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15 Dec 2016
New drug applications approved by US FDA as of 1 - 15 December 2016 which includes New Molecular Entities (NMEs) and new biologics. It does not include Tentative Approvals. Supplemental approvals may have occurred since the original approval date.

Asthma drug lebrikizumab shows potential in atopic dermatitis

Audrey Abella
06 Feb 2018

The addition of the anti-interleukin (IL)-13 monoclonal antibody lebrikizumab to a rigorous topical corticosteroid (TCS) regimen provided significant dermatologic benefit among patients with moderate-to-severe atopic dermatitis (AD), the TREBLE* study shows.

Two hundred and nine patients with inadequate TCS response for moderate-to-severe AD (≥10 percent of body surface area) were randomized 1:1:1:1 to receive subcutaneous injections of lebrikizumab (125 mg single dose [SD], 250 mg SD, or 125 mg once every 4 weeks [q4w]) or placebo q4w for 12 weeks following a 2-week, twice-daily TCS (0.1 percent triamcinolone acetonide or 2.5 percent hydrocortisone for facial or intertriginous lesions) run-in period. To qualify, patients needed an EASI** score of ≥14 and an IGA*** score of ≥3 at screening and end of run-in period, and pruritus VAS# score of ≥3 (as part of SCORAD##) at screening. [J Am Acad Dermatol 2018;doi:10.1016/j.jaad.2018.01.017]

At week 12, more lebrikizumab 125 mg q4w than placebo recipients achieved EASI-50 and EASI-75 responses (82.4 percent vs 62.3 percent; p=0.026 and 54.9 percent vs 34.0 percent; p=0.036, respectively).

The researchers noted that there was an upward sloping trajectory in the response curve in the q4w arm during the final weeks of treatment. “[This suggests] that the response plateau might not have been reached by week 12 … and that a longer treatment duration may lead to improved efficacy,” they said.

Furthermore, compared with placebo, more lebrikizumab 125 mg q4w recipients achieved IGA 0/1 at week 12 (33.3 percent vs 18.9 percent; p=0.098), as well as greater reductions in sleep loss VAS (53.6 percent vs 22.6 percent; p=0.023).

Although nonsignificant, the lebrikizumab 125 mg q4w regimen also led to reductions in the affected body surface area (57.7 percent vs 47.4 percent) and in pruritus VAS (40.7 percent vs 27.5 percent).

SCORAD-50 at week 12 was achieved by more lebrikizumab 125 mg q4w (51.0 percent vs 26.4 percent; p=0.012) and 250 mg SD (47.2 percent vs 26.4 percent; p=0.030) vs placebo recipients.

The researchers noted that the numerically higher responses with lebrikizumab 250 mg SD at earlier timepoints for certain outcomes could suggest the potential benefit of either a higher and/or a loading dose.

It is important to treat AD given its intensely pruritic nature and consequent impact on health-related quality of life. [Allergy Asthma Proc 2012;33:227-234; Cutis 2016;97:267-271; J Am Acad Dermatol 2016;74:491-498] Several treatment options for moderate-to-severe AD are calcineurin inhibitors, conventional immunosuppressants (ie, cyclosporine), and phototherapy. [Am Acad Dermatol 2014;71:116-132] However, topical treatments may have side effects and limited efficacy, the researchers pointed out.

Given its efficacy in asthma treatment, [Thorax 2015;70:748-756; Clin Exp Allergy 2014;44:38-46; Lancet Respir Med 2016;4:781-796] lebrikizumab may represent a novel targeted therapy in AD.

“[Our findings] suggest that IL-13-mediated signaling pathways play an important role in the pathogenesis of AD, and the blockade of this cytokine could lead to significant clinical benefit,” said the researchers.

“Targeting … IL-13 may also offer the advantage of a linear PK profile … [which, when] combined with the long half-life of lebrikizumab (19–22 days), in part explains for the ability to dose lebrikizumab q4w, and may allow for less frequent dosing during maintenance,” they added.

Due to the limitation potentially caused by TCS involvement, the researchers called for monotherapy and longer-duration trials on a larger population using higher and less frequent dosing to elucidate the safety and long-term efficacy of lebrikizumab in targeting IL-13 in AD.

 

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Most Read Articles
15 Dec 2016
New drug applications approved by US FDA as of 1 - 15 December 2016 which includes New Molecular Entities (NMEs) and new biologics. It does not include Tentative Approvals. Supplemental approvals may have occurred since the original approval date.