Secukinumab Effective for Psoriasis

Langley RG, Elewski BE, Mark Lebwohl M, et al., for the ERASURE and FIXTURE Study Groups. Secukinumab in Plaque Psoriasis - Results of Two Phase 3 TrialsN Engl J Med  (2014) 371:326-338. July 24, 2014. doi: 10.1056/NEJMoa1314258

Secukinumab, a fully human interleukin-17A monoclonal antibody, was more effective than placebo or etanercept for moderate to severe psoriasis, in two randomized trials, ERASURE and FIXTURE.

The ERASURE trial randomized 738 patients to a high or low dose of secukinumab, or to placebo. The FIXTURE trial randomized 1,306 patients to a high or low dose of secukinumab, to placebo, or to etanercept.

The eligibility criteria for the two studies were similar: a score of ≥12 on the psoriasis area-and-severity index (PASI), and 3 or 4 on the modified investigator’s global assessment (IGA).

The co-primary efficacy end points were a reduction of 75% in the PASI (PASI 75) and a response of 0 or 1 on the IGA at week 12, the induction phase.

Patients were given secukinumab as induction therapy, in either 300 or 150 mg doses, with an assessment at 12 weeks, and then a dose as maintenance therapy, with an assessment at 52 weeks. Secukinumab was given weekly for four weeks, and then tapered to every four weeks. In each group, placebo patients who didn’t reach PASI 75 were randomized again to secukinumab or placebo.

Results were as follows:

PASI 75 at 12 weeks

IGA = 0 or 1 at 12 weeks

ERASURE
N=738

300 mg

81.6%

65.3%

150 mg

71.6%

51.2%

Placebo

4.5%

2.4%

FIXTURE
n=1,306

300 MG

77.1%

62.5%

150 MG

67.0%

51.1%

Placebo

4.9%

2.8%

Etanercept

44.0%

27.2%

The rates of response on PASI and IGA increased up to week 16, then stabilized, and were sustained through week 52.

The incidence of adverse events, notably infections, were higher with secukinumab than with placebo, and were similar to etanercept.