Key clinical-trial evidence for apremilast
On September 23, 2014 the US Food and Drug Administration (FDA) approved apremilast for treatment of patients with moderate-to-severe plaque psoriasis mostly on the basis of results from 2 multicentre clinical trials — ESTEEM 1 and ESTEEM 2.
- FDA approval for moderate-to-severe plaque psoriasis was based on results from the ESTEEM trials.
- In these trials, 1257 patients with moderate-to-severe plaque psoriasis were randomized 2:1 to apremilast 30 mg twice daily (after a titration period) or placebo.
- The primary end point was the number of patients with a 75% improvement in the Psoriasis Area and Severity Index (PASI-75).
- In ESTEEM 1, significantly more patients receiving apremilast achieved a 75% reduction in PASI (psoriasis area severity index – a tool used to measure the severity and extent of psoriasis) score compared to placebo (33.1% vs 5.3%; P<.0001) at 16 weeks.
- In ESTEEM 2, significantly more patients receiving apremilast also achieved PASI-75 compared to placebo (28.8% vs 5.8%; P<.0001) at 16 weeks.
- In the ESTEEM trials, the majority of adverse events with apremilast were considered mild to moderate in severity and consisted primarily of nausea and vomiting, which generally resolved within 1 month.
- Notably, key clinical trials with Enbrel® (etanercept) have found that approximately 38% to 40% of patients achieve PASI-75 within a similar timeframe. Key trials with Remicade® (infliximab) and Humira® (adalimumab) have found that approximately 60% to 64% and 49% to 59%, respectively, achieve PASI-75 within a similar time frame.
The proportion of subjects who achieved PASI-75 responses, and sPGA (static physician global assessment score — physician's impression of the disease at a single point) of clear (0) or almost clear (1), are presented in Table 1.
|ESTEEM - 1||ESTEEM 2|
|PASI 75%; no. (%)||15 (5.3)||186 (33.1)||8 (5.8)||79 (28.8)|
|sPGA no. (%)||11 (3.9)||122 (21.7)||6 (4.4)||56 (20.4)|
- The safety of apremialst has been assessed in 3 randomised, double-blind, placebo-controlled trials involving 1426 adult subjects with moderate to severe plaque psoriasis.
- Subjects were randomized to 30 mg twice daily apremilast or placebo.
- Subjects ranged in age from 18 to 83 years, with an overall median age of 46 years.
- Adverse reactions are summarised in Table 2.
Table 2 Adverse reactions reported in >1% of subjects on apremilst and with greater frequency than in subjects on placebo; up to day 112 (Week 16)
|Adverse reaction||Placebo (N= 506) no. (%)||Apremilast (N= 920) no. (%)|
|Diarrhea||32 (6)||160 (17)|
|Nausea||35 (7)||155 (17)|
|Upper respiratory tract infection||31 (6)||84 (9)|
|Tension headache||21 (4)||75 (8)|
|Headache||19 (4)||55 (6)|
|Abdominal pain||11 (2)||39 (4)|
|Vomiting||8 (2)||35 (4)|
|Fatigue||9 (2)||29 (3)|
|Dyspepsia||6 (1)||29 (3)|
|Decrease appetite||5 (1)||26 (3)|
|Insomnia||4 (1)||21 (2)|
|Back pain||4 (1)||20 (2)|
|Migraine||5 (1)||19 (2)|
|Frequent bowel movements||1 (0)||17 (2)|
|Depression||2 (0)||12 (1)|
|Bronchitis||2 (0)||12 (1)|
|Tooth abscess||0 (0)||10 (1)|
|Folliculitis||0 (0)||9 (1)|
|Sinus headache||0 (0)||9 (1)|
- Apremilast has demonstrated safety and efficacy in the treatment of psoriatic arthritis and plaque psoriasis.
- However, apremilast has not been compared to other approved treatments for psoriasis, and results from the placebo-controlled trials suggest a degree of efficacy that may be less than most FDA-approved biologic alternatives.
- Apremilast likely offers an oral alternative to biologics in patients not responding adequately to biologics (e.g. adalimumab, infliximab, etanercept, ustekinumab), those with a diminished response over time, and those who are unable to take or tolerate the biologic agents.
- Further clinical trial data and real-world experience are required to assess apremilast's true value versus other agents in the management of psoriasis.