Case Report: Differential response to IL-13 inhibition: lebrikizumab following primary tralokinumab failure in atopic dermatitis.

BACKGROUND

Atopic dermatitis is a chronic inflammatory skin disorder driven largely by type 2 immune pathways, with interleukin-13 (IL-13) playing a central role in disease pathogenesis. Biologics targeting IL-13, including tralokinumab and lebrikizumab, have demonstrated efficacy in clinical trials; however, the therapeutic value of intra-class switching following primary treatment failure remains poorly defined, and existing real-world reports rarely distinguish primary from secondary failure. This gap is particularly relevant for patients with limited systemic treatment options, in whom treatment sequencing decisions carry greater clinical weight.

CASE PRESENTATION: We report a 29-year-old man with lifelong moderate atopic dermatitis and limited systemic treatment options due to contraindications and prior treatment inefficacy. He demonstrated confirmed primary failure to tralokinumab, with persistent disease activity, despite good adherence. Prior to switching to lebrikizumab, EASI was 9, POEM 16, and DLQI 8, with the patient achieving marked improvement in disease severity within four months (EASI 0, POEM 5, DLQI 7), alongside early improvement in pruritus. At six months, disease control remained substantially improved (EASI 1.4), with good tolerability and no requirement for rescue systemic therapy.

DISCUSSION: Despite targeting the same cytokine, tralokinumab and lebrikizumab exhibit distinct receptor-binding properties, with lebrikizumab preserving IL-13 interaction with the IL-13Ra2 decoy receptor, potentially enhancing cytokine clearance and modulating downstream signalling. This case demonstrates a clinically meaningful improvement in disease severity following primary failure to tralokinumab, supporting the concept of functional heterogeneity within IL-13 inhibition and suggesting that primary failure does not imply class-wide inefficacy.

CONCLUSION

This case provides evidence that primary failure to tralokinumab may not preclude response to lebrikizumab, possibly supporting intra-class heterogeneity among IL-13 inhibitors. Sequential IL-13 inhibition may represent a rational therapeutic option in patients with limited treatment options. Further studies are needed to identify predictors of response and optimise biologic sequencing in atopic dermatitis.