Summary
Background
Most patients with psoriasis have nail changes, and treating nail psoriasis is challenging.
Objectives
To assess improvement in fingernail psoriasis with ustekinumab treatment in ...the PHOENIX 1 trial.
Methods
Patients received ustekinumab 45 mg or 90 mg, or placebo at weeks 0 and 4. Ustekinumab‐randomized patients continued maintenance dosing every 12 weeks, while patients receiving placebo crossed over to receive ustekinumab 45 mg or 90 mg at weeks 12/16 followed by dosing every 12 weeks. At week 40, initial responders those with ≥ 75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75) were rerandomized either to continue maintenance dosing or to withdraw from treatment. Nail involvement was evaluated using the Nail Psoriasis Severity Index (NAPSI) on a target fingernail, Nail Physician's Global Assessment (Nail PGA) and mean number of nails involved.
Results
Of 766 randomized patients, 545 (71·1%) had nail psoriasis. At week 24, the percentage improvement from baseline NAPSI score was 46·5% (ustekinumab 45 mg) and 48·7% (ustekinumab 90 mg). Percentage improvements in NAPSI ranged from 29·7% (PASI < 50) to 57·3% (PASI ≥ 90). Mean NAPSI scores improved from 4·5 at baseline to 2·4 at week 24 (45 mg) and from 4·4 to 2·2 (90 mg). Nail PGA scores and the mean number of psoriatic nails improved by week 24. Further improvement was observed for all end points among initial responders continuing maintenance treatment through week 52.
Conclusions
Ustekinumab significantly improves nail psoriasis, and improvements continue over time until up to 1 year of treatment in those receiving maintenance treatment.
What's already known about this topic?
The majority of patients with moderate‐to‐severe psoriasis have nail manifestations, for which limited therapies are available.
What does this study add?
Beyond the recognized benefit to the skin in psoriasis, ustekinumab significantly improves nail psoriasis over time.
Both nail and skin manifestations of psoriasis should be considered when choosing treatment.
Summary
Background
Adalimumab (ADA) (Humira®, AbbVie Inc., U.S.A.) is approved by the European Medicines Agency for children aged ≥ 4 years with severe plaque psoriasis.
Objectives
To evaluate the ...long‐term efficacy and safety of ADA in children with severe plaque psoriasis.
Methods
Results are presented from the 52‐week long‐term extension (LTE) of the randomized, double‐blind, double‐dummy, phase III trial, in children with severe plaque psoriasis (results from prior periods have been published). Patients aged ≥ 4 and < 18 years were randomized 1 : 1 : 1 to ADA 0·8 mg kg−1 (40 mg maximum) or 0·4 mg kg−1 (20 mg maximum) every other week or to methotrexate (MTX) 0·1–0·4 mg kg−1 (25 mg maximum) weekly. The 16‐week initial treatment (IT) period was followed by a 36‐week withdrawal period and a 16‐week retreatment period. Patients could enter the LTE at prespecified time points to receive ADA 0·8 mg kg−1 (blinded or open label) or ADA 0·4 mg kg−1 (blinded), or to remain off treatment. Efficacy is reported for patient groups according to doses received in the IT and LTE periods.
Results
Of the 114 patients randomized in the IT period, 108 entered the LTE (n = 36 in each group); 93 received ADA 0·8 mg kg−1. Efficacy (≥ 75% improvement from baseline in Psoriasis Area and Severity Index) was maintained or improved from entry to the end of the LTE: MTX(IT)/ADA 0·8(LTE) 31–86% of patients; ADA 0·4(IT)/0·4 or 0·8(LTE) 28–47%; ADA 0·8(IT)/0·8(LTE) 50–72%. No serious infections occurred in the LTE.
Conclusions
After 52 weeks of long‐term ADA treatment in children aged 4–18 years with severe plaque psoriasis, disease severity was reduced and maintained or further improved, as demonstrated by efficacy outcomes. No new safety risks were identified.
What's already known about this topic?
The results from the first three periods of this phase III trial in children aged 4–18 years with severe plaque psoriasis suggest that adalimumab is a safe and efficacious treatment option in this population.
What does this study add?
This is the first study to evaluate long‐term treatment of adalimumab in children with severe psoriasis, and the first to evaluate switching from methotrexate to adalimumab in this population.
Linked Comment: Belloni Fortina and Caroppo. Br J Dermatol 2019; 181:1127–1128.
Respond to this article
Summary
Background Data are lacking on the use of topical therapies in combination with tumour necrosis factor blockers for the treatment of psoriasis.
Objectives To assess the efficacy and safety ...of adalimumab (ADA) with topical calcipotriol/betamethasone (C/B) in patients with psoriasis resembling those treated in routine clinical practice.
Methods A 16‐week, randomized, vehicle‐controlled trial was conducted in patients with moderate to severe psoriasis and previous failure, intolerance or contraindications to two or more systemic treatments. All patients received ADA (80 mg, week 0; 40 mg every other week, weeks 1–15) in addition to either topical C/B or drug‐free vehicle applied once daily for 4 weeks, and as needed thereafter. The primary endpoint was 75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75) at week 16.
Results A total of 730 patients received either ADA + C/B (n = 366) or ADA + vehicle (n = 364). PASI 75 response was initially higher with the combination therapy 14·8% for ADA + C/B vs. 5·8% for ADA + vehicle at week 2 (P < 0·001); and 40·7% vs. 32·4%, respectively, at week 4 (P = 0·021). After week 4, the trend was towards a higher response with ADA monotherapy, with no statistical difference in the PASI 75 response at week 16 (64·8% for ADA + C/B vs. 70·9% for ADA monotherapy, P = 0·086). Safety findings were consistent with previous ADA trials.
Conclusions ADA + C/B resulted in more rapid and higher efficacy within the first 4 weeks; thereafter, the trend was towards a higher response with ADA monotherapy. There was no statistical difference in the PASI 75 response at week 16. Both treatment regimens were well tolerated.
Summary Background Long‐term safety evaluations of biologics are needed to inform patient management decisions.
Objectives To evaluate the safety of ustekinumab in patients with moderate‐to‐severe ...psoriasis treated for up to 5 years.
Methods Safety data were pooled from four studies of ustekinumab for psoriasis. Rates of adverse events (AEs), serious AEs (SAEs) and AEs of interest infections, nonmelanoma skin cancers (NMSCs), other malignancies and major adverse cardiovascular events (MACE) per 100 patient‐years (PY) of follow‐up were analysed by ustekinumab dose (45 or 90 mg) and by year of follow‐up (years 1–5) to evaluate the dose response and impact of cumulative exposure. Observed rates of overall mortality and other malignancies were compared with those expected in the general U.S. population.
Results Analyses included 3117 patients (8998 PY) who received one or more doses of ustekinumab, with 1482 patients treated for ≥ 4 years (including 838 patients ≥ 5 years). At year 5, event rates (45 mg, 90 mg, respectively) for overall AEs (242·6, 225·3), SAEs (7·0, 7·2), serious infections (0·98, 1·19), NMSCs (0·64, 0·44), other malignancies (0·59, 0·61) and MACE (0·56, 0·36) were comparable between dose groups. Year‐to‐year variability was observed, but no increasing trend was evident. Rates of overall mortality and other malignancies were comparable with those expected in the general U.S. population.
Conclusions No dose‐related or cumulative toxicity was observed with increasing duration of ustekinumab exposure for up to 5 years. Rates of AEs reported in ustekinumab psoriasis trials are generally comparable with those reported for other biologics approved for the treatment of moderate‐to‐severe psoriasis.
What’s already known about this topic?
•
Short‐term studies of ustekinumab in patients with moderate‐to‐severe psoriasis indicated a favourable benefit–risk profile. Long‐term safety evaluations are needed to inform patient management decisions.
What does this study add?
•
This report evaluated the largest psoriasis clinical trial cohort to date with the longest duration of follow‐up. Safety outcomes after 5 years of ustekinumab treatment are consistent with shorter‐term reports and are generally comparable with observations from studies of other biologics in patients with psoriasis.
Objective
Treat‐to‐target (T2T) is an algorithm to reach a predefined outcome. Here, we define a T2T outcome for moderate‐to‐severe psoriasis vulgaris.
Methods
Briefly, the study included a ...literature review, discussions with key opinion leaders, recruitment of additional dermatologists with experience in managing moderate‐to‐severe psoriasis, 3 eDelphi survey rounds and a patient focus group. Relevant topics were selected during discussions prior to the survey for the statements. Surveys were based on the eDelphi methodology for consensus‐building using a series of statements. Consensus was defined as at least 80% of participants agreeing. A psoriasis patient focus group provided feedback on topic selection and outcome.
Results
A total of 5 discussions were held, and 3 eDelphi rounds were conducted with an average of 19 participants per round. The T2T outcome was set assuming shared decision between patient and dermatologist, awareness and referral for comorbidities by the dermatologist and appropriate treatment adherence by the patient. We defined ‘ideal’ and ‘acceptable’ targets; the latter referring to conditions restricting certain drugs. The T2T outcome was multidimensional, including ≥ ΔPASI90/75 or PGA ≤ 1, itch VAS score ≤ 1, absence of disturbing lesions, DLQI ≤ 1/3, incapacity daily functioning VAS score ≤ 1, safety ≤ mild side‐effects and full/mild tolerability of treatment for the ideal and acceptable target, respectively. Finally, time to achieve the T2T outcome was set at 12 weeks after initiation for all treatments. At all times, safety should not exceed the presence of mild side‐effects.
Conclusion
With this novel T2T composite outcome for psoriasis, clinicians and patients can make shared decisions on the treatment goals they envisage, as a guidance for future treatment steps – leading to a tight control management of the disease.
We describe a mass spectrometry (MS) analytical platform resulting from the novel integration of acoustic droplet ejection (ADE) technology, an open-port interface (OPI), and electrospray ionization ...(ESI)-MS that creates a transformative system enabling high-speed sampling and label-free analysis. The ADE technology delivers nanoliter droplets in a touchless manner with high speed, precision, and accuracy. Subsequent sample dilution within the OPI, in concert with the capabilities of modern ESI-MS, eliminates the laborious sample preparation and method development required in current approaches. This platform is applied to a variety of experiments, including high-throughput (HT) pharmacology screening, label-free in situ enzyme kinetics, in vitro absorption, distribution, metabolism, elimination, pharmacokinetic and biomarker analysis, and HT parallel medicinal chemistry.
Background
Epithelial surface disruption in genital psoriatic lesions may manifest as erosions, fissures and/or ulcers, causing pain and significantly impacting a patient's sexual health.
Objective
...To evaluate the impact of erosions, fissures and/or ulcers in genital psoriatic lesions on pain and sexual activity in patients with moderate‐to‐severe genital psoriasis (GenPs) and treatment responses to ixekizumab vs. placebo until Week 12.
Methods
This post hoc subgroup analysis of patients presenting with and without erosions, fissures and/or ulcers in genital lesions from a phase IIIb multicentre, randomized, double‐blind, placebo‐controlled study (IXORA‐Q; NCT02718898) in 149 adults with moderate‐to‐severe GenPs treated with subcutaneous ixekizumab (80 mg every 2 weeks; n = 75) or placebo (n = 74) evaluated outcomes for clinician‐rated GenPs severity (static Physician's Global Assessment of Genitalia; sPGA‐G) and patient‐reported genital pain and itch (Genital Psoriasis Symptoms Scale; GPSS) and sexual health (Genital Psoriasis Sexual Frequency Questionnaire; GenPs‐SFQ).
Results
At baseline, 38% (n = 57) of patients presented with genital erosions, fissures and/or ulcers independent of overall body surface area involvement (<10% or ≥10%). These signs were associated with higher scores for disease severity (sPGA‐G) and pain (GPSS) but not sexual health (GenPs‐SFQ). Complete resolution of these signs was observed in 62% of ixekizumab‐treated patients (25% for placebo) at Week 1 and 83% (21% for placebo) at Week 12. Patients treated with ixekizumab reported significant improvements in pain, itch, disease severity and sexual health over 12 weeks compared to placebo and irrespective of the presence/absence of genital erosions, fissures and/or ulcers at baseline.
Conclusion
Ixekizumab led to rapid and sustained resolution of erosions, fissures and/or ulcers and significant improvements in GenPs severity, genital pain and sexual health. Ixekizumab may help to improve the well‐being of patients with GenPs.
Background
Randomized controlled trials of secukinumab have shown sustained efficacy and a favourable safety profile in multiple manifestations of psoriatic disease.
Objectives
To assess the ...long‐term, real‐world retention, effectiveness and safety of secukinumab in routine clinical practice for the treatment of moderate‐to‐severe plaque‐type psoriasis (PsO).
Methods
SERENA (CAIN457A3403) is a large, ongoing, longitudinal, observational study conducted at 438 sites and 19 countries for an expected duration of up to 5 years in adult patients with moderate‐to‐severe PsO, psoriatic arthritis and ankylosing spondylitis. Patients received ≥16 weeks of secukinumab treatment before enrolment. This interim analysis presents data from PsO patients, who were enrolled in the study between October‐2016 and October‐2018 and were observed for ≥2 years.
Results
In total, 1756 patients (67.3% male) with a mean age of 48.4 years and body mass index of 28.8 kg/m2 were included in the analysis. The secukinumab treatment retention rates after 1, 2 and 3 years in the study were 88.0%, 76.4% and 60.5%, respectively. Of the 648 patients who discontinued the study, the most common reasons included lack of efficacy (42.6%), adverse event (17.4%), physician decision (12.2%) and subject decision (11.6%). Mean ± SD absolute PASI was 21.0 ± 13.0 at the start of treatment (n = 1,564). At baseline, the mean ± SD PASI score reduced to 2.6 ± 4.8 and remained low at Year 1 (2.3 ± 4.3), Year 2 (1.9 ± 3.6) and Year 3 (1.9 ± 3.5). The safety profile of secukinumab during the SERENA study was consistent with its known safety profile, with no new safety signals reported. Particularly, low rates of inflammatory bowel disease (0.3%; Incidence Rate IR:0.15), candida infections (3.1%; IR:1.43) and MACE (0.9%; IR:0.37) were observed.
Conclusions
Secukinumab showed high treatment persistence, sustained effectiveness and a favourable safety profile up to 3 years of follow‐up in the real‐world population of PsO patients observed in SERENA.
Background
Paediatric atopic dermatitis (AD) can be burdensome, affecting mental health and impairing quality of life for children and caregivers. Comprehensive guidelines exist for managing ...paediatric AD, but practical guidance on using systemic therapy is limited, particularly for new therapies including biologics and Janus kinase (JAK) inhibitors, recently approved for various ages in this indication.
Objectives
This expert consensus aimed to provide practical recommendations within this advancing field to enhance clinical decision‐making on the use of these and other systemics for children and adolescents aged ≥2 years with moderate‐to‐severe AD.
Methods
Nineteen physicians from Northern Europe were selected for their expertise in managing childhood AD. Using a two‐round Delphi process, they reached full or partial consensus on 37 statements.
Results
Systemic therapy is recommended for children aged ≥2 years with a clear clinical diagnosis of severe AD and persistent disease uncontrolled after optimizing non‐systemic therapy. Systemic therapy should achieve long‐term disease control and reduce short‐term interventions. Recommended are cyclosporine A for short‐term use (all ages) and dupilumab or methotrexate for long‐term use (ages ≥6 years). Consensus was not reached on the best long‐term systemics for children aged 2–6 years, although new systemic therapies will likely become favourable: New biologics and JAK inhibitors will soon be approved for this age group, and more trial and real‐world data will become available.
Conclusions
This article makes practical recommendations on the use of systemic AD treatments for children and adolescents, to supplement international and regional guidelines. It considers the systemic medication that was available for children and adolescents with moderate‐to‐severe AD at the time this consensus project was done: azathioprine, cyclosporine A, dupilumab, methotrexate, mycophenolate mofetil and oral glucocorticosteroids. We focus on the geographically similar Northern European countries, whose healthcare systems, local preferences for AD management and reimbursement structures nonetheless differ significantly.
PDF
