Aim

The international TREatment of ATopic eczema (TREAT) Registry Taskforce seeks to find consensus on core domains and domain items for atopic eczema (AE, syn. ‘atopic dermatitis’) research registries and to harmonise data collection on adult and paediatric patients receiving photo- and/or systemic immuno-modulatory therapies (e.g. cyclosporine, methotrexate, azathioprine or biologics and small molecules). Our ultimate goal is to design a core set used across national AE patient registries, enhance interoperability of the national registries, allowing direct comparability of individual country data and facilitate potential data pooling between countries.

This will help to gain greater insight into the effectiveness, safety and cost-effectiveness of photo- and systemic immuno-modulatory therapies across country borders. The evidence derived from these registries will inform treatment guidelines. The national registry will also act as platforms for biomarker discovery and stratified medicine research.

 

Background

There is an urgent need for novel immuno-modulatory treatments for patients with AE; in particular for those with disease recalcitrant to topical therapies. The only conventional systemic therapy approved by the European Medicines Agency (EMA) is cyclosporine; and only in adults. In the US, only oral corticosteroids and dupilumab have Food and Drug Administration (FDA) approval.

At present, the main evidence to inform clinical practice around conventional systemic immuno-modulatory treatments is derived from a rather small body of randomised controlled trials (RCTs) (Roekevisch et al., 2014) as well as case series (i.a. (Garritsen et al., 2015; van der Schaft et al., 2015)). Despite this, in the absence of approved alternatives, immuno-modulatory treatments are frequently prescribed as off-label therapies in children and adults, as shown in our recent European and North American surveys (Proudfoot et al., 2013; Taylor et al., 2016; Totri et al., 2017). Inclusion criteria for clinical trials are stringent. Research in psoriasis suggests that around 30% of patients on systemic therapies entered into registries (in itself a very selected subgroup of all patients on systemic therapy) would not be eligible for a clinical trial, underscoring the value of ‘real world’ patient data (Garcia-Doval et al., 2012).

With the dawn of a new therapeutic era of biologic and small molecule therapies for AE, some of which have shown great promise in placebo-controlled studies and have been approved by the FDA (Beck et al., 2014; Simpson et al., 2016; Thaci et al., 2016), we need more evidence with regard to the effectiveness, safety and cost-effectiveness of such therapies compared to currently used treatment modalities, such as phototherapy and systemic immuno-modulatory drugs (cyclosporine, methotrexate, azathioprine and others).

Apart from the need for comparative real life clinical data of conventional and new therapies, clinical decision-making requires long-term follow-up data on such treatments to generate information on disease control/disease trajectory modification (even after treatment has been discontinued) and drug safety, including rare adverse events. Generation of reliable data to address these issues requires observation of large patient cohorts for several years. Comprehensive health economic evaluation of these different treatments is routinely required by many national health technology assessment organizations and third party payers to inform the allocation of health care resources. Consequently, independent prospective multi-centre registries are a logical step, as has been successfully developed in psoriasis. This is all the more important in the light of emerging evidence that suggests that industry-funded post-marketing studies, which are often conducted to detect rare adverse events, are not improving drug safety surveillance (Spelsberg et al., 2017).