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Background: Atopic dermatitis (AD) is associated with a substantial burden on quality of life (QoL)., Objective: To evaluate the effects of tralokinumab on health-related QoL in patients with moderate-to-severe AD using patient-reported outcomes., Methods: This was a phase 2b, randomized, double-blind, placebo-controlled, dose-ranging study in adults with moderate-to-severe AD. The patients received subcutaneous tralokinumab or placebo (1:1:1:1) every 2 weeks for 12 weeks and class 3 topical corticosteroid cream or ointment at least once daily from the run-in to end of follow-up. Patient-reported outcome end points were change from baseline to week 12 in the Dermatology Life Quality Index (dermatology life quality index (DLQI); prespecified secondary objective), the Short Form 36 Health Survey (SF-36) version 2, and sleep interference numeric rating scale score (prespecified exploratory objectives)., Results: A total of 204 patients were randomized to placebo (n = 51) or tralokinumab (45 mg, n = 50; 150 mg, n = 51; 300 mg, n = 52). Tralokinumab 300 mg every 2 weeks improved total Dermatology Life Quality Index vs placebo at week 12 (placebo-adjusted mean change, -3.51 [95% confidence interval, -6.00 to -1.02]). At week 12, both the mental component summary (4.23 [0.98-7.47]) and the physical component summary (4.26 [1.83-6.69]) and all 8 domains of the Short Form 36 Health Survey were improved in patients treated with tralokinumab 300 mg vs placebo. Sleep interference was improved at week 12 with all tralokinumab doses vs placebo., Conclusion: Tralokinumab improved health-related QoL in patients with moderate-to-severe atopic dermatitis, providing further evidence of the value of targeting interleukin-13 in such patients., Trial Registration: ClinicalTrials.gov identifier: NCT02347176; https://clinicaltrials.gov/ct2/show/NCT02347176., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Two randomized controlled trials (reSURFACE 1 and 2) have demonstrated the effectiveness of tildrakizumab, a high-affinity, humanized, IgG1κ, anti-interleukin-23 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in the first 28 weeks., Objectives: To examine the efficacy of tildrakizumab and its impact on quality of life (QoL) in patients with different levels of week-28 Psoriasis Area and Severity Index (PASI) improvement., Methods: Patients treated with tildrakizumab 100 mg or 200 mg from baseline to week 28 were pooled from reSURFACE 1 and reSURFACE 2 and classified into five mutually exclusive week-28 PASI improvement groups for each dose: PASI 0-49, 50-74, 75-89, 90-99 and 100. Mean PASI improvement and Dermatology Life Quality Index (DLQI) 0/1 over time were examined for each group., Results: Of 1156 patients, 575 were in the 100-mg and 578 in the 200-mg cohorts, respectively. At week 28, 8.3%, 14.3%, 23.8%, 30.4% and 23.1% in the 100-mg and 4.0%, 18.1%, 19.6%, 29.1% and 29.3% in the 200-mg cohort achieved PASI < 50, 50-74, 75-89, 90-99 and 100, respectively. Patients with PASI < 50 at week 28 could be identified as early as week 8, and those with week-28 PASI ≥ 90 had approximately 50% PASI improvement by week 4. Among patients achieving PASI > 50 at week 28 who continued the same dose of tildrakizumab to week 52, mean PASI improvement was maintained or improved over time. Similar results were observed for both doses. Higher proportions of patients achieved DLQI 0/1 in higher week-28 PASI groups, and DLQI 0/1 was maintained or improved to week 52. However, not all patients with PASI 100 had DLQI 0/1., Conclusion: Patients unlikely to respond to tildrakizumab could be identified by week 8, and those likely to achieve a PASI ≥ 90 response could be identified as early as week 4. Week-28 PASI improvement level correlated with QoL improvement., (© 2019 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Patients with psoriasis are at an increased risk for depression. However, the impact of treatment on this risk is unclear., Objective: Evaluate the incidence and impact of treatment on depression among patients with moderate-to-severe psoriasis., Methods: We defined a study population within the Psoriasis Longitudinal Assessment and Registry and measured the incidence of depressive symptoms (Hospital Anxiety and Depression Scale-Depression score ≥8) and adverse events (AEs) of depression within cohorts receiving biologics, conventional systemic therapies, or phototherapy. Patients were evaluated at approximately 6-month intervals. Multivariate modeling determined the impact of treatment on risk., Results: The incidence rates of depressive symptoms were 3.01 per 100 patient-years (PYs) (95% confidence interval [CI], 2.73-3.32), 5.85 per 100 PYs (95% CI, 4.29-7.97), and 5.70 per 100 PYs (95% CI, 4.58-7.10) for biologics, phototherapy, and conventional therapy, respectively. Compared with conventional therapy, biologics reduced the risk for depressive symptoms (hazard ratio, 0.76; 95% CI, 0.59-0.98), whereas phototherapy did not (hazard ratio, 1.05; 95% CI, 0.71-1.54). The incidence rates for AEs of depression were 0.21 per 100 PYs (95% CI, 0.15-0.31) for biologics, 0.55 per 100 PYs (95% CI, 0.21-1.47) for phototherapy, and 0.14 per 100 PYs (95% CI, 0.03-0.55) for conventional therapy; the fact that there were too few events (37 AEs) precluded modeling., Limitations: Incomplete capture of depression and confounders in the patients on registry., Conclusion: Compared with conventional therapy, biologics appear to be associated with a lower incidence of depressive symptoms among patients with psoriasis., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Patients with moderate-to-severe psoriasis report impaired health-related quality of life (HRQoL)., Objective: To assess speed of onset of ixekizumab-induced clinically relevant improvement in HRQoL., Methods: This post hoc analysis used pooled data from patients randomized in UNCOVER-2 and UNCOVER-3, and treated with 80 mg ixekizumab every 2 weeks (IXEQ2W), 80 mg ixekizumab every 4 weeks (IXEQ4W), 50 mg etanercept (ETN) twice weekly or placebo (PBO) for 12 weeks. HRQoL and pruritus were assessed using the Dermatology Life Quality Index (DLQI) and Itch Numeric Rating Scale (NRS), respectively. Minimally clinical important differences (MCID) in DLQI and Itch NRS were defined as ≥5-point and ≥4-point improvements from baseline, respectively. Time to response from randomization was estimated using Kaplan-Meier methodology and the log-rank test. Hazard ratios between treatments were calculated using a Cox proportional hazards regression model adjusting for studies., Results: A total of 2570 patients were included: 361 PBO; 740 ETN; 733 IXEQ4W and 736 IXEQ2W. Significantly greater differences in time to DLQI ≥5 point or Itch NRS ≥4 point improvement for IXEQ2W or IXEQ4W compared with ETN and PBO (P < 0.001) were observed. The median time when 50% of patients reached a ≥5-point reduction in DLQI was shorter for ixekizumab-treated patients (2 weeks, both schedules) compared with ETN- (4 weeks) or PBO-treated (>12 weeks) patients. Likewise, the median time when 50% of patients reached a ≥4-point reduction in Itch NRS was shorter for ixekizumab-treated patients (2 weeks, both schedules) compared with ETN- (8 weeks) or PBO-treated (>12 weeks) patients. Significantly more ixekizumab-treated patients were likely to achieve MCIDs in DLQI or itch reduction compared with ETN or PBO after 12 weeks of treatment., Conclusion: Ixekizumab-treated patients achieved more rapid improvements both in HRQoL and itch compared with patients treated with ETN and PBO., (© 2017 European Academy of Dermatology and Venereology.)

Aims: To determine if EuroQoL 5-Dimension Health Questionnaire (EQ-5D) health utility scores were able to discriminate among different levels of improvement in psoriasis severity following therapy., Materials and Methods: Data were from three placebo-controlled phase 3 ixekizumab studies (UNCOVER-1, UNCOVER-2, and UNCOVER-3) with patients who had baseline Dermatology Life Quality Index scores >10 (DLQI >10). Psoriasis severity (Psoriasis Area and Severity Index [PASI]), general health utility (EQ-5D), and psoriasis-specific utility (EQ-PSO, UNCOVER-3 only) were assessed. EQ-5D-5L utility scores were generated using the England EQ-5D-5L value set, a crosswalk applied to the EQ-5D-3L United States (US) and United Kingdom (UK) value sets, and a regression-based exploratory scoring function for the EQ-PSO (UK). Analysis of variance was used to estimate change in EQ-5D-5L from baseline to Week 12 per PASI improvement level: PASI <50, PASI 50 to <75, PASI 75 to <90, PASI 90 to <100, and PASI 100. Missing data were imputed using the last observation carried forward method. Value sets for the UK, England, and the US were applied., Results: In total, 2085 patients across UNCOVER-1, UNCOVER-2, and UNCOVER-3 had baseline DLQI >10 and available utility scores. At Week 12, mean EQ-5D utility scores increased with increasing PASI improvement levels (p < 0.001, all analyses). Mean health utilities for PASI 90 to <100 and PASI 100 were similar when based on the generic classifier, whereas a clear differentiation between PASI 90 to <100 and PASI 100 was observed for EQ-PSO mean scores (UNCOVER-3 only, n = 645; PASI 90 to <100: 0.141, PASI 100: 0.200; adjusted p = 0.043)., Limitations: EQ-5D-5L index-based scores have limited ability to differentiate among psoriasis patients at the highest PASI improvement levels. ConclusionsL Adding psoriasis-specific EQ-PSO dimensions to the EQ-5D may enhance responsiveness to improvement in skin clarity at the highest PASI levels, and, therefore, generate utility scores that better reflect treatment benefit in cost-utility models.

Increasingly, quality of life data are being captured along with other measures to evaluate success in the treatment of numerous disease states. This is no less true in hidradenitis suppurativa (HS), an inflammatory condition that features multiple symptoms, including abscesses that can develop in multiple sites on the body, often in sensitive areas, that can be painful, can rupture, and can produce malodorous pus. The collection of baseline data with respect to the personal impact of HS is a necessary first step to determine if various interventions enhance the quality of life for patients with HS. While no particular tool provides sufficient insight about the psychosocial impairment that HS promotes, myriad instruments that have been used to measure the quality of life of HS patients have consistently shown that the disease has a substantial adverse impact on the physical, social, and emotional well-being of patients., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Once‐daily abrocitinib treatment provided meaningful improvements in signs and symptoms of moderate‐to‐severe atopic dermatitis (AD) in randomized controlled studies. Objective: To evaluate proportions of patients with responses meeting higher threshold efficacy responses than commonly used efficacy end points and to determine if these responses were associated with quality‐of‐life (QoL) benefits. Methods: Data from a phase 2b (NCT02780167) and two phase 3 studies (NCT03349060/JADE MONO‐1; NCT03575871/JADE MONO‐2) in adult and adolescent patients (N = 942) with moderate‐to‐severe AD receiving once‐daily abrocitinib 200 mg, abrocitinib 100 mg or placebo were pooled. Commonly used (Eczema Area and Severity Index [EASI]‐75 and ≥4‐point improvement in Pruritus Numerical Rating Scale [PP‐NRS4]) and higher threshold efficacy end points (EASI‐90 to

Background: Risankizumab has demonstrated durable, high rates of efficacy in patients with moderate‐to‐severe plaque psoriasis as assessed by the achievement of relative Psoriasis Area and Severity Index (PASI) improvement and Dermatology Life Quality Index (DLQI) 0/1. Objectives: The aim of this post hoc analysis is to assess the achievement of absolute PASI thresholds and related improvements in health‐related quality of life (HRQoL) in patients with moderate‐to‐severe plaque psoriasis treated with (i) risankizumab compared with ustekinumab, and (ii) long‐term (>52 weeks to 172 weeks) risankizumab. Methods: Data from patients randomised to 150 mg risankizumab or 45 or 90 mg ustekinumab in replicate randomised controlled trials UltIMMa‐1 and UltIMMa‐2 were analysed for the achievement of absolute PASI thresholds PASI ≤ 3, PASI ≤ 1, and PASI = 0, time to achieve these thresholds, and combined PASI and DLQI endpoints. Data from pat ients initially randomised to risankizumab who continued on risankizumab in the open‐label extension study LIMMitless were analysed for the achievement of absolute PASI levels, mean DLQI scores, and DLQI 0/1. Results: Significantly greater proportions of patients treated with risankizumab compared with ustekinumab achieved PASI ≤ 3, PASI ≤ 1, and PASI = 0, as well as combined endpoints for absolute PASI and DLQI [(PASI ≤ 3 and DLQI ≤ 5) or (PASI ≤ 1 and DLQI 0/1)]. The median time to first achieve PASI ≤ 3, PASI ≤ 1, and PASI = 0 was significantly lower for risankizumab‐treated patients compared with ustekinumab‐treated patients. Among patients treated with long‐term risankizumab, more than 90% achieved PASI ≤ 3 though week 172 and more than 80% achieved DLQI 0/1. Low absolute PASI scores corresponded with low mean absolute DLQI scores through week 172 of continuous risankizumab treatment. Conclusions: Risankizumab treatment demonstrated high rates of rapid and durable efficacy as measured by absolute PASI thresholds and improvements in patient HRQoL. [ABSTRACT FROM AUTHOR]

Background: Psoriasis has important physical and psychosocial effects that extend beyond the skin. Understanding the impact of treatment on health‐related quality of life (HRQoL) and patient‐perceived symptom severity in psoriasis is key to clinical decision‐making. Objectives: This post hoc analysis of the PSO‐LONG trial data assessed the impact of long‐term proactive or reactive management with fixed‐dose combination calcipotriene 50 µg/g and betamethasone dipropionate 0.5 mg/g (Cal/BD) foam on patient‐reported outcomes (PROs) in patients with psoriasis vulgaris. Methods: Five hundred and twenty‐one patients from the Phase 3, randomized, double‐blind PSO‐LONG trial were included. An initial 4‐week, open‐label phase of fixed‐dose combination Cal/BD foam once daily (QD) was followed by a 52‐week maintenance phase, at the start of which patients were randomized to a proactive management arm (Cal/BD foam twice weekly) or reactive management arm (vehicle foam twice weekly). Patient‐perceived symptom severity and HRQoL were assessed using the Psoriasis Symptom Inventory (PSI), the Dermatology Life Quality Index (DLQI) and the EuroQol‐5D for psoriasis (EQ‐5D‐5L‐PSO). Results: Statistically and clinically significant improvements were observed across all PRO measures. The mean difference (standard deviation) from baseline to Week 4 was −8.97 (6.18) for PSI, −6.02 (5.46) for DLQI and 0.11 (0.15) for EQ‐5D‐5L‐PSO scores. During maintenance, patients receiving reactive management had significantly higher DLQI (15% [p = 0.007]) and PSI (15% [p = 0.0128]) and a numerically lower EQ‐5D‐5L‐PSO mean area under the curve score than patients receiving proactive management (1% [p = 0.0842]). Conclusions: Cal/BD foam significantly improved DLQI, EQ‐5D‐5L‐PSO and PSI scores during the open‐label and maintenance phases. Patients assigned to proactive management had significantly better DLQI and PSI scores and numerically better EQ‐5D‐5L‐PSO versus reactive management. Additionally, baseline flare was associated with worse PROs than the start of a relapse, and patients starting a relapse also had worse PROs than patients in remission. [ABSTRACT FROM AUTHOR]

Summary: Background: Significantly more patients with moderate‐to‐severe plaque psoriasis treated with the interleukin (IL)‐17A inhibitor ixekizumab vs. the IL‐23p19 inhibitor guselkumab in the IXORA‐R head‐to‐head trial achieved 100% improvement in Psoriasis Area and Severity Index (PASI 100) at week 12. Objectives: To compare skin and nail clearance and patient‐reported outcomes for ixekizumab vs. guselkumab, up to week 24. Methods: IXORA‐R enrolled adults with moderate‐to‐severe plaque psoriasis, defined as static Physician's Global Assessment ≥ 3, PASI ≥ 12 and involved body surface area ≥ 10%. Statistical comparisons were performed using the Cochran–Mantel–Haenszel test stratified by pooled site. Time‐to‐first‐event comparisons were performed using Kaplan–Meier analysis, and P‐values were generated using adjusted log‐rank tests stratified by treatment group. Cumulative days at clinical and patient‐reported responses were compared by ancova. The trial was registered with ClinicalTrials.gov (NCT03573323). Results: Of the 1027 patients randomly assigned, 90% completed the trial (465 of 520 ixekizumab and 459 of 507 guselkumab). As early as week 2 and through week 16, more patients on ixekizumab achieved PASI 100 (P < 0·01). At week 24, ixekizumab was noninferior to guselkumab (50% vs. 52%, difference −2·3%), with no statistically significant difference in PASI 100 (P = 0·41). More patients receiving ixekizumab showed completely clear nails at week 24 (52% vs. 31%, P = 0·007). The median time to first PASI 50/75/90 and PASI 100 were 2 and 7·5 weeks shorter, respectively, for patients on ixekizumab vs. guselkumab (P < 0·001). Patients on ixekizumab also had a greater cumulative benefit, with more days at PASI 90 and 100, with Dermatology Life Quality Index of 0 or 1, and itch free (P < 0·05). The frequency of serious adverse events was 3% for each group, with no new safety signals. Conclusions: Ixekizumab was noninferior to guselkumab in complete skin clearance and superior in clearing nails at week 24. Ixekizumab cleared skin more rapidly in patients with moderate‐to‐severe plaque psoriasis, with a greater cumulative benefit, than guselkumab. Overall, the safety findings were consistent with the known safety profile for ixekizumab. What is already known about this topic?Patients with plaque psoriasis desire both high levels of clearance and rapid onset of treatment effects.Ixekizumab is a high‐affinity monoclonal antibody that selectively targets interleukin (IL)‐17A.In the 12‐week report of the IXORA‐R study, ixekizumab demonstrated significantly higher efficacy at early timepoints than the IL‐23p19 inhibitor guselkumab, with more patients achieving 100% improvement in Psoriasis Area and Severity Index (PASI 100) and improved quality of life as early as week 4. What does this study add?Patients on ixekizumab vs. guselkumab achieved similar levels of skin clearance and superior efficacy in the resolution of nail psoriasis at week 24.Patients on ixekizumab vs. guselkumab had a greater cumulative benefit, with more days at PASI 90 and 100, more days when psoriasis did not impact their quality of life, and more itch‐free days.The safety profiles of both drugs were consistent with those in previous studies. Linked Comment: Puig. Br J Dermatol 2021; 184:992–993. [ABSTRACT FROM AUTHOR]

Background Apremilast, an oral phosphodiesterase 4 inhibitor, regulates immune responses associated with psoriasis. Objectives ESTEEM 2 evaluated the efficacy and safety of apremilast 30 mg twice daily for moderate-to-severe plaque psoriasis. Methods This phase III, double-blind, placebo-controlled trial randomized adults to apremilast or placebo (2 : 1). At week 16, placebo patients switched to apremilast. At week 32, apremilast patients achieving ≥ 50% reduction in Psoriasis Area and Severity Index (PASI 50) were rerandomized (1 : 1) to continue apremilast or receive placebo. Upon loss of 50% of PASI improvement obtained at week 32, patients rerandomized to placebo resumed apremilast. Results The modified intention-to-treat population (full analysis set) included 137 placebo and 274 apremilast patients. At week 16, significantly more apremilast patients achieved PASI 75 (28·8%), PASI 50 (55·5%) and static Physician's Global Assessment score of 0 or 1 (20·4%) vs. placebo (5·8%, 19·7%, 4·4%, respectively; P < 0·001). Most patients rerandomized to apremilast at week 32 had a PASI 50 response at week 52 (80%). Patients treated with apremilast showed significant improvements in quality of life (as assessed by the Dermatology Life Quality Index) and pruritus at week 16 compared with placebo ( P < 0·001). The exposure-adjusted incidence of adverse events did not increase with continued apremilast treatment for up to 52 weeks. The most common adverse events were nausea, diarrhoea, nasopharyngitis and upper respiratory tract infection. Conclusions Apremilast was effective in the treatment of moderate-to-severe plaque psoriasis over 52 weeks. [ABSTRACT FROM AUTHOR]