Polymorphisms in CD84, IL12B and TNFAIP3 are associated with response to biologics in patients with psoriasis.

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.

Comparing treatment goals for psoriasis with treatment decisions in daily practice: results from a prospective cohort of patients with psoriasis treated with biologics: BioCAPTURE.

BACKGROUND: Treatment goals have been developed to optimize daily clinical practice psoriasis care, but have not yet been studied in real life. OBJECTIVES: To investigate to what extent treatment decisions made by dermatologists in daily clinical practice for patients with psoriasis on biologics are already in accordance with treatment goals without the active application of the treatment goals algorithm. METHODS: Data were extracted from a prospective daily practice cohort of patients with psoriasis on biologics. Analysis was done on effectiveness (Psoriasis Area and Severity Index score) and quality of life (Dermatology Life Quality Index questionnaire). Treatment decisions such as dosage adjustments, combination treatments, or switching therapy were compared with the treatment goals algorithm. RESULTS: In 64% (253 of 395) of visits, physicians followed the treatment goals algorithm. There were 162 (41%) visits in which there should have been a treatment modification according to treatment goals (group Modify) and a modification was indeed made in 59 of these 162 visits (36%). In 233 (59%) visits no treatment modification was necessary (group Continue) and therapy was indeed not modified in 194 of 233 visits (83%). CONCLUSIONS: Physicians acted in accordance with treatment goals in the majority of patient visits. In the patient group not achieving these goals, physicians should have modified therapy according to treatment goals but continued the same therapeutic regimen in the majority of visits. Optimizing therapy and defining barriers in the latter group might increase treatment results in daily practice psoriasis care.

'Happy' drug survival of adalimumab, etanercept and ustekinumab in psoriasis in daily practice care: results from the BioCAPTURE network.

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.

Summary of the Dutch S3-guidelines on the treatment of psoriasis 2011. Dutch Society of Dermatology and Venereology.

This document provides a summary of the Dutch S3-guidelines on the treatment of psoriasis. These guidelines were finalized in December 2011 and contain unique chapters on the treatment of psoriasis of the face and flexures, childhood psoriasis as well as the patient's perspective on treatment. They also cover the topical treatment of psoriasis, photo(chemo)therapy, conventional systemic therapy and biological therapy.

Propranolol in a case series of 174 patients with complicated infantile haemangioma: indications, safety and future directions.

BACKGROUND: Infantile haemangioma (IH) is a benign, common and self-limiting tumour of infancy; only a minority of cases need active treatment. Currently, propranolol appears superior to classic treatments. OBJECTIVES: To document in a prospective study indications and side-effects of propranolol for complicated IH in a large patient group. METHODS: Analysis of prospectively collected data was performed on 174 patients with IH treated with propranolol in a tertiary referral centre from September 2008 to January 2012. RESULTS: The group consisted of children with a potentially threatening and/or complicated IH; the girl/boy ratio was 123/51, and the mean age at the start of treatment was 4·8 months. In 173 cases (99·4%), treatment was successful, as assessed nonquantitatively by clinical observation. This striking effect was characterized by immediate cessation of growth, softening, fading of the erythema and rapid induction of regression. The mean duration of treatment was 10·7 months. The most important adverse effects were hypotension (3·4%), wheezing (9·2%), nocturnal restlessness (22·4%) and cold extremities (36·2%). In one patient, propranolol was stopped. In 15 patients it was necessary to reduce the dose, although the lower dose was still effective. CONCLUSIONS: In this study, propranolol was effective and safe in almost all patients with complex IH. Administration of systemic medication to an infant with a benign condition requires careful consideration, as only a minority of patients with IH require an active medical intervention. A shift of the indication of propranolol for IH is evident, expanding its application for life-threatening situations or severe functional impairment to early prevention of disfigurement or cosmetically permanent sequelae. However, the indication for such an active approach should be determined by experienced physicians.