D1.446 - Lebrikizumab in patients with urticarial vasculitis - a case series

Urticarial vasculitis (UV) is a rare, chronic inflammatory disease characterized by a small-vessel leukocytoclastic vasculitis, recurrent long-lasting wheals and systemic manifestations. To date, no approved treatment for UV is available. There is a significant unmet need for effective and well-tolerated therapies in UV.

Emerging evidence suggests a role of type 2 immune pathways, including mast cell activation via C5a-C5aR signaling, IgE/IgG-mediated mechanisms and interleukin (IL)-4/IL-13 driven inflammation in UV.

Lebrikizumab, a monoclonal antibody selectively targeting IL-13, is approved for the treatment of moderate-to-severe atopic dermatitis and offers a targeted, non-immunosuppressive therapeutic approach.

We treated three UV patients, patient 1 and 2 with normocomplementamic UV, patient 3 with hypocomplementamic UV, who were refractory to prior therapies, including oral corticosteroids, hydroxychloroquine and methotrexate, with Lebrikizumab administered per atopic dermatitis dosing regimen. Treatment response was assessed using the Urticaria Control Test (UCT), the Dermatology Life Quality Index (DLQI), and the Daily Health Assessment Form (DHAF) for UV. Patient consented in publication of their cases.

Baseline UCT scores were 12, 5 and 0, respectively. Initial DLQI scores were 10, 24 and 26, and baseline total DHAF-UV scores were 20, 36 and 43. The maximum UCT scores achieved were 14 (+2), 16 (+11) and 8 (+8), while the lowest DLQI scores reached were 0 (-10), 2 (-22) and 11 (-15). Correspondingly, DHAF-UV total scores decreased to 0 (-20), 4 (-32) and 6 (-37). Patient 1 initially received prednisolone 50 mg daily and gradually tapered the dose to 2 mg over time. Patient 2 did not receive any additional immunosuppressant. Patient 3 was on continuous treatment with MTX 15 mg weekly and prednisolone 5 mg daily, with only marginal improvement of arthritis and persistent, severe cutaneous symptoms before initiation of lebrikizumab. Lebrikizumab was well tolerated, with no adverse events reported.

All patients reported a marked clinical improvement under treatment with lebrikizumab, reflected to varying degrees by improved UCT, DLQI and DHAF-UV scores. Anti-IL-13 therapy may represent a promising target in UV. Further studies in larger patient cohorts are required to obtain representative data.