Etanercept, improved dosage schedules and combinations in the treatment of psoriasis: an update

Etanercept, a subcutaneously administered fully human soluble tumor necrosis factor (TNF) receptor, was initially approved for the treatment of psoriasis at a dose of 25 mg twice weekly in repeated 24-week cycles with the possibility to double the dose in the first 12 weeks of the first cycle. During intermittent treatment, patients retain their ability to respond to etanercept. Recently, a new dosing schedule of etanercept 50 mg once weekly was approved, based on a study in which PASI-75 (75% improvement of Psoriasis Area and Severity Index) was achieved by 37% and 71% of patients at week 12 and 24. Another study demonstrated a PASI-75 of 57% and 69% in pediatric psoriasis patients receiving etanercept 0.8 mg/kg (up to 50 mg) once weekly for 12 and 24 weeks respectively, resulting in European approval from age 8. Based on recent clinical trials, the antipsoriatic effect of etanercept can be markedly increased in combination with acitretin, methotrexate or UVB. The combination with acitretin appears attractive because of its non-immunosuppressive and chemopreventive properties. Etanercept–methotrexate combination therapy is well established in rheumatologic patients. From a long-term perspective, the combination of TNF-inhibitors with phototherapy (photocarcinogenesis) or cyclosporine (carcinogenesis, infections) warrants great caution however. Finally, combination with topical calcipotriol–betamethasone ointment may increase the speed of response to TNF-inhibitors in the first 4 weeks of treatment

Optimizing Anti-Inflammatory and Immunomodulatory Effects of Corticosteroid and Vitamin D Analogue Fixed-Dose Combination Therapy

Abstract: Fixed-dose combination topical therapy with corticosteroid and vitamin D analog provides effective treatment and possible long-term management of psoriasis. The anti-inflammatory and immunomodulatory effects of corticosteroids and vitamin D analogs in treating psoriasis are well investigated; their complementary effects lead to the disruption of the inflammatory feedback loop underlying psoriasis pathogenesis. Recent preclinical data showed that combination therapy is more effective than monotherapies of the active ingredients in preventing activation of resting pro-inflammatory cells, inducing immunomodulation, reducing inflammatory responses by regulating T cell production, and normalizing keratinocytes. The increased understanding of the mechanism of action of fixed-dose combination therapy from preclinical studies is supported by several clinical studies. As the efficacy of topical therapy is correlated with the skin penetration of the active ingredients, new drug delivery systems have been developed. The fixed-dose combination Cal/BD aerosol foam creates a modified supersaturated formulation when applied to the skin, which is maintained for at least 26 h in the laboratory setting. Clinical studies have demonstrated superior efficacy of fixed-dose combination calcipotriol (Cal) 50 µg/g and betamethasone dipropionate (BD) 0.5 mg/g aerosol foam compared with monotherapies of the active ingredients. Furthermore, Cal/BD aerosol foam has shown significantly improved efficacy compared with more traditional formulations, such as Cal/BD ointment and gel, in other studies. Calcipotriol also mitigates risks associated with betamethasone dipropionate and vice versa, resulting in the favorable safety profile observed with fixed-dose combination treatment. Recent data also suggest that fixed-dose combination treatment could provide long-term management of psoriasis, although further clinical investigations are needed. Overall, these data support the value of fixed-dose combination therapy of corticosteroid and vitamin D analog and highlight the added potential of innovative drug delivery for the treatment of psoriasis. Funding: LEO Pharma

Long-term topical management of psoriasis: the road ahead

AbstractTopical therapies have been available for the treatment of psoriasis for several decades. Despite this and the availability of several types of topicals, with varying potency, and numerous ..

Dermatological side effects of hepatitis C and its treatment: Patient management in the era of direct-acting antivirals

SummaryDermatological adverse events (AEs) are an existing concern during hepatitis C virus (HCV) infection and peginterferon/ribavirin treatment. HCV infection leads to dermatological and muco-cutaneous manifestations including small-vessel vasculitis as part of the mixed cryoglobulinemic syndrome. Peginterferon/ribavirin treatment is associated with well-characterized dermatological AEs tending towards a uniform entity of dermatitis. New direct-acting antivirals have led to significant improvements in sustained virologic response rates, but several have led to an increase in dermatological AEs versus peginterferon/ribavirin alone. In telaprevir trials, approximately half of treated patients had rash. More than 90% of these events were Grade 1 or 2 (mild/moderate) and in the majority (92%) of cases, progression to a more severe grade did not occur. In a small number of cases (6%), rash led to telaprevir discontinuation, whereupon symptoms commonly resolved. Dermatological AEs with telaprevir-based triple therapy were generally similar to those observed with peginterferon/ribavirin (xerosis, pruritus, and eczema). A few cases were classified as severe cutaneous adverse reaction (SCAR), also referred to as serious skin reactions, a group of rare conditions that are potentially life-threatening. It is therefore important to distinguish between telaprevir-related dermatitis and SCAR. The telaprevir prescribing information does not require telaprevir discontinuation for Grade 1 or 2 (mild/moderate) rash, which can be treated using emollients/moisturizers and topical corticosteroids. For Grade 3 rash, the prescribing information mandates immediate telaprevir discontinuation, with ribavirin interruption (with or without peginterferon) within 7days of stopping telaprevir if there is no improvement, or sooner if it worsens. In case of suspicion or confirmed diagnosis of SCAR, all study medication must be discontinued

A Belgian consensus on the definition of a treat‐to‐target outcome set in psoriasis management

Objective: Treat-to-target (T2T) is an algorithm to reach a predefined outcome. Here, we define a T2T outcome for moderate-to-severe psoriasis vulgaris. Methods: Briefly, the study included a literature review, discussions with key opinion leaders, recruitment of additional dermatologists with experience in managing moderate-to-severe psoriasis, 3 eDelphi survey rounds and a patient focus group. Relevant topics were selected during discussions prior to the survey for the statements. Surveys were based on the eDelphi methodology for consensus-building using a series of statements. Consensus was defined as at least 80% of participants agreeing. A psoriasis patient focus group provided feedback on topic selection and outcome. Results: A total of 5 discussions were held, and 3 eDelphi rounds were conducted with an average of 19 participants per round. The T2T outcome was set assuming shared decision between patient and dermatologist, awareness and referral for comorbidities by the dermatologist and appropriate treatment adherence by the patient. We defined 'ideal' and 'acceptable' targets; the latter referring to conditions restricting certain drugs. The T2T outcome was multidimensional, including >= Delta PASI90/75 or PGA <= 1, itch VAS score <= 1, absence of disturbing lesions, DLQI <= 1/3, incapacity daily functioning VAS score <= 1, safety <= mild side-effects and full/mild tolerability of treatment for the ideal and acceptable target, respectively. Finally, time to achieve the T2T outcome was set at 12 weeks after initiation for all treatments. At all times, safety should not exceed the presence of mild side-effects. Conclusion: With this novel T2T composite outcome for psoriasis, clinicians and patients can make shared decisions on the treatment goals they envisage, as a guidance for future treatment steps - leading to a tight control management of the disease

The epidermal vitamin D system and innate immunity: Some more light shed on this unique photoendocrine system?

SCOPUS: ed.jinfo:eu-repo/semantics/publishe

Calciphylaxis : de huidige stand van zaken

Calciphylaxis, ook wel calcific uremic arteriolopathy (CUA) genoemd, is een zeldzame, maar levensbedreigende aandoening die vooral voorkomt bij mensen met terminaal nierlijden. Daarnaast wordt het gezien bij tal van andere aandoeningen zoals primaire hyperparathyreoïdie, maligniteiten, systeemziekten en levercirrose. De exacte incidentie en prevalentie zijn niet bekend vanwege de zeldzaamheid en vaak ook miskenning van de ziekte. De incidentie wordt geschat op 1% tot 5% bij patiënten met terminaal nierlijden, maar anderen melden een prevalentie van ongeveer 4% bij dialysepatiënten. De mortaliteit na diagnose is rond de 60-80% en de meest voorkomende doodsoorzaken zijn sepsis en orgaanfalen. De aandoening komt meer voor bij vrouwen dan bij mannen met een ratio van 3:1 en kan op elke leeftijd voorkomen. De kliniek is zeer divers en kan gaan van cutane aantasting met een beeld van livedo reticularis/racemosa tot uitgeponste stervormige ulcera en soms zelfs tot systemische aantasting. De exacte pathofysiologie is onbekend, maar er zijn recent steeds meer aanwijzingen dat de NFkB-pathway hierin centraal zou staan. Momenteel is natriumthiosulfaat de hoeksteen van de behandeling. In dit artikel geven wij een update van de huidige stand van zaken rond etiologie, pathogenese en behandeling van deze zeldzame aandoening.Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is a rare but life-threatening disease that is primarily seen in patients with end-stage kidney disease. It is also associated with numerous other conditions such as primary hyperparathyroidism, malignancies, systemic diseases and liver cirrhosis. The exact incidence and prevalence are unknown due to the rarity and misdiagnosis of the disease. The incidence is estimated at 1-5% in patients with endstage kidney disease, though others report a prevalence of around 4% in patients on dialysis. The mortality rate is around 60-80% and the most common causes of death are sepsis and multi-organ failure. It is more common in women than in men with a ratio of 3:1 and can occur at any age. It can manifest itself cutaneously with livedo reticularis/racemosa and painful ulcera or systemically. The exact pathophysiology is unknown, however, there is increasing evidence that the NFkB pathway plays a crucial role. Sodium thiosulphate is a key element in the treatment of calciphylaxis. In this article we will provide an update on the etiology, pathophysiology and treatment of this rare disease

An observational study of the real-life management of psoriasis patients treated with etanercept according to the new reimbursement criteria (in Belgium).

BACKGROUND: This study described the number of patients with psoriasis receiving flexible (continuous/intermittent) dosing with etanercept (ETN) and the real-world economic impact. METHODS: BeFlex was a prospective, observational study with a ≥1 year follow-up. Patients ≥18 years with moderate-to-severe psoriasis who were starting or re-starting treatment with ETN in alignment with Belgian reimbursement criteria were included. Cost of ETN was compared with cost of adalimumab, ustekinumab and infliximab using estimates from the National Institute for Sickness and Disability Insurance (INAMI/RIZIV). RESULTS: In the flexible-dosing cohort (n = 121 with dose-regimen data), 66% were treated continuously and 34% intermittently. Baseline characteristics were similar across dosing cohorts. In the per-protocol cohort (n = 138), average ETN treatment duration/year was 40 weeks; 43 weeks continuous and 33 weeks intermittent. The overall mean interruption duration was 3.9 weeks/treatment cycle; 0.2 week continuous and 11.1 weeks intermittent. Mean dose/year was 2065 mg; 2182 mg continuous and 1660 mg intermittent. Flexible ETN dosing reduced the cost by 20% versus INAMI/RIZIV estimates. The theoretical cost of the other continuously-dosed biologics was 28-44% higher than that of flexible ETN. CONCLUSION: Approximately one-third of Belgian patients received intermittent ETN treatment. Flexible ETN dosing was more cost-effective than treatment with biologic agents that require continuous dosing

Current practice of therapeutic drug monitoring of biopharmaceuticals in psoriasis patients

The high prevalence of psoriasis and the high spending on pharmaceuticals motivate a more evidence-based and cost-effective usage of biopharmaceuticals. A growing body of evidence exists that the implementation of therapeutic drug monitoring (TDM) for biopharmaceuticals in psoriasis patients optimizes patient management and clinical outcome and enhances their efficacy. Therefore, the aim of this review is to give an overview of the literature on TDM of biopharmaceuticals in the treatment of psoriasis and to provide the useful information to dermatologists to improve health care in psoriasis patients.status: publishe