Arthritis Care & Research最新文献

Objectives: 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 JIA patients at baseline and after 18 weeks of open-label tofacitinib treatment (clinical trial NCT02592434). Patients who achieved a JIA-American College of Rheumatology (ACR) response of 70 or above at week 18 were classified as treatment-responders (TR) while those with at most a JIA-ACR30 response were classified as poor-responders (PR). Differential gene expression and gene ontology (GO) over-representation 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 at week 18 were analyzed. Following 18 weeks of tofacitinib treatment across all JIA subjects, 883 genes showed significant differential expression (week 18 - baseline). The most strongly downregulated genes were over-represented within IL-7, type I, and type II interferon pathways, while upregulated genes were enriched in ontologies related to neuronal cell processes and cell signaling. Comparing PR and TR at baseline, 663 genes showed differential expression. Upregulated genes were over-represented within ontologies including activation of MAPK activity (p=9.40x10^-5), myeloid cell development (p=8.13 x10^-5), activation of GTPase activity (p=0.00015), and organelle transport along microtubules (p=0.00021).

Conclusions: Tofacitinib treatment in JIA downregulated genes in interferon and IL-7 signaling pathways regardless of effectiveness. Furthermore, baseline upregulation of MAPK signaling may predict poor response to tofacitinib treatment in JIA.

Objective: Individuals with inflammatory arthritis (IA) require long-term rheumatologist care for optimal outcomes. We sought to determine if socioeconomic status (SES) influences general practitioner (GP) and specialist physician visit frequency and out of pocket (OOP) visit costs.

Methods: We linked data from Australian Rheumatology Association Database (ARAD) participants with rheumatoid arthritis or psoriatic arthritis to the Pharmaceutical Benefits (PBS) and Medicare Benefits Schedule (MBS) from 2011-2018. Small-area SES was approximated as quintiles of the Index of Relative Socieconomic Advantage and Disadvantage. A comorbidity index (Rx-Risk) was determined from PBS data. Analysis was performed using panel regression methods.

Results: We included 1916 ARAD participants (76.3% rheumatoid arthritis, 71.1% women, mean [SD] age 54 [12] years and disease duration 6 [4] years). Participants averaged 9.0 (95% CI 8.6, 9.4) annual GP visits and 3.9 (3.8 to 4.1) annual specialist physician visits. After adjustment for sex, age, education, remoteness and comorbidity, there was an inverse relationship between annual GP visit frequency and higher SES quintile (-0.6 [-0.9, -0.3] visits/quintile) and a direct relationship between more frequent specialist visits and higher SES (linear slope 0.3 [0.2, 0.5] visits/quintile). Average OOP costs/visit were higher for specialist physician (AUD$38.43 [37.34, 39.53] versus GP visits (AUD$7.86 [7.42, 8.31], and higher SES was associated with greater OOP cost.

Conclusion: Higher SES patients have relatively fewer GP visits and more specialist physician visits compared with lower SES patients, suggesting lower SES patients may receive suboptimal specialist physician care. OOP costs may be a contributing factor.

Objective: The objective was to examine potential pathways linking neighborhood disadvantage to pain severity in individuals with knee pain consistent with or at risk for Knee Osteoarthritis (KOA).

Methods: The current investigation is a cross-sectional analysis. Data were collected from 140 mid-to older non-Hispanic White and non-Hispanic Black adults from the Understanding Pain and Limitations in Osteoarthritic Disease Study 2 (UPLOAD 2). Relationships among neighborhood disadvantage, sleep efficiency, pain catastrophizing, and pain severity were assessed. Neighborhood disadvantage was quantified using the Area Deprivation Index (ADI) and actigraphy data were used to assess sleep efficiency. The Coping Strategies Questionnaire-Revised catastrophizing subscale and WOMAC (Western Ontario and McMaster Universities Arthritis Index) pain severity scale were used to assess pain catastrophizing, and pain severity, respectively. A serial mediation model assessed the neighborhood➔sleep➔catastrophizing➔pain pathway, as well as neighborhood➔sleep➔pain, and neighborhood➔catastrophizing➔pain pathways.

Results: Greater neighborhood disadvantage was associated with worse sleep efficiency, ultimately contributing to greater pain severity. While neither neighborhood disadvantage nor sleep efficiency were associated with pain catastrophizing, pain catastrophizing itself was associated with greater KOA pain.

Conclusion: Neighborhood disadvantage impacts KOA pain outcomes through sleep efficiency, but not pain catastrophizing, thereby highlighting environmental aspects that impact sleep as potential targets for intervention.

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/MPA. Disease rarity has limited feasibility of similar trials in pediatrics. We aim to evaluate the relative efficacy and toxicity of CYC and RTX for childhood GPA/MPA through registry-based comparative evaluation.

Methods: From A Registry of Childhood Vasculitis we identified GPA/MPA patients who received induction with RTX or CYC. Pediatric vasculitis activity score (PVAS) and pediatric vasculitis damage index (pVDI) evaluated disease activity and damage. Descriptive statistics summarized patient characteristics. RTX/CYC comparisons used logistic regression for primary outcomes of post-induction remission (PVAS=0) or low disease activity (PVAS<2). Hospital admission for adverse events and pVDI 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 between groups (63% overall; OR 1.07, 95% CI: 0.45, 2.52). Hospitalizations occurred in 22% of RTX patients versus 10% on CYC (OR 2.27, 95% CI: 0.73, 7.05). The median 12-month pVDI was one 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/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.

Background: Racial and ethnic disparities in rheumatoid arthritis (RA) outcomes are well recognized. However, whether disparities in RA treatment selection and outcomes differ by urban versus rural residence, independent of race, have not been studied. Our objective was to evaluate whether biologic disease modifying anti-rheumatic drugs (bDMARD) initiation after methotrexate use differs by rural versus urban residence among Veterans with RA.

Methods: In this retrospective cohort study utilizing national U.S. Veterans Affairs databases, we identified adult patients with RA based on presence of diagnostic codes and DMARD use. We included patients receiving an initial prescription of methotrexate (index date) between 2005 and 2014, with data through 2016 used for follow-up. Urban-rural status was categorized using the Veteran Health Administration's Urban/Rural classification. Our primary outcome of interest was time to biologic initiation within two years of starting methotrexate. Multivariable Cox proportional hazards models were conducted adjusting for demographics, comorbidities, and rheumatoid factor or anti-CCP positivity.

Results: Among 17,395 veterans with RA (88% male, 42% with rural residence) fulfilling eligibility criteria, 3,259 (19%) initiated a biologic within the first two years of follow up. In multivariable models, residence in an urban area was associated with a statistically significant higher biologic use compared to rural areas (adjusted hazard ratio (aHR) 1.10, 95% CI 1.02-1.18).

Conclusion: Our study found only modest differences in initiation of biologic therapies among rural versus urban residing Veterans with RA in the VA healthcare system. These findings suggest that disparities are not easily explained by rurality within the VA healthcare system.

Objective: The objectives were to determine the prevalence of meeting criteria for symptoms suggestive of early osteoarthritis (OA) after anterior cruciate ligament reconstruction (ACLR) and to characterize the longitudinal changes in these symptoms during the first two years post-ACLR.

Methods: We analyzed data from 10,231 patients aged 14 to 40 years in the New Zealand ACL Registry who completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) at 6, 12, and 24 months post-ACLR. Symptoms suggestive of early OA were defined as scoring ≤85% on at least two of four KOOS subscales. Longitudinal patterns of change were categorized as persistent, resolution, new, inconsistent, or no symptoms across the three visits. Prevalence and odds ratios (ORs) of symptoms were compared across visits, sex, and age groups using generalized estimating equations, and longitudinal patterns of symptom change were analyzed using multinomial logistic regression.

Results: Prevalence of meeting criteria of symptoms suggestive of early OA was 68% at 6 months, 54% at 12 months, and 46% at 24 months post-ACLR. Longitudinally, 33% had persistent symptoms, 23% had no symptoms, 29% showed symptom resolution, 6% developed new symptoms, and 9% had inconsistent symptoms. Women consistently showed higher odds of symptoms (OR range 1.17-1.52). Older age groups demonstrated higher odds of symptoms, particularly at 6 months (OR range 1.64-2.45).

Conclusion: Symptoms suggestive of early OA are highly prevalent within two years post-ACLR, with one third of patients experiencing persistent symptoms. These findings indicate that symptoms are more likely to persist rather than newly develop, emphasizing the importance of early identification and targeted interventions.

Objective: The aim of this study was to determine the impact of season, temperature and humidity on the severity of Raynaud phenomenon (RP) in systemic sclerosis.

Methods: Data from the Australian Scleroderma Cohort Study were used to assess associations of patient-reported worsened RP in the month preceding each study visit. Mean monthly weather data were obtained from the closest weather station to the patient's address. We evaluated the relationship between worsened RP and health-related quality of life (HRQoL) measured using the Short Form 36 instrument.

Results: Among 1,972 patients with systemic sclerosis, RP was a near-universal finding, and worsened RP in the preceding month was reported in 26.7% of 9,175 visits. "Worsened RP" showed significant environmental variability. On multivariable analysis, worsened RP was associated with low mean maximum temperatures (odds ratio [OR] 0.91, 95% confidence interval [95% CI] 0.90-0.92, P < 0.001), high relative humidity (OR 1.05, 95% CI 1.04-1.05, P < 0.001) and lower mean daily evaporation (OR 0.77, 95% CI 0.73-0.81, P < 0.001). Worsened RP was strongly associated with telangiectasia, calcinosis, and digital ulceration, as well as demonstrating an association with anticentromere antibody and gastroesophageal reflux disease and a negative correlation with diffuse disease. Worsened RP was also strongly associated with worse HRQoL.

Conclusion: Lower environmental temperature and higher relative humidity had significant associations with worsened RP in this systemic sclerosis cohort, suggesting an important role for dry warmth in managing this condition.

Objective: This study aimed to identify modifiable determinants of self-management behavior in gout.

Methods: Four databases (MEDLINE, Embase, PsycINFO and CINAHL) were searched using terms related to gout, self-management and determinants of behavior as described in the Theoretical Domains Framework (TDF). Two reviewers independently selected relevant studies via screening of title/abstract and full text. Thematic synthesis was performed for qualitative data; quantitative data was summarized using cross-tabulation displaying the investigated associations of determinants with self-management behavior. The TDF facilitated identification and grouping of determinants.

Results: From 2087 unique articles found, 56 studies were included in this review, of which 27 qualitative and 29 quantitative studies. Eight themes were identified: knowledge and skills for self-management, acceptance of disease, beliefs about necessity of self-management to improve gout-related health, resistance and reluctance for medication adherence and dietary alteration/changes, negative emotions influencing self-management, social support and interactions, environmental context, and self-regulation of behavior. Quantitative determinants associated with self-management behavior, predominantly medication adherence, were mapped to 12 of the 14 domains of the TDF. No determinants regarding skills and goals have been identified in quantitative research.

Conclusion: Intervention targets for self-management behavior in gout mainly included determinants related to knowledge, implicit and explicit beliefs and attitudes, the environmental context and resources, (social) support and reinforcement.