Arthritis Care & Research最新文献

Objective: The 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).

Methods: 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 patients with early dcSSc 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 end points 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.

Results: We matched 208 patients (mean 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% confidence interval {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.

Conclusion: 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.

Objective: Organ 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Objective: This 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).

Methods: In an open-label, phase 1 study (SELECT-YOUTH), enrolled patients, aged 2 to <18 years with pcJIA, received body weight-based upadacitinib doses using a twice-daily oral solution or once-daily 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.

Results: A total of 57 patients received upadacitinib. The median time to maximum upadacitinib concentration was approximately three hours and one hour for the tablet and oral solution regimens, respectively; the harmonic mean functional half-life was approximately five hours and two hours, respectively. Juvenile idiopathic arthritis American College of Rheumatology 30, 50, 70, 90, and 100 responses at week 12 were 91.8%, 89.8%, 69.4%, 49.0%, and 32.7%, respectively. Efficacy was generally maintained through week 48, and improvement in additional efficacy end points 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.

Conclusion: This interim analysis demonstrates that the bodyweight-based dosing regimen of upadacitinib was well tolerated and efficacious in pediatric patients with pcJIA.

Objective: The 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Objective: Osteoporosis, 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 patients with RA treated with contemporary treatment strategies are lacking. The objectives were (1) estimate age-specific and sex-specific incidence rates and compare the risk of hip fractures in RA relative to age-matched and sex-matched general population controls, and (2) compare the risk of all-cause mortality in RA and general population controls after hip fracture.

Methods: A longitudinal study of a population-based incident cohort of patients with RA diagnosed between 1997 and 2009, followed until 2014, with age-matched and sex-matched controls from the general population of British Columbia, using administrative health data. Hip fracture outcomes (International Classification of Diseases, Ninth Edition, Clinical Modification [ICD-9-CM] codes 820.0 or 820.2; ICD-10-Canada code S72.0 to S72.2) and mortality at predefined 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 (IRRs), were calculated. Cox proportional hazards models compared hip fracture and mortality risk in RA versus controls; logistic regression compared in-hospital mortality risk.

Results: Overall, 1,314 hip fractures over 360,521 person-years were identified in 37,616 individuals with RA and 2,083 over 732,249 person-years in 75,213 controls, yielding a 28% greater fracture risk in RA (IRR 1.28 [95% confidence interval 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 years). Postfracture mortality risk at one-year and five-years did not differ between RA and general population controls. Results were similar in a sensitivity analysis including only individuals with RA who received disease-modifying antirheumatic drugs.

Conclusion: 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.

Objective: This work describes the demographics and practice characteristics of physician assistants/associates (PAs) practicing in rheumatology.

Methods: We examined 2022 cross-sectional data from the National Commission on Certification of PAs. The investigation included demographics and practice characteristics of PAs working in rheumatology compared to those working in all other specialties. We analyzed data using descriptive and bivariate statistics comparing the two groups.

Results: In 2022, 430 PAs self-reported practicing in rheumatology. The median age of these PAs was 39 years, and 84.7% self-identified as female. They primarily (78.8%) worked in office-based private practices and were more likely to engage in telemedicine services (62.5%) than their colleagues in all other specialties. PAs in rheumatology typically worked similar hours as their peers in other medical disciplines but saw a higher proportion of patients in the 61 to 80 range. At the same time, PAs in rheumatology reported slightly higher job satisfaction and lower burnout symptom rates compared to PAs practicing in other disciplines.

Conclusion: Understanding the characteristics and employment settings of PAs in rheumatology is crucial to estimating the health workforce supply and demand in this discipline. Further research should explore the economics of PAs in rheumatology, including aspects of teamwork, scope of practice, patient outcomes, and satisfaction.

Objective: To assess changes in gene expression following tofacitinib treatment and investigate transcription patterns as potential predictors of treatment response in patients with active juvenile idiopathic arthritis (JIA).

Methods: Whole-blood samples were collected from patients with JIA at baseline and after 18 weeks of open-label tofacitinib treatment. Patients who achieved a JIA-American College of Rheumatology (ACR) response of 70% or above at week 18 were classified as treatment responders (TRs), whereas those with at most a JIA-ACR30 were classified as poor responders (PRs). Differential gene expression and gene ontology overrepresentation analyses were performed to compare RNA expression between week 18 and baseline samples, as well as between PR and TR samples at baseline.

Results: Samples from 67 patients at baseline and 60 patients at week 18 were analyzed. After 18 weeks of tofacitinib treatment across all patients with JIA, 883 genes showed significant differential expression (week 18 to baseline). The most strongly down-regulated genes were overrepresented within interleukin-7 (IL-7) and type I and type II interferon pathways, whereas up-regulated genes were enriched in ontologies related to neuronal cell processes and cell signaling. Comparing PRs and TRs at baseline, 663 genes showed differential expression. Up-regulated genes were overrepresented within ontologies including activation of MAPK activity (P = 9.40 × 10^-5), myeloid cell development (P = 8.13 × 10^-5), activation of GTPase activity (P = 0.00015), and organelle transport along microtubules (P = 0.00021).

Conclusion: Tofacitinib treatment in JIA down-regulated genes in interferon and IL-7 signaling pathways regardless of effectiveness. Furthermore, baseline up-regulation of MAPK signaling may predict poor response to tofacitinib treatment in JIA.

Objective: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are chronic life-threatening vasculitides requiring substantial immunotherapy. Adult trials identified rituximab (RTX) as an alternative to cyclophosphamide (CYC) for remission induction of GPA and MPA. Disease rarity has limited feasibility of similar trials with pediatric patients. We aim to evaluate the relative efficacy and toxicity of CYC and RTX for patients with childhood GPA and MPA through registry-based comparative evaluation.

Methods: From A Registry of Childhood Vasculitis, we identified patients with GPA and MPA who received induction with RTX or CYC. Pediatric Vasculitis Activity Score (PVAS) and Pediatric Vasculitis Damage Index (pVDI) score evaluated disease activity and damage. Descriptive statistics summarized patient characteristics. RTX and CYC comparisons used logistic regression for primary outcomes of postinduction remission (PVAS = 0) or low disease activity (PVAS ≤ 2). Hospital admission for adverse events and pVDI scores were compared using logistic regression and ordinal regression, respectively.

Results: Among 104 patients, 43% received RTX, 46% CYC, 11% both. Treatment groups did not significantly differ for diagnosis PVAS and onset age. There was no difference in remission among the groups (63% overall; odds ratio [OR] 1.07, 95% confidence interval [CI] 0.45-2.52). Hospitalizations occurred in 22% of patients receiving RTX versus 10% patients receiving CYC (OR 2.27, 95% CI 0.73-7.05). The median 12-month pVDI score was 1 in both groups (OR 0.98, 95% CI 0.43-2.22).

Conclusion: This is the first study comparing CYC and RTX for induction in pediatric GPA and MPA. No significant differences were shown in rates of remission, severe adverse events, or organ damage. Limitations included lack of standardized treatment regimens, retrospectivity, and lack of longitudinal adverse drug-related event data.

Objective: The Osteoarthritis Chronic Care Program (OACCP) has been implemented in Australian public hospitals to deliver best evidence osteoarthritis (OA) care. It is important to ensure that the OACCP continues to deliver evidence-based OA care as intended. We aimed to identify barriers and enablers to delivering the OACCP, prioritize the barriers, and generate strategies to address them.

Methods: This study provides a worked example of a seven-step theory-informed codesign framework. We invited OACCP coordinators to participate in semistructured interviews (analyzed thematically) and complete a questionnaire to identify barriers and enablers to delivery of the OACCP. We then invited a broader group of stakeholders (OACCP coordinators, health managers, policy makers, consumers, and researchers) to prioritize the barriers via a short survey (survey 2). We held five codesign workshops in which we mapped the priority barriers to the Theoretical Domains Framework and developed strategies to address them.

Results: Sixteen coordinators were interviewed, and the main barriers identified were as follows: (1) patients often have beliefs that are inconsistent with best evidence care, (2) there are aspects of clinical care that are not delivered optimally, and (3) system-level factors are a barrier to optimal patient care and sustainability of the OACCP. We codesigned a plan for action with patient educational materials, shared decision-making tools, and health professional education and training.

Conclusion: Our worked example of codesign used a theory-based, data-driven approach with key stakeholders, identified and prioritized barriers to the delivery of the OACCP, acknowledged enablers, and generated a plan for feasible strategies to improve the program.