IMPORTANCE Biologics revolutionized the treatment of psoriasis. Biologics are given in a fixed dose, but lower doses might be possible. OBJECTIVE To investigate whether dose reduction (DR) of biologics in patients with stable psoriasis is noninferior to usual care (UC). DESIGN, SETTING, AND PARTICIPANTS 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. INTERVENTIONS 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. MAIN OUTCOMES AND MEASURES 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 Ն3 months), and proportion of patients with successful dose tapering. RESULTS 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. CONCLUSIONS AND RELEVANCE 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.

IMPORTANCEThe number of very elderly (Ն80 years) is rapidly growing worldwide. Basal cell carcinoma (BCC) are common in this age group and treatment is often challenging in this population.OBJECTIVE Obtaining an overview of the epidemiology and clinicopathological features of BCC in the very elderly to guide clinicians and policy makers.EVIDENCE REVIEW A systematic review of literature was performed using PubMed, Excerpta Medica Database (EMBASE), and the Cochrane Library. Study selection, quality assessment, and data extraction was performed by 2 independent reviewers. For quality assessment (including the risk of bias) the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist was used, combined with the Quality Rating Scheme for Studies and Other Evidence. Data were described though a narrative synthesis and tabulation.FINDINGS Of 13 628 studies identified, 83 studies were included and quality assesment was performed for 76 studies; 27 studies (representing >350 000 patients) were found that included age-specific incidence rates of BCC in the very elderly. High and increasing incidence rates of BCC in the very elderly were found ranging from 13 to 12 112 per 100 000 person-years, strongly depending on factors like study population and clinical setting. Basal cell carcinoma in the very elderly were more common in men, mostly of the nodular subtype, and located in the head and neck region. Interpretation and generalization of the data was limited by the heterogeneity of study populations, methods, and outcomes. Data concerning impact on health-related quality of life (HRQoL) and prognostication were scarce. CONCLUSIONS AND RELEVANCEThe incidence of BCC among the very elderly is high and increasing. Epidemiologic and clinicopathological data from current literature provide only limited guidance in clinical decision making owing to heterogeneity and scarcity. Future research should focus more specifically on BCC in the very elderly, together with prognostication and their relation with HRQoL in both the short and longer term.

Interleukin 17-antagonist secukinumab demonstrated high efficacy for treatment of psoriasis in randomized controlled trials. However, performance in daily practice may differ from trials. Drug survival is a comprehensive outcome covering effectiveness and safety, suitable for analyses of daily practice. The aim of this study was to evaluate drug survival of secukinumab in a daily practice psoriasis cohort. Data were collected from 13 hospitals. Drug survival was analysed using Kaplan-Meier survival curves, split for reason of discontinuation. In total, 196 patients were included (83% biologic experienced). Overall, 12 and 18 months drug survival of secukinumab was 76% and 67%, respectively, and was mostly determined by ineffectiveness. There was a trend towards shorter drug survival in women and in biologic experienced patients. Thirteen percent of patients experienced at least one episode of fungal infection. This is one of the first studies of drug survival of secukinumab in patients with psoriasis treated in daily practice.

IMPORTANCE Previous research showed a differential response to ustekinumab therapy based on HLA-C*06:02 status in patients with psoriasis but consisted mostly of small (and sometimes inconclusive) cohort studies. OBJECTIVE To assess whether HLA-C*06:02 status is associated with a differential response to ustekinumab therapy in patients with psoriasis through a systematic review and a meta-analysis of available data. DATA SOURCES A comprehensive search was conducted using MEDLINE, Embase, the Cochrane Library, Web of Science, and gray literature sources. Databases were searched from January 1, 2000, to May 14, 2018. Search strategies included terms and synonyms for psoriasis, HLA-C, and ustekinumab. Languages were restricted to English, French, German, and Dutch. STUDY SELECTION Studies were included if they reported the association between HLA-C*06:02 status and 75% improvement in Psoriasis Area and Severity Index (PASI75) response to ustekinumab therapy in patients with plaque psoriasis after 6 and/or 3 months of treatment. Randomized clinical trials and observational studies were included. Screening and selection were performed independently by 2 reviewers. DATA EXTRACTION AND SYNTHESIS HLA-C*06:02 genotype status and PASI75 response rates were extracted by 2 reviewers. Data were pooled using random-effects models. Heterogeneity was assessed using the τ 2 and I 2 statistic. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines were followed. MAIN OUTCOME AND MEASURE The primary outcome was the risk difference of achieving PASI75 after 6 months of ustekinumab therapy between HLA-C*06:02-positive and HLA-C*06:02-negative patients. RESULTS A total of 8 studies were reviewed; 1048 patients were included for meta-analyses, and 937 patients were included for the primary analysis of PASI75 response after 6 months of treatment. Random-effects meta-analysis showed a risk difference of 0.24 (95% CI, 0.14-0.35; P < .001) in favor of HLA-C*06:02-positive patients. The median PASI75 response rate in the HLA-C*06:02-positive group was 92% (pooled, 89%; range, 62%-98%). For HLA-C*06:02-negative patients, the median response rate was 67% (pooled, 62%; range, 40%-84%). Substantial heterogeneity may have been present, with an I 2 of 82%. CONCLUSIONS AND RELEVANCE The meta-analysis showed a differential response to ustekinumab therapy based on HLA-C*06:02 status in patients with psoriasis. Although HLA-C*06:02-positive patients had high PASI75 response rates after 6 months, the PASI75 response rate was also high in the HLA-C*06:02-negative group. There appears to be no rationale for excluding patients from ustekinumab treatment based on a negative HLA-C*06:02 status.

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.

Pharmacogenetic studies in psoriasis have generated divergent results. Replication of findings in larger cohorts is required. Large-scale hypothesis-free searches for genetic biomarkers are needed to uncover the complete genetic background of outcomes for treatment with biologics.

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Dose reduction of biologics for psoriasis could contribute to lower drug exposure. This study evaluated a one-step, tightly controlled, biologic dose reduction strategy in a prospective daily practice cohort. In patients with psoriasis with low disease activity using adalimumab, etanercept or ustekinumab for at least 6 months, the dosing interval was prolonged with 33%. Patients could return to their normal dosing interval in case of disease flare. Of 108 eligible patients, 80 started dose reduction and were analysed. In total, 36/80 patients (45.0%) discontinued dose reduction after 19 months (95% confidence interval 14.9–23.1 months). Of 67 patients with 1-year follow-up, 45 (67.2%) still used the lower dose after 1 year. No serious adverse events related to dose reduction occurred. Cumulative dose and costs decreased by 22.7% during 1 year. In conclusion, a one-step tightly controlled dose reduction strategy for adalimumab, etanercept and ustekinumab has considerable potential to safely decrease biologic dosages in patients with psoriasis in daily practice.