INDIVIDUAL ARTICLE: Impact of Acne Vulgaris and Sarecycline on Social/Emotional Functioning and Daily Activities: PROSES Study.

BACKGROUND: Concise patient-reported outcome (PRO) instruments addressing the consequences of facial acne vulgaris (AV) on patients’ functioning and activities of daily living (ADL) are needed. METHODS: A 12-week, single-arm, prospective cohort study was conducted in patients ≥9 years old with moderate/severe non-nodular facial AV prescribed sarecycline as part of usual care. The primary endpoint included AV-specific patient- and caregiver-reported outcomes assessed with the expert panel questionnaire (EPQ, developed by 10 experts using a Delphi method) in patients (>12 years) and caregivers (for patients 9-11 years). Additional assessments included parental/caregiver perspectives on children’s AV. RESULTS: A total of 253 patients completed the study. Following 12-weeks of treatment, there were significant (P ≤.0001) changes from baseline in the proportion of patients responding that they never or rarely: felt angry (31.6%), worried about AV worsening (28.9%), had thoughts about AV (20.9%), had a certain level of worries about AV (38.7%), altered their social media/selfie activity (23.7%), had an impact on real-life plans due to AV (22.9%), made efforts to hide AV (21.3%), felt picked-on/judged due to AV (15.0%), were concerned about their ability to reach future goals due to AV (13.8%), or had sleep impacted due to AV (18.2%). No significant change from baseline was observed for parent/caregiver’s understanding of the child’s AV concerns, from both patient and parent/caregiver perspectives. CONCLUSIONS: Over 12 weeks of AV management with oral sarecycline, patients reported significant reductions in AV-related effects on emotional/social functioning and ADL as measured by the EPQ, a simple PRO with potential for use in clinical practice. J Drugs Dermatol. 2024;23:1(Suppl 1):s4-11.

INDIVIDUAL ARTICLE: Sarecycline Improves Acne Severity, Symptoms, and Psychosocial Burden in Non-nodular Acne Vulgaris: PROSES Study.

BACKGROUND: Patient-reported outcomes (PROs) are emerging as a fundamental component of disease impact assessment in acne vulgaris (AV), complementing clinician-reported outcomes. No data is available on PROs for patients with AV using sarecycline in real-world settings. METHODS: A single-arm, prospective cohort study that included patients ≥9 years old diagnosed with moderate or severe non-nodular AV was implemented as part of routine care in clinical practices (N=30). Patients received oral sarecycline (60 mg, 100 mg, or 150 mg) for 12 weeks, as part of usual care. The primary endpoint was Acne Symptom and Impact Scale (ASIS) responses from patients (≥12 years) and caregivers (for patients 9-11 years) at week 12 and change from baseline (CFB). Investigator’s Global Assessment (IGA) of AV severity and adverse events (AEs) were also recorded. RESULTS: A total of 253 patients with AV completed the study (adults: 60.1%, females: 77.6%). ASIS mean scores significantly decreased (P <.0001) at week 12 for: signs (mean CFB ± standard deviation [SD]: –0.8 ± 0.7), impact (–1.0 ± 1.0), emotional impact (–1.2 ± 1.1), and social impact (0.6 ± 1.1). Significant reductions in AV severity (P <.0001) were reported by patients and caregivers. The IGA success rate was 58.9% and physician satisfaction with treatment outcomes was 88.1%. A total of 31 (10.3%) patients reported ≥1 AE during the study. CONCLUSIONS: Patients with moderate-to-severe AV receiving acne management with an oral antibiotic for 12 weeks experienced a significant improvement in AV-related symptoms and psychosocial burden. J Drugs Dermatol. 2024;23:1(Suppl 1):s12-18.

Implementing well-being in the management of psoriasis: An expert recommendation.

Psoriasis causes detriment in a person's physical, mental and social health which impairs their quality of life (QoL). However, the current psoriasis management may not adequately address all relevant health domains. Since the goal of healthcare is to restore or maintain health, health outcomes should include all areas of the patient's overall health. Life satisfaction, QoL and patient well-being are essential to a comprehensive approach to the disease. With the inclusion of more people-centred policies, care of patients with psoriasis should evolve towards a holistic and integrated assessment of the disease impact, including subjective measures of well-being in order to encompass all aspects of health. The main objective of this expert review is to give the concept of well-being a place as an entity within the holistic therapeutic approach for patients with psoriasis. Identifying and defining common goals beyond the skin with the patient and testing them throughout the course of treatment will benefit and enhance treatment success. We propose a series of recommendations for application in clinical practice, providing tangible clinical guidance for implementing well-being in the management of psoriasis. Among the recommendations are the need to initially listen to the patient, to know their level of empowerment or what they want to achieve, their preferences in decision making, the evaluation of not only the physical but also the emotional impact of the disease (well-being), the definition of the aspects that can generate a cumulative deterioration of the disease throughout life, and a continuous assessment of the patient's preferences with the opinion of the expert clinician and the integration of the knowledge of external clinical evidence.

Tildrakizumab improves high burden skin symptoms, impaired sleep and quality of life of moderate-to-severe plaque psoriasis patients in conditions close to clinical practice.

BACKGROUND: Tildrakizumab (TIL) is an interleukin (IL)-23p19 inhibitor for the treatment of moderate-to-severe plaque psoriasis with long-term efficacy and safety demonstrated in Phase III trials. Studies conducted in conditions closer to clinical practice are needed. OBJECTIVES: The TRIBUTE study (open-label, Phase IV) assessed the efficacy and impact on health-related quality of life (HRQoL) of TIL 100 mg in adult moderate-to-severe psoriasis patients (naïve to IL-23/Th17 pathway inhibitors) in conditions similar to clinical practice. METHODS: Key efficacy measure was Psoriasis Area Severity Index (PASI). HRQoL was evaluated using the Dermatology Life Quality Index (DLQI) and Skindex-16. Additional patient-reported outcomes included Pain-, Pruritus- and Scaling-Numerical Rating Scale (NRS), Medical Outcome Study (MOS)-Sleep, Work Productivity and Activity Impairment (WPAI), Patient Benefit Index (PBI) and Treatment Satisfaction Questionnaire for Medication (TSQM). RESULTS: One hundred and seventy-seven patients were enrolled (six patients did not complete the study). After 24 weeks, the proportion of patients achieving PASI scores ≤ 3, PASI 75, PASI 90 and DLQI 0/1 was 88.4%, 92.5%, 74.0% and 70.4%, respectively. Skindex-16 overall score improved (mean absolute change from baseline, MACB [95%CI]: -53.3 [-58.1, -48.5]). Significant benefits (MACB [95%CI]) were found on pruritus-, pain- and scaling-NRS scores (-5.7 [-6.1, -5.2], -3.5 [-4.1, -3.0] and -5.7 [-6.2, -5.2], respectively), MOS-Sleep (-10.4 [-13.3, -7.4] Sleep problems Index II) and WPAI (-36.4 [-42.6, -30.2] activity impairment, -28.2 [-34.7, -21.7] productivity loss, -27.0 [-32.9, -21.1] presenteeism and -6.8 [-12.1, -1.5] absenteeism). 82.7% of patients reported PBI ≥ 3 and the mean (SD) global TSQM score was high (80.5 [18.5]). Only one serious treatment-emergent adverse event was reported (not-related to TIL). CONCLUSIONS: TIL 100 mg treatment after 24 weeks in conditions close to real clinical practice showed a quick and high improvement in psoriasis signs and HRQoL. Patient reported improvements in sleep outcomes and work productivity, relevant benefits and high treatment satisfaction. The safety profile was favourable and consistent with Phase III trials.

Patient-reported well-being in value-based care using tildrakizumab in a real-world setting: protocol of a multinational, phase IV, 1-cohort prospective observational study (the POSITIVE study).

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease that negatively impacts the quality of life of patients and their families. However, the most commonly used decision-making tools in psoriasis, Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA) and Dermatology Life Quality Index (DLQI), do not fully capture the impact of psoriasis on patients' lives. In contrast, the well-established 5-item WHO Well-being Index (WHO-5) assesses the subjective psychological well-being of patients. Moreover, while drug innovations became available for psoriasis, data on the impact of these therapies on patients' lives and their closest environment (family, physicians) are limited. This study will assess the effect of tildrakizumab, an interleukin-23p19 inhibitor, on the overall well-being of patients with moderate-to-severe psoriasis. Moreover, the long-term benefit of tildrakizumab on physicians' satisfaction and partners' lives of patients with psoriasis will be evaluated. METHODS AND ANALYSIS: This non-interventional, prospective, observational, real-world evidence study will involve multiple sites in Europe and approximately 500 adults with moderate-to-severe psoriasis treated with tildrakizumab. Each patient will be followed for 24 months. The primary endpoint is well-being measured by the WHO-5 questionnaire. Key secondary endpoints include Physician's Satisfaction and partner's quality of life (FamilyPso). Other endpoints will evaluate skin-generic quality of life (DLQI-R), Treatment Satisfaction Questionnaire for Medication (TSQM-9), Treatment-related Patient Benefit Index 'Standard', 10 items (PBI-S-10) and work productivity and activity impairment due to psoriasis (WPAI:PSO). Statistical analyses will be based on observed cases. Multiple imputations will be performed as a sensitivity analysis, and adverse events will be reported. ETHICS AND DISSEMINATION: The study will be conducted according to the protocol, which received ethics committee approval and applicable regulatory requirements of each participating country. The results will be disseminated through scientific publications and congress presentations. TRAIL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04823247 (Pre-results).

A Retrospective Real-World Study of the Effectiveness and Tolerability of Tildrakizumab in UK Adults with Moderate-to-Severe Chronic Plaque Psoriasis.

INTRODUCTION: As with most medicines historically, clinicians prescribing tildrakizumab have relied on information derived from registration studies undertaken in a prospective controlled clinical trial setting. More recently, clinicians, policymakers, and commissioners increasingly rely on real-world data to inform both policy and practice. METHODS: A retrospective real-world data study was undertaken at four specialist dermatology departments in the United Kingdom. All adult patients treated with tildrakizumab for moderate-to-severe plaque psoriasis were included, with data being collected for 122 patients. RESULTS: Psoriatic patients on tildrakizumab tended to be overweight (median body mass index of 32 (range 19-59) (n = 61); 26/68 (38%) < 90 kg, 32/68 (47%) between 90 and 120 kg, and 10/68 (15%) > 120 kg). The study population had high levels of comorbidities (83/116, 72%), multiple special sites (39/117, 33%), and histories of biological treatments (81/100, 81%). Most patients (61/80, 76%) initiated on tildrakizumab were switched from another biological treatment. Tildrakizumab was effective, with 91/122 (75%) patients remaining on treatment for the duration of the study-a median of 12 months per patient (range 1-29 months)-and achieving a change in median Psoriasis Area and Severity Index (PASI) from 12 to 0.35 and in Dermatology Life Quality Index (DLQI) from 20 to 0. The response rate was 57/66 (86%) when tildrakizumab was used as the first- or second-line biologic compared to 19/31 (61%) when used as the third- to seventh-line. Thirty-three (78.6%) patients over 90 kg of weight received the 200-mg dose of tildrakizumab. All but one (n = 8) patient with body weight over 120 kg maintained response over time. There was one treatment discontinuation; a patient who had a local sensitivity reaction. CONCLUSIONS: In UK clinical practice, tildrakizumab was well tolerated and effective at doses of 100 mg or 200 mg in a range of patient phenotypes.

Application of the Statistical Method to Convert Published PASI 50/75/90/100 into Absolute PASI Response Rate in Patients with Moderate-to-Severe Plaque Psoriasis Treated with Tildrakizumab Based on Data from the Two Pivotal Phase 3 Studies reSURFACE 1 and reSURFACE 2.

BACKGROUND: Absolute Psoriasis Area and Severity Index (PASI) is a key endpoint in psoriasis management. Petto et al. [Pharm Stat. 2019;18(1):4-21] developed a statistical method to estimate the proportion of patients reaching absolute PASI response given baseline PASI score and proportion of patients achieving relative improvements at predefined time points. OBJECTIVES: To test this method on clinical data from two phase 3 tildrakizumab trials (reSURFACE 1/2) comparing estimated absolute PASI ≤1/≤2/≤3/≤5 responses with reference responses from clinical databases. METHODS: Reference PASI responses of ≤1/≤2/≤3/≤5 were extracted from clinical databases. Estimation of absolute PASI ≤1/≤2/≤3/≤5 response rates at week (W) 12 and W28 by treatment and trial were performed. Differences between estimated and reference responses were analysed. Bland-Atman limits of agreement and Passing-Bablok regression to assess variations between estimated and reference responses were performed. RESULTS: Differences between estimated and reference absolute PASI ≤1/≤2/≤3/≤5 responses at W12 and W28 by treatment and trial were of little clinical relevance with an overall mean difference in PASI response proportion of -2.2% (e.g., for the tildrakizumab 100-mg arm, original proportions of patients achieving PASI of ≤1/≤2/≤3/≤5 at W28 were 38.5%/52.2%/63.5%/73.9% and 39.8%/54.8%/63.6%/76.9% [reSURFACE 1 and 2, respectively] vs. estimated proportions of 33.2%/49.8%/62.5%/78.3% and 34.3%/51.6%/64.5%/79.9%). Limits of agreement were -7.1% to 1.4% at W12 and -6.8% to 4.3% at W28. Scatterplots revealed linearity that stood the cusum test in Passing-Bablok regression with slope 1.14 (95% confidence intervals: 1.06 to 1.20). CONCLUSION: Good estimates of absolute PASI response rates were achieved with the application of the statistical method to tildrakizumab data reported in the phase 3 studies, in particular in the verum study arms. Our data support the method provided by Petto et al. [2019] to estimate proportions of psoriasis patients reaching absolute PASI value thresholds using relative PASI improvements.

Non-Alcoholic Fatty Liver Disease (NAFLD) in Patients with Psoriasis: A Review of the Hepatic Effects of Systemic Therapies.

There is increasing interest in the association between psoriasis and non-alcoholic fatty liver disease (NAFLD), which is a prevalent liver disease characterized by excessive fat storage and inflammation that can progress to fibrosis and cancer. Patients with psoriasis have a two-fold higher risk to develop NAFLD and a higher risk to progress to more severe liver disease. Psoriasis and NAFLD share common risk factors such as smoking, alcohol consumption, and the presence of metabolic syndrome and its component disorders. In addition, both psoriasis and NAFLD hinge upon a systemic low-grade inflammation that can lead to a vicious cycle of progressive liver damage in NAFLD as well as worsening of the underlying psoriasis. Other important shared pathophysiological pathways include peripheral insulin resistance and oxidative stress. NAFLD should receive clinical awareness as important comorbidity in psoriasis. In this review, we assess the recent literature on the epidemiological and pathophysiological relationship of psoriasis and NAFLD, discuss the clinical implications of NAFLD in psoriasis patients, and summarize the hepatotoxic and hepatoprotective potential of systemic psoriasis therapies.

Still Fighting for Breath: a patient survey of the challenges and impact of severe asthma.

We conducted a large global survey, Still Fighting for Breath, in patients with severe persistent asthma, 10 years after the Fighting for Breath survey to assess the impact of disease on patients' lives and to determine if control and management have changed in recent years. Data were collected from 1333 adults (aged >18 years) and caregivers of children (aged 6-17 years) with severe persistent asthma from nine countries through an online survey conducted in 2016 by GfK. A decade after the first survey, our results showed that the impact of severe asthma has not changed significantly and a high proportion of patients with severe asthma remain inadequately controlled. A large discrepancy was observed between the proportion of patients who perceived their asthma to be well controlled (42%) and the proportion of patients who reported to be well controlled as per the Global Initiative for Asthma (GINA) assessment (6%). Although most patients perceived their asthma to be controlled, many experienced frequent symptoms that affected their daily lives. Thus, there is a need for improved management (support and strategies) of patients with severe persistent asthma and improved coordination of efforts that would enable these patients to achieve better disease control.

Is IgE or eosinophils the key player in allergic asthma pathogenesis? Are we asking the right question?

Bronchial asthma (BA) is a chronic inflammatory disease with a marked heterogeneity in pathophysiology and etiology. The heterogeneity of BA may be related to the inducing mechanism(s) (allergic vs non-allergic), the histopathological background (eosinophilic vs non-eosinophilic), and the clinical manifestations, particularly in terms of severity and frequency of exacerbations. Asthma can be divided into at least two different endotypes based on the degree of Th2 inflammation (T2 'high' and T2 'low'). For patients with severe uncontrolled asthma, monoclonal antibodies (mAbs) against immunoglobulin E (IgE) or interleukin (IL)-5 are now available as add-on treatments. Treatment decisions for individual patients should consider the biological background in terms of the "driving mechanisms" of inflammation as this should predict the patients' likely responses to treatment. The question is not whether an anti-IgE or an anti-eosinophilic strategy is more effective, but rather what the mechanism is at the origin of the airway. While IgE is involved early in the inflammatory cascade and can be considered as a cause of allergic asthma, eosinophilia can be considered a consequence of the whole process. This article discusses the different roles of the IgE and IL-5/eosinophil pathways in the pathogenic mechanisms of airway inflammation occurring in allergic asthma, and the possible reasons to choose an anti-IgE mAb or anti-IL-5 treatment.

Longterm clinical outcomes of omalizumab therapy in severe allergic asthma: Study of efficacy and safety.

Omalizumab has been shown to be an effective add-on therapy for patients with uncontrolled severe persistent allergic asthma. There has been a steady accumulation of evidence on the long-term effectiveness of omalizumab; however, data on real-life outcomes beyond one year of treatment is limited. In this study, we report on long-term outcomes of omalizumab treatment. We collected data from our severe asthma registry on hospitalisations, exacerbations, corticosteroid sparing, asthma control, lung function, biomarkers and side effects, to determine if the benefit was sustained and treatment was safe on the long term. Forty-five patients [mean age 44.9 years (range 19-69), females 37/45 (82%), mean duration of omalizumab treatment = 60.7 ± 30.9 months (range 23-121) were included in the analysis. We observed a reduction in the annual acute asthma related hospital admissions for the total population from 207 at baseline to 40 on treatment (80.7% reduction), whilst the per patient annual hospitalisations were reduced from a mean of 4.8 to 0.89 post-omalizumab treatment (p < 0.00001). There was a 76.7% reduction in daily mean maintenance OCS dose (prednisolone equivalent) from 25.8 mg (n = 43) to 6.0 mg (p < 0.0001), associated with clinically significant improvement in asthma control questionnaire (ACQ) from mean score of 4.1 (range 3.7-4.7) to 2.27 (range 0.5-4.1) p < 0.0001. The mean % predicted FEV1 has improved from 59.2% at baseline to 75.7% on treatment (p = 0.001). There was a statistically non-significant reduction in median peripheral blood eosinophils (PBE) from 300 cells/µl (range 40-1050) at baseline to 175 cells/µl (range 0-1500) post-treatment (p = 0.068), and statistically significant reduction of median fraction exhaled nitric oxide (FeNO) level from 37 parts per billion (range 12-178) to 24 ppb (range 7-50) (p = 0.0067). The work/school missed days were reduced in 17/19 patients who were at employment or school. The overall safety profile of the treatment seemed acceptable and was consistent with published experience. In conclusion, results from this real-life study demonstrate that improved outcomes in patients with severe allergic asthma are sustained with longer-term omalizumab therapy.