Global Disease Activity Research Articles

Neutrophil and mononuclear leukocyte pathways and upstream regulators revealed by serum proteomics of adult and juvenile dermatomyositis.

Serum protein abundance was assessed in adult and juvenile dermatomyositis (DM and JDM) patients to determine differentially regulated proteins, altered pathways, and candidate disease activity biomarkers. Serum protein expression from 17 active adult DM and JDM patients each was compared to matched, healthy control subjects by a multiplex immunoassay. Pathway analysis and protein clustering of the differentially regulated proteins were examined to assess underlying mechanisms. Candidate disease activity biomarkers were identified by correlating protein expression with disease activity measures. Seventy-eight of 172 proteins were differentially expressed in the sera of DM and JDM patients compared to healthy controls. Forty-eight proteins were differentially expressed in DM, 32 proteins in JDM, and 14 proteins in both DM and JDM. Twelve additional differentially expressed proteins were identified after combining the DM and JDM cohorts. C-X-C motif chemokine ligand 10 (CXCL10) was the most strongly upregulated protein in both DM and JDM sera. Other highly upregulated proteins in DM included S100 calcium binding protein A12 (S100A12), CXCL9, and nicotinamide phosphoribosyltransferase (NAMPT), while highly upregulated proteins in JDM included matrix metallopeptidase 3 (MMP3), growth differentiation factor 15 (GDF15), and von Willebrand factor (vWF). Pathway analysis indicated that phosphoinositide 3-kinase (PI3K), p38 mitogen-activated protein kinase (MAPK), and toll-like receptor 7 (TLR7) signaling were activated in DM and JDM. Additional pathways specific to DM or JDM were identified. A protein cluster associated with neutrophils and mononuclear leukocytes and a cluster of interferon-associated proteins were observed in both DM and JDM. Twenty-two proteins in DM and 24 proteins in JDM sera correlated with global, muscle, and/or skin disease activity. Seven proteins correlated with disease activity measures in both DM and JDM sera. IL-1 receptor like 1 (IL1RL1) emerged as a candidate global disease activity biomarker in DM and JDM. Coordinate analysis of protein expression in DM and JDM patient sera by a multiplex immunoassay validated previous gene expression studies and identified novel dysregulated proteins, altered signaling pathways, and candidate disease activity biomarkers. These findings may further inform the assessment of DM and JDM patients and aid in the identification of potential therapeutic targets.

Disabling foot pain and its impact on daily living among people with psoriatic arthritis in Singapore: a cross-sectional observational investigation

BackgroundPsoriatic Arthritis (PsA)-related foot involvement has been shown to have a profound impact on daily functioning, with most studies having focused on predominantly Caucasian populations. The aim was to describe disabling foot pain (DFP) and its impact on daily living in PsA in Singapore.MethodsA cross-sectional, retrospective study was conducted using clinical data collected during a single-visit to a rheumatology clinic in Singapore. Records for adults with physician-diagnosed PsA were reviewed for sociodemographic information, disease characteristics, global disease activity and burden. Foot-specific measures included clinical assessment and the Manchester Foot Pain and Disability Index used to define DFP and evaluate between-group differences.ResultsForty-two participants with PsA (83% female, 57% Chinese, 31% Malay, 9.5% Indian, mean (SD) age 54-years (16)) attended the rheumatology clinic over the study-period. The median (IQR) disease duration was 2-years (11) and all were taking current DMARDs. Global disease measures demonstrated mild-to-moderate global disease activity and mild functional impairment, and were significantly higher in those with DFP. Despite 90% reporting to be coping well with their condition, self-care and having emotional support (n = 38), this study sample demonstrated high levels of anxiety/depression (29%), sleep disturbance (34%) and fatigue (24%), and a lack of disease- and drug-specific knowledge (64%). Further management was indicated for medication adherence counselling (48%), occupational therapy (43%), physiotherapy (36%) and podiatry (30%). Nearly half had current foot pain with 40% reporting DFP (n = 17), which caused significantly greater difficulty walking 3 km than those without DFP (p < 0.05). Rearfoot enthesitis (plantar fasciitis, Achilles enthesitis) was the most common cause of DFP (67%) with pain lasting longer than 1-year. 72% were overweight or obese, with a high proportion not engaging in any cardiovascular exercise (70%). Three of 42 participants had previously seen a podiatrist.ConclusionsPeople with DFP in PsA experience more severe global disease activity, reduced mobility and higher levels of negative impact on their daily lives in Singapore. In the absence of working in a multidisciplinary-team, there is value in comprehensive assessments that have potential to capture a holistic view of personal impact and improve person-centred care in PsA.

Pulmonary and extra-pulmonary effects of lung transplantation in an Italian cohort of patients with systemic sclerosis

Abstract Objectives Lung transplantation (LuTx) is a life-saving intervention for SSc patients with end-stage lung disease. The aim of this study was to evaluate patients’ survival and LuTx outcomes on systemic disease manifestations. Methods A retrospective evaluation was conducted on SSc patients who underwent LuTx between 2010 and 2021. Outcomes assessed at baseline, 6, 12 and 24 months post-LuTx included skin involvement by modified Rodnan skin score (mRSS), and global disease activity using a modified EUSTAR index (0–9 scale). Lung function rescue was evaluated by forced vital capacity (FVC). Patient survival was assessed by Kaplan–Meier analysis. Results Thirteen SSc patients were included, with a male/female ratio 9/4 and a median age of 48.7 years. Nine patients were affected by diffuse cutaneous scleroderma (dcSSc) and four by limited cutaneous scleroderma (lcSSc). FVC significantly increased from 56% of the predicted value at baseline to 78% at 2 years (P = 0.003). mRSS decreased from 7.4 ± 3.8 to 3.3 ± 2.5 in patients with dcSSc (P = 0.02). The modified EUSTAR index score decreased from 2.54 ± 1.8 at baseline to 0.49 ± 0.5 at 2 years (P = 0.02). Survival rate was 92.3% at 2 years, and 76.9% at 5 years. No unexpected adverse events were observed. Conclusions In SSc patients undergoing LuTx, an excellent 2-year survival was observed, without any disease-related adverse events. Our study supports LuTx as a viable option in SSc patients with end-stage lung disease. Apart from expected recovery of lung function, LuTx was associated with improvement of mRSS and global systemic disease activity.

Associations between 6-minute walk distance and physiologic measures and clinical outcomes in myositis-associated interstitial lung disease.

The 6-min walk test (6MWT) is a simple test widely used to assess sub-maximal exercise capacity in chronic respiratory diseases. We explored the relationship of 6-min walk distance (6MWD) with measurements of physiological, clinical, radiographic measures in patients with myositis-associated interstitial lung disease (MA-ILD). We analyzed data from the Abatacept in Myositis Associated Interstitial lung disease (Attack My-ILD) study, a 48-week multicentre randomized trial of patients with anti-synthetase antibodies and active MA-ILD. 6MWD, forced vital capacity (FVC), diffusing capacity (DLCO), high resolution CT, and various physician/patient reported outcome measures were obtained during the trial. Spearman's correlations and repeated-measures analysis with linear mixed-effects models were used to estimate the associations between 6MWD and various physiologic, clinical and radiographic parameters both cross-sectionally and longitudinally. Twenty participants with a median age of 57, 55% male and 85% white were analyzed. Baseline 6MWD did not associate with baseline PFTs. Repeated-measures analysis showed 6MWD over time associated with FVC over time, but not with DLCO. 6MWD over time also correlated with UCSD dyspnea score, Borg scores, as well as global disease activity and muscle strength over time. Emotional role functioning, vitality, general health and physical functioning scores by short form 36 also correlated with 6MWD over time. : Exploratory work in a small cohort of MA-ILD demonstrated 6MWD over time associated with parallel changes in FVC and patient reported outcomes of dyspnea, but not with DLCO. Larger studies are needed to validate the reliability, responsiveness and utility of the 6MWT in MA-ILD. ClinicalTrials.gov, NCT03215927.

Transition to Adulthood through Coaching and Empowerment in Rheumatology (TRACER): A feasibility study protocol.

The transition from pediatric to adult care for patients with chronic disease is a vulnerable period, with risks of disengagement from care and subsequent complications of inadequately managed disease. This period comes at a time when there are many other transitions occurring in the young person's life, including changes to vocation, social supports, and to their physiology. The aim of the TRACER study is to assess the feasibility of conducting a multi-center, randomized-controlled trial of a virtual Transition Coach Intervention in youth transferring from pediatric to adult rheumatology care. Patients are being recruited at their last pediatric rheumatology visit from McMaster Children's Hospital and Children's Hospital, London Health Sciences Centre in Ontario, Canada. Participants are then randomized to standard of care or to eight transition coaching sessions, covering topics around health management, future planning, and self-advocacy. The primary outcomes of the study are to demonstrate protocol feasibility, including optimal recruitment and consent rates, ≥ 90% coaching session completion, and complete data collection with ≤ 5% missing data. Baseline demographics, transition readiness, global functional assessment, disease activity, and self-efficacy will be collected to characterize the study population. Recruitment has begun and is estimated to last 19 months. This study will inform the design of a robust, multi-centered, randomized-controlled study to investigate the impact of a virtual transition coaching program in supporting the physical, mental, and social well-being of youth with rheumatic disease transitioning into adult care. Clinical trial registration: ClinicalTrials.Gov protocol ID: 14499.

Construct validity of PROMIS pain interference, fatigue, and physical function as patient-reported outcomes in adults with idiopathic inflammatory myopathies: An international study from the OMERACT myositis working group

BackgroundValidated patient-reported outcome measures to assess disease impact in patients with adult idiopathic inflammatory myopathies (IIMs) are needed. The objective of this study was to assess the construct validity of PROMIS Pain Interference, Fatigue, and Physical Function measures in comparison with core disease activity measures. MethodsAdults with IIM, excluding inclusion body myositis, from OMERACT Myositis Working Group (MWG) clinic sites completed PROMIS Short Form v1.0—Pain Interference 6a, PROMIS Short Form v1.0—Fatigue 7a, and PROMIS Short Form v2.0—Physical Function 8b measures. Core disease activity measures including patient and physician global disease activity assessments, manual muscle testing, serum creatine kinase activity, and Health Assessment Questionnaire Disability Index (HAQ-DI) were simultaneously assessed. To evaluate construct validity, a priori hypotheses for the expected correlations between PROMIS measures, age, and core disease measures were determined by >70 % agreement among MWG members and were compared against observed Pearson's correlations. Internal consistency of items and floor or ceiling effects for the PROMIS measures were also assessed. Subgroup analysis according to IIM subtype (dermatomyositis vs. non-dermatomyositis IIM) was performed. Results135 adults with IIM from 5 countries across North America, Europe, Asia, and Australia were included. For construct validity, a priori hypotheses were confirmed for 5 of 6 (83 %) PROMIS Pain Interference, 4 of 5 (80 %) PROMIS Fatigue, and 3 of 4 (75 %) PROMIS Physical Function correlations. Internal consistency was high for each PROMIS measure (Cronbach's alpha >0.9). Ceiling effects were observed only for PROMIS Pain Interference, with low/no pain in 29 % of patients. Subgroup analysis between dermatomyositis (n = 65) and non-dermatomyositis (n = 70) subtypes demonstrated similar correlations between PROMIS measures and disease activity measures. ConclusionsPROMIS Short Form v1.0—Pain Interference 6a, PROMIS Short Form v1.0—Fatigue 7a, and PROMIS Short Form v2.0—Physical Function 8b measures demonstrate strong construct validity when compared to core disease activity measures in IIM, with consistent results across IIM subtypes. These findings support the use of these selected PROMIS measures to assess core domains of interest for measuring life impact in IIMs.

Overexpression of BAG3 (Bcl2-associated athanogene 3) in serum and skin of patients with systemic sclerosis.

BAG3 (Bcl2-associated athanogene3) is able to induce the transformation of cancer-associated fibroblasts to alpha smooth muscle actin (a-SMA) positive (+) myofibroblasts. In systemic sclerosis (SSc), a-SMA+ myofibroblasts also play an important role in the progression of fibrosis in the skin and involved internal organs. The aim of the study was to investigate whether BAG3 is overexpressed in SSc and may be a biomarker of fibrogenesis. BAG3 serum levels were measured in 106 patients with SSc, 47 with the limited (lc) and 59 the diffuse (dc) SSc, and in age- and sex-matched healthy controls (HC). BAG3 levels were then compared according to their clinical subset, nailfold video-capillaroscopic (NVC) patterns, interstitial lung disease (ILD, and correlated with modified Rodnan skin score (mRSS) and global disease activity. BAG3 expression was also investigated in skin biopsies of 8 dcSSc patients. BAG3 serum levels were significantly higher in dcSSc (143.3 pg/mL, 95%CI 78-208.5) than in HC (0.68 pg/mL, 95%CI 0.13-1.23), and were significantly higher in patients with late NVC pattern and ILD but did not correlate with disease activity and mRSS. Of note, BAG3 was strongly expressed in the skin biopsies of dcSSc patients. BAG3 is overexpressed in dcSSc patients and may contribute to skin and organ fibrosis by prompting the transition of fibroblasts into myofibroblasts and increasing their survival. Thus, BAG3 may play an important role in SSc fibrotic pathogenesis and be a potential biomarker of fibrosis. Further research on its role as a therapeutic target is warranted.

Inflammation dynamically regulates steroid hormone metabolism and action within macrophages in rheumatoid arthritis

RationaleIn inflammatory diseases such as rheumatoid arthritis (RA), steroid metabolism is a central component mediating the actions of immuno-modulatory glucocorticoids and sex steroids. However, the regulation and function of cellular steroid metabolism within key leukocyte populations such as macrophages remain poorly defined. In this study, the inflammatory regulation of global steroid metabolism was assessed in RA macrophages. MethodsBulk RNA-seq data from RA synovial macrophages was used to assess transcripts encoding key enzymes in steroid metabolism and signalling. Changes in metabolism were assessed in synovial fluids, correlated to measures of disease activity and functionally validated in primary macrophage cultures. ResultsRNA-seq revealed a unique pattern of differentially expressed genes, including changes in genes encoding the enzymes 11β-HSD1, SRD5A1, AKR1C2 and AKR1C3. These correlated with disease activity, favouring increased glucocorticoid and androgen levels. Synovial fluid 11β-HSD1 activity correlated with local inflammatory mediators (TNFα, IL-6, IL-17), whilst 11β-HSD1, SRD5A1 and AKR1C3 activity correlated with systemic measures of disease and patient pain (ESR, DAS28 ESR, global disease activity). Changes in enzyme activity were evident in inflammatory activated macrophages in vitro and revealed a novel androgen activating role for 11β-HSD1. Together, increased glucocorticoids and androgens were able to suppress inflammation in macrophages and fibroblast-like-synoviocytes. ConclusionsThis study underscores the significant increase in androgen and glucocorticoid activation within inflammatory polarized macrophages of the synovium, contributing to local suppression of inflammation. The diminished profile of inactive steroid precursors in postmenopausal women may contribute to disturbances in this process, leading to increased disease incidence and severity.

Clinical and prognostic associations of anti-Jo-1 antibody levels in patients with antisynthetase syndrome

ObjectiveTo investigate the association of serum anti-Jo-1 antibody levels with the disease activity and prognosis in anti-Jo-1-positive patients with antisynthetase syndrome (ASS).MethodsThis study included 115 anti-Jo-1-positive patients with ASS who were admitted to China-Japan Friendship Hospital between 2009 and 2019. Anti-Jo-1 antibody serum levels at initial admission and follow-up were determined by enzyme-linked immunosorbent assay (ELISA). Global and organ disease activity was assessed at baseline and follow-up according to the International Myositis Assessment and Clinical Studies guidelines.ResultsAmong enrolled patients, 70 (60.9%) patients initially presented with interstitial lung disease (ILD), and 46 (40%) patients presented with with muscle weakness at initial admission. At baseline, patients with ILD had lower levels of anti-Jo-1 antibodies than those without ILD (p = 0.012). Baseline anti-Jo-1 antibody levels were higher in patients with muscle weakness, skin involvement, and arthritis (all p < 0.05) compared to those without these manifestations. Baseline anti-Jo-1 antibody levels were positively correlated with skin visual analogue scale (VAS) scores (r = 0.25, p = 0.006), but not with disease activity in other organs. However, changes in anti-Jo-1 antibody levels were significantly positively correlated with the changes in PGA (β = 0.002, p = 0.001), muscle (β = 0.003, p < 0.0001), and pulmonary (β = 0.002, p = 0.013) VAS scores, but not with skin and joint VAS scores. Older age of onset (hazard ratio [HR] 1.069, 95% confidence interval [CI]:1.010–1.133, p = 0.022) and higher C-reactive protein (CRP) levels (HR 1.333, 95% CI: 1.035–1.717, p = 0.026) were risk factors for death.ConclusionAnti-Jo-1 titers appear to correlate more with disease activity changes over time rather than with organ involvement at baseline, which provides better clinical guidance for assessing the disease course using anti-Jo-1 levels.

The impact of pain on daily activities in patients with idiopathic inflammatory myopathies: Report from the OMERACT myositis working group

BackgroundInternational focus groups with patients with idiopathic inflammatory myopathies (IIM) conducted by the OMERACT Myositis Working Group over the years demonstrated the pain as an important symptom experienced by these patients. In this study, we aimed to examine the frequency and degree of pain interference, the aspects of daily life impacted by pain, and the factors associated with pain interference in adults with IIM. MethodsThis was a prospective observational study with two visits. The patients who fulfilled the probable/definite IIM (ACR/EULAR Myositis Classification Criteria) were enrolled. Pain interference was assessed with PROMIS pain interference form (6a). Myositis core set measures and PROMIS fatigue (7a) and physical function (8b) were obtained at both visits. Logistic regression and linear mixed models were performed to assess the association between pain interference and other parameters. ResultsA total of 129 patients with IIM (60 % females) were recruited from U.S., South Korea, Netherlands, Sweden, and Australia. Approximately 71 % reported pain interference. The patients in the greater pain interference group were more likely to be female, had significantly worse patient/physician global disease activity, fatigue, and physical function than those in the lower pain interference group. The most commonly impacted life aspect was household chores. Manual muscle testing, patient/physician global disease activity, fatigue, and physical function were all significantly associated with pain interference score >60. ConclusionThe majority of the patients with IIM experience the impact of pain on their daily activities, particularly household chores. Myositis disease activity, duration, and subtype could be associated with greater pain interference.

Serum and urine interferon-inducible protein 10, galectin-9, and SIGLEC-1 as biomarkers of disease activity in systemic lupus erythematosus.

In this prospective study, we aimed to investigate the association of serum (s) and urine (u) IP-10, galectin-9, and SIGLEC-1 with disease activity in patients with systemic lupus erythematosus (SLE). Sixty-three patients with active SLE (31 renal, 32 extrarenal) were included. Thirty patients with inactive SLE (15 renal, 15 extrarenal), 17 with renal active AAV, and 32 healthy volunteers were selected as control groups. Serum and urine IP-10, galectin-9, and SIGLEC-1 were tested using ELISA. Levels of sIP-10 (p = 0.046), uIP-10 (p < 0.001), sGalectin-9 (p = 0.03), and uSIGLEC-1 (p = 0.006) were significantly higher in active SLE group compared to the inactive SLE; however, no differences were detected in the comparison of uGalectin-9 (p = 0.18) and sSIGLEC-1 (p = 0.69) between two groups. None of the biomarkers discriminated patients with active renal SLE from active extrarenal SLE. ROC analyses revealed an AUC of 0.63 (0.52-0.73) for sIP-10, 0.78 (0.68-0.86) for uIP-10, 0.64 (0.53-0.74) for sGalectin-9, and 0.68 (0.57-0.77) for uSIGLEC-1 in discriminating disease activity in SLE, which did not outperform C3 (0.75, 0.64-0.84) and C4 (0.72, 0.61-0.82). sIP-10 (p = 0.001), uIP-10 (p = 0.042), and uGalectin-9 (p = 0.009) were significantly increased in patients with active renal SLE compared to active renal AAV. sGalectin-9 (p < 0.001) and sIP-10 levels (p = 0.06) were decreased after 8 (5-22.5) months of treatment. sIP-10, uIP-10, sGalectin-9, and uSIGLEC-1 reflect global disease activity in SLE but do not outperform C3 and C4. sIP-10 and uIP-10 may be specific for active SLE compared to active AAV. sIP-10 and sGalectin-9 might be valuable in monitoring response after treatment.

Efficacy and safety of apremilast in pediatric patients with moderate-to-severe plaque psoriasis: 16-week results from SPROUT, a randomized controlled trial

Approved systemic treatment options are limited for pediatric patients with moderate to severe plaque psoriasis. To assess the efficacy and safety of apremilast over 16weeks in pediatric patients with plaque psoriasis. SPROUT (NCT03701763) was a phase 3, multicenter, randomized, double-blind, placebo-controlled study of apremilast in patients aged 6-17years with moderate-to-severe psoriasis (Psoriasis Area and Severity Index [PASI] ≥12, body surface area ≥10%, static Physician Global Assessment [sPGA] ≥3) inadequately controlled by/inappropriate for topical therapy. Patients were stratified by age group and randomized (2:1) to apremilast (20 or 30mg BID based on weight) or placebo for 16weeks, followed by apremilast extension to 52weeks. Of 245 patients randomized (apremilast: 163; placebo: 82), 221 (90%) completed the double-blind phase (apremilast: 149; placebo: 72). Significantly more patients achieved sPGA response and ≥75% reduction in PASI with apremilast than placebo, regardless of baseline age, weight, or disease severity. No new safety signals were observed. Sample size of subgroup analyses. Improvements in global disease activity and skin involvement were significantly greater in pediatric patients treated with apremilast versus placebo. Adverse events were consistent with the known apremilast safety profile.

Patient-reported outcomes in large vessel vasculitis: insights from a retrospective analysis of disease activity and associated factors

BackgroundPatient-reported outcomes (PROs) play a crucial role in assessing rheumatic diseases, offering insights into disease evaluation and treatment efficacy. This study focuses on PRO assessment in large vessel vasculitides, including Takayasu Arteritis and Giant Cell Arteritis (GCA).MethodsWe retrospectively analyzed routine data from patients treated at our rheumatology clinic over a 10-year span. Patient and physician-rated global disease activity scale (G-DAS) scores, measured on a numeric rating scale (0–10 points), were collected at each visit. Clinical variables like age, sex, body mass index (BMI), disease duration, lab values, pain perception, and questionnaire responses were recorded. Linear regression and generalized additive linear regression (GAM analysis) examined associations between PROs and these factors.ResultsThe study included 138 patients, primarily diagnosed with GCA (94.4%). Mean follow-up was 2.5 years (0-7.7). Patient and physician G-DAS exhibited a moderate correlation (Pearson R 0.19, CI 0.14–0.24, p < 0.001). Higher patient G-DAS correlated with younger age (CI -3.4 - -1.5, p < 0.001), increased pain (CI 3.5-4, p < 0.001), functional limitations (HAQ, CI 0.5–0.6, p < 0.001), reduced physical (CI 2.3–2.7, p ≤ 0.001) and psychological well-being (CI 2.1–2.5, p < 0.001), and higher BMI (CI 1.3–2.4, p < 0.001). Physician G-DAS correlated with Birmingham Vasculitis Activity Score (V3.0; R 0.42, p 0.046) and were significantly linked to serum CRP elevations (β = 0.04, CI 0.0-0.08, p 0.028).ConclusionsThese findings underscore the need to integrate PRO measures into vasculitis disease management strategies, enhancing the understanding of disease activity from the patient’s perspective.

The Neutrophil-to-Lymphocyte Ratio as a Surrogate Marker for Disease Activity in Systemic Lupus Erythematosus: A Correlation Study Using the SLE-DAS

Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder mainly affecting women of childbearing age. Mortality and organ damage of SLE is mainly due to uncontrolled disease activity and treatment-related toxicities. Thus, assessment of disease activity is important during routine clinical practice. In recent years, neutrophil-to-lymphocyte ratio (NLR) has been explored as a marker of disease in many autoimmune disorders including SLE. As such, our study objective is to investigate the correlation between neutrophil-to-lymphocyte ratio (NLR) and disease activity of SLE using the SLE disease activity score (SLE-DAS) in our local population. Methods: Consecutive adult patients who fulfilled the ACR or SLICC criteria for SLE were recruited between March 2023 and February 2024. SLE activity was assessed by SLE-DAS, physicians’ global assessment (PGA) and SLE disease activity index-2000 (SLEDAI-2K). The calculated NLR was correlated with disease activity indices and serological parameters (anti-dsDNA, C3/4) by Spearman’s rank correlation. Patients were stratified into remission, low and moderate/severe disease activity as defined by the SLE-DAS and comparison of the NLR was performed among these subgroups by one-way ANOVA. Results: A total of 420 SLE patients were studied (96.2% women, age 46.0± 11.0 years, SLE duration 16.4± 8.3 years). Moderate/severe, low disease activity and SLE-DAS remission was present in 70(16.7%), 66(15.7%), and 284(67.6%) patients, respectively. SLE-DAS correlated significantly with SLEDAI-2K (rho 0.9; p&lt;0.001) and PGA (Rho 0.60; p&lt;0.001). The mean NLR of all patients was 3.54± 4.0 and NLR correlated significantly with SLE-DAS (Rho 0.17; p&lt;0.001). The NLR was significantly higher in active renal (urine P/Cr &gt;0.5, active sediments or histological features) than inactive SLE (4.62 vs 3.27; p=0.02). The NLR in patients with moderate/severe SLE-DAS activity was significantly higher than those in remission (4.87 vs 3.27; p=0.007). ROC analysis showed that a NLR cut-off of 3.11 showed a sensitivity of 55.6% and specificity of 68.7% in detecting moderate/severe SLE-DAS (AUC 0.67[0.6-0.7]; p&lt;0.001). Conclusion: The NLR is a satisfactory and convenient marker that correlates significantly with disease activity in SLE.

Responsiveness and meaningful thresholds of PROMIS pain interference, fatigue, and physical function forms in adults with idiopathic inflammatory myopathies: Report from the OMERACT Myositis Working Group

BackgroundA series of qualitative studies conducted by the OMERACT Myositis Working Group identified pain interference, fatigue, and physical function as highly important life impact domains for adults with idiopathic inflammatory myositis (IIM). In this study, our goal was to assess the responsiveness and minimal important difference of PROMIS pain interference (6a), fatigue (7a), and physical function (8b). MethodsAdults with IIM from USA, Netherlands, Korea, Sweden, and Australia with two "clinical" visits were enrolled in this prospective study. Anchor questions on a Likert scale were collected at baseline, and manual muscle testing (MMT), physician and patient reported global disease activity, and PROMIS instruments were collected at both visits. Responsiveness was assessed with i) ANOVA, ii) paired t-test, effect size and standardized response mean, and iii) Pearson correlation. Minimal important difference (MID), minimal important change (MIC) and minimal detectable change (MDC) values were calculated. Results114 patients with IIM (median age 60, 60 % female) completed both visits. Changes in PROMIS instruments were significantly different among anchor categories. Patients who reported improvement had a significant improvement in their PROMIS scores with at least medium effect size, while patients who reported worsening and stability did not show a significant change with weak effect size. PROMIS instruments had weak to moderate correlations with MMT, patient and physician global disease activity. MID was approximately 2–3 points for Pain Interference and 3–4 points for Fatigue and Physical Functionforms based on the method used. MIC was approximately 4–5 for improvement of all the instruments, while MDC was 1.7–2 points for Pain Interference and Physical Function and 3.2–3.9 for Fatigue. ConclusionThis study provides evidence towards the responsiveness of the PROMIS instruments in a large international prospective cohort of adults with IIM supporting their use as PROMs in adult myositis.

Long-term follow-up of children with chronic non-bacterial osteomyelitis—assessment of disease activity, risk factors, and outcome

IntroductionChronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone-disease of unknown origin. The National Pediatric Rheumatologic Database (NPRD) collects long-term data of children and adolescents with rheumatic diseases including CNO.ObjectiveTo assess characteristics, courses, and outcomes of CNO with onset in childhood and adolescence and to identify outcome predictors.MethodsFrom 2015 to 2021 patients with a confirmed diagnosis of CNO, who were registered in the NPRD during their first year of disease and at least one follow-up visit, were included in this analysis and observed for up to 4 years.ResultsFour hundred patients with recent diagnosis of CNO were enrolled in the NRPD during the study period. After 4 years, patient data documentation was sufficient to be analyzed in 81 patients. A significant decline of clinical and radiological lesions is reported: at inclusion in the registry, the mean number of clinical lesions was 2.0 and 3.0 MRI lesions per patient. A significant decrease of manifestations during 4 years of follow-up (mean clinical lesions 0.5, p < 0.001; mean MRI lesions 0.9 (p < 0.001)) was documented. A significant improvement of physician global disease activity (PGDA), patient-reported overall well-being, and childhood health assessment questionnaire (C-HAQ) was documented. Therapeutically, an increase of disease-modifying anti-rheumatic drugs over the years can be stated, while bisphosphonates rather seem to be considered as a therapeutic DMARD option in the first years of disease. Only 5–7% of the patients had a severe disease course as defined by a PGDA > = 4. Predictors associated with a severe disease course include the site of inflammation (pelvis, lower extremity, clavicle), increased erythrocyte sedimentation rate, and multifocal disease at first documentation. The previously published composite PedCNO disease activity score was analyzed revealing a PedCNO70 in 55% of the patients at 4YFU.ConclusionAn improvement of physician global disease activity (PGDA), patient reported overall well-being and imaging-defined disease activity measures was documented, suggesting that inactivity of CNO disease can be reached. PedCNO score and especially PGDA, MRI-defined lesions and in a number of patients also the C-HAQ seem to be reliable parameters for describing disease activity. The identification of risk factors at the beginning of the disease might influence treatment decision in the future.

In early rheumatoid arthritis, anticitrullinated peptide antibodies associate with low number of affected joints and rheumatoid factor associates with systemic inflammation

ObjectivesTo investigate how individual rheumatoid arthritis (RA) autoantibodies associate with individual signs and symptoms at the time of RA diagnosis.MethodsIgA, IgG, IgM rheumatoid factor (RF), antibodies against cyclic citrullinated peptide...

Effects of Mirikizumab on Histologic Resolution of Crohn's Disease in a Randomized Controlled Phase 2 Trial

Histologic evaluation of mucosal healing in Crohn's disease (CD) is an evolving treatment target. We evaluated histologic outcomes for mirikizumab efficacy and associations with endoscopic and 1-year outcomes. Biopsies from 1 ileal and 4 colonic segments were evaluated at Weeks 0, 12, and 52 from each 170 SERENITY participants. Criteria for the Weeks 12 and 52 histologic response (a) no epithelial neutrophils or epithelial damage, or (b) >50% decrease in either Robarts Histopathology Index or active Global Histologic Disease Activity Score and remission (no mucosal neutrophils and no epithelial damage) had to be met in all biopsies. Agreement was evaluated between histologic and endoscopic endpoints. Associations between 1-year outcomes and Week 12 histologic and endoscopic response were evaluated. At Week 12, 1000 mg mirikizumab resulted in greater rates of histologic response (66% vs 27%, P<0.001) and remission (26% vs 6%, P<0.01) than placebo. Rates were numerically similar at 1-year (mirikizumab pooled response: 46-69%, remission: 13-31%). Agreement between Week 12 histologic and endoscopic response was 69% (Cohen's Kappa coefficient (κ)=0.40) and remission was 83% (κ=0.38) in all pooled arms, including placebo. At 1-year, the percentage of participants who received any dose of mirikizumab and achieved endoscopic remission differed by their Week 12 response: histologic (20%), endoscopic (25%), combined histology-endoscopy (45%), or neither (4%) (.003). In a post-hoc analysis of phase 2 data, mirikizumab induced and sustained histologic response and remission in CD over 52 weeks. Early combined histologic-endoscopic response was associated with endoscopic remission after 1 year of treatment with mirikizumab (ClinicalTrials.gov NCT02891226.

Prognostic factors associated with non-remission and low disease activity status af ter one year of psoriatic arthritis patients treatment in real practice

Background. Remission/low disease activity (LDA) are acceptable goal of psoriatic arthritis (PsA) treatment. Prognostic factors for non-remission/LDA hasn’t been fully studied yet and data is limited. The aim – to determine the prognostic factors associated with non-remission/LDA status within 1 year of treatment in PsA pts in real practice. Methods. 292 pts (M/F=122/170) with active PsA fulfilling the CASPAR criteria were included. Mean age 46.1±12.5 years (yrs), PsA duration 10.4±7.1 months (mos), psoriasis (Ps) duration 19.32±12.08 mos, body mass index (BMI) 27.7±5.6 kg/m2 , median (Me) of DAPSA – 23.8 [14.7; 37.4]. 182 pts was given therapy with synthetic (s) DMARDs predominantly methotrexate (MTX), 110 pts – bDMARDs as monotherapy or with combination with MTX or other sDMARDs. At baseline (BL) and at 1 year of therapy PsA activity by tender/swelling joint count (TJC)/68, (SJC)/66, pain (VAS), Patient global assessment disease activity (PtGA, VAS), CRP (mg/l), dactylitis, enthesitis by LEI and plantar fascia, BSA (%), HAQ, DAPSA were evaluated. DAPSA&gt;28 indicate high disease activity (HDA), DAPSA=15–28 – moderate activity (MoDA), DAPSA=5–14 – LDA, DAPSA≤4 – remission. By 1 year of therapy the proportion of pts who had not reached remission or LDA were calculated. The one-factor model of logistic regression was used to identify a group of features that are associated with remission or LDA nonachievement. M±SD, Me [Q25; Q75], Min–Max, %, t-test, Peаrson χ2 , Mann – Whitney tests, ORs with 95% CI were performed. All p&lt;0.05, were considered to indicate statistical significance. Results. At 1 year of therapy 116 pts of 292 (40%) have HDA/MoDA by DAPSA. Remission/LDA was reached in 176 (60%) pts, 110 of them (62.5%) were treated with bDMARDs. Comparative analysis in both groups and one-factor model of logistic regression showed the following features at BL were associated with non-remission/LDA status: TJC&gt;5 (p&lt;0.001), SJC&gt;3 (p&lt;0.001), CRP&gt;10 mg/l (p&lt;0.001), HAQ&gt;0.5 (p&lt;0.001), presence of enthesitis (p&lt;0.001), dactylitis (p&lt;0.001), BMI&gt;30 (p&lt;0.002) and had to be treated with sDMARDs. PsA pts with combination of these clinical features at first visit have a higher risk of not achieving remission/LDA status in comparison to PsA pts without them, OR with 95% CI. Conclusion. In real practice remission/LDA cannot achieve 40% PsA pts despite going through therapy. It is a combination of clinical fea tures at BL – TJC&gt;3, SJC&gt;5, CRP&gt;10 mg/l, HAQ&gt;0.5, presence of enthesitis, dactylitis, BMI&gt;30 kg/m2 and sDMARDs monotherapy – that constitutesa prognostic factor with negative impact on achievement remission/LDA after 1 year of treatment.

Subcutaneous immunoglobulin for patients with idiopathic inflammatory myopathies: a real-world, single-centre experience.

Idiopathic inflammatory myopathies (IIMs) are heterogeneous diseases characterized by skeletal muscle inflammation associated with cutaneous, pulmonary and/or other visceral organ involvement. IVIG has been recommended as an adjunct therapy for IIM patients refractory to conventional therapy. However, IVIG has high resource needs and increased risk of adverse reactions. Subcutaneous immunoglobulin (SCIG) therapy has been used as an alternative to IVIG in primary immunodeficiencies and neuroinflammatory disorders. We assessed the satisfaction, patient preference and effectiveness in IIM patients who transitioned from IVIG to SCIG. We retrospectively reviewed consecutive 20 patients with IIM who were transitioned from IVIG to SCIG therapy for >12 months. Patient preference between IVIG and SCIG was surveyed using a questionnaire previously used in studies of neuroinflammatory conditions. In addition, disease flares, changes in immunosuppression, cumulative prednisone doses and global disease activity were evaluated using the Myositis Intention to Treat Index (MITAX) 12 months pre- and post-SCIG initiation. Most patients (78.9%) preferred SCIG over IVIG and preferred home-based therapies to hospital-based therapies. There was no significant difference in global disease activity (MITAX 3.31 vs 3.02) or in cumulative steroid doses 12 months pre- or post-SCIG initiation. Three patients experienced disease flares, five escalated in immunosuppression, while four patients deescalated in immunosuppressive medications. SCIG is preferred by most patients over IVIG without a substantial increased disease activity or need for additional CS. Future cost-effectiveness studies may provide an additional rationale for utilizing SCIG over IVIG for maintenance therapy for IIM.