July 2026 digest

Standardizing the approach without standardizing the patient

The rapid expansion of effective systemic treatments has made Treat-to-Target a natural next step in atopic dermatitis. Once substantial improvement becomes achievable for many patients, it is no longer sufficient to ask whether a treatment works. We must determine what level of control should be reached, when it should be assessed, and what action should follow when the target is missed. Recent publications illustrate both the promise of this approach and the difficulty of translating it into a standardized strategy.

A Taiwanese real-world study of combined treatment targets is particularly instructive [1]. Rather than examining each outcome separately, the investigators used principal component analysis to identify the dimensions accounting for most of the variation across clinical and patient-reported measures, and latent class analysis to identify groups of patients with distinct patterns of response. This revealed that satisfactory control of skin signs did not always coincide with satisfactory quality of life. One subgroup achieved favorable cutaneous outcomes while continuing to report substantial life impact, and quality-of-life variables explained much of the remaining variance. A composite target may therefore be missed not only because inflammation remains visibly active, but because itch, sleep disturbance, psychological burden, treatment constraints or impaired daily functioning persist beyond what the skin examination captures.

This approach also recalls the construction of SCORAD more than three decades ago [2]. SCORAD was not assembled by simply adding convenient items: principal component analysis was used to derive the relative contribution of extent, intensity signs and the two subjective symptoms, pruritus and sleep loss. The resulting weighting gave approximately 60% of the total score to intensity signs and about 20% each to extent and subjective symptoms. This was a major step toward multidimensional assessment, but it also illustrates an enduring difficulty: every composite score embeds choices about which domains matter and how much weight each should carry.

Recent clinical-trial analyses sharpen the same question by combining almost complete skin clearance with an itch-free or nearly itch-free state. In pooled analyses of the JADE DARE, JADE COMPARE and JADE EXTEND trials, Weidinger et al. used the stringent composite endpoint EASI-90 plus Peak Pruritus NRS 0/1[3]. Patients reaching this endpoint also experienced substantial quality-of-life improvement, supporting deeper, multidimensional targets rather than relative improvement alone. Yet these analyses leave open whether skin clearance and itch should be weighted equally, whether both must be achieved simultaneously, and how to classify a patient with minimal visible disease but persistent nocturnal symptoms.

A recent paediatric report makes this discordance tangible.[4] Two children with relatively mild visible lesions had severe persistent itch and sleep disturbance that improved markedly after IL-31 receptor blockade. These observations cannot define treatment policy, but they show how a low lesion score may coexist with a high disease burden. The cases are therefore less an argument for one drug than a reminder that a composite assessment must remain sensitive to the dimension that matters most to the individual patient.

The question becomes still more complex after good control has been achieved. A real-world study of extended-interval dupilumab treatment found that some patients could increase the interval between injections, while 16 of 81 patients discontinued treatment after achieving remission without relapse during follow-up [5]. Baseline EASI and TARC values did not clearly predict these long-term trajectories. Treat-to-Target therefore cannot stop at the moment a threshold is crossed. It must also address durability of control, flare prevention, rescue-treatment needs, treatment burden and the possibility of dose reduction or withdrawal.

These examples show why AD cannot be managed through a single universal numerical threshold. Visible inflammation, itch, sleep, quality of life, daily functioning, flare frequency, rescue treatment, safety and stability over time all contribute to meaningful control, but their relative importance varies with age, phenotype, disease duration, comorbidities, treatment mechanism and healthcare setting. The appropriate target for a young child whose principal burden is nocturnal itch may not be identical to that of an adult with extensive chronic lesions, occupational impairment and several previous systemic treatments.

Standardization nevertheless remains essential. Without shared definitions, studies cannot be compared, therapeutic strategies cannot be evaluated consistently, and clinicians lack clear guidance on when to maintain, intensify, switch or reduce treatment. The challenge is therefore to standardize the method of assessment and therapeutic decision-making without standardizing the patient.

A useful framework should define a limited core set of outcomes, specify assessment intervals and establish principles for adapting treatment. At the same time, it should preserve individualized priorities and shared decision-making. Earlier international Treat-to-Target recommendations already placed patient global assessment at the centre of decisions, requiring improvement in patient global status together with at least one specific domain [6]. As proposed in by ISAD at Melbourne Rajka 2025, this principle should be broadened by using the patient global assessment of health as an anchor: the different domains and scores should ultimately be interpreted against the patient’s overall perception of whether health and daily life have meaningfully improved.

This is the purpose of the international ISAD Treat-to-Target initiative. The aim is not to create another collection of severity thresholds, but to develop a longitudinal strategy centred on what matters most to patients: fewer flares, less itch, better sleep, reduced rescue treatment, stable participation in daily life and durable disease control. The therapeutic revolution has made increasingly ambitious outcomes possible. The next step is to agree not only on how improvement is measured, but on what meaningful control of atopic dermatitis truly means.

References

Chen YW, Chen YH, Yen TH, et al. Achieving targeted combined endpoints in patients with atopic dermatitis: a real-world study. J Dermatol. Published online July 3, 2026. doi:10.1111/1346-8138.70369.
European Task Force on Atopic Dermatitis. Severity scoring of atopic dermatitis: the SCORAD index. Consensus report of the European Task Force on Atopic Dermatitis. Dermatology. 1993;186(1):23-31. doi:10.1159/000247298.
Weidinger S, Reich K, Issa N, et al. Abrocitinib achieves early and complete/near-complete skin clearance plus itch-free state in atopic dermatitis: phase 3 pooled post hoc analysis. Dermatol Ther (Heidelb). Published online June 27, 2026. doi:10.1007/s13555-026-01833-8.
Fujita Y, Miyamoto M, Kato M, Shiraishi H, Yoshihara S. Nemolizumab efficacy for severe sleep disturbance in pediatric atopic dermatitis with mild skin lesions. JAAD Case Rep. 2026;73:72-74. doi:10.1016/j.jdcr.2026.04.027.
Saito R, Sasaki W, Watanabe H, et al. Extended-interval dosing and discontinuation of dupilumab in atopic dermatitis: a real-world retrospective study. J Dermatol. Published online June 11, 2026. doi:10.1111/1346-8138.70350.
de Bruin-Weller M, Biedermann T, Bissonnette R, et al. Treat-to-target in atopic dermatitis: an international consensus on a set of core decision points for systemic therapies. Acta Derm Venereol. 2021;101(2):adv00402. doi:10.2340/00015555-375