NYC area clinical trial for eczema therapy recruiting participants

A research group at Rockefeller University in New York City seeks participants for a clinical trial of an experimental therapy for atopic dermatitis. See below for details.

Dr. Emma Guttman-Yassky, Dr. Saakshi Khattri and others are exploring whether Stelara (ustekinumab), currently approved in the US for treatment of psoriasis, might benefit patients with moderate to severe AD whose condition has not improved with conventional treatment.

Ustekinumab is a monoclonal antibody to the p40 subunit of the signaling proteins IL-12 and IL-23. It binds to these proteins and prevents them from working. Since IL-12 and IL-23 are involved in the development of certain kinds of T cells, ustekinumab will put a damper on a subset of the T cell arm of the immune system.

I started to speculate about exactly how ustekinumab might work for AD but then I wisely looked at the researchers' own explanation on clinicaltrials.gov. I was only 25% right, so you'd do well to look at their writeup if you're interested.

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Randomized Pilot Study of Ustekinumab for Subjects with Chronic Atopic Dermatitis Who Have Sub-optimal Response to Prior Therapy

This study is currently recruiting participants.
Verified March 2013 by Rockefeller University

Sponsor:
Rockefeller University

Information provided by:
Rockefeller University

ClinicalTrials.gov Identifier: NCT01806662

Purpose
We are carrying out a clinical trial with the drug Stelara (ustekinumab), which is already FDA approved for Psoriasis, in patients with moderate to severe eczema, ages 18 years - 75 years.  In order to be eligible, a patient must have failed at least topical steroids and either light therapy or oral steroids. Patients will have 15 visits over the course of a year at Rockefeller University, which is located on the Upper East Side of New York City. Patients are guaranteed to receive 3 doses of Stelara throughout the study. Patients will also be allowed to use Triamcinolone 0.025% during the course of the study.  If the medication is effective at clearing a patient’s eczema, they will be eligible to receive an extra dose at the completion of the study.  For full participation, patients are compensated $600.

Name/Title of the Principal Investigator: Dr. Emma Guttman, MD/PhD

Contact Information:
Saakshi Khattri, MD - Clinical Research Fellow
1230 York Avenue
New York, NY  10065
Business number: 212-327-8354/8333
Fax number: 212-327-8232
Recruitment Office 1-800-782-2737
email: skhattri@rockefeller.edu

For more information, please visit:
http://clinicaltrials.gov/ct2/show/NCT01806662

Antibody therapy appears powerful against psoriasis

A biotechnology therapeutic for psoriasis appears to clear most of the symptoms in many patients, according to recently published results of clinical trials.

The therapeutic is “ixekizumab,” an antibody that inactivates a “cytokine” or signaling molecule produced by a subset of white blood cells called type 17 helper T cells.* Researchers at the pharmaceutical company Eli Lilly and university colleagues published the Phase 2 results in the New England Journal of Medicine in March. I learned about ixekizumab from a JACI paper published last week, reporting on aspects of the earlier Phase 1 trial.

Th17 are thought to be overactive in psoriasis patients. That is not the case in patients with atopic dermatitis, for whom helper T cells of types 2 and 22 generally exist in higher numbers and are more active than they are in the average person. The authors of the JACI paper speculate that tailored antibody therapy could prove as effective in controlling eczema as ixekizumab has for psoriasis.

In the Phase 2 trial, researchers injected 142 patients with various doses of ixekizumab at regular intervals over a 16-week period. They found that, for all but the lowest dosage, the antibody mostly cleared up psoriasis—as measured by a standard set of measures—for more than 75% of the patients in the trial.

The authors did not present data showing how long the effects lasted. But they did note that hardly anyone dropped out of the trial because of adverse effects. (From what I can tell, those who dropped out came from the lowest dosage group.)

Nor was there any indication how expensive ixekizumab might be. I imagine that, compared to drugs such as steroids, custom-produced antibodies would be extremely expensive for patients and insurers.

Nevertheless, the results are unusually positive. A blog post on the JACI website called the results “near-astonishing.” Keeping in mind that all trials and papers published on them are bankrolled by pharma companies (who else can pay for clinical trials?) this area of antibodies against T cell cytokines seems worth watching closely.

* I am pretty sure that Th17 cells are not the seventeenth type of helper T cells. The only ones I've ever heard of are Th1, Th2, Th17, and Th22. I don't know why the last two are numbered 17 and 22 instead of 3 and 4. This sort of thing is why I got out of immunology.

Here comes the asthma

So it happened, a few weeks ago: Voov showed the first signs of developing asthma. We were always aware that she might, because eczema runs in the family and my sister has eczema and asthma, and asthma is the final part of the famous Atopic Triad. Still, it is a bummer to see your two-year-old with a rubber mask over her face taking her twice-daily dose of an inhaler.

Voov had had a cold, and was in for a checkup, and the doctor noted that she had a slight wheeze; her blood oxygenation was at 95%. So, with her history, the doctor tentatively diagnosed asthma and sent her home with the inhaler and a special mask. Voov was initially pretty excited about the attention, but after a few days, applying the inhaler took two adults, one to straitjacket the kid and the other to handle the inhaler.

Then she got better or at least well enough that she didn't have a wheeze. For now, the inhaler's packed away. Voov is healthy and upbeat and I think she'll cruise right through childhood just fine even if she has to carry an inhaler with her.

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I thought I'd mention this great review I read recently titled "Epidermal Barrier Dysfunction in Atopic Dermatitis." It's from 2009 and provides an encyclopedic view of how known genetic factors are related to the breakdown of the skin barrier, and how many factors such as pH and enzymes and antimicrobial peptides are involved. It also has an interesting section toward the end featuring this graphic

with an accompanying explanation of how it is that many more kids than adults have eczema, and how the condition improves with age for the lucky majority. Basically, when we're newborn, our skin barrier is terrible, the worst it'll ever be. In the first few years of childhood, the quality of our skin improves. In those people who have minor genetic defects that affect the skin barrier, eczema develops early on but fades away as the skin improves past some threshold. People with serious genetic defects like major filaggrin mutations never see their skin improve past the threshold, so they never escape eczema.

At least that's how the authors put it. It's a pretty hand-waving theory. For one thing, many scientists think that a poor skin barrier lets in pathogens and allergens that trigger a heavy immune response early on, and that this response imprints a permanent memory in the body (in the form of antibodies) that powers reactions to certain foods. So if this "memory" is made early on in the 20% of kids who have eczema, why does it go away for most of them after the skin barrier improves?

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One final item: Anacor Pharmaceuticals has begun phase 2 clinical trials of two novel anti-inflammatory ointments for treatment of eczema. The two compounds are boron-based (this is unusual) and have shown promise for treating psoriasis in more advanced clinical trials. For a thorough comparison of psoriasis and eczema, see the most recent JACI Journal Club, which discusses a two-part review paper on the topic.