Construct validity and responsiveness of feasible composite disease activity measures for use in daily clinical practice in patients with psoriatic arthritis

OBJECTIVE: There is a need for a widely accepted comprehensive disease activity measure for use in daily practice in patients with psoriatic arthritis (PsA). For this reason, the 3-item Visual Analogue Scale (3VAS) and 4-item Visual Analogue Scale (4VAS) were developed. This study aimed to test construct validity and responsiveness of the 3VAS and 4VAS in a population of patients with newly diagnosed PsA receiving usual care. METHODS: Components of the 3VAS (physician global, patient global, patient skin) and 4VAS (physician global, patient pain, patient joint, patient skin) were scored on 0-10 VAS scales. Agreement of low disease activity (LDA) state between 3VAS/4VAS and other composite measures was tested using Venn diagrams. Construct validity and responsiveness (3-month interval) were assessed using Spearman correlation coefficients and standardised response means (SRM) with effect sizes (ES), respectively, following hypothesis generation. Both 3VAS/4VAS were also compared with several patient-reported outcome measures. RESULTS: Data from 629 patients were used. Both 3VAS (ES=0.48, SRM 0.52) and 4VAS (ES=0.48, SRM=0.50) showed responsiveness similar to Disease Activity in PSoriatic Arthritis (DAPSA) and Disease Activity Score-28 (DAS28). Both measures had a strong correlation with DAPSA (r=0.80-0.87), Psoriatic Arthritis Disease Activity Score (PASDAS) (r=0.89) and Routine Assessment of Patient Index Data 3 (RAPID3) (r=0.84-0.92). 3VAS and 4VAS had the highest agreement with PASDAS in categorising patients to LDA at 12 months. CONCLUSION: This is the first study assessing the performance of the 3VAS and 4VAS in an observational cohort of patients with early PsA. Both measures have promising performance characteristics, showing strong correlations and good discrimination with existing composite measures. The 4VAS may be the preferred version with better face validity.</p

A trial-based economic evaluation of the CaFaSpA referral strategy for axial spondyloarthritis

Objective: To assess the cost–utility from healthcare and societal perspectives of the digital CaFaSpA referral strategy (CS) for axial spondyloarthritis (axSpA) in primary care patients with chronic low back pain (CLBP). Method: A cluster randomized controlled trial was performed in the Netherlands. General practice units were randomized into CS or usual care (UC). Economic evaluation was performed from the healthcare and societal perspectives within a 12-month time horizon. Outcome measures encompassed disability [Roland–Morris Disability Questionnaire (RMDQ)] and health-related quality of life (EQ-5D-3L). Direct medical (iMTA Medical Consumption Questionnaire) and indirect costs (iMTA Productivity Cost Questionnaire), including productivity loss, were evaluated. Incremental cost–utility ratios (ICURs) were calculated. Results: The study included 90 GP clusters with 563 patients (CS: n = 260; UC: n = 303) (mean ± sd age 36.3 ± 7.5 years; 66% female). After 12 months, no minimal important differences in outcomes were observed for RMDQ (−0.21, 95%CI −1.52 to 1.13) or EQ-5D (−0.02, 95%CI −0.08 to 0.05). However, total costs were significantly lower in the CS group owing to lower productivity loss costs. The ICUR for RMDQ was €18,059 per point decrease and €220,457 per quality-adjusted life year increase. Conclusions: Digital referral did not decrease the overall healthcare status of patients after 1 year of follow-up and appears to be more cost-effective than UC. Therefore, CS can be used as an appropriate primary care referral model for CLBP patients at risk for axSpA. This will accelerate timely provision of care by the right caregiver.</p

Validation of a clinical pharmacogenetic model to predict methotrexate nonresponse in rheumatoid arthritis patients

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Cartilage evaluation in finger joints in healthy controls and early hand osteoarthritis patients using high-resolution MRI

Objective: To compare direct evaluation of cartilage with high resolution MRI (hrMRI) to indirect cartilage evaluation using MRI inter-bone distance in hand OA patients and healthy controls. Design: 41 hand OA patients and 18 healthy controls underwent hrMRI of the 2nd and 3rd metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. The images were read by two independent readers using OMERACT hand OA MRI inter-bone distance score (0–3 scale) and a new hrMRI cartilage score with direct evaluation of the cartilage (0–3 scale). Inter-reader and intra-reader reliability was calculated using exact and close agreement and kappa values. The prevalence of abnormal scores and agreement between methods was assessed in both hand OA patients and healthy controls. Results: The intra- and inter-reader reliability of both scores was comparable, with exact agreement in 73–83% and close agreement in 95–100%. In hand OA patients 27% of 161 joints had both cartilage damage and loss of inter-bone distance, cartilage damage by hrMRI only was present in 20% of joints and reduced inter-bone distance only in 4% of joints. In the healthy controls, 1 of 71 joints were scored as abnormal by both hrMRI and inter bone distance scoring, 1 joint was scored as abnormal using the hrMRI cartilage score only, whereas 15% of joints had only reduced inter bone distance. Conclusions: Direct cartilage evaluation of MCP and PIP joints using hrMRI has a good reliability, and the higher prevalence of hrMRI cartilage damage in hand OA patients and the lower prevalence in healthy controls in comparison to evaluation of inter-bone distance suggests a better validity

Th17 cells, but not Th1 cells, from patients with early rheumatoid arthritis are potent inducers of matrix metalloproteinases and proinflammatory cytokines upon synovial fibroblast interaction, including autocrine interleukin-17A production

Objective Both Th1 cells and Th17 cells have been recognized in rheumatoid arthritis (RA); however, it remains unclear whether Th1 cells and/or Th17 cells are involved in driving disease chronicity and destructiveness. The aim of this study was to identify and characterize the functional role of Th17 cells in early RA. Methods Flow cytometry analysis was performed on peripheral blood mononuclear cells (PBMCs) from treatment-naive patients with early RA and age-matched healthy volunteers. PBMCs from these patients, naive T cells, and primary CCR6- Th1 cells and CCR6+ Th17 cells were sorted and cultured in the absence or presence of synovial fibroblasts from patients with early RA (RASFs), and cytokine expression and gene transcription were analyzed. In addition, tumor necrosis factor α (TNFα)- and interleukin-17A (IL-17A)-blocking experiments were performed. Results In the PBMCs of treatment-naive patients with early RA, an increased fraction of IL-17A-and TNFα-producing CCR6+ Th17 cells was observed. When cocultured with RASFs, these primary Th17 cells were potent inducers of IL-6 and IL-8 and the tissue-destructive enzymes matrix metalloproteinase 1 (MMP-1) and MMP-3, whereas primary Th1 cells or naive T cells were not. Importantly, specific up-regulation of IL-17A but not TNFα or interferon-γ was observed in RASF/Th17 cell cocultures. In addition to TNFα blocking, IL-17A neutralization was required to further down-regulate Th17 activity in RASF/Th17 cell cocultures. Conclusion Th17 cells, but not Th1 cells, cooperated with RASFs in a proinflammatory feedback loop, revealing a potential mechanism by which human Th17 cells drive chronic destructive disease in patients with RA. Furthermore, the neutralization of IL-17A activity is essential in current anti-TNF therapies to suppress Th17 cell activity in patients with early RA and potentially other Th17 cell-mediated disorders

Very different performance of the power Doppler modalities of several ultrasound machines ascertained by a microvessel flow phantom

Introduction: In many patients with rheumatoid arthritis (RA) subclinical disease activity can be detected with ultrasound (US), especially using power Doppler US (PDUS). However, PDUS may be highly dependent on the type of machine. This could create problems both in clinical trials and in daily clinical practice. To clarify how the PDUS signal differs between machines we created a microvessel flow phantom.Methods: The flow phantom contained three microvessels (150, 1000, 2000 microns). A syringe pump was used to generate flows. Five US machines were used. Settings were optimised to assess the lowest detectable flow for each US machine.Results: The minimal detectable flow velocities showed very large differences between the machines. Only two of the machines may be able to detect the very low flows in the capillaries of inflamed joints. There was no clear relation with price. One of the lower-end machines actually performed best in all three vessel sizes.Conclusions: We created a flow phantom to test the sensitivity of US machines to very low flows in small vessels. The sensitivity of the power Doppler modalities of 5 different machines was very different. The differences found between the machines are probably caused by fundamental differences in processing of the PD signal or internal settings inaccessible to users. Machines considered for PDUS assessment of RA patients should be tested using a flow phantom similar to ours. Within studies, only a single machine type should be used

1,25-Dihydroxyvitamin D3 modulates Th17 polarization and interleukin-22 expression by memory T cells from patients with early rheumatoid arthritis

Objective. To examine the immunologic mechanism by which 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) may prevent corticosteroid-induced osteoporosis in patients with early rheumatoid arthritis (RA), with a focus on T cell biology. Methods. Peripheral blood mononuclear cells (PBMCs) and CD4+CD45RO+ (memory) and CD4+CD45RO- (non-memory) T cells separated by fluorescence-activated cell sorting (FACS) from treatment-naive patients with early RA were stimulated with anti-CD3/anti-CD28 in the absence or presence of various concentrations of 1,25(OH) 2D3, dexamethasone (DEX), and 1,25(OH)2D 3 and DEX combined. Levels of T cell cytokines were determined by enzyme-linked immunosorbent assay and flow cytometry. Results. The presence of 1,25(OH)2D3 reduced interleukin-17A (IL-17A) and interferon-γ levels and increased IL-4 levels in stimulated PBMCs from treatment-naive patients with early RA. In addition, 1,25(OH)2D 3 had favorable effects on tumor necrosis factor α (TNFα):IL-4 and IL-17A:IL-4 ratios and prevented the unfavorable effects of DEX on these ratios. Enhanced percentages of IL-17A- and IL-22-expressing CD4+ T cells and IL-17A-expressing memory T cells were observed in PBMCs from treatment-naive patients with early RA as compared with healthy controls. Of note, we found no difference in the percentage of CD45RO+ and CD45RO- cells between these 2 groups. Interestingly, 1,25(OH)2D3, in contrast to DEX, directly modulated human Th17 polarization, accompanied by suppression of IL-17A, IL-17F, TNFα, and IL-22 production by memory T cells sorted by FACS from patients with early RA. Conclusion. These data indicate that 1,25(OH)2D3 may contribute its bone-sparing effects in RA patients taking corticosteroids by the modulation of Th17 polarization, inhibition of Th17 cytokines, and stimulation of IL-4

A systematic review on time trend incidence of rheumatoid arthritis in outpatient rheumatology clinics

Objectives: To classify patients with rheumatoid arthritis (RA) in an earlier stage of the disease, the ACR/EULAR classification criteria were updated in 2010. These criteria might have led to an increased incidence of RA in the rheumatology clinic. Since a higher incidence increases the socio-economic burden of RA, it is worthwhile to evaluate whether there is a time effect. Materials and methods: A systematic review was conducted using Embase, Medline Ovid, Cochrane Central, and Web of Science from database inception to February 2021. Included were only articles that addressed incidence rates of rheumatoid arthritis from rheumatology outpatient clinics. Results: Of the 6,289 publications only 243 publications on RA were found eligible for full-text review. Nine studies were included reporting incidence. The pooled incidence for RA was 11% (95% CI 6–16%) per year. Over time the incidence increased after the introduction of the 2010 ACR/EULAR classification criteria. Overall there was a high intragroup heterogeneity (I2 = 97.93%, p < 0.001), caused by geographical area, study design and differences in case definitions. Conclusion: Although the incidence seems to increase after the introduction of the 2010 ACR/EULAR criteria, no conclusions can be drawn on this time effect due to heterogeneity