Otezla vs Skyrizi

Otezla: An oral pill for plaque psoriasis, psoriatic arthritis and the mouth ulcers of Behcet's disease. It needs no routine blood tests, and it is gentler and less powerful than the injected treatments. Skyrizi: An injected biologic for moderate to severe plaque psoriasis. It blocks interleukin-23, a signal that sits high up in the psoriasis chain, and after two starting doses it is given about four times a year.

Reviewed by Dr. Schwarz, Board-Certified Dermatologist
An amber pill bottle labeled Otezla tipped over with white tablets spilling outSkyrizi shown in recognizable white injection pen with blue and turquoise accents.

Which one is right for you?

Choose Otezla if…

Choose for moderate psoriasis or psoriatic arthritis when you want a pill with no routine blood tests, accepting it's gentler than injections.

  • Moderate psoriasis or scalp psoriasis
  • You'd rather avoid injections
  • No routine blood tests appeals

Choose Skyrizi if…

Choose for moderate to severe psoriasis when you want high clearance with only about four injections a year.

  • Moderate to severe plaque or scalp psoriasis
  • You want infrequent injections
  • No active TB
Alternatives, not combined

Can you take them together?

These are different options for psoriasis and are not usually taken together. Otezla is a tablet; Skyrizi is a more effective injection.

At a glance

● Otezla
● Skyrizi
Type
Oral PDE4 inhibitor (apremilast)
Biologic injection (risankizumab, IL-23 blocker)
What it does
Turns down several inflammation signals
Blocks IL-23, high up in the psoriasis chain
Best for
Moderate plaque psoriasis and psoriatic arthritis
Moderate to severe plaque psoriasis and psoriatic arthritis
Prescription
Yes
Yes
Form
Tablet
Injection under the skin
How often
Twice daily after a 5-day start
Weeks 0 and 4, then every 12 weeks
Course length
Ongoing
Ongoing
Time to results
12–16 weeks
16 weeks
Main side effect
Diarrhea and nausea early on
Colds; injection-site reactions
Blood tests
None
TB test before starting
Pregnancy
Check with your clinician
Check with your clinician
Cost
High; generic arriving
High; no generic

What it treats

Compare uses by strength of evidence. Evidence level describes confidence in a benefit, not its size.

Evidence level
Otezla
Skyrizi
Strong evidenceMost established uses
Two thick, sharply bordered plaques on a knee on fair light skin. They are salmon-pink to red with loose silvery-white scale on top.

Psoriasis

Improves moderate plaque psoriasis.
Psoriatic Arthritis on light skin.

Psoriatic Arthritis

Eases joint pain and swelling.
Two thick, sharply bordered plaques on a knee on fair light skin. They are salmon-pink to red with loose silvery-white scale on top.

Psoriasis

Clears or nearly clears skin in most patients.
Psoriatic Arthritis on light skin.

Psoriatic Arthritis

Reduces joint symptoms.
Parted hair on fair scalp skin showing a raised salmon-pink plaque topped with dry silvery-white scale, with a sharply drawn border against normal skin.

Scalp Psoriasis

Improves scalp plaques.
Moderate evidenceSome supportive research
Parted hair on fair scalp skin showing a raised salmon-pink plaque topped with dry silvery-white scale, with a sharply drawn border against normal skin.

Scalp Psoriasis

Approved for scalp involvement.
—
Little evidence
Extreme close-up of light skin in an active eczema flare, too close to tell which part of the body it is. Blotchy pink-red inflammation covers the whole frame with no clear edge, with small raised bumps, fine dry scale and a few fresh scratch marks.

Eczema

Trials in eczema were disappointing.
An inflamed lump in the armpit on fair skin. The skin over it is swollen, shiny and red, with a pair of small blackhead-like openings in the skin beside it.

Hidradenitis Suppurativa

Trials were disappointing.
Not effective
A round smooth bald patch on the scalp.

Alopecia Areata

Not effective in trials.
Extreme close-up of light skin in an active eczema flare, too close to tell which part of the body it is. Blotchy pink-red inflammation covers the whole frame with no clear edge, with small raised bumps, fine dry scale and a few fresh scratch marks.

Eczema

Doesn't target eczema inflammation.
How it works

Otezla

Otezla. Apremilast turns down inflammation inside skin. 1. Blocks PDE4: Inhibits an enzyme that breaks down cAMP. 2. Raises cAMP inside cells: Preserves a signal involved in regulating inflammation. 3. Helps inflamed skin settle: Psoriasis plaques become less inflamed.
Open full-size diagram
Diagram explanation and sources

Blocks PDE4: Inhibits an enzyme that breaks down cAMP. Raises cAMP inside cells: Preserves a signal involved in regulating inflammation. Helps inflamed skin settle: Psoriasis plaques become less inflamed.

PDE4 inhibition and increased intracellular cAMP are established. The exact link to clinical improvement is not fully defined; this is a simplified overview, not every downstream pathway.

Source 1

Skyrizi

Skyrizi. Risankizumab interrupts the IL-23 psoriasis pathway. 1. Blocks IL-23: Binds this immune messenger before it reaches its receptor. 2. Turns down inflammatory T cells: Reduces signals that keep the psoriasis cycle active. 3. Helps plaques clear: Excess skin buildup and inflammation gradually decrease.
Open full-size diagram
Diagram explanation and sources

Blocks IL-23: Binds this immune messenger before it reaches its receptor. Turns down inflammatory T cells: Reduces signals that keep the psoriasis cycle active. Helps plaques clear: Excess skin buildup and inflammation gradually decrease.

Risankizumab selectively targets the p19 subunit of IL-23, not IL-12. The T-cell and skin changes are a simplified downstream interpretation.

Source 1

How you take it

Treatment plan

Nothing about the dose depends on weight or on how severe your disease is. It is built up gradually only to give your stomach time to settle.

Starting dose: A five-day starter pack, beginning at 10 mg on day one and climbing in 10 mg steps, morning and evening doses in turn, until you reach 30 mg twice a day on day six.

Usual dose: 30 mg twice a day, about 12 hours apart.

If your kidneys are significantly impaired: The dose is halved to 30 mg once a day, and the starter pack is used differently.

Total course: No fixed course. It is taken as long as it helps, judged at about 16 weeks, and the benefit stops when the drug stops.

Two starting doses close together, then a long steady interval. Not adjusted for body weight.

Starting dose: 150 mg as one injection.

Second dose: 150 mg, four weeks after the first.

Usual dose: 150 mg every 12 weeks — about four injections a year after the first year.

If it stops working: There is no approved higher dose or shorter interval for psoriasis. Losing response means reviewing the diagnosis, not injecting more often.

How long: Long term, with no set end point, while it works and is tolerated.

When to take it

Twice a day, roughly 12 hours apart, with or without food — food helps some people with nausea. Swallow the tablets whole; do not crush, split or chew them.

Any time of day. The calendar matters more here than with a weekly drug. Twelve weeks is long enough that people lose track, so put every dose date in your phone and book the next reminder the day you inject.

Take it out of the fridge 15 to 30 minutes before and let it warm on the counter. Cold liquid stings. No hot water, no microwave.

Inject into the front of the thigh or the belly, at least two inches from the navel. The back of the upper arm works if someone else is doing it. Rotate the site, avoid skin that is bruised, tender, hard or scarred, and never inject through a plaque. Ask for training before the first dose. Used devices go in a sharps container.

If you miss a dose

Take it as soon as you remember, unless the next dose is close, in which case skip it. Never take two at once. If you have stopped for more than a few days, ask before restarting; the full dose brings the stomach side effects straight back, so the starter pack is usually repeated.

Inject as soon as you remember, then count twelve weeks from that day. If it has been much longer than twelve weeks, call the prescriber first so the schedule can be reset.

Monitoring

The absence of blood tests is why many people choose this drug. No baseline blood count, no liver panel, no tuberculosis test, no hepatitis screen, nothing repeated. Kidney function is checked once before starting, because severe impairment halves the dose.

What replaces it is clinical monitoring, which is not lighter, only different. Weight comes first. Weight loss is common and can be substantial, with some people losing five to ten percent of their body weight. If you wanted that, it is welcome. If you are older, frail or already underweight, it is a reason to reconsider, and unexplained loss should prompt a review.

Mood is second. Depression, low mood and, rarely, suicidal thoughts have been reported and appear on the label. The risk is low, but new or worsening depression should be reported promptly, and a history of depression belongs on the record before you start.

Diarrhea and nausea are third. They usually settle within the first few weeks, but severe or persistent diarrhea is not something to push through. In older adults, and in anyone on a water tablet or a blood pressure medicine, it has caused dehydration and kidney injury.

The one scheduled checkpoint is the 16-week review of skin or joints. If nothing meaningful has changed, continuing is not useful.

Everyone is screened for tuberculosis before the first dose — a skin test or TB blood test, plus a chest X-ray if that is positive. Dormant TB is treated first. This class probably carries less TB risk than the TNF blockers, but screening is not optional.

Hepatitis B and C are usually checked at the same time.

After that there is no fixed blood test schedule. Risankizumab does not need the regular liver and blood count testing methotrexate does. Monitoring is clinical: the skin, whether infections are more frequent, whether the dose dates are kept. TB testing is repeated yearly or by exposure risk.

There is no boxed warning. The most common side effects reported are upper respiratory infections, headache, tiredness, fungal skin infections and injection site reactions. Serious allergic reactions are rare but are why the first dose is often given with someone trained nearby.

When you’ll see results

Approximate windows, not promises.

● Otezla
● Skyrizi
First dose

First doseStarting: The starter pack steps the dose up over the first week, which softens the early side effects.

Days 1 to 14

Days 1 to 14Adjusting: Loose stools, nausea and headache usually start in the first week or two and settle within a month.

Weeks 2 to 4

Weeks 2 to 4Itch: Usually the first thing to change, ahead of the plaques. Behcet's mouth ulcers settle here too, one of the faster and more reliable responses.

Weeks 4 to 8

Weeks 4 to 8Working: The first visible change in the skin. Scale lifts before the redness fades.

Weeks 12 to 16

Weeks 12 to 16Judge it here: In the trials roughly one in three people reached a 75 percent improvement. Scalp psoriasis responds better than thick body plaques, a common reason to choose it.

Weeks 16 to 24

Weeks 16 to 24Psoriatic arthritis: Joint pain, swelling and tenderness improve.

Months 3 and onward

Months 3 and onwardWeight and mood: Weight loss comes on gradually, so weigh yourself regularly rather than going by how clothes feel. Mood changes are uncommon but worth watching.

Months 6 and beyond

Months 6 and beyondNails: The slowest of all, because a nail has to grow out before improvement shows.

First few minutes

First few minutesThe injection: A sharp sting for a few seconds, then redness or a small welt. Settles within a day or two.

Weeks 1 to 4

Weeks 1 to 4Starting: Itch settles first. Scale lifts and plaques thin.

Weeks 4 to 16

Weeks 4 to 16Working: Most of the change happens here, from the second dose on. Plaques flatten and redness fades from the middle out, often leaving a paler or darker mark.

Week 16

Week 16Judge it here: Most people reached 90 percent clearer skin, and many were clear or nearly clear. Joints improve on the same timeline.

3 to 6 months

3 to 6 monthsScalp, palms and soles: Slower than the trunk and limbs.

6 to 12 months

6 to 12 monthsNails: Last to change, because a nail takes months to grow out.

Between doses

Between dosesSteady state: Most people notice no dip. If plaques reliably return in the last few weeks, say so.

Side effects

Sorted by what to do about them.

Otezla

Skyrizi

Common
Common
  • Diarrhea and nausea in the first weeks
  • Headache
  • Weight loss
Common
  • Colds and upper respiratory infections
  • Headache, tiredness
  • Injection-site reactions
Tell your doctor
Tell your doctor
  • Ongoing weight loss
Tell your doctor
  • Persistent cough or night sweats
Stop and get care
Stop and get care
  • Low mood or thoughts of self-harm
  • Severe diarrhea or vomiting
Stop and get care
  • Fever with serious infection
  • Swelling of face or throat

Safety and who should avoid it

Pregnancy
Ask first
Discuss with your clinician.
Use care
Discuss with your clinician.
Breastfeeding
Ask first
Discuss with your clinician.
Use care
Discuss with your clinician.
Children
6 and older
Approved from 6 for psoriasis.
Not used
Adults for psoriasis.
Monitoring
None
Weight checks.
Sometimes
TB test before starting; liver tests for Crohn's dosing.
Key interactions
Check
Rifampin and some anti-seizure drugs reduce it.
Check
Avoid live vaccines.
Other cautions
Discuss
History of depression; kidney problems.
Avoid
Active TB or serious infection.

Cost and getting it

Getting it and cost

Apremilast is expensive, priced far closer to the biologics than to older oral drugs such as methotrexate or acitretin.

So insurers commonly ask that cheaper options be tried first, and prior authorization is usual. The manufacturer runs a copay assistance program, which typically helps people with commercial insurance and is not available on government plans.

What it saves is indirect: no injection supplies, no screening tests, no repeated laboratory work. That does not close the gap with a generic tablet, but it is part of the comparison.

The list price runs to tens of thousands of dollars a year. Almost nobody pays that; what you pay depends on your plan.

It is brand only — no generic, no biosimilar — so there is no cheaper equivalent to switch to. That is a real difference from adalimumab.

Prior authorization is close to universal. Most plans require documented failure of something cheaper first — phototherapy, methotrexate, sometimes another biologic. Denials are usually about missing records rather than the drug, and appeals succeed reasonably often when the history is documented.

Manufacturer copay cards can cut the cost to very little with commercial insurance. By law they cannot be used with Medicare or Medicaid. For those plans, or no insurance, the manufacturer's patient assistance program and independent foundations are the usual routes. Terms change often.

One practical note: because doses are twelve weeks apart, a change of insurance or a formulary switch in January can land in the middle of a dosing gap. Check coverage before the next dose is due, not the week it is.

When you stop

Comes back?
Psoriasis usually returns over weeks to months.
Psoriasis returns slowly, often over many months.
Taper needed?
No.
No.
After the last dose
Stomach effects resolve quickly.
Restarting usually works again.

Common questions

Otezla:Do I really need no blood tests?

Correct. No monitoring schedule, no tuberculosis screen, no repeated bloodwork. Kidney function is checked once before starting, because severe impairment halves the dose.

Otezla:Will the diarrhea stop?

For most people it is worst in the first two weeks and settles within a month, which is what the five-day starter pack softens. Diarrhea that is severe or lasts past a month is a reason to be reviewed.

Otezla:Will I lose weight?

Some people do, and some of them lose five to ten percent of their body weight. It happens gradually, so weigh yourself every few weeks rather than judging by how clothes fit.

Otezla:How does it compare with the injections?

Less effective for thick plaques — about one in three reached a seventy-five percent improvement at 16 weeks, where biologics reach much higher figures. What it offers is a tablet, no needles, no screening, no monitoring.

Otezla:Can it affect my mood?

Low mood and depression are uncommon but on the label, and rare reports of suicidal thoughts exist. Report any new or worsening low mood promptly.

Otezla:How long until I know whether it is working?

About 16 weeks for the skin, up to 24 weeks for joints. If nothing meaningful has changed, continuing is not worthwhile.

Skyrizi:What does biologic mean?

A large protein grown in living cells rather than a chemical made in a factory. That is why it is injected, and why it lives in the fridge.

Skyrizi:Really only four injections a year?

After the first two doses, four weeks apart, yes. The drug stays in the body long enough that the gap can be twelve weeks.

Skyrizi:Does the injection hurt?

A few seconds of stinging. Letting it warm to room temperature first makes a noticeable difference.

Skyrizi:Do I need blood tests while I am on it?

Tuberculosis and hepatitis before you start, and TB testing often repeated yearly. Beyond that, no routine schedule.

Skyrizi:What happens if I am late with a dose?

Inject when you remember and count twelve weeks from that day. If you are weeks or months late, call first.

Skyrizi:Can I have vaccines?

Yes, apart from live ones. The flu shot, COVID vaccines and Shingrix are not live. Have any live ones before starting.

Dermapedia on YouTube