The FDA has said “yes” to a supplemental biologics license application for the expanded use of etanercept (Enbrel, Amgen), making it the first systemic therapy to treat pediatric patients (4 to 17 years of age) with chronic moderate-to-severe plaque psoriasis.
The approval was based on positive efficacy results from a 48-week, phase 3 study, which consisted of three phases: an initial 12-week, double-blind, placebo-controlled treatment period (day 1 to week 12) aimed at establishing efficacy; a 24-week, open-label treatment period (weeks 13 to 36) to assess the efficacy of etanercept therapy in all patients; and a 12-week, randomized, double-blind, withdrawal–retreatment period (weeks 37 to 48) to examine the effects of withdrawal of the study drug and subsequent retreatment. The primary efficacy endpoint was a Psoriasis Area and Severity Index score of at least 75 (PASI 75) at week 12. Secondary efficacy endpoints included PASI 50, PASI 90, and the physician's global assessment of “clear” or “almost clear” (score of 0 or 1).
At week 12, significantly more patients who received etanercept than those who received placebo achieved PASI 75 (57% versus 11%, respectively; P < 0.001); a significant difference was observed as early as week 4. The proportions of patients who achieved PASI 50 (75% versus 23%; P < 0.001) and PASI 90 (27% versus 7%; P < 0.001) were also significantly greater in the etanercept group than in the placebo group at week 12.
During the open-label phase, 62% of patients in the original placebo group (i.e., those who received placebo first and then received etanercept during the open-label period) and 69% of patients in the original etanercept group (i.e., those who received etanercept throughout) achieved PASI 75 at week 24. This response was maintained through week 36.
Etanercept, a soluble form of a tumor necrosis factor (TNF) receptor, was first approved in 1998 for the treatment of patients with moderate-to-severe rheumatoid arthritis (RA). The drug was subsequently approved in 1999 to treat moderate-to-severe polyarticular juvenile idiopathic arthritis; in 2002 to treat psoriatic arthritis; in 2003 to treat ankylosing spondylitis; and in 2004 to treat moderate-to-severe plaque psoriasis in adults.
Patients receiving etanercept are at increased risk of developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants, such as methotrexate or corticosteroids, or were predisposed to infection because of their underlying disease.
In clinical trials of all TNF blockers in adults, more cases of lymphoma were seen compared with control patients. The risk of lymphoma may be up to several-fold higher in RA patients. The role of TNF-blocker therapy in the development of malignancies is unknown.