Effect of Delgocitinib Cream on Health-Related Quality of Life in Patients With Moderate to Severe Chronic Hand Eczema.

IntroductionChronic Hand Eczema (CHE) is a multifactorial, burdensome, inflammatory skin disease, with limited treatment options. In a double-blind dose-ranging phase 2b clinical trial, participants with CHE received delgocitinib cream, a topical pan-Janus kinase (JAK) inhibitor, or cream vehicle (clinical results published elsewhere). The objectives were to analyse patient-reported outcomes (PROs) in participants with mild and moderate to severe CHE at screening, and to investigate the impact on PROs during treatment in participants with moderate to severe CHE.MethodsFirstly, Dermatology Life Quality Index (DLQI), EQ-5D-5L, and Hand Eczema Impact Scale (HEIS) per severity were analysed at screening. Secondly, PROs were analysed in the subset of participants with moderate to severe CHE; participants receiving delgocitinib cream 20 mg/g were compared with participants receiving cream vehicle for 16 weeks.ResultsAt screening, mean (SD) DLQI, EQ-5D-5L, and HEIS were 8.1 (5.8), 0.788 (0.175), and 1.7 (0.8), respectively for mild CHE (n = 93), and 12.1 (6.9), 0.689 (0.236), and 2.3 (0.9) for participants with moderate to severe CHE (n = 202), respectively. Among the participants with moderate to severe CHE who received delgocitinib (n = 41), the least squares mean [SE] change from baseline to week 16 improved compared to cream vehicle (n = 38) in DLQI (− 7.1 [0.9] vs. − 4.6 [0.9]), EQ-5D-5L (0.228 [0.032] vs. 0.096 [0.034]), and HEIS (− 1.5 [0.2] vs. − 0.8 [0.2]) (P < 0.05).ConclusionsMild CHE had a moderate effect, whereas moderate to severe CHE had a very large effect on patients’ Health-Related Quality of Life at screening. Treatment with delgocitinib cream was associated with considerable improvement in PROs and represents a potentially valuable treatment option.Trial RegistrationClinicalTrials. gov identifier NCT03683719.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-025-01384-4.

Little is known about the socio-economic burden of severe chronic hand eczema in patients refractory to treatment with potent corticosteroids. To estimate the socio-economic burden of severe chronic hand eczema refractory to potent topical corticosteroids, and to establish an algorithm for the estimation of the health-related quality of life EuroQol five-dimensional (EQ-5D) utility index from the Dermatology Life Quality Index (DLQI) summary score. A multicentre cost of illness study was conducted, adopting the societal perspective. Adult patients with severe and refractory chronic hand eczema were enrolled. Direct (e.g. drug treatment and travel) and indirect (i.e. loss of productivity) mean costs/patient-month were estimated. Health-related quality of life was assessed with the EQ-5D and DLQI questionnaires. An ordinary least square regression model was used to investigate relationships between health-related quality of life scores. One hundred and four valid patients (mean age 44.5 years, 39.4% male) participated. Overall mean costs were €418.3/patient-month: loss of productivity contributed 43.7%, followed by hospitalization (16.1%) and travel (10.3%). Health-related quality of life scores were, on average, 0.50 (EQ-5D utility) and 11.3 (DLQI). Utility and DLQI summary were significantly related to each other. Wellbeing and loss of productivity are the most important consequences in these patients. Appropriate treatment is necessary to improve patient health and productivity, which will contribute to reducing societal costs.

The importance of quality of life issues in health care practice and research is steadily growing. This growing interest fits into the definition of health as proposed by the World Health Organization (WHO) in 1948 (1). The WHO defines health as 'a state of complete physical, mental and social well-being and not merely the absence of disease and infirmity'. The attention to health-related quality of life is reflected in the increase in the use of quality-of-life evaluation as a technique of clinical research since 1973, when only five articles listed 'quality of life' as a reference key word in the Medline data base; during the subsequent five-year periods there were 195, 273, 490, and 1252 such articles (2). Also in the field of allergy it has been recognized that allergic disease comprise more than the classical signs and symptoms being part of physical disorders such as allergic rhinitis, asthma and the atopic eczema/dermatitis syndrome (AEDS) (3). In the last decades an increasing effort has been made to understand the socioeconomic burden of atopic disease in terms of effects on health-related quality of life (HRQL) and healthcare costs. It has been acknowledged in several consensus reports that rhinitis and asthma are associated with impairments in the patients' functioning in day-to-day life at home, at work and at school 4-8). With the introduction of questionnaires designed to measure asthma- 9-11) and rhinitis-associated impairments of quality of life (12) it is clear that patients may be bothered by sleep disorders, emotional problems, impairment in activities and social functioning. Also, in general terms, patients with asthma (13) and allergic rhinitis (14) are impaired in their physical and mental functioning, including vitality and the perception of general health. From daily medical practice it can be easily understood that AEDS has a major impact on HRQL. In a way, the use of questionnaires focused on skin disease 15-17) formally confirms this association. Quality of life, QOL, has divergent meanings for different people. Also, HRQL may be considered as ill-defined. More agreement has been reached about the four domains of QOL which are considered to be important: 1) physical status and functional abilities; 2) psychological status and well-being; 3) social functioning; 4) economic and/or vocational status and factors ( 18 ). As the true quality of life value cannot be measured directly, researchers and clinicians have to resort to series of questions (items) to measure this construct indirectly. Combinations of items yield scores referring to physical, mental and social domains. An HRQL instrument must meet several criteria. It should address each component (symptom, condition) that is important to the patient. Attributes of an instrument are described in Table 1. It will be clear that the construction of quality of life questionnaires is a complex task, drawing from the fields of clinimetrics, psychometrics and clinical decision-making (2). Differences in approach, for instance item selection using factor analysis vs the impact method which select items that are most frequently perceived as important by patients -- yields different questionnaires (19). In general two types of instruments, generic and specific, have been used in allergy research. Generic questionnaires measure physical, psychological and social domains in all health conditions irrespective of the underlying disease. A frequently used generic instrument is the Medical Outcomes Survey Short Form 36 (SF-36) (20). The SF-36 was developed as part of the Medical Outcomes Study and analyzes health status using 36 questions to measure nine different health dimensions. It has been used to characterize patients with asthma. Bousquet (13) compared the FEV1 and a clinical score of asthma severity for 252 asthmatic patients. There was a significant positive correlation between all nine quality of life domains of the SF-36 and the clinical score of Aas. Eight of the nine domains also correlated with the FEV1. Also in perennial rhinitis there was a significant impairment in eight of nine QOL dimensions in patients compared with healthy subjects (14). Furthermore, the SF-36 is used to evaluate the effects of a nonsedating antihistamine on quality of life. In this study all of the nine quality of life dimensions improved significantly after one and six weeks of cetirizine treatment compared with placebo (21). Other generic instruments that have been used in allergy research are the Sickness Impact Profile (SIP) (22) and the Nottingham Health Profile (NHP) (23). The 136 items in 12 categories of the SIP describe activities of everyday living. This instrument has been used to evaluate the effect of salmeterol on asthma (24). Salmeterol led to significant improvements over salbutamol on virtually all clinical outcomes. Although all four quality of life instruments used in this study showed the same trend in favor of salmeterol, only the disease-specific Asthma Quality of Life Questionnaire (AQLQ) and the Rating Scale utilities showed significantly greater improvement on salmeterol than on salbutamol. In severe AEDS it was shown, using the SIP, that cyclosporin improves quality of life significantly (25). In particular, the SIP has been used for comparison with disease-specific instruments (24, 26-28). The NHP, the only generic instrument derived entirely from lay people, has been used to validate a disease-specific instrument for patients with dermatitis and psoriasis (29). In asthma the NHP was not able to capture clinical improvement by treatment with pulmonary steroids (30). The latter observations underline the disadvantage that the generic instruments miss depth and therefore may not be responsive enough to detect changes in general health states in spite of important changes in disease-related problems (26). The advantage of generic instruments, however, is that the burden of illness across different disorders and patient populations can be compared. In a comparison between asthma and epilepsy the major finding was that children with epilepsy had a relatively more compromised quality of life in the psychological, social, and school domains (31. In contrast, children with asthma had a more compromised quality of life in the physical domain. These findings suggested that attention simply to seizure control in the clinical setting will not address the full range of quality of life problems in children with epilepsy. Specific instruments have been designed by asking patients what kind of problems they experience from their disease. Both the frequency and the importance of impairments are measured by means of the questionnaires. These instruments have the advantage that they describe the disease-associated problems of the patients. As stated above, they seem to be more responsive to changes in HRQL than do the generic instruments. Several instruments for patients with asthma have been developed. The Asthma Quality of Life Questionnaire of Juniper is focused on symptoms, emotions, exposure to environmental stimuli, and activity limitation (32). Modifications of this questionnaire have been published recently (33, 34). When using HRQL outcome in clinical trials, the question arises whether a change in HRQL is of clinical importance. For the AQLQ, which uses a seven-point scale, the minimal important difference of quality of life score per item is considered to be very close to 0.5 (35). A change of 1.0 in the score represents a moderate change and a change in score of greater than 2.0 represents a large change in HRQL. The minimal important difference as described by Juniper is based upon patient opinions. Measures such as the standardized response mean or the effect size can be used to standardize changes. These measures are based solely upon the distribution of the observed data, in particular upon the variance (36). Recently, it has been shown that both the SF-36 and AQLQ were able to characterize a group of patients with moderate asthma very well, whereas the AQLQ domains were found to have the best discriminative properties (37. The Asthma Quality of Life Questionnaire of Marks captures breathlessness, physical restrictions, mood disturbance and concerns for health (38). St. George's Respiratory Questionnaire (11) is designed for patients with asthma and chronic obstructive pulmonary disorder COPD. It can be applied in both reversible and fixed airway obstruction. In contrast to other questionnaires, the Living with Asthma Questionnaire (10) does not include impairments experienced as a direct consequence of asthma symptomatology. Other instruments are presented in Table 2. The properties of the most frequently used questionnaire are described in Table 3. Specific instruments have been developed for children and caregivers (Table 2). In addition, questionnaires have been constructed for different age-groups of patients with rhinitis (12, 39-41). A simple practical questionnaire technique for routine clinical use, the Dermatology Life Quality Index (DLQI) has been introduced to characterize patients with skin disorders (15). This instrument has been used to compare patients with psoriasis and dermatitis (42). Also versions for children are available: the Children's Dermatology Life Quality Index (CDLQI) and the Infant's Dermatology Life Quality Index (IDLQI) (16). Other questionnaires are the Skindex (43) the Dermatology-Specific Quality of Life (DSQL) (17) and the patient-generated Dermatology Quality of Life Scales (DQOLS) (44). Recently, a questionnaire has been developed to measure HRQL in patients with allergy to insect stings. Subsequently, this instrument has been used in the evaluation of venom immunotherapy (45). It appeared that venom immunotherapy resulted in a statistically and clinically significant improvement in HRQL. Both in clinical practice and in research physicians and investigators rely on physiological and objective measures, whenever possible. However in asthma an increase in FEV1 or a decrease in PC20 histamine or methacholine may occur without any improvement experienced by the patient. Medical intervention may improve physiologic measures, whereas for instance side-effects of drugs or the cumbersome aspects of subcutaneous immunotherapy may unfavorably influence day-to-day life and compliance with treatment. It has been put forward that the classical outcome variables may only partially characterize the disease of the patient. From that point of view it has been advocated to measure HRQL along with the conventional clinical indices (46). In line with this reasoning is the weak association between classical asthma measures and the outcome of HRQL questionnaires. Comparison between de AQLQ of Marks with asthma symptoms and lung function variables revealed that a change in AQLQ score was weakly correlated with change in symptom score (r = 0.37, 95% CI 0.04–0.64) and change in BHR (r = 0.38, 95% CI 0.06–0.64). The association with change in peak flow variability was weak (r = 0.12, 95% CI 0.26–0.47) (27). Similar observations have been reported by others 47-50). An interesting study shows that the mere presence of respiratory symptoms or a (gradually) reduced lung function is insufficient reason for patients to seek medical help. Subjects are more likely to consult their general practitioner once their quality of everyday life is affected or they experience variability in lung function (51). Also, rhinitis related quality of life appears to be moderately correlated to the more classical outcome variables used in clinical trials, such as daily symptom scores and nasal hyperreactivity (52). Another argument to use quality of life instruments lies in the headstart with respect to the knowledge of their validation, reliability and responsiveness compared to the common symptom scores or visual analogue scores (VAS) scales used at clinical trials. In the field of nasal allergy, validation or standardization of symptom scores has rarely been the subject of research. In asthma, even quite recently introduced measures, such as the number of symptom-free days, merit more attention in terms of standardization and validation (53). Other reasons to assess quality of life are conceivable. Measurement of quality of life can also be useful for screening purposes or for evaluation of therapy. Quality of life may be a determinant of effectiveness or efficacy of treatment. Moreover, its assessment might be relevant to striving for optimal decision-making. As the perception of patients is clearly important in the management of disease and patient compliance (Fig. 1), measurement of this 'dimension' by HRQL questionnaires in clinical trials may be justified. The emphasis on quality of life has sometimes resulted in a routine inclusion of HRQL questionnaires in clinical trials. The inclusion of such an instrument is valuable only if the changes can be interpreted by clinicians and contributes to optimal medical decision-making. In an editorial, criticism has been directed to the routine inclusion of such instruments when the structure of the evaluation and its rationale appears ill-defined (54). A model representing the relationships between clinical aspects of therapy, HRQL and factors influencing HRQL (adapted from Cramer and Spilker (17)). Generally in clinical trials the effect of treatment or intervention on HRQL runs parallel with the effect on conventional medical outcome measures. However, in some studies differences can be found. In a study evaluating the combined effect of steroids and antihistamines no differences were demonstrated between patients treated with antihistamine and steroids vs steroids alone in terms of quality of life, whereas for some patient-rated symptoms the combination turned out to be superior (55). In a large multicenter study comparing budesonide and fluticasone it was found that both drugs were equally effective in suppressing symptoms (56), although budesonide had a better effect on general quality of life (57). This might indicate that patients perceive differences not captured by conventional symptom scores. The reverse situation, i.e. significant effects on classical outcomes (symptom scores, medication use, peak flow or FEV1) without important change in two generic and two specific HRQL measures has been described in a study on the effect of formoterol, a long-acting α2-agonist, in mild to moderate asthmatic patients (58). The latter discrepancies can be explained by a limited performance of HRQL measures in mild asthmatic patients. Alternatively, it is possible that the minor changes in symptom scores and lung function due to the intervention are not perceived by patients as relevant. Moreover, patients with a chronic condition may adapt themselves to their disease. The strength of HRQL questionnaires, that is the patient-centred approach, is also one of its weaknesses. Perceptions of quality of life experienced by persons may shift in time. It is easy to understand that a dramatic personal accident or a serious disease will not only cause deterioration in quality of life but will eventually also influence the patient's values and internal standards. For instance, in a study of quality of life after radiotherapy for laryngeal cancer, a temporary deterioration of physical functioning and symptoms was reported, mostly caused by side-effects of treatment. Despite physical deterioration, there was an improvement of emotional functioning and mood after treatment, probably as a result of psychological adaptation and coping processes (59). It is possible also that in less dramatic circumstances, disease and treatments will induce shifts in perception due to changes in the patient's values. Such subjective changes in patients' perception are known as response shift. Socioeconomic status is an additional important independent factor influencing HRQL. In a recent study with asthmatic patients it was shown that socioeconomic status attributes to HRQL. More importantly, in this study it was difficult to separate out the unique effects of socioeconomic status and race/ethnicity (60). Recently, a significant relationship between the mental health of children with asthma and family functioning has been shown (61). These findings suggest that the domains comprising the HRQL of children with asthma are related to both disease and non-disease factors. Psychological functioning influences the burden of a specific disease. A study designed to assess the effects of depressive symptoms on asthma patients' reports of functional status and health-related quality of life revealed that asthma patients with more depressive symptoms reported worse health-related quality of life than asthma patients with similar disease activity, but fewer depressive symptoms (62). Interestingly, these findings were seen not only in generic (SF-36) but also in specific (AQLQ) instruments. This means that a disease-specific instrument may be also influenced by phenomena such as fear and depression. Finally, patients may either intentionally or unconsciously mask their symptoms or trivialize their diseases. They may tend to ignore or discount those problems which they believe are unrelated to their illness. Others may tend to give socially desirable answers. Response shifts and illusory mental health (63) are not easily captured with HRQL instruments, but they will certainly influence the outcome of a clinical trial, when HRQL is chosen as the primary endpoint. In summary, one has to realize that the translation of clinical effects of treatment into perceived and reported changes in quality of life finds a place at the integration level of the patient and this is, in a way, a black box which is not easy to assess (Fig. 1). For these reasons it is strongly recommended to use HRQL outcome measures in parallel with conventional physiological outcome measures. Asthma, allergic rhinitis and AEDS often coexist. The question to what extent concomitant allergic disease affects quality of life has infrequently been addressed. In a recent study the SF-36 questionnaire from 850 subjects recruited in two French centers participating in the European Community Respiratory Health Survey was evaluated. Both asthma and allergic rhinitis were associated with impairment in quality of life. However, 78% of asthmatics also had allergic rhinitis. Subjects with allergic rhinitis but not asthma were more likely to report problems with social activities, difficulties with daily activities as a result of emotional problems, and low mental well-being than subjects with neither asthma nor rhinitis. Patients with both asthma and allergic rhinitis experienced more physical limitations than patients with allergic rhinitis alone, but no difference was found between these two groups for concepts related to social/mental health (64). 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Introduction/Background Chronic Hand Eczema (CHE) is a frequent inflammatory skin disease associated with pain, pruritus, and significant occupational, functional, social, and psychological burden. Delgocitinib is a topical pan-JAK inhibitor which showed a dose-dependent efficacy in adults with CHE in a Phase 2b trial. Objectives The objectives of this analysis were to study (1) the efficacy of twice-daily applications of delgocitinib cream 20 mg/g, as assessed by Investigator's Global Assessment for CHE treatment success (primary outcome), and the secondary outcomes ≥75%/≥90% improvement in Hand Eczema Severity Index and ≥4-point improvement in the Dermatology Life Quality Index, and (2) the safety of twice-daily applications of delgocitinib cream 20 mg/g compared with cream vehicle in the treatment of adults with moderate to severe CHE in a pooled analysis of the DELTA-1 and DELTA-2 trials. Methods In the Phase 3 DELTA-1 (NCT04871711) and DELTA-2 (NCT04872101) trials, adults with moderate to severe CHE were randomized 2:1 to twice-daily delgocitinib cream 20 mg/g or cream vehicle for 16 weeks. The primary endpoint was the Investigator's Global Assessment for CHE (IGA-CHE) treatment success at Week 16, defined as IGA-CHE score of 0/1 (clear/almost clear, i.e., no/barely perceptible erythema and no other signs), with a ≥2-step improvement from baseline. Key secondary endpoints included ≥75%/≥90% improvement in Hand Eczema Severity Index (HECSI-75/90) and ≥4-point improvement in the Dermatology Life Quality Index (DLQI). This DELTA-1 and -2 pooled analysis included 639 patients treated with delgocitinib cream and 321 with cream vehicle. Results At Week 16, a significantly greater proportion of delgocitinib-treated patients, versus cream vehicle, achieved IGA-CHE treatment success (24.3% vs. 8.4%; P&amp;lt;0.001), HECSI-75 (49.4% vs. 20.9%; P&amp;lt;0.001), HECSI-90 (30.3% vs. 10.6%; P&amp;lt;0.001), and DLQI ≥4-point improvement (73.3% vs. 47.8%; P&amp;lt;0.001). Most frequent adverse events (occurring in ≥5% of patients) were COVID-19, nasopharyngitis, and headache with similar rates in both treatment groups. Conclusions In the DELTA-1 and -2 pooled analysis, delgocitinib cream twice-daily confirmed its clinical efficacy in patient- and clinician-reported efficacy outcomes versus cream vehicle in adult CHE patients and suggests an innovative treatment option in this often difficult-to-treat patient population.

Patient-reported outcome measures (PROMs) provide an important complement to physician-assessed clinical outcome measures in dermatologic diseases such as atopic dermatitis (AD) and chronic hand eczema (CHE). AD and CHE are chronic and relapsing inflammatory skin conditions that often co-occur. While both diseases result in various signs and symptoms that are burdensome and can negatively affect patients’ lives, there may be distinct differences in the signs, symptoms, burden, and health-related quality of life (HRQOL) impact of these diseases. The objective of this study was to identify and evaluate PROMs used in studies of AD and CHE. The aim was to explore the assessment of key symptoms and impacts, and identify any gaps in the measures in use. A structured review of the PubMed database was conducted to identify PROMs used or developed for use in AD or CHE. The Dermatology Life Quality Index (DLQI), the Pruritus/Itch Numeric Rating Scale (NRS), the Patient-Oriented Eczema Measure (POEM), and the Quality of Life in Hand Eczema Questionnaire (QOLHEQ) were identified and reviewed in detail. With these measures, the AD and CHE symptoms and impacts most commonly evaluated in the literature include dermatology-related HRQOL in the domains of symptoms and feelings, daily activities, leisure, work and school, personal relationships, and adverse effects; pruritus; sleep disturbance; AD-specific symptoms (dryness, itching, flaking, cracking, bleeding, and weeping/oozing); and CHE-specific symptoms (pain, itch, fissuring, redness, bleeding, and dryness). A review of regulatory labels of drugs approved for AD by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) found that, among the four measures reviewed, the Pruritus NRS was included in the FDA and EMA labels for dupilumab, the DLQI was included in the EMA labels for dupilumab and tacrolimus, and the POEM was included in the EMA label for dupilumab. Key symptoms of AD (e.g. itching, flaking, cracking) and CHE (e.g. pain, itching, fissuring) are increasingly being assessed with PROMs; however, primary endpoints in clinical trials are often based on clinician-reported outcome measures. As therapeutic strategies in dermatology are targeted at specific dermatologic symptoms and diseases affecting specific sites (e.g. CHE), future research should explore patients’ experiences with these symptoms and sites and the changes with treatment that are most meaningful to them.Electronic supplementary materialThe online version of this article (10.1007/s40271-019-00373-y) contains supplementary material, which is available to authorized users.

PSY52 PATIENT-REPORTED OUTCOME MEASURES IN ATOPIC DERMATITIS AND CHRONIC HAND ECZEMA IN ADULTS

Hand eczema (HE) is a common skin disease with major medical psychological and socio-economic implications. Onset and prognosis of HE are determined by individual as well as environmental factors. So far, most epidemiological data on HE have been reported from Scandinavian and recently German studies. To investigate the characteristics and medical care of patients with chronic HE (CHE) in Switzerland, and identify risk factors. In this cross-sectional study, data from patients with chronic HE were obtained by means of medical history, dermatological examination and patient questionnaires. Multiple logistic regression analysis was applied to identify risk factors for high severity and dermatology life quality index (DLQI). In seven dermatology departments, 199 patients (mean age 40.4years, 50.8% female) with CHE (mean duration 6.6years) were enrolled. Moderate to severe HE was reported by 70.9% of patients, and was associated with age <30 or >50years, localization of lesions and pruritus. Because of the CHE, 37.3% of patients were on sick leave over the past 12months, 14.8% had changed or lost their job. Practically all patients applied topical therapy, 21% were treated with alitretinoin, and 21% with psoralen plus UVA light (PUVA). The effects on the health-related quality of life was moderate to large in 33.7% and 39.4% of CHE patients, respectively. Factors associated with a high impact on DLQI (mean 9.7±5.8) were female sex, lesions on back of the hands and pruritus as well as mechanical skin irritation and wearing gloves. In agreement with recent studies, the Swiss data demonstrate the high impact of CHE on medical well-being, patient quality of life and work ability. As it is associated with an intense use of health care services, high rate of sick leave, job loss and change, CHE may cause a high socio-economic burden.

Chronic hand eczema (CHE) is a complex, multifactorial inflammatory skin disease that significantly impairs patients’ quality of life. Objectives:This multinational, prospective, observational study evaluated the burden of CHE on health-related quality of life (HRQoL) in adults across six countries: Canada, France, Germany, Italy, Spain, and the United Kingdom. Methods:Participants who self-reported a physician-diagnosed CHE completed the patient-reported outcome measures, including the Hand Eczema Impact Scale (HEIS), Dermatology Life Quality Index (DLQI), and EQ-5D 5 Level Version (EQ-5D-5L). Data were stratified by disease severity, history of suboptimal response to topical corticosteroids (TCS), and current treatment type. Results:Results demonstrated a substantial HRQoL burden associated with CHE, specifically in participants with moderate to severe CHE compared to those with mild CHE (DLQI: 7.7 ± 6.3 vs 3.7 ± 4.7; EQ-5D-5L: 0.682 ± 0.259 vs 0.742 ± 0.237; HEIS total score: 1.5 ± 1.0 vs 0.7 ± 0.8; p < 0.001 for all). A particularly high burden was reported among participants for whom TCS was suboptimal and those receiving systemics/phototherapy. Conclusions:Present study findings highlight the need for more effective management strategies and targeted treatment options to improve the HRQoL of individuals suffering from CHE.

BackgroundBaricitinib is an oral, selective, reversible Janus kinase 1/2 inhibitor approved in the European Union and Japan and under investigation in the United States for treatment of atopic dermatitis (AD).ObjectivesTo evaluate the impact of baricitinib plus background topical corticosteroids (TCS) on health‐related quality of life (HRQoL), how AD symptoms impact work productivity and life functioning, and treatment benefit using patient‐reported outcome (PRO) assessments in patients with moderate‐to‐severe AD previously experiencing inadequate response to TCS.MethodsAdult patients with AD in BREEZE‐AD7, a Phase 3, multicentre, double‐blind trial, were randomised 1 : 1 : 1 to daily oral placebo (control) or baricitinib 4‐ or 2‐mg plus TCS. PROs reported Week 1 through Week 16: Dermatology Life Quality Index (DLQI), Work Productivity and Activity Impairment‐AD (WPAI‐AD); Patient‐Reported Outcomes Measurement Information System (PROMIS) Itch and Sleep measures, and Patient Benefit Index (PBI). Data were analysed using logistic regression (categorical) and mixed model repeated measures (continuous). PBI scores were analysed using analysis of variance.ResultsA total of 329 patients were randomised. Treatment with baricitinib 4‐mg (N = 111) or 2 mg (N = 109) plus TCS led to rapid, statistically significant improvements [vs. TCS plus placebo (N = 109)] in DLQI ≥4‐point improvement starting at Week 2 (4‐mg plus TCS, P ≤ 0.001; 2‐mg plus TCS P ≤ 0.05), change from baseline in WPAI‐AD presenteeism at Week 1 (4‐mg plus TCS, P ≤ 0.01; 2‐mg plus TCS P ≤ 0.05) and PROMIS itch interference at Week 2 (4‐mg plus TCS P ≤ 0.01). Improvements were sustained through Week 16 for baricitinib 4‐mg. Statistically significant improvements were observed at Week 16 for PBI global score (4‐mg plus TCS, P ≤ 0.001; 2‐mg plus TCS P ≤ 0.05).ConclusionsBaricitinib plus TCS vs. placebo plus TCS showed significant improvements in treatment benefit at Week 16 and rapid significant improvements in HRQoL and impact of AD symptoms on work productivity and functioning through 16 weeks.

Background:Inflammatory bowel disease (IBD) is characterized by a chronic relapsing inflammation of the gastrointestinal tract. Adult IBD patients suffer from a disabling disease which greatly affects health-related quality of life (HRQoL). A worse HRQoL in these patients may result in a defensive and ineffective use of medical attention and thus higher medical costs. Because of its chronic nature, IBD may also cause psychological problems in many patients which may also influence HRQoL and care-seeking behavior. An important factor reducing HRQoL is disease activity. Induction of remission and long-term remission are important goals for improving HRQoL. Furthermore, remission is associated with a decreased need for hospitalization and surgery and increased employment, which in turn improve HRQoL. Treatment strategies available for many years are corticosteroids, 5-aminosalicylates and immunnosuppressants, but these treatments did not show significant long-term improvement on HRQoL. The biologics, which induce rapid and sustained remission, may improve HRQoL.Objective:To review and evaluate the current literature on the effect of biologics on HRQoL of IBD patients.Methods:We performed a MEDLINE search and reviewed the effect of different biologics on HRQoL. The following subjects and synonyms of these terms were used: inflammatory bowel disease, Crohn’s disease, ulcerative colitis, quality of life, health-related quality of life, fatigue, different anti-TNF medication, and biologicals/biologics (MESH). Studies included were limited to English-language, adult population, full-text, randomized, double-blind, placebo-controlled in which HRQoL was measured.Results:Out of 202 identified articles, 8 randomized controlled trials (RCT) met the inclusion criteria. Two RCTs on infliximab showed significant improvement of HRQoL compared to placebo which was sustained over the long term. One RCT on adalimumab showed a significant and sustained improvement of HRQoL compared to placebo. This study showed also significant decrease of fatigue in the adalimumab-treated patients. Three RCTs on certolizumab showed a significant improvement of HRQoL in the intervention group compared to placebo. Two RCTs of natalizumab treatment were found. One study showed significant and sustained improvement compared to placebo, and also scores of HRQoL comparable to that in the general population, but in the other no significant results were found.Conclusion:The biologics infliximab, adalimumab, certolizumab, and natalizumab demonstrated significant improvement of HRQoL of IBD patients compared with placebo. However, we found differences in improvement of HRQoL between the different biologics.

Health-related quality of life before and after pediatric epilepsy surgery: The influence of seizure outcome on changes in physical functioning and social functioning

This is a summary of the original article: “Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema (DELTA 1 and DELTA 2): results from multicentre, randomised, controlled, double-blind, phase 3 trials”. Chronic Hand Eczema (CHE) is a heterogeneous, multifactorial, fluctuating, and chronic inflammatory disease associated with pain, itch, and a significant quality-of-life burden for patients. The phase 3 DELTA 1 and DELTA 2 trials assessed the efficacy and safety of twice-daily delgocitinib cream 20 mg/g, a pan-Janus kinase inhibitor, compared with cream vehicle in adults with moderate to severe CHE. Delgocitinib cream demonstrated superior efficacy versus cream vehicle in outcomes reported by clinicians (e.g., Investigator’s Global Assessment for CHE [IGA-CHE] treatment success [IGA-CHE 0 (clear)/1 (almost clear)] and ≥75/90% improvement in Hand Eczema Severity Index) and patients (e.g., itch, pain, and Dermatology Life Quality Index). Delgocitinib cream exhibited a favorable safety profile in both trials. These results suggest that delgocitinib cream is a treatment option for the relief of clinical signs and symptoms among patients with moderate to severe CHE for whom topical corticosteroids are inadequate or inappropriate.

Hepatitis C treatment and quality of life – You can’t always get what you want, but you might get what you need

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of alitretinoin for the treatment of adults with severe chronic hand eczema refractory to topical steroid treatment in accordance with the licensed indication, based upon the evidence submission from Basilea Pharmaceuticals Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The clinical evidence came from a single placebo-controlled randomised controlled trial of daily treatment with alitretinoin for 12-24 weeks, with follow-up for a further 24 weeks, in patients with severe chronic hand eczema (CHE) unresponsive to topical steroids. A statistically significantly greater proportion of patients using alitretinoin achieved the primary end point of clear or almost clear hands by week 24 than did those with placebo. Dose-dependent headache was the most commonly reported adverse event in patients treated with alitretinoin. Serious adverse events were rare, but alitretinoin was associated with increases in both total cholesterol and triglycerides, which has implications for risks of future cardiovascular events. The manufacturer submitted a de novo decision analytic model to estimate, over a time horizon of 3 years, the cost-effectiveness of alitretinoin versus the other relevant comparators identified by NICE. In response to the points of clarification put to it by the ERG regarding the initial submission, the manufacturer provided additional evidence and a revised decision analytic model with a 'placebo' arm. In the manufacturer's original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for alitretinoin were 8614 pounds per quality-adjusted life-year (QALY) versus ciclosporin, -469 pounds per QALY versus psoralen + UVA (with alitretinoin dominant) and 10,612 pounds per QALY versus azathioprine. These ICERs decreased as the time horizon was extended in sensitivity analyses. In patients with hyperkeratotic CHE and in women of child-bearing potential, the ICER remained below 20,000. pounds When the health-related quality of life (HRQoL) values used in the model were replaced with those derived from an alternative study, these ICERs increased significantly (to 22,312 pounds per QALY for alitretinoin versus azathioprine). In the revised model, alitretinoin was reported to have an ICER of 12,931 pounds per QALY gained versus supportive care (placebo). However, the model underestimates the costs of treatment associated with alitretinoin. The manufacturer assumed that patients receiving alitretinoin visited the dermatologist every 4 weeks and ceased treatment as soon as they responded to it. If, in practice, patients would receive treatment for longer than this, then the manufacturer's model will have significantly underestimated the costs to the NHS. Additional analyses undertaken by the ERG produced ICERs close to 30,000 pounds per QALY gained for alitretinoin versus supportive care. This was largely due to uncertainty surrounding the impact of alitretinoin on HRQoL. The placebo-controlled trials conducted to date have established that alitretinoin can be efficacious for the treatment of severe CHE refractory to topical steroids, but longer term follow-up of trials or the implementation of registries is required to better establish the longer term efficacy or safety of alitretinoin. NICE recommended the use of alitretinoin for patients with severe CHE and a Dermatology Life Quality Index (DLQI) score of at least 15. Treatment was recommended to be stopped as soon as an adequate response was observed, or if CHE remained severe at 12 weeks, or if response was inadequate at 24 weeks.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of alitretinoin for the treatment of adults with severe chronic hand eczema refractory to topical steroid treatment in accordance with the licensed indication, based upon the evidence submission from Basilea Pharmaceuticals Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The clinical evidence came from a single placebo-controlled randomised controlled trial of daily treatment with alitretinoin for 12–24 weeks, with follow-up for a further 24 weeks, in patients with severe chronic hand eczema (CHE) unresponsive to topical steroids. A statistically significantly greater proportion of patients using alitretinoin achieved the primary end point of clear or almost clear hands by week 24 than did those with placebo. Dose-dependent headache was the most commonly reported adverse event in patients treated with alitretinoin. Serious adverse events were rare, but alitretinoin was associated with increases in both total cholesterol and triglycerides, which has implications for risks of future cardiovascular events. The manufacturer submitted a de novo decision analytic model to estimate, over a time horizon of 3 years, the cost-effectiveness of alitretinoin versus the other relevant comparators identified by NICE. In response to the points of clarification put to it by the ERG regarding the initial submission, the manufacturer provided additional evidence and a revised decision analytic model with a ‘placebo’ arm. In the manufacturer’s original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for alitretinoin were £8614 per quality-adjusted life-year (QALY) versus ciclosporin, –£469 per QALY versus psoralen + UVA (with alitretinoin dominant) and £10,612 per QALY versus azathioprine. These ICERs decreased as the time horizon was extended in sensitivity analyses. In patients with hyperkeratotic CHE and in women of child-bearing potential, the ICER remained below £20,000. When the health-related quality of life (HRQoL) values used in the model were replaced with those derived from an alternative study, these ICERs increased significantly (to £22,312 per QALY for alitretinoin versus azathioprine). In the revised model, alitretinoin was reported to have an ICER of £12,931 per QALY gained versus supportive care (placebo). However, the model underestimates the costs of treatment associated with alitretinoin. The manufacturer assumed that patients receiving alitretinoin visited the dermatologist every 4 weeks and ceased treatment as soon as they responded to it. If, in practice, patients would receive treatment for longer than this, then the manufacturer’s model will have significantly underestimated the costs to the NHS. Additional analyses undertaken by the ERG produced ICERs close to £30,000 per QALY gained for alitretinoin versus supportive care. This was largely due to uncertainty surrounding the impact of alitretinoin on HRQoL. The placebo-controlled trials conducted to date have established that alitretinoin can be efficacious for the treatment of severe CHE refractory to topical steroids, but longer term follow-up of trials or the implementation of registries is required to better establish the longer term efficacy or safety of alitretinoin. NICE recommended the use of alitretinoin for patients with severe CHE and a Dermatology Life Quality Index (DLQI) score of at least 15. Treatment was recommended to be stopped as soon as an adequate response was observed, or if CHE remained severe at 12 weeks, or if response was inadequate at 24 weeks.