Posted on May 14, 2015 in: Professional Practice
by Haya Abu-Seir, Pharm.D., Jessica Probst-Wesolek, Pharm.D., Jordan Masse, Pharm.D., and Jordan Sedlacek, Pharm.D., PGY1 pharmacy residents, St. John Hospital and Medical Center
Psoriasis is a chronic, inflammatory, immunologic skin disease that affects approximately 2 percent of the United States population. Treatment for psoriasis is tailored to the patient and typically begins with topical corticosteroids for limited psoriasis. Treatment can be escalated to ultraviolet radiation, vitamin D analogues, topical tacrolimus and oral immunosuppressive agents such as methotrexate and cyclosporine. When such modalities fail or are not tolerated, injectable biologic agents are an effective option for most patients. The purpose of this article is to discuss two recently approved agents: secukinumab (Cosentyx™) and apremilast (Otezla®).
Secukinumab is a human monoclonal antibody that acts as a selective IL-17A antagonist for psoriasis. The regimen consists of five weekly subcutaneous injections followed by an injection every four weeks. While the manufacturer recommends 300 mg per dose, 150 mg may be sufficient for some patients. Common adverse events include upper respiratory infections, nasopharyngitis and diarrhea.
The study that led to secukinumab’s approval combined two double-blind phase III trials comparing secukinumab (300 mg and 150 mg doses) to placebo and etanercept using the Psoriasis Area and Severity Index (PASI) as a major outcome. In one trial, a significantly higher proportion of patients achieved 75 percent improvement in PASI score using either dose of secukinumab compared to placebo at week 12 (81.6 percent, 71.6 percent and 4.5 percent, respectively). Adversely, the second study demonstrated a similar statistically significant outcome with secukinumab (300 mg and 150 mg) compared to placebo and etanercept (62.5 percent, 51.1 percent, 2.8 percent and 27.2 percent, respectively; p-value < 0.0001). These results indicate that secukinumab is superior to etanercept, a second line agent for psoriasis.
Apremilast (Otezla®), an oral psoriatic arthritis agent, is a selective PDE-4 inhibitor that increases intracellular cAMP and IL-10, and attenuates INF-γ, TNF-α, IL-12 and IL-23. The dose is titrated to 30 mg twice daily and requires renal adjustment. Adverse events include headache, diarrhea, depression, weight loss, upper respiratory infections, nasopharyngitis and nausea.
There have been two randomized controlled trials investigating the use of apremilast. Both used the American College of Rheumatology Criteria for 20 percent improvement (ACR20) as a primary endpoint. The first study compared 20 mg twice daily or 40 mg daily of apremilast versus placebo. At 12 weeks, both apremilast doses yielded a significantly higher percentage of patients achieving an ACR20 response than placebo (43.5 percent, 35.8 percent and 11.8 percent, respectively). The second study compared 20 mg and 30 mg twice daily of apremilast to placebo for 24 weeks, which also showed significantly more patients achieving ACR20 than placebo. At the end of a 24-week extension period, the treatment groups had a sustained response of achieving ACR 20 at week 52.
In conclusion, secukinumab and apremilast could be considered for patients who have not responded to first-line treatment of psoriasis and psoriatic arthritis. Further research will elucidate their role in practice.
References available upon request from MPA office.