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Five-year tildrakizumab safety data have been reported as exposure-adjusted incidence rates (EAIRs) of patients with events per 100 patient-years (PYs) of exposure. To present 5-year safety data from reSURFACE 1/2 phase 3 trials as EAIRs of events per 100 PYs of exposure, and the number needed to harm (NNH) for one adverse event of special interest (AESI) to occur. Pooled analysis from two randomized controlled trials in patients with moderate-to-severe plaque psoriasis (n = 1800). PSOLAR registry was used as safety reference data for NNH estimation. Rates of AESI with tildrakizumab were comparable with rates reported in PSOLAR. The NNH for one-year severe infection occurrence was 412 with tildrakizumab 200 mg, and negative for tildrakizumab 100 mg due to lower rates in reSURFACE trials; the NNH for malignancy was 990 for one year with tildrakizumab 100 mg (negative for tildrakizumab 200 mg); and the NNH for major adverse cardiovascular events was 355 for one year with tildrakizumab 200 mg (negative for tildrakizumab 100 mg). Tildrakizumab demonstrated a favorable safety profile over 5 years with low rates of AESI, comparable to those of the PSOLAR. Consequently, the NNH for AESI with tildrakizumab were very high or negative due to lower event rates for tildrakizumab.

Tildrakizumab (TIL), a monoclonal antibody that selectively targets interleukin-23p19, has been approved for the treatment of moderate-to-severe plaque psoriasis. According to the European Medicines Agency Summary of Product Characteristics, the recommended dose is 100 mg, but a 200 mg dose can be used in patients with certain characteristics, such as a high disease burden or body weight (BW) ≥ 90 kg. Fixed one-dose biological therapies tend to become less effective in patients with high BW. This post-hoc study describes the long-term efficacy of TIL across different BWs in pivotal clinical trials. A 5-year pooled analysis of two double-blind, randomised, controlled phase III trials-reSURFACE 1 and 2-was performed. Efficacy measures were the proportions of the patients with an absolute Psoriasis Area and Severity Index (PASI) of < 3 and < 1 and a Dermatology Life Quality Index (DLQI) of 0/1. The study population included patients randomised to TIL 100 mg or TIL 200 mg who received ≥ 1 TIL dose up to week 12 (part 1 of the trial) or up to week 28 (part 2) and patients who were responders (≥ 75% improvement in PASI) to TIL 100 or TIL 200 mg at week 28 and who were maintained on the same dose up to week 244. Efficacy was evaluated by analysing BW subgroups at weeks 28, 52 and 244. Missing data were analysed using multiple imputation. Safety was assessed in the all-patients-as-treated population. The proportions of TIL-treated patients with PASI < 3 and < 1 (up to week 244) and DLQI 0/1 (up to week 52) were similar for patients with BW < 90 or ≥ 90 kg, regardless of dose. Patients ≥ 120 kg had greater efficacy outcomes at the 200 mg dose. Safety outcomes were similar regardless of treatment dose and weight (< 120/≥ 120 kg). In patients with BW ≥ 120 kg, TIL 200 mg is more efficacious than TIL 100 mg, with similar favourable safety profiles obtained regardless of dose and BW group. ClinicalTrials.gov NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2).

Introduction Deucravacitinib is an oral, selective tyrosine kinase 2 inhibitor that demonstrated therapeutic benefit in a Phase 2 clinical trial of adults with moderate to severe plaque psoriasis. This analysis was designed to evaluate the effect of deucravacitinib on additional clinical and quality-of-life (QoL) outcomes and assess the relationship between these outcomes in adults with psoriasis. Methods Post-hoc analysis of a 12-week Phase 2 trial was conducted for the three most efficacious dosage groups (3 mg twice daily, 6 mg twice daily, 12 mg once daily) and placebo. Investigator assessments for efficacy included Psoriasis Area and Severity Index (PASI), body surface area (BSA) involvement, and static Physician's Global Assessment; QoL was assessed using the Dermatology Life Quality Index (DLQI). Treatment responses and their associations were evaluated over time. Results Deucravacitinib elicited improvement versus placebo as early as Week 4 for most efficacy measures (including changes in absolute PASI and BSA), with efficacy trends observed from Week 2 to Week 12. Improvements in QoL, assessed by achievement of a DLQI overall score of 0/1 (no effect at all on patient's life), followed a pattern similar to deucravacitinib-related clinical outcomes over 12 weeks. Overall, patients with greater improvements in psoriasis-related clinical signs and symptoms also reported greater improvement in QoL. However, complete skin clearance was not required for achieving DLQI 0/1. Conclusion Deucravacitinib treatment produced early response and similar trends in improvements across multiple efficacy assessments and QoL in moderate to severe plaque psoriasis. Deucravacitinib has the potential to become a promising new oral therapy for this condition. Plain Language Summary Psoriasis is a skin disease that affects up to 2% of the population. In psoriasis, red, scaly lesions develop on the skin driven by an aberrant immune response. Psoriasis impacts not only physical and mental health but also quality of life (QoL). Deucravacitinib is being investigated as a treatment for psoriasis. We performed a Phase 2 dose-ranging, placebo-controlled, 12-week study of deucravacitinib in adults with moderate to severe psoriasis. Patients in the USA, Australia, Canada, Germany, Japan, Latvia, Mexico, and Poland participated. The study showed that oral treatment with deucravacitinib was effective using a disease severity score (percentage of patients with >= 75% reduction from baseline in Psoriasis Area and Severity Index score) at Week 12-placebo 7% and deucravacitinib 67%-75% for the three highest dosages-and was generally well tolerated. We further analyzed the association between efficacy and a QoL measure, the Dermatology Life Quality Index (DLQI), in patients who received placebo or the most effective dosages of deucravacitinib (>= 3 mg twice daily). Deucravacitinib was effective at the three dosage levels tested. Skin improvement occurred early during treatment and was mirrored by improvements in DLQI score during the 12 weeks of treatment. Although some patients did not have complete clearance of their psoriasis, a large percentage of those patients still achieved considerable improvement in QoL as measured by achieving a DLQI score of 0/1 (i.e., no effect at all on the patient's QoL).

Background: In a phase 3 clinical study, patients from Germany with moderate to severe psoriasis who were naïve to systemic treatment and received risankizumab had greater and more rapid disease improvements compared with those who received fumaric acid esters (FAEs). Objective: To evaluate patient-reported outcomes (PROs) in patients treated with risankizumab compared with FAEs. Methods: Adult patients were randomized 1:1 to receive either risankizumab 150 mg subcutaneous injections at weeks 0, 4 and 16 or FAEs (Fumaderm®) provided according to the prescribing label. PRO secondary endpoints assessed were Psoriasis Symptom Scale (PSS), Dermatology Life Quality Index (DLQI), 36-Item Short Form Health Survey, version 2 (SF-36v2), Patient Benefit Index (PBI), Hospital Anxiety and Depression Scale (HADS), Patient Global Assessment (PtGA) and European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L). PROs were assessed at weeks 0, 16 and 24. Results: Sixty patients each were randomized to receive risankizumab or FAEs. A significant PSS improvement was observed with risankizumab vs. FAEs at weeks 16 and 24 for total and psoriasis-associated redness, itching and burning scores (P < 0.001). DLQI scores were significantly lower (reflecting better health-related quality of life) with risankizumab vs. FAEs, with least squares (LS) mean differences of −7.4 and −7.6 at weeks 16 and 24, respectively (both P < 0.001). Patients randomized to risankizumab also had larger improvements in SF-36 Physical and Mental Component Summary scores, HADS anxiety and depression scores, PtGA, and EQ-5D-5L index and visual analogue scale scores (all P ≤ 0.002) at weeks 16 and 24 compared with FAEs. PBI was significantly higher, indicating greater benefit, with risankizumab vs. FAEs, with an LS mean difference of 1.1 and 1.3 at weeks 16 and 24, respectively (both P < 0.001). Conclusions: Risankizumab provides significant benefits over FAEs in improving PROs across several dimensions in patients with moderate to severe psoriasis.

Altres ajuts: The authors thank Dhaval Gupta, MPH (Novartis Healthcare Pvt Ltd, India), and Jackie L. Johnson, PhD (Novartis Ireland Ltd), for providing medical writing support, which was funded by Novartis Pharma AG, Basel, Switzerland, in accordance with Good Publication Practice guidelines (http://www.ismpp.org/gpp3).

Summary Background Although existing psoriasis treatments are effective and well tolerated in many patients, there is still a need for new effective targeted treatment options. Tofacitinib is an oral Janus kinase inhibitor that has been investigated in patients with moderate‐to‐severe chronic plaque psoriasis. Objectives To consider the benefits and risks of tofacitinib in patients with moderate‐to‐severe psoriasis. Methods Data were pooled from one phase II, four phase III and one long‐term extension study comprising 5204 patient‐years of tofacitinib treatment. Efficacy end points included patients achieving Physician's Global Assessments of ‘clear’ or ‘almost clear’, ≥ 75% and ≥ 90% reduction in Psoriasis Area and Severity Index (coprimary end points) and improvements in Dermatology Life Quality Index score, Hospital Anxiety and Depression Scale depression score and Itch Severity Item score, at weeks 16 and 52. Safety data were summarized for 3 years of tofacitinib exposure. Results Tofacitinib 5 and 10 mg twice daily (BID) showed superiority over placebo for all efficacy end points at week 16, with response maintained for 52 weeks of continued treatment. Tofacitinib improved patients’ quality of life and was well tolerated. Rates of safety events of interest (except herpes zoster) were similar to those in the published literature and healthcare databases for other systemic psoriasis therapies. Tofacitinib 10 mg BID demonstrated greater efficacy than 5 mg BID. Conclusions Tofacitinib has a benefit–risk profile in moderate‐to‐severe psoriasis consistent with that of other systemic treatments., What's already known about this topic? Psoriasis is a chronic, systemic inflammatory disease, which has a significant impact on patients’ health‐related quality of life.Although several existing psoriasis treatments are efficacious and well tolerated in many patients, some patients require treatment switching, and a proportion of patients remain untreated or undertreated.Potential challenges to the use of existing therapies include safety issues and limited efficacy in some patients with conventional oral psoriasis treatments, inconvenience of topical treatments and the requirement for parenteral administration of biologics. What does this study add? Consistent efficacy and a safety profile consistent with that seen in rheumatoid arthritis, psoriatic arthritis and ulcerative colitis were demonstrated for oral tofacitinib in patients with moderate‐to‐severe psoriasis.Tofacitinib has a benefit–risk profile in patients with moderate‐to‐severe psoriasis that is consistent with that of other systemic psoriasis treatments. Linked Comment: Fleming. Br J Dermatol 2019; 180:13–14. Plain language summary available online Respond to this article

Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin 17A, a key cytokine involved in the development of psoriasis. Secukinumab has shown long-lasting efficacy and safety in the complete spectrum of psoriatic disease, including disease localized to nails, scalp, palms and soles, and joints (peripheral and axial arthritis). Given the chronic and relapsing nature of psoriasis, long-term data might help to fully characterize the efficacy and safety profile of secukinumab as well as its impact on quality of life.

Altres ajuts:This study was sponsored by LEO Pharma. Article-processing charges were funded by LEO Pharma. Medical writing support was provided by Mai Kurihara, PhD, from Mudskipper Business Limited, funded by LEO Pharma. Fixed-dose combination topical therapy with corticosteroid and vitamin D analog provides effective treatment and possible long-term management of psoriasis. The anti-inflammatory and immunomodulatory effects of corticosteroids and vitamin D analogs in treating psoriasis are well investigated; their complementary effects lead to the disruption of the inflammatory feedback loop underlying psoriasis pathogenesis. Recent preclinical data showed that combination therapy is more effective than monotherapies of the active ingredients in preventing activation of resting pro-inflammatory cells, inducing immunomodulation, reducing inflammatory responses by regulating T cell production, and normalizing keratinocytes. The increased understanding of the mechanism of action of fixed-dose combination therapy from preclinical studies is supported by several clinical studies. As the efficacy of topical therapy is correlated with the skin penetration of the active ingredients, new drug delivery systems have been developed. The fixed-dose combination Cal/BD aerosol foam creates a modified supersaturated formulation when applied to the skin, which is maintained for at least 26 h in the laboratory setting. Clinical studies have demonstrated superior efficacy of fixed-dose combination calcipotriol (Cal) 50 µg/g and betamethasone dipropionate (BD) 0.5 mg/g aerosol foam compared with monotherapies of the active ingredients. Furthermore, Cal/BD aerosol foam has shown significantly improved efficacy compared with more traditional formulations, such as Cal/BD ointment and gel, in other studies. Calcipotriol also mitigates risks associated with betamethasone dipropionate and vice versa, resulting in the favorable safety profile observed with fixed-dose combination treatment. Recent data also suggest that fixed-dose combination treatment could provide long-term management of psoriasis, although further clinical investigations are needed. Overall, these data support the value of fixed-dose combination therapy of corticosteroid and vitamin D analog and highlight the added potential of innovative drug delivery for the treatment of psoriasis. LEO Pharma.

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by impaired epidermal skin barrier and a mainly Th2 deviated immune profile. Filaggrin is an important protein of the skin barrier, and loss-of-function (null) mutations in the filaggrin gene (FLG) are the most significant genetic risk factor of AD. Genetic factors cannot explain the rapid increase of AD, and gene–environment interactions seem important. Outcome-predicting biomarkers could help in identifying the patients in need of closer follow-up. FLG null mutations and serum total immunoglobulin E (IgE), a general marker of Th2 immune deviation, are proposed biomarkers. Adulthood AD is often accompanied by atopic blepharoconjunctivitis that can at worst lead to vision-threatening complications. Topical calcineurin inhibitors (TCIs) pimecrolimus and tacrolimus are commonly used for this indication, but the long-term ocular safety data are scarce. There is a paucity of epidemiological research on adulthood AD and little is known about the effect of acquired factors. We investigated associations of FLG mutations with AD in the Finnish population and tested the usefulness of these mutations and total IgE as outcome-predicting biomarkers. Addi¬tionally, we explored the effect of other patient-related deter¬minants on the long-term outcome and gained novel ocular safety data of TCIs. We determined the prevalence of adulthood AD in Finland and explored the effect of acquired risk factors. We utilized university clinic cohorts of 501 patients with AD and 338 ophthalmologist-followed patients with atopic blepharoconjunctivitis, and a nationally representative cohort of 8,026 Finns ≥ 30 years of age. FLG mutations were associated with AD, asthma, early onset, palmar hyperlinearity, and keratosis pilaris but they did now show associations with long-term outcome. Only a fraction of patients carried the common European FLG mutations—a possibility of an unrecognized Finnish-specific mutation remains. Their value as a predictive biomarker in adulthood AD seems low. Conversely, total IgE seems an inexpensive outcome-predicting biomarker in adulthood AD with values ≥ 10,000 IU/ml being the most significant factor predicting poor outcome. Both TCIs demonstrated good safety in the treatment of atopic blepharoconjunctivitis with no long-term safety concerns. Tacrolimus seemed better tolerated and more effective than pimecrolimus. Female sex and current smoking were associated with AD in adult subjects of 30–50 years of age. Ex-smokers and subjects with highly educated parents had more AD. The prevalence of adulthood AD in Finland is among the highest in the world with a lifetime prevalence of 21.8% and a 12-month prevalence of 10% making it an important public health issue. Atooppinen ihottuma (atooppinen ekseema) on yleinen kutiseva ihosairaus, jolle on tyypillistä heikentynyt ihon läpäisyesteen toiminta ja ihon atooppinen tulehdus eli inflammaatio. Terve ihon läpäisyeste estää veden haihtumista ja bakteerien, ärsyttävien aineiden ja allergeenien pääsyä elimistöön. Filaggriini on yksi tärkeimmistä ihon läpäisyesteen proteiineista ja mutaatiot sitä koodaavassa geenissä ovat tärkein atooppiselle ihottumalle altistava tekijä useimmissa väestöissä. Ympäristötekijöillä sekä geenien ja ympäristön vuorovaikutuksella on kuitenkin myös tärkeä merkitys. Aikuisiän atooppista ihottumaa on tutkittu vain vähän. Atooppisen ihottuman taudinkuva vaihtelee iästä riippuen. Aikuisiällä siihen liittyy usein silmäoireita, joiden hoitona käytetään usein pimekrolimuusi- ja takrolimuusivoiteita. Tutkimme filaggriinigeenin mutaatioiden vaikutusta atooppisen ihottuman riskiin suomalaisilla ja selvitimme ennustavatko nämä ja atoopikoilla usein koholla oleva kokonais-IgE (immunoglobuliiini E) pitkäaikaishoitovastetta. Keräsimme myös uutta tietoa pimekrolimuusin ja takrolimuusin silmäturvallisuudesta, josta aiemmin on ollut melko vähän julkaistua tietoa. Selvitimme atooppisen ihottuman esiintyvyyttä suomalaisilla aikuisilla ja arvioimme ympäristötekijöiden ja elämäntapojen vaikutusta ihottumariskiin. Tutkimuksessa hyödynnettiin Terveys 2000 –tutkimuksen suomalaista yli 30-vuotiasta väestöä edustavaa 8 028 henkilön aineistoa sekä 501 ihoatoopikon ja 338 silmäatoopikon aineistoja Helsingin Iho- ja allergiasairaalasta. Tulostemme mukaan filaggriinimutaatiot lisäävät atooppisen ihottuman riskiä myös suomalaisessa väestössä ja suurentavat lisäksi astmariskiä ihottumapotilailla. Ne eivät kuitenkaan vaikuta pitkäaikaishoitotuloksiin. Korkea kokonais-IgE oli yhteydessä huonompaan pitkäaikaisennusteeseen. Takrolimuusi ja pimekrolimuusi ovat turvallisia atooppisia silmäoireita sairastavien hoidossa; pitkäaikaishaittoja ei havaittu. Takrolimuusin siedettävyys ja teho vaikuttivat pimekrolimuusia paremmilta. Tupakointi ja naissukupuoli ovat yhteydessä kohonneeseen ihottumariskiin 30-50-vuotiailla ja myös ex-tupakoijilla vaikuttaisi olevan enemmän atooppista ihottumaa. Tutkimushenkilöiden vanhempien korkea koulutustaso suurensi ihottumariskiä. Ylipaino, D-vitamiinitasot, elinympäristö, sisarusten lukumäärä, alkoholin ja liikuntatottumukset eivät vaikuttaneet riskiin. Aikuisiän atooppisen ihottuman esiinty¬vyys on Suomessa maailman korkeimpia tehden siitä merkittävän kansanterveydellisen ongelman: elämänaikainen esiintyvyys oli yli 30-vuotiailla suomalaisilla 22% ja 10% oli kärsinyt aktiivisesta atooppisesta ihottumasta viimeisen vuoden aikana.