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.
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Summary
Background
Long‐term data of etanercept drug survival in patients with psoriasis in daily practice are scarce.
Objectives
The primary objective was to describe drug survival for etanercept in ...a long‐term daily practice cohort of patients with psoriasis. The secondary objective was to identify determinants of drug survival for etanercept in general and separately for discontinuation due to adverse events or ineffectiveness of therapy.
Methods
Data were extracted from a prospective daily practice cohort of patients treated with biologics for psoriasis. Drug survival was analysed by Kaplan–Meier survival curves and split for two reasons for discontinuation: adverse events and ineffectiveness. Determinants of drug survival were analysed using univariate Cox regression analysis and multivariate Cox regression analysis with backward selection.
Results
We included 193 patients (512 patient‐years treated) with a maximum treatment duration of 7·5 years. The overall drug survival rates were 77%, 41% and 30% after 1, 4 and 7·5 years, respectively. The mean survival duration was 3·8 years (95% confidence interval 3·4–4·3). Reasons for discontinuation were ineffectiveness (33·7%), adverse events (11·9%), both ineffectiveness and adverse events (4·7%) or other reasons (e.g. pregnancy planned) (5·7%). Determinants related to longer general drug survival were male sex hazard ratio (HR) 0·55, prior anti‐tumour necrosis factor (TNF)‐α use (HR 0·57) and lower etanercept dose (HR 0·65). Younger age (HR 0·83), lower body mass index (HR 0·63) and lower etanercept dose (HR 0·71) were related to a decreased risk of discontinuation due to side‐effects. A lower mean weekly dose of etanercept (HR 0·63) was related to a decreased risk of discontinuation due to ineffectiveness of therapy.
Conclusions
We present the longest analysis of drug survival for etanercept in psoriasis to date. Determinants of longer overall etanercept drug survival were male sex, prior anti‐TNF therapy and lower etanercept dose. The determinants of longer drug survival depended on the reason for discontinuation of etanercept.
What's already known about this topic?
Etanercept has proven to be effective and well tolerated in patients with psoriasis in several randomized controlled trials.
What does this study add?
This is the first daily practice study calculating drug survival rates of patients treated with etanercept for a maximum observation period of 7·5 years.
Determinants of longer drug survival were calculated for general drug survival, and separately for discontinuation due to adverse events or ineffectiveness of therapy.
Summary
Background
Evidence on the effectiveness and safety of short‐contact dithranol therapy in paediatric psoriasis is sparse and based only on retrospective data. The best results are achieved in ...a time‐consuming day‐care setting.
Objectives
To study prospectively the effectiveness and safety of short‐contact dithranol therapy in paediatric psoriasis. In addition, the effectiveness, safety, duration of treatment and number of visits between regular day care and day care with telemedicine were compared.
Methods
Data were collected from the prospective observational Child‐CAPTURE registry of children with psoriasis. Effectiveness was measured as the mean percentage improvement in Psoriasis Area and Severity Index (PASI). Safety was assessed by recording adverse events. The number of visits and duration of treatment were reported.
Results
For all patients a mean percentage reduction in PASI score of −69·3% was found, with no significant differences between regular day care and day care with telemedicine. The only adverse event reported was irritation of the skin. Neither the frequency of irritation during treatment nor the mean duration of treatment significantly differed between the two groups. Patients with telemedicine had significantly fewer visits.
Conclusions
This first prospective observational study demonstrates that short‐contact dithranol therapy in paediatric psoriasis is effective and safe. Regular day care and day care with telemedicine are equally effective. Telemedicine can be of additional value as it is less time consuming. We hope it will therefore make dithranol treatment appropriate for a larger number of children with psoriasis.
What's already known about this topic?
Dithranol is a proven effective treatment for psoriasis in adults, without known long‐term side‐effects; in children only retrospective studies have been performed.
The best results with short‐contact dithranol therapy are achieved when it is administered in a day care centre.
What does this study add?
In this first prospective observational study, short‐contact dithranol therapy was demonstrated to be effective and safe in daily clinical practice in paediatric psoriasis.
Short‐contact dithranol therapy by day care with telemedicine has extra advantages for children and parents as it is less time consuming.
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder that affects one or two individuals per 100,000. The disease is caused by an extended CAG repeat in exon 8 of ...the
gene and is characterized mostly by a profound loss of cerebellar Purkinje cells, leading to disturbances in coordination, balance, and gait. At present, no curative treatment is available for SCA1. However, increasing knowledge on the cellular and molecular mechanisms of SCA1 has led the way towards several therapeutic strategies that can potentially slow disease progression. SCA1 therapeutics can be classified as genetic, pharmacological, and cell replacement therapies. These different therapeutic strategies target either the (mutant)
RNA or the ataxin-1 protein, pathways that play an important role in downstream SCA1 disease mechanisms or which help restore cells that are lost due to SCA1 pathology. In this review, we will provide a summary of the different therapeutic strategies that are currently being investigated for SCA1.
Psoriasis may express as active severe disease or as mild stable disease. In particular, patients with active severe disease present systemic involvement, including comorbidities and increased values ...of parameters reflecting an active state of innate immunity. In contrast, patients with mild stable disease show a dominancy of acquired immunity. In this review article, we report the clinical aspects of disease manifestations of both active and quiescent psoriasis as well as the immunological aspects, as well as the impact on antimicrobial resistance. The activity of psoriasis is not captured in the present outcome measures for severity assessment. The present review suggests that incorporating disease activity may be important in the assessment of the efficacy of treatments.
Background
Concerns exist about a risk of non‐melanoma skin cancer (NMSC) in psoriasis patients and rheumatoid arthritis (RA) patients treated with TNF‐inhibitors. However, current data also show ...that in some psoriasis patients, NMSC is diagnosed relatively short after the start of TNF‐inhibitors, which suggests that these NMSC can be explained by previous therapies instead of by TNF‐inhibitor therapy.
Objective
To investigate whether there was a difference in time until first NMSC and the rate of NMSC between psoriasis and RA patients on TNF‐inhibitors.
Methods
Time until first NMSC and the rate of NMSC were compared between psoriasis and RA patients from the same region treated with TNF‐inhibitors and followed up for at least one year in prospective cohort studies, by using Cox regression and Poisson regression. Both analyses were corrected for confounders (age, gender, disease duration, prior NMSC, duration of anti‐TNF and other systemic therapies).
Results
The NMSC risk was significantly higher in the psoriasis group fully adjusted HR 6.0 (1.6–22.4 95%CI) with a shorter time until first NMSC in psoriasis compared to RA. By Poisson regression, psoriasis patients had a 5.5 (2.2–13.4 95%CI) higher rate of NMSC.
Conclusion
The time until first NMSC was significantly shorter and the rate of NMSC was significantly higher in psoriasis compared with RA. This indicates that disease‐related factors like phototherapy may be important contributing factors to NMSC diagnosed in psoriasis patients treated with TNF‐inhibitors.
Summary
In vivo examination of the skin by reflectance confocal microscopy (RCM) has been performed for about 20 years, leading to a broad spectrum of imaged infectious and inflammatory skin diseases ...(ISD) with many described RCM features. We systematically reviewed all available literature concerning ISD evaluated by RCM. Furthermore, we assessed the accuracy of the features and defined recommendations for future studies after indicating the limitations in the current published literature. PubMed, Embase, Cochrane Library and Web of Science databases were searched for literature. All studies on RCM and ISD were reviewed and quality assessment was determined by using the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist. The literature search revealed 77 eligible studies for inclusion. Different RCM features in a broad spectrum of ISD have been described. Further, RCM has been used for monitoring treatment and evolution of ISD, as well as for diagnostic purposes. This systematic review provides an overview of the broad spectrum of ISD imaged by RCM. Although RCM seems to be a promising monitoring and diagnostic tool for ISD, studies with appropriate methodological quality are necessary to create adequate guidelines and protocols for further implementation of RCM in clinical practice.
What's already known about this topic?
Many inflammatory and infectious skin diseases have been imaged by in vivo reflectance confocal microscopy (RCM).
What does this study add?
This systematic review provides an overview and accuracy assessment of RCM features and diagnoses.
This review facilitates further implementation of RCM in dermatological practice.
Summary
Background In previous studies, etanercept 25 mg twice weekly (BIW) or 50 mg BIW significantly reduced disease severity in patients with plaque psoriasis and demonstrated a favourable safety ...profile.
Objectives To assess the efficacy and safety of etanercept 50 mg administered once weekly (QW) compared with placebo in patients with moderate‐to‐severe plaque psoriasis over 24 weeks.
Methods This study was conducted in two parts: (i) a 12‐week, double‐blind, placebo‐controlled phase, in which patients received etanercept 50 mg QW or placebo QW; and (ii) a 12‐week, open‐label extension phase, in which all patients received etanercept 50 mg QW. Primary endpoint was a 75% or greater improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at week 12. Secondary endpoints included percentage PASI improvement and Physician’s Global Assessment (PGA).
Results One hundred and forty‐two patients were analysed in the double‐blind phase; 126 patients entered the open‐label phase. At week 12, significantly more patients receiving etanercept 50 mg QW (37·5%) achieved PASI 75 response than patients receiving placebo (2·2%; P < 0·0001). At week 24, 71·1% in the etanercept–etanercept group and 44·4% in the placebo–etanercept group achieved PASI 75. Mean percentage of PASI improvement from baseline was 55·4% with etanercept vs. 9·4% worsening with placebo at week 12 (P < 0·0001), with 77·4% and 57·7% improvement in the etanercept–etanercept and placebo–etanercept groups at week 24. A PGA score of 0–1 (clear–almost clear) was achieved by 64% and 42% in the etanercept–etanercept and placebo–etanercept groups at week 24, respectively. Etanercept 50 mg QW was well tolerated. No deaths, serious infections, opportunistic infections (including tuberculosis), demyelinating disorders, malignancies or new safety signals were reported.
Conclusions Nearly three‐quarters of patients with moderate‐to‐severe psoriasis receiving etanercept 50 mg QW achieved significant improvement in disease severity over 24 weeks. This study also showed a favourable tolerability and safety profile with etanercept 50 mg QW.
Background
A considerable disease period often precedes initiation of a biologic in patients with psoriasis. Little is known about this important period in patients’ lives. Evaluation of this ...‘journey’ can reveal important insights and opportunities for physicians and healthcare decision makers.
Objectives
(i) To describe patient and treatment characteristics until the start of biologic treatment in patients with severe psoriasis, (ii) to assess shifts in early (2005–2009) versus established (2010–2015) biologics prescription periods, (iii) to assess changes in hospital/day care admissions before vs. after starting biologics.
Methods
Explorative, retrospective study on the treatment characteristics of the disease period until first biologic, presented with descriptive statistics of patients included in the BioCAPTURE registry. Journeys of 2005–2009 and 2010–2015 were compared with statistical tests to identify important shifts.
Results
Median TUS (time until conventional systemic) was 11.0 years and median TUB (time until biologic) was 18.9 years for all patients treated from 2005 to 2015. Most patients received three different conventional antipsoriatic systemic therapies. We noticed a small trend towards a shorter journey (TUB) with only two conventional systemic agents instead of three before initiating a biologic in later years (2010–2015, vs. 2005–2009). We also noticed a significant decrease in (day care) admissions comparing the two years before, versus the first two years after the start of a biologic treatment (17.7 vs. 8.6 admissions/100 follow‐up years, P < 0.001). Cyclosporine, intensive topical treatment (dithranol), retinoids and PUVA therapy lost popularity in recent years.
Conclusion
The ‘journey’ of patients with psoriasis towards a biologic is still long and characterized by many different treatments. Shifts towards fewer conventional drugs before biologic initiation and a clear decrease in hospital and day care admissions before vs. after a biologic are seen. Improvement of this journey, especially in young or recently diagnosed patients, can decrease negative influences on patients’ lives and reduce societal impact.
Summary
Background Knowledge about quality of life and sexual health in patients with genital psoriasis is limited.
Objectives We studied quality of life and sexual function in a large group of ...patients with genital psoriasis by means of validated questionnaires. In addition, we evaluated whether sufficient attention is given by healthcare professionals to sexual problems in patients with psoriasis, as perceived by the patients.
Methods A self‐administered questionnaire was sent to 1579 members of the Dutch Psoriasis Association. Sociodemographic patient characteristics, medical data and scores of several validated questionnaires regarding quality of life (Dermatology Life Quality Index) and sexual health (Sexual Quality of Life Questionnaire for use in Men, International Index of Erectile Function, Female Sexual Distress Scale and Female Sexual Function Index) were collected and analysed.
Results This study (n = 487) shows that psoriasis has a detrimental effect on quality of life and sexual health. Patients with genital lesions reported even significantly worse quality of life than patients without genital lesions (mean ± SD quality of life scores 8·5 ± 6·5 vs. 5·5 ± 4·6, respectively, P < 0·0001). Sexual distress and dysfunction are particularly prominent in women (reported by 37·7% and 48·7% of the female patients, respectively). Sexual distress is especially high when genital skin is affected (mean ± SD sexual distress score in patients with genital lesions 16·1 ± 12·1 vs. 10·1 ± 9·7 in patients without genital lesions, P = 0·001). The attention given to possible sexual problems in the psoriasis population by healthcare professionals is perceived as insufficient by patients.
Conclusions In addition to quality of life, sexual health is diminished in a considerable number of patients with psoriasis and particularly women with genital lesions have on average high levels of sexual distress. We underscore the need for physicians to pay attention to the impact of psoriasis on psychosocial and sexual health when treating patients for this skin disease.
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