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In this article, we take a look at the development of new treatments for atopic dermatitis.
The future of biologic treatment for atopic dermatitis may be quite diverse. While dupilumab represents the approved first biologic therapy for atopic dermatitis, 2018 may bring news on a variety of subcutaneously or intravenously administered biologic drugs under investigation that target specific molecules including IL13, IL17, and more.
The developments are part of a “growing movement towards the use of targeted therapies in treating atopic dermatitis, parallel to that which occurred in psoriasis,” write Lindsay C. Strowd, M.D., and Nupur Patel, MS, in a review published in Advances in Experimental Medicine and Biology.
Ongoing clinical trials may shed more light on the role of dupilumab, a human monoclonal IgG4 antibody that inhibits IL-4 and IL-13 by binding the IL-4Rα subunit that the IL-4 and IL-13 receptor complexes share, wrote the authors, both from Wake Forest University School of Medicine in North Carolina.
Phase 3 trial data already reported from the identically designed SOLO1 and SOLO2 trials should that dupilumab improved the signs and symptoms of atopic dermatitis versus placebo in adults after 16 weeks of treatment. More recently, the LIBERTY AD CHRONOS study showed that dupilumab, added to standard topical corticosteroid treatment for 1 year had acceptable safety and improved atopic dermatitis in adults.
Other studies of dupilumab are ongoing, including a Phase 3 study evaluating the efficacy and safety of dupilumab vs placebo in patients between 12 and 18 years of age with moderate-to-severe atopic dermatitis.
But dupilumab may be just the beginning in terms of effective biologic therapies for atopic dermatitis in 2018 and beyond.
Tralokinumab and lebrikizumab are IL-13 specific monoclonal antibodies originally were developed for treating asthma and other inflammatory conditions. Both drugs have completed phase 2 trials in AD patients.
“The results of both studies suggest that further study of anti- IL-13 therapies in AD are warranted, and they have the potential to provide a valuable treatment option in the future,” Patel and Strowd wrote in their review.
Results of the tralokinumab study showed that patients in the highest two dose groups had significant improvement in baseline EASI score vs placebo, as well as significant improvements in the Dermatology Life Quality Index (DLQI) according to the authors.
Likewise, in the randomized phase 2 study of lebrikizumab, which included 209 adults with moderate-to-severe AD who had failed topical corticosteroids, patients randomized to monthly dosing of lebrikizumab had EASI 50 and EASI 75 response rates that were significantly better than placebo and continued to improve over the course of the 12 week trial, according to Patel and Strowd.
Two IL-31 targeting agents to watch are BMS-981164, an anti IL-31 monoclonal antibody that can be given subcutaneously or intravenously, and nemolizumab (also called CIM331), which blocks binding to the IL31 alphareceptor (IL-31RA) and is primarily being studied as an injectable treatment for pruritus.
Overexpression of IL-31 leads to pruritus, alopecia, and skin lesions in mice, the authors wrote, and in humans, has been associated with late onset itch and is thought to promote AD and pruritus pathophysiology through the “scratch-itch cycle.”
A phase 1 trial of BMS-981164 has been completed but not reported, authors said, and a randomized, placebo-controlled phase 2 trial of nemolizumab showed that tin patients with previously uncontrolled moderate-to-severe AD, the agent “rapidly and consistently” improved AD as well as pruritus and sleep disturbance.
Initial studies of ILV-094, a novel antibody which targets IL-22, showed that this agent has favorable pharmacokinetics and toxicity. It’s now being evaluated as an intravenous treatment in a randomized, placebo-controlled phase 2 trial in adults with moderate-to-severe AD.
“Because IL-22 is a potential key cytokine in AD, its inhibition may provide advantages over other available treatments through potentially increased safety and specific targeting compared with other immunosuppressants,” Patel and Strowd said in their review.
IL-17 production plays a significant role in the pathogenesis of psoriasis, and is present in smaller amounts in AD lesions, according to the authors. As a result, some biologic medications evaluated in psoriasis patients are now being studied as treatments for AD.
The IL-17 antibody secukinumab is being evaluated in one randomized, placebo-controlled phase 2 trial that is currently recruiting patients with moderate-to-severe AD.
There are several case reports on patients with AD receiving ustekinumab, an anti-IL12/23 biologic medication that is effective in psoriasis. Some of the case reports say the AD patient responded well to ustekinumab treatment, while others reported only partial or no response, according to Patel and Strowd.
In a 33-patient randomized, placebo-controlled phase 2 study, AD patients treated with ustekinumab had higher SCORAD50 scores vs placebo, investigators reported. However, results did not reach statistical significance, possibly due to background use of topical glucocorticosteroids or insufficient dosing, they said.