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.
The selection below is filtered by medical specialty. Registered users get access to the Plexa Intelligent Filtering System that personalises your dashboard to display only content that is relevant to you.
Want more personalised results?
Request AccessReal-life use of the PEXIVAS reduced-dose glucocorticoid regimen in granulomatosis with polyangiitis and microscopic polyangiitis.
Annals of the Rheumatic DiseasesThe PEXIVAS (Plasma exchange and glucocorticoids in severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis) trial showed that a reduced-dose glucocorticoid regimen (redGC) was non-inferior to a standard-dose regimen (standGC) with respect to death or end-stage kidney disease (ESKD) in patients with ANCA-associated vasculitis (AAV). However, the primary endpoint did not include disease progression or relapse, cyclophosphamide was the main induction therapy and rituximab (RTX)-treated patients tended to have a higher risk of death or ESKD with redGC. We aimed to evaluate the real-world use of redGC.
We conducted a retrospective, multicentre study comparing PEXIVAS redGC with standGC in patients with AAV. The primary composite outcome was the occurrence of death, ESKD, AAV progression before remission or relapse within the 12 months following induction. Inverse probability of treatment weighting was used to correct for baseline imbalance between groups. Factors associated with the occurrence of the primary outcome were estimated.
A total of 234 patients were included. The primary composite outcome occurred in 42/126 (33%) patients with redGC versus 20/108 (19%) with standGC. In unweighted multivariable analysis and in weighted analysis, redGC was independently associated with the primary outcome but not with death or ESKD. Among redGC-treated patients, those with serum creatinine>300 µmol/L were more likely to achieve the primary outcome. RTX-treated patients who received redGC were more likely to experience death or ESKD and to achieve the primary outcome.
In this study of patients with AAV primarily treated with RTX, redGC was associated with an increased risk of the primary outcome consisting of death, ESKD, AAV progression before remission or relapse.
Safety and Efficacy of Ianalumab in Patients With Sjögren's Disease: 52-Week Results From a Randomized, Placebo-Controlled, Phase 2b Dose-Ranging Study.
Arthritis RheumatolTo report 52-week safety and efficacy of ianalumab from phase 2b dose-finding study in patients with Sjögren's disease (SjD).
Patients randomly received (1:1:1:1) ianalumab (5, 50, or 300 mg) or placebo subcutaneously every 4 weeks till week 24 (treatment period [TP]1). At week 24, patients on 300 mg were re-randomized to continue 300 mg or receive placebo till week 52 (TP2), patients on placebo were switched to ianalumab 150 mg, while patients on 5 and 50 mg directly entered post treatment safety follow-up. Patients who discontinued treatment early or completed treatment entered safety follow-up (≥20 weeks).
During TP1, 190 patients were randomized (placebo=49, 5 mg=47, 50 mg=47, 300 mg=47). Of these 190 patients, 90 (47.4 %; 43 continued 300 mg and 47 received placebo) entered TP2, and 81/90 (90.0%) completed the study treatment. By week 52, efficacy was sustained in patients who continued 300 mg in TP2 (ESSDAI, ESSPRI, PaGA, PhGA change from week 24: -1.45, -0.46, -4.69, -6.86, respectively). Stimulated salivary flow rates and autoantibody levels numerically improved in the 300 mg group. Treatment-emergent adverse events were not dose-dependent, except for injection-site reactions. Cases of decreased neutrophil counts (CTCAE v4.03 grade 3 according to laboratory listings) were observed in 3 patients during the post-treatment follow-up, occurring at 3.5, 5.5, and 3 months, after the last ianalumab administration. None were associated with infection except one incidental finding of asymptomatic cytomegalovirus infection (IgM+).
In patients with SjD, ianalumab 300 mg demonstrated sustained efficacy through week 52 and a favorable safety profile up to two years of follow-up.
Psoriatic arthritis phenotype clusters and their association with treatment response: a real-world longitudinal cohort study from the psoriatic arthritis research consortium.
Annals of the Rheumatic DiseasesTo identify phenotype clusters and their trajectories in psoriatic arthritis (PsA) and examine the association of the clusters with treatment response in a real-world setting.
In the multicentre PsA Research Consortium (PARC) study, we applied factor analysis of mixed data to reduce dimensionality and collinearity, followed by hierarchical clustering on principal components. We then evaluated the transition of PsA clusters and their response to new immunomodulatory therapy and tumour necrosis factor inhibitor (TNFi).
Among 627 patients with PsA, three clusters were identified: mild PsA and psoriasis only (PsO) (Cluster 1, 47.4%), severe PsA and mild PsO (Cluster 2, 34.3%) and severe PsA and severe PsO (Cluster 3, 18.3%). Among 339 patients starting or changing, significant differences in response were observed (mean follow-up of 0.7 years, SD 0.8), with Cluster 3 showing the largest improvements in cDAPSA and PsAID. No differences were found among those starting TNFi (n=218). cDAPSA remission and PsAID patient acceptable symptom state were achieved in 10% and 54%, respectively. Clusters remained stable over time despite treatment changes, though some transitions occurred, notably from Cluster 3 to milder clusters.
Data-driven clusters with distinct therapy responses identified in this real-world study highlight the extensive heterogeneity in PsA and the central role of psoriasis and musculoskeletal severity in treatment outcomes. Concurrently, these findings underscore the need for better outcome measures, particularly for individuals with lower disease activity.
Incidence of and risk of mortality after hip fractures in Rheumatoid Arthritis relative to the general population.
Arthritis Care ResOsteoporosis, a known complication of rheumatoid arthritis (RA), increases the risk of hip fracture, which is associated with high morbidity and mortality. Fracture risk estimates in RA patients treated with contemporary treatment strategies are lacking. The objectives were 1) to estimate age- and sex-specific incidence rates and compare the risk of hip fractures in RA relative to age and sex-matched general population controls, and 2) to compare the risk of all-cause mortality in RA and general population controls after hip fracture.
A longitudinal study of a population-based incident cohort of RA patients diagnosed between 1997 and 2009, followed until 2014, with age- and sex-matched controls from the general population of British Columbia, using administrative health data. Hip fracture outcomes (ICD9-CM codes 820.0 or 820.2; ICD10-CA code S72.0 to S72.2) and mortality at pre-defined intervals after fracture (in-hospital, 90 days, 1-year, 5-year) were identified. Hip fracture incidence rates for RA and controls, and incidence rate ratios (IRR) were calculated. Cox proportional hazards models compared hip fracture and mortality risk in RA vs. controls; logistic regression compared in-hospital mortality risk.
Overall, 1314 hip fractures over 360,521 person-years were identified in 37,616 RA individuals and 2083 over 732,249 person-years in 75,213 controls, yielding a 28% greater fracture risk in RA (IRR 1.28 [95%CI, 1.20;1.37]). Mean age at time of fracture was slightly younger for RA than controls (79.6 + 10.8 vs. 81.6 + 9.3 yrs). Post-fracture mortality risk at 1- and 5-years did not differ between RA and general population controls. Results were similar in a sensitivity analysis including only RA individuals who received disease-modifying antirheumatic drugs (DMARDs).
People with RA had a greater risk of hip fractures, but no greater risk of mortality post fracture, than the general population. The relative risk of hip fractures observed was not as high as previously reported, likely reflecting better treatment of inflammation and management of osteoporosis and its risk factors.
Immunosuppressive Drugs in Early Limited Cutaneous Systemic Sclerosis May Prevent Global Damage Accrual.
Arthritis Care ResOrgan damage in systemic sclerosis (SSc) in individual organs such as the lungs may be prevented by immunosuppressive drugs (IS). A new measure of global organ damage, the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI), has allowed us to investigate whether IS may reduce global organ damage accrual in early SSc.
This was a retrospective study of patients with < 2 years disease duration in Canadian and Australian SSc cohorts. Patients with either limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) SSc were observed separately and divided into ever or never exposed to IS groups. The SCTC-DI was the outcome and inverse probability of treatment weighting (IPTW) was used to balance the study groups and to fit a marginal structural generalized estimating equation (GEE) model.
In the lcSSc cohort, there were 210 subjects of which 34% were exposed to IS at some time. Exposure to IS was associated with lower damage scores. In the dcSSc cohort, there were 192 subjects of which 76% were exposed to IS at some time. Exposure to IS was not associated with damage scores.
In this retrospective observational cohort study, using IPTW to adjust for confounders, we found a protective effect of the use of IS on damage accrual in lcSSc. We were unable to determine such an effect in dcSSc but unknown confounders may have been present and prospective studies of IS in dcSSc should include the SCTC-DI to determine the possible effect of IS on damage accrual.
Pharmacokinetics, Efficacy, and Safety of Upadacitinib in Pediatric Patients with Polyarticular-Course Juvenile Idiopathic Arthritis: An Interim Analysis of an Open-label, Phase 1 Trial.
Arthritis Care ResThis work aimed to evaluate the pharmacokinetics, efficacy, and safety of upadacitinib, an oral selective JAK inhibitor, in pediatric patients with polyarticular-course juvenile idiopathic arthritis (pcJIA).
In an open-label, phase 1 study (SELECT-YOUTH), enrolled patients, aged 2 to <18 years with pcJIA, received bodyweight-based upadacitinib doses using a twice-daily (BID) oral solution or once-daily (QD) extended-release tablet based on their body weight and ability to swallow tablets. The study included a 7-day pharmacokinetic assessment, followed by a long-term efficacy and safety evaluation for up to 156 weeks, including an additional long-term safety cohort. This interim analysis included available pharmacokinetic and safety data and efficacy data collected through Week 48.
A total of 57 patients received upadacitinib. The median time to maximum upadacitinib concentration was approximately 3 hours and 1 hour for the tablet and oral solution regimens, respectively; the harmonic mean functional half-life was approximately 5 hours and 2 hours, respectively. Juvenile idiopathic arthritis (JIA) American College of Rheumatology (ACR)30/50/70/90/100 responses at Week 12 were 91.8/89.8/69.4/49.0/32.7%, respectively. Efficacy was generally maintained through Week 48, and improvement in additional efficacy endpoints was also observed. At a median exposure duration of 412 days, 52 of 57 patients reported adverse events, of these 6 experienced serious adverse events. Adverse events were predominately mild to moderate in severity and consistent with the known safety profile of upadacitinib.
This interim analysis demonstrates that the bodyweight-based dosing regimen of upadacitinib was well tolerated and efficacious in pediatric patients with pcJIA.
National Institute of Health and Care Excellence Clinical Criteria for the Diagnosis of Knee Osteoarthritis: A Prospective Diagnostic Accuracy Study in Individuals with Type 2 Diabetes.
Arthritis Care ResThe National Institute of Health and Care Excellence (NICE) criteria for osteoarthritis (OA) obviate the need for physical exam or imaging, and their use may improve timely diagnosis of OA. However, they have not been validated.
Within a larger study of individuals with type 2 diabetes, participants with and without self-reported knee pain underwent assessment of the NICE criteria for knee OA by questionnaire (index test), and clinical evaluation for established or possible knee OA by a rheumatologist (reference standard). We calculated the sensitivity, specificity, likelihood ratio positive (LR+) and likelihood ratio negative (LR-) of the NICE criteria and modified NICE criteria without the stiffness criterion.
Our study included 96 participants: mean age 65.4 (SD 8.3) years and 52% were women. Individuals who fulfilled NICE criteria for knee OA (55.2%) included a spectrum of pain severity on a 11-point pain numeric rating scale with a median score of 5 (range: 1-9). Rheumatologist assessment identified 56 (58.3%) participants with symptomatic knee OA. The sensitivity, specificity, LR+, and LR- of NICE criteria for symptomatic knee OA were 0.84 (95% CI 0.74, 0.94), 0.85 (95% CI 0.74, 0.96), 5.6 and 0.19, respectively. For modified NICE criteria, these were 0.89 (95% CI 0.82, 0.97), 0.85 (95% CI 0.74, 0.96), 5.93 and 0.13.
The NICE criteria have high sensitivity and specificity for detecting symptomatic knee OA in a population with type 2 diabetes. We found that a modified version, omitting the stiffness criterion, performed similarly. These criteria should be validated in other settings and populations.
Oral glucocorticoids for skin fibrosis in early diffuse systemic sclerosis: a target trial emulation study from the European Scleroderma Trials and Research group database.
Arthritis Care ResThe objective of this study is to evaluate whether adding oral glucocorticoids to immunosuppressive therapy improves skin scores and ensures safety in patients with early diffuse cutaneous systemic sclerosis (dcSSc).
We performed an emulated randomized trial comparing the changes from baseline to 12±3 months of the modified Rodnan skin score (mRSS: primary outcome) in early dcSSc patients receiving either oral glucocorticoids (≤20 mg/day prednisone-equivalent) combined with immunosuppression (treated), or immunosuppression alone (controls), using data from the European Scleroderma Trials and Research Group. Secondary endpoints were the difference occurrence of progressive skin or lung fibrosis, and scleroderma renal crisis. Matching propensity score was used to adjust for baseline imbalance between groups.
We matched 208 patients (age 49 years; 33% male; 59% anti-Scl70), 104 in each treatment group, obtaining comparable characteristics at baseline. In the treated group, patients received a median prednisone dose of 5 mg/day. Mean mRSS change at 12±3 months was similar in the two groups (decrease of 2.7 [95% CI 1.4 - 4.0] in treated vs. 3.1 [95% CI 1.9 - 4.4] in control, p = 0.64). Similar results were observed in patients with shorter disease duration (≤ 24 months) or with mRSS ≤22. There was no between-group difference for all prespecified secondary outcomes. A case of scleroderma renal crisis occurred in both groups.
We did not find any significant benefit of adding low-dose oral glucocorticoids to immunosuppression for skin fibrosis, and at this dosage, glucocorticoid did not increase the risk of scleroderma renal crisis.
Barriers to Total Joint Arthroplasty: A Comparison of High-Poverty and Low-Poverty Communities.
Arthritis Care ResOur aim was to determine the most significant barriers to total joint arthroplasty (TJA) for people living in high-poverty communities relative to low-poverty communities.
We created a 21-question survey based on interviews with underrepresented minority patients with osteoarthritis targeting five barriers to TJA: trust in surgeon, recovery concerns, cost / insurance issues, fear of poor surgical outcomes, and timing considerations. Participants rated the importance of each barrier on a 5-point Likert scale, dichotomized into very / extremely important and not as important. The survey was distributed at New York City clinics and nationally through an arthritis advocacy group. We used geocoding to link addresses to census tracts, defining "high-poverty communities" as those with ≥20% of residents living below the poverty level. Logistic regression models assessed the association between community poverty status and rating barriers as very / extremely important, adjusting for demographic and clinical factors.
Of the 702 survey participants, 16.8% were residents of high-poverty communities. After adjustment, participants from high-poverty communities were more likely to rate trust in surgeon (adjusted odds ratio (aOR): 1.87 [1.24, 2.82]) and fear of poor surgical outcome (aOR: 1.68 [1.08, 2.61]) as very / extremely important.
People from high-poverty communities identified lack of trust in surgeons and fear of poor surgical outcomes as more significant barriers to TJA compared to people from low-poverty communities.
Evaluation and prediction of relapse risk in stable systemic lupus erythematosus patients after glucocorticoid withdrawal (PRESS): an open-label, multicentre, non-inferiority, randomised controlled study in China.
Annals of the Rheumatic DiseasesTo explore the relapse rate after glucocorticoid (GC) withdrawal with or without hydroxychloroquine (HCQ) maintenance in sustained clinically inactive systemic lupus erythematosus (SLE).
The PRESS trial is a multicentre, 33-week, open-label, three-arm, non-inferiority designed, randomised controlled trial. SLE patients with sustained clinically inactive disease who were maintained on low-dose GC plus HCQ therapy were screened and qualified patients were randomly assigned to three groups: drug-free group (both GC and HCQ withdrawal); HCQ group (discontinued GC but maintained HCQ); dual maintenance group (both GC and HCQ continued). The primary endpoint was to compare the proportion of patients experiencing a relapse as defined by the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index flare index by 33 weeks. Two parallel non-inferiority analyses were performed (drug-free group vs dual maintenance group and HCQ group vs dual maintenance group).
From 3 November 2016 to 13 August 2021, 333 participants complied with the protocol after randomisation were analysed. The relapse rates in the three groups were 26.1%, 11.2% and 4.7%, respectively. Compared with dual maintenance group, drug-free group failed to achieve non-inferiority significance (relapse rate difference 21.4%; 95% CI 12.3% to 30.5%; Pnon-inferiority=0.238), whereas HCQ group achieved non-inferiority (relapse rate difference 6.5%; 95% CI -0.5% to 13.5%; Pnon-inferiority=0.034). HCQ group also exhibited fewer relapses than drug-free group (p=0.006). Adverse events were similar among all three groups.
GC withdrawal may be feasible in sustained clinically inactive SLE patients. HCQ maintenance can exert a protective role in preventing disease relapse after GC withdrawal.
NCT02842814.
The essential roles of memory B cells in the pathogenesis of systemic lupus erythematosus.
Nature Reviews RheumatologyEmerging evidence indicates that memory B cells are dysfunctional in systemic lupus erythematosus (SLE). They are hyporesponsive to signalling thro...
Molecular basis for the disease-modifying effects of belimumab in systemic lupus erythematosus and molecular predictors of early response: blood transcriptome analysis implicates the innate immunity and DNA damage response pathways.
Annals of the Rheumatic DiseasesBelimumab is a putative disease-modifying agent in systemic lupus erythematosus (SLE), yet the molecular underpinnings of its effects and the ability to predict early clinical response remain unexplored. To address these, we undertook a longitudinal, in-depth blood transcriptome study.
RNA-sequencing was performed in the blood of active SLE patients at baseline and following 6 months of belimumab treatment (n=45 paired samples). Clinical response was determined according to the SLE Responder Index (SRI)-4 and Lupus Low Disease Activity State (LLDAS). Weighted correlation network analysis (WGCNA) was used to uncover gene module trait associations. Reversibility of SLE susceptibility and severity gene signatures was assessed. Machine learning was used to build models predictive of response.
Belimumab induced widespread transcriptome changes with downregulation of pathways related to B cells, type I/II interferon, IL-6/STAT3 and neutrophil activation. These effects were more pronounced among patients with LLDAS+ compared with to SRI-4+/LLDAS- response, with amelioration of the SLE 'susceptibility' signature observed in the former group. Unsupervised analysis unveiled gene modules enriched in neutrophil degranulation, type I interferon signalling and cytokine production to correlate positively with response at 6 months. Using neural networks, a set of 50 genes (including CCL4L2, CARD10, MMP15 and KLRC2) predicted response to belimumab with a cross-validated 84% specificity (test set). Lack of response was linked to perturbations of the cell cycle checkpoints, PI3K/Akt/mammalian target of rapamycin and TGF-beta signalling pathways.
Belimumab treatment ameliorates multiple innate and adaptive immunity dysregulations of SLE and may reverse the disease signature, consistent with the drug effects on reducing activity and preventing flares. Fingerprints of innate immunity correlate with robust improvement whereas DNA damage response with less responsive disease to BAFF inhibition.
