On September 23, 2014, the US Food and Drug Administration (FDA) approved apremilast for the 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 endpoint 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 apremilast 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 apremilast 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. (%)|
|Diarrhoea||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.
We suggest you refer to your national drug approval agency such as the Australian Therapeutic Goods Administration (TGA), US Food and Drug Administration (FDA), UK Medicines and Healthcare products regulatory agency (MHRA) / emc, and NZ Medsafe, or a national or state-approved formulary eg, the New Zealand Formulary (NZF) and New Zealand Formulary for Children (NZFC) and the British National Formulary (BNF) and British National Formulary for Children (BNFC).