Tildrakizumab Improves Disease Severity and Patient-Reported Outcomes in Moderate-to-Severe Chronic Plaque Psoriasis: A Prospective Real-World Study.

Surgery is considered to be the best treatment for recurrent hidradenitis suppurativa (HS). Although it is necessary to assess the effect on health-related quality of life (HR-QoL), patient-reported outcome measures (PROMs) are scarce and heterogeneously used in the literature about the surgical treatment of HS. The aim of this study was to provide a review of the complete literature for different PROMs used in the surgical treatment of HS and to assess their methodological qualities. A systematic literature search of PubMed, Medline, Cochrane, CINAHL, and Embase with an assessment following the COnsensus-based standards for the Selection of health status Measurement INstrument criteria. The search identified 218 articles, with the inclusion of 6 studies for analysis. Identified PROMs were as follows: the Dermatology Life Quality Index (DLQI), the Derriford Appearance Scale-24 (DAS-24), and the Work Productivity and Activity Impairment (WPAI). These non-disease-specific PROMs seem to have poor results concerning development and content validation. The DLQI, WPAI, and DAS-24 are generic PROMs with poor methodological qualities for PROM development and content validation. Hidradenitis suppurativa-specific instruments are not used in available studies because they have been developed recently and, therefore, partially validated. More research is needed to further investigate methodological qualities of HS-specific instruments.

BackgroundChronic psoriasis can negatively affect patients' lives. Assessing the impact of treatment on different aspects of a patient's health-related quality of life (HRQOL) is therefore important and relevant in trials of anti-psoriasis agents. The recombinant humanized IgG1 monoclonal antibody efalizumab targets multiple T-cell-dependent steps in the immunopathogenesis of psoriasis. Efalizumab has demonstrated safety and efficacy in several clinical trials, and improves patients' quality of life. Objective: To evaluate the impact of efalizumab on HRQOL and other patient-reported outcomes in patients with moderate to severe plaque psoriasis, including a large cohort of High-Need patients for whom at least 2 other systemic therapies were unsuitable because of lack of efficacy, intolerance, or contraindication.MethodsA total of 793 patients were randomized in a 2:1 ratio to receive efalizumab 1 mg/kg/wk (n = 529) or placebo (n = 264) for 12 weeks. The study population included 526 High-Need patients (342 efalizumab, 184 placebo). The treatment was evaluated by patients using the HRQOL assessment tools Short Form-36 (SF-36) and Dermatology Life Quality Index (DLQI). Other patient-reported assessments included the Psoriasis Symptom Assessment (PSA), a visual analog scale (VAS) for itching, and the Patient's Global Psoriasis Assessment (PGPA).ResultsEfalizumab was associated with improvements at Week 12 from baseline in patient-reported outcomes, both in the total study population and in the High-Need cohort. Among all efalizumab-treated patients, the DLQI improved by 5.7 points from baseline to Week 12, relative to an improvement of 2.3 points for placebo patients (P < .001). Corresponding improvements in DLQI in the High-Need cohort were 5.4 points for efalizumab compared to 2.3 for placebo (P < .001). Improvements from baseline on the SF-36, PSA, PGPA, and itching VAS at Week 12 were also significantly greater in efalizumab-treated patients than for placebo.ConclusionA 12-week course of efalizumab improved HRQOL and other patient-reported outcomes in patients with moderate to severe plaque psoriasis. The benefits of efalizumab therapy in High-Need patients were similar to those observed in the total study population, indicating that the beneficial impact of efalizumab on QOL is consistent regardless of disease severity, prior therapy, or contraindications to previous therapies.

Psoriasis is a common, chronic inflammatory skin disease which typically follows a relapsing and remitting course, and is associated with joint disease in approximately 25% of patients.1 The significant reduction in quality of life and the psychosocial disability suffered by patients underline the need for prompt, effective treatment, and long-term disease control (reviewed2, 3). Localized, limited disease can usually be managed satisfactorily with topical agents. Those with moderate to severe disease often require systemic treatment. Phototherapy and traditional 'standard' systemic therapies, while often effective, can be associated with long-term toxicity; some are expensive, and some patients have treatment-resistant disease.4 Also, phototherapy is not available to many due to geographical, logistical or other constraints. Patients themselves demonstrate high levels of dissatisfaction with standard approaches to treatment.5, 6 Biologic therapies for psoriasis utilize molecules designed to block specific molecular steps important in the pathogenesis of psoriasis and now comprise a number of well-established, licensed, treatment options for patients with severe disease. Since 2005, when the British Association of Dermatologists (BAD) first published guidance on the use of biologic therapies in psoriasis,7 much has changed. There is a substantial body of new evidence pertinent to the clinical use of these treatments, the U.K. National Institute for Health and Clinical Excellence (NICE) has approved the use of a number of biologic therapies in severe chronic plaque psoriasis and the BAD Biologic Interventions Register (BADBIR) has been successfully launched. Despite these developments, use of biologic therapy in clinical practice remains limited in the U.K., with a shortfall in funding cited as a significant obstacle to prescribing in approximately 40% of units recently surveyed.8 These guidelines have been revised and updated in accordance with a predetermined scope. This is based on the original scope used in 2005, and extended to include additional areas of practice. Recommendations in this guideline supersede those in the 2005 guideline. The overall objective of these guidelines is to provide up-to-date, evidence-based recommendations on use of biologic therapies (infliximab, adalimumab, etanercept, ustekinumab) in adults and children with all types of psoriasis and, where relevant, psoriatic arthritis, for clinical staff involved in the care of patients treated with biologic therapies. Efalizumab remains in the scope of the guideline in relation to safety only, given that the European Medicines Agency has withdrawn the marketing authorization of this drug because of concerns over the development of progressive multifocal leukoencephalopathy (PML). This guidance does not cover agents licensed outside the U.K. (alefacept) or use of biologic therapies for indications other than psoriasis and psoriatic arthritis. The guideline working group represents all relevant stakeholders including dermatologists, nurses, rheumatologists and patients. Draft guidance was made available for consultation and review by patients, the BAD membership and the British Dermatological Nursing Group (BDNG). Advice relating to tuberculosis was reviewed and approved by the British Thoracic Society. The guideline has been developed using the BAD's recommended methodology9 and with reference to the AGREE (Appraisal of Guidelines Research and Evaluation) instrument.10 Recommendations were developed for implementation in the National Health Service using a process of considered judgment based on the evidence and an awareness of the European product licence of the various treatments. Cochrane, EMBASE and Medline databases were searched between 1990 and June 2009 for clinical trials involving adalimumab, efalizumab, etanercept, infliximab and ustekinumab using an agreed protocol. Two reviewers screened all titles and abstracts independently, and full papers of relevant material were obtained. In relation to efficacy, only randomized controlled trials (RCTs) of high quality (1+ or more; see Appendix 1) were included for chronic plaque psoriasis, whereas in other clinical phenotypes, given the paucity of published data, all data were included. Data from each paper were extracted by two members of the guideline group using standardized literature evaluation forms in order to create evidence tables. Evidence on safety was extracted from literature on use of biologic agents for any indication in view of the relatively limited data specifically relating to use in psoriasis. The methodological limitations of the safety analysis are detailed in section 15. The guideline was peer reviewed by the Clinical Standards Unit of the BAD (made up of the Therapy & Guidelines and Audit & Clinical Standards Subcommittees) prior to publication. These guidelines have been prepared on behalf of the BAD and reflect the best data available at the time the report was prepared. Caution should be exercised in interpreting the data; the results of future studies may require alteration of the conclusions or recommendations in this report. It may be necessary or even desirable to depart from the guidelines in the interests of specific patients and special circumstances. Just as adherence to guidelines may not constitute defence against a claim of negligence, so deviation from them should not necessarily be deemed negligent. This field of psoriasis biologic therapeutics is in a rapid phase of development, and revision of the scope and content of the guidelines will therefore occur on an annual basis. Where necessary, the guideline will be updated via the BAD website, and a fully revised version is planned for 2012. Most patients with moderate to severe disease achieve satisfactory disease control (i.e. significant or complete clearing of disease) in the short term with at least one of the systemic agents currently available.4 Long-term disease control frequently requires some form of continuous therapy and consequent, predictable risks of toxicity. At present, the risks and benefits of biologic therapies relative to standard systemic therapy are largely unknown. Widespread use of these agents in uncomplicated moderate to severe psoriasis is inappropriate and is not supported by the licensed indications for these drugs. Eligibility criteria should encompass both objective measures of disease severity and the impact the disease has on quality of life. All existing disease severity assessment tools are imperfect11-13 and most require some training to complete. The Psoriasis Area and Severity Index (PASI) is a measure of disease severity in chronic plaque psoriasis12 and has been chosen for the purposes of this guideline as it has been widely used in clinical trials including those investigating biologic therapies, and has also been adopted by NICE. A PASI score of ≥ 10 (range 0–72) has been shown to correlate with a number of indicators commonly associated with severe disease such as need for hospital admission or use of systemic therapy,14 and reflects the minimal level of disease severity required for patient inclusion in most of the clinical trials of biologic therapies to date. Where the PASI is not applicable (e.g. pustular psoriasis), body surface area (BSA) affected should be used, with severe disease defined as > 10% BSA affected.14 The Dermatology Life Quality Index (DLQI) is a validated tool for the measurement of quality of life across all skin diseases, including psoriasis, and has been used in both trial and clinical practice settings.13, 15 A score of > 10 (range 0–30) has been shown to correlate with at least 'a very large effect' on an individual's quality of life.12, 14, 16 When using the PASI and DLQI to determine whether or not a patient should be considered for biologic therapy, clinicians should take into account the applicability of these measures to each individual patient. There are circumstances where the use of these tools fails to give a sufficiently accurate assessment of the clinical situation. With respect to the PASI, this is especially pertinent in patients with localized disease that involves special 'high-impact' sites (genitalia, hands, feet, head and neck) where highly significant functional and/or psychosocial morbidity may exist with a PASI < 10. The DLQI may be a poor indicator of emotional disabilities resulting from psoriasis and the validity of the DLQI (and of other quality of life measures) may also be undermined due to linguistic or other communication difficulties.13 Patients with psoriasis may be considered eligible to receive treatment with any of the licensed biologic interventions when they fulfil the eligibility criteria set out below. However, the decision to proceed with treatment must be made in collaboration with the patient and include a careful assessment of the associated risks and benefits17 Eligibility criteria To be considered eligible for treatment, patients must have severe disease as defined in (a) and fulfil one of the clinical categories outlined in (b): (a) Severe disease defined as a PASI score of 10 or more (or a BSA of 10% or greater where PASI is not applicable) and a DLQI > 10. In exceptional circumstances (for example, disease affecting high-impact sites with associated significant functional or psychological morbidity such as acral psoriasis), patients with severe disease may fall outside this definition but should be considered for treatment (Strength of recommendation D; level of evidence 3) AND (b) Fulfil at least one of the following clinical categories (Strength of recommendation D; level of evidence 3, and formal consensus) where phototherapya and alternative standard systemic therapyb are contraindicated or cannot be used due to the development of, or risk of developing, clinically important treatment-related toxicity. are intolerant to standard systemic therapy are unresponsive to standard systemic therapyb have significant, coexistent, unrelated comorbidity which precludes use of systemic agents such as ciclosporin or methotrexate have severe, unstable, life-threatening disease Eligibility criteria for patients with skin and joint disease patients with active psoriatic arthritis or skin disease that fulfils defined British Society for Rheumatology (BSR)18 or BAD guideline criteria, respectively patients with severe skin psoriasis and psoriatic arthritis who have failed or cannot use methotrexate may need to be considered for biologic treatment given the potential benefit of such treatment on both components of psoriatic disease aPhototherapy may be inappropriate in patients (i) who have exceeded safe exposure limits (150–200 treatments for PUVA, 350 treatments for narrowband UVB19, 20), (ii) who are nonresponsive or relapse rapidly, (iii) who have a history of skin cancer or repeated episodes of severe sunburn, (iv) who are intolerant of UV exposure, especially if skin phototype I (sun-sensitive), or (v) for logistical reasons bStandard systemic therapy includes ciclosporin (2·5 mg kg−1 daily; up to 5 mg kg−1 daily), and in men, and women not at risk of pregnancy, methotrexate [single dose (oral, subcutaneous, intramuscular) of 15 mg weekly; max 25 mg weekly] and acitretin (25–50 mg daily) An adequate response to treatment is defined as either (i) a 50% or greater reduction in baseline PASI (PASI 50 response) (or % BSA where the PASI is not applicable) and a 5-point or greater improvement in DLQI4, 21-23or (ii) a 75% reduction in PASI score compared with baseline (PASI 75 response). Initial response to therapy should be assessed at time points appropriate for the drug in question (Table 1). For patients on tumour necrosis factor (TNF) antagonist treatment with psoriasis and psoriatic arthritis, treatment may be continued if there has been a sufficient response in at least one of these components (see BSR guidelines18 for definition of disease response in psoriatic arthritis). TNF is a proinflammatory cytokine produced by a wide variety of cell types including keratinocytes. It plays a central role in the pathogenesis of psoriasis, psoriatic arthritis and a number of other disease states. TNF is released from cells as a soluble cytokine (sTNF) following cleavage from its cell surface-bound precursor (transmembrane TNF, tmTNF). Both sTNF and tmTNF are biologically active, and bind to either of two distinct receptors: TNF receptor 1 (TNFR1, p55) and TNF receptor 2 (TNFR2, p75). This leads to NF-κB activation (which promotes inflammation) and/or cell apoptosis. In addition, tmTNF can itself act as a ligand (via a process of reverse signalling) to induce cell activation, cytokine suppression or apoptosis of the tmTNF-bearing cell. Soluble forms of the TNF receptors also exist and, by binding and neutralizing sTNF, may act as natural TNF antagonists. There are currently two approved groups of biologic agents that target TNF: anti-TNF monoclonal antibodies (adalimumab and infliximab), and sTNF receptors (etanercept). Infliximab is a chimeric human–murine monoclonal antibody (∼ 25% mouse-derived protein) whereas adalimumab is fully human. Etanercept is a genetically engineered fusion protein composed of a dimer of the extracellular portions of human TNFR2 (p75) fused to the Fc domain of human IgG1. All three agents specifically bind both soluble and transmembrane forms of TNF and act by (i) blocking TNFR-mediated mechanisms and (ii) inducing tmTNF (reverse-signalling) events. Etanercept also binds members of the lymphotoxin family [LTα3 (also known as TNF-β) and LTα2β1] although the biological significance of this is unclear. Aside from the latter, there are important differences between the three agents with respect to pharmacokinetics, immunogenicity and structure-based mechanisms of action (only some of which are completely understood).24 It is likely that these differences, in the context of the highly complex biology of TNF, account for observed differences in the efficacy and adverse events profile of TNF antagonists. Lymphocyte function-associated antigen-1 (LFA-1) is a cell surface protein that binds to intracellular adhesion molecule (ICAM) 1–3 and plays a key role in T-lymphocyte recirculation, trafficking to sites of inflammation, antigen presentation by dendritic cells and other activated cells including keratinocytes, and T-cell costimulation. Efalizumab is a recombinant humanized IgG1 monoclonal antibody that binds specifically to the CD11a subunit of LFA-1, which by interfering with LFA-1/ICAM binding inhibits several key steps important in the pathogenesis of psoriasis including T-cell migration into the skin and T-cell activation. More recently, in vivo data have shown that efalizumab induces a state of reversible T-cell 'hyporesponsiveness' including downregulation of a number of T-cell surface molecules unrelated to LFA-1 both in the circulation and in psoriatic plaques.25, 26 Interleukin (IL)-12 and IL-23 are heterodimeric cytokines secreted by activated antigen-presenting cells, and share a common protein subunit, p40. Of relevance to psoriasis, IL-12 activates CD4 and natural killer cells to induce expression of type 1 cytokines (TNF and interferon-γ) while IL-23 stimulates survival and proliferation of a subset of T cells that produce IL-17 (Th17 cells). Recent immunological27 and genetic studies indicate a central role for IL-23 in the pathogenesis of psoriasis.28Ustekinumab is a fully human IgG1κ monoclonal antibody which acts as an IL inhibitor by binding with high affinity and specificity to the p40 protein subunit. It thus prevents IL-12 and IL-23 from binding to their IL-12Rβ1 receptor protein expressed on the surface of immune cells. Three large RCTs demonstrate that etanercept is effective in chronic plaque psoriasis.29-31 Onset of action is slower than that seen with the monoclonal antibodies, with clinically significant improvement in disease severity scores evident between 4 and 8 weeks after initiation of treatment.30 Response is dose related, with 34% (25 mg biweekly) and 48% (50 mg biweekly) of patients achieving PASI 75 by 12 weeks (Table 2). Continuing therapy up to 6 months improves response rates further (43% and 57% for 25 mg biweekly and 50 mg biweekly, respectively).29, 30, 32 While there are no RCT data establishing efficacy beyond 6 months, data from a 2-year, open-label etanercept 50 mg biweekly extension study32 (following the phase III study reported by Tyring et al.31) suggest that efficacy is maintained for up to 1 year, with approximately 75% of patients maintaining their PASI 75 response over the ensuing year. Overall, continuous therapy provides better disease control and higher levels of patient satisfaction compared with interrupted therapy. When treatment is stopped, disease relapses slowly: median time to disease relapse as defined by loss of PASI 50 in those who achieved PASI 75 after 24 weeks of continuous etanercept 25 or 50 mg biweekly, was 85 and 91 days, with no evidence of disease PASI scores were with the of patients achieving efficacy after 12 further weeks (i.e. and of PASI 75 achieved this level of efficacy on Aside from objective measures of disease improvement studies also report associated clinically in quality of life reduction in and and of patients in analysis of two of these RCTs that response rates in those over were the as those although in the group were The 25 mg and 50 mg are given that their are that the number of patients achieving PASI 75 at 12 weeks following etanercept 50 mg an RCT compared with was with that seen in other RCTs investigating etanercept 25 mg biweekly and that no significant differences were observed in PASI or DLQI in a of patients open-label etanercept 25 mg biweekly and etanercept 50 mg In the RCTs the of adverse events or adverse events in patients etanercept was no greater than in the control patients, with the of in each treatment RCT has shown efficacy of etanercept 25 mg compared with acitretin mg kg−1 at 24 weeks (see the role of TNF in levels of TNF in patients, and the used for etanercept, response rates may occur in patients, with This is in by published RCT and data cited in the study by et The of etanercept and methotrexate has been shown to be more effective in arthritis than either with no significant additional toxicity. data suggest that the of methotrexate may also etanercept efficacy in psoriasis. A RCT the efficacy and safety of etanercept (25 mg biweekly) in patients on and reported of patients or at 24 weeks on therapy, as compared with those in methotrexate was A reported both efficacy with the of methotrexate in patients on etanercept and loss of efficacy on of methotrexate from patients on Data from a RCT reported that the of etanercept 25 mg with acitretin mg kg−1 is as effective as etanercept 25 mg and that both these interventions are more effective that acitretin These data suggest that in the short term at the may additional efficacy as there is no additional associated toxicity. The patient in the cited RCTs may not be of patients likely to be treated in clinical practice as to the studies required patients only to be considered or have or systemic therapy. However, objective disease severity criteria were the as those currently recommended by the BAD and and PASI scores on to studies were higher from 16 to studies of practice report response rates in patients who have failed systemic therapies, all of which that data from the RCTs can be to clinical 50 There is a of long-term RCT data beyond 6 months, and only limited data on the two published studies one is and both report following one of treatment RCT data indicate that 50 mg biweekly is more effective than 25 mg biweekly, but there are no trial data whether the dose to 50 mg biweekly in patients who to achieve or adequate on 25 mg biweekly results in disease This is especially pertinent given guidance which currently limits treatment to the 25 mg biweekly dose (see Etanercept is licensed for use in moderate to severe psoriasis at either 50 or 25 mg biweekly for the first months, and 25 mg biweekly for up to 24 therapy beyond 24 weeks may be appropriate for some patients has approved use of etanercept in severe plaque psoriasis to defined disease at the 25 mg biweekly dose only, and not the 50 mg dose effective, with therapy to be continued only in those patients achieving disease response at months (Table 1). Etanercept is recommended for the treatment of patients with severe psoriasis who fulfil the disease severity criteria to section (Strength of recommendation level of evidence Etanercept therapy may be at either 50 or 25 mg and disease response assessed at months (Strength of recommendation level of evidence The of which dose to use will on clinical disease body and, in the U.K., the dose that will be (Strength of recommendation level of evidence Patients on etanercept 25 mg may to to etanercept 50 mg as these two are in of efficacy (Strength of recommendation level of evidence In patients who treatment may be continued to clinical although long-term data on efficacy are limited to 2 (Strength of recommendation level of evidence may be risk of disease although there may be a response on therapy (Strength of recommendation level of evidence may be recommended in clinical where it is required for associated or to efficacy (Strength of recommendation level of evidence Three large indicate that infliximab therapy is highly effective in chronic plaque psoriasis (Table Onset of action is with evidence of significant improvement the first 2 weeks of treatment and benefit by 10 when of patients achieve PASI 75 (Table (and in DLQI of This response is largely maintained over time with and achieving PASI 75 at 6 and 12 months, respectively (Table 2). of efficacy with development of antibodies to which in of patients continuous therapy and 5 mg following a standard 2 and 6 continuous therapy at 5 mg kg−1 8 weeks achieved to relapse in the by loss of PASI was as and in the of although data were not An that 50% patients relapse of PASI by There are no published trial data beyond 1 year. study assessed disease using the Psoriasis Severity Index to a a improvement in from baseline was observed at 10 with a of improvement reported at This was maintained of patients with complete of disease the target continued to between weeks 24 and 50 and There are no RCT data on use of methotrexate in with infliximab in psoriasis. In both and psoriatic arthritis, with methotrexate is a licensed and response rates and are at least in these disease levels of infliximab have been reported with methotrexate which may in of mg also the of antibodies to The patient in the cited RCTs may not be of patients likely to be treated in clinical practice. The PASI at baseline was ≥ 10 in all the studies However, of systemic therapy was not an in that most studies required patients to be for systemic therapy and/or failed A of patients in the study by et indicate that baseline PASI > and the of treatments two or more systemic therapies, or biologic no on treatment The of the study investigating continuous infliximab therapy is in that study at patients randomized to receive therapy receive infliximab at PASI 75 was not and in both were reported as Infliximab is licensed for use mg kg−1 8 in moderate to severe plaque psoriasis. has approved use of infliximab in patients with severe (PASI ≥ DLQI ≥ with treatment beyond 10 weeks recommended only in those who achieve response Infliximab is recommended for the treatment of patients with severe psoriasis who fulfil the disease severity criteria to section (Strength of recommendation level of evidence Infliximab therapy should be at a dose of 5 mg kg−1 at weeks 2 and 6 and disease response assessed at months (Strength of recommendation level of evidence In patients who mg should be given at to disease control although long-term data are available only up to 1 (Strength of recommendation level of evidence therapy should be given the associated risk of and disease control (Strength of recommendation level of evidence may be recommended in clinical where it is required for associated to efficacy or to the development of antibodies to infliximab (Strength of recommendation D; level of evidence 3) Three large RCTs demonstrate that adalimumab is a highly effective treatment for chronic plaque psoriasis (Table Onset of action is with significant in disease severity evident 2 weeks of treatment and disease response seen between weeks 12 and Response is dose with of patients achieving PASI 75 at 12 with adalimumab mg other (i.e. the licensed dose for psoriasis), and achieving PASI 75 with adalimumab mg relevant in quality of life indicators are also In one a subset of patients who failed to achieve PASI 50 following at least 24 weeks of adalimumab other was to the dose for the of the study 40% of this PASI 50 that dose may further data are available up to 1 year, with no evidence of significant loss of response over time in those patients who and are continued on of response on treatment was also in the phase of the study reported by et those who maintained PASI 75 by were to receive either or a further weeks of adalimumab While time to relapse was not of patients PASI 50 response relative to baseline with a of a in PASI score relative to compared with relapse in those on adalimumab by of this patients who

Patients with moderate-to-severe psoriasis often experience significant physical symptoms and notable psychosocial distress. Pruritus is the most bothersome symptom and a key contributor to sleep disturbances and reduced quality of life (QoL). Though biologics such as risankizumab have advanced clinical management, real-world evidence of patient-reported outcomes (PROMs) and objective pruritus assessment remains limited. This study assessed risankizumab's effectiveness in improving QoL, symptom burden, and sleep and evaluated the feasibility of nocturnal scratch monitoring using a wearable sensor. PRIMMA was a multicenter, prospective, non-interventional study conducted in Israel among adults with moderate-to-severe psoriasis initiating label-approved risankizumab therapy. Outcomes were assessed at baseline and week 52, and included Dermatology Life Quality Index (DLQI), static Psoriasis Global Assessment (sPGA), Pruritus Numeric Rating Scale (PNRS), Psoriasis Symptoms Scale (PSS), Medical Outcomes Study Sleep Scale (MOS-SS), Work Productivity and Activity Impairment (WPAI), and adverse events. Objective nocturnal scratch activity was measured using ADAM digital patch sensors in a subgroup of patients. In 136 participants, the median age was 51years, 57% were male, 43% were female, and 35% were bio-naïve. At week 52, 58% achieved DLQI 0/1 (versus 5.1% at baseline; p < 0.001) and 81% had PNRS 0-3 (versus 21% at baseline; p < 0.001). sPGA 0/1 was reached by 77% at week 52, and components of PSS and WPAI improved significantly. In patients who achieved any favorable outcome (DLQI 0/1, PNRS 0-3, sPGA 0/1) at week 24, ≥ 68% maintained it at week 52, demonstrating treatment durability. In the digital subcohort (n = 14), sensor data confirmed significant reduction in nocturnal scratch duration at week 4 and week 16 compared to baseline (both p ≤ 0.032). Adverse events were mostly mild to moderate. In real-world practice, risankizumab showed substantial improvements in QoL, pruritus, sleep, and work/activity impairment in moderate-to-severe psoriasis. Digital scratch monitoring showed reduction in nocturnal scratch duration. Integrating objective digital measures with PROMs may enable more data-driven, individualized management in psoriasis care. ClinicalTrials.gov Identifier NCT04780516.

The appearance and lifelong, chronic nature of psoriasis result in considerable burden to patients, such as sleep impairment, depressive symptoms, negative self-esteem and reduced work productivity. To examine direct and indirect (mediated) effects of secukinumab vs. ustekinumab on quality of life, work productivity and activity impairment based on psoriasis severity and symptoms. Analyses were based on data from the CLEAR study. Structural equation modelling examined the effects of secukinumab vs. ustekinumab on the Dermatology Life Quality Index (DLQI) and on the Work Productivity and Activity Impairment (WPAI) questionnaire using Psoriasis Area and Severity Index (PASI) severity and symptoms (pain, itching and scaling) as potential mediators. Analyses were conducted primarily for patients achieving a PASI 90 response (90% or greater reduction in PASI from baseline) at week 16 (repeated at week 52) and for PASI 50, 75 and 100. Results at weeks 16 and 52 showed that the effect of treatment on change in DLQI score was mediated by the PASI 90 response and by improvements in itching, pain, and scaling. Achieving any PASI response as early as week 16 directly resulted in significantly better WPAI scores. At week 52, both PASI response and improvement in scaling directly resulted in significantly better WPAI scores. Pain, itching and scaling were correlated (r = 0·51-0·68); improvement in any of these had a significant effect (directly or indirectly) on WPAI. All results favoured secukinumab over ustekinumab. The results underscore the important role of both PASI response and reduction in symptoms on improvements in health-related quality of life and work and daily activity in favour of secukinumab vs. ustekinumab.

IntroductionClinical trials have shown that psoriasis patients who achieve complete skin clearance are more likely to report no impairment in health-related quality of life (HRQoL) and no psoriasis symptoms versus patients who achieve almost complete skin clearance. However, real-world data are lacking. The objective of this study was to estimate the real-world proportion of moderate-to-severe psoriasis patients on biologic treatment who achieved a Psoriasis Symptom Inventory (PSI) total score of 0 (PSI 0; no symptoms) and a Dermatology Life Quality Index (DLQI) score of 0/1 (DLQI 0/1; no impact on HRQoL), and to study the relationship between patient-reported symptoms and HRQoL versus physician-reported psoriasis severity (Psoriasis Area and Severity Index [PASI]).MethodsThe PSO-BIO-REAL study was a multinational, prospective, real-world, non-interventional study that included patients aged ≥ 18 years with moderate-to-severe plaque psoriasis who had initiated biologic therapy (either biologic-naïve or had switched biologics [biologic-experienced]). Psoriasis symptoms were evaluated using the PSI, and HRQoL was assessed using the DLQI. Assessments were conducted at baseline and at 6 and 12 months after initiating biologic treatment. Associations between PSI and DLQI with PASI were evaluated using Spearman correlation coefficients. Post-hoc analyses evaluated individual PSI items and the association to PASI response, DLQI and PSI by index biologic.ResultsAt 12 months, 25.5% of patients achieved PSI 0, and 51.2% achieved DLQI 0/1, with greater proportions achieving these scores among biologic-naïve than among biologic-experienced patients. There was a moderate-to-strong correlation between PSI and DLQI scores and PASI scores, with 64.8% of patients with absolute PASI 0 and 19.4% with absolute PASI > 0 ≤ 2 achieving PSI 0 (6 and 12 months pooled). Achievement of response varied by index biologic.ConclusionThis study demonstrates that in a real-world setting patients’ QoL improves with skin clearance. The results also demonstrate that the correlation between skin clearance and improvements in HRQoL (DLQI) and psoriasis symptoms (PSI) is not complete, which highlights the importance of considering both patient- and physician-reported outcomes in the assessment of psoriasis treatment outcomes.

Psoriasis is a chronic inflammatory condition that can significantly impact the quality of life (QoL), regardless of the level of skin involvement. Apremilast is indicated for the treatment of moderate to severe psoriasis. Real-world data regarding the impact of apremilast on patient-reported outcomes in clinical practice in the Netherlands is lacking. The prospective, multicenter observational Apremilast in Real-Life Psoriasis Treatment (APRIL) study enrolled patients ≥ 18years old with moderate to severe plaque psoriasis receiving apremilast in clinical practice in the Netherlands. Patients were followed-up for 12 months, with assessments scheduled at 6 and 12 months. The primary outcome was Dermatology Life Quality Index (DLQI) response (score ≤ 5 or ≥ 5-point improvement from baseline) at 6 months. Secondary patient-reported outcomes included EQ-5D and skin-specific parameters; exploratory outcomes were Patient Benefit Index (PBI) and Work Productivity and Activity Impairment (WPAI). Of the 155 patients enrolled (February 2016-June 2019), 153 received apremilast; 69 (45%) and 39 (26%) continued treatment at 6 and 12months, respectively. Psoriasis in special areas was common (scalp, 65%; nail, 51%; palmoplantar, 27%). Most patients (92%) had received prior systemic antipsoriatic therapies. Of the 151 patients with a baseline DLQI value, 56 (37%) achieved DLQI response at 6months. Mean (standard deviation) PBI scores were 3.5 (1.2) and 3.8 (1.1) at 6 and 12months, respectively. Improvements in DLQI, EQ-5D, and WPAI scores and disease signs and symptoms, including itch and special areas, were observed at 6 and 12months. Adverse events were consistent with the known safety profile. In the Netherlands, patients with moderate to severe psoriasis receiving apremilast for up to 12months reported improved disease-related QoL, skin involvement, and patient-reported outcomes. These data add to the growing body of evidence demonstrating apremilast is an effective treatment for psoriasis, itch, and special areas (scalp and palms). ClinicalTrials.gov, NCT02652494.

Introduction Psoriasis (PsO) is a chronic inflammatory disease of the skin. While skin clearance, as measured by the Psoriasis Area and Severity Index (PASI), is a clinical goal, PsO patients also suffer from reduced health-related quality of life (HRQoL). In the Phase 3 VOYAGE 1 trial, guselkumab (GUS) demonstrated improvements on patient reported outcomes compared with placebo (PBO) and adalimumab (ADA). Here we report an analysis of the estimated time to onset of the minimal clinically important difference (MCID) in HRQoL, as measured by the Dermatology Quality of Life Index (DLQI) and associated PASI response in GUS-treated patients from VOYAGE 1.&#x0D; Methods The VOYAGE 1 trial enrolled patients with moderate-to-severe PsO who were randomized to receive PBO, GUS, or ADA. The DLQI is a self-report measure for HRQoL ranging from 0 (no impact) to 30 (maximum impact) that assesses the effect of skin problems on 6 HRQoL domains. An accepted MCID in DLQI is 4, previously reported as the smallest difference in DLQI total score that patients’ rate as beneficial. DLQI score and PASI improvement (percent change from baseline) were analyzed at Weeks 0, 8, 16, and 24 for the subset of VOYAGE 1 patients with a baseline DLQI score &gt;4. Earliest time to onset of MCID in mean DLQI and corresponding mean PASI improvement were estimated using linear interpolation for the GUS group between Weeks 0 and 8.&#x0D; Results Among patients randomized to GUS, n=279 (85%) had DLQI &gt;4 at baseline. By first assessment at Week 8 (W8), we observed a reduction in the mean DLQI score from 15.6 (baseline) to 5.0 (W8) with median DLQI decreasing from 15.0 (baseline) to 3.0 (W8). The interpolated onset of MCID in DLQI occurred at 21.1 days (W3) following the initial GUS dose. In GUS-treated patients, the estimated mean PASI improvement corresponding to the onset of MCID in mean DLQI occurring at Week 3 was 29.2%.&#x0D; Conclusions These data indicate that the onset of clinically meaningful improvements in mean DLQI occur as early as after the first dose of GUS in patients with moderate-to-severe PsO.

Psoriasis is associated with poor health-related quality of life, including sleep impairment. To assess the extent of sleep impairment, the effect of adalimumab on sleep and other patient-reported outcomes, and correlations between changes in these outcomes and sleep quality in patients with psoriasis. Patients in the 16-week, open-label, Phase IIIb PROGRESS trial had chronic plaque psoriasis and suboptimal response to prior therapy (etanercept, methotrexate or narrowband ultraviolet B phototherapy). Adalimumab was self-injected subcutaneously (80 mg at week 0, then 40 mg every other week from week 1). The focus for this analysis was the Medical Outcomes Study Sleep Scale. Other patient-reported outcomes included the Dermatology Life Quality Index (DLQI), Psoriasis Area and Severity Index (PASI), Physician's Global Assessment, a visual analogue scale for psoriasis/psoriatic arthritis (PsA) pain, and the Work Productivity and Activity Index Questionnaire-Specific Health Problems. Patients with psoriasis had impaired sleep at baseline. The degree of sleep impairment was significantly associated with the extent of work productivity for all sleep measures and, for some sleep measures, was associated with DLQI impairment, clinical severity measured by PASI, the presence of PsA, and depression. Adalimumab treatment significantly improved sleep quality by 15% from baseline, as well as DLQI score, pain and work productivity. The improvement in sleep was partially explained (R(2 ) = 0·16, P < 0·001) by improvements in the objectively measured psoriasis signs in PASI. Adalimumab treatment improved sleep outcomes and other patient-reported outcomes including health-related quality of life, work productivity, daily activity and disease-related pain.

Clinical trials show improvement in physical and health-related quality of life (HRQoL) measures in patients with psoriasis treated with biologics compared with placebo. However, these reports only give limited interpretation of the meaning of Dermatology Life Quality Index (DLQI) scores and provide limited comparison data. The aim of this paper is to identify which biological therapy provides the greatest improvement in HRQoL following treatment of patients with chronic plaque psoriasis, as assessed by the DLQI. We reviewed all data published up to August 2006 of randomized placebo-controlled trials (RCTs) of the four biologics currently licensed in some countries for clinical use in chronic plaque psoriasis (alefacept, efalizumab, etanercept and infliximab) which have used the DLQI as an outcome measure. The DLQI data were assessed based on overall improvement according to the DLQI descriptor bands and on clinically meaningful improvement of > or = 5. Fifteen peer-reviewed articles and 59 abstracts describing 11 multicentre, double-blind RCTs were reviewed. Treatment with any one of the four biologics led to a clinically meaningful improvement in the DLQI of > or = 5. However, when applying the DLQI banding concept, infliximab and etanercept provided the greatest improvement in the overall HRQoL from a 'very large effect on overall HRQoL' at baseline to 'a small effect on overall HRQoL' following treatment. The DLQI banding concept provides a further tool to assess the impact of biologics on HRQoL of patients with psoriasis. Based on retrospective application of DLQI bands to published RCT data, infliximab, followed by etanercept, showed the greatest improvement in the overall HRQoL paralleled by a 75% improvement in the Psoriasis Area and Severity Index. However, some publications did not provide absolute baseline DLQI values, making interpretation of data and comparison between the agents difficult. Side-to-side comparative studies between biologics and between biologics and nonbiological psoriasis treatments will aid evidence-based psoriasis management decisions in the future.

Certolizumab pegol (CZP) is an Fc-free, PEGylated, anti-tumour necrosis factor biologic. Safety and efficacy data for CZP over 3years have been previously reported. We report 3-year quality of life (QoL) outcomes for patients treated with CZP, pooled from two phase 3 trials. Adults with moderate-to-severe plaque psoriasis for ≥ 6months were initially randomised 1:2:2 to double-blinded placebo every 2weeks (Q2W), CZP 200mg Q2W (loading dose of CZP 400mg at weeks0/2/4) or CZP 400mg Q2W. All patients received open-label CZP (200mg or 400mg Q2W) from week48. Dermatology Life Quality Index(DLQI), 36-Item ShortForm Survey (SF-36), EuroQol 5-Dimensions 3-Level(EQ-5D-3L) and Work Productivity and Activity Impairment (WPAI) scores are reported as observed. At week0, 100 patients were randomised to placebo, 186 to CZP 200mg Q2W and 175 to CZP 400mg Q2W. For CZP-randomised patients, 60.9% had a DLQI score of 0 or 1 by week48. Both the physical and mental component scores of SF-36 also improved from baseline to week48 (mean change from baseline: 4.4 and 5.4, respectively). The proportion of patients with a score of 1 in the EQ-5D-3L Pain/Discomfort dimension increased (week0, 21.1%; week48, 66.2%), and WPAI Presenteeism, Work Impairment, and Activity Impairment improved from baseline to week48, with the strongest gains observed for Activity Impairment (week0, 33.3% of time impaired; week48, 6.7%). Across patient-reported outcomes, gains were sustained through week144, with durable improvements observed regardless of sex, psoriatic arthritis status or prior exposure to biologics. CZP treatment was associated with sustained and tangible improvements in health-related QoL (DLQI and SF-36), health status (EQ-5D-3L) and functional impairment at work and in other daily activities (WPAI). ClinicalTrials.gov NCT02326298 (CIMPASI-1) and NCT02326272 (CIMPASI-2).

Psoriasis Area and Severity Index (PASI) 90 is suggested to be the new standard endpoint for randomized controlled trials of biologics for psoriasis, whereas treatment guidelines often still refer to PASI 75. To analyse in a real-world setting: firstly, what factors are associated with higher levels of treatment response to biologics; secondly, the health-related quality of life gains associated with different response levels in clinical practice. Biologically naïve patients with PASI, Dermatology Life Quality Index (DLQI) and EuroQol (EQ)-5D outcomes before (maximum 6 months) and after (3-12 months) switch to biologics during registration in the Swedish National Registry for Systemic Treatment of Psoriasis (PsoReg) were included (n = 515). Patient characteristics associated with higher treatment response were analysed by regression analyses. Improvements in absolute PASI, DLQI and EQ-5D were assessed in different PASI percentage response levels. High PASI percentage response was associated with higher PASI before switch and lower body mass index. DLQI and EQ-5D improved within all responder groups (P < 0·001). The magnitude of improvements in DLQI (P = 0·02) differed between responder groups. The mean (SD) DLQI improvements for PASI 75<90 responders, PASI 90<100 responders and patients achieving complete skin clearance (PASI 100) were 9·9 (7·4), 11·5 (7·0) and 8·0 (6·1), respectively. PASI percentage change is largely dependent on absolute PASI before switch. Patients in clinical practice lack 'baseline' PASI values as they may switch directly from one treatment to another or stay successfully treated for a longer time period. Treatment goals such as PASI 90 are thus not suitable for treatment guidelines or for follow-up in clinical practice. What's already known about this topic? Randomized clinical trials of biologics as well as treatment guidelines include treatment goals based on a percentage improvement compared with baseline Psoriasis Area and Severity Index (PASI), such as PASI 75 or PASI 90. Few studies have assessed which factors are associated with high skin clearance rates, or health-related quality of life (HRQoL) improvements associated with different levels of skin clearance in clinical practice. What does this study add? A high absolute PASI before switch to biologics and low body mass index are associated with higher PASI percentage response. Few patients with baseline PASI >30 achieved complete skin clearance (CSC). All responder groups achieved significant HRQoL improvements. Patients achieving CSC (PASI 100) had lower absolute PASI before switch and lower improvements in absolute PASI and HRQoL than patients with almost cleared skin. What are the clinical implications of this work? Relative measures based on PASI percentage, such as PASI 75 or PASI 90, are not suitable for treatment guidelines or for follow-up in clinical practice.

Background/ObjectivesInformation is limited on the relationship between skin clearance, resolution of challenging body areas, and improvement of patient‐reported outcomes (PROs) in pediatric psoriasis. Ixekizumab, a high‐affinity monoclonal antibody that selectively targets interleukin‐17A, is approved for the treatment of moderate‐to‐severe psoriasis in patients aged 6 to <18 years. This study examines improvement in psoriasis clearance in challenging body areas in pediatric patients relative to health‐related quality of life.MethodsData from the IXORA‐PEDS trial (NCT03073200) were analyzed, and changes from baseline were measured for overall Psoriasis Area and Severity Index (PASI), static Physicians' Global Assessment of psoriasis (sPGA), Psoriasis Scalp Severity Index (PSSI), Palmoplantar Psoriasis Area and Severity Index (PPASI), and Nail Psoriasis Severity Index. Rates of Dermatology Life Quality Index (DLQI), or Children's DLQI (CDLQI), scores of 0 or 1 were evaluated using the Cochran‐Armitage trend test.ResultsHigher rates of DLQI/CDLQI (0,1) scores were significantly associated with greater PASI and PSSI responses at both Week 12 and Week 48 (p < .0001). A significant association was also observed between DLQI/CDLQI (0,1) and sPGA scores (p < .0001). Significantly higher rates of DLQI/CDLQI (0,1) scores were achieved in patients with greater levels of palmoplantar clearance as measured by PPASI at Week 12 (p = .0139), but significance was not sustained at Week 48 (p = .0896).ConclusionsGreater skin clearance and scalp resolution are associated with better PROs over a short‐term (12‐week) and long‐term (48‐week) period. This demonstrates that greater improvement of skin clearance and scalp resolution may benefit quality of life in pediatric patients with psoriasis.

Remibrutinib, an oral, highly selective Bruton tyrosine kinase inhibitor, has shown efficacy and favourable safety in the REMIX-1/2 studies in patients with chronic spontaneous urticaria (CSU). Herein, we report the impact of remibrutinib treatment on Work Productivity and Activity Impairment (WPAI) and Dermatology Life Quality Index (DLQI) outcomes. REMIX-1 and REMIX-2 were identical, phase III, double-blind, placebo-controlled studies in patients aged ≥ 18 years diagnosed with CSU (≥ 6 months) who remained symptomatic despite treatment with second-generation H1-antihistamines. Patients were randomized 2 : 1 to add-on remibrutinib 25 mg twice daily or placebo over a 24-week double-blind period, followed by 28 weeks’ open-label add-on remibrutinib 25 mg twice daily (patients on placebo transitioned to remibrutinib at week 24). Patients completed WPAI and DLQI questionnaires in their eDiary at baseline and weeks 4 (DLQI only), 12, 24 and 52. At baseline, WPAI and DLQI scores (Table) were comparable for remibrutinib vs. placebo in both REMIX-1 and REMIX-2. By week 24, remibrutinib treatment improved both WPAI and DLQI scores. The responses were generally sustained up to week 52 for remibrutinib-treated patients; for patients on placebo who transitioned to remibrutinib at week 24, a comparable improvement in WPAI and DLQI responses was achieved at week 52. Overall, treatment with remibrutinib improved WPAI and DLQI outcomes in REMIX-1/2 and the improvement was sustained to 52 weeks in patients with CSU. This study was funded by Novartis Pharma AG, Basel, Switzerland.TableTreatment response in REMIX-1 and REMIX-2 BaselineWeek 24Week 52RemibrutinibPlaceboRemibrutinibPlaceboRemibrutinibPlacebo → remibrutinibREMIX-1WPAI Absenteeism7.8 (15.8)9.5 (21.3)3.7 (15.8)4.9 (12.1)3.1 (11.8)3.9 (13.7) Presenteeism47.4 (25.8)42.7 (24.9)16.5 (24.6)24.9 (24.6)15.7 (22.7)15.0 (21.5) Work productivity loss50.0 (27.4)45.2 (26.4)17.3 (25.4)27.8 (26.4)16.9 (24.1)17.2 (24.7) Activity impairment48.0 (25.8)44.2 (25.0)16.0 (23.7)24.0 (25.2)16.0 (23.3)16.6 (23.1)DLQI total score14.2 (7.0)13.5 (6.8)4.3 (6.2)6.1 (6.2)4.6 (6.0)4.1 (5.5)REMIX-2WPAI Absenteeism10.0 (19.0)6.1 (13.5)3.5 (13.6)4.8 (18.9)2.8 (10.8)3.4 (14.4) Presenteeism45.1 (26.3)44.2 (26.3)10.3 (15.7)21.6 (23.3)12.6 (19.9)15.1 (22.2) Work productivity loss48.3 (27.9)46.4 (27.0)11.9 (19.2)22.8 (25.2)14.3 (22.8)16.5 (23.7) Activity impairment45.9 (26.8)43.3 (27.3)11.4 (18.0)20.4 (23.2)12.9 (21.0)15.7 (21.7)DLQI total score14.0 (7.5)13.6 (6.7)4.5 (5.8)7.2 (6.6)4.3 (5.5)5.0 (6.4)Data are shown as the mean (SD) as observed (full analysis set) in 912 patients. REMIX-1: n = 309 remibrutinib and n = 153 placebo. REMIX-2: n = 297 remibrutinib and n = 153 placebo. DLQI, Dermatology Life Quality Index; WPAI, Work Productivity and Activity Impairment.

BackgroundUp to 40% of patients with psoriasis (PsO) develop psoriatic arthritis (PsA), which can have a significant impact on health-related quality of life (HRQoL) [1]. Among patients with both PsO...