Nocebo effects, i.e., adverse treatment effects which are induced by patients' expectations, are known to contribute to the experience of physical symptoms such as pain and itch. A better ...understanding of how to minimize nocebo responses might eventually contribute to enhanced treatment effects. However, little is known about how to reduce nocebo effects. In the current randomized controlled study, we tested whether nocebo effects can be minimized by positive expectation induction with respect to electrical and histaminic itch stimuli. First, negative expectations about electrical itch stimuli were induced by verbal suggestion and conditioning (part 1: induction of nocebo effect). Second, participants were randomized to either the experimental group or one of the control groups (part 2: reversing nocebo effect). In the experimental group, positive expectations were induced by conditioning with verbal suggestion. In the control groups either the negative expectation induction was continued or an extinction procedure was applied. Afterwards, a histamine application test was conducted. Positive expectation induction resulted in a significantly smaller nocebo effect in comparison with both control groups. Mean change itch NRS scores showed that the nocebo effect was even reversed, indicating a placebo effect. Comparable effects were also found for histamine application. This study is the first to demonstrate that nocebo effects can be minimized and even reversed by conditioning with verbal suggestion. The results of the current study indicate that learning via counterconditioning and verbal suggestion represents a promising strategy for diminishing nocebo responses.
Summary
Background
The effectiveness of biologics for psoriasis shows heterogeneity among patients. With pharmacogenetic markers, it might be possible to predict treatment response.
Objectives
We ...aimed to test the association between genetic markers and the response to biologics in psoriasis (etanercept, adalimumab, ustekinumab) in a prospective cohort.
Methods
We investigated the copy number variation in the LCE3B and LCE3C genes, and eight single‐nucleotide polymorphisms (SNPs) in HLA‐C*06, CD84, IL12B, IL23R, TRAF3IP2, ERAP1, IFIH1 and TNFAIP3. The decrease in Psoriasis Area and Severity Index (PASI) was calculated as ∆PASI (absolute PASI decrease compared with baseline) and PASI 75 (proportion of patients with ≥ 75% improvement vs. baseline). Associations between genetic variants and treatment outcome were assessed using multivariable linear regression analysis (∆PASI corrected for baseline PASI, primary analysis) and Pearson's χ2‐test or Fisher's exact test (PASI 75, secondary analysis).
Results
We included 348 treatment episodes in 234 patients. Patients heterozygous (GA) for the SNP in CD84 (rs6427528) had a better ∆PASI response to etanercept after 3 months (P = 0·025) than the homozygous reference group (GG). In addition, patients heterozygous (CT) for the IL12B variant showed a better response (∆PASI) to ustekinumab (P = 0·017) than the reference group (CC). Patients homozygous (GG) for the SNP in TNFAIP3 showed a worse response (∆PASI) to ustekinumab (P = 0·031) than the reference group (TT). The associations with ustekinumab resulting from the primary analysis were not confirmed in the secondary (PASI 75) analysis.
Conclusions
We demonstrated a strong association between etanercept use in psoriasis and variations in CD84, a gene that was previously found to be a predictor of response to etanercept in rheumatoid arthritis.
What's already known about this topic?
Pharmacogenetic studies in psoriasis have identified targets that may be promising in predicting treatment response to biologics.
A genome‐wide association study in rheumatoid arthritis identified a genetic variant in CD84 (rs6427528) as a predictor of response to etanercept.
What does this study add?
Genetic variation in CD84 (rs6427528) predicted etanercept response in our cohort of patients with psoriasis.
Genetic variations in IL12B (rs3213094) and TNFAIP3 (rs610604) were associated with ustekinumab response.
What is the translational message?
Using pharmacogenetics we aim to predict treatment outcome of psoriasis based on genetic factors. In the future, we hope to give patients the therapy expected to be most effective based on their genetic constitution.
With our study we have demonstrated, for instance, that patients carrying an A allele for a genetic variant in CD84 responded better to etanercept than patients with two G alleles at the same position.
Respond to this article
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.
Nail psoriasis: a questionnaire-based survey Klaassen, K.M.G.; van de Kerkhof, P.C.M.; Pasch, M.C.
British journal of dermatology (1951),
August 2013, Letnik:
169, Številka:
2
Journal Article
Recenzirano
Summary
Background
Skin manifestations are the most characteristic finding of psoriasis. However, nail involvement is also a clinical feature of disease although it is often overlooked. The ...documented prevalence of nail psoriasis varies between 10·0% and 81·1%.
Objectives
The aim of this investigation is to gain knowledge about the prevalence and clinical manifestations of nail psoriasis and patient experiences of treatment of nail psoriasis.
Methods
A structured, self‐administered questionnaire was distributed to all members (n = 5400) of the Dutch Psoriasis Association. The questionnaire enquired about sociodemographic patient characteristics, disease‐related data and treatment of nail psoriasis. Patients reported their nail manifestations with photographs after instruction. Patients with nail psoriasis were compared with patients without nail psoriasis.
Results
A response rate of 27% was achieved. The prevalence of nail psoriasis was 66·0%. The most frequently observed psoriatic nail manifestation was pitting (65·4%), whereas red spots in the lunula were infrequently seen (6·5%). Patients with nail psoriasis more frequently stated psoriasis capitis (75·8% vs. 65·7%), genital psoriasis (32·7% vs. 20·3%) and psoriatic arthritis (46·4% vs. 30·6%) compared with patients with psoriasis without nail involvement. Only 16·0% of patients received treatment for nail psoriasis. Systemic therapies were most frequently stated as being effective for nail lesions.
Conclusions
Nail manifestations seem to be more prevalent in patients with psoriasis than previously thought. In addition, nail psoriasis is shown to be associated with widespread and more severe forms of psoriasis, and different treatment options are experienced as being effective for nail psoriasis. Notwithstanding, nail psoriasis is still an often overlooked feature of the disease.
What's already known about this topic?
The reported prevalence of nail psoriasis varies between 10% and 81%.
Clinical manifestations depend on the involvement of the nail matrix and/or nail bed.
Psoriatic arthritis is more prevalent in patients with nail psoriasis.
What does this study add?
We provide accurate prevalence rates of nail psoriasis, and insight into the association between nail psoriasis and different types of psoriasis.
This is the first article to present patients' experiences of the effects of psoriasis therapies on nail lesions.
Summary
Background In previous studies, etanercept significantly improved plaque psoriasis and was well tolerated.
Objectives To examine further the efficacy and safety of etanercept and to assess ...maintenance of treatment effect after dose reduction of etanercept.
Methods In this multicentre 24‐week study in the U.S.A., Canada and Western Europe, patients were at least 18 years old; had active, clinically stable plaque psoriasis involving at least 10% of body surface area; had a minimum Psoriasis Area and Severity Index (PASI) of 10 at screening; and had received or were a candidate to receive systemic psoriasis therapy or phototherapy. During the first 12 weeks of the study, patients were randomly assigned to receive by subcutaneous injection etanercept twice weekly (BIW) at a dose of 50 mg or 25 mg, or placebo BIW in a double‐blind fashion. During the second 12 weeks, all patients received etanercept 25 mg BIW. The primary endpoint was a 75% or greater improvement from baseline in PASI (PASI 75) at 12 weeks.
Results Five hundred and eighty‐three subjects were randomized and received at least one dose of study drug. At week 12, a PASI 75 was achieved by 49% of patients in the etanercept 50 mg BIW group, 34% in the 25 mg BIW group, and 3% in the placebo group (P < 0·0001 for each etanercept group compared with placebo). At week 24 (after 12 weeks of open‐label 25 mg etanercept BIW), a PASI 75 was achieved by 54% of patients whose dose was reduced from 50 mg BIW to 25 mg BIW, by 45% of patients in the continuous 25 mg BIW group, and by 28% in the group that received placebo followed by etanercept 25 mg BIW. Etanercept was well tolerated throughout the study.
Conclusions Etanercept provided clinically meaningful benefit to patients with chronic plaque psoriasis, with no apparent decrease in efficacy after dose reduction.
Background
Acne vulgaris is a multifaceted skin disorder, affecting more than 85% of young individuals worldwide. Pharmacological therapy is not always desirable because of the development of ...antibiotic resistance or the potential risk of adverse effects. Non‐pharmacological therapies can be viable alternatives for conventional therapies. However, sufficient evidence‐based support in the efficacy and safety of non‐pharmacological therapies is lacking.
Objective
To assess the efficacy and safety of several non‐pharmacological therapies in the treatment of acne vulgaris.
Methods
A systematic literature review, including a best‐evidence synthesis, was performed to identify literature. Three electronic databases were accessed and searched for studies published between January 2000 and May 2017.
Results
Thirty‐three eligible studies were included in our systematic review. Three main types of non‐pharmacological therapies were identified laser‐ and light‐based therapies, chemical peels and fractional microneedling radiofrequency. The majority of the included studies demonstrated a significant reduction in acne lesions. However, only seven studies had a high methodologic quality. Based on these seven trials, a best‐evidence synthesis was conducted. Strong evidence was found for glycolic acid (10–40%). Moderate evidence was found for amino fruit acid (20–60%), intense pulsed light (400–700 and 870–1200 nm) and the diode laser (1450 nm). Initially, conflicting evidence was found for pulsed dye laser (585–595 nm). The most frequently reported side‐effects for non‐pharmacological therapies included erythema, tolerable pain, purpura, oedema and a few cases of hyperpigmentation, which were in most cases mild and transient.
Conclusion
Circumstantial evidence was found for non‐pharmacological therapies in the treatment of acne vulgaris. However, the lack of high methodological quality among included studies prevented us to draw clear conclusions, regarding a stepwise approach. Nevertheless, our systematic review including a best‐evidence synthesis did create order and structure in resulting outcomes in which a first step towards future research is generated.
Summary
Background
Dermatology Life Quality Index (DLQI) and Children's Dermatology Life Quality Index (CDLQI) are widely used to assess quality of life (QoL) in adults (≥ 16 years) and children ...(4–16 years) with psoriasis. In the age group 16–17 years, it is not known whether DLQI and CDLQI reflect QoL impairment in the same way.
Objectives
To compare DLQI and CDLQI scores in patients with psoriasis aged 16–17 years.
Methods
Patients with psoriasis aged 16–17 years were asked to complete both the DLQI and CDLQI.
Results
Fifty‐six patients were included. There was a high correlation between DLQI and CDLQI scores (r = 0·90, P < 0·001). The mean DLQI score (5·41 ± 5·20) was lower than the mean CDLQI (6·61 ± 5·74) (P < 0·001). The major part of this difference (∆0·61) was caused by the low score regarding sexual difficulties in the DLQI (0·11 ± 0·49) and the high score concerning sleep in the CDLQI (0·71 ± 0·93). In addition, the question related to sports scored 0·34 in the DLQI but 0·86 in the CDLQI (∆0·52). The question related to work/study in the DLQI scored lower than the question on school/holiday in the CDLQI (∆0·41).
Conclusions
In patients with psoriasis aged 16–17 years, DLQI and CDLQI scores closely correlate, but the mean DLQI score was lower than the mean CDLQI score. This was caused primarily by differences in the answers to questions regarding sexual difficulties and sleep. As the QoL impacts experienced by people aged 16–17 may differ from those experienced by children or adults, QoL measures designed for use in this age range may have advantages over both child‐ and adult‐specific measures.
What's already known about this topic?
Psoriasis can have a negative impact on quality of life (QoL).
Dermatology Life Quality Index (DLQI) and Children's Dermatology Life Quality Index (CDLQI) are commonly used dermatology‐specific QoL questionnaires used in adults (≥ 16 years) and children (4–16 years), respectively.
What does this study add?
In patients with psoriasis aged 16–17 years, DLQI and CDLQI scores closely correlated. Overall, DLQI scored lower than CDLQI.
QoL measures designed for people aged 16–17 years may have advantages over both child‐ and adult‐specific measures.
Linked Comment: Beattie, Br J Dermatol 2016; 174:21.
Plain language summary available online
Treating older adults with psoriasis can be challenging owing to comorbidities, concomitant medication use, and consequent safety risks. Although many studies focus on the effectiveness and safety of ...systemic antipsoriatic therapies in the general population, their effectiveness in older adults with psoriasis has not been systematically assessed.
To evaluate the effectiveness and safety of systemic antipsoriatic therapies in patients 65 years or older.
A systematic literature search was conducted in Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) on November 11, 2019. No date limit was used. Randomized clinical trials, cohort studies, large case series, and meta-analyses assessing efficacy (or effectiveness) and/or safety of systemic antipsoriatic therapies in patients 65 years or older were included.
The initial search yielded 11 096 results, of which 31 unique articles with 39 561 patients were included in analysis. Overall, limited data were available per systemic agent, and overall quality of the included studies on conventional systemic therapies was low. At the end of the induction phase (12-16 weeks after start of treatment), a reduction of 75% in Psoriasis Area and Severity Index was achieved in 49% of 74 methotrexate sodium users 65 years or older, 46% to 52.6% of 178 older cyclosporin users, 27% to 47.8% of 108 older acitretin users, 15.6% to 64% of 256 etanercept users 65 years or older, 66.7% to 93% of 43 infliximab users 65 years or older, 60.7% to 65% of 100 adalimumab users 65 years or older, 56.5% of 46 ustekinumab users 65 years or older, and 86.4% of 67 secukinumab users 65 years or older. Effectiveness of acitretin, etanercept, adalimumab, and secukinumab appeared not to be associated with age; studies regarding other systemic antipsoriatic therapies did not provide age group comparisons. Older age was significantly associated with renal function deterioration in cyclosporin users and with lymphopenia in fumaric acid esters users (hazard ratio, 2.42; 95% CI, 1.65-3.55; P < .001). Infections were the most frequently reported adverse event in patients 65 years or older using biologics, but no significant association with age was found.
On the basis of limited available evidence, age alone should not be a limiting factor in psoriasis management. Awareness of comorbidities and concomitant medication use is very important, as well as appropriate dosing and frequent laboratory and clinical monitoring. More real-world evidence and (sub)analyses of prospective cohort studies on the effectiveness and safety of systemic therapies in older adults are critical to optimize personalized, effective, and safe antipsoriatic management in this growing patient group.
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.
Fumaric acid esters (FAEs) are a group of small molecules that were first investigated for the treatment of psoriasis in 1959. The first fumarate‐based drug – Fumaderm® – was approved in Germany in ...1994 for severe psoriasis and then in 2008, the label was expanded to include moderate psoriasis. Fumaderm is a combination of different FAEs: dimethyl fumarate (DMF), which is regarded as the main active component, plus calcium, magnesium and zinc salts of monoethyl fumarate (MEF). FAEs are the most frequently used first‐line systemic psoriasis treatment in Germany, with an overall treatment experience comprising more than 220 000 patient‐years. FAEs have demonstrated good, sustained clinical efficacy with an acceptable safety profile for the long‐term treatment of patients with moderate‐to‐severe psoriasis. Indeed, the European S3‐Guideline on the systemic treatment of Psoriasis vulgaris recommends FAEs for induction and long‐term treatment. Until recently, FAEs were only licensed (for the psoriasis indication) in Germany, but were imported to many other European countries, such as The Netherlands, UK, Ireland, Austria and Italy, for the treatment of psoriasis. In 2017, the European Medicines Agency (EMA) approved Skilarence®, a new oral formulation of DMF, for the treatment of adult patients with moderate‐to‐severe chronic plaque psoriasis in need of systemic therapy. Skilarence only contains DMF and is the first FAE for the treatment of psoriasis that has been approved by the EMA. This approval has given rise to a new oral treatment option for patients with moderate‐to‐severe plaque psoriasis across Europe. Here, we report the results of an expert meeting which was convened to deliver clinician‐agreed consensus and real‐world guidance on the clinical use of DMF in moderate‐to‐severe chronic plaque psoriasis. Guidance on appropriate patient selection, DMF dosage considerations, monitoring and side‐effect management is offered based upon available evidence and collective real‐world clinical experience.
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