Numeric Rating Scale Research Articles

Deucravacitinib, an Oral, Selective, Allosteric Tyrosine Kinase 2 (TYK2) Inhibitor, in Patients With Moderate to Severe Scalp Psoriasis: Improvement in Scalp-Related Quality of Life and Symptoms in the Phase 3b/4 Multicenter, Randomized, Double-Blinded, Placebo-Controlled PSORIATYK SCALP Trial

Introduction: PSORIATYK SCALP (NCT05478499)—an ongoing 52-week, phase 3b/4, multicenter, randomized, double-blinded, placebo-controlled trial—assesses the efficacy and safety of deucravacitinib in patients aged ≥18 years with moderate to severe scalp psoriasis (Psoriasis Scalp Severity Index ≥12, scalp-specific Physician Global Assessment ≥3, scalp surface area involvement ≥20%, and body surface area [BSA] involvement ≥3%). We assessed Week 16 patient-reported outcomes using Scalpdex, a validated, scalp-specific quality-of-life instrument, and numeric rating scales (NRSs) for scalp-specific symptoms. Methods: Patients were randomized 1:2 to placebo or deucravacitinib 6 mg for 16 weeks, stratified by previous biologic use (yes or no) and body weight (<90 or ≥90 kg). Changes from baseline in Scalpdex total score and NRS scores for scalp-specific itch, pain, and flaking were assessed with an analysis of covariance (ANCOVA) model with treatment and randomization stratification factors as fixed effects and the baseline value as a covariate. Scalpdex total score change from baseline was further assessed in BSA subgroups (BSA 3–10%, BSA >10%), using an ANCOVA model with treatment as a fixed effect and the baseline value as a covariate. P values are nominal. Results: Mean baseline scores (placebo: n=51; deucravacitinib: n=103) indicated severe impact on quality of life (Scalpdex total score >44.0) and moderate to severe symptoms (NRS ≥4.0). At Week 16, adjusted mean change from baseline (95% CI) in Scalpdex total score was greater in patients receiving deucravacitinib versus placebo (−22.3 [−26.1, −18.6] vs −10.5 [−15.7, −5.2]; P=0.0003). Changes from baseline (95% CI) in scalp-specific NRS measures were greater in patients receiving deucravacitinib versus placebo (itch: −3.2 [−3.7, −2.7] vs −0.7 [−1.4, 0.0]; pain: −2.1 [−2.6, −1.6] vs −0.1 [−0.8, 0.5]; flaking: −3.9 [−4.5, −3.4] vs −1.0 [−1.8, −0.2]; all P<0.0001). In each BSA subgroup, patients receiving deucravacitinib versus placebo reported greater Week 16 change from baseline in Scalpdex total score (BSA 3–10%: −19.8 [−23.9, −15.6] vs −10.5 [−16.1, −4.9]; P=0.0096; BSA >10%: −26.2 [−33.2, −19.3] vs −11.2 [−22.3, 0.0]; P=0.0263). Conclusion: Deucravacitinib was efficacious in improving scalp-specific psoriasis symptoms and quality of life. Furthermore, scalp-related quality of life was improved in patients receiving deucravacitinib in both BSA subgroups.

Development, Validation, and Visualization of a Web-Based Nomogram to Predict the Risk of Psychological Distress in Patients Undergoing Chemotherapy After Breast Cancer Surgery

Background Psychological distress of postoperative chemotherapy patients with breast cancer is significant and has a serious impact on their quality of survival. Risk prediction models can efficiently assess patients’ psychological distress and risk factors. Objectives To investigate the factors influencing psychological distress in postoperative chemotherapy patients with breast cancer and construct a nomogram model to predict the occurrence of psychological distress in patients. Methods Two hundred forty-seven women in treatment for breast cancer who were postoperative and receiving chemotherapy were recruited. Participants completed a distress management screening measure, a numerical rating scale, the Pittsburgh Sleep Quality Index, and demographic and clinical items. Results Experiencing significant psychological distress was reported by 65.6% of participants. The psychological distress risk prediction model included 5 variables: financial problems, appearance/shape, distant metastases, the Numerical Rating Scale Pain score, and fatigue. A web calculator was designed based on the model (https://77nomogram.shinyapps.io/dynnomapp/). Conclusions This study found that financial and appearance/shape problems, distant metastases, pain scores, and fatigue were predictors of greater psychological distress in women undergoing chemotherapy after breast cancer surgery. The model constructed in this study has good predictive efficacy. Implications for practice This web-based nomogram model can help healthcare professionals quickly assess the likelihood of psychological distress in patients and screen for risk factors for psychological distress.

Efficacy and Safety of Ruxolitinib Cream for the Treatment of Moderate to Severe Chronic Hand Eczema: Top-Line Results From a 16-Week, Multicenter, Randomized, Double-Blind Study

Hand eczema is a common inflammatory disorder involving skin of the hands. Chronic hand eczema (CHE) is defined as hand eczema that persists for >3 months or recurs ≥2 times within a 12-month period. The efficacy and safety of ruxolitinib (selective Janus kinase [JAK] 1/JAK2 inhibitor) cream was investigated in adults with moderate to severe CHE in a phase 2, randomized, double-blind, vehicle-controlled study (NCT05906628). Patients aged ≥18 years with a diagnosis of CHE for ≥6 months, an Investigator’s Global Assessment (IGA)-CHE score of 3 or 4, and no current or history (≤5 y) of atopic dermatitis were randomized 1:1 to apply twice-daily 1.5% ruxolitinib cream or vehicle cream for 16 weeks of double-blind treatment. Patients (N=186) had a median (range) age of 50.0 (18–80) years, and 59.7% were female. The median (range) Itch numerical rating scale (NRS) score was 6.6 (2.1–10), and 72.6% of patients had an IGA-CHE score of 3. At Week 16, significantly more patients who applied ruxolitinib cream versus vehicle achieved IGA-CHE treatment success (primary endpoint; 53.2% vs 10.9%; P<0.0001), defined as an IGA-CHE score of 0 (clear) or 1 (almost clear) with a ≥2-grade improvement from baseline. Significantly more patients who applied ruxolitinib cream versus vehicle achieved a ≥4-point improvement from baseline in Itch NRS score (Itch NRS4) at Week 4 (46.7% vs 17.6%; P<0.0001; key secondary endpoint) and Week 16 (52.2% vs 23.1%; P<0.0001; key secondary endpoint). Numerical improvements in Itch NRS4 with ruxolitinib cream versus vehicle were observed at Day 2 with statistically significant improvement observed on Day 7 (27.4% vs 9.0%; P=0.0024; key secondary endpoint). Substantially more patients who applied ruxolitinib cream versus vehicle achieved a ≥75% or ≥90% improvement from baseline in Hand Eczema Severity Index (HECSI) score at Week 16 (80.2% vs 26.9% and 64.0% vs 11.5%, respectively). Ruxolitinib cream was generally well tolerated through Week 16 with no new safety signals; no serious infections, major adverse cardiovascular events, malignancies, or thromboses were observed. Application site reactions were infrequent. No treatment-related grade ≥3 treatment-emergent adverse events (TEAEs) were reported, and no patients discontinued owing to a TEAE. In conclusion, ruxolitinib cream demonstrated significant reductions of CHE signs and symptoms versus vehicle through Week 16 and was generally well tolerated, consistent with the known safety profile. (Funding, Incyte Corporation)

Deucravacitinib, an Oral Selective Tyrosine Kinase 2 (TYK2) Inhibitor, in Patients with Moderate to Severe Scalp Psoriasis: Efficacy and Safety Results of a Phase 3b/4, Multicenter, Randomized, Double-blinded, Placebo-controlled Trial (PSORIATYK SCALP)

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. PSORIATYK SCALP, an ongoing, 52-week, phase 3b/4, multicenter, randomized, double-blinded, placebo-controlled trial, evaluated deucravacitinib efficacy/safety in patients with moderate to severe scalp psoriasis, including those with more limited overall psoriasis. Methods: Adults with moderate to severe scalp psoriasis defined by more focused and objective inclusion criteria (ss-PGA ≥3, scalp surface area involvement ≥20%, and PSSI ≥12 at baseline) and BSA involvement ≥3% were randomized 1:2 to oral placebo or deucravacitinib 6 mg once daily through Week 16. The primary efficacy outcome was ss-PGA 0/1; key secondary outcomes were PSSI 90, change from baseline in scalp-specific itch numeric rating scale (NRS), and sPGA 0/1 at Week 16. Efficacy outcomes were evaluated at Week 16 for the overall population and the subpopulation with global sPGA ≥3. Nonresponder imputation and modified baseline observation carried forward were used for patients who discontinued or had missing data for binary and continuous outcomes, respectively. Results: 154 patients were randomized (placebo, n=51; deucravacitinib, n=103). Baseline characteristics were similar in each group (placebo: mean BSA 10.0%, PASI 9.4, PSSI 32.2; deucravacitinib: mean BSA 10.5%, PASI 10.2, PSSI 33.5). In the overall population, a higher proportion of patients receiving deucravacitinib versus placebo achieved ss-PGA 0/1 at Week 16 (48.5% vs 13.7%; P<0.0001). Deucravacitinib was superior to placebo for PSSI 90 (38.8% vs 2.0%; P<0.0001) and mean change from baseline in scalp-specific itch NRS (−3.2 vs −0.7; P<0.0001). In the subpopulation (sPGA ≥3), a greater proportion achieved sPGA 0/1 with deucravacitinib versus placebo (51.0% vs 4.3%; P<0.0001). The most common adverse events (AEs) in the deucravacitinib group (≥5%) were nasopharyngitis (14.6%), upper respiratory tract infection (11.7%), acne (9.7%), headache (7.8%), COVID-19 (5.8%), and pustular acne (5.8%). Two serious AEs were reported (1/group); neither was considered treatment related or led to discontinuation. Conclusion: Deucravacitinib was efficacious and well tolerated in patients with moderate to severe scalp psoriasis, including those with less extensive overall psoriasis (BSA ≥3%). The overall psoriasis response rate (sPGA 0/1) was consistent with POETYK trial results, despite including patients with more limited BSA involvement. Safety findings were consistent with the known deucravacitinib safety profile.

Efficacy of Deucravacitinib in Plaque Psoriasis Across a Range of Body Surface Area Involvement: Post hoc Analysis of the Randomized, Double-Blinded, Placebo-Controlled, Phase 3b/4 PSORIATYK SCALP Trial

Introduction: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 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. Scalp involvement affects approximately 80% of patients with plaque psoriasis. PSORIATYK SCALP (NCT05478499) is an ongoing, 52-week, multicenter, phase 3b/4 trial evaluating deucravacitinib in patients with moderate to severe scalp psoriasis, including those with a range of total body surface area (BSA) involvement (≥3%). These patients are candidates for systemic therapy, according to the AAD/NPF and IPC treatment guidelines. This post hoc analysis assessed efficacy in overall body psoriasis. Methods: Adults (age ≥18 years) with moderate to severe scalp psoriasis (scalp-specific Physician Global Assessment [PGA] ≥3, scalp surface area involvement ≥20%, and Psoriasis Scalp Severity Index ≥12 at baseline) and BSA involvement ≥3% were eligible for inclusion. Patients were randomized 1:2 to oral placebo (n=51) or deucravacitinib 6 mg once daily (n=103) through Week 16. Stratification factors included prior biologic use and body weight. Outcomes at Week 16 included static PGA score of 0 (clear) or 1 (almost clear) (sPGA 0/1), change from baseline in Psoriasis Area and Severity Index (PASI), and change from baseline in whole-body itch numeric rating scale (NRS). Nonresponder imputation (binary outcomes) and modified baseline observation carried forward (continuous outcomes) were used for patients with missing data. All P values are nominal. Results: Baseline characteristics were similar between groups (deucravacitinib: mean [SD], BSA 10.5% [9.6%], PASI 10.2 [6.7], whole-body itch NRS 5.8 [2.8]; placebo: mean [SD], BSA 10.0% [8.1%], PASI 9.4 [5.6], whole-body itch NRS 5.8 [2.4]). Baseline total BSA involvement was 3%-10% in most patients (deucravacitinib, 68.0%; placebo, 74.5%). At Week 16, a significantly higher proportion of patients receiving deucravacitinib versus placebo achieved sPGA 0/1 (47.6% [95% CI, 37.6%-57.6%] vs 3.9% [0.5%-13.5%], respectively; P<0.0001). Similarly, patients treated with deucravacitinib achieved greater decreases in adjusted mean change from baseline in PASI (−6.4 [95% CI, −7.3 to −5.5] vs −1.3 [−2.6 to −0.1]; P<0.0001) and whole-body itch NRS (−2.9 [−3.4 to −2.4] vs −0.4 [−1.1 to 0.3]; P<0.0001). Conclusion: In the phase 3b/4 PSORIATYK SCALP trial, deucravacitinib was efficacious in improving overall psoriasis. Efficacy was consistent with the results observed in the phase 3 POETYK PSO-1/PSO-2 trials, despite including patients with less extensive total BSA involvement.

Dupilumab Improves Patient-Reported Outcomes as Early as 1 Month among Adults with Prurigo Nodularis in Clinical Practice: Initial Results from the RELIEVE-PN Study

Introduction: Dupilumab is a monoclonal antibody approved in the United States (US) for patients aged ≥18 years with prurigo nodularis (PN). This analysis evaluated the real-world initial impact of dupilumab therapy on symptoms and treatment satisfaction among US adults with PN. Methods: RELIEVE-PN is an ongoing longitudinal prospective patient survey study assessing the real-world effectiveness of dupilumab in the treatment of adult patients with PN. Adults with PN were recruited through the US dupilumab patient support program and surveyed before (baseline) and 1 month after dupilumab initiation. PN symptoms over the last 7 days were assessed using the worst-itch numeric rating scale (WI-NRS), average-itch NRS, skin pain NRS, and skin burning or stinging/tingling NRS (range 0 [no symptom] to 10 [most severe symptom] for all). Treatment satisfaction with current therapy was evaluated using a 7-point Likert scale from “extremely satisfied” to “extremely dissatisfied”. Results: Of 84 patients (mean age, 57.5 years; 79.8% female; 83.3% White) completing the baseline survey and initiating dupilumab, 62 (mean age, 56.4 years; 77.4% female; 83.9% White) completed the Month 1 survey. At baseline, mean (SD) WI-NRS, average itch NRS, skin pain NRS, and skin burning/tingling NRS were 7.70 (2.24), 6.45 (2.25), 5.06 (2.87), and 5.51 (3.02), respectively. By month 1, mean (SD) WI-NRS, average itch NRS, skin pain NRS, and skin burning or stinging/tingling NRS improved to 5.56 (2.89), 4.35 (2.23), 3.40 (2.46), and 3.76 (2.60), respectively (p<0.001 for all). Additionally, significantly more patients reported they were satisfied with current PN treatment(s) at 1 month after dupilumab treatment initiation vs prior to starting dupilumab (77.4% vs 13.1%; p<0.001). Conclusion: Early results from the RELIEVE-PN study demonstrate improvement in symptoms and patient satisfaction with therapy as early as 1-month from treatment initiation of dupilumab. Further comparative research is needed to confirm these findings. Acknowledgment: Research was funded by Sanofi and Regeneron Pharmaceuticals Inc.

Dupilumab Demonstrates a Higher Likelihood of Achieving Improvements in Signs, Symptoms, and Quality of Life vs. Tralokinumab at Week 16: Results from a Bucher Indirect Treatment Comparison

Background: Dupilumab and tralokinumab are biologics approved by the US Food and Drug Administration (FDA) for the treatment of patients with moderate-to-severe atopic dermatitis (AD), aged ≥6 months and ≥12 years, respectively. Dupilumab and tralokinumab have demonstrated efficacy and safety in clinical trials. However, no direct head-to-head trials have been performed to compare the efficacy of dupilumab vs tralokinumab. The Bucher indirect treatment comparison (ITC) is a robust, placebo-adjusted, and accepted method to evaluate the relative efficacy of drugs in the absence of direct comparisons. The objective of this analysis was to report results from a Bucher ITC comparing the efficacy of dupilumab+topical corticosteroid (TCS) vs tralokinumab+TCS at Week 16. Methods: The placebo-adjusted Bucher ITC included published data from the two similarly designed phase 3 trials, LIBERTY AD CHRONOS (NCT02260986) and ECZTRA 3 (NCT03363854). For both studies, data from the 16-week period were used, employing non-responder imputation, with the following doses: 300mg dupilumab every 2 weeks (q2w)+TCS or placebo+TCS, and 300mg tralokinumab q2w+TCS or placebo+TCS. The evaluated endpoints included the proportions of patients achieving an Investigator’s Global Assessment score 0/1 (IGA 0/1; clear/almost clear), 75% and 90% improvements from baseline in Eczema Area and Severity Index (EASI-75 and EASI-90), ≥4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale score (PP-NRS >4), and ≥4-point improvement from baseline in the Dermatology Life Quality Index (DLQI >4). The Bucher ITC with the frequentist approach was performed using R software (v 4.20; netmeta package) with a fixed-effect model. Results were reported as odds ratio (OR) with 95% confidence interval (CI). Results: A total of 801 patients (LIBERTY AD CHRONOS: placebo+TCS: 315; dupilumab+TCS: 106; ECZTRA 3: placebo+TCS: 127; tralokinumab+TCS: 253) were included in the Bucher ITC. Baseline disease characteristics indicated comparable severity between the two trial populations based on IGA and PP-NRS. However, CHRONOS showed slightly higher baseline EASI scores (median [Q1, Q3] score 30.9 [22.3, 41.6] vs. ECZTRA 3: 24.7 [18.4, 35.9]), while ECZTRA 3 showed slightly higher DLQI scores (median [Q1, Q3] score 18.0 [12.0, 23.0] vs. CHRONOS: 13.5 [8.0, 20.0]). Patients treated with dupilumab+TCS had a significantly higher likelihood of achieving IGA 0/1 (OR=2.49, 95%CI 1.24–5.00), EASI-75 (OR=3.21, 95%CI 1.66–6.19), EASI-90 (OR=2.92, 95%CI 1.41–6.02), PP-NRS ≥4 (OR=3.62, 95%CI 1.87–7.00), and DLQI ≥4 (OR=2.16, 95%CI 1.03–4.54) at Week 16 vs those treated with tralokinumab+TCS. Conclusions: A placebo-adjusted Bucher ITC showed that the likelihood of achieving improvements in signs, symptom, and quality of life is significantly higher for patients treated with dupilumab+TCS vs tralokinumab+TCS at Week 16.

Persistent Inadequate Disease Control and Therapeutic Inertia in Moderate-to-Severe Atopic Dermatitis: A 12-month Longitudinal Analysis of Real-world Outcomes from the TARGET-DERM AD registry

Background: Therapeutic inertia refers to the delay or failure in treatment escalation in patients not achieving adequate disease control; it is a challenge in the management of moderate-to-severe atopic dermatitis (AD). Despite the availability of conventional (CST) and advanced systemic therapies (AST) utilized for the treatment of moderate to severe AD, many patients do not achieve treatment success. However, the extent of this inadequacy in real-world clinical practice remains underexplored. Objectives: This study evaluates the occurrence of therapeutic inertia and the proportion of patients with moderate-to-severe AD who continue to show inadequate response after receiving systemic therapies for a duration from 3 to 12 months Methods: We conducted a longitudinal analysis of patients with moderate-to-severe AD (vIGA-AD≥3) from the TARGET-DERM AD registry, including 3,457 participants from 39 centers in the U.S. and Canada. Eligible patients had documented outcomes at the initiation of systemic therapy and after 3 months up to 12 months of follow up. We assessed clinician- and patient-reported outcomes to identify the proportion of patients not meeting treatment targets based on expert consensus. An inadequate response was defined as not achieving a validated Investigator Global Assessment (vIGA-AD) score ≤2, a 50% improvement in Body Surface Area (BSA), and a ≥4-point reduction in the Worst Pruritus Numeric Rating Scale (WP-NRS). An optimal response was defined as a vIGA-AD score ≤1 (clear or almost clear skin), BSA ≤2%, and WP-NRS itch score of 0/1 (complete or almost complete skin resolution). Results: Out of 2,107 patients with moderate-to-severe AD, 445 met the inclusion criteria. The majority were adults (63.8%), female (62.0%), and Non-Hispanic White (45.4%), with an average age of 31 years. Most patients (88.8%) initiated treatment with AST, with dupilumab being the most common (86.5%). The mean vIGA-AD was 3.3 for AST and 3.6 for CST at initiation (P<0.01). At 6 months, 37% and 67% of AST-treated patients had inadequate responses in terms of skin clearance and itch outcomes, respectively, while 82% and 79% did not achieve optimal responses. At 12 months, these figures were approximately 30% and 66% for inadequate responses and 85% and 88% for not achieving optimal responses, respectively. CST-treated patients showed a similar trend. Conclusions: The study reveals that a significant portion of moderate-to-severe AD patients fail to achieve adequate disease control with systemic therapies over 12 months, indicating substantial presence of therapeutic inertia. These findings suggest a need for more proactive management strategies in AD treatment.

Achievement of No-to-minimal Itch and Sleep Improvement with Tapinarof Cream 1% Once Daily in Two Pivotal Phase 3 Trials in Adults and Children Down to 2 Years of Age with Atopic Dermatitis

Introduction: Itch frequently causes sleep disturbance in patients with atopic dermatitis (AD). The gold-standard Peak Pruritus Numerical Rating Scale (PP-NRS) improvement from baseline is 4 points; however, more stringent outcomes include achieving no-to-minimal itch (PP-NRS ≤1). Tapinarof cream 1% once daily (QD) demonstrated superior efficacy, including itch reduction, versus vehicle and was well tolerated in adults and children down to 2 years of age with AD in the ADORING 1 and 2 pivotal phase 3 trials. Here we present highly stringent itch outcomes and sleep improvement with tapinarof from these trials. Methods: In ADORING 1 and 2, patients with a Validated Investigator Global Assessment for Atopic Dermatitis™ score ≥3 (moderate or severe), Eczema Area and Severity Index score ≥6, and body surface area involvement of 5–35% were randomized to tapinarof cream or vehicle QD for 8 weeks. Stringent PP-NRS assessments were analyzed post hoc and included achieving no‑to‑minimal itch (PP-NRS ≤1) or PP-NRS score <2. Mean weekly PP-NRS scores were assessed on an 11-point scale (0 indicates “no itch” and 10 is “worst imaginable itch”). The Patient Oriented Eczema Measure (POEM) question 2 evaluated sleep disturbance on a 5-point scale (0 indicates “no days” and 4 is “every day”); outcomes were pooled and stratified by age. Results: 407 and 406 patients were randomized in ADORING 1 and 2. Mean baseline scores were similar across ADORING 1 and 2 treatment groups: PP-NRS, 6.7 and 6.8; pooled POEM sleep disturbance scores, 2.0 (aged ≥12 years) and 2.4 (<12 years), respectively. Statistically significant achievement of no-to-minimal itch (PP-NRS ≤1), PP-NRS <2, and improvement in sleep were achieved with tapinarof versus vehicle as early as Week 1, the first assessment, and continued through Week 8. Stringent itch outcomes were achieved with tapinarof versus vehicle at Week 8: no-to-minimal itch, 31.4% versus 17.4% (P=0.0072) and 33.0% versus 14.0% (P=0.0003); and PP-NRS <2, 48.1% versus 28.4% (P=0.0006) and 46.8% versus 19.6% (P<0.0001) in ADORING 1 and 2, respectively. Sleep scores improved with tapinarof versus vehicle at Week 8: –1.4 versus –0.8 (≥12 years); –1.7 versus –1.0 (<12 years; both P<0.0001). Conclusion: Tapinarof cream 1% QD demonstrated early, significant, and meaningful achievement of no-to-minimal itch and improvement of sleep in adults and children down to 2 years of age with AD.

Long-Term Maintenance of Optimal Treatment Targets for Skin and Itch Outcomes With Upadacitinib in Moderate-to-Severe Atopic Dermatitis: 140-Week Results From the Phase 3 Measure Up 1 and 2 Studies

Introduction: Despite undergoing prolonged systemic therapy, many patients with moderate-to-severe atopic dermatitis (AD) do not achieve optimal targets for skin and itch outcomes as defined by Aiming High in Eczema/AD (AHEAD) recommendations (eg, ≥90% improvement from baseline in Eczema Area and Severity Index [EASI 90] and Worst Pruritus Numerical Rating Scale [WP-NRS] score of 0/1 [no/minimal itch]). We evaluated long-term maintenance of optimal treatment targets with upadacitinib, an oral selective JAK inhibitor approved for moderate-to-severe AD in adolescents and adults. Methods: This 140-week interim analysis included adolescents and adults with moderate-to-severe AD who were randomized at baseline to upadacitinib 15 mg (UPA15) or 30 mg (UPA30) in the ongoing, phase 3, double-blind Measure Up 1 and 2 studies. Assessments included the proportion of patients (at the population level) who maintained EASI 90, WP-NRS 0/1, or simultaneous achievement of EASI 90 + WP-NRS 0/1 responses from week 16 (end of the placebo-controlled period) onwards. Data are reported as observed cases with no imputation for missing data. Results: Among patients who achieved EASI 90 at week 16 (UPA15, n=298; UPA30, n=384), EASI 90 was maintained by 79.8% (UPA15) and 83.7% (UPA30) at week 52, 76.7% (UPA15) and 83.0% (UPA30) at week 100, and 74.0% (UPA15) and 84.2% (UPA30) at week 140. Of patients achieving WP-NRS 0/1 at week 16 (UPA15, n=193; UPA30, n=281), WP-NRS 0/1 was maintained by 69.4% (UPA15) and 72.0% (UPA30) at week 52, 65.6% (UPA15) and 68.4% (UPA30) at week 100, and 62.3% (UPA15) and 66.0% (UPA30) at week 140. Of patients simultaneously achieving EASI 90 + WP-NRS 0/1 at week 16 (UPA15, n=156; UPA30, n=243), maintenance was achieved by 68.1% (UPA15) and 70.8% (UPA30) at week 52, 62.7% (UPA15) and 66.5% (UPA30) at week 100, and 58.7% (UPA15) and 64.4% (UPA30) at week 140. Among patients who did not maintain optimal outcomes, most still achieved clinically meaningful responses. Conclusion: Most patients maintained optimal skin and itch outcomes through 140 weeks of upadacitinib treatment, demonstrating its potential to provide sustained long-term disease control in atopic dermatitis.

Effects of ultrasound-guided external oblique intercostal plane block on the postoperative analgesia after open liver surgery: study protocol for a randomised controlled trial.

Open liver surgery remains a primary surgical approach for complex liver resections and liver transplantation. However, the postoperative pain management is still a major challenge. Ultrasound-guided external oblique intercostal (EOI) plane block is a novel approach of regional anaesthesia and has a great potential to relieve postoperative pain after upper abdominal surgeries. This study aims to investigate the efficacy and safety of ultrasound-guided EOI plane block in managing postoperative pain after open liver surgery. Seventy-four participants scheduled for open liver surgery will be randomly assigned to either the intervention group, receiving an ultrasound-guided EOI plane block with a single dose of 30ml 0.375% ropivacaine, or the control group, which will not receive this block. All participants will be provided with opioid-based patient-controlled intravenous analgesia (PCIA) postoperatively. The primary outcome is resting pain score at 3h postoperatively, assessed using numerical rating scale. Secondary outcomes include pain score at 6, 24, 48, and 72h postoperatively, perioperative opioid consumption, remedial analgesics within 72h postoperatively, PCIA usage within postoperative 72h, postoperative recovery, length of hospital stay, postoperative side effects, block-related complications, and ropivacaine plasma concentration of participants receiving the block. This study is a randomised controlled trial to evaluate the efficacy and safety of ultrasound-guided EOI plane block for postoperative analgesia after open liver surgery. As regional anaesthesia plays an important role in the multimodal pain management, EOI plane block may prove to be an effective regional technique for enhancing postoperative pain relief and contributing to enhanced recovery after open liver surgery. Chinese Clinical Trial Registry ChiCTR2200065745. Registered on November 14, 2022.

Causes of chronic pain unrelated to surgical trauma after groin hernia repair: a prospective cohort study.

Chronic inguinal pain (CIP) can be caused by musculoskeletal or neurological pathologies and by surgical trauma after inguinal hernia repair among other. The aim of this prospective cohort observational study was to find the incidence and causes of CIP unrelated to surgical trauma 12 months after inguinal hernia repair. During sixteen months patients consulting a hernia center for groin-related symptoms were included in the study. Patients were evaluated by surgeons and filled out preoperatively the Inguinal Pain Questionnaires and a Numerical Rating Scale pain-questionnaire. For patients undergoing inguinal hernia repair, postoperative questionnaires similar to the pre-operative ones were sent out at 12 months. Patients scoring pain on pain questionnaires were evaluated by phone and physical examination. 289 patients (78.1%) of 370 repaired patients filled in the postoperative questionnaires. 62 (21.4%) patients scored pain, of these patients 5 (1.7%, 5/289) answered incorrectly in the pain questionnaires and 14 (4.8%, 14/289) had non-surgical trauma causes of pain: 5 musculoskeletal, 4 neurological and 3 other medical pathologies. This cohort study found CIP unrelated to surgical trauma in 4.8% of patients undergoing a groin hernia repair. Most causes of pain unrelated to surgical trauma were musculoskeletal and neurological pathologies. Nearly a third of patients scoring inguinal pain on pain-questionnaires did not have chronic post-surgical pain (CPSP), therefore incidence of CPSP should not be based solely on pain questionnaires. Clinical assessment of patients with pain is necessary to excluded CIP unrelated to the surgical trauma.

Shear wave elastography based analysis of changes in fascial and muscle stiffness in patients with chronic non-specific low back pain

BackgroundThe quantitative assessment of individual muscle and fascial stiffness in patients with low back pain remains a challenge. This study aimed to compare the stiffness of the thoracolumbar fascia (TLF), erector spinae (ES), and multifidus (MF) in patients with and without chronic non-specific low back pain (CNLBP) using shear wave elastography (SWE). It also sought to explore the relationship between muscle and fascial stiffness and the levels of pain and dysfunction in patients with CNLBP.MethodsIn this cross-sectional study, 30 patients with CNLBP (age 27.40 ± 4.57 years, 19 males, 11 females, BMI 22.96 ± 2.55 kg/m2) and 32 healthy controls (age 27.94 ± 4.94 years, 15 males, 17 females, BMI 22.52 ± 2.26 kg/m2) were enrolled. Stiffness of the TLF, ES, and MF was measured using SWE, and Young’s modulus values were recorded. The numeric rating scale (NRS) for quantifying pain intensity and the Oswestry Disability Index (ODI) scores were recorded for the case group to examine their correlations with the resilience index.ResultsThe CNLBP group exhibited significantly higher shear modulus values at the L4-5 bilateral TLF (left: p = 0.014, d = 0.64; right: p = 0.002, d = 0.86), ES (left: p = 0.013, d = 0.66; right: p = 0.027, d = 0.58), and MF (left: p = 0.009, d = 0.69; right: p = 0.002, d = 0.85) compared to the control group. Comparable findings were observed for the right ES (p = 0.026, d = 0.59) and left MF (p = 0.020, η2 = 0.09) at L1-2. Strong correlations were observed between the shear modulus of the bilateral TLF (left: r = 0.57, p = 0.001; right: r = 0.65, p < 0.001) at L4-5 and the NRS scores. Moderate correlations were noted between the shear modulus of the ES (left: r = 0.42, p = 0.022; right: r = 0.48, p = 0.007) and MF (left: r = 0.50, p = 0.005; right: r = 0.42, p = 0.023) at L4-5 and the NRS scores. Additionally, the shear modulus of the MF (r = 0.50, p = 0.005) on the left side of L1-2 showed similar correlations. Strong correlations were observed between the shear modulus of the bilateral TLF (left: r = 0.60, p < 0.001; right: r = 0.58, p < 0.001) at L4-5 and the ODI scores. Moderate correlations were observed between the shear modulus of the right TLF (r = 0.43, p = 0.017), ES (r = 0.38, p = 0.037), and MF (r = 0.44, p = 0.015) at L1-2, as well as the bilateral MF (left: r = 0.46, p = 0.011; right: r = 0.45, p = 0.012) at L4-5, and the ODI scores. No significant correlations were found at other measurement sites.ConclusionIn patients with CNLBP, the stiffness of the lumbar fascia and muscles is generally higher than in individuals without LBP. However, this increase is not uniform across all lumbar regions, with the most significant changes observed in the L4-5 segments. In addition, higher stiffness may be associated with pain and dysfunction, primarily manifested in the TLF.

Ruxolitinib Cream Monotherapy Improved Symptoms and Quality of Life in Adults and Adolescents with Mild-to-Moderate Atopic Dermatitis: Patient-Reported Outcomes from Two Phase III Studies.

Atopic dermatitis (AD) is associated with itch, skin pain, sleep disturbances, and diminished quality of life (QoL). Ruxolitinib (Janus kinase [JAK] 1/JAK2 inhibitor) cream demonstrated efficacy and safety in adults and adolescents with mild-to-moderate AD in two phase III studies (TRuE-AD1/TRuE-AD2). In TRuE-AD1/TRuE-AD2, significant improvements in itch were observed as early as 12 h following application of ruxolitinib cream. The aim of this paper was to assess additional patient-reported outcomes (PROs) in the vehicle-controlled (VC) and long-term safety (LTS) periods of TRuE-AD1/TRuE-AD2. In the TRuE-AD studies, patients aged ≥12 years with AD were randomized 2:2:1 to apply twice-daily 1.5% ruxolitinib cream, 0.75% ruxolitinib cream, or vehicle cream continuously for 8weeks (VC period). During the LTS period, patients applied the same ruxolitinib cream strength, but on an as-needed basis; patients who initially applied vehicle were re-randomized to apply 0.75% or 1.5% ruxolitinib cream. Pooled data from both study periods were analyzed. PRO assessments included symptoms (itch [Patient-Oriented Eczema Measure, POEM], skin pain [numerical rating scale], and sleep [POEM and Patient-Reported Outcomes Measurement Information System]) and assessments of disease-specific QoL (Dermatology Life Quality Index [DLQI] and the children's version [CDLQI]). A total of 1208 and 1031 patients from the VC and LTS periods, respectively, were included in the analysis. Significant improvements in skin pain were observed within 12h among patients who applied ruxolitinib cream versus vehicle; improvements continued throughout the VC period. Improvements in patient-reported symptoms (including sleep) were observed within 2 weeks (first assessment) of ruxolitinib cream application. At Week 2, significant improvements in symptom burden and overall QoL were observed with ruxolitinib cream (0.75%/1.5%) versus vehicle in POEM (-8.9/-9.8 vs -2.2; both p<0.0001), DLQI (mean changes from baseline, -5.8/-6.1 vs -1.2; both p<0.0001), and CDLQI (-4.3/-5.3 vs -1.3; both p<0.0001). Further symptom burden and QoL improvements were reported during the VC period and were maintained through the end of the LTS period (Week 52). Consistent with the previously reported itch response data, ruxolitinib cream improved skin pain within 12 h of application. Ruxolitinib cream improved patient-reported AD symptom burden and overall QoL by Week 2. Improvements continued or were maintained for 52 weeks. (Graphical abstract and plain language summary available). ClinicalTrials.gov identifiers, NCT03745638 and NCT03745651 (both studies were registered on November 19, 2018).

Sequential adaptive e-learning and hands-on simulator training for unilateral biportal endoscopy (UBE) of the lumbar spine - results from an EANS Young Neurosurgeons hands-on course.

Unilateral biportal endoscopy (UBE) is a minimally invasive surgical (MIS) technique utilized for lumbar decompression, which has recently gained popularity in Europe. We aimed to explore the value of sequential adaptive e-learning, followed by simulator-based hands-on training modules for UBE at the occasion of the 2024 EANS Young Neurosurgeons meeting. An adaptive e-learning was designed by learning engineers (Area 9 Lyceum), based on theoretical content provided by two endoscopic spine surgeons. A two-module simulator training, consisting of an insight-the-box model (basic tasks for eye-hand coordination), followed by a realistic lumbar spine model (execution of an endoscopic decompression) was developed. Course participants completed the e-learning before the hands-on training course. Course experience was evaluated through a standardized self-assessment questionnaire containing a 5-point Likert scale and a 10-point numeric rating scale. Eleven of eighteen (61%) participants with different levels of professional education (62.5% residents in 1st -6th year of training, 37.5% board-certified) completed both trainings. Thirteen participants (72%) had no prior experience with UBE. The perception of knowledge after the e-learning module increased from 2.5 (SD 2) to 6.5 (SD 1.8; p = 0.039). The usefulness, enjoyment, and efficiency of the courses averaged a score of 8.0 (SD 1.8). Regarding the hands-on training, participants estimated an average increase in their skills from 2.9 (SD 1.8) to 6.8 (SD 2, p = 0.028). The overall rating of the two-module course was 7.9 (SD 2.2). Sequential e-learning and simulator training appear to be an effective educational adjunct to establish novel, MIS-techniques such as UBE.

Real-world efficacy and safety of dupilumab for paediatric atopic dermatitis: a multicentre retrospective study.

Real-world data regarding the use of dupilumab in children with atopic dermatitis (AD) are limited. To evaluate the real-world efficacy of dupilumab in children with moderate-to-severe AD over an extended follow-up period. This was a retrospective study of patients (≤ 18 years) with moderate-to-severe AD treated with dupilumab in four Israeli tertiary centres. Efficacy and safety were assessed using descriptive statistics. In total, 230 patients were included in the analysis [age 9.9 years (SD 4.3), male/female 1 : 1 ratio)]. Of them, 59.6% (137/230) had ≥ 1 atopic comorbidity. The follow-up duration ranged from 2 to 248 weeks, with a median of 52 weeks (interquartile range 24-96). Within 12 weeks of treatment, 41.7% (68/163) of patients had reached Investigator Global Assessment 0-1. The mean body surface area was reduced from 58.0% (SD 20.5%) at baseline to 27.8% (SD 20.2%) at 12 weeks. The average Pruritus Numeric Rating Scale score was reduced from 7.9 (SD 2.2) at baseline to 2.3 (SD 2.8) at 12 weeks. Adverse events, in 210 patients, included conjunctivitis in 34 patients (16.2%), injection-site reactions in 11 patients (5.2%) and dupilumab-associated head and neck dermatitis in 6 patients (2.9%). Overall, 26 of 210 patients (12.3%) discontinued the treatment: 9 of the 26 patients (35%) because of adverse events and 15 patients (58%) because of inadequate efficacy. The overall probability of dupilumab survival at 52 weeks was 94.0%. Real-world data presented here for 230 paediatric and adolescents with moderate-to-severe AD reinforce dupilumab's efficacy and safety and highlight dupilumab's high survival rate after 1 year of treatment in the paediatric population.

Intra-articular corticosteroid injections versus platelet-rich plasma as a treatment for cervical facetogenic pain: a randomized clinical trial

ObjectiveThe study’s primary objective was to compare the effectiveness of intra-articular platelet-rich plasma injections versus corticosteroid injections for the treatment of cervical facetogenic pain. Secondary aims were to compare self-rated...

National Institute of Health and Care Excellence Clinical Criteria for the Diagnosis of Knee Osteoarthritis: A Prospective Diagnostic Accuracy Study in Individuals with Type 2 Diabetes.

The National Institute of Health and Care Excellence (NICE) criteria for osteoarthritis (OA) obviate the need for physical exam or imaging, and their use may improve timely diagnosis of OA. However, they have not been validated. Within a larger study of individuals with type 2 diabetes, participants with and without self-reported knee pain underwent assessment of the NICE criteria for knee OA by questionnaire (index test), and clinical evaluation for established or possible knee OA by a rheumatologist (reference standard). We calculated the sensitivity, specificity, likelihood ratio positive (LR+) and likelihood ratio negative (LR-) of the NICE criteria and modified NICE criteria without the stiffness criterion. Our study included 96 participants: mean age 65.4 (SD 8.3) years and 52% were women. Individuals who fulfilled NICE criteria for knee OA (55.2%) included a spectrum of pain severity on a 11-point pain numeric rating scale with a median score of 5 (range: 1-9). Rheumatologist assessment identified 56 (58.3%) participants with symptomatic knee OA. The sensitivity, specificity, LR+, and LR- of NICE criteria for symptomatic knee OA were 0.84 (95% CI 0.74, 0.94), 0.85 (95% CI 0.74, 0.96), 5.6 and 0.19, respectively. For modified NICE criteria, these were 0.89 (95% CI 0.82, 0.97), 0.85 (95% CI 0.74, 0.96), 5.93 and 0.13. The NICE criteria have high sensitivity and specificity for detecting symptomatic knee OA in a population with type 2 diabetes. We found that a modified version, omitting the stiffness criterion, performed similarly. These criteria should be validated in other settings and populations.

CLINICAL EFFECTIVENESS AND FEATURES OF THE POSTOPERATIVE PERIOD IN PATIENTS AFTER OSTEOSYNTHESIS OF THE MANDIBLE USING CELL TECHNOLOGIES

Due to a signifi cant increase in the frequency and complexity of maxillofacial injuries, one of the priorities in the development of modern surgical dentistry is the search for new eff ective methods of treating facial bone fractures. In recent decades, the attention of clinicians has been focused on biological treatment methods aimed at restoring bone defects using cell technologies and biological transplants.The aim of the study was to determine the eff ect of using osteoplastic materials based on multipotent adipose- derived mesenchymal stromal cells in dental patients in the surgical treatment of mandibular fractures.Materials and methods. The clinical material included 56 patients, 13 of whom underwent mandibular osteosynthesis with hydroxyapatite bone graft substitute (subgroup 1I), 25 of whom underwent surgery with a combination of multipotent adipose tissue mesenchymal stromal cells, hydroxyapatite bone graft substitute and platelet-rich plasma (subgroup 1B), and 18 of whom underwent spontaneous healing of the fracture line (subgroup 1C). Patients were clinically evaluated on a daily basis. Clinical parameters were assessed on days 1, 3, 5, 7, 10, 14 and 28 after surgery. The postoperative pain syndrome was assessed using the Numerical Rating Scale (NRS), considering the subjective signs of pain in the operated patients.The statistical processing of the study results was performed using the statistical analysis software for biomedical research ‘Microsoft Excel 21’ and ‘Statistica’ (licence number STA862D175437Q). In the statistical processing of the results, we used the variational analysis of series – calculation of the arithmetic mean and its standard error (Mim) – and assessed the signifi cance of diff erences in the results obtained in the comparison groups using the Student’s t-test method. p&lt;0.05 was considered a signifi cant diff erence. [17]. The study was conducted in accordance with the basic provisions of the «Rules of Ethical Principles for Scientifi c Medical Research Involving Human Subjects» approved by the Declaration of Helsinki (1964-2013), ICH GCP (1996), EEC Directive 609 (24.11.1986), Orders of the Ministry of Health of Ukraine ¹ 690 of 23.09.2009, ¹ 944 of 14.12.2009, ¹ 616 of 03.08.2012. The Commission on Biomedical Ethics of the Bukovinian State Medical University found no violations of ethical and moral standards in the conduct of the research (ProtocolNo. 6, 16.03.2023). Patients signed informed consent to participate in this study and all measures were taken to ensure their anonymity.The results. The comparative analysis of the clinical eff ectiveness of the use of various osteoplastic materials in the performance of osteosynthesis surgery of the lower law confi rmed the advantages of the use of bone tissue substitute based on hydroxyapatite and its combination with multipotent adipose tissue mesenchymal stromal cells before spontaneous augmentation. It is confi rmed by the data of subjective and objective symptoms of patients during the postoperative period.Conclusions. Our data show that osteoplastic material based on multipotent mesenchymal stromal cells of adipose tissue, bone substitute based on hydroxyapatite and platelet-rich blood plasma is a promising biological material. Its application improves the regenerative and reparative properties of bone tissue, facilitates the postoperative period and shortens the duration of hospitalization, promotes the development of innovative ways of reconstructive osteogenesis in modern maxillofacial surgery.

Efficacy and Safety Analysis in Chinese Patients with Moderate-to-Severe Psoriasis from a Phase 3 Trial: Impact of Treatment Withdrawal and Retreatment of Ixekizumab.

In China, approximately 2.3 million people have psoriasis. Continuous treatment is recommended for moderate-to-severe psoriasis. This study aimed to evaluate the outcomes of continuous versus interrupted ixekizumab (IXE) treatment and retreatment with IXE after disease worsening in Chinese patients. In this Phase 3, multicenter, randomized, double-blind, placebo-controlled study, patients were randomized to IXE or placebo at Week 0. At Week 12, IXE responders (static Physician's Global Assessment [sPGA] score, 0 or 1 [0,1]) were re-randomized (2:1) to IXE (IXE/IXE, continuous treatment) or placebo (IXE/PBO, interrupted treatment). After re-randomization, treatment in IXE/PBO patients with disease worsening (relapse, sPGA ≥ 3) was switched to IXE every 4weeks (IXE/PBO + IXEQ4W, retreatment). Efficacy was assessed by evaluating the response rates of Psoriasis Area and Severity Index (PASI) 75/90/100, sPGA (0,1), Dermatology Life Quality Index (DLQI) (0,1), mean PASI, and Itch Numerical Rating Scale (NRS) scores and improvements of special body areas. Safety was evaluated by assessing treatment-emergent adverse events (AEs) and serious AEs. At Week 12, 289 IXE responders were re-randomized to the IXE/IXE group (192 patients) and IXE/PBO group (97 patients). High rates of PASI 75 and sPGA (0, 1) responses were maintained in the IXE/IXE group until Week 60. At Week 60, 88 (90.7%) patients in the IXE/PBO group had disease relapse; the median time to relapse was approximately 20weeks. After 24weeks of retreatment, PASI 75 and sPGA (0, 1) were recaptured (97.2% and 74.6%, respectively, in the IXE/PBO + IXEQ4W group). AEs were comparable in patients who received continuous treatment and retreatment. In Chinese patients who received continuous IXE treatment, high response rates were maintained through 60weeks. Most patients had disease relapse after treatment withdrawal. After retreatment, most of these patients had regained and maintained response since Week 12. NCT03364309.