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Background: Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease with different clinical phenotypes based on factors such as age, race, comorbidities, and clinical signs and symptoms. The effect of these factors on therapeutic responses in AD has only been scarcely studied and not for upadacitinib. Currently, there is no biomarker predicting response to upadacitinib. Objectives: Evaluate the efficacy of the oral Janus kinase inhibitor upadacitinib across patient subgroups (baseline demographics, disease characteristics and prior treatment) in patients with moderate‐to‐severe AD. Methods: Data from phase 3 studies (Measure Up 1, Measure Up 2 and AD Up) were utilized for this post hoc analysis. Adults and adolescents with moderate‐to‐severe AD were randomized to receive once daily oral upadacitinib 15 mg, upadacitinib 30 mg or placebo; patients enrolled in the AD Up study received concomitant topical corticosteroids. Data from the Measure Up 1 and Measure Up 2 studies were integrated. Results: A total of 2584 patients were randomized. A consistently greater proportion of patients achieved at least 75% improvement in the Eczema Area and Severity Index, a 0 or 1 on the validated Investigator Global Assessment for Atopic Dermatitis, and improvement in itch (including an achievement of a reduction of ≥4; and score of 0/1 in Worst Pruritus Numerical Rating Scale) with upadacitinib compared with placebo at Week 16, regardless of age, sex, race, body mass index, AD severity, body surface area involvement, history of atopic comorbidities or asthma, or previous exposure to systemic therapy or cyclosporin. Conclusions: Upadacitinib had consistently high skin clearance rates and itch efficacy across subgroups of patients with moderate‐to‐severe AD through Week 16. These results support upadacitinib as a suitable treatment option in a variety of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2) and NCT03568318 (AD Up). [ABSTRACT FROM AUTHOR]

With the increasing number of options for the treatment of moderate‐to‐severe atopic dermatitis, clinicians need guidance on a practical approach to selecting a systemic agent for specific patient populations. We convened an expert panel consisting of 12 members to conduct a literature review and summarize relevant data related to six scenarios of clinical interest: comorbid asthma, ocular surface disease, history of cancer, past and ongoing infections of interest (including herpes simplex virus, herpes zoster, hepatitis B, and tuberculosis), pregnancy and lactation, and the elderly. We performed a literature search and examined each clinical scenario with respect to three major categories of available systemic agents: traditional systemics (azathioprine, cyclosporine A, methotrexate, and mycophenolate mofetil), Janus kinase inhibitors (abrocitinib, baricitinib, and upadacitinib), and biologics (dupilumab, lebrikizumab, and tralokinumab). The expert panel and steering committee met virtually to review the data and discuss the drafted consensus statements. A modified Delphi process was used to arrive at a set of final consensus statements related to the systemic treatment of AD in these specific patient populations. To provide practical guidance on the choice of systemic therapy for atopic dermatitis in these six topics of clinical interest, 25 expert consensus statements and a summary of the supporting data are presented herein. [ABSTRACT FROM AUTHOR]

Background: Limited data are available on long‐term efficacy and safety of biologics in patients with psoriasis and metabolic syndrome (MetS), a common comorbidity. Objectives: This analysis updates tildrakizumab efficacy and safety for up to 5 years in patients with and without MetS. Methods: This was a post hoc analysis of the double‐blind, randomized, placebo‐controlled, phase 3 reSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754) trials in adult patients with moderate to severe chronic plaque psoriasis. Analyses included data through Week 244 from patients who continuously received tildrakizumab 100 (TIL100) or 200 mg (TIL200) and entered the extension studies, stratified by baseline MetS status. Efficacy was assessed via Psoriasis Area and Severity Index (PASI) scores. Safety was evaluated from exposure‐adjusted incidence rates (EAIRs) of treatment‐emergent adverse events (TEAEs). Results: reSURFACE 1 and reSURFACE 2 analyses included 26 and 44 TIL100‐treated patients with MetS, 98 and 167 TIL100‐treated patients without MetS, 34 and 30 TIL200‐treated patients with MetS, and 111 and 130 TIL200‐treated patients without MetS, respectively. There were no clinically relevant differences in PASI 75/90/100 response rates at Week 244 between patients with vs without MetS. The proportion of patients with vs without MetS achieving absolute PASI score <3 at Week 244 was 53.8% vs 69.4% and 77.3% vs 80.8% in reSURFACE 1 and 2, respectively, for TIL100‐treated patients and 58.8% vs 72.1% and 63.3% vs 72.3%, respectively, for TIL200‐treated patients. In both studies, median reduction from baseline PASI score at all time points in patients with vs without MetS was >83% vs >89% for TIL100 and >85% vs >90% for TIL200. Pooled EAIRs of TEAEs, serious TEAEs, and TEAEs of special interest were similar in patients with and without MetS. Conclusions: Tildrakizumab maintains efficacy and a favorable safety profile over 5 years in patients with psoriasis regardless of MetS status. [ABSTRACT FROM AUTHOR]

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

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

Hundred percent of patients who had no response to CA received three or fewer treatments and 72% received a concomitant therapy. Patient baseline characteristics, lesion location, number/quantity of CA dosages, concomitant therapies, adverse events and CA response were extracted. Most patients (81.3%) received a concomitant treatment, often cryotherapy (43.8%), with or without an adjunctive topical therapy for home application. [Extracted from the article]

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

In addition, two patients used concomitant methotrexate for psoriatic arthritis and one concomitant alitretinoin for persistent palmoplantar involvement. A sub-analysis of 24 patients who had been on risankizumab for 12 months or greater revealed 46% of these patients had an IGA of 0, 37% IGA 1 and 17% IGA 2 (Fig. While most patients used 150 mg risankizumab every 12 weeks after the loading period, four had their frequency increased to every 8 weeks, one to every 6 weeks and one patient extended frequency to every 16 weeks. [Extracted from the article]

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

Coronavirus disease 2019 (COVID‐19) is caused by SARS‐CoV‐2, a novel RNA virus that was declared a global pandemic on 11 March 2020. The efficiency of infection with SARS‐CoV‐2 is reflected by its rapid global spread. The SARS‐CoV‐2 pandemic has implications for patients with inflammatory skin diseases on systemic immunotherapy who may be at increased risk of infection or more severe infection. This position paper is a focused examination of current evidence considering the mechanisms of action of immunotherapeutic drugs in relation to immune response to SARS‐CoV‐2. We aim to provide practical guidance for dermatologists managing patients with inflammatory skin conditions on systemic therapies during the current pandemic and beyond. Considering the limited and rapidly evolving evidence, mechanisms of action of therapies, and current knowledge of SARS‐CoV‐2 infection, we propose that systemic immunotherapy can be continued, with special considerations for at risk patients or those presenting with symptoms. [ABSTRACT FROM AUTHOR]

Background: Janus kinase (JAK) inhibition is a new mode of action in atopic dermatitis (AD); clarity about drug class safety considerations in the context of AD is important. Baricitinib, an oral, reversible, selective inhibitor of JAK1/JAK2, is in late‐stage development for adult patients with moderate‐to‐severe AD. Objective: To report pooled safety data for baricitinib in patients with moderate‐to‐severe AD in the clinical development program including long‐term extension (LTE) studies. Methods: This analysis included patient‐level safety data from six double‐blinded, randomized, placebo‐controlled studies (one phase 2 and five phase 3), one double‐blinded, randomized, LTE study and one open‐label LTE study, reported in three data sets: placebo‐controlled, 2‐mg – 4‐mg extended and All‐bari AD. Safety outcomes include treatment‐emergent adverse events, adverse events of special interest and abnormal laboratory changes. Proportions of patients with events and incidence rates were calculated. Results: Data were collected for 2531 patients who were given baricitinib for 2247 patient‐years (median duration 310 days). The frequency of serious infections, opportunistic infections and conjunctival disorders was low and similar between treatment groups in the placebo‐controlled period. The most common serious infections were eczema herpeticum [n = 11, incidence rates (IR) = 0.5], cellulitis (n = 6, IR = 0.3) and pneumonia (n = 3, IR = 0.1). There were four opportunistic infections (IR = 0.2). No malignancies, gastrointestinal perforations, positively adjudicated cardiovascular events or tuberculosis were reported in the placebo‐controlled period in baricitinib‐treated patients. Frequency of herpes simplex was higher in the 4‐mg group (6.1%) vs. the 2‐mg (3.6%) and placebo group (2.7%); IRs in the extended data set (2‐mg IR = 9.6; 4‐mg IR = 14.5) were lower vs. the placebo‐controlled data set (2‐mg IR = 12.4; 4‐mg IR = 21.3). In the All‐bari AD data set, there were two positively adjudicated major adverse cardiovascular events (2‐mg group): two venous thrombosis events (4‐mg group) and one death. Conclusion: This integrated safety analysis in patients with moderate‐to‐severe AD confirms the established safety profile of baricitinib. [ABSTRACT FROM AUTHOR]

Background: Patients treated with tumour necrosis factor (TNF) inhibitors are at risk of new‐onset tuberculosis (TB) or reactivation of latent tuberculosis infection (LTBI). Association between TB/LTBI and interleukin (IL)‐23 inhibitors for psoriasis is unclear. Patients with LTBI typically initiate LTBI therapy before receiving biologics. Objectives: Safety in moderate‐to‐severe psoriasis patients with LTBI treated with guselkumab (IL‐23 inhibitor) and LTBI treatment was evaluated. Methods: In the VOYAGE 1 & VOYAGE 2 studies, patients screened for LTBI were randomized to guselkumab, placebo, or adalimumab (TNF inhibitor) at baseline. Placebo → guselkumab crossover occurred at week 16 and adalimumab → guselkumab at week 52 (VOYAGE 1), or at week 28 or later (VOYAGE 2). Incidence of active TB, adverse events (AEs), serious AEs (SAEs), and markedly abnormal liver function tests [alanine aminotransferase test (ALT); aspartate aminotransferase test (AST)] were evaluated using pooled data through week 100 in guselkumab‐treated patients receiving and not receiving LTBI treatment. Results: At baseline, 130 randomized patients (guselkumab: n = 69; adalimumab: n = 36; placebo: n = 25) tested positive for LTBI and received concomitant LTBI treatments (LTBI+). No active TB was reported among guselkumab‐treated patients without LTBI (LTBI−) through week 100. Two cases of active TB occurred in LTBI− patients treated with adalimumab. Through week 16, across all treatment groups, greater proportions of LTBI+ patients reported ALT and AST elevations compared with LTBI− patients. Through week 100, proportions of patients experiencing AEs and SAEs were comparable between LTBI+ and LTBI− patients. Conclusions: No cases of active TB, including reactivation of LTBI, were reported in patients with or without LTBI treated with guselkumab through up to 2 years. LTBI treatment was effective across all treatment groups in preventing reactivation of LTBI. Long‐term treatment with guselkumab was generally well‐tolerated through up to 2 years in patients receiving LTBI medications. [ABSTRACT FROM AUTHOR]

Summary: Background: Long‐term efficacy and safety of ixekizumab [160 mg at week 0, then 80 mg every 2 weeks (Q2W) for 12 weeks, followed by every 4 weeks (Q4W) thereafter (i.e. Q2W/Q4W), which is the labelled psoriasis dosing where approved, except in Japan] have been established for the treatment of adults with moderate‐to‐severe plaque psoriasis. However, some patients may benefit from remaining on Q2W dosing beyond 12 weeks. Methods: Among patients who had static Physician's Global Assessment (sPGA) > 1 at week 12, efficacy through week 52 of continuous Q2W dosing in the IXORA‐P study was compared indirectly with Q2W/Q4W in the integrated data from the UNCOVER‐1, UNCOVER‐2 and UNCOVER‐3 studies. The continuous Q4W dose group, which had comparable results across studies, was used as the common comparator. Results: In the IXORA‐P study, among patients with sPGA > 1 at week 12, 64% of patients in the continuous Q2W group achieved sPGA ≤ 1 at week 52, which was statistically significantly higher than the 36% of patients with sPGA > 1 in the Q2W/Q4W group based on the integrated data from the UNCOVER studies (P = 0·0007). There were no clinically meaningful differences in frequencies of safety events between patients with sPGA ≤ 1 and patients with sPGA > 1 at week 12 in the IXORA‐P study. Conclusions: Among patients who did not have clear or almost clear skin at week 12, nearly 30% more patients who were treated continuously with ixekizumab Q2W in IXORA‐P had clear or almost clear skin at week 52 when compared indirectly with those who were treated using the labelled psoriasis dosing in integrated UNCOVER studies. What's already known about this topic? Most patients with moderate‐to‐severe psoriasis who were given the labelled psoriasis dosing of ixekizumab [160‐mg loading dose at week 0, 80 mg every 2 weeks (Q2W) through week 12, and 80 mg every 4 weeks (QW4) thereafter] respond quickly with a high percentage of skin clearance.Additionally, patients who achieve static Physician's Global Assessment (sPGA) ≤ 1 by week 12 tend to maintain this response, even after switching to Q4W. What does this study add? Here, we assessed whether patients with sPGA > 1 at week 12 benefited from receiving more frequent dosing beyond the first 12 weeks.The results showed that Q2W dosing beyond 12 weeks resulted in more patients achieving sPGA ≤ 1 by week 52 than the labelled psoriasis dosing among patients with sPGA > 1 at week 12. Linked Comment: Kim. Br J Dermatol 2020; 183:6. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Summary: Background: Chronic psoriasis may require medication adjustments over time. Objectives: To evaluate the efficacy/safety of tildrakizumab in subgroups from the reSURFACE studies (N = 1862) that received continuous dosing, higher/lower dosing, treatment interruption/reinitiation and initiation. Methods: Responders [Psoriasis Area and Severity Index (PASI) ≥ 75%] and partial responders (PASI ≥ 50% to < 75%) in Part 3 of the reSURFACE studies (weeks 28–52 or week 64) who received tildrakizumab 200 mg or 100 mg were rerandomized to the same dosage (T100/T100 or T200/T200), a higher/lower dosage (T100/T200 or T200/T100) or placebo (PBO) (T100/PBO or T200/PBO). Patients receiving PBO who relapsed were reinitiated to tildrakizumab. Etanercept (ETN) week‐28 partial responders and nonresponders (PASI < 50%) received tildrakizumab 200 mg (ETN/T200). Results: Among T100/T100 and T200/T200 week‐28 partial responders, the proportion of patients who achieved as‐observed PASI 75 responses increased over time. Among T100/T200 week‐28 partial responders, PASI 75 responses increased from week 32 (38·5%) to week 52 (63·2%) and remained consistent in T200/T100 week‐28 responders. Among patients who relapsed in the T100/PBO and T200/PBO groups, 86% and 83% of those who reinitiated tildrakizumab achieved PASI 75 by week 64, respectively. Among ETN/T200 week‐28 partial responders, PASI 75 responses (nonresponder imputation) increased from week 32 (24·1%) to week 52 (74·7%). PASI 90, PASI 100 and Physician's Global Assessment responses were consistent with PASI 75 results. Treatment was well tolerated. Conclusions: Patients generally fared well with tildrakizumab maintenance, reinitiation, dose adjustment or initiation. What's already known about this topic? Tildrakizumab demonstrated significant efficacy vs. placebo with a positive safety profile during the first 28 weeks of treatment in two randomized double‐blind trials. What does this study add? Treatment scenarios with tildrakizumab, such as long‐term continuous dosing (up to 64 weeks), treatment interruption/reinitiation and switching from another biologic, can be part of the management of plaque psoriasis with a reasonable expectation of efficacy and tolerability. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

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

Background: Efficacy of tildrakizumab for plaque psoriasis was demonstrated in randomized, placebo‐controlled trials. Objective: To consolidate tildrakizumab efficacy results by pooling data. Methods: Data (N = 2081) from tildrakizumab 100 mg, tildrakizumab 200 mg and placebo groups in three trials were pooled. Results: Proportions of Psoriasis Area and Severity Index (PASI) 75 responders at week 12 were better with tildrakizumab 100 mg (62.3%) and tildrakizumab 200 mg (64.8%) vs. placebo (5.6%; P < 0.0001) and for PASI 90, PASI 100 and Physician's Global Assessment (PGA) 'clear' or 'minimal' vs. placebo (P < 0.0001). Responses increased from weeks 12 to 28. Week 12 PASI and PGA responses to tildrakizumab vs. placebo were numerically greater in patients with lower vs. higher bodyweight and were better with tildrakizumab 200 mg than tildrakizumab 100 mg for patients with higher bodyweight. Week 12 PASI 75 responses vs. placebo with tildrakizumab 100 mg were similar between patients with (55.0%) or without (56.7%) prior biologics. PASI 90, PASI 100 and PGA responses were generally higher in patients without prior biologics. Week 8 PASI 50 response predicted PASI 90 response. Conclusion: Pooled data confirmed the efficacy of tildrakizumab for moderate‐to‐severe plaque psoriasis. [ABSTRACT FROM AUTHOR]

Summary: Background: The relevance of granulocyte–macrophage colony‐stimulating factor (GM‐CSF) in the management of psoriasis has not been studied previously. GM‐CSF is important in the initiation and maintenance of chronic inflammatory processes. Objectives: To investigate the clinical use of GM‐CSF neutralization by evaluating the efficacy and safety of namilumab (AMG203), a monoclonal antibody GM‐CSF inhibitor, in patients with moderate‐to‐severe plaque psoriasis. Methods: A phase II, multicentre, randomized, double‐blind, placebo‐controlled, parallel‐group, dose‐finding, proof‐of‐concept study (NEPTUNE) was conducted. Four doses of namilumab (20, 50, 80 and 150 mg, via subcutaneous injection) were compared with placebo. Assessment of the primary end point – the proportion of patients achieving ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75 treatment response) – was performed at week 12. Exploratory investigation at the tissue level was conducted in a subset of the overall study population. The trial was registered with the number NCT02129777. Results: In total, 122 patients were enrolled and 106 (86·9%) completed the double‐blind treatment; 16 (13·1%) prematurely discontinued study medication. Serum concentration–time profiles were as expected for subcutaneous delivery of an IgG1 monoclonal antibody, and exposure increased proportionally with dose elevation. The number of patients showing PASI 75 treatment response at week 12 was low in all groups; no significant difference was recorded in this end point between placebo and any namilumab group. Similar outcomes were recorded for other clinical study end points. Moreover, no significant treatment‐related changes from baseline were observed in laboratory investigations of cell types or subpopulations, or cytokines relevant to inflammatory pathways in psoriasis. Conclusions: GM‐CSF blockade is not critical for suppression of key inflammatory pathways underlying psoriasis. What's already known about this topic? Blockade of granulocyte–macrophage colony‐stimulating factor (GM‐CSF) signalling is effective in rheumatoid arthritis.Potential relevance for psoriasis has been indicated by the presence of GM‐CSF in psoriasis‐related skin blister fluid and the serum of patients with psoriasis, and also by elevated expression in psoriatic skin lesions. What does this study add? This is the first clinical investigation into the efficacy and safety of an anti‐GM‐CSF antibody in plaque psoriasis.This study provides no evidence of benefit for GM‐CSF neutralization in the treatment of plaque psoriasis.Safety profiles were comparable in the placebo and anti‐GM‐CSF treatment groups, and no incidences of pulmonary alveolar proteinosis or clinically significant changes in lung function were recorded throughout the short‐term duration of study treatment.Overall, the findings point to key differences in the role of GM‐CSF in the pathogeneses of psoriasis and rheumatoid arthritis. Linked Comment: Crowley. Br J Dermatol 2019; 180:1286–1287. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Summary: Background: Short‐term interleukin‐23p19 inhibition by tildrakizumab improves plaque psoriasis and appears to be well tolerated. Objectives: Safety and tolerability were assessed for up to 64 weeks of tildrakizumab therapy using pooled data from three randomized controlled trials for moderate‐to‐severe psoriasis. Methods: Data pools for the placebo‐controlled (up to 16 weeks) and full trial periods (up to 64 weeks) were analysed (n = 2081). Results: In the placebo‐controlled period, frequencies of treatment‐emergent adverse events (TEAEs; range 47·9–54·0%), serious TEAEs (range 1·4–2·3%), discontinuations due to AEs (range 0·6–1·9%), major adverse cardiovascular events (MACEs; range 0·0–0·1%) and severe infections (range 0·0–0·3%) were comparable between tildrakizumab 100 mg, tildrakizumab 200 mg, placebo and etanercept. In the full trial period, exposure‐adjusted rates (patients per 100 patient‐years) for TEAEs, serious TEAEs and discontinuations due to AEs with tildrakizumab 100 mg and 200 mg were lower than or comparable with the placebo rates, and lower than with etanercept. Exposure‐adjusted rates of MACEs (range 0·0–0·5) and severe infections (range 0·9–2·0) were comparable among groups. No TEAEs of inflammatory bowel disease or suicide were reported. Candida skin infections were infrequent at frequencies of 0·1%, 0·3%, 0·0% and 0·0% for the tildrakizumab 100 mg, tildrakizumab 200 mg, placebo and etanercept groups, respectively, in the placebo‐controlled period, and exposure‐adjusted rates of 0·2, 0·7, 0·0 and 0·0, respectively, in the full trial period. Oral candidiasis was also infrequent. Conclusions: Up to 64 weeks of tildrakizumab was well tolerated, with low rates of serious TEAEs, discontinuations due to AEs, and AEs of clinical interest. [ABSTRACT FROM AUTHOR]

Abstract: Insights into the pathophysiology of autoimmune inflammatory diseases including psoriasis have advanced considerably in recent years, and in parallel, so too have the available treatment options. Current clinical paradigms for the treatment of psoriasis have evolved to include targeted biologic therapies, starting with tumour necrosis factor‐alpha (TNF‐α) inhibitors and later, agents targeting interleukin (IL)‐12/23 and IL‐17. The most recent evidence suggests that IL‐23 might be an even more potent target for the effective treatment of psoriasis and other autoimmune inflammatory disorders. This review will describe recent developments leading to the current understanding of the key role of IL‐23 as a ‘master regulator’ of autoimmune inflammation and the clinical evidence for agents that specifically target this modulator in the context of treating psoriasis, spondyloarthropathy and inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Summary: Background: Ixekizumab is an interleukin‐17A antagonist approved for treatment of moderate‐to‐severe plaque psoriasis with a recommended 160‐mg starting dose, then 80 mg every 2 weeks (Q2W) to week 12, and every 4 weeks (Q4W) thereafter. Objective: To evaluate continuous Q2W dosing over 52 weeks. Methods: In this phase III, multicentre, double‐blinded, parallel‐group trial, three ixekizumab dosing regimens were assessed for efficacy and safety at week 52 in patients with moderate‐to‐severe plaque psoriasis randomized at a 2 : 1 : 1 ratio to continuous Q2W (n = 611), continuous Q4W (n = 310) or dose adjustment per protocol (Q4W/Q2W, n = 306), each with a 160‐mg starting dose. Dose adjustment was determined by predefined criteria to which investigators were blinded; 72 (23?5%) patients in the Q4W/Q2W group adjusted dose. Efficacy outcomes were evaluated using logistic regression. Results: Co‐primary end points were met at week 52: Psoriasis Area and Severity Index 75 responses for Q2W and Q4W dose groups were 85·9% and 79·0%, respectively (P = 0·006), and static patient global assessment 0/1 responses for Q2W and Q4W dose groups were 78·6% and 70·6%, respectively (P = 0·005). Treatment‐emergent and serious adverse events were comparable across dose groups. Conclusions: Ixekizumab Q2W had higher efficacy at week 52 than ixekizumab Q4W, with no increase in safety events. [ABSTRACT FROM AUTHOR]

Abstract: Background: Apremilast, an oral phosphodiesterase‐4 inhibitor, has demonstrated efficacy in patients with moderate to severe psoriasis. Objective: To evaluate long‐term efficacy and safety of apremilast in biologic‐naive patients with moderate to severe plaque psoriasis and safety of switching from etanercept to apremilast in the phase 3b LIBERATE trial. Methods: Two hundred fifty patients were randomized to placebo, apremilast 30 mg BID or etanercept 50 mg QW through Week 16; thereafter, all patients continued or switched to apremilast through Week 104 (extension phase). Skin, scalp and nail involvement at Weeks 16, 52 and 104 were assessed using the Psoriasis Area and Severity Index (PASI; 0–72), Scalp Physician Global Assessment (ScPGA; 0–5) and Nail Psoriasis Severity Index (NAPSI; 0–8); patient‐reported outcomes (PROs) were assessed using the Dermatology Life Quality Index (DLQI; 0–32) and pruritus visual analog scale (VAS; 0–100 mm). Results: The apremilast‐extension phase (Weeks 16–104) included 226 patients in the placebo/apremilast (n = 73), apremilast/apremilast (n = 74) and etanercept/apremilast (n = 79) groups, and at Week 104, 50.7%, 45.9% and 51.9% of these patients, respectively, maintained ≥75% reduction from baseline in PASI score (based on last‐observation‐carried‐forward analysis). Across treatment groups, ScPGA 0 (clear) or 1 (minimal) was achieved by 50.0%–59.2% of patients; NAPSI mean change from baseline was −48.1% to −51.1%; DLQI score ≤5 was achieved by 66.0%–72.5% of patients; and pruritus VAS mean change from baseline was −24.4 to −32.3. AEs in ≥5% of patients (diarrhoea, nausea, nasopharyngitis, upper respiratory tract infection and headache) did not increase with prolonged apremilast exposure. Conclusions: Apremilast demonstrated significant and sustained improvements in skin, scalp, nails and PROs (pruritus and quality of life) over 104 weeks in patients with moderate to severe plaque psoriasis. Safety was consistent with the known safety profile of apremilast. [ABSTRACT FROM AUTHOR]

Abstract: Background: Palmoplantar psoriasis is a variant of psoriasis vulgaris which can severely impair quality of life. Objectives: The main objectives of this double‐blind, placebo‐controlled, randomized study were to assess the efficacy and impact on quality of life and work productivity of apremilast for the treatment of moderate‐to‐severe palmoplantar psoriasis. Methods: A total of 100 patients with moderate‐to‐severe palmoplantar psoriasis were randomized to either apremilast 30 mg bid or placebo for 16 weeks. At Week 16, all patients received apremilast 30 mg bid until Week 32. The primary endpoint was the proportion of patients who achieved a Palmoplantar Psoriasis Physician Global Assessment (PPPGA) of 0/1 at Week 16. Results: There was no significant difference in the proportion of patients who achieved a PPPGA of 0/1 at Week 16 between patients randomized to apremilast (14%) and placebo (4%; P = 0.1595). After 32 weeks of treatment with apremilast, 24% of patients achieved a PPGA of 0/1. In addition, apremilast was superior to placebo in achieving Palmoplantar Psoriasis Area Severity Index (PPPASI) 75 (apremilast: 22%; placebo: 8%; P = 0.0499), in improving PPPASI (apremilast: −7.4 ± 7.1; placebo: −3.6 ± 5.9; P = 0.0167), Dermatology Life Quality Index score (apremilast: −4.3 ± 5.1; placebo: −0.8 ± 4.5; P = 0.0004) and in reducing activity impairment (apremilast: −11.0 ± 22.3; placebo: 2.5 ± 25.5; P = 0.0063). Conclusion: Despite the absence of a significant difference between apremilast and placebo in proportion of patients achieving a PPPGA of 0/1, the presence of significant differences observed for several secondary endpoints suggests that apremilast may have a role in the treatment of moderate‐to‐severe palmoplantar psoriasis. [ABSTRACT FROM AUTHOR]

Summary: Background: ABP 501, a U.S.A. Food and Drug Administration‐ and European Medicines Agency‐approved biosimilar, is highly similar to adalimumab in structure, function and pharmacokinetics. Objectives: To demonstrate similarity in efficacy, safety and immunogenicity of ABP 501 vs. adalimumab for moderate‐to‐severe plaque psoriasis (clinical trial: NCT01970488). Methods: Patients were randomized (1 : 1) to receive ABP 501 or adalimumab 40 mg every 2 weeks for 16 weeks. At week 16, patients with ≥ 50% improvement from baseline in Psoriasis Area and Severity Index (PASI) score were eligible to continue to week 52. Patients receiving ABP 501 continued; adalimumab patients were rerandomized (1 : 1) to continue adalimumab or undergo a single transition to ABP 501. Key efficacy assessments included percentage PASI improvement from baseline, PASI responders and mean change in affected body surface area from baseline to weeks 16, 32 and 50. Safety was monitored via adverse events (AEs) and antidrug antibodies (ADAs) were assessed. Results: A total of 308 patients were rerandomized at week 16 (ABP 501/ABP 501, n = 152; adalimumab/adalimumab, n = 79; adalimumab/ABP 501, n = 77). PASI percentage improvements from baseline were similar across groups for weeks 16, 32 and 50 (range: 85·8–88·2%), with no significant differences detected across groups in percentages of PASI 50, 75, 90 and 100 responders. Changes from baseline in percentage body surface area affected were similar across groups and time points. No new safety signals were detected. AEs were balanced between groups. Percentages of patients with binding and neutralizing ADAs were similar across treatments. Conclusions: ABP 501 and adalimumab have similar clinical efficacy, safety and immunogenicity profiles over 52 weeks, including after single transition, in this patient population. [ABSTRACT FROM AUTHOR]

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

Background Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, has demonstrated efficacy in patients with moderate-to-severe psoriasis. Objective Evaluate efficacy and safety of apremilast vs. placebo in biologic-naive patients with moderate-to-severe plaque psoriasis and safety of switching from etanercept to apremilast in a phase IIIb, randomized, double-blind, placebo-controlled study ( NCT01690299). Methods Two hundred and fifty patients were randomized to placebo ( n = 84), apremilast 30 mg BID ( n = 83) or etanercept 50 mg QW ( n = 83) through Week 16; thereafter, all patients continued or switched to apremilast through Week 104. The primary efficacy endpoint was achievement of PASI-75 at Week 16 with apremilast vs. placebo. Secondary endpoints included achievement of PASI-75 at Week 16 with etanercept vs. placebo and improvements in other clinical endpoints vs. placebo at Week 16. Outcomes were assessed through Week 52. This study was not designed for apremilast vs. etanercept comparisons. Results At Week 16, PASI-75 achievement was greater with apremilast (39.8%) vs. placebo (11.9%; P < 0.0001); 48.2% of patients achieved PASI-75 with etanercept ( P < 0.0001 vs. placebo). PASI-75 response was maintained in 47.3% (apremilast/apremilast), 49.4% (etanercept/apremilast) and 47.9% (placebo/apremilast) of patients at Week 52. Most common adverse events (≥5%) with apremilast, including nausea, diarrhoea, upper respiratory tract infection, nasopharyngitis, tension headache and headache, were mild or moderate in severity; diarrhoea and nausea generally resolved in the first month. No new safety or tolerability issues were observed through Week 52 with apremilast. Conclusion Apremilast demonstrated significant efficacy vs. placebo at Week 16 in biologic-naive patients with psoriasis, which was sustained over 52 weeks, and demonstrated safety consistent with the known safety profile of apremilast. Switching from etanercept to apremilast did not result in any new or clinically significant safety findings, and efficacy was maintained with apremilast through Week 52. [ABSTRACT FROM AUTHOR]

All adverse events (AEs) were reviewed; exposure-adjusted incidence rates (number of events/100 patient-years) of serious GI AEs and cases of new onset or exacerbations of pre-existing IBD were compared across treatment groups. In total, seven patients had a history of IBD: three patients had ulcerative colitis, 1 in each of the tildrakizumab and placebo groups; two patients had Crohn's disease, both from the tildrakizumab 200-mg group; and two patients had IBD (unclassified), both from the tildrakizumab 100-mg group. Serious GI AEs were infrequent and observed in one patient (0.46/100 patient-years) who received placebo, eight patients (0.80/100 patient-years) who received tildrakizumab 100 mg and four patients (0.43/100 patient-years) who received tildrakizumab 200 mg. [Extracted from the article]

Background Despite unmet need, 15 years have passed since a topical therapy with a new mechanism of action for atopic dermatitis ( AD) has been approved. Janus kinase ( JAK) inhibitor treatment effect via topical application in patients with AD is unknown. Objectives Tofacitinib, a small-molecule JAK inhibitor, was investigated for the topical treatment of AD. Methods In this 4-week, phase IIa, randomized, double-blind, vehicle-controlled study ( NCT02001181), 69 adults with mild-to-moderate AD were randomized 1:1 to 2% tofacitinib or vehicle ointment twice daily. Percentage change from baseline ( CFB) in Eczema Area and Severity Index ( EASI) score at week 4 was the primary end point. Secondary efficacy end points included percentage CFB in body surface area ( BSA), CFB in EASI Clinical Signs Severity Sum Score, proportion of patients with Physician's Global Assessment ( PGA) response and CFB in patient-reported pruritus. Safety, local tolerability and pharmacokinetics were monitored. Results The mean percentage CFB at week 4 in EASI score was significantly greater ( P < 0·001) for tofacitinib (−81·7%) vs. vehicle (−29·9%). Patients treated with tofacitinib showed significant ( P < 0·001) improvements vs. vehicle across all prespecified efficacy end points and for pruritus at week 4. Significant improvements in EASI, PGA and BSA were observed by week 1 and improvements in pruritus were observed by day 2. Safety/local tolerability were generally similar for both treatments, although more adverse events were observed for vehicle vs. tofacitinib. Conclusions Tofacitinib ointment showed significantly greater efficacy vs. vehicle across end points, with early onset of effect and comparable safety/local tolerability to vehicle. JAK inhibition through topical delivery is potentially a promising therapeutic target for AD. [ABSTRACT FROM AUTHOR]

Background Drug survival is a marker for treatment sustainability in chronic diseases such as psoriasis. Objective The aim of these analyses was to assess survival of biologic treatments in the PSOriasis Longitudinal Assessment and Registry ( PSOLAR). Methods PSOLAR is a large, prospective, international, disease-based registry of patients with psoriasis receiving (or eligible for) systemic therapy in a real-world setting. Drug survival is defined as the time from initiation to discontinuation (stop/switch) of biologic therapy on registry. The number of patients who discontinued each treatment and the duration of therapy were recorded. Using Kaplan-Meier survival curves and Cox-regression analyses [hazard ratios ( HR) and 95% confidence intervals ( CIs)], time to discontinuation was compared across cohorts undergoing first-, second- or third-line treatment with ustekinumab, infliximab, adalimumab or etanercept. Results As of the 2013 data cut, 12 095 patients with psoriasis were enrolled in PSOLAR. Of the 4000 patients initiating any new biologic therapy, approximately 3500 started a first-line, second-line or third-line biologic therapy during the registry. Lack of effectiveness was the most common reason for discontinuation across biologic therapies. Based on the multivariate analysis, significantly shorter times to discontinuation were observed for infliximab [ HR (95% CI) = 2.73 (1.48 -5.04), P = 0.0014]; adalimumab [4.16 (2.80 -6.20), P < 0.0001]; and etanercept [4.91 (3.28 -7.35) P < 0.0001] compared with ustekinumab [reference treatment]) for first-line biologic use; results were similar for treatment effects for second/third-line therapies. Although limited in power, analyses in patients with concurrent psoriatic arthritis confirmed by a rheumatologist reflect observations in the overall psoriasis population. Conclusion Drug survival was superior for ustekinumab compared with infliximab, adalimumab and etanercept in patients with psoriasis. [ABSTRACT FROM AUTHOR]

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

Background Oral isotretinoin ( ISO) is the gold standard for severe nodular acne. However, as some patients are unwilling or unable to take, or are intolerant to, ISO, other options are needed. Objectives To compare efficacy and safety of oral ISO vs. doxycycline 200 mg plus adapalene 0·1%/benzoyl peroxide 2·5% gel (D+A/ BPO) in severe nodular acne over 20 weeks. Methods This was a multicentre, randomized, controlled, noninferiority investigator-blinded study involving 266 subjects. Results D+A/ BPO showed a significantly earlier onset of action in reducing nodules, papules/pustules and total lesions at week 2. ISO was superior in reducing nodules (95·6% vs. 88·7%), papules/pustules (95·2% vs. 79·6%) and total lesions (92·9% vs. 78·2%; all P < 0·01) at week 20. Half as many subjects for D+A/ BPO compared with ISO had treatment-related, medically relevant adverse events (33 events in 18·0% of subjects vs. 73 in 33·8% of subjects, respectively). D+A/ BPO was noninferior to ISO in the intent-to-treat population [95% confidence interval ( CI) −2·7 to 20·8 ( P = 0·13); 63·9% vs. 54·9% of subjects, respectively] and per-protocol population [95% CI 3·9-28·6 ( P = 0·01); 74·3% vs. 58% of subjects, respectively), based on the composite efficacy/safety end point. Conclusions D+A/ BPO showed a favourable composite efficacy/safety profile compared with ISO. This combination is an alternative to ISO in patients intolerant to, or unable or unwilling to take, oral ISO, and is an option for treatment of severe nodular acne. [ABSTRACT FROM AUTHOR]

Background Plaque psoriasis has a relatively high prevalence in adolescence, resulting in a significant impact on quality of life, including social interactions. Objectives The primary objective was to assess the safety of once-daily application of fixed-combination calcipotriol plus betamethasone dipropionate gel in adolescent scalp psoriasis. Assessment of efficacy was a secondary objective. Methods This phase II, multicentre, single-arm, open-label, 8-week trial included patients aged 12-17 years with moderate-to-very severe scalp psoriasis according to Investigator's Global Assessment ( IGA) (≥ 10% of the scalp area affected). Results Seventy-eight patients received treatment. Twenty-seven patients (35%) reported a total of 64 adverse events ( AEs); most were mild (33/64) or moderate (22/64) in severity and there were no serious AEs. No cases of hypercalcaemia were reported, and the mean changes from baseline to end of treatment in albumin-corrected serum calcium (0·00 mmol L−1), 24-h urinary calcium excretion (−0·03 mmol per 24 h) and urinary calcium-to-creatinine ratio (−0·12 mmol g−1) were not considered clinically relevant. At the end of treatment 66 patients (85%) were clear or almost clear according to IGA. There was an 80% improvement in mean Total Sign Score from baseline to end of treatment. In total, at the end of treatment, 87% of patients rated their scalp psoriasis as clear or very mild, and 75 (96%) had no or mild pruritus compared with 14 (18%) at baseline. Conclusions Once-daily calcipotriol plus betamethasone dipropionate gel is well tolerated and efficacious for scalp psoriasis in adolescents. [ABSTRACT FROM AUTHOR]

Summary: Tildrakizumab 是一种相当新型的药物,称为生物制剂,用于治疗中度至重度牛皮癣。这种药物可以防止体内一种与炎症有关的特定分子的活动,这种分子被称为细胞因子白细胞介素 (IL)‐23p19。 先前的研究表明,它优于安慰剂(一种非活性物质,像"糖丸"一样)和一种旧的生物制剂,即 TNF 抑制剂 Etanercept。然而,试验很少反映出现实世界的经历,患者可能会从一种药物换到另一种药物,改变药物剂量或中断治疗,例如因为感染而这样做。 作者(位于美国、加拿大和德国)回顾了两项研究的结果,一项是将两种不同剂量的 Tildrakizumab(每天 100 mg 或 200 mg)与安慰剂进行比较,另一项是将其与 Etanercept 进行比较,其中纳入总共 1862 名患有中度到重度斑块型银屑病的成年患者。 在研究过程中,重新随机分配治疗。他们发现,对 Tildrakizumab 的应答是持续的(这意味着它持续起作用),没有出现一些使用 Etanercept 的患者中出现的继发性失败(在最初满意的应答后对药物的应答性下降),并且在治疗中断后,重新使用药物仍能有效地控制银屑病。总体而言,该药物耐受性良好,这意味着其副作用很小。 本摘要涉及研究:在持续给药、治疗中断、剂量调整和从 Etanercept 转换过来的情况下 Tildrakizumab 治疗斑块型银屑病的有效性和安全性: 来自 III 期研究的结果。 Linked Article: Kimball et al. Br J Dermatol 2020; 182:1359–1368 [ABSTRACT FROM AUTHOR]

Summary: Tildrakizumab is a fairly new type of medicine called a biologic, used for the treatment of moderate‐to‐severe psoriasis. The drug prevents the action of a specific molecule in the body involved in inflammation, known as cytokine interleukin (IL)‐23p19. Previous studies have shown it to be superior to a placebo (an inactive substance, like a "sugar pill") and to an older biologic drug, the TNF inhibitor etanercept. However, trials rarely reflect real‐world experience, where patients may switch from one drug to another, change drug dosage or interrupt treatment, e.g. because of an infection. The authors, based in U.S.A., Canada and Germany, reviewed results from two studies, one comparing two different doses of tildrakizumab (100mg or 200mg per day) with placebo, and the other comparing it with etanercept, including a total of 1862 adults with moderate‐to‐severe plaque psoriasis. Treatments were re‐randomised during the course of the study. They found that the response to tildrakizumab was sustained (meaning it kept working), without the secondary failure (decreasing responsiveness to a drug after an initial satisfactory response) seen in some patients on etanercept, and the drug regained effective control of the psoriasis after treatment was interrupted. Overall the drug was well tolerated, meaning that side effects were minimal. This is a summary of the study: Efficacy and safety of tildrakizumab for plaque psoriasis with continuous dosing, treatment interruption, dose adjustments and switching from etanercept: results from phase III studies Linked Article: Kimball et al. Br J Dermatol 2020; 182:1359–1368 [ABSTRACT FROM AUTHOR]

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Summary: Psoriasis is a long‐lasting disease involving inflammation of the skin. In the most common form of this disease ‐ plaque psoriasis ‐ the inflammation is visible as raised, reddened and often scaly areas which may extend widely over the body. Although not generally a life‐threatening condition, psoriasis may increase the risk of other serious disorders (such as cardiovascular disease), and often leads to much reduced quality of life for patients ‐ through physical discomfort (itching, pain), disability, and related emotional trauma. Furthermore, psoriasis occurs worldwide (affecting up to 3% of the populations in various countries) and cannot be completely cured by available treatments. Together, these issues make the disease a serious global burden. Granulocyte‐Macrophage Colony‐Stimulating Factor (GM‐CSF) is made in the body and is important in controlling functions of the body's immune system and the processes involved in inflammation. Therefore, this study was carried out to establish whether blocking the activities of GM‐CSF in patients with moderate or severe plaque psoriasis could result in significant improvement of the disease. In total, 122 patients were enrolled from Canada, Denmark, Germany, Latvia and Poland. The patients were treated over 10 weeks either with namilumab (GM‐CSF blocker) or a placebo (inactive): assessments of their psoriasis were made during this period, and completed after an additional 2 weeks. Notably, throughout the 12‐week study duration no significant improvement was detected for namilumab‐treated patients ‐ in marked contrast to treatment benefit found in a similar study involving patients with rheumatoid arthritis. These findings point to different roles for GM‐CSF in the two diseases, and suggest that blocking GM‐CSF activity alone is not enough for effective treatment of plaque psoriasis. Linked Article: Papp et al. Br J Dermatol 2019; 180:1352–1360 [ABSTRACT FROM AUTHOR]