ACR Open Rheumatology最新文献

Objective: A skewed percentage of industry payments goes to "key opinion leaders" (KOLs) whose prominence and influence has increased with time. Given that KOL is neither precisely defined nor quantifiable, we turned to the level of industry payments as a surrogate quantifiable metric and assessed the associations between industry payments to US rheumatologists and their authorships of publications in high-impact rheumatology journals.

Methods: Payments to US rheumatologists during the 2015-2020 interval were obtained from the Centers for Medicare and Medicaid Services Open Payments database, and authorships were tallied for calendar year 2021 publications in the four rheumatology journals (Lancet Rheumatol, Nat Rev Rheumatol, Ann Rheum Dis, Arthritis Rheumatol) with the highest 2021 journal impact factors and journal citation indicators. Differences between groups were determined by chi-squared test, unpaired Student's t-test, one-way analysis of variance (ANOVA), Mann-Whitney rank sum test, and Kruskal-Wallis one-way ANOVA on ranks. Correlations were calculated using Spearman rank order. A P value ≤0.05 was considered significant.

Results: There were 278 individual US rheumatologists who received industry payments and served as authors of publications in the four high-impact rheumatology journals. Non-research-associated payments to these individuals strongly correlated with research-associated payments. Payments to male US rheumatologists were greater than those to their female counterparts, and payments strongly correlated with the number of publications among male authors but only weakly, and often not significantly, among female authors.

Conclusion: A substantial fraction of the authorships in calendar year 2021 publications in four high-impact rheumatology journals arose from a very small percentage of all US rheumatologists who had received industry payments during the 2015-2020 interval. Payments to male US rheumatologist-authors were strikingly different from those to female US rheumatologist-authors, and further investigation is needed to explain the glaring difference in payments.

Objective: Progressive pulmonary fibrosis (PPF) is the leading cause of death in systemic sclerosis (SSc). This study aimed to develop a clinical prediction nomogram using clinical and biological data to assess risk of PPF among patients receiving treatment of SSc-related interstitial lung disease (SSc-ILD).

Methods: Patients with SSc-ILD who participated in the Scleroderma Lung Study II (SLS II) were randomized to treatment with either mycophenolate mofetil (MMF) or cyclophosphamide (CYC). Clinical and biological parameters were analyzed using univariable and multivariable logistic regression, and a nomogram was created to assess the risk of PPF and validated by bootstrap resampling.

Results: Among 112 participants with follow-up data, 22 (19.6%) met criteria for PPF between 12 and 24 months. An equal proportion of patients randomized to CYC (n = 11 of 56) and mycophenolate mofetil (n = 11 of 56) developed PPF. The baseline severity of ILD was similar for patients who did, compared to those who did not, experience PPF in terms of their baseline forced vital capacity percent predicted, diffusing capacity for carbon monoxide percent predicted, and quantitative radiological extent of ILD. Predictors in the nomogram included sex, baseline CXCL4 level, and baseline gastrointestinal reflux score. The nomogram demonstrated moderate discrimination in estimating the risk of PPF, with a C-index of 0.72 (95% confidence interval 0.60-0.84).

Conclusion: The SLS II data set provided a unique opportunity to investigate predictors of PPF and develop a nomogram to help clinicians identify patients with SSc-ILD who require closer monitoring while on therapy and potentially an alternative treatment approach. This nomogram warrants external validation in other SSc-ILD cohorts to confirm its predictive power.

Objective: To analyze a RheuMetric checklist, which includes four feasible physician 0 to 10 scores for DOCGL, inflammation (DOCINF), damage (DOCDAM), and distress (DOCSTR) for criterion and discriminant validity against standard reference measures.

Methods: A prospective, cross-sectional assessment was performed at one routine care visit at Liverpool Hospital, Sydney, Australia. Rheumatologists recorded DOCGL, DOCINF, DOCDAM, DOCSTR, and 28 joint counts for swelling (SJC), tenderness (TJC), and limited motion/deformity (DJC). Patients completed a multidimensional health assessment questionnaire (MDHAQ), which includes routine assessment of patient index data (RAPID3), fibromyalgia assessment screening tool (FAST4), and MDHAQ depression screen (MDS2). Laboratory tests and radiographic scores were recorded. RheuMetric estimates of inflammation, damage, and distress were compared with reference and other measures using correlations and linear regressions.

Results: In 173 patients with RA, variation in RheuMetric DOCINF was explained significantly by SJC and inversely by disease duration; variation in DOCDAM was explained significantly by DJC, radiographic scores, and physical function; and variation in DOCSTR was explained significantly by fibromyalgia and depression.

Conclusion: RheuMetric DOCINF, DOCDAM, and DOCSTR estimates were correlated significantly and specifically with reference measures of inflammation, damage, and distress, documenting criterion and discriminant validity.

Objective: To determine whether prescribing practices for Janus kinase inhibitors (JAKi), tumor necrosis factor inhibitors (TNFi), and non-TNFi biologic agents changed after the results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance trial were released in January 2021.

Methods: This is a retrospective study in adult patients with rheumatoid arthritis (RA) receiving advanced therapies within the Veterans Affairs Health System from January 2012 through September 2022. Eligible patients were required to have at least one diagnosis code for RA and to have received a biologic disease-modifying antirheumatic drug or JAKi. Treatment courses were defined from pharmacy dispensing data and the number of new courses of each advanced therapy was quantified over time. We assessed changes in the use of each therapy before and after the release of safety data (January 2021).

Results: A total of 88,253 individual drug courses (in 34,656 unique patients) were included in the study. There was a consistent increase in the number and proportion of new courses of JAKi leading up to January 2021, which was followed by a significant net decrease in JAKi use through September 2022. There was significantly less tofacitinib use after the release of safety data, with a significant difference in the slope of change in use with time. In contrast, whereas TNFi use declined leading up to 2021, its use significantly increased after January 2021.

Conclusion: Changes in prescribing in response to new evidence emphasize the impact that safety trials have on prescribing practices. Ongoing study in this area, with attention to specific patient characteristics and risk profiles, will help characterize these changes in practice.

Objective: To use cell-based gene signatures to identify patients with systemic lupus erythematous (SLE) in the phase II/III APRIL-SLE and phase IIb ADDRESS II trials most likely to respond to atacicept.

Methods: A published immune cell deconvolution algorithm based on Affymetrix gene array data was applied to whole blood gene expression from patients entering APRIL-SLE. Five distinct patient clusters were identified. Patient characteristics, biomarkers, and clinical response to atacicept were assessed per cluster. A modified immune cell deconvolution algorithm was developed based on RNA sequencing data and applied to ADDRESS II data to identify similar patient clusters and their responses.

Results: Patients in APRIL-SLE (N = 105) were segregated into the following five clusters (P1-5) characterized by dominant cell subset signatures: high neutrophils, T helper cells and natural killer (NK) cells (P1), high plasma cells and activated NK cells (P2), high B cells and neutrophils (P3), high B cells and low neutrophils (P4), or high activated dendritic cells, activated NK cells, and neutrophils (P5). Placebo- and atacicept-treated patients in clusters P2,4,5 had markedly higher British Isles Lupus Assessment Group (BILAG) A/B flare rates than those in clusters P1,3, with a greater treatment effect of atacicept on lowering flares in clusters P2,4,5. In ADDRESS II, placebo-treated patients from P2,4,5 were less likely to be SLE Responder Index (SRI)-4, SRI-6, and BILAG-Based Combined Lupus Assessment responders than those in P1,3; the response proportions again suggested lower placebo effect and a greater treatment differential for atacicept in P2,4,5.

Conclusion: This exploratory analysis indicates larger differences between placebo- and atacicept-treated patients with SLE in a molecularly defined patient subset.

Objective: Lung disease (LD) is an increasingly recognized complication of systemic juvenile idiopathic arthritis (sJIA). As there are no currently available guidelines for pulmonary screening in sJIA, we sought to develop such an algorithm at our institution.

Methods: A multidisciplinary workgroup was convened, including members representing rheumatology, pulmonary, stem cell transplantation, and patient families. The workgroup leaders drafted an initial algorithm based on published literature and experience at our center. A modified Delphi approach was used to achieve agreement through three rounds of anonymous, asynchronous voting and a consensus meeting. Statements approved by the workgroup were rated as appropriate with moderate or high levels of consensus. These statements were organized into the final approved screening algorithm for LD in sJIA.

Results: The workgroup ultimately rated 20 statements as appropriate with a moderate or high level of consensus. The approved algorithm recommends pulmonary screening for newly diagnosed patients with sJIA with clinical features that the workgroup agreed may confer increased risk for LD. These "red flag features" include baseline characteristics (young age of sJIA onset, human leukocyte antigen type, trisomy 21), high disease activity (macrophage activation syndrome [MAS], sJIA-related ICU admission, elevated MAS biomarkers), respiratory symptoms or abnormal pulmonary examination findings, and features of drug hypersensitivity-like reactions (eosinophilia, atypical rash, anaphylaxis). The workgroup achieved consensus on the recommended pulmonary work-up and monitoring guidelines.

Conclusion: We developed a pulmonary screening algorithm for sJIA-LD through a multidisciplinary consensus-building process, which will be revised as our understanding of sJIA-LD continues to evolve.

Objective: Hypophosphatasia (HPP) is a rare disease characterized by incomplete or defective bone mineralization due to a mutation in the alkaline phosphatase (ALP) gene causing low levels of ALP. Disease presentation is heterogeneous and can present as a chronic pain syndrome like fibromyalgia (FM). Our objective was to determine if there are any potential patients with HPP in the group of patients who were diagnosed with FM. Antiresorptive therapy use can trigger atypical femur fractures in patients with HPP.

Methods: We performed a retrospective chart review of all patients 18 years or older at a single academic center who were diagnosed with FM and had either a low or a normal ALP level. The following characteristics were reviewed: biological sex; age; history of fractures; diagnosis of osteoporosis, osteopenia, osteoarthritis, and chondrocalcinosis; genetic testing; vitamin B6 level testing; and medications.

Results: Six hundred eleven patients with FM were identified. Two hundred had at least one low ALP level, and 57 had at least three consecutively low measurements of ALP, 44% of which had a history of fractures. No patients had vitamin B6 levels checked. None of the patients had previous genetic testing for HPP or underwent testing for zinc or magnesium levels.

Conclusion: The percentage of patients with FM who were found to have consistently low ALP levels was 9.3%. None had vitamin B6 level or genetic testing, suggesting that the diagnosis was not suspected. It is important to diagnose HPP given the availability of enzyme replacement therapy to prevent complications from HPP such as fractures. Our data support screening for this condition as a part of the initial workup of FM.

Objective: In the Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial, 65% of patients with rheumatoid arthritis (RA) in low disease activity (LDA) on stable biologic therapy successfully tapered glucocorticoids. We aimed to evaluate real-world rates of glucocorticoid tapering among similar patients in the Veterans Affairs Rheumatoid Arthritis registry.

Methods: Within a multicenter, prospective RA cohort, we used registry data and linked pharmacy claims from 2003 to 2021 to identify chronic prednisone users achieving LDA after initiating a new biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD). We defined the index date as first LDA occurring 60 to 180 days after b/tsDMARD initiation. The primary outcome of successful tapering, assessed at day 180 after LDA, required a 30-day averaged prednisone dose both less than or equal to 5mg/day and at least 50% lower than at the index date. The secondary outcome was discontinuation, defined as a prednisone dose of 0 mg/day at days 180 through 210. We used univariate statistics to compare patient characteristics by fulfillment of the primary outcome.

Results: We evaluated 100 b/tsDMARD courses among 95 patients. Fifty-four courses resulted in successful tapering; 33 resulted in discontinuation. Positive rheumatoid factor, higher erythrocyte sedimentation rate, more background DMARDs, shorter time from b/tsDMARD initiation to LDA, and higher glucocorticoid dose 30 days before LDA were associated with greater likelihood of successful tapering.

Conclusion: In a real-world RA cohort of chronic glucocorticoid users in LDA, half successfully tapered and a third discontinued prednisone within 6 months of initiating a new b/tsDMARD. Claims-based algorithms of glucocorticoid tapering and discontinuation may be useful to evaluate predictors of tapering in administrative data sets.