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Thursday, June 28, 2012

Anti-IL17 mAb shows promising results in psoriasis treatment


Exciting – and surprising – results from a clinical trial for psoriasis are presented in this month’s issue by Krueger et al (J Allergy Clin Immunol 2012;130:145-154.e9). The authors report on a randomized trial of a new humanized IgG4 monoclonal antibody, ixekizumab. It would be fair to say the results from their phase I trial are near astonishing.

Based on published evidence that psoriasis is a TH17-mediated disease, the authors postulate that IL-17 acts as a “gatekeeping” cytokine in the pathogenesis of psoriasis, noting that much of the evidence from animal studies points to IL-22. They point out that IL-22 in humans is produced from a different T cell subset, TH22 cells, unlike mice where TH17 cell produce both.

Their speculation paid off. Krueger et al. report dose-dependent, significant improvement in both pathophysiology and clinical presentation of psoriasis subjects after only 2 weeks of ixekizumab treatment. Skin biopsies from subjects demonstrated rapid improvements in keratinocyte proliferation, hyperplasia, epidermal thickness, T cell and dendritic cell infiltration of the dermis and significantly suppressed expression of innate immunity peptides. After 6 weeks of treatment, the authors report that subjects’ skin appeared normal. Interestingly, 100% of subjects in the 150mg dosing group no longer presented clinically with psoriasis at 6 weeks of therapy. Krueger et al. comment that the effectiveness of ixekizumab at 2 and 6 weeks was surprising since other antibody therapies typically require 12 weeks to demonstrate efficacy. They also note that the adverse effects profile is agreeable and the drug well-tolerated.

Noting that many genes associated with psoriasis are co-regulated by IL-17 and TNF-α, Krueger et al. show that IL-17 blockade with ixekizumab is far more effective in suppressing the co-regulated genes than TNF-α blockade by etanercept. They suggest that their evidence shows that IL-17 is a pivotal cytokine in the pathology of psoriasis, affecting many effector functions of other T cell subsets.  

22 comments:

  1. Anyone know why this paper, which reports on the phase 1 trial, was published three months after the NEJM paper reporting on the phase 2 trial?

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    1. We forwarded your question to senior author James Krueger, from The Rockefeller University in New York. Here is his response: "While the phase 1 trial took place before the phase 2 trial and its clinical outcomes were known for the design of the phase 2 study, it took us a while in the laboratory to do more complex cellular and genomic measures in this study. It also became clear in having this paper reviewed elsewhere that reviewers had a hard time determining the level of improvement in disease activity, as there was not a non-lesional biopsy included in the analysis. We realized that a solution was to conduct a meta-analysis using prior data we had generated with etanercept treatment of psoriasis that had more controls in it. Thus, it took some additional time to re-analyze our study results within the context of additional patients and samples. If our first presentation of the data (without a comparison to non-lesional skin) had been accepted, then the publication order would have been phase 1, followed by phase 2 data. The process of publishing papers today and timing of getting it to print is more a function of reviewers and editorial tastes, particularly in high impact journals, than it is the time sequence of actual submission of articles. The roll-out of data for the other IL-17 antagonist, AMG 827 (Amgen) has followed a similar path in which there is close publication of phase 1 and phase 2 data, but the phase 1 data are essential to interpreting mechanisms and designs of phase 2 trials that had more of a clinical focus."

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  2. A comprehensive and interesting answer! Thank you.

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  3. Hello,

    Anti-IL-17 antibodies are identified that are characterized as having a high affinity and slow off rate for human IL-17. These antibodies of the invention may be chimeric, humanized or fully human antibodies, immunoconjugates of the antibodies or antigen-binding fragments thereof. Thanks a lot for creating this type of valuable site...

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  4. I could not find microarray samples for lower doses and time points longer than 2 weeks and wondering whether the authors are planning to make them available to the public. Would it be possible to take a look on them?

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  5. Really Helpful Blog That's Obviously Help For Psoriasis Injured People.Here m Get Something New Details about Anti-IL17 mAb.Thanks For Putting this Cool Post!!!!!!!

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  6. my daughter has psoriatic arthritis. She has taken Enbrel, Humeria and Symponi. She got incredibly great results from all three, but developed an anaphylaxis reaction to Enbrel after several months, V-tac from Humeria after several months and she quit taking Symponi after 6 months when she got a large injection site reaction. Any chance that she might be able to tolerate this new drug?

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    1. While we cannot comment on specific cases, studies are still underway and definitive answers are not yet available. To monitor the progress of these studies, we recommend the NIH's clinicaltrials.gov website. Information on this particular topic can be found at http://www.clinicaltrials.gov/ct2/show/study/NCT01107457.

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  7. Its a good news that researches are being carried out for psoriasis treatment and positive results are coming out. This was really a very informative post.

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  8. If psoriasis is so complicated and genetically caused disease, how it may be that some people have improvements just by taking tea or sun exposure, for example? Thanks.

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  9. The effects of psoriasis can truly be life altering depending on the severity. Some people can begin to withdraw from the world around them and become isolated and depressed because of this chronic skin disease.

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  10. This comment has been removed by a blog administrator.

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  11. maggie.danhakl@healthline.comFebruary 1, 2015 at 10:36 PM

    Hello,

    I hope you’re doing well. I wanted to let you know about a couple programs Healthline launched this year to support the psoriasis and psoriatic arthritis community. I wanted to spread the word about these great programs, so I thought I would share them with you.

    -First, our #pselfie program is a collection of photos from people living with psoriasis. Users can upload a photo on Instragram or Twitter with the hashtag #pselfie or upload a photo directly onto our page. You can view the photos here: http://www.healthline.com/health/psoriasis/selfie/photos-and-quotes For every photo we receive, we will donate $10 to the National Psoriasis Foundation.

    -Next, we have launched You’ve Got This, a collection of videos submitted by those living with psoriasis giving hope and encouragement to others with the condition. Again, for every video we receive we’ll donate $10 to the National Psoriasis Foundation. You can view the videos here: http://www.healthline.com/health/psoriasis/youve-got-this

    -Lastly, we have this great visual of ‘Words You Should Know’ for psoriasis and psoriatic arthritis. All of the terms and definitions were submitted by users from our Facebook community for psoriasis sufferers. You can check it out here: http://www.healthline.com/health/psoriatic-arthritis/words-you-should-know

    I’d love if you can share one or all of these with your social networks or include them as resources on your site. We’d also love if you wanted to participate in the You’ve Got This or #pselfie program. Please let me know if you can help spread the word about these programs.

    Thanks so much,
    Maggie Danhakl • Assistant Marketing Manager
    Healthline • The Power of Intelligent Health
    660 Third Street, San Francisco, CA 94107
    www.healthline.com | @Healthline | @HealthlineCorp

    About Us: corp.healthline.com

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  17. I'm Naomi, i reside in Austin texas U.S i'm 24 years old i suffered with server Gullatte psoriasis which has dramatically taken over my whole life. I've tried everything from topical treatments to lighting therapy to home remedies unfortunately nothing has worked nor eased my pain and embarrassment. luckily I recently just ended a herbal trial from a trustful herbalist doctor which cleared my skin completely. I'm so much exited the diseases has finally eliminated with natural herbal treatment from herbalist Dr. Here is the email to contact the herbal centre; drgaligaherbalcenter@gmail.com

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