Twenty to thirty percent of psoriasis (Pso) patients will develop psoriatic arthritis (PsA). Detection of Pso patients that are (at risk for) developing PsA is essential to prevent structural damage. ...We conducted a systematic search of five bibliographic databases, up to May 2020. We searched for studies assessing markers (clinical, laboratory, genetic) associated with the development or presence of PsA in Pso patients. Study selection and quality assessment of the included studies was performed, followed by a qualitative best evidence synthesis to determine the level of evidence for a marker and its association with concomitant/developing PsA in Pso. Overall, 259 possible markers were identified in 119 studies that met the inclusion criteria. Laboratory markers related to inflammation and bone metabolism reached a strong level of evidence for the association (not prediction) of PsA in Pso. Only CXCL10 showed strong evidence for a positive predictive value for PsA in Pso. The importance of timely detecting PsA in a Pso population, and finding more (bio)markers contributing to early detection, remains high.
Biologics revolutionized the treatment of psoriasis. Biologics are given in a fixed dose, but lower doses might be possible.
To investigate whether dose reduction (DR) of biologics in patients with ...stable psoriasis is noninferior to usual care (UC).
This pragmatic, open-label, prospective, controlled, noninferiority randomized clinical trial was conducted from March 1, 2016, to July 22, 2018, at 6 dermatology departments in the Netherlands. A total of 120 patients with plaque psoriasis and stable low disease activity who were receiving treatment with adalimumab, etanercept, or ustekinumab were studied.
Patients were randomized 1:1 to DR (n = 60) or UC (n = 60). In the DR group, injection intervals were prolonged stepwise, leading to 67% and 50% of the original dose.
The primary outcome was between-group difference in disease activity corrected for baseline at 12 months compared with the predefined noninferiority margin of 0.5. Secondary outcomes were Psoriasis Area and Severity Index (PASI) score and health-related quality of life (including Dermatology Life Quality Index DLQI and Medical Outcomes Study 36-Item Short Form Health Survey scores), proportion of patients with short and persistent flares (defined as PASI and/or DLQI scores >5 for ≥3 months), and proportion of patients with successful dose tapering.
Of 120 patients (mean SD age, 54.0 13.2 years; 82 68% male), 2 patients were lost to follow-up, 2 patients had a protocol violation, and 5 patients had a protocol deviation, leaving 111 patients for the per-protocol analysis (53 in the DR group and 58 in the UC group). The median PASI scores at month 12 were 3.4 (interquartile range IQR, 2.2-4.5) in the DR group and 2.1 (IQR, 0.6-3.6) in the UC group (mean difference, 1.2; 95% CI, 0.7-1.8). This indicates that noninferiority was not demonstrated for DR compared to UC. The median DLQI score at month 12 was 1.0 (IQR, 0.0-2.0) in the DR group and 0.0 (IQR, 0.0-2.0) in the UC group (mean difference, 0.8; 95% CI, 0.3-1.3), indicating noninferiority for DR compared with UC. No significant difference was found regarding persistent flares between groups (n = 5 in both groups). Twenty-eight patients (53%; 95% CI, 39%-67%) in the DR group tapered their dose successfully at 12 months. No severe adverse events related to the intervention occurred.
In this trial, noninferiority was not demonstrated for DR of adalimumab, etanercept, and ustekinumab based on the PASI in patients with psoriasis compared with UC with the chosen noninferiority margin. However, the strategy was noninferior based on the DLQI. Dose tapering did not lead to persistent flares or safety issues.
ClinicalTrials.gov Identifier: NCT02602925.
Long-term data on dupilumab drug survival in patients with atopic dermatitis (AD) are scarce. Furthermore, little is known about the factors associated with drug survival of dupilumab in AD.
To ...describe the drug survival of dupilumab in patients with AD and to identify associated predictors.
This cohort study was based on data from the multicenter prospective daily practice BioDay registry, in which 4 university and 10 nonuniversity hospitals in the Netherlands participated. Analysis included patients (age ≥18 years) participating in the BioDay registry with a follow-up of at least 4 weeks. The first patient treated with dupilumab was recorded in the BioDay registry in October 2017; data lock took place in December 2020, and data analysis was performed from October 2017 to December 2020.
Drug survival was analyzed by Kaplan-Meier survival curves and associated characteristics by using univariate and multivariate Cox regression analysis.
A total of 715 adult patients with AD (mean SD age, 41.8 16.0 years; 418 58.5% were male) were included with a 1-year, 2-year, and 3-year overall dupilumab drug survival of 90.3%, 85.9%, and 78.6%, respectively. Characteristics associated with shorter drug survival owing to ineffectiveness were the use of immunosuppressant drugs at baseline (hazard ratio HR, 2.64; 95% CI, 1.10-6.37) and being a nonresponder at 4 weeks (HR, 8.68; 95% CI, 2.97-25.35). Characteristics associated with shorter drug survival owing to adverse effects were the use of immunosuppressant drugs at baseline (HR, 2.69; 95% CI, 1.32-5.48), age 65 years or older (HR, 2.94; 95% CI, 1.10-7.87), and Investigator Global Assessment score of very severe AD (HR, 3.51; 95% CI, 1.20-10.28).
This cohort study demonstrated a good overall 1-year, 2-year, and 3-year dupilumab drug survival. Patients using immunosuppressive therapy at baseline and those with an absence of treatment effect at week 4 tended to discontinue treatment owing to ineffectiveness more frequently. Using immunosuppressant drugs at baseline, older age, and Investigator Global Assessment score of very severe AD were characteristics associated with an increased risk for discontinuation owing to adverse effects. These data provide more insight and new perspectives regarding dupilumab treatment in AD and can contribute to the optimization of patient outcomes.
Psoriasis (Pso) is a chronic inflammatory skin disease, and up to 30% of Pso patients develop psoriatic arthritis (PsA), which can lead to irreversible joint damage. Early detection of PsA in Pso ...patients is crucial for timely treatment but difficult for dermatologists to implement. We, therefore, aimed to find disease-specific immune profiles, discriminating Pso from PsA patients, possibly facilitating the correct identification of Pso patients in need of referral to a rheumatology clinic. The phenotypes of peripheral blood immune cells of consecutive Pso and PsA patients were analyzed, and disease-specific immune profiles were identified via a machine learning approach. This approach resulted in a random forest classification model capable of distinguishing PsA from Pso (mean AUC = 0.95). Key PsA-classifying cell subsets selected included increased proportions of differentiated CD4+CD196+CD183-CD194+ and CD4+CD196-CD183-CD194+ T-cells and reduced proportions of CD196+ and CD197+ monocytes, memory CD4+ and CD8+ T-cell subsets and CD4+ regulatory T-cells. Within PsA, joint scores showed an association with memory CD8+CD45RA-CD197- effector T-cells and CD197+ monocytes. To conclude, through the integration of in-depth flow cytometry and machine learning, we identified an immune cell profile discriminating PsA from Pso. This immune profile may aid in timely diagnosing PsA in Pso.
Background
Evidence on safety and effectiveness of omalizumab for treatment of chronic urticaria in pediatric patients is scarce and limited to case reports. In particular, drug survival of ...omalizumab has not yet been investigated, which is a key element in the evaluation of its clinical performance. The aim of this study was to investigate safety, effectiveness, and drug survival rates of omalizumab in a daily practice cohort of pediatric patients with chronic urticaria (CU).
Methods
This is a multicenter study including all pediatric patients from an academic center (Wilhelmina Children's Hospital) and a general center (Diakonessenhuis Hospital) in the Netherlands, who started omalizumab treatment before the age of 18 years. Data on safety, effectiveness, time to discontinuation, and reasons for discontinuation of treatment were assessed. Drug survival of omalizumab was estimated using the Kaplan‐Meier survival analysis.
Results
A total of 38 patients, who started treatment between January 2014 and January 2020, were included. Most patients (68.4%) used omalizumab without reporting any side effects and a complete or good response to treatment was achieved in 76.3% of patients. The 1‐ and 2‐year drug survival rates were 62% and 50%, respectively, with well‐controlled disease activity as the most frequent reason for discontinuation in 69.2% of patients, followed by ineffectiveness in 23.1% and side effects in 7.7% of patients.
Conclusions
This study demonstrates high safety and effectiveness of omalizumab treatment in pediatric patients with CU, which will aid clinical decision making and management of expectations when choosing omalizumab treatment for pediatric patients with CU.
Background
Time trend analysis of cutaneous melanoma (CM) mortality in fair skin populations shows both a gradual decrease and/or an increase. To explain these differences, we analyzed long‐term time ...trends in the incidence of the most common histological subtypes of CM: superficial spreading melanoma (SSM), lentigo maligna melanoma (LMM), and nodular melanoma (NM).
Methods
Using data from the Netherlands Cancer Registry and Statistics Netherlands, the number and rates of cases diagnosed with SSM, LLM, and NM from 1989 to 2016 were analyzed by age, calendar period, and birth cohort of people born in successive periods from 1925 to 1973.
Results
Primary CM was diagnosed in 52,000 men and 66,588 women in the study period. The annual age‐standardized incidence rate increased three‐fold from 14 to 42 per 100,000 person‐years. The most common subtype was SSM (50%), followed by LMM (23%) and NM (14%). Age‐specific subtype rates showed an upward trend over time for both men and women. Younger birth cohorts had higher rates of SSM and LMM diagnosis than older birth cohorts. This birth cohort pattern was not observed for NM.
Conclusions
We observed a strong increase in the melanoma epidemic curves in the light‐skinned Dutch population over the last three decades. This increase is explained by younger generations having higher rates of SSM and LMM than older generations.
We present a large population-based study on the prevalence and healthcare usage of patients with chronic urticaria (CU) in primary care. The observed annual point prevalence of 0.48–0.30% and a ...median follow-up duration of 1.5 years provides new and reliable insight into the vastness, relatively modest healthcare usage and estimated disease duration of CU in the general population, which is useful knowledge when counselling new patients with CU in both primary and specialist care settings.
Adalimumab has proven to be effective in suppressing psoriasis disease activity and is administered in a standard dose.
To establish a therapeutic range for adalimumab trough levels in the treatment ...of plaque-type psoriasis, leading to a more personalized treatment.
A multicenter, prospective, observational, daily practice cohort study conducted at an academic hospital with affiliated secondary care hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2). Both cohorts included adult patients treated with adalimumab for plaque-type psoriasis. Cohort 1 comprised 73 patients who were being treated with adalimumab for more than 24 weeks until 401 weeks. In cohort 2 (n = 62), serum samples were obtained between weeks 24 and 52 of treatment.
Before the start of adalimumab therapy and at time of serum sampling, Psoriasis Area and Severity Index (PASI) scores were determined.
Adalimumab trough level and PASI score at the time of serum sampling to determine the receiver-operator characteristics analyses and concentration effect curve.
By means of receiver-operator characteristics analyses with an area under the curve of 0.756 (SD, 0.046; 95% CI, 0.666-0.847) and a sensitivity of 78% and a specificity of 70%, 3.51 mg/L was established as the lower margin for the therapeutic range. By means of a concentration effect curve, 7 mg/L was established as the upper margin. One-third of patients had an adalimumab trough concentration exceeding 7 mg/L.
A therapeutic range of adalimumab trough levels of 3.51 mg/L to 7.00 mg/L, which corresponds to an optimal clinical effect, was identified. In one-third of patients, it was observed that trough concentrations exceeded the therapeutic window. Based on the established range, a therapeutic algorithm for adalimumab treatment for patients with psoriasis can be developed and validated in a prospective patient cohort. By identifying this range, a step has been taken toward a more rational use of biological therapy in psoriasis. Developing a therapeutic algorithm may lead to less overtreatment of patients and cost savings.
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.
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