Choosing an Oral Therapy: Deucravacitinib vs Apremilast

Defining the oral advantage in psoriasis treatment 

In this episode of Topical Conversations, Dr Shahriari and Dr Bunick explore the evolving oral treatment landscape for plaque psoriasis, focusing on head-to-head comparisons between apremilast, a phosphodiesterase 4 (PDE4) inhibitor, and deucravacitinib, a selective tyrosine kinase 2 (TYK2) inhibitor. The discussion provides practical guidance for clinicians navigating therapeutic choices based on long-term efficacy, tolerability, and patient preference.

Efficacy and tolerability 

Deucravacitinib demonstrated superior efficacy compared with apremilast in 2 phase 3 trials (POETYK PSO-1 and PSO-2). At week 16, Psoriasis Area and Severity Index (PASI) 90 response rates were 36% vs 20% in PSO-1 and 27% vs 18% in PSO-2, respectively. At week 52, 19% of patients receiving deucravacitinib achieved PASI 100.

Regarding tolerability, common adverse events associated with apremilast (eg, nausea, diarrhea, headache) remain frequent. In contrast, deucravacitinib’s adverse event profile was comparable to or lower than placebo across clinical trials.

Molecular mechanisms: explaining the difference 

Dr Bunick explains how apremilast’s chemical structure limits its mimicry of cyclic adenosine monophosphate (cAMP), potentially reducing potency. Deucravacitinib, by contrast, exerts selective allosteric inhibition of TYK2. Dr Bunick references his recent laboratory findings, which show TYK2 contains more phosphotyrosine sites than other Janus kinase (JAK) family members, enabling high STAT phosphorylation activity and robust cytokine suppression.

Oral vs injectable 

Although biologic agents remain widely used, oral therapies play a growing role in psoriasis management, particularly for patients seeking noninjectable options or those already managing multiple conditions with injectable drugs. Dr Shahriari and Dr Bunick stress the importance of shared decision-making in determining patient preference.

Sustained effects after discontinuation 

A notable finding: following discontinuation of deucravacitinib, patients maintained a PASI 75 response for a median of 12 weeks. This contrasts with JAK inhibitors used in atopic dermatitis, where symptom recurrence often occurs within 1 week of withdrawal. The speakers attribute this durability to TYK2’s upstream modulation of the Th17 axis and inflammatory cytokines.

Key takeaways

• Deucravacitinib demonstrated superior efficacy over apremilast in PASI 90 rates at week 16, with 19% of patients on deucravacitinib achieving PASI 100 by week 52
• Deucravacitinib is well tolerated, with adverse event rates similar to placebo
• Some patients prefer oral therapy due to convenience, control, or injection fatigue
• Discontinuation of deucravacitinib does not lead to immediate loss of efficacy, supporting its role in long-term disease control