Apremilast的治疗效果和用药注意事项？

Apremilast has a good therapeutic effect, is well tolerated in moderate to severe plaque psoriasis, has high efficacy and safety, and is a new choice for psoriasis patients.

About Apremilast

It is an orally administered small molecule that specifically inhibits the enzyme phosphodiesterase-4 and modulates the immune system by increasing intracellular cyclic adenosine monophosphate (cAMP) levels and inhibiting the production of IL-2 & 8, interferon-γ, and tumor necrosis factor (TNF). Apremilast is FDA-approved for the treatment of oral ulcers in psoriasis, psoriatic arthritis, and Behcet's disease.

Apremilast for the treatment of psoriasis

The efficacy of Apremilast in moderate to severe psoriasis has been demonstrated in the pivotal trial, with a PASI-75 response rate of 30% at week 16, and this efficacy was sustained through week 52. Apremilast has also achieved significant results in diseases involving specific sites, such as palmoplantar, nail and scalp psoriasis, improving patients' quality of life and achieving rapid improvement in pruritus.

Most patient-reported outcomes, including pruritus and total dermatology quality of life index, also improved to a greater extent in the apremilast group than in the placebo group, with significant improvements in pruritus and skin discomfort/pain visual analogue scores as early as week 2 in the apremilast group.

In the Phase 3 PALACE trial, apremilast 30 mg twice daily improved signs and symptoms of active psoriatic arthritis in both disease-modifying antirheumatic drug (DMARD)-naïve and DMARD-taking patients. Apremilast also improves enthesitis, dactylitis, physical function and fatigue, with effects lasting up to 208 weeks.

Apremilast has an early onset of action in patients with active psoriatic arthritis, and at week 2 of the Phase 3b active trial, apremilast (30 mg twice daily) achieved a ≥20% improvement in modified American College of Rheumatology response criteria in significantly more patients than placebo recipients. Apremilast is generally well tolerated in patients with psoriasis and psoriatic arthritis.

Efficacy and safety of Apremilast

In a phase III, multicenter, double-blind, placebo-controlled study, 844 patients were randomly assigned to apremilast (n=562) or placebo (n=282). At week 16, the placebo group switched to apremilast at week 32 and then entered a randomized treatment withdrawal period through week 52.

At week 16, patients taking apremilast experienced a 75% or greater reduction from baseline in the Psoriasis Area and Severity Index score (PASI-75) compared to the placebo group. 61% of patients were randomized again to apremilast at week 32 and reached a PASI score of -75 at week 52, while 11.7% were randomized again to placebo.

Among patients who were rerandomized to receive apremilast at Week 32, the mean percentage change from baseline in PASI score was -88% to -81%. During the placebo-controlled period, 55.7% and 69.3% of patients randomized to placebo and ampremilast experienced 1 or more adverse events, respectively. Most adverse events were mild/moderate in severity. There were no new significant adverse events with continued exposure to apremilast compared with the placebo-controlled period.

Apremilast usage and dosage

The dosage of Apremilast from day 1 to day 2 is 10 mg in the morning and evening, 10 mg in the morning and 20 mg in the evening on the third day, 20 mg in the morning and evening on the fourth day, 20 mg in the morning and 30 mg in the evening on the fifth day, and 30 mg in the morning and evening on the sixth day and thereafter.

Apremilast can be taken with or without food. Tablets should be swallowed whole and should not be crushed, broken, or chewed.

Apremilast

1. Diarrhea, nausea and vomiting:

Patients who are more likely to develop diarrhea or vomiting complications should be monitored during treatment. Recovery usually occurs quickly when the dose is reduced or Apremilast is discontinued. If severe diarrhea, nausea, or vomiting occurs, a dose reduction or temporary discontinuation of Apremilast should be considered.

2. Depression:

Before using Apremilast in patients with a history of depression or suicidal thoughts or behaviors, physicians are advised to carefully weigh the risks and benefits of treatment with Apremilast and inform patients, their caregivers, and family members about the need to be alert for the emergence or worsening of depression, suicidal thoughts, or other mood changes.

3. Weight loss:

Body weight should be monitored regularly during treatment, and if unexplained or clinically significant weight loss occurs, weight loss should be evaluated and discontinuation of Apremilast should be considered.

4. Drug interactions:

Concomitant use of rifampin, a potent cytochrome P450 enzyme inducer, may result in decreased systemic exposure of apremilast, which may result in loss of efficacy of apremilast. Therefore, the combined use of cytochrome P450 enzyme inducers such as rifampicin and carbamazepine with Apremilast is not recommended.

Summary

Apremilast is a new type of oral drug that has significant therapeutic effects on psoriasis and other diseases. Patients need to take the drug under the guidance of a doctor.

References:

1. Carrascosa JM, Del-Alcazar E. Apremilast for psoriasis treatment. G Ital Dermatol Venereol. 2020 Aug;155(4):421-433. doi: 10.23736/S0392-0488.20.06684-5. Epub 2020 Jun 15. PMID: 32545946.

2. Papp K, Reich K, Leonardi CL, Kircik L, Chimenti S, Langley RG, Hu C, Stevens RM, Day RM, Gordon KB, Korman NJ, Griffiths CE. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015 Jul;73(1):37-49. doi: 10.1016/j.jaad.2015.03.049. PMID: 26089047.

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