Physician Global Assessment Research Articles

Usefulness of Belimumab in Adult Patients With Systemic Lupus Erythematosus Evaluated Using Single Indexes: A Meta-Analysis and Systematic Review

BackgroundBelimumab is the first antibody drug approved for systemic lupus erythematosus (SLE), and is a fully human monoclonal antibody that inhibits soluble B lymphocyte stimulator protein. In clinical trials, a composite index was used to assess efficacy of belimumab. However, clinical guidelines on SLE treatment currently use single efficacy indexes. ObjectiveThe main objective of this study was to perform a meta-analysis to evaluate the efficacy of belimumab utilizing single indexes used in routine clinical practice, rather than the composite efficacy index used in clinical trials during the development phase. As a secondary endpoint, safety was also evaluated. MethodsSeveral databases were searched to identify reports published up to December 1, 2021 on randomized controlled trials examining the efficacy of belimumab in adult patients with SLE. From the clinical trial data, efficacy was evaluated using single indexes including the SLE Disease Activity Index (SLEDAI), British Isles Lupus Assessment Group Index, and Physician Global Assessment. Safety was also assessed. Data were synthesized and analyzed using Review Manager 5.4. This study protocol was registered in the UMIN Clinical Trials Registry (Registration number: UMIN000052846). ResultsThe search identified 12 reports that met the inclusion criteria. Five reports were included in efficacy evaluation and 9 in safety evaluation. The primary endpoint was SLEDAI. Significantly more belimumab-treated patients achieved a ≥4-point reduction in SLEDAI (relative risk 1.28; 95% confidence interval, 1.16–1.40; P < 0.00001) compared with placebo. Other efficacy endpoints were also improved significantly in the belimumab group. No difference in safety was found between belimumab and placebo. ConclusionsThe present meta-analysis evaluating clinical trial data using various single indexes recommended by clinical guidelines for SLE verifies that addition of belimumab to standard of care is efficacious for moderate-to-severe SLE.

The importance of ultrasound examination in care of juvenile idiopathic arthritis patients: 9 months follow-up study.

Juvenile idiopathic arthritis (JIA) is a group of rare musculoskeletal disorders with chronic inflammation of joints, typically manifesting before the age of 16 years. The assessment of disease activity remains pivotal in JIA treatment decisions, particularly during clinical remission. While musculoskeletal ultrasound (MSUS) has shown promise in detecting subclinical synovitis, longitudinal data on MSUS features in JIA remains limited. The aim of this study was to evaluate the prevalence of subclinical synovitis observed in MSUS over a follow-up period in JIA patients. Additionally, it sought to assess the consistency and correlation between clinical findings, standardized composite clinical score (JADAS10), and MSUS-detected synovitis during 9 months follow-up. a prospective single-center study was conducted, enrolling all consecutive JIA patients (excluding systemic JIA) seen at the study center in one year period. At three-months intervals over a 9 months period (M0, M3, M6 and M9), patients underwent clinical examination, laboratory tests, and MSUS assessment. Data on demographic characteristics, disease profile, and treatment were collected. Patients were categorized into active disease (ACT) or remission (REM) groups based on Wallace criteria and JADAS10 scores using previously validated thresholds. The ultrasound assessments adhered to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) pediatric group, covering 40 joints, were performed by two ultrasonographers at every visit. Subclinical synovitis was defined as synovitis detected exclusively by MSUS. Spearman's correlation coefficients (rs) were used to evaluate the association between MSUS, clinical data, and outcome measures, such as active joint count (ACJ), patient's/parent's global assessment of disease activity (PaGA), physician's global assessment of disease activity (PhGA) and JADAS10. subclinical synovitis was evident in 5.2% of all joints and in 80.6% of the patients at baseline. During the follow-up period, signs of subclinical synovitis decreased to 3.8% of joints, however, the proportion of affected patients remained high (67.7%), with the majority in REM group. Despite the consistent strong correlation between PaGA and PhGA throughout the study (rs > 0.895; p < 0.001), both measures displayed moderate (rs = 0.647; p < 0.001) to weak (rs = 0.377; p = 0.04) correlations with MSUS findings. Notably, PaGA remained significantly correlated with MSUS at the M9 visit (rs = 0.377, p = 0.04), while PhGA showed no correlation (p = 0.094). The study results indicate the persistence of subclinical inflammation detected by MSUS in a significant proportion of JIA patients, even during clinical remission. Moreover, the findings suggest that conventional measurements of JIA activity may be insufficient for assessing patients in clinical remission.

Deucravacitinib for Moderate-to-Severe Psoriasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

There is contrasting evidence regarding the efficacy and safety of JAK (Janus kinase) inhibitors in the treatment of psoriasis. This systematic review and meta-analysis assessed deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, as the therapy of choice for moderate-to-severe psoriasis. PubMed, Embase, and Cochrane databases were searched for randomized controlled trials, including patients with moderate-to-severe psoriasis. Outcomes of interest were serious adverse events (SAEs), the severity of illness, as measured by the validated questionnaires: Psoriasis Area and Severity Index (PASI) and scalp-specific Physician's Global Assessment (ss-PGA); and quality of life, measured by the Dermatology Life Quality Index (DLQI). Four studies with 1663 patients were included in the meta-analysis, of whom 1123 (67.5%) were treated with deucravacitinib during a 12-to-16-week follow-up. The mean age was 45.4 &plusmn; 13.3 years, and 70.2% were male. Two-thirds had a history of scalp psoriasis. Achievement of PASI 75 was significantly higher in the deucravacitinib group, as compared with placebo (RR 5.7; 95% CI 4.32-7.53; P&lt;0.001). Similarly, ss-PGA 0/1 (RR 3.86; 95%CI 3.02-4.94; P&lt;0.001) and DLQI 0/1 (RR 3.89; 2.89-5.22; P&lt;0.001) were also significantly more frequent in the deucravacitinib group. The incidence of SAEs was similar between groups. These findings suggest that patients with moderate-to-severe psoriasis treated with deucravacitinib for 12 to 16 weeks had significantly decreased severity of illness and improved quality of life, without a concerning increase in the incidence of SAEs. J Drugs Dermatol. 2024;23(2):67-73.&nbsp; doi:10.36849/JDD.7539.

Using a collaborative learning health system approach to improve disease activity outcomes in children with juvenile idiopathic arthritis in the Pediatric Rheumatology Care and Outcomes Improvement Network.

The Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) is a North American learning health network focused on improving outcomes of children with juvenile idiopathic arthritis (JIA). JIA is a chronic autoimmune disease that can lead to morbidity related to persistent joint and ocular inflammation. PR-COIN has a shared patient registry that tracks twenty quality measures including ten outcome measures of which six are related to disease activity. The network's global aim, set in 2021, was to increase the percent of patients with oligoarticular or polyarticular JIA that had an inactive or low disease activity state from 76% to 80% by the end of 2023. Twenty-three hospitals participate in PR-COIN, with over 7,200 active patients with JIA. The disease activity outcome measures include active joint count, physician global assessment of disease activity, and measures related to validated composite disease activity scoring systems including inactive or low disease activity by the 10-joint clinical Juvenile Arthritis Disease Activity Score (cJADAS10), inactive or low disease activity by cJADAS10 at 6 months post-diagnosis, mean cJADAS10 score, and the American College of Rheumatology (ACR) provisional criteria for clinical inactive disease. Data is collated to measure network performance, which is displayed on run and control charts. Network-wide interventions have included pre-visit planning, shared decision making, self-management support, population health management, and utilizing a Treat to Target approach to care. Five outcome measures related to disease activity have demonstrated significant improvement over time. The percent of patients with inactive or low disease activity by cJADAS10 surpassed our goal with current network performance at 81%. Clinical inactive disease by ACR provisional criteria improved from 46% to 60%. The mean cJADAS10 score decreased from 4.3 to 2.6, and the mean active joint count declined from 1.5 to 0.7. Mean physician global assessment of disease activity significantly improved from 1 to 0.6. PR-COIN has shown significant improvement in disease activity metrics for patients with JIA. The network will continue to work on both site-specific and collaborative efforts to improve outcomes for children with JIA with attention to health equity, severity adjustment, and data quality.

Clinical characteristics and disease course before and after SARS-CoV-2 infection in a large cohort of systemic sclerosis patients.

The objective of this study is to evaluate the clinical presentations and adverse outcomes of Coronavirus Disease 2019 (COVID-19) in patients with systemic sclerosis (SSc) and assess the impact of SSc features on the clinical course of COVID-19. In this multicenter, retrospective study, SSc patients with COVID-19 were included. Clinical features of SSc, along with detailed COVID-19 data, were extracted from medical records and patient interviews. The study included 112 patients (mean age 51.4 ± 12.8 years; 90.2% female). SSc-associated interstitial lung disease (ILD) was evident in 57.1% of the patients. The findings revealed hospitalization in 25.5%, respiratory support in 16.3%, intensive care unit admission in 3.6%, and a mortality rate of 2.7% among SSc patients with COVID-19. Risk factors for respiratory failure, identified through univariate analysis, included ILD (OR: 7.49, 95% CI: 1.63-34.46), ≥1 comorbidity (OR: 4.55, 95% CI: 1.39-14.88), a higher physician global assessment score at the last outpatient visit (OR 2.73, 95% CI: 1.22-6.10), and the use of mycophenolate at the time of infection (OR: 5.16, 95 %CI: 1.79-14.99). Notably, ≥1 comorbidity emerged as the sole significant predictor of the need for respiratory support in COVID-19 (OR: 5.78, 95% CI: 1.14-29.23). In the early post-COVID-19 period, 17% of patients reported the progression of the Raynaud phenomenon, and 10.6% developed new digital ulcers. Furthermore, progression or new onset of dyspnea and cough were detected in 28.3% and 11.4% of patients, respectively. This study suggests a potential association between adverse outcomes of COVID-19 and SSc-related ILD, severe disease activity, and the use of mycophenolate. Additionally, it highlights that having comorbidities is an independent risk factor for the need for respiratory support in COVID-19 cases.

Efficacy and safety of intravenous belimumab in a subgroup of South Korean patients with systemic lupus erythematosus enrolled into a Phase 3, randomized, placebo-controlled trial in North East Asia.

This post hoc analysis evaluated the efficacy and safety of intravenous belimumab 10 mg/kg in the South Korean subgroup of patients with systemic lupus erythematosus (SLE) enrolled in the North East Asia (NEA) study (GSK Study BEL113750; NCT01345253). NEA was a double-blind, placebo-controlled, randomized Phase 3 trial. Patients with active, autoantibody-positive SLE were randomized 2:1 to belimumab or placebo plus standard therapy administered on Days 0, 14, and 28, and then every 28 days up to Week 48. The primary efficacy endpoint in this analysis was SLE Responder Index 4 (SRI-4) response rate at Week 52, defined as the proportion of patients achieving a ≥4-point reduction in Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score, no worsening (<0.3 increase from baseline) in Physician Global Assessment, no new British Isles Lupus Assessment Group (BILAG) A domain and <2 new BILAG B domain scores. Among 100 South Korean patients enrolled in NEA, 54/66 (81.8%) belimumab- and 24/34 (70.6%) placebo-treated patients completed the double-blind phase. Significantly more belimumab- than placebo-treated patients achieved SRI-4 response at Week 52 (n = 35/66, 53.0% vs. n = 8/34, 23.5%; odds ratio [OR; 95% confidence interval (CI)]: 3.67 [1.45, 9.28]; p = .0061). The proportion of patients experiencing ≥1 adverse event was similar between groups (belimumab: n = 60/66, 90.9% vs. placebo: n = 31/34, 91.2%). No new safety signals emerged in this subgroup analysis. Belimumab was efficacious for the treatment of SLE and well tolerated among the South Korean subgroup of patients from the NEA study.

Hormone Replacement Therapy Is Associated with Disease Activity Improvement among Post-Menopausal Women with Inflammatory Bowel Disease.

(1) Background: There are limited data available to guide clinical decision-making regarding the effects of hormone replacement therapy (HRT) in post-menopausal women with inflammatory bowel disease (IBD). In this study, we sought to characterize a population of post-menopausal women with IBD and to determine the effects of HRT on their disease activity. (2) Methods: A multicenter, retrospective, case-control cohort study of post-menopausal women with IBD was conducted. The physician global assessment (PGA) score was used to quantify disease activity. To control for the effects of menopause, IBD patients who had not undergone HRT were used as controls. (3) Results: There was a significant reduction in the frequency of PGA scores ≥2 post HRT treatment (p < 0.01). HRT treatment was associated with a 5.6× increase in the odds of post-HRT PGA score improvement compared to controls (OR 5.6; 95% CL 1.6, 19.7) in our univariate logistic regression analysis. (4) Conclusion: Post-menopausal IBD women who underwent HRT therapy showed an improvement in their disease symptoms following HRT compared to post-menopausal women without HRT therapy, who showed no change.

The Combined Application of Bleomycin and Triamcinolone for Treating Refractory Keloids.

Triamcinolone acetate injections are considered the first treatment option for keloids, but quite high proportions of keloids either do not respond to triamcinolone or develop recurrence. Beneficial effects of intralesional bleomycin have been recently shown in the treatment of keloids and hypertrophic scars. However, the efficacy of combination therapy using intralesional triamcinolone and bleomycin remains undetermined. The purpose of this study was to evaluate the efficacy of using bleomycin and triamcinolone mixture to treat refractory keloids. In total, 33 patients with resistant keloids (including 8 men and 25 women) and a mean age of 36.52 years (age range of 18-65 years) were enrolled in this study. A mixture of bleomycin (1 u/cc) with triamcinolone acetonide (13.3 mg/cc) was injected intralesionally into the keloids every 4 to 6 weeks for a maximum of 6 cycles. The clinical improvement was evaluated using the Japan Scar Scale (JSS) and the physician's global assessment of the flattening of the lesions. Side effects were also noted and recorded. In all patients, the total JSS scores decreased significantly after treatment (2.33 ± 1.05), compared with baseline (11.61 ± 2.59), ( p < .001); 26 keloids (78.8%) showed an excellent response (75%-100% flattening), 7 keloids (21.2%) showed a fair response (25%-75% flattening), and 0 keloids (0%) showed a poor response (<25% flattening). Observed side effects were ulceration (33.3%), hyperpigmentation (33.3%), hypopigmentation (15.15%), secondary infection (33.3%), and telangiectasis (15.15%). The combined use of bleomycin and triamcinolone offers a promising treatment option for individuals who have not responded well to traditional therapies.

Comparative Effectiveness and Durability of Biologics in Clinical Practice: Month12 Outcomes from the International, Observational Psoriasis Study of Health Outcomes (PSoHO).

Given the chronic nature of psoriasis (PsO), more studies are needed that directly compare the effectiveness of different biologics over long observation periods. This study compares the effectiveness and durability through 12months of anti-interleukin (IL)-17A biologics relative to other approved biologics in patients with moderate-to-severe psoriasis in a real-world setting. The Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year, prospective, non-interventional cohort study of 1981 adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. The study compares the effectiveness of anti-IL-17A biologics with other approved biologics and provides pairwise comparisons of seven individual biologics versus ixekizumab. The primary outcome was defined as the proportion of patients who had at least a 90% improvement in Psoriasis Area and Severity Index score (PASI90) and/or a score of 0 or 1 in static Physician Global Assessment (sPGA). Secondary objective comparisons included the proportion of patients who achieved PASI90, PASI100, a Dermatology Life Quality Index (DLQI) score of 0 or 1, and three different measures of durability of treatment response. Unadjusted response rates are presented alongside the primary analysis, which uses frequentist model averaging (FMA) to evaluate the adjusted comparative effectiveness. Compared to the other biologics cohort, the anti-IL-17A cohort had a higher response rate (68.0% vs. 65.1%) and significantly higher odds of achieving the primary outcome at month12. The two cohorts had similar response rates for PASI100 (40.5% and 37.1%) and PASI90 (53.9% and 51.7%) at month12, with no significant differences between the cohorts in the adjusted analyses. At month12, the response rates across the individual biologics were 53.5-72.6% for the primary outcome, 27.6-48.3% for PASI100, and 41.7-61.4% for PASI90. These results show the comparative effectiveness of biologics at 6 and 12months in the real-world setting.

Clinical Trial Design in Ulcerative Colitis: Interpreting Evolving Endpoints Based on Post Hoc Analyses of the Vedolizumab Phase 3 Trials GEMINI 1 and VISIBLE 1.

The 12-point total Mayo score including a Physician's Global Assessment (PGA) of disease activity has been used to assess outcomes in clinical trials for ulcerative colitis (UC). In 2016, the US Food and Drug Administration (FDA) issued guidance advising the removal of the PGA in future trials. We examined how endpoints in UC trials have evolved and conducted a post hoc analysis of the GEMINI 1 and VISIBLE 1 trials to understand how the use of a 9-point modified Mayo score, excluding PGA, compares with the total Mayo score. Endpoint definitions of clinical remission in phase 3 trials were extracted from published literature and ClinicalTrials.gov. The difference (%Δ) between the proportions of patients in GEMINI 1 and VISIBLE 1 achieving clinical remission with vedolizumab versus placebo at week 52 was measured according to 4 endpoint definitions. Trials completed up to the end of 2019 used the total Mayo score to assess clinical remission. Most trials that were completed or estimated to be completed by June 2020 or later used modified Mayo scores. Post hoc analysis revealed decreasing endpoint stringency was associated with increasing %Δ values. The modified Mayo score definition most like the definition recommended by the FDA produced %Δ values like those reported using the total Mayo score in GEMINI 1 and VISIBLE 1. Endpoint definitions for UC clinical trials have evolved following FDA guidance. The efficacy of vedolizumab, measured using modified Mayo scoring, was comparable to values reported using the total Mayo score.

Deucravacitinib, a selective, allosteric tyrosine kinase 2 inhibitor, in scalp psoriasis: A subset analysis of two phase 3 randomized trials in plaque psoriasis

Scalp involvement in plaque psoriasis is challenging to treat. To evaluate the efficacy and safety of deucravacitinib (DEUC) in scalp psoriasis. POETYK PSO-1 and PSO-2 were global phase 3, 52-week, double-blinded trials in adults with moderate to severe psoriasis. Patients were randomized 1:2:1 to oral placebo, DEUC 6mg once daily, or apremilast 30mg twice daily. This pooled secondary analysis evaluated scalp-specific Physician Global Assessment score of 0 or 1 (0/1), ≥90% improvement from baseline in Psoriasis Scalp Severity Index, and change from baseline in Psoriasis Scalp Severity Index. Adverse events were evaluated through week 16. Overall, 1084 patients with moderate to severe scalp psoriasis at baseline were included. At week 16, response rates were greater with DEUC versus placebo or apremilast for scalp-specific Physician Global Assessment 0/1 (64.0% vs 17.3% vs 37.7%; P<.0001), ≥90% improvement from baseline in Psoriasis Scalp Severity Index (50.6% vs 10.5% vs 26.1%; P<.0001), and change from baseline in Psoriasis Scalp Severity Index. Responses were maintained through 52weeks with continuous DEUC. Safety was consistent with the entire study population. Lack of data in milder scalp psoriasis. DEUC was significantly more efficacious than placebo or apremilast in improving moderate to severe scalp psoriasis and was well tolerated.

Implementation of the Treat-to-Target Approach in Psoriatic Arthritis and Its Outcomes in Routine Clinical Practice.

Background Measuring disease activity in psoriatic arthritis using validated tools and treating to a target (T2T) is advocated. It improves quality of life and delays radiographic progression. In clinical practice, it guides therapy escalation to achieve better disease control. This study aimed to assess the real-life implementation of the T2T concept in daily clinical practice and the proportion of patients achieving the target of low disease activity or remission. Methodology In this study, a retrospective review of patients diagnosed with psoriatic arthritis having clinical visits from January 2020 to February 2023 was done. The proportion of patients in whom disease activity was monitored using the Disease Activity Index for Psoriatic Arthritis (DAPSA) 28 and Physician Global Assessment (PGA) and those achieving the target was calculated using SPSS version 21 (IBM Corp., Armonk, NY, USA). Results A total of 89 patients were included in the study after fulfilling the inclusion and exclusion criteria. Overall, 56.2% (50) of patients were males and 43.8% (39) were females, with a mean age of 43.5 ± 14.5 years, mean disease duration of 6.6 ± 3.8 years, and mean follow-up duration of 2.8 ± 1.6 years. Of the study population, 43.8% (39) had axial involvement, 23.6% (21) had dactylitis, and 12.4% (11) had enthesitis. Skin psoriasis was present in 84.3% (75), 11.2% (10) had a family history of psoriasis, 19.1% (17) had nail changes, 1.1% (1) had uveitis, and in 94.8% (73) of patients skin psoriasis presented before arthritis. Overall, 97.7% (85) of patients were on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), with the most common being methotrexate in 77%, followed by leflunomide in 8%. Further, 34.8% (31) were using biological DMARDs (bDMARDs), with the most common being tofacitinib (33.7%), infliximab (28.1%), and secukinumab (24.7%) being other choices. Overall, 21.1% (18) of patients experienced adverse events with csDMARDs and 3.2% (1) with biological DMARDs. DAPSA28 was recorded in 44.9% (40), Psoriasis Area and Severity Index in 16.8% (15), and PGA in 100% of patients. Target of low disease activity (LDA)/remission was achieved in 50.6% (45) patients, as assessed by PGA or DAPSA28 cutoff. The LDA/remission target was achieved in 51.2% of patients taking csDMARDs, and 74.2% in those who were on bDMARDs. Conclusions It is crucial to measure the disease activity using validated tools and treat the patient to target for achieving better disease control and improved quality of life. Despite the evidence that T2T improves outcomes, it is not widely practiced in routine clinical practice.

Organ damage is a major determinant of work productivity impairment in Behçet’s syndrome: a post hoc analysis of the BODI validation study

Abstract Objectives To evaluate the prevalence, magnitude and potential determinants of work productivity impairment in patients with Behçet’s syndrome (BS), focusing on the role of irreversible organ damage. Methods A post hoc analysis of the BS Overall Damage Index (BODI) prospective validation study was performed. Demographics and clinical features were recorded in all patients. The Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire was administered to assess the work limitation and the BODI to measure organ damage. The independent effect of BS features on WPAI:GH outcomes was evaluated by regression analysis. Results Of 148 patients, 34.5% were unemployed, with age [odds ratio (OR) 1.035] and BODI score (OR 1.313 for a 1-unit increase) as the only factors significantly (P &amp;lt; 0.05) associated with the unemployment state. Overall work impairment was reported in ≈64.2% of the employed patients. Indeed, 22.7% reported missing work hours due to their health (absenteeism), with a mean time loss of 34.4%, whereas 60.2% declared reduced performance at work because of their health (presenteeism), with a mean productivity impairment of 45.4%. Ocular damage was associated with absenteeism (β = 0.225); female sex (β = 0.260), physician global assessment of disease activity (β = 0.502) and an increased BODI score (β = 0.166 for 1-point increase) with presenteeism; and fibromyalgia (β = 0.246), Physician Global Assessment (β = 0.469) and musculoskeletal damage (β = 0.325) with overall work impairment. Conclusions Disease activity and organ damage accrual remarkably affect work productivity in BS patients. Achieving remission and preventing damage accrual are crucial and complementary objectives.

The contributions of clinical disease activity, functional disability, and illness intrusiveness to depressive symptoms in pediatric inflammatory bowel disease.

Clinical disease activity associated with inflammatory bowel disease (IBD)can place physical limitations on youths' activities of daily living. In turn, functional limitations potentially contribute to youths' heightened experience of IBD-induced intrusions on a wide range of routine and valued activities (i.e., illness intrusiveness), which can increase their risk for depressive symptoms. The present study examined the contributions of clinical disease activity, functional disability, and illness intrusiveness to depressive symptoms in youth with IBD. Youth (N = 180) completed the Functional Disability Inventory (FDI),Illness Intrusiveness Scale-Child (IIS-C),and Children's Depression Inventory-2 (CDI-2).Physicians completed the Physicians Global Assessment of disease activity (PGA). Results revealed a mediating effect for functional disability in the association between disease activity and depressive symptoms (PGA → FDI → CDI-2);illness intrusiveness mediated the association between functional disability and depressive symptoms (i.e., FDI → IIS-C → CDI-2).Serial mediation revealed that clinical disease activity conferred an indirect effect on youth depressive symptoms through the sequential effects of functional disability and illness intrusiveness (i.e., PGA → FDI → IIS-C → CDI-2). Taken together, these findings indicate that youth who encounter more physical limitations as a function of clinical disease activity are more likely to experience an amplified sense of IBD-related intrusions on their ability to participate in meaningful activities. In turn, heightened illness intrusiveness increases the likelihood of depressive symptoms. Clinical interventions that help youth maintain adequate functional ability in the face of IBD disease activity and encourage involvement in positively valued activities could decrease the negative impact of IBD on youths' emotional adjustment.

The emerging role of Growth Differentiation Factor 15 as a potential disease biomarker in juvenile dermatomyositis.

We aimed to investigate the potential of Growth Differentiation Factor 15 (GDF-15) as a novel biomarker for disease activity in Juvenile Dermatomyositis (JDM). We recruited children with juvenile myositis including juvenile dermatomyositis (n = 77), polymyositis (n = 6), and healthy controls (n = 22). GDF-15 levels in plasma were measured using ELISA. Statistical analyses were performed using non-parametric tests. Levels of GDF-15 were significantly elevated in JDM compared with healthy controls (p< 0.001). GDF-15 levels exhibited strong positive correlations with disease activity scores, including the Disease Activity Score (DAS) total score, DAS skin score, DAS muscle score, and Childhood Myositis Assessment Scale (CMAS). Additionally, GDF-15 levels could differentiate between active disease and remission based on the Physician Global Assessment of muscle score. Positive correlations were observed between levels of GDF-15 and creatine kinase, neopterin, and nailfold end row loops, indicating the potential involvement of GDF-15 in muscle damage, immune activation, and vascular pathology. ROC curve analysis showed GDF-15 to be more effective in assessing disease activity in JDM than creatine kinase (AUC 0.77, p= 0.001 and AUC 0.6369, p= 0.0738, respectively). GDF-15 may serve as a valuable biomarker for assessing disease activity in JDM. It exhibits better sensitivity and specificity than creatine kinase, and the levels correlate with various disease activity scores and functional measures. GDF-15 may provide valuable information for treatment decision-making and monitoring disease progression in JDM.

Efficacy and Safety of the Heat Shock Protein 90 Inhibitor RGRN-305 in Hidradenitis Suppurativa

Hidradenitis suppurativa is a painful immune-mediated disorder with limited treatment options; hence, a need exists for new treatments. To evaluate the feasibility of heat shock protein 90 inhibition by RGRN-305 as a novel mechanism of action in treating moderate to severe hidradenitis suppurativa. This was a parallel-design, double-blind, proof-of-concept, placebo-controlled randomized clinical trial conducted between September 22, 2021, and August 29, 2022, at the Department of Dermatology, Aarhus University Hospital in Denmark. The study included a 1- to 30-day screening period, a 16-week treatment period, and a 4-week follow-up period. Eligibility criteria included age 18 years or older and moderate to severe hidradenitis suppurativa with 6 or more inflammatory nodules or abscesses in at least 2 distinct anatomic regions. Of 19 patients screened, 15 patients were enrolled in the study. Intention-to-treat analysis was performed. Patients were randomly assigned (2:1) to receive oral RGRN-305, 250-mg tablet, or matching placebo once daily for 16 weeks. The primary efficacy end point was the percentage of patients achieving Hidradenitis Suppurativa Clinical Response 50 (HiSCR-50) at week 16. Secondary efficacy end points included HiSCR-75 or HiSCR-90, Hidradenitis Suppurativa Physician's Global Assessment, Dermatology Life Quality Index scores, and a pain numeric rating scale. Safety was assessed by adverse events, physical examinations, clinical laboratory measurements, and electrocardiograms. A total of 15 patients were enrolled, completed the study, and were included in all analyses (10 [67%] female; median age, 29 [IQR, 23-41] years). The primary end point HiSCR-50 at week 16 was achieved by a higher percentage in the RGRN-305 group (60% [6 of 10]) than in the placebo group (20% [1 of 5]). Improvements were also observed across all secondary end points at week 16, including higher rates of the harder-to-reach HiSCR levels; 50% (5 of 10) achieved HiSCR-75 and 30% (3 of 10) achieved HiSCR-90, whereas none of the placebo-treated patients achieved HiSCR-75 or HiSCR-90. RGRN-305 was well tolerated, with no deaths or serious adverse events, and treatment-emergent adverse events were similarly frequent between the RGRN-305 and placebo groups. The findings of this trial suggest that heat shock protein 90 inhibition by RGRN-305 offers a novel mechanism of action in treating hidradenitis suppurativa, warranting further evaluation in larger trials. ClinicalTrials.gov Identifier: NCT05286567.

Associations Between Patient-Reported Outcome Measures of Physical and Psychological Functioning and Willingness to Share Social Media Data for Research Among Adolescents With a Chronic Rheumatic Disease: Cross-Sectional Survey.

Social media data may augment understanding of the disease and treatment experiences and quality of life of youth with chronic medical conditions. Little is known about the willingness to share social media data for health research among youth with chronic medical conditions and the differences in health status between sharing and nonsharing youth with chronic medical conditions. We aimed to evaluate the associations between patient-reported measures of disease symptoms and functioning and the willingness to share social media data. Between February 2018 and August 2019, during routine clinic visits, survey data about social media use and the willingness to share social media data (dependent variable) were collected from adolescents in a national rheumatic disease registry. Survey data were analyzed with patient-reported measures of disease symptoms and functioning and a clinical measure of disease activity, which were collected through a parent study. We used descriptive statistics and multivariate logistic regression to compare patient-reported outcomes between youth with chronic medical conditions who opted to share social media data and those who did not opt to share such data. Among 112 youths, (age: mean 16.1, SD 1.6 y; female: n=72, 64.3%), 83 (74.1%) agreed to share social media data. Female participants were more likely to share (P=.04). In all, 49 (43.8%) and 28 (25%) participants viewed and posted about rheumatic disease, respectively. Compared to nonsharers, sharers reported lower mobility (T-score: mean 49.0, SD 9.4 vs mean 53.9, SD 8.9; P=.02) and more pain interference (T-score: mean 45.7, SD 8.8 vs mean 40.4, SD 8.0; P=.005), fatigue (T-score: mean 49.1, SD 11.0 vs mean 39.7, SD 9.7; P<.001), depression (T-score: mean 48.1, SD 8.9 vs mean 42.2, SD 8.4; P=.003), and anxiety (T-score: mean 45.2, SD 9.3 vs mean 38.5, SD 7.0; P<.001). In regression analyses adjusted for age, sex, study site, and Physician Global Assessment score, each 1-unit increase in symptoms was associated with greater odds of willingness to share social media data, for measures of pain interference (Adjusted Odds Ratio [AOR] 1.07, 95% CI 1.001-1.14), fatigue (AOR 1.08, 95% CI 1.03-1.13), depression (AOR 1.07, 95% CI 1.01-1.13), and anxiety (AOR 1.10, 95% CI 1.03-1.18). High percentages of youth with rheumatic diseases used and were willing to share their social media data for research. Sharers reported worse symptoms and functioning compared to those of nonsharers. Social media may offer a potent information source and engagement pathway for youth with rheumatic diseases, but differences between sharing and nonsharing youth merit consideration when designing studies and evaluating social media-derived findings.

Development and psychometric evaluation of a physician global assessment for type 2 systemic lupus erythematosus symptoms

ObjectiveManifestations of SLE can be categorised as type 1 (classic signs and symptoms of SLE) or type 2 (fatigue, widespread pain and brain fog with an unclear relationship to inflammation)....

Clinical value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography combined with computed tomography angiography in large-vessel vasculitis

Abstract OBJECTIVES: The objectives of this study were to investigate the clinical application of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) combined with CT angiography (CTA) fusion images at diagnosis and assessment in large-vessel vasculitis (LVV). MATERIALS AND METHODS: Forty-six patients with LVV who underwent both 18F-FDG-PET/CT and CTA procedures were studied in the Second Hospital of Harbin Medical University from September 2019 to June 2022, and the clinical disease activity of patients was judged by the Physician Global Assessment. Clinical data, acute-phase reactants (APRs), and imaging data were collected. Meanwhile, the APRS must be obtained within 1 week of 18F-FDG-PET/CT. 18F-FDG-PET/CT was primarily used to evaluate LVV activity, while CTA was primarily used to observe morphological changes in arteries, including arterial wall thickening, narrowing, and corresponding complications. PET/CT images were evaluated by two nuclear medicine physicians, both of them unaware of the patients’ laboratory tests and clinical signs. Two nuclear medicine specialists evaluated the PET/CT images and PET/CTA images, who were blinded to the patients’ information. The concordance of two physicians in the LVV visual grading scale was studied by calculating the Cohen’s kappa index (k) which evaluates the power of concordance. The paired t-test was used to analyze the differences between PET/CTA images and PET/CT images. RESULTS: The sensitivity and specificity of the semi-quantitative analysis to assess LVV activity was 94.1% and 93.1%, respectively, when a cutoff of the mean SUVmax/SUVmeanliver of 1.15. It was found that the images obtained after delayed phase were clearer and the contrast between the arterial wall and the lumen was higher in 19 patients. We also concluded that PET/CTA examinations were able to detect more lesion sites compared to PET/CT examinations in 28 patients (P &lt; 0.001), especially for patients with long-term treatment, and the interpretation of PET/CTA images took less time than PET/CT images(P &lt; 0.001), ultimately achieving a shorter time, more comprehensive and accurate interpretation. CONCLUSION: Although 18F-FDG-PET/CT can assess the activity of LVV, it is poor at observing morphological changes in arteries. The use of 18F-FDG-PET/CTA imaging scans in LVV can accurately assess disease activity while at the same time providing a comprehensive, accurate, and efficient determination of disease severity, allowing patients to receive comprehensive diagnostic information from PET/CTA examination.

Management of Moderate to Severe Plaque Psoriasis with Brodalumab in Daily Practice: Real-World Evidence from the LIBERO Study in the Czech Republic.

Psoriasis is a chronic, immune-mediated inflammatory skin disease. Despite the availability of several therapies, many patients affected by this disease remain untreated, do not have adequate response, or suffer from treatment-related toxic effects. It has been shown that the interleukin (IL)-17 pathway plays a key role in the immunopathogenesis of psoriasis. Brodalumab, the first human monoclonal IgG2 antibody that selectively binds to subunitA of the human IL-17 receptor, blocking interactions with a number of cytokines of the IL-17 family, has confirmed fast onset of action, high complete clearance rates, and sustained efficacy. Nevertheless, there is only a limited amount of published real-world evidence (RWE) data. This was an open-label, multicenter, real-world, prospective, non-interventional, non-controlled (single-arm) observational study (LIBERO-CZ) assessing the management of moderate to severe psoriasis with brodalumab in daily practice for up to 52weeks of treatment. Fifty-four patients (70.4% male, mean age 46.9 ± 13.4years, weight 95.6 ± 22.7kg, disease duration 18.6 ± 12.7years) were enrolled and included in the final analysis. Forty-nine of the patients completed the study and five discontinued prematurely; 51.8% of all the enrolled patients were biologic-naïve. At baseline, 28% patients were classified as severe (psoriasis area severity index (PASI) ≥ 20). Overall, the mean PASI decreased by 15.6 from 16.1 (± 5.0) at baseline to 0.5 (± 1.2) at the last visit. The primary endpoint of an absolute PASI ≤ 3 at week12 (as observed analysis) was achieved by 95.9% of patients. The static Physician's Global Assessment (sPGA) success (defined as clear = 0 and almost clear = 1) at week52 was achieved by 92.1% of patients. PASI75, PASI90, and PASI100 were achieved by 98.0%, 87.8%, and 75.5% of patients, respectively, after approximately 52weeks of treatment. The study also recorded very positive results concerning patient-reported outcomes. LIBERO-CZ confirms the fast onset and high clearance rates of brodalumab in real life in both biologic-naïve and biologic-experienced patients.