Immunological and clinical heterogeneity in cutaneous lupus erythematosus

Abstract

cantly better perceived outcome in Japanese patients. Beside the results, the interest of the paper is to highlight differences in the current management of adult patients with AD in Japan compared with the Netherlands, with limited prescription of systemic therapies except for short courses of ciclosporin or oral corticosteroids, monitoring of topical corticosteroid (TCS) response with serum thymus and activationregulated chemokine (TARC) levels. Also, the profile of Japanese patients at inclusion shows marked differences with overrepresentation of male sex, higher EASI, and lower body mass index (BMI). In addition, dupilumab reimbursement is 70% in Japan compared with 100% in the Netherlands. How much are these variables important before considering sociocultural differences as the main causative factor underlying the data? Standard doses of dupilumab have been used in the Netherlands and Japan. Addition of BMI as a covariate in the analyses did not change the results, according to the authors. However, BMI does not take into account the breakdown of an individual’s body fat weight and lean mass weight, and the Japanese cohort is mostly male. A possible related point is how much the relief gained by less topical treatment under systemic therapy influences PROMs, but the information is lacking on how many patients in each country are controlled without TCSs/topical calcineurin inhibitors. If a higher dose of dupilumab relative to lean mass weight is given in Japan, we may expect more patients without need of topical treatments. However, a result that mitigates this interpretation is that TARC levels in Japanese patients seem to follow the curve of the Patient-Oriented Eczema Measure (POEM) in Dutch patients and increase after around 100 days of treatment, apparently uncoupled to the POEM values in Japan. Is the discrepancy in PROMs possibly linked to the healthcare system, or other factors such as climate? The predominance of topical treatment in Japan may explain higher objective scores at baseline for patients of similar severity profile, and possibly better overall responses to dupilumab. However, this point is difficult to analyse, because a significant subset of patients in Japan were also treated with ciclosporin, although the dosing period might be shorter in Japan. Another major difference is the cost supported by the Japanese patients, which on the one hand was the cause for withdrawal by 11 of 153 Japanese patients, but on the other hand may also increase adherence and perceived efficiency of a novel high-cost drug. Also to consider is a difference in aggravating factors: for example, a much higher house dust mite concentration in mattresses and a hotter and more humid summer climate in Japan might contribute to the difference not only in baseline severity but also in the emergence pattern of dupilumab’s effect on signs and symptoms. Considering education and sociocultural values, some occupational health studies have shown higher coping/resilience in Japanese patients compared with that in western countries, with lower absenteeism as a consequence, which may apply to AD pruritus thresholds and perception of a drug’s overall efficacy. However, a first hurdle to overcome in comparing data is that there is currently very limited transcultural validation of AD PROMs. Ultimately, which tools should we recommend to discriminate real-life outcomes in AD? The current trend to dissociate objective and subjective items render difficult a global assessment on how the efficacy of a drug is perceived both by doctors and patients. Relying on Physician’s Global Assessment (cleared, almost cleared) is a common ‘regressive’ position advocated by health agencies like the US Food and Drug Administration. Composite scales like Scoring Atopic Dermatitis (SCORAD), which can be derived as a PROM (Patient Oriented-SCORAD), have a big advantage because in addition to a unique figure they describe the key components of AD, and can discriminate which component (intensity of lesions, extent, sleep, pruritus) respond or not to treatment.