Apremilast

Oral thalidomide analog(phosphodiesterase-4 inhibitor) developed by Celegene for the indications spondylitis, psoriatic arthritis or psoriasis arthropathica, and moderate to severe psoriasis vulgaris (S3 guideline). A small monocentric study is available for lichen planus. Others for Behcet's disease and rheumatoid arthritis and atopic eczema. In the phase III study (ESTEEM), patients with moderate to severe psoriasis were treated with 2x30mg/day apremilast for 52 weeks. At week 16, 28.8% of those treated achieved a PASI-75 response (5.8% with placebo).

Good success can be achieved with 2x30mg/day apremilast in psoriasis capitis as well as in nail psoriasis (LAPIS-PSO study - cited in Reich K et al. 2016/2018).

Apremilast has also been used successfully in lichen planus of the nails (Skullerud KH et al 2021) .

Moderate to severe psoriasis vulgaris and psoriatic arthritis. Apremilast was approved in mid-January 2015.

see also under folliculitis decalvans

The use of apremilast during pregnancy and breastfeeding is not recommended.

Women of childbearing age should be instructed to use a reliable method of contraception during treatment with apremilast

The most frequently reported adverse drug reactions of apremilast are gastrointestinal disorders, including diarrhea (15.7%) and nausea (13.9%). Upper respiratory tract infections (8.4%), headache (7.9%) and tension headache (7.2%) were also reported. As a rule, these side effects were mild to moderate.

Furthermore, upper abdominal pain (8.7%), vomiting (8.7%) and back pain (7.7%) of mild to moderate severity occurred.

The gastrointestinal side effects usually occur within the first two weeks of treatment and usually subside within four weeks.

Hypersensitivity reactions are possible.

CYP-P450 inducers(e.g. rifampicin, phenobarbital, carbamazepine, phenytoin and St. John's wort) can lead to reduced therapeutic efficacy of apremilast.

^Otezla® (Celgene)

Apremilast should not be used in children and adolescents up to the age of 17 years. There have been post-marketing reports of severe cases of diarrhea, nausea and vomiting associated with the use of apremilast. Most events occurred within the first weeks of treatment. In some cases, patients were hospitalized. There may be an increased risk of complications in patients over 65 years of age. If patients develop a severe form of diarrhea, nausea or vomiting, discontinuation of treatment with apremilast may be necessary.

Apremilast is associated with an increased risk of psychiatric disorders, such as insomnia and depression. Cases of suicidal ideation and behavior, including suicide, have been observed in patients with or without a history of depression. The risks and benefits of initiating or continuing treatment should be carefully weighed when patients report previous or existing psychiatric symptoms or when concomitant treatment with other drugs likely to cause psychiatric events is intended. Patients and caregivers should be instructed to inform the prescribing physician of any behavioral or mood changes or suicidal ideation. If patients experience new psychiatric symptoms or worsening of existing symptoms, or if suicidal ideation or attempt is detected, it is recommended that treatment with the active substance be discontinued.

Patients who are underweight at the start of treatment should have their body weight checked regularly. In the event of unexplained and clinically relevant weight loss, these patients should be examined by a doctor and treatment discontinuation should be considered.

1. De Souza A et al (2012) Apremilast for discoid lupus erythematosus: results of a phase 2, open-label, single-arm, pilot study. J Drugs Dermatol 11:1224-1226
2. Gottlieb AB et al (2008) An open-label, single-arm pilot study in patients with severe plaque-type psoriasis treated with an oral anti-inflammatory agent, apremilast. Curr Med Res Opin 24:1529-1538.
3. Paul J et al (2012) An open-label pilot study of apremilast for the treatment of moderate to severe lichen planus: A case series. J Am Acad Dermatol PubMed PMID: 22910104.
4. Reich K et al. (2016) Annual meeting of the Austrian Society of Dermatology and Venereology (ÖGDV), Vienna, lecture FV 10.
5. Reich K et al. (2018) Annual Meeting of the American Academy of Dermatology(AAD), February 18-20, 2018, San Diego , USA, poster 7104.
6. Samrao A et al (2012) A pilot study of an oral phosphodiesterase inhibitor (apremilast) for atopic dermatitis in adults. Arch Dermatol 148:890-897

7. Skullerud KH et al (2021) Apremilast for genital erosive lichen planus in women (the AP-GELP Study): study protocol for a randomised placebo-controlled clinical trial. Trials 22:469.