Clinical Consequences of Antibody Formation, Serum Concentrations, and HLA-Cw6 Status in Psoriasis Patients on Ustekinumab.

BACKGROUND: Ustekinumab for the treatment of psoriasis is currently administered in a standard dosing regimen. However, some patients tend to benefit from alternative dosing regimens, a step toward personalized medicine. METHODS: To investigate the role of ustekinumab serum concentrations, anti-ustekinumab antibodies [AUA] and HLA-Cw6 status as tools for optimizing ustekinumab treatment, a multicenter prospective cohort study was conducted at an academic hospital with affiliated nonacademic hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2 and 3). Patients with plaque-type psoriasis were eligible if treated with ustekinumab for ≥16 weeks. Serum samples and Psoriasis Area and Severity Index scores were obtained at baseline, week 16, 28, 40, 52, and/or ≥64 of ustekinumab treatment. RESULTS: A total of 137 patients with 229 observations for serum concentrations and AUA and 61 observations for HLA-Cw6 status were included. Presence of AUA (prevalence of 8.7%) was significantly associated with a diminished clinical response (P = 0.032). The median ustekinumab trough concentration was 0.3 mcg/mL (<0.02-3.80). No differences in serum concentrations were observed between moderate to good responders and nonresponders (P = 0.948). Serum trough concentrations were not affected by methotrexate comedication. Prevalence of HLA-Cw6 positivity was 41% with no statistically significant difference in clinical response between HLA-Cw6-positive and HLA-Cw6-negative patients (P = 0.164). CONCLUSIONS: The presence of AUA was associated with treatment failure in this patient population; measurement of AUA may therefore be a candidate marker for personalized pharmacotherapy. The clinical utility of ustekinumab serum trough concentrations or HLA-Cw6 status determination remains less clear. Further exploration on the potential of measuring ustekinumab serum concentrations and other biomarkers in predicting therapy outcomes should be encouraged.

Effectiveness of Biologic and Conventional Systemic Therapies in Adults with Chronic Plaque Psoriasis in Daily Practice: A Systematic Review.

The efficacy of biologic or conventional systemic therapies for psoriasis has been shown in randomized controlled trials. Effectiveness, however, has been studied in daily practice cohorts, and no aggregation of effectiveness data is available. This systematic review searched PubMed and EMBASE and summarized the real-world evidence on effectiveness of biologics (adalimumab, etanercept, infliximab and ustekinumab) and conventional systemic therapies (acitretin, cyclosporine, fumarates and methotrexate) for the treatment of plaque psoriasis in adults. Thirty-two studies were included. Few data were available on infliximab, ustekinumab and conventional systemics. Results show that biologics and conventional systemics were effective in real-life treatment of psoriasis, with large ranges in the percentage of patients reaching 75% improvement in psoriasis area and severity index score compared with baseline, especially for etanercept and adalimumab treatment. Combination therapies of biologics with conventional systemics, and dose adjustments of biologics were frequently applied strategies and may explain the large range in improvements between cohorts.

Combined use of systemic agents for psoriasis: a systematic review.

IMPORTANCE: Combined use of systemic agents may be necessary to achieve disease control in therapy-resistant patients. However, to our knowledge, an overview of evidence, including quality assessments, is not yet available, and no guidance on monitoring, contraindications, and interactions exists. OBJECTIVES: To summarize and critically appraise the evidence on efficacy and safety of combination therapy with systemic agents in plaque-type psoriasis. EVIDENCE REVIEW: Through March 2013, an electronic search limited to randomized clinical trials was performed in MEDLINE, EMBASE, The Cochrane Library, and ongoing trial registers. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. FINDINGS: The initial search retrieved 2583 records, of which 17 met the inclusion criteria. Most studies favored combination therapy, albeit with low significance and low quality of evidence. Etanercept plus methotrexate was the only combination therapy investigated with an adequate sample size (n = 478). In the short term, this combination had superior efficacy with a moderate quality of evidence compared with etanercept monotherapy (Psoriasis Area and Severity Index, 75; relative risk, 1.28; 95% CI, 1.14-1.45). Although this finding coincided with an increase in adverse events (relative risk, 1.25; 95% CI, 1.10-1.42), the overall safety profile remained acceptable. CONCLUSIONS AND RELEVANCE: This systematic review provides a comprehensive overview on the validity of different systemic combination therapies. For most combinations, insufficient evidence is available. Initial results indicate that combined therapy with etanercept plus methotrexate may be beneficial in patients that are therapy resistant under intensive follow-up. Dose reductions should be taken into account to minimize adverse effects.

Parental experiences with propranolol versus oral corticosteroids for complicated infantile hemangioma, a retrospective questionnaire study.

BACKGROUND: Infantile hemangiomas (IHs) are common and mostly emerge in the head-neck area. Recently, propranolol has been replacing oral corticosteroids (OCS) as the main treatment modality. OBJECTIVES: The aim of this study was to explore the impact of treatment, contentment with treatment outcome and quality of life for families and patients with cervicofacial IHs, treated with propranolol versus OCS. MATERIALS AND METHODS: This study was performed using questionnaires administered by a phone interview. Parents of 16 patients with a cervicofacial IH treated by OCS and 16 patients with an IH of similar localization and overall severity treated with propranolol were interviewed. The questions concerned the impact of treatment at different time periods and the contentment with treatment results. Parents were also asked to give a quality of life (QoL) score (1 to 10) for different time-points. RESULTS: Parents from the OCS group seemed to feel significantly more worried during treatment. Moreover, parents from the propranolol group perceived less negative impact on normal life issues, including work and vaccination of their child. During and after treatment, the parents of propranolol-treated IH patients gave significantly higher QoL scores. CONCLUSION: Propranolol seems to change the impact of IHs, their treatment and the quality of life. Propranolol treatment interferes less with normal issues in daily life, compared to OCS. These findings underline propranolol as the first choice treatment for life- or function-threatening IHs.

Effectiveness of adalimumab dose escalation, combination therapy of adalimumab with methotrexate, or both in patients with psoriasis in daily practice.

BACKGROUND: To increase effectiveness of standard adalimumab treatment 40 mg every other week (EOW) for patients with psoriasis, dose escalation to 40 mg every week or addition of methotrexate (MTX) are possible strategies. METHODS: Daily practice data about adalimumab treatment were extracted from a prospective observational cohort. We analyzed all patients with insufficient efficacy of adalimumab EOW who received 1) adalimumab dose escalation, 2) addition of MTX to adalimumab EOW, or 3) both. Effectiveness was analyzed after 12 and 24 weeks using PASI50, PASI75, and mean differences in PASI. RESULTS: Forty-seven treatment episodes (TE) of adalimumab dose escalations, 11 of MTX addition and six combinations were analyzed. After a first episode of adalimumab dose escalation, 25% and 35% achieved PASI50 after 12 and 24 weeks, respectively. After MTX introduction to adalimumab EOW, 9% and 18% achieved PASI50 after 12 and 24 weeks, respectively. No related serious adverse events were reported. CONCLUSIONS: Twenty-five percent of first TE with adalimumab dose escalation induced a PASI50 response after 12 weeks and 35% after 24 weeks. Addition of MTX to adalimumab EOW resulted in PASI50 in 9% after 12 weeks and 18% after 24 weeks. Defining patient-groups that will benefit from these interventions is important.

[A woman with skin abnormalities around the mouth]. / Een vrouw met huidafwijkingen rond de mond.

A 33-year-old healthy woman consulted her dermatologist when an acute and painful perioral pustular dermatosis erupted one day after she had taken azitromycin for a throat infection. A preliminary diagnosis of acute localized exanthematous pustulosis (ALEP) was made, which was later confirmed by cultures and histopathological examination. Medication was cessated immediately and the dermatosis disappeared completely afterwards.

The psychosocial impact of an infantile haemangioma on children and their parents.

Infantile haemangiomas (IHs) are common, benign vascular tumours in children that appear soon after birth and regress before the age of 12 years. Physicians have always been concerned about the considerable psychosocial impact these lesions might have on children and their parents. This is the first critical review of studies on the psychosocial impact of IHs on children and their families. Future directions for research are suggested. As propranolol is becoming the most common first choice treatment for IHs, this article discusses its use in the light of this review.