ACR Open Rheumatology最新文献

Objective: Self-efficacy, the internal belief that one can perform a specific task successfully, influences behavior. To promote critical appraisal of medical literature, rheumatology training programs should foster both competence and self-efficacy for critical appraisal. This study aimed to investigate whether select items from the Clinical Research Appraisal Inventory (CRAI), an instrument measuring clinical research self-efficacy, could be used to measure critical appraisal self-efficacy (CASE).

Methods: One hundred twenty-five trainees from 33 rheumatology programs were sent a questionnaire that included two sections of the CRAI. Six CRAI items relevant to CASE were identified a priori; responses generated a CASE score (total score range 0-10; higher = greater confidence in one's ability to perform a specific task successfully). CASE scores' internal structure and relation to domain-concordant variables were analyzed.

Results: Questionnaires were completed by 112 of 125 (89.6%) trainees. CASE scores ranged from 0.5 to 8.2. The six CRAI items contributing to the CASE score demonstrated high internal consistency (Cronbach's α = 0.95) and unidimensionality. Criterion validity was supported by the findings that participants with higher CASE scores rated their epidemiology and biostatistics understanding higher than that of peers (P < 0.0001) and were more likely to report referring to studies to answer clinical questions (odds ratio 2.47, 95% confidence interval 1.41-4.33; P = 0.002). The correlation of CASE scores with percentage of questions answered correctly was only moderate, supporting discriminant validity.

Conclusion: The six-item CASE instrument demonstrated content validity, internal consistency, discriminative capability, and criterion validity, including correlation with self-reported behavior, supporting its potential as a useful measure of critical appraisal self-efficacy.

Objective: Evobrutinib is a highly selective, orally administered Bruton's tyrosine kinase (BTK) inhibitor. The objective of this phase II, multicenter, randomized, double-blind, placebo-controlled trial was to evaluate the efficacy and safety of evobrutinib in patients with active autoantibody-positive systemic lupus erythematosus (SLE).

Methods: Patients were diagnosed with SLE by either the Systemic Lupus International Collaborating Clinics criteria or at least four American College of Rheumatology criteria 6 months or more prior to screening, had an SLE Disease Activity Index-2000 score of 6 or more, were autoantibody-positive and on standard-of-care therapy. Randomization was 1:1:1:1 to oral evobrutinib 25 mg once daily (QD), 75 mg QD, 50 mg twice daily, or placebo. Primary efficacy endpoints were SLE responder index (SRI)-4 response at week 52 and SRI-6 response at week 52 in the high disease activity subpopulation. Safety endpoints included treatment-emergent adverse events (TEAEs).

Results: A total of 469 patients were randomized and received at least one dose of evobrutinib or placebo at the time of primary analysis. Mean (SD) age at baseline was 40.7 (±12.3) years; 94.9% of patients were female. Neither primary efficacy endpoint was met. All doses of evobrutinib were well tolerated, and there was no clear dose effect on the incidence of reported TEAEs, or serious TEAEs, including severe infections.

Conclusion: This phase II, dose-ranging trial in SLE failed to show a treatment effect of evobrutinib versus placebo at any dose. Evobrutinib was generally well tolerated, with no dose effect observed for TEAEs. These results suggest that BTK inhibition does not appear to be an effective therapeutic intervention for patients with SLE.

Objective: Giant cell arteritis (GCA) requires treatment with high-dose, long-term glucocorticoids (GCs). A score assessing and quantifying patients' baseline GC-related toxicity may be important to risk stratification and therapeutic decision-making in patients initiating immunosuppression.

Methods: We analyzed patients with GCA enrolled in the Tocilizumab in Giant Cell Arteritis (GiACTA) trial. Baseline GC-related toxicity scores for 12 domains were derived from the Glucocorticoid Toxicity Index using baseline medications, medical history, vital signs, and laboratory values. The 12 domains examined were body mass index, glucose tolerance, blood pressure, lipid metabolism, bone and/or tendon, GC myopathy, skin toxicity, neuropsychiatric effects, infection, ocular toxicity, gastrointestinal injury, and adrenal function. Potential scores ranged from 0 to 538. We compared differences between those with newly diagnosed versus relapsing disease at baseline.

Results: A total of 250 patients were included (75% female, mean age 69 years). The mean ± SD baseline GC-related toxicity score among all patients was 111.3 ± 53.2. The domains that contributed most to the overall scores were blood pressure (24.0% of the overall score), followed by glucose tolerance (22.6%) and neuropsychiatric effects (15.9%). Baseline GC-related toxicity scores were higher in patients with relapsing disease compared with those with newly diagnosed disease (mean of 122.5 vs. 98.9; P < 0.001). The body mass index and neuropsychiatric domain scores were significantly higher in patients with relapsing disease.

Conclusion: This approach to the assessment of baseline GC-related toxicity distinguished patients with relapsing GCA from those with newly diagnosed disease. Baseline GC-related toxicity scores may be useful in therapeutic decision-making for patients beginning immunosuppressive treatment.

Objective: To evaluate effects of general osteoarthritis (OA) information in addition to a treatment option grid and general practitioner (GP) recommendation to exercise on treatment beliefs and intentions.

Methods: An online randomized trial of 735 people 45 years old or older without OA who were recruited from a consumer survey network. Participants read a hypothetical scenario about visiting their GP for knee problems and were randomized to the following: i) 'general information', ii) 'option grid' (general information plus option grid), or iii) 'option grid plus recommendation' (general information plus option grid plus GP exercise recommendation). The primary outcome was an agreement that exercise is the best management option (0-10 numeric rating scale; higher scores indicating higher agreement that exercise is best). The secondary outcomes were beliefs about other management options and management intentions. Linear regression models estimated the mean (95% confidence interval [CI]) between-group difference in postintervention scores, adjusted for baseline.

Results: Option grid plus recommendation led to higher agreement that exercise is the best management by a mean of 0.4 units (95% CI: 0.1-0.6) compared with general information. There were no other between-group differences for the primary outcome. Option grid led to higher agreement that surgery was best, and x-rays were necessary, compared with general information (mean between-group differences: 0.7 [CI: 0.2-1.1] and 0.5 [CI: 0.1-1.0], respectively) and option grid plus recommendation (0.5 [CI: 0.1-0.9] and 0.9 [CI: 0.4-1.3]).

Conclusion: Addition of an option grid and GP exercise recommendation to general OA information led to more favorable views that exercise was best for the hypothetical knee problem. However, differences were small and of unclear clinical importance.

Objective: The rationale for this study was based on reports that valosin-containing protein (VCP) mutations are found in hereditary inclusion body myositis (IBM) and VCP was detected in rimmed vacuoles of sporadic IBM (sIBM) muscle biopsies. Autoantibodies to VCP have not been reported in sIBM or other inflammatory myopathies (IIMs). The aim of this study was to determine the frequency and clinical significance of anti-VCP antibodies in sIBM and other IIMs.

Methods: Sera were collected from 73 patients with sIBM and 383 comparators or controls, including patients with IIM (n = 69), those with juvenile dermatomyositis (JDM) (n = 67), those with juvenile idiopathic arthritis (JIA) (n = 47), those with primary biliary cholangitis (PBC) (n = 105), controls that were age matched to patients with sIBM (similarly aged controls [SACs]) (n = 63), and healthy controls (HCs) (n = 32). Immunoglobulin G antibodies to VCP were detected by addressable laser bead immunoassay using a full-length recombinant human protein.

Results: Among patients with sIBM, 26.0% (19/73) were positive for anti-VCP. The frequency in disease controls was 15.0% (48/320). Among SACs, the frequency was 1.6% (1/63), and in HCs 0% (0/32). Frequencies were 17.5% (11/63) for IIM, 25.7% (27/105) for PBC, 3.0% (2/67) for JDM, and 17.0% (8/47) for JIA. The sensitivity, specificity, positive predictive value, and negative predictive value of anti-VCP for sIBM were 26.0%, 87.2%, 28.4%, and 85.9%, respectively. Of patients with sIBM, 15.1% (11/73) were positive for both anti-VCP and anti-cytosolic 5'-nucleotidase 1A (NT5c1A). Eleven percent of patients (8/73) were positive for anti-VCP, but negative for anti-NT5c1A.

Conclusion: Anti-VCP has low sensitivity and moderate specificity for sIBM but may help fill the seronegative gap in sIBM. Further studies are needed to determine whether anti-VCP is a biomarker for a clinical phenotype that may have clinical value.

Objective: This study assessed patient-reported outcomes (PROs) in individuals with persistently positive antiphospholipid antibodies (aPL) to better understand how living with aPL may affect their quality of life.

Methods: Patients completed Patient-Reported Outcomes Measurement Information System Physical Function (PF) and Cognitive Function (CF) Short Forms as well as the pain intensity (PI) rating (scale of 1-10). Patients were characterized for demographics, clinical manifestations of antiphospholipid syndrome (APS), cardiovascular risk factors, laboratory test results, and medication usage. Multivariate modeling was done via linear regression.

Results: Of 139 patients, 89 had primary APS, 21 had secondary APS, and 29 had persistent aPL without meeting clinical criteria for APS. The average T scores (±SD) for PF and CF were 45.4 ± 9.2 and 48.6 ± 11.6, respectively; the average for PI was 3.0 ± 2.6. Approximately half of the patients (47%) endorsed at least mild impairment in PF (T score < 45). Mean PF, CF, and PI did not differ between diagnostic groups. Individuals who endorsed more impairment on one measure also tended to endorse more impairment on another (Pearson r = 0.43-0.59). In the multivariate models, age, smoking, pain medications, and serotonergic medications were associated with impairment in at least one PRO domain. The Damage Index for APS was significantly correlated with both PF and CF.

Conclusion: Individuals living with APS endorsed more impairment in PF (and potentially CF) than expected for the general population. The relationship between certain medications and PROs warrants further study, as does the longitudinal trajectory of these and other PROs.

Objective: Most studies consider either medications ordered or filled, but not both. Medication underuse based on filling data cannot necessarily be ascribed to patient nonadherence. Using both data sources, we quantified primary medication adherence in a cohort of prevalent systemic lupus erythematosus (SLE) pregnancies.

Methods: We identified 419 pregnancies in Kaiser Permanente Northern California in patients with prevalent SLE from 2011 to 2020. We calculated the number of physician-initiated orders or pharmacy-initiated reorders during pregnancy and a comparable 9-month window the year before (prepregnancy) and the proportion of orders ever filled and filled within 30 days for hydroxychloroquine (HCQ), azathioprine, and corticosteroids. For pregnancies without an order or reorder, we identified the proportion with previous prescription fills overlapping into the respective study period.

Results: New orders for lupus medications were usually filled. HCQ was prescribed most often (45.8% pregnancies) and usually filled (89.7% in prepregnancy, 93.2% during pregnancy). The majority filled within 30 days (80.5% prepregnancy, 83.3% pregnancy). Some pregnancies without new HCQ orders had continuous refills from prior orders; 53% of 2011-2015 pregnancies either had a new order or fill coverage from a previous period, compared to 63.2% of pregnancies delivering in 2016-2019. Corticosteroid fill frequencies were 90.6% in prepregnancy and 83.6% during pregnancy. Fewer patients used azathioprine; however, most new orders were filled (94.3% prepregnancy, 91.7% pregnancy). For azathioprine and corticosteroids, fill rates were modestly higher in prepregnancy compared to pregnancy.

Conclusion: We observed that patients have high adherence to filling new orders for lupus medications, such as HCQ and azathioprine, in pregnancy.