“It’s finally here,” says Dr. Mark Lebwohl, professor of dermatology and chairman of the department of dermatology at the Mount Sinai School of Medicine in New York, of the September 25 FDA approval of Stelara (generic: ustekinumab) for moderate to severe plaque psoriasis. “I can tell you it has been long-awaited by my psoriasis patients who have not responded, or had contraindications, to available treatments.”
Psoriasis, an autoimmune disorder that occurs when skin cells grow too quickly, affects about 6 million Americans. And nearly 1 million adults might be candidates for the new treatment, which is not indicated for children. Stelara disables proteins released by the immune system that play a role in the overproduction of skin cells and inflammation.
At the close of a busy afternoon at his dermatology practice, Dr. Lebwohl, who was involved in the clinical testing of the new drug, discussed with us the promise (and potential drawbacks) of Stelara and other drugs that treat disease by targeting the immune system.
Q: What sets Stelara apart from conventional therapies for moderate-to-severe psoriasis?
Dr. Lebwohl: We have never had anything that works precisely this way. It is the first drug therapy that requires just four shots a year, and the overwhelming majority of patients improve dramatically. The approved treatment schedule is two injections four weeks apart, followed by maintenance injections every 12 weeks. Other injectable therapies are given weekly, twice a week, or every other week.
Q: What type of benefit have you observed with Stelara in your patients or study participants?
Dr. Lebwohl: We have seen benefit in many patients. In fact, it would be unusual for it not to work. On day one, people get the first injection. Four weeks later, there is a dramatic benefit. They get the second injection at that time and then return three months later for a third shot. At that visit, most patients are clear or close to clear.
Q: Has Stelara been tested for the type of psoriasis that affects people’s joints?
Dr. Lebwohl: It has been studied for joint disease, and it was beneficial. The study dose was higher than the one used for skin disease, and given once a week for four weeks.
Q: Do people inject themselves with Stelara or come to the doctor’s office?
Dr. Lebwohl: It is approved for administration in the doctor’s office. If you review the FDA deliberations on this approval, it seems their conclusion is based on the fact that Stelara is a systemic drug, it affects the immune system, and patients ought to be seen by doctors at least four times a year.
Q: Any word yet on insurance coverage?
Dr. Lebwohl: We expect approval from federal insurers, and the drugmaker, Centocor Ortho Biotech, has set up a phone line for physicians to check with the other insurances. However, the insurers have not yet had time to respond.
Q: What do people considering treatment with Stelara need to know?
Dr. Lebwohl: Clinical trials of Stelara were conducted in more than 2,000 patients. Some have taken the drug for longer than three years, and many for a shorter period of time. No clear side effect that emerged.
Stelara is an antibody that blocks a component of two chemicals: IL (interleukin) 12 and IL 23. It turns out that some people are born without that target component. In other words, they are born as though they had Stelara on board. Research on 41 of these people shows that their main problem has been susceptibility to Salmonella infections and also mycobacterial infections, such as tuberculosis.
In the studies of Stelara, there were no cases of either kind of infection–perhaps because we are giving the drug intermittently as opposed to having a lifelong genetic abnormality.
Nonetheless, people should be tested for tuberculosis prior to initiating Stelara therapy. In addition, they should never receive BCG (bacille Calmette-Guérin) vaccines, a type of vaccine used in other countries (but not in the United States) that contains mycobacteria. The usually harmless bacteria caused serious infections in those 41 people; that’s how their genetic abnormality was discovered. People on Stelara should get flu vaccines, but not one containing the live virus. For example, patients on this treatment should not get the seasonal flu vaccine in the inhaled form that has a live virus. They should instead get the shot that contains inactive virus and has no chance of infecting them.
Q: Are you involved in clinical trials of other dermatologic treatments or promising research projects?
Dr. Lebwohl: Yes. At least two experimental biologic agents for psoriasis act upon newly identified molecular targets and appear to be effective. We will be seeing more biologics as time goes on.
Highly targeted biologic therapies are very effective and safe. The drawback, however, is they are very expensive to make. The same is true for biologics to treat diseases other than psoriasis. For example, some cancer drugs target the tumor and spare normal cells that are nearby. Biologics are very costly but have the potential of significantly changing our lives for the better. It’s important that we figure out better ways to develop and manufacture these promising therapies.
Dr. Mark Lebwohl is president of the New York State Society of Dermatology and has served as chairman of the Section on Dermatology of the New York Academy of Medicine. Dr. Lebwohl is a member of the medical advisory board of the National Psoriasis Foundation and editor of Psoriasis Forum as well as medical editor of The Bulletin of the National Psoriasis Foundation.