New findings on Apremilast ( Otezla ), a selective inhibitor of phosphodiesterase 4 ( PDE4 ), from the ESTEEM 1 and 2 phase III studies in patients with moderate to severe plaque psoriasis were presented.
In ESTEEM 1 and 2 patients received Apremilast 30 mg twice daily ( BID ) or placebo for the first 16 weeks, followed by a maintenance phase through week 32 in which patients on placebo for 16 weeks were switched to Apremilast.
Patients initially randomized to Apremilast 30 mg BID and who were PASI 75 ( Psoriasis Area and Severity Index ) responders at week 32 were re-randomized to either Apremilast 30 mg BID or placebo.
ESTEEM 1 has demonstrated a stable mean PASI improvement of 81 to 88% between weeks 32 and 52 for those patients who were treated for 52 weeks with Apremilast 30 mg BID and who achieved a PASI-75 score at week 32 ( n=77 ). These data are consistent with the mean PASI-75 improvement observed between weeks 16 and 32.
In the same group of patients, Apremilast 30 mg BID continued to demonstrate improvements in difficult-to-treat areas affected by plaque psoriasis.
Among patients who had nail psoriasis at baseline ( n=46 ), the majority showed meaningful improvement in their nails. A mean percent decrease from baseline in the Nail Psoriasis Severity Index ( NAPSI ) of 60.2% was observed at week 52. Of those patients who had scalp psoriasis defined as moderate or greater at baseline (n=49), the majority continued to demonstrate meaningful improvement in their scalp psoriasis with 72.9% having reduction of their scalp symptoms to clear or almost clear ( ScPGA 0 or 1 ) at week 52.
In ESTEEM 2, a significantly higher percentage of patients receiving Apremilast 30 mg BID has achieved a PASI-75 response at week 16 ( primary endpoint ) compared with patients who received placebo ( 28.8 vs 5.8% ).
The beneficial effects of Apremilast on psoriasis in difficult-to-treat areas of scalp, nails, palms and soles were also demonstrated in ESTEEM 2.
After 16 weeks of treatment, Apremilast 30 mg BID has demonstrated significantly higher response rates versus placebo for psoriasis affecting the scalp ( ScPGA 0-1: 40.9 vs 17.2% ).
A separate analysis of long-term ( 52-week ) safety and tolerability data from ESTEEM 1 identified no new or unexpected adverse events for patients treated with Apremilast compared with results at week 16.
The most frequently reported adverse reactions during the placebo-controlled period and the long-term 52-week Apremilast-exposure period were diarrhea, upper-respiratory tract infection, nausea, nasopharyngitis, tension headache, and headache.
Discontinuation rates for diarrhea and nausea were each less than 2% in the Apremilast 30 mg BID group through week 52.
No serious adverse events of diarrhea and nausea were reported in all groups through 52 weeks. Serious adverse events were similar between placebo and Apremilast in the first 16 weeks, and the rate did not change through the 52-week Apremilast-exposure period. No clinically meaningful changes in laboratory measurements were identified over the Apremilast 52-week exposure period.
No new or unexpected adverse effects were identified for patients treated with Apremilast in ESTEEM 2.
In a pooled analysis of ESTEEM 1 and 2, exposure-adjusted incidence rates ( per 100 patient-years ) for major adverse cardiac events, serious infections including systemic opportunistic infection, or malignancies were comparable between placebo and Apremilast treatment groups. ( Xagena )
Source: 72nd Annual Meeting of the American Academy of Dermatology ( AAD ), 2014