Sebastian Eduardo Sattui

Objectives: To study the implementation of the 2015 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) management recommendations for polymyalgia rheumatica (PMR) among rheumatologists and general practitioners (GPs). Methods: An online survey (Survey Monkey) comprising 28 questions was distributed among members of the EULAR Study Group on PMR and giant cell arteritis (n=375). Each member was asked to invite at least one GP (snowball principle) with experience in PMR to participate. Statistical analysis included descriptive statistics; differences were tested using Fisher’s exact test. Results: There were 308 respondents from 37 countries including data from 211 rheumatologists and 73 GPs. Adherence to the 2015 EULAR/ACR recommendations was higher among rheumatologists (83%) than GPs (35%). Rheumatologists (96%) prescribed glucocorticoids more frequently at dosages within the recommended range than GPs (84%). Concerning tapering, a similar proportion of rheumatologists (83%) and GPs (72%) reached the suggested 10 mg prednisone equivalent after 4–8 weeks. Almost all rheumatologists used methotrexate as a glucocorticoid-sparing agent (95%) as compared with only 26% of GPs. Similarly, 70% of rheumatologists, but only 2% of GPs, had experience with interleukin-6 receptor inhibitors for PMR. For follow-up, more rheumatologists preferred scheduled (as opposed to on demand) visits than GPs (99% vs 82%), while more GPs than rheumatologists (47% vs 31%) planned a short follow-up interval (4–8 weeks) in the first year of disease. Conclusion: Implementation of the EULAR/ACR recommendation for the management of PMR remains incomplete, particularly among GPs. Future updates should incorporate projects to foster diffusion and implementation of the recommendations among all professionals managing this disease.

Objective: Cognitive impairment is prevalent in rheumatoid arthritis (RA), yet risk factors are not well understood. We explored associations between clinical characteristics and cognitive impairment in an RA cohort. Methods: Data were from a longitudinal RA cohort at Veterans Affairs Puget Sound Health Care System. Cognition was evaluated using the Saint Louis University Mental Status (SLUMS) examination. Demographics and health factors, objectively measured physical function, participant‐reported symptoms, RA disease characteristics, and comorbidities were evaluated. Univariable linear regressions explored the association between clinical factors and SLUMS scores. Those with P < 0.1 in the univariable models were evaluated in separate multivariable linear regressions controlling for age, sex, and years of education. Results: A total of 145 participants with RA were included, with a mean age of 64.5 (SD 11.6) years, and were predominantly male (74%). Using SLUMS, 42 participants (29%) had normal cognition, 83 (57%) had mild cognitive impairment, and 20 (14%) had dementia. Physical performance (aβ: 0.35, confidence interval [CI] 0.11 to 0.59), self‐reported exhaustion (aβ: −2.22, CI −3.44 to −0.99), pain (aβ: −0.25, CI −0.50 to −0.00), disability (aβ: −1.79, CI −3.16 to −0.42), and trouble falling asleep (aβ: −2.57, CI −4.00 to −1.14) were all independently associated with a lower SLUMS score (all P < 0.05). Conclusion: Cognitive impairment was prevalent in our cohort of veterans with RA and was associated with several modifiable clinical factors. Future longitudinal studies are needed to determine the directionality of these associations and evaluate interventions for modifiable risk factors that may mitigate cognitive dysfunction. image

The Reducing Inflammation for Greater Health Trial's (RIGHT) study is a single‐center, randomized, double‐blind, placebo‐controlled trial designed to test whether clazkizumab, an interleukin‐6 (IL‐6) inhibitor, can improve or slow decline in physical, cognitive, and vascular function in older adults, when compared to a placebo. The trial will enroll participants meeting the following inclusion criteria: (1) ≥ 70 years of age, (2) with low to moderate physical function, defined as self‐reported difficulty walking 1/4 mile or climbing a flight of stairs, but able to walk 400 m at baseline exam, (3) usual walking speed between ≥ 0.44 and < 1.0 m/s on a 4‐m walk or a body mass index of ≥ 28 kg/m ² , (4) average IL‐6 level between 2.0 and 30 pg/mL on two tests, and (5) no active infection, cancer, or other serious health conditions. Clazakizumab, a monoclonal antibody targeting IL‐6, 5 mg via subcutaneous injection every 4 weeks for 24 weeks compared to a placebo. The primary outcome will be walking speed over 400 m. Secondary outcomes include other measures of physical function (short physical performance battery, oxygen consumption with walking on a treadmill, fatigability), cognitive function, vascular stiffness and endothelial function, IL‐6 and C‐reactive protein levels, other markers of inflammation, safety, and tolerability. Findings will evaluate acceptability, safety and 6‐months change in mobility and other outcomes. The study was approved by the IRB and is registered with ClinicalTrials.gov (NCT05727384). The RIGHT study will inform the geroscience hypothesis that modifying aging itself will lead to improvement in multiple aspects of health.

Objective: We quantified the prevalence of self‐reported frailty and identified associated factors in a US‐wide cohort of people with rheumatic and musculoskeletal diseases (RMDs).Methods: Frailty was measured using the FRAIL scale, a patient‐reported frailty instrument, in FORWARD, The US‐based National Databank for Rheumatic Diseases. Frailty prevalence was determined overall and by individual RMD, which included rheumatoid arthritis, connective tissue diseases (CTDs), osteoarthritis (OA), fibromyalgia, spondyloarthritis (SpA), and vasculitis. Multivariable logistic regression models evaluated the cross‐sectional associations between RMDs and frailty, as well as factors associated with frailty within each RMD.Results: Among 4,345 individuals, 1,422 were frail (33%). Participants were on average 67.1 ± 11.6 years of age, 82% were female, and 89% self‐identified as White. Difficulty with ambulation was the most common frailty feature. With OA as referent, those with CTD had a higher odds of frailty (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.01–2.04), and those with SpA had a lower odds (OR 0.45, 95% CI 0.31–0.67). Age, female sex, pain, disease severity, disease duration, and elevated body mass index categories were all associated with frailty. In the RMD‐stratified analyses, disease severity remained associated with frailty in all RMDs except vasculitis.Conclusion: Frailty was present in 1 in 3 participants with RMDs, a higher prevalence than estimates from the general population, and primarily manifests as difficulty with mobility. Disease severity was consistently associated with an increased odds of frailty across RMDs. Future interventions to improve physical activity and prevent disease damage may improve frailty status in people with RMDs.

For years, polymyalgia rheumatica (PMR) has been conceptualized as a condition with a relatively benign disease course typified by bilateral shoulder pain and stiffness that requires a limited glucocorticoid taper in most.¹ However, over the past decade, our understanding of PMR, including its immunopathogenesis, heterogeneity in disease course, and effect on patients9 health-related quality of life (HRQOL) and functioning, has dramatically evolved.

Objective: The number of randomized clinical trials (RCTs) with patients with idiopathic inflammatory myopathies (IIMs) has grown exponentially over the last decade. Race, ethnicity, and sex reporting and representation of participants as well as the geographic distribution of enrolling sites in IIM RCTs are unknown. This information can provide critical insights into the current state of enrollment practices and generalizability in IIM RCTs.Methods: A systematic literature review assessed IIM RCTs published between 2010 to 2023. Sex and gender reporting was analyzed per Sex and Gender Equity in Research guidelines. Appropriate reporting of race and ethnicity was defined as reporting them for all trial participants. Countries were categorized based on the Human Development Index. US enrollment sites were grouped using the National Center for Health Statistics Urban‐Rural Classification Scheme and medically underserved areas (MUAs).Results: Of the 19 RCTs included, race was appropriately reported in 58%. Black, Asian, and Hispanic or Latino participants represented 3%, 7%, and 2% of the enrollees, respectively. Ethnicity was only reported in 26% of RCTs, and 16% conflated race and ethnicity. Temporal trends showed encouraging results for race and ethnicity representation. Most trials (90%) had greater than 45% women participants. Geographic regions of sites included North America, Europe, Asia, and Australasia, with no sites in South America or Africa. The majority of US sites were located in large metropolitan areas, whereas none were in nonmetropolitan areas, and only 31% in MUAs.Conclusion: Racial, ethnic, and geographic representation in IIM RCTs remains a critical issue. Inadequate reporting of race and ethnicity and limited sociodemographic and geographic representation of participants raise concerns about the generalizability of findings of IIM RCTs.

Objective: To describe the frequency and outcomes associated with self-reported frailty in patients with vasculitis.Methods: VascStrong is a longitudinal study using the Vasculitis Patient-Powered Research Network, an internet-based cohort of patients with vasculitis. Data collected included patient global assessment (PtGA) and several domains of the Patient-Reported Outcomes Measurement Information System (PROMIS). Frailty was measured at baseline and 1-year follow-up using the FRAIL scale, a 5-domain self-reported measure. Patients were classified as nonfrail, prefrail, and frail based on 0, 1-2, or ≥ 3 criteria, respectively. At follow-up, patients reported the occurrence over the prior year of hospitalizations, infections, fractures, and disease flares. A multivariable logistic regression was performed to identify factors associated with frailty.Results: The baseline survey included 328 patients. Patients had a mean age of 59.5 years, were predominantly female (71.6%) and non-Hispanic White. Prevalence of prefrailty and frailty was 42.1% and 21.6%, respectively. The majority of patients with each form of vasculitis were classified as frail or prefrail. Prefrail and frail patients reported worse PROMIS scores at baseline and follow-up. Frailty was independently associated with female sex, higher PtGA scores, being overweight, and obesity, but not with age. At 1 year, 272 of 328 (82.9%) patients answered the follow-up survey. Transitions in frailty status were observed in 99 (36.4%) patients. Hospitalizations and flares were more frequent in frail patients.Conclusion: Self-reported frailty or prefrailty is common in the majority of patients with multiple forms of vasculitis, indicating there is a substantial subset of patients at risk for worse outcomes.

Objectives: To evaluate the efficacy and safety of avacopan in patients aged ≥65 years with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in the phase 3 ADVOCATE trial of avacopan vs a prednisone taper, plus either rituximab or cyclophosphamide. Methods: In this descriptive, post hoc analysis, patients receiving avacopan or a prednisone taper were stratified by age. Key efficacy outcomes included the rate of remission at week 26 and sustained remission at week 52. Results: Of 160 patients aged ≥65, 109 were aged 65–74 and 51 were ≥75. Remission at week 26 was achieved in 71.7% vs 69.4% of patients aged 65–74 and 73.1% vs 72.0% aged ≥75 in the avacopan vs prednisone taper groups, respectively. Sustained remission at week 52 was observed in 65.0% vs 55.1% of patients aged 65–74 and 65.4% vs 56.0% aged ≥75. Relapse rates in the avacopan vs prednisone taper groups were 12.3% vs 18.8% and 3.8% vs 20.8% in the 65–74 and ≥75 subgroups, respectively. Improvements in estimated glomerular filtration rate and health-related quality of life were observed in both treatment groups. Use of avacopan compared with a prednisone taper was associated with a 61% and 49% reduction in mean glucocorticoid dose in the 65–74 and ≥75 subgroups, respectively, and lower glucocorticoid toxicity. The proportions of patients with adverse events were similar between treatment groups within each age subgroup. Conclusion: These data support the efficacy and safety of an avacopan-based regimen to treat patients with GPA or MPA aged ≥65.