Treatment: Biologics
Ustekinumab

FDA approved to treat:

• Plaque psoriasis (moderate to severe)

• Patient must be 18 years or older and a candidate for phototherapy or systemic (works throughout the body) therapy

• Psoriasis is the first disease for which the U.S. Food and Drug Administration (FDA) has approved ustekinumab

What’s involved in taking ustekinumab?

• Patients receive injections from a health-care provider. After the initial injection, the patient returns 4 weeks later for the next injection. The patient then returns once every 12 weeks for an injection.

• A health-care provider gives the injections to ensure that each patient is carefully monitored at regular intervals.

• The patient’s weight determines the dosage. For patients weighing 220 pounds or less, the recommended dose is 45 milligrams. The recommended dose for patients who weigh more than 220 pounds is 90 milligrams.

• Before ustekinumab is prescribed, the patient has screenings tests for the hepatitis B virus and latent (not causing symptoms) tuberculosis (TB).

How does ustekinumab work? Psoriasis occurs when the body produces skin cells too quickly. Ustekinumab blocks 2 proteins in the skin, IL-12 and IL-23, which are believed to lead to an overproduction of skin cells and the inflammation of psoriasis. This is the first medication approved for treatment of psoriasis that works this way.

Effectiveness: More than 2,200 patients with moderate to severe psoriasis were enrolled in the clinical trials for ustekinumab. The results from these clinical trials show that ustekinumab may more effectively clear the skin than the other biologics currently approved for the treatment of psoriasis. Here is what the studies show:

• In the first phase of clinical trials, 77% of the patients who received ustekinumab had a significant reduction in the severity of their psoriasis between weeks 4 and 24. The researchers observed that 77% of the patients given ustekinumab had a 75% reduction in their PASI scores. PASI stands for Psoriasis Area and Severity Index. It allows researchers to assign numbers to determine the severity of a person’s psoriasis.
   

• Favorable results also were seen during Phase 3 of the clinical trials. It is during this phase that the long-term safety and efficacy of a medication are assessed. The data from Phase 3 show that more than half (67%) of the patients who received ustekinumab had a 75% reduction of their psoriasis. In this same study, 3% of the patients who received the placebo (inactive ingredient) had a 75% reduction.
   

• It is important to know that not every patient sees clearer skin with ustekinumab. In some cases, the psoriasis does not respond at all or responds partially. The people in the Phase 3 clinical trial who responded partially had a tendency to weigh more, have more severe psoriasis, have had a skin disease for a longer time, not get relief from other biologic medications, and have psoriatic arthritis.
   

• The clinical trials show that when the patient stops receiving ustekinumab, the psoriasis gradually returns. To continue seeing results, a patient may need to take ustekinumab indefinitely.

Safety and side effects: Continued regular dosing brings up concerns about safety and side effects. It was such concerns that delayed the FDA’s approval of ustekinumab for several months. This medication was approved because more than 2,200 patients were enrolled in the clinical trials and the trials showed that ustekinumab is generally well tolerated. The trials did not show any major safety issues in the patients who have received ustekinumab for as long as 18 months.

Side effects seen during the clinical trials were generally mild. The most commonly reported mild side effects were upper respiratory problems such as cough and congestion, headache, joint pain, and mild skin reactions at the injection site. Lab tests showed a reduced number of white blood cells in the patients given ustekinumab. This was expected as ustekinumab suppresses the immune system.

The primary concerns for any medication that suppresses the immune system are an increased risk for a serious infection and an increased risk for developing cancer.

During the clinical trials, 2 patients were hospitalized for a serious infection. One developed cellulitis (a serious infection deep within the skin), and one developed herpes zoster (shingles). It is important to remember that more than 2,200 patients were enrolled in these clinical trials.

Two patients enrolled in a clinical trial were diagnosed with skin cancer. One patient who did not receive ustekinumab was diagnosed with squamous cell carcinoma (a common type of skin cancer). One patient receiving ustekinumab was diagnosed with basal cell carcinoma (the most common type of skin cancer).

To learn about the long-term safety and possible side effects, studies continue to monitor patients receiving ustekinumab.

References:
O'Neill JL, Kalb RE. “Ustekinumab in the therapy of chronic plaque psoriasis.” Biologics 2009; 3: 159-68.

Patel RV, Clark LN, Lebwohl M et al. “Treatments for psoriasis and the risk of malignancy.” Journal of the American Academy of Dermatology June 2009; 60: 1001-17.

U.S. Food and Drug Administration, Center for Drug Evaluation and Research. “FDA Advisory Committee Unanimously Recommends Approval of Ustekinumab for Treatment of Moderate to Severe Plaque Psoriasis.” June 17, 2008.