Physician Global Assessment Score Research Articles

Consistent Efficacy of Apremilast in Patients with Psoriasis Regardless of Baseline Disease Severity or Special Area Involvement: Subgroup Analysis from PROMINENT.

Psoriasis involvement in special areas (e.g., scalp or nails) is associated with a great disease burden yet it is often inadequately treated with topical treatments. The efficacy and tolerability of apremilast plus existing topical therapy in Japanese patients with mild to moderate plaque psoriasis were demonstrated in PROMINENT, a phase 3b, multicenter, open-label, single-arm study. We evaluated the efficacy of apremilast across disease severities and special areas involved in these patients. In PROMINENT, patients received apremilast 30mg twice daily for 16weeks in addition to their existing topical therapy, with the option of topical therapy reduction at the discretion of their physician while continuing apremilast treatment from Weeks 16 to 32. We performed a post hoc analysis, assessing apremilast efficacy and safety in Japanese patients stratified by baseline static Physician Global Assessment (sPGA) score (2 [mild] or 3 [moderate]) and special area involvement. Of patients with baseline sPGA = 2 and sPGA = 3, 62.7% and 30.7%, respectively, achieved sPGA score 0 or 1 at Week 32. At Week 32, improvements in skin, nail, scalp, and quality of life assessments were observed regardless of baseline sPGA score. Improvements in these endpoints at Week 32 were also observed in patients with special area (scalp or nail) involvement (n = 134). Incidence of adverse events was similar between patients with baseline sPGA = 2 and sPGA = 3. Apremilast in combination with topical therapy may be a beneficial treatment for Japanese patients, who have limited systemic treatment options for mild to moderate psoriasis or psoriasis in special areas. NCT03930186.

Exploring the Severity Strata of Disease Activity and Repigmentation in Vitiligo Based on Validated Physician Global Assessment (PGA) Scores.

Background/Objectives: There is currently no guidance on how to interpret the global degrees of activity (worsening) and repigmentation (improvement) in vitiligo. Stratification into global degrees can be completed for static evaluations (e.g., visible disease activity signs) and dynamic assessments (e.g., evolution over time). For the latter, the Vitiligo Disease Activity Score (VDAS15&60) and Vitiligo Disease Improvement Score (VDIS15&60) were recently validated. Methods: In the current study, a Physician Global Assessment (PGA) for disease activity (worsening) and repigmentation (improvement) was evaluated for validity (construct) and reliability (inter- and intrarater) based on a photo set of 66 patients. Subsequently, the PGA activity (worsening) and repigmentation (improvement) were used to stratify the Vitiligo Extent Score plus (VESplus), VDAS15&60 or VDIS15&60 into three global categories (slightly, moderately and much worse/improved), based on ROC analysis. Results: For the VESplus, cut-off values for the categories 'slightly, moderately and much worse' were >0.3%, >27.71% and >128.75% BSA (relative changes in the affected total BSA), respectively. For the categories 'slightly, moderately and much improved', they were >0%, >4.87% and >36.88% BSA (relative changes in the affected total BSA), respectively. The optimal cut-off values of the number of active (VDAS15) body areas were >0 areas for slightly worse, >2 areas for moderately worse and >7 for much worse. For VDIS15, the cut-off values for slightly improved and moderately improved were >0 and >1. For VDAS60 and VDIS60, the cut-off points were >0.5, >3, >9.5 and >0.5 and >1.5, respectively. The results should be interpreted with caution in patients with extensive vitiligo due to the rather limited disease extent of the included patient population (VESplus (median: 3.2%)). Conclusions: This research will aid in the development of more detailed international definitions.

Efficacy and Tolerability of a Hyaluronic Acid-Based Extracellular Matrix for Labia Majora Rejuvenation and Augmentation: A Pilot Study.

A new injectable solution containing low-molecular-weight hyaluronic acid (HA) and a specific amino acid mixture was formulated with proper aesthetic performance for the main signs of facial skin photoaging. The present study aimed to investigate its new application for rejuvenating and augmenting labia majora using clinical and biometric assessments. Three sessions of intradermal injections were performed using 3 ml of test extracellular matrix (ECM) for 10 eligible post-menopause female subjects (age 53.6 ± 7.93 years). The effectiveness of the intervention was assessed by an independent physician using before-and-after pictures based on the physician's global assessment score. Objective biophysical skin assessments, including skin hydration, skin erythema, and melanin index, as well as elasticity parameters including firmness (R0), gross elasticity (R2), and net elasticity (R5), were also performed before the first injection and then on the 2nd and 12th weeks after the last session. Patients' satisfaction and all reported or observed adverse events were documented. At week 12, all the subjects reported an aesthetic improvement of 25% or more in rejuvenation and sagging of the labia major area. A statistically significant improvement was also detected in R0 and R5 at week 12 (p-values 0.005 and 0.022, respectively). Patient satisfaction surveys revealed a median score of 8 at both follow-up visits. The results showed a new indication of the tested HA ECM for providing a beneficial, durable, rejuvenating effect on the labia majora with a good safety profile.

E058 Disease activity measurement in rheumatoid arthritis - simpler in not always better!

Abstract Background/Aims Rheumatoid arthritis is one of the commonest inflammatory arthritis (1). The traditional method of disease activity assessment would incorporate activity measures like DAS 28, CDAI and SDAI which have been validated in clinical research (2). All these indices use 28 joint assessment method. These measures use different aspects of disease activity including swollen joint count, tender joint count, patient global scores and physician global assessment scores and inflammatory markers are included in some of the measures. We conducted a small study to compare these outcome measures in patients with moderate RA (per DAS criteria) who were recruited for disease activity assessment through MSK ultrasound. Methods Of the 30 biologic naive patients recruited, 27 were included in this study. Patients with moderate disease activity (per DAS criteria) were recruited for MSK ultrasound evaluation by a single rheumatologist. Patients with a diagnosis of fibromyalgia were excluded. These patients had been reviewed by two assessors prior to USS assessment and disease activity measures updated. Patient data was collected through electronic patient records. Data was analysed through MS Excel. Results The median age was 63. There were 66% females and 34% male patients. Majority were sero positive for either RhF, Anti CCP or both (77%). Mean DAS-28 score was 4.4 and corresponding mean CDAI and SDAI scores were 22.8 and 23.5 respectively. Mean HAQ score 1.08 and median CRP was 8.6. The median composite EULAR OMERACT synovitis score was 9.18. The average physician global assessment score for disease activity before USS was 4.9/10 and it correlated well with decision to escalate treatment in 41% patients as a result of USS assessment. Conclusion With a small sample size, this project shows that simplified disease activity measures do not necessarily provide clear evidence of disease activity and are heavily influenced by patient reported outcome measures (tender joint count and global pain scores). CDAI scores can be slightly higher compared to DAS and SDAI scores for the similar patients. Physician assessment and ultrasound can provide robust evaluation of disease activity and help in decision-making. A multicentric study with a large simple size to evaluate these findings would be helpful. Judicious use of clinical evaluation and imaging can help in tailoring treatment according to patient’s clinical condition and can also save money. Disclosure H. Crawshaw: None. E. Gates: None. C. Acebes: None. M. Jamal: None.

The use of belimumab on patients with both systemic lupus erythematosus and immune thrombocytopenia: A retrospective cohort study.

The objective of this study is to provide a description of a group of retrospective cohort outcomes in patients with systemic lupus erythematosus (SLE) complicated with immune thrombocytopenia (ITP) receiving belimumab. This study reports on the treatment of 10 female patients (mean age 34.3 ± 14.0years, mean weight 58.7 ± 18.2kg) with both SLE and ITP who received belimumab in addition to basic drug therapy. The belimumab treatment regimen consisted of a dosage of 10mg/kg, with an initial infusion every 2weeks for the first 3 doses, followed by an infusion every 4weeks. Ten patients were included in the study. The overall response rate of thrombocytopenia was 90% after treatment. The parameters such as platelet count, lymphocyte count, erythrocyte count, hemoglobin, dsDNA, C3, and C4 were significantly improved (p < .05). The SLE Disease Activity Index (SLEDAI), British Islet lupus Assessment Group 2004 (BILAG-2004), and Physician Global assessment (PGA) scores were significantly decreased (p < .05). There were no significant differences in glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), and serum creatinine (Scr) before and after treatment (p > .05). Belimumab shows promising clinical outcomes in the treatment on patients with both SLE and ITP. Further studies are needed to validate these findings in larger patient populations and compare the efficacy of belimumab with other treatments for SLE complicated with ITP. Long-term response rates and adverse events associated with belimumab treatment also warrant further investigation.

Tapinarof Cream 1% Once Daily is Efficacious in the Treatment of Mild to Severe Plaque Psoriasis in the Head and Neck Region

Introduction: Tapinarof cream 1% (VTAMA®, Dermavant Sciences, Inc.) is a non-steroidal, topical aryl hydrocarbon receptor agonist approved for the treatment of plaque psoriasis in adults, with no restrictions on location, extent, or duration of use. In the phase 3 PSOARING trial program, tapinarof cream 1% once daily (QD) was efficacious and well tolerated for treating psoriasis, including the head and neck region. However, efficacy data specific to scalp treatment were not captured.Objective: To assess efficacy, safety, and tolerability of tapinarof cream for the treatment of adults with plaque psoriasis affecting the head and neck region, including the scalp. Methods: In this phase 4, open-label trial, adults received tapinarof for 12 weeks. Patients had plaque psoriasis affecting the head and neck (stable for ≥3 months), and a target lesion Physician Global Assessment (tPGA) score of 2 (mild), 3 (moderate), or 4 (severe). The primary endpoint was the proportion achieving a tPGA response (tPGA score of clear [0], or almost clear [1] and ≥2-grade improvement from baseline at Week 12). Additional endpoints included time to achieve tPGA response; proportion with complete clearance (tPGA score=0); and with ≥75% and ≥90% improvement in Psoriasis Area and Severity Index score (PASI; head and neck region). Safety and tolerability evaluations included adverse events (AEs) and investigator-assessed Local Tolerability Scale (LTS) scores. Results: 31 patients with mild to severe plaque psoriasis affecting the head and neck region received tapinarof. At baseline, 54.8% had a tPGA score of 3 and 58.1% (18/31) had the target lesion on the scalp. At Week 12, 88.5% (n=23/26) achieved a tPGA response and 80.8% (n=21/26) achieved complete clearance (tPGA=0). There was rapid onset of efficacy, with both tPGA response and complete clearance achieved as early as Week 1, the first assessment, in some patients. Median times to tPGA response and complete clearance were ~4 and 8 weeks, respectively. At Week 12, 96.2% (n=25/26) and 84.6% (n=22/26) achieved a ≥75% and ≥90% improvement in PASI (head and neck region), respectively. Most AEs were mild or moderate, consistent with previous trials; the most frequent were contact dermatitis, folliculitis, and headache. Most patients had no irritation of the head and neck region (LTS score=0) at all visits.Conclusions: Tapinarof cream 1% QD demonstrated rapid onset of clinically meaningful efficacy as early as Week 1 in patients with plaque psoriasis affecting the head and neck region, including for scalp lesions. Tapinarof cream is a cosmetically elegant, well-tolerated, non-steroidal treatment option in adults with mild to severe plaque psoriasis, including in the head and neck region.Funding Support: Dermavant Sciences, Inc.

Tapinarof Cream 1% Once Daily Improves Patient-Reported Outcomes in the Treatment of Mild to Severe Plaque Psoriasis in the Head and Neck Region

Introduction: Tapinarof cream 1% (VTAMA®, Dermavant Sciences, Inc.) is a non-steroidal, topical aryl hydrocarbon receptor agonist approved for the treatment of plaque psoriasis in adults with no restrictions on location, extent, or duration of use. In the phase 3 PSOARING trial program, tapinarof cream 1% once daily (QD) for the treatment of plaque psoriasis was efficacious and well tolerated. Plaque psoriasis affecting the head and neck region occurs commonly, with a high impact on patients’ health-related quality of life, through pruritus and psychological distress. Patients may consider topicals unacceptable for scalp/facial use due to poor cosmetic properties (e.g., greasiness), leading to low medication adherence. There is a need for efficacious, cosmetically elegant, non-steroidal topicals that can be used without restrictions.Objective: To assess patient-reported outcomes (PROs) with tapinarof cream for adults with mild to severe plaque psoriasis in the head and neck region, including the scalp, in a phase 4, open-label trial.Methods: Adults with head and neck region target lesion Physician Global Assessment (tPGA) score of 2 (mild), 3 (moderate), or 4 (severe) received tapinarof for 12 weeks. PROs included Peak Pruritus Numerical Rating Scale (PP-NRS) score for the head and neck region; achievement of ≥4-point reduction in PP-NRS score; Dermatology Life Quality Index (DLQI) score by visit; and responses to a Patient Satisfaction Questionnaire© (PSQ) at Week 12.Results: 31 patients received tapinarof; 58.1% (18/31) had the target lesion on the scalp. Baseline mean PP-NRS (head and neck region) and total DLQI scores were 5.8 and 9.7, respectively, demonstrating significant pruritus and disease impact. Improvement in mean PP-NRS score was demonstrated at Week 1 (–1.6), the earliest assessment, surpassing the minimal clinically important ≥4-point improvement by Week 12 (−4.2). At Week 12, 70.0% (n=14/20) achieved ≥4-point reduction in PP-NRS score. Mean DLQI minimal clinically important difference of −4.0 was demonstrated as early as Week 1 (−4.0), improving to −7.2 at Week 12. Most patients strongly agreed or agreed with PSQ questions assessing satisfaction with cosmetic elegance (93.3%), quick absorption (96.7%), application ease (86.7%), efficacy (83.3%), and confidence in tapinarof (83.3%). Compared with topicals used previously for plaque psoriasis, most strongly agreed or agreed that tapinarof was more effective (76.9%) and easier to use (76.9%).Conclusions: In patients with plaque psoriasis affecting the head and neck region, tapinarof cream 1% QD demonstrated rapid and clinically meaningful improvements in patient-reported pruritus and disease impact as early as Week 1, the first assessment, with continued improvement through Week 12. Patients reported high rates of satisfaction and positive perceptions of tapinarof.Funding Support: Dermavant Sciences, Inc.

Deucravacitinib Long-Term Efficacy in Week 16 Placebo Crossovers: 3-year Results from the POETYK PSO Program

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in the US, EU, and other countries for treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was efficacious and well-tolerated in the global, 52-week, phase 3 POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) trials and through 2 additional years in the POETYK long-term extension (LTE) (NCT04036435) trial in patients treated with deucravacitinib from Day 1 of PSO-1/PSO-2. Here, long-term efficacy was assessed through 3 years in patients who crossed over from placebo to deucravacitinib at Week 16 in PSO-1 or PSO-2 and entered the LTE trial.&#x0D; Methods: PSO-1 and PSO-2 randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At Week 16, patients randomized to placebo crossed over to deucravacitinib. At Week 52, patients could enroll in the LTE and receive open-label deucravacitinib. Efficacy was evaluated in patients who crossed over from placebo to deucravacitinib at Week 16 of the parent trial and received continuous deucravacitinib through 3 years (Week 148; cutoff June 15, 2022). Outcomes included ≥75%/≥90% reduction from baseline in Psoriasis Area and Severity Index (PASI 75/90) and static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1). Efficacy is reported using modified nonresponder imputation (mNRI) in patients who reached the Week 148 assessment and those who discontinued before Week 148.&#x0D; Results: Of 421 patients originally randomized to placebo, 348 crossed over to deucravacitinib at Week 16; of these, 298 completed the parent trials and entered the LTE, with 254 meeting mNRI criteria Efficacy response rates improved from Week 16 on placebo (PASI 75, 13.4%; PASI 90, 4.3%; sPGA 0/1, 11.0%) through Week 52 on deucravacitinib (PASI 75, 75.9%; PASI 90, 47.5%; sPGA 0/1, 59.4%), were generally maintained well through Week 112 (PASI 75, 78.4%; PASI 90, 52.0%; sPGA 0/1, 57.8%), with persistent responses overall observed through Week 148 (PASI 75, 74.4%; PASI 90, 48.1%; sPGA 0/1, 51.1%). Conclusion: These findings further confirm earlier results of once-daily oral deucravacitinib as an effective long-term treatment for patients with moderate to severe plaque psoriasis.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

The evaluation of gastrointestinal involvement and nutritional status in systemic sclerosis: identifying risk factors for malnutrition in a cross-sectional study

Aims: Gastrointestinal (GI) involvement is frequently observed in Systemic sclerosis (SSc). Considering the effect of GI involvement on SSc patients, the risk of malnutrition might be increased. The study aimed to evaluate GI involvement and the risk for malnutrition and to demonstrate the relationship between disease-related features and risk factors for malnutrition in SSc patients. &#x0D; Methods: SSc-related clinical features and disease severity evaluated with Physician Global Assessment (PGA) were recorded. Detailed GI symptoms and the impact of GI involvement on patients were assessed with the UCLA SCTC GIT 2.0 questionnaire. Nutritional status was evaluated with Body Mass Index (BMI) and the Malnutritional Universal Screening Tool (MUST).&#x0D; Results: 104 SSc patients were involved in the study. Mean age of patients with SSc was 52.24±12.82 years. GI involvement was found in 85.7% of patients. 76% of patients had GI symptoms. The median BMI of patients was 25.3 (9) kg/m² with 4.8% of patients categorized as underweight. The assessment of risk for malnutrition using MUST showed 74% of patients at low risk, 16% at moderate risk, and 9.6% at high risk. No important association was detected between risk groups for malnutrition and UCLA GIT 2.0 score. A significant association was found between moderate to high risk for malnutrition and dcSSc (OR 3.12, %95 CI:1.26-7.73; P=0.01), the presence of GI symptoms (OR 5.32, %95 CI:1.16-24.36; P=0.03), the decrease in oral aperture (OR 0.35, %95 CI:0.15-0.79; p:0.02), and severity of the disease investigated by PGA score (OR 1.52, %95 CI:1.09-2.13; p=0.01).&#x0D; Conclusion: GI involvement is a common manifestation in SSc patients. Approximately 26% of patients were at moderate to high risk for malnutrition. Several SSc-specific clinical features, including disease severity, the presence of GI symptoms, dcSSc, and a decrease in oral aperture were related to a higher risk for malnutrition.

Evaluation of Type 2 SLE symptoms in patients with a range of lupus nephritis activity.

Type 2 systemic lupus erythematosus (SLE) symptoms, including fatigue, fibromyalgia, and brain fog, contribute to poor health-related quality of life (HRQoL) in patients with lupus. To test the hypothesis that Type 1 (classical inflammatory lupus) activity is associated with Type 2 SLE activity, we characterized the features of Type 2 SLE in patients with a range of lupus nephritis (LN) activity. This was a cross-sectional study of SLE patients [American College of Rheumatology (ACR) 1997 or Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria] from June 2018 to March 2020. Patients completed the Systemic Lupus Activity Questionnaire (SLAQ) and the Polysymptomatic Distress Scale. Patients were divided into groups based on their renal status. Active nephritis was defined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) lupus nephritis parameter. Differences across groups were analyzed by Fisher's exact test and ANOVA. In this cohort of 244 patients (93% female, mean age 43years, 58% Black), 10% had active nephritis, 35% had historical nephritis, and 55% never had nephritis (non-nephritis). Active nephritis and non-nephritis patients had a similar burden of Type 2 SLE symptoms, despite a difference in Type 1 SLE activity. Patients with active nephritis had higher Type 2 PGA (Physician Global Assessment) scores and reported more Type 2 SLE symptoms than inactive nephritis patients. Patients with inactive nephritis had the lowest Type 2 SLE activity. While Type 2 SLE symptoms are common in SLE, our findings suggest that patients with active nephritis experience significant Type 2 SLE symptoms that may be ameliorated as nephritis improves. We also observed that non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. Therefore, the etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors. Key Points • Patients with active nephritis experienced significant Type 2 symptoms that may be ameliorated as nephritis improves. • Non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. • Because etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors.

A264 IDENTIFYING CLINICAL PREDICTORS FOR SUCCESS OF EXCLUSIVE ENTERAL NUTRITION INDUCTION THERAPY IN PEDIATRIC CROHN DISEASE

Abstract Background Current treatments for IBD focus on reducing inflammation, mostly through suppression of the immune system. Exclusive enteral nutrition (EEN) is recognized as the first line therapy for mild-to-moderate luminal pediatric Crohn disease patients pCD. Although EEN is safe, as it does not suppress the immune system, it poses considerable challenges to patients, mostly due to palatability and monotony of the formula and treatment costs. Moreover, the efficacy of EEN varies greatly from patient to patient. Therefore, there is a need to distinguish between responders and non-responder patients. Aims Identify clinical features associated with efficacy of EEN induction therapy and apply machine learning to build a classifier to identify EEN non-responders. Methods The Canadian Children Inflammatory Bowel Disease Network prospectively enrolled and followed new onset pediatric IBD cases. Prospective data for 308 pCD with EEN as their first treatment for CD are available. Patients with weighted Pediatric CD Activity Indexes (wPCDAI) collected after at least 4 weeks on EEN were compiled into a dataset (n=108). For this analysis, treatment response was defined as a wPCDAI reduction of at least 12.5 points of a patient’s wPCDAI baseline score. The dataset includes 26 features for each of the 108 pCD patients at time of diagnosis. This included blood test results (Hgb, ESR, CRP, Alb, Htc, Plt), Paris Classifications, height, and weight Z-scores, as well as wPCDAI, SES-CD (simple endoscopic score, CD), PGA (physician global assessment), and Mayo scores. Odds ratios were calculated to determine whether any features were associated with response to EEN induction therapy. Then, the most relevant features were identified with regularization techniques and a machine learning classifier for predicting response to EEN was built. Results Results showed that the appropriate subset of features to include for optimal accuracy over model simplicity are n=4 (PUCAI, PGA, SES-CD scores, and hematocrit). Also, an increase in PGA score (e.g., moving from “mild disease” to “moderate disease”) was associated with an increase in the chance of EEN failure (OR 3.1, 95% CI [1.7,5.8], p=0.0001). The best classifier for predicting EEN response was a random forest consisting of 20 decision trees. The classifier achieved an area under the ROC curve of 0.75 ± 0.07 Conclusions Our results suggest that it is possible to produce a classifier capable of predicting EEN clinical remission with an accuracy over 60%. Higher PGA, PUCAI, and SES-CD scores show potential for predicting patients less likely to respond to EEN induction. This research has the potential to provide better quality of life for children who live with IBD. Funding Agencies CIHRIMAGINE SPOR Network , Women and Children's Health Research Institute

A250 CYTOKINE MULTI-OMICS AND MACHINE LEARNING IDENTIFY MIP1ALPHA AS A NOVEL MEDIATOR IN INFLAMMATORY BOWEL DISEASE

Abstract Background Macrophage inflammatory protein 1 alpha (MIP1a) is a proinflammatory cytokine previously related to murine models of inflammatory bowel disease (IBD), but not definitively in the human disease. MIP1a acts as a chemoattractant of immune cells from the blood to the gut mucosa. We aimed to delineate the alterations to MIP1a and macrophages in relation to a range of IBD severity. Aims To characterize the changes to MIP1a production and localization in response to disease activity in IBD. Methods Both IBD (n=63) and control patients (n=118) were enrolled in this study (HSREB 6033229). Cytokine profiles were investigated using a 17-plex multi-fluorescent bead-based immunoassay (FirePlex, Abcam, Cambridge, UK) on serum from a subset of patients. Disease activity and macrophage levels were extracted from the clinical record. Activity was quantified using the Physician Global Assessment Score. Machine learning (ML) was performed with custom R scripts utilizing the tidymodels package (version 1.1) to determine the optimal model. Immunohistochemistry (IHC) was used to localize MIP1a in patient biopsies and quantified using QuPath software (v0.4). Results An extreme gradient boost ML model was found to have optimal sensitivity and specificity for predicting disease activity based on serum cytokine levels. Within this model lower levels of serum MIP1a were associated with higher severity of IBD activity. However, in GI mucosal biopsies, the percentage of MIP1a positive cells in colon tissue increased with the severity of IBD. Macrophage concentrations in the peripheral blood were higher in patients on prednisone, and relatively similar across all other medications used in our cohort. Conclusions With the data collected, we identify MIP1a as a possible prognostic tool for quantifying IBD activity. Funding Agencies CIHR

Efficacy and Durability of Intravenous Ertapenem Therapy for Recalcitrant Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a debilitating follicular skin disorder in which bacterial colonization is typical. Oral antibiotic efficacy can be unreliable; however, selective intravenous antibiotics, specifically ertapenem, may provide favorable clinical outcomes. To explore optimal course duration, efficacy, and patient satisfaction associated with intravenous ertapenem for HS. This retrospective review of the medical records of 98 patients with HS between 2018 and 2022 measured and evaluated patient outcomes before and after treatment with intravenous ertapenem. Participants were followed up in a telephone survey assessing patient perspectives and satisfaction. All of those included in this study received medical care from the Albert Einstein College of Medicine's Montefiore HS Center. Patients were treated with 1 g of ertapenem that was self-administered at home through a peripheral intravenous central catheter using an elastomeric pump for 12 to 16 weeks. Antiandrogens and immunomodulatory biologic therapies initiated prior to ertapenem were maintained throughout the treatment course. The primary outcomes, encompassing clinical severity (evaluated through the HS Physician Global Assessment score [a 6-point scale ranging from clear to very severe] and a numerical rating scale for pain [an 11-point scale in which a score of 0 indicates no pain and a score of 10 indicates the worst possible pain]) and markers of inflammation (such as leukocytes, erythrocyte sedimentation rate, C-reactive protein, and interleukin-6), were measured at baseline, the midcourse of intravenous ertapenem treatment, at the end of the course, and posttherapy. Bacterial abundance was also examined at these 4 points, and patient satisfaction was assessed during follow-up. A total of 98 patients (mean [SD] age, 35.8 [13.0] years; 61 [62.2%] female) with HS were treated with intravenous ertapenem. The self-reported racial distribution included 3 individuals identifying as Asian (3.1%), 59 as Black/African American (60.2%), 13 as White (13.3%), and 23 as either other or unknown (23.5%). Additionally, 24 participants (24.5%) reported Spanish/Hispanic/Latino ethnicity. The mean (SD) treatment duration spanned 13.1 (4.0) weeks, with posttherapy follow-up occurring after 7.8 (3.6) weeks. From baseline to posttherapy follow-up, significant reductions were found in the mean (SD) HS Physician Global Assessment scores (3.9 [1.0] vs 2.7 [1.2]; P < .001) and the numerical rating scale for pain (4.2 [3.3] vs 1.8 [2.7]; P < .001), C-reactive protein (5.4 [11.4] vs 2.4 [2.0] mg/dL; P < .001), interleukin-6 (25.2 [21.1] vs 13.7 [13.9]; P < .001), and leukocytes (11.34 [3.9] vs 10.0 [3.4]; P < .001). At follow-up, 76 patients (78.0%) participated in the telephone survey, where 63 (80.3%) reported medium to high satisfaction; further, 69 (90.8%) would recommend ertapenem to other patients. In this retrospective review of medical records and telephone survey, treating HS with intravenous ertapenem, administered for a mean of 13 weeks, was associated with improvement in clinical and inflammatory markers, as well as heightened patient satisfaction. Nonetheless, this approach should be monitored for the emergence of antimicrobial resistance given a longer than standard treatment course.

CYTOKINE MULTI-OMICS AND MACHINE LEARNING IDENTIFY MIP1ALPHA AS A NOVEL MEDIATOR IN INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND Macrophage inflammatory protein 1 alpha (MIP1a) is a proinflammatory cytokine previously related to murine models of inflammatory bowel disease (IBD), but not definitively in the human disease. MIP1a acts as a chemoattractant of immune cells from the blood to the gut mucosa. We aimed to delineate the alterations to MIP1a and macrophages in relation to a range of IBD severity. HYPOTHESIS To characterize the changes to MIP1a production and localization in response to disease activity in IBD. APPROACH Both IBD (n=63) and control patients (n=118) were enrolled in this study (HSREB 6033229). Cytokine profiles were investigated using a 17-plex multi-fluorescent bead-based immunoassay (FirePlex, Abcam, Cambridge, UK) on serum from a subset of patients. Disease activity and macrophage levels were extracted from the clinical record. Activity was quantified using the Physician Global Assessment Score. Machine learning (ML) was performed with custom R scripts utilizing the tidymodels package (version 1.1) to determine the optimal model. Immunohistochemistry (IHC) was used to localize MIP1a in patient biopsies and quantified using QuPath software (v0.4). RESULTS An extreme gradient boost ML model was found to have optimal sensitivity and specificity for predicting disease activity based on serum cytokine levels. Within this model lower levels of serum MIP1a were associated with higher severity of IBD activity. However, in GI mucosal biopsies, the percentage of MIP1a positive cells in colon tissue increased with the severity of IBD. Macrophage concentrations in the peripheral blood were higher in patients on prednisone, and relatively similar across all other medications used in our cohort. CONCLUSIONS With the data collected, we identify MIP1a as a possible prognostic tool for quantifying IBD activity.

Clinical Evaluation of an Ayurvedic Preparation “Sangfer” for the Treatment of Anemia in Pregnant Women: An Open-labeled Clinical Study

Background: Iron deficiency during pregnancy is one of the primary causes of anemia in infants and young children. Ithas a negative impact on maternal and fetal health throughout pregnancy with higher likelihood of adverse maternal andfetal outcomes. Maternal iron supplementation is a critical tool to address the global problem of iron deficiency and preventits negative consequences. Method: An open-label non-comparative prospective clinical trial was carried out to evaluatethe effectiveness of “Sangfer” liquid in 16 pregnant women with anemia. “Sangfer” is a polyherbal Ayurvedic proprietarymedication containing elemental iron and zinc and four medicinal herbs viz. Withania somnifera, Emblica officinalis, Asparagusracemosus and Pueraria tuberosa. The aim of the study was to examine its efficacy and safety in treating anemia in pregnantwomen. The dose administered was 10 mL twice daily after food for 12 weeks (84 days). Patients were evaluated at screening(Visit 1 at Day 0), baseline (Visit 2 at Day 1) and during follow-ups (Visit 3 at Day 28, Visit 4 at Day 56 and Visit 5 atDay 84). Results: There was a significant increase in mean hemoglobin levels from 8.08% at Day 1 to 11.19% at the finalvisit at Day 84. The anemia sign and symptom scores also significantly reduced from Day 1 to different follow-up visits.The mean Physician Global Assessment (PGA) score was found to reduce from 1.0 at Day 1 to 0.0 at the final follow-upvisit. Conclusion: “Sangfer” is highly effective for the treatment of anemia during pregnancy. No adverse effects includingserious adverse effects were observed during the study period.

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.

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.

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.

Sex differences in the association between plasma polyunsaturated fatty acids levels and moderate-to-severe plaque psoriasis severity: a cross-sectional and longitudinal study

BackgroundPsoriasis is a chronic inflammatory skin disease with metabolic abnormalities serving as important contributors for pathogenesis and progression. Polyunsaturated fatty acids (PUFAs) have been found to be associated with human diseases, including psoriasis. However, differences and controversies exist regarding their content and roles.MethodsPlasma PUFAs concentrations were measured in 296 patients with moderate-to-severe plaque psoriasis from the Shanghai Psoriasis Effectiveness Evaluation CoHort. Disease severity was assessed using Clinician-Reported Outcomes (ClinROs), including Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and Physician Global Assessment (PGA), as well as Patient-Reported Outcomes (PROs), including Patient Global Assessment (PtGA) and Dermatology Life Quality Index (DLQI). Multivariate generalized linear regression models (GLMs), subgroup and interaction analysis, and restricted cubic spline were used to estimate the cross-sectional associations between PUFAs concentrations and disease severity. Longitudinal assessments of PASI scores and PASI response were conducted at a 12-week follow-up. Associations between baseline plasma PUFAs levels and prospective PASI scores or PASI response were assessed using multivariate GLMs or logistic regression models.ResultsMales suffered severer psoriasis and presented lower plasma docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels compared to females. Among males, plasma eicosadienoic acid (EDA) level was positively associated with PASI, BSA and PGA scores, while total Omega-3 PUFAs and/or eicosapentaenoic acid (EPA) levels exhibited non-linear associations with PASI and/or BSA scores. α-Linolenic acid (ALA) was negatively, whereas ARA was positively, associated with DLQI scores. In females, Omega-3 PUFAs, including EPA, DHA, and total Omega-3 PUFAs, showed inverse associations with PASI and BSA scores. Longitudinally, plasma total Omega-6 PUFAs were positively associated with the likelihood of achieving PASI 100 at 12 weeks in males. In females, concentrations of dohomo-γ-linolenic acid were prospectively associated with an increase in PASI scores, and DHA was associated with the likelihood of achieving PASI 75 and PASI 90 decline.ConclusionsSex differences cross-sectionally exist in disease severity and plasma PUFAs levels. The association between PUFAs and psoriasis severity also varies cross-sectionally and longitudinally between males and females. Sex differences should be considered when studying the function and clinical application of PUFAs in psoriasis.

Deucravacitinib in Plaque Psoriasis: 3-Year Safety and Efficacy Results From the Phase 3 POETYK PSO-1 and PSO-2 Trials

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, EU, and other countries for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was superior to placebo and apremilast in the POETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) parent trials in moderate to severe plaque psoriasis. The POETYK long-term extension (LTE; NCT04036435) trial enrolled patients who completed PSO-1/PSO-2. We report safety and efficacy of deucravacitinib for up to 3 years (Week 148; through cutoff 6/15/2022).&#x0D; Methods: PSO-1/PSO-2 randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily (QD), or apremilast twice daily. At Week 52, patients enrolled in the LTE received open-label deucravacitinib 6 mg QD. Safety was evaluated in patients who received ≥1 dose of deucravacitinib using exposure-adjusted incidence rate per 100 person-years (EAIR/PY). Efficacy outcomes (≥75%/≥90% reduction from baseline in Psoriasis Area and Severity Index [PASI 75/90]; static Physician Global Assessment score of 0 [clear] or 1 [almost clear] with a ≥2-point improvement from baseline [sPGA 0/1]) were analyzed using modified nonresponder imputation (mNRI) in patients who received continuous deucravacitinib treatment from Day 1 of the parent trial and were treated in the LTE.&#x0D; Results: Of 1519 patients who received ≥1 dose of deucravacitinib (3294.3 PY cumulative exposure), 513 patients received continuous deucravacitinib treatment from Day 1 in PSO-1/PSO-2 and were treated in the LTE. EAIRs/100 PY were comparable, or decreased, between the 2-year and 3-year cumulative periods, respectively, for AEs (154.4, 144.8), serious AEs (6.1, 5.5), discontinuations due to AEs (2.8, 2.4), herpes zoster (0.7, 0.6), malignancies (0.9, 0.9), major adverse cardiovascular events (0.4, 0.3), venous thromboembolism (0.1, 0.1), and deaths (0.4, 0.3). Response rates were maintained at Week 148 by mNRI (PASI 75, 73.2%; PASI 90, 48.1%; sPGA 0/1, 54.1%).&#x0D; Conclusion: Deucravacitinib maintained a consistent safety profile and durable efficacy for up to 3 years.