Psoriasis Biologics Pioneer Talks Access, Efficacy, and Outcomes Measures

Alice Gottlieb, MD, PhD, has played an intrinsic role in the evolution of the treatment of psoriasis and psoriatic arthritis. Her research, using targeted immunobiologics as pathogenic probes, provided new understanding of the pathogenesis of psoriasis and provided the foundation for biologic drug development in psoriasis and psoriatic arthritis. Throughout her career, she has taught dermatologists how to diagnose and manage psoriatic arthritis. She has been involved in initiatives aimed at preventing disability due to psoriatic arthritis and developing outcome measures for use in clinical practice.



Dr Gottlieb is the founder and president of the International Dermatology Outcome Measures consortium and has received numerous awards for mentoring and teaching including the National Psoriasis Foundation’s Outstanding Educator in Psoriatic Disease Award in 2016 and multiple Excellence in Teaching Awards from the department of dermatology at Tufts University Medical School/Tufts Medical Center, with which she was affiliated for many years. She has since returned to her home state of New York and is a professor at New York Medical College and affiliated with Metropolitan Hospital in New York City.


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Dr Gottlieb is triple boarded in dermatology, rheumatology, and internal medicine, and she is one of only a handful of physicians in the United States to be certified in all 3 of these specialties. She has authored more than 300 peer-reviewed articles, presented her research at more than 200 dermatology and rheumatology conferences worldwide, and in 2016 was awarded with Honorary Membership in the American Academy of Dermatology in recognition of “outstanding leadership and service” and affirming her “uncommon and sustained dedication to dermatology and the goals and mission of the Academy.”  

Her list of degrees, awards, accolades, and titles is lengthy and impressive, but the one she mentions fondly in a conversation with The Dermatologist is the informal moniker, “Jewish Mother of Biologics for Psoriasis.”

Below Dr Gottlieb talks about her past and current research and the exciting outlook for psoriasis treatment, among other topics.
 
Q. How did psoriasis become the main focus of your research?
a. One of the main personal reasons that I became interested in this is because my mother has psoriasis and psoriatic arthritis; and now she’s on one of the drugs that I helped develop.

Q. Tumor necrosis factor (TNF) blockers have revolutionized the care of psoriasis and psoriatic arthritis patients. What role did you play in that?
a. My translational research provided the first double-blind, randomized, placebo-controlled study of the efficacy of TNF blockers as monotherapy for moderate to severe psoriasis, and this work led to multiple TNF blockers being FDA approved for psoriasis. The way this happened is that I had a patient with Crohn disease who also had psoriasis. Infliximab (Remicade) was approved for Crohn disease. I asked to follow that patient along with the gastroenterologist because I thought there was a common mechanism to Crohn and psoriasis. Both the psoriasis and Crohn waxed and waned together dependent on when the infliximab was given, thus it became very clear that they had a common TNF-mediated presence.  

We published that case report, and I said, “this is an amazing drug for psoriasis because the patient really clears.” Based on that single case report, we initiated a single center, double-blind, randomized, placebo-controlled study of infliximab vs placebo in psoriasis, and 80% of patients cleared at week 10, which was after only 3 doses of drugs. A month later the study was published in Lancet and it was the first monotherapy, double-blind, randomized, placebo-controlled study of the TNF blocker in psoriasis.

Q. You were one of the first scientists to demonstrate that psoriasis is a T-cell mediated disease. How did that happen and what resulted from that?
a. I was doing an experiment in the early 1980s, and we were using psoriasis as a “nonimmune” control, and as the experiment continued it was very obvious to me that there was a lot of immune activity going on in the psoriatic plaques. I initially demonstrated increased numbers of activated T cells and increased expression of a number of immunologic cytokines in psoriatic plaques, then I (and my colleagues) showed that treatment with a T-cell specific immunotoxin cleared psoriasis clinically and histologically.

Through my published studies and public presentations, I have convinced a number of pharmaceutical companies to use psoriasis as their proof-of-concept disease when testing new immunomodulators that may decrease T cell and dendritic cell cytokine production.
My work has affected drug development in psoriasis, psoriatic arthritis, and inflammatory bowel disease. As a direct result of my work, many biotechnology-engineered immunomodulators are FDA and/or European Medicines Evaluation Agency approved for psoriasis and psoriatic arthritis.

Q. Talk about your work with the International Dermatology Outcome Measures Organization.
a. The International Dermatology Outcome Measures Organization is a consortium of patients, physicians, pharmaceutical scientists, and other stakeholders that is dedicated to bringing clinically practical outcome measures to dermatologic practice and improved outcomes to clinical research.      

This is important because judgments are being made about doctors without good outcome measures, and in the absence of outcome measures, cost is the only determinant. Case mix is not considered, disease severity is not considered, and whether or not the disease clears is not considered. So the doctor who treats a patient with moderate psoriasis with only topical medications gets rated as highly efficient, while someone like me who treats psoriatic arthritis and clears 90% of psoriasis patients is rated as an inefficient and expensive doctor, and the consequence of that is that patients pay higher copays to see that doctor.  

Q. What is one of the main socioeconomic issues at play in psoriasis treatment?
a. The biggest problem is access. We have wonderful treatments for patients who are not going to get them. They are not going to get them because of many reasons, including that a lot of dermatologists are not willing to offer all these treatments.

The other reason patients do not have access to these new drugs is because they are expensive, and some insurances do not cover the cost and patients cannot afford them. Medicare is a case in point. It’s important to point out that all of the coupon programs and free drug programs work only for commercial payers—by law, they cannot be used for Medicare or Medicaid patients.

Another major challenge is that we are losing mid-level, academically-oriented dermatologists because they do not have enough protected time to do research and their salaries are less than half of what they can make in private practice. We are ultimately losing a generation of research-oriented dermatologists. We will not feel it immediately, but we will feel it eventually.
 
Q. This is an exciting time for psoriasis research. What’s the current status?
a. There is more refinement. There clearly is an important role for IL-23 and IL-17 in psoriasis—the TH17 pathway. There is a large degree of overlap in what TNF does and what some of these other cytokines do. Now we have drugs that target IL-17, we soon will have drugs that target only IL-23; there are currently at least 4 in development. In the joints, psoriatic arthritis is a major comorbidity of psoriasis. Infliximab, adalimumab (Humira), and etanercept (Enbrel) are the only drugs that are currently FDA approved to inhibit radiographic progression of psoriatic arthritis.

I am hoping that in the future some of these newer drugs will be equally effective. We already have secukinumab (Cosentyx) and ustekinumab (Stelara) approved for at least controlling the signs and symptoms of psoriatic arthritis.
Psoriasis is a lifelong disease, it often starts when people are young, and as many drugs as we have now we need more because most drugs lose a little bit of efficacy every year.

Q. What is a challenge facing the psoriasis treatment community?
a. We need better topicals for the mild to moderate cases of psoriasis—which comprise most of psoriasis—but Pharma does not see this as a big area of opportunity. There are very few companies interested in investing in topicals, but it’s an area where we still have a huge need. Pharma is looking for drugs that will make billions, not hundreds of millions of dollars. In the absence of a cure, we need better topicals and orals that are as safe and as effective as the biologics.

Q. What’s ahead on the psoriasis treatment landscape?
a. The real excitement is in the biologics. Clearly, we are going to have ones that work even better on the skin than the TNF blockers. Whether they work equally well on the joints as TNF blockers remains to be seen, but there are going to be comparative studies. I also think we are going to see more pediatric approvals, which we need; and I think we will see more approvals of biologics for the treatment of hidradenitis suppurativa and atopic dermatitis.