk test (6MWT) is increasingly being used in research to evaluate functional exercise capacity of children with juvenile idiopathic arthritis (JIA), psychometric properties with this population have not been well evaluated. The objective of this study was to evaluate reproducibility (agreement and test re-test reliability) and to determine standard error of measurement and smallest detectable difference in children and youth with juvenile idiopathic arthritis.
Participants (n=22, x - age =13.1±1.1 years, 63.6% females) completed a 6MWT as part of their routine clinical assessment and repeated it in the same clinical setting with the same rater ( x - = 8 ± 1.2 days later).
ICC (95% CI) was 0.86 (0.66-0.94), standard error of measurement and smallest detectable difference were 23.5 and 65.1 meters, respectively.
The results provide evidence of good-excellent reproducibility of the 6MWT with children and youth with JIA and support the use of the 6MWT as a measure of exercise capacity in clinical practice and research.