Summary
Background
Drug survival is a marker for treatment success. To date, no analyses relating dermatological quality‐of‐life measures to drug survival have been published.
Objectives
(i) To ...describe 1‐year drug survival for adalimumab, etanercept and ustekinumab in a daily practice psoriasis cohort, and (ii) to introduce the concept of ‘happy’ drug survival, defined as Dermatology Life Quality Index (DLQI) ≤ 5 combined with being ‘on drug’ at a specific time point.
Methods
Data were extracted from a prospective registry. Drug survival was analysed using Kaplan–Meier estimates. ‘Happy’ drug survival was calculated, with data split into ‘happy’ (DLQI ≤ 5) vs. ‘unhappy’ (DLQI > 5) at baseline and months 3, 6, 9 and 12.
Results
249 treatment episodes were included (101 adalimumab, 82 etanercept, 66 ustekinumab). The 1‐year drug survival rates for ustekinumab, adalimumab and etanercept were 85%, 74% and 68%, respectively. Ustekinumab showed a better confounder‐corrected drug survival vs. etanercept hazard ratio (HR) 3·8, P = 0·02 and a trend towards better survival vs. adalimumab (HR 2·3, P = 0·1). At baseline, the majority (n = 115, 73%) was considered ‘unhappy’ and a minority ‘happy’ (n = 42, 27%) (ratio ‘happy’:‘unhappy’ was 1 : 2.7). The percentage of treatment episodes with ‘happy’ on‐drug patients increased to 79% after 1 year.
Conclusions
Ustekinumab showed a better overall drug survival than etanercept, and a trend towards a better overall drug survival than adalimumab. After 1 year, patients reported to be ‘happy’ in 79% of episodes and ‘unhappy’ in 21%. We introduced the new concept of ‘happy’ drug survival because the proportion of on‐drug patients with good quality of life is an important indicator for treatment success.
What's already known about this topic?
The Dermatology Life Quality Index is a validated score for dermatology‐specific quality‐of‐life measurements.
Drug survival studies of biologics for psoriasis show varying results and differ in study design and population.
To date, studies including drug survival rates for ustekinumab are scarce.
What does this study add?
The introduction of a concept named ‘happy’ drug survival, which combines drug survival rates with dermatology‐specific quality‐of‐life measures to evaluate treatments for psoriasis.
Analysis of ‘happy’ drug survival showed that the proportion of ‘on‐drug’ biologic users with a good quality of life increased from 27% to 79% after 1 year of treatment.
Ustekinumab showed a better overall drug survival vs. etanercept and a trend towards a better survival vs. adalimumab.
Background
Available literature on psoriasis and psoriatic arthritis (PsA) demonstrates a tremendous burden of disease and suggests underdiagnosis and undertreatment.
Objective
To obtain real‐world ...physician perspectives on the impact of psoriasis and PsA and its treatment on patients' daily lives, including perceptions of, and satisfaction with, current therapies.
Methods
The Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) surveyed dermatologists (n = 391) and rheumatologists (n = 390) in North America (Canada and the United States) and Europe (France, Germany, Italy, Spain and United Kingdom).
Results
Dermatologists classified 20.3% and 25.7% of their patients as having severe psoriasis and severe PsA respectively; rheumatologists indicated that 48.4% of their PsA patients had active disease. Of the psoriasis patients complaining of joint pain, only 33.0% had a diagnosis of PsA. An impact on daily activities or social/emotional well‐being was recognized by 57.2% to 79.3% of physicians. In patients with moderate‐to‐severe psoriasis, dermatologists reported 74.9% were receiving topical therapy, 19.5% conventional oral therapy and 19.6% biologics. Dermatologists and rheumatologists reported similar rates of topical (≈45%) and biologic (≈30%) therapy utilization for their PsA patients; conventional oral therapy was more often prescribed by rheumatologists (63.4%) vs. dermatologists (35.2%). Reasons for not initiating or maintaining systemic therapies were related to concerns about long‐term safety, tolerability, efficacy and costs (biologics).
Conclusion
Physicians in North America and Europe caring for patients with psoriasis and PsA acknowledge unmet treatment needs, largely concerning long‐term safety/tolerability and efficacy of currently available therapies; evidence suggests underdiagnosis of PsA and undertreatment of psoriasis among dermatologists.
Placebo and nocebo effects are known to play a key role in treatment effects in a wide variety of conditions. These effects have frequently been investigated with regard to pain and also in other ...physical sensations, but have hardly been investigated with regard to itch. In addition, neither in pain nor in any other physical sensation, the single and combined contribution of the expectancy mechanisms of conditioning and verbal suggestion have ever been investigated in both placebo and nocebo effects within one design. For the first time, the role of verbal suggestion and conditioning in placebo and nocebo effects on itch was experimentally investigated. Expectations about itch stimuli were induced in healthy subjects by verbal suggestion, conditioning, or a combination of both procedures, and compared with a control group without expectation induction. Itch was induced electrically by means of quantitative sensory testing. Significant placebo and nocebo effects were induced in the group in which combined procedures of conditioning and verbal suggestion were applied in comparison with the control group. The conditioning and verbal suggestion procedures applied individually did not induce significant placebo and nocebo effects when compared with the control group. The results of this study extend existing evidence on different physical sensations, like pain, by showing that also for itch, the combination of conditioning and verbal suggestion is most promising in inducing both placebo and nocebo effects. More research on placebo and nocebo effects at a perceptive and neurobiological level is warranted to further elucidate the common and specific mechanisms underlying placebo and nocebo effects on itch and other physical sensations.
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.
Summary
Background
Balancing treatment decisions in frail older adults with nonmelanoma skin cancer (NMSC) can be challenging. Clinical practice guidelines (CPGs) could provide assistance.
Objectives
...To collect and prioritize items related to frail older adults with NMSC for integration into CPGs and to assess the current extent of this integration.
Methods
Items were collected and prioritized by a multidisciplinary working group (29 members) using a modified Delphi procedure and a five‐point Likert scale. To assess current integration of these items in CPGs, a systematic review was subsequently performed by two independent reviewers using five medical databases (PubMed, Embase, Cochrane Library, SUMsearch and Trip Database), websites of guideline developers/databases, and (inter)national dermatological societies.
Results
Prioritization of a final 13‐item list showed that ‘limited life expectancy’ (4·5 ± 0·9) and ‘treatment goals other than cure’ (4·4 ± 0·7) were most desired to be integrated into CPGs; both were included in six (46%) of the CPGs found (n = 13). Attention to ‘tumour characteristics’ and ‘comorbidities’ were included in CPGs most often (100% and 77%, respectively).
Conclusions
More attention to items related to frail older adults in NMSC CPGs is broadly desired, but CPG integration of these items is currently limited. More integration might stimulate more holistic, personalized and patient‐centred care in frail older adults.
What's already known about this topic?
Nonmelanoma skin cancer is common among the growing population of frail older adults worldwide.
Treatment decisions in frail older adults with nonmelanoma skin cancer can be challenging.
Clinical practice guidelines are intended to assist healthcare providers to optimize patient care in daily clinical practice, but balancing the extensiveness and specificity of clinical practice guidelines might be a challenge.
What does this study add?
More attention to several frailty‐related items in clinical practice guidelines on nonmelanoma skin cancer is broadly desired.
Integration of these items into current clinical practice guidelines on nonmelanoma skin cancer is limited.
More integration is expected to optimize current nonmelanoma skin cancer care and might stimulate more holistic, personalized and patient‐centred care in frail older adults.
Plain language summary available online
Video Commentary
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.
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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
We systematically reviewed all available literature concerning the prevalence of onychomycosis in patients with nail psoriasis and the distribution of pathogens causing onychomycosis in this specific ...group of patients. Databases searched were Pubmed, EMBASE and the Cochrane Controlled Clinical Trial Register. All studies reporting on the prevalence of onychomycosis in nail psoriasis were obtained, and quality assessment was determined by the STrengthening the Reporting of OBservational studies in Epidemiology checklist. Literature search revealed 720 studies, of which 10 studies met the inclusion criteria. The major limitation of the review was the heterogeneity of the included studies, which prevented the possibility to conduct a meta analysis. However, the average prevalence of 18.0% of onychomycosis in psoriatic patients seems to be increased when compared with control groups and literature on healthy population, even though the ultimate evidence remains lacking. As in the literature hypothesized shift in causative agents from dermatophytes to yeasts and/or moulds could not be confirmed. The clinical consequence of the relatively high prevalence of onychomycosis in psoriasis may be a general advice to rule out onychomycosis or concomitant onychomycosis in these patients with (suspected) nail psoriasis. This advice is stressed by the relative simplicity of treating the contribution of onychomycosis in the nail dystrophy but also the fact that nail psoriasis mostly is treated by immunosuppressive drugs, like steroids, methotrexate or biologics which may aggravate mycotic nail infections.
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