Background

Oral small-molecule drugs, including tyrosine kinase 2 (TYK2) inhibitors and phosphodiesterase 4 (PDE4) inhibitors, offer alternative options for patients with psoriasis and psoriatic arthritis who are non-responsive or experience a loss of efficacy with biologic agents, while providing advantages in terms of patient convenience and improved quality of life. Apremilast and deucravacitinib are two classes of promising oral small-molecule drugs approved by the U.S. Food and Drug Administration (FDA) for treating plaque psoriasis and psoriatic arthritis. Understanding the variances in the adverse event (AE) profiles of both medications can assist clinicians in making appropriate treatment decisions.

 

Objective

This study aimed to characterize and compare the AE profiles of two different marketed oral small-molecule drugs (apremilast and deucravacitinib) in the treatment of psoriasis, based on real-world data.

 

Methods

Data were extracted from the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2014 to the fourth quarter of 2023 and were further analyzed using disproportionality and Bayesian methods to assess the AE signals of apremilast and deucravacitinib in indications of psoriasis and psoriatic arthritis.

 

Results

We retrieved 95734 AE reports for apremilast and 760 AE reports for deucravacitinib from the FAERS database, predominantly involving elderly women. The quarterly number of AEs reported after the marketing of apremilast and deucravacitinib is shown in Figure 1. We compared the AE signals in four system organ classes and found that the safety signals of different drugs had their unique characteristics, as illustrated in Figure 2. By comparing the drug-related AEs between females and males, we found that different sex may be more prone to certain specific AEs (Figure 3). We also conducted a time-based analysis of safety signals for several specific AEs related to apremilast and deucravacitinib, as shown in Figure 4. Beyond the recurring nature of the disease, diarrhea is the most common AE for apremilast, followed by nausea and headache. Skin-related AEs, including acne, pruritus, rash, and erythema, are the most frequent for deucravacitinib. The top 10 AEs based on case reports for both drugs are listed in Table 1.

 

Conclusions

Likely due to different underlying mechanisms, apremilast is more inclined to induce gastrointestinal and nervous system AEs than deucravacitinib, whereas deucravacitinib has a higher risk of cutaneous AEs, such as acne, pruritus, rash, and erythema, than apremilast. Clinicians may need to balance the benefits and risks of these oral small-molecule drugs when treating certain cases of psoriasis and psoriatic arthritis.

 

Figure 1. (A) The number of adverse events reported quarterly after the marketing of apremilast and deucravacitinib. (B) Comparison of four system organ classes safety signals between apremilast and deucravacitinib. (C) Safety signals over time for apremilast and deucravacitinib-associated adverse events. (D) World map of adverse event reports related to apremilast and deucravacitinib.

 

Table 1. Top 10 in the number of adverse events reports of apremilast and deucravacitinib.

Apremilast	n	Deucravacitinib	n
recurrence or exacerbation of psoriasis	17193	acne	104
diarrhoea	16691	pruritus	93
nausea	14782	rash	78
headache	11490	erythema	66
abdominal discomfort	4319	skin burning sensation	35
recurrence or exacerbation of psoriatic arthritis	4303	mouth ulceration	29
depression	3046	folliculitis	28
weight decreased	3043	burning sensation	25
product dose omission issue	3015	urticaria	21
abdominal pain upper	2451	oral herpes	17