Deucravacitinib vs Apremilast for Plaque Psoriasis

Research-informed explainer — last updated May 6, 2026

Deucravacitinib (brand name Sotyktu) is a once-daily pill that cleared plaque psoriasis better than apremilast (Otezla) in two large head-to-head trials. About 58% of people on deucravacitinib hit a 75% improvement in their psoriasis at 16 weeks, compared with 35% on apremilast and 13% on placebo ¹. Both drugs are oral, so there are no injections, but they work through different pathways and feel quite different to take day to day.

This explainer pulls together what the POETYK PSO-1 and POETYK PSO-2 phase 3 trials actually showed, and what that means if your dermatologist is offering you a choice between the two pills. The trials cited here were led or co-led by Dr. April Armstrong at UCLA and Dr. Jerry Bagel of the Psoriasis Treatment Center of Central New Jersey, both of whom appear in the Convene directory.

What's the difference?

Plaque psoriasis is an autoimmune condition where the immune system speeds up skin cell turnover and creates raised, scaly patches. Both deucravacitinib and apremilast are oral pills that quiet down that overactive immune signal, but they target different proteins inside the immune cell.

• Deucravacitinib blocks an enzyme called TYK2 (tyrosine kinase 2). TYK2 helps relay the signals from interleukin-23 and type I interferons that drive the inflammation in psoriasis. Deucravacitinib was specifically designed to block TYK2 without hitting the closely related JAK1, JAK2, or JAK3 enzymes — which is why it does not carry the boxed warnings that apply to the broader JAK inhibitor class.
• Apremilast blocks an enzyme called PDE4 (phosphodiesterase 4) inside immune cells. Blocking PDE4 raises a small molecule called cyclic AMP, which dials down the production of inflammatory signals. Apremilast was approved in 2014 and was the first widely used oral systemic option for psoriasis after years of patients having no good pill choices.

At a glance

The PASI 75 numbers in the table come from the POETYK PSO-1 trial, which randomized 666 adults with moderate to severe plaque psoriasis to deucravacitinib, placebo, or apremilast and followed them for 52 weeks ¹. POETYK PSO-2 was a separate phase 3 trial of similar size and design that confirmed the same pattern: deucravacitinib was superior to both placebo and apremilast and was well tolerated ².

What the head-to-head trials actually showed

Most psoriasis drug trials only compare a new drug to placebo. The POETYK trials are different because they included apremilast as an active comparator, so you can see how the new pill stacks up against the older pill that many patients have already tried.

POETYK PSO-1

In POETYK PSO-1, 332 people received deucravacitinib, 168 received apremilast, and 166 received placebo. At 16 weeks ¹:

• 58.4% of the deucravacitinib group had at least a 75% reduction in their psoriasis (PASI 75), compared with 35.1% of the apremilast group and 12.7% of the placebo group.
• 53.6% of the deucravacitinib group had clear or almost-clear skin on the static Physician's Global Assessment, versus 32.1% on apremilast and 7.2% on placebo.
• Skin clearance kept improving past week 16 and was held through week 52.
• Side effect rates with deucravacitinib were similar to placebo and apremilast.

Dr. Armstrong was the first author and corresponding author on POETYK PSO-1 ¹, which was published in the Journal of the American Academy of Dermatology and has been cited 325 times.

POETYK PSO-2

POETYK PSO-2 was the second phase 3 trial in the program. The 52-week study confirmed deucravacitinib's superiority over placebo and apremilast in moderate to severe plaque psoriasis and reported a similar safety profile ². Dr. Bagel was a contributing investigator on this trial, which has been cited 261 times.

Two independent phase 3 trials reaching the same result is a stronger signal than any single study. It is the kind of replication regulators look for before approving a drug, and it is why deucravacitinib reached the U.S. market in 2022.

How they feel to take

Numbers on a chart don't tell you what a year on the medicine is like. Here is what tends to matter day to day.

Apremilast is a six-week titration. You start with a 10 mg dose and work up to 30 mg twice a day to reduce the chance of stomach side effects. Even with the slow start, diarrhea, nausea, and headache are common in the first few weeks. Most people who tolerate it past the first month do fine, but the early stretch can be rough. Some people lose a few pounds on it.

Deucravacitinib is one pill, once a day, with no titration. The most common side effects in the trials were upper respiratory tract infections, mild mouth sores, and acne-like breakouts ¹. There is no routine lab monitoring required, which is a meaningful difference from biologic injections and from broader JAK inhibitors.

Neither drug is an injection, which is the main reason some patients pick a pill over a biologic in the first place — even though biologics like ustekinumab, risankizumab, and ixekizumab tend to clear psoriasis even more completely than oral pills do.

When each pill is typically recommended

Both drugs are FDA-approved for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. In practice, dermatologists tend to think about them this way:

• Apremilast is often the first oral systemic chosen for milder moderate disease, for patients who specifically want to avoid biologics, for those with overlapping psoriatic arthritis, or for patients whose insurance requires it as a step-therapy gate before approving newer or more expensive options.
• Deucravacitinib is increasingly the preferred oral option when the patient wants higher skin clearance from a pill, has not tolerated apremilast's stomach side effects, or has tried and failed apremilast. Insurance coverage has been the main barrier since approval, and step therapy through apremilast is still common.

Patients who need rapid, deep clearance — for example, someone with widespread disease causing major work or quality-of-life problems — are often steered toward biologic injections rather than either oral pill, because biologics still produce the highest rates of completely clear skin.

What's changing in the field

Three things are worth knowing if you are choosing a treatment now.

First, deucravacitinib was the first TYK2 inhibitor approved for any disease. More TYK2 inhibitors are in late-stage trials for psoriasis and other autoimmune conditions, so this class is likely to grow.

Second, the POETYK trials only ran for 52 weeks. Real-world experience past one year is still being collected, and longer-term safety data continues to accrue.

Third, head-to-head data versus biologics is limited. The POETYK trials compared deucravacitinib to apremilast and placebo, not to ustekinumab, risankizumab, or ixekizumab. If your dermatologist is helping you decide between deucravacitinib and a biologic, that comparison is being made indirectly across separate trials, not from a single study.

Questions to ask your doctor

• Based on how much skin is involved and how it affects my daily life, would you treat me with a pill, an injection, or phototherapy?
• Will my insurance require me to try apremilast before they cover deucravacitinib?
• If I have psoriatic arthritis as well, does that change which pill you recommend?
• What side effects should I watch for in the first month, and when should I call you?
• How will we decide whether the medicine is working, and at what point would we switch?
• Are there any infections, vaccines, or pre-existing conditions that would make either drug a poor fit for me?

The bottom line

If the choice in front of you is deucravacitinib versus apremilast for moderate to severe plaque psoriasis, the trial data is consistent: deucravacitinib clears more skin, hits clear-or-almost-clear status more often, and tends to be easier on the stomach in the first month ^{1 2}. Apremilast remains a reasonable starting option, especially when insurance requires it first or when psoriatic arthritis is part of the picture. Either way, the right next step is a dermatologist who treats psoriasis often enough to know how each drug performs outside the trial setting.