Proactive maintenance therapy of canine atopic dermatitis with the anti‐IL‐31 lokivetmab. Can a monoclonal antibody blocking a single cytokine prevent allergy flares?

Abstract

Background -Once the signs of canine atopic dermatitis (AD) are controlled, the proactive application of topical glucocorticoids can delay disease flares.Objectives -We wished to determine if the proactive administration of the anti-IL-31 lokivetmab would prevent or delay flares of canine AD.Animals -We tested this strategy in four Maltese-beagle atopic dogs before enrolling 21 dogs with spontaneous AD.Methods and materials -In our acute AD model, house dust mite (HDM)-sensitized dogs were injected once with lokivetmab. After seven days, an HDM suspension was applied epicutaneously, and both skin lesions and pruritus manifestations were quantified for 24 h. In a second study, 21 dogs with spontaneous AD controlled with anti-allergic drugs were treated with lokivetmab per manufacturer's recommendations; all anti-allergic drugs were discontinued within four weeks after the first injection. All dogs were followed prospectively for at least one year and the time-to-flare (TTF) of AD after the last day of anti-allergic treatment was determined.Results -In the experimental study, one injection of lokivetmab prevented nearly all expected allergen-induced pruritus manifestations but not skin lesion development. In dogs with spontaneous AD, the median TTF after lokivetmab proactive therapy was 63 days. One-fourth of dogs did not exhibit a flare for at least one year while receiving lokivetmab monotherapy.Conclusions -Although lokivetmab seems more effective to prevent pruritus than skin lesions in dogs with experimental AD' it also can delay disease flares in some dogs with the spontaneous disease. Studies are needed to identify those patients most likely to respond to such a proactive regimen.Abbreviations: AD, atopic dermatitis; DPM, duration of pruritus manifestations; HCA, hydrocortisone aceponate; HDM, house dust mite; mAb, monoclonal antibody; SLS, skin lesion score; TSLP, thymic stromal lymphopoietin; TTF, time-to-flare. Accepted 18 November 2018 Sources of funding: Chie Tamamoto-Mochizuki received a graduate student stipend by Zoetis. Conflict of interest: Thierry Olivry has received lecture honorarium and research funding from Zoetis.

Interleukin 31 in insect bite hypersensitivity—Alleviating clinical symptoms by active vaccination against itch

“…When comparing the clinical benefit of blocking IL-31 in horses with other species, we noticed a reduction of skin lesion severity in IBH-affected horses, which is in contrast to atopic dermatitis trials in dogs and humans that only showed reduction of pruritus whereas no improvement of eczema. 37,42 This suggests a meaningful impact of the self-inflicted trauma in horses with IBH. Although an anti-IL-31 therapy will not prevent the allergic reaction itself, it might represent an option stopping the vicious circle of self-reinforcing pruritus to alleviate clinical symptoms.…”

“…Comparably to the mAb against IL‐31, we suggest that the vaccine‐induced anti‐IL‐31 antibodies mitigate the IL‐31‐mediated pruritus and thus lowering the self‐inflicted trauma caused by the horse scratching its skin. When comparing the clinical benefit of blocking IL‐31 in horses with other species, we noticed a reduction of skin lesion severity in IBH‐affected horses, which is in contrast to atopic dermatitis trials in dogs and humans that only showed reduction of pruritus whereas no improvement of eczema . This suggests a meaningful impact of the self‐inflicted trauma in horses with IBH.…”

Interleukin-31 and Pruritic Skin

“…Moreover, in canine atopic dermatitis, anti-canine IL-31 antibody (lokivetmab) significantly inhibited scratching in dogs with canine atopic dermatitis [82][83][84][85]. Proactive treatment with lokivetmab also reduced the flare of canine atopic dermatitis [85].…”

Role of the Pruritic Cytokine IL-31 in Autoimmune Skin Diseases

“…Such approaches using nemolizumab (CIM331) have recently been tested successfully (also in terms of reducing itch) in atopic dermatitis in both humans and other primates (19, 20, 44–46). Similarly, the anti-canine-IL-31 monoclonal antibody, lokivetmab, has been used to treat atopic dermatitis in dogs (47–49). However, the potential clinical benefits of anti-IL-31 monoclonal antibodies have yet to be reported for CsU (and indeed other autoimmune skin diseases).…”