Psoriasis
Clears moderate to severe plaques.
Methotrexate vs Skyrizi
Methotrexate: An old, inexpensive tablet or injection for severe psoriasis and psoriatic arthritis. It is taken once a week, not daily, and it needs regular blood tests. 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.
Which one is right for you?
Choose Methotrexate if…
Choose for severe psoriasis, especially with joint pain, as an inexpensive weekly treatment with regular blood tests.
- Psoriasis with psoriatic arthritis
- Cost matters and biologics aren't covered
- You can avoid alcohol and keep up blood tests
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 usually used one at a time for psoriasis. Methotrexate is a lower-cost tablet with blood tests; Skyrizi is a more effective injection with fewer checks.
At a glance
● Methotrexate
● Skyrizi
Type
Oral or injected immune suppressant
Biologic injection (risankizumab, IL-23 blocker)
What it does
Calms overactive immune cells and skin-cell growth
Blocks IL-23, high up in the psoriasis chain
Best for
Severe psoriasis and psoriatic arthritis
Moderate to severe plaque psoriasis and psoriatic arthritis
Prescription
Yes
Yes
Form
Tablet or injection
Injection under the skin
How often
Once a week — never daily
Weeks 0 and 4, then every 12 weeks
Course length
Ongoing
Ongoing
Time to results
4–12 weeks
16 weeks
Main side effect
Nausea and tiredness the day after
Colds; injection-site reactions
Blood tests
Required
TB test before starting
Pregnancy
Never
Check with your clinician
Cost
Low; generic available
High; no generic
What it treats
Compare uses by strength of evidence. Evidence level describes confidence in a benefit, not its size.
Evidence level
Methotrexate
Skyrizi
Strong evidenceMost established uses
Psoriasis
Clears or nearly clears skin in most patients.
Psoriatic Arthritis
Reduces joint symptoms.
Scalp Psoriasis
Improves scalp plaques.
Moderate evidenceSome supportive research
Psoriatic Arthritis
Reduces joint symptoms.
Eczema
An option for severe eczema.
—
Little evidence
Alopecia Areata
Mixed results in small studies.
Hidradenitis Suppurativa
Trials were disappointing.
Not effective
Acne
No role in acne.
Eczema
Doesn't target eczema inflammation.
How it works
Methotrexate
Diagram explanation and sources
Interferes with cell replication: Blocks folate-dependent processes used to make DNA. May increase adenosine signaling: This calming messenger can limit immune-cell activity. Reduces skin inflammation: Inflammatory activity and plaque buildup can decrease.
The psoriasis mechanism is not fully established. Folate antagonism affects replication, while low-dose anti-inflammatory actions include proposed adenosine pathways supported by experimental work; their precise clinical contributions are unresolved.
Skyrizi
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.
How you take it
Treatment plan
This drug is taken once a week. Taking it every day can cause fatal bone marrow failure. Pick one day of the week, write it down, and keep to it.
Test dose: A single small dose, often 2.5 mg to 5 mg, with blood counts checked about a week later before going further. A safety check, not the treatment dose.
Starting dose: Commonly 7.5 mg to 15 mg once weekly, adjusted for age, weight, kidney function and other illnesses. Lower in older people and in reduced kidney function.
Going up: Small steps, usually 2.5 mg to 5 mg every few weeks with blood tests in between, until the psoriasis responds or side effects set the ceiling.
Usual dose: Most people settle between 15 mg and 25 mg once weekly. Above about 15 mg tablet absorption gets unreliable, a common point to switch to the injection.
Folic acid alongside it: It reduces nausea, mouth ulcers and blood count problems. Usually a daily dose on the days you are not taking methotrexate, or one larger weekly dose on a different day. It does not stop the drug working.
Total course: No fixed course. It continues as long as it works and blood tests stay normal, which for some people is years.
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
Once a week, on the same day every week. Choose a day you will remember and write it somewhere visible. Some people take the whole dose at once; some split it into two portions about twelve hours apart on the same day to reduce nausea. Do not spread it across different days unless you were told to.
Take tablets with water, and with food if they upset your stomach. An evening dose means the tiredness and mild nausea happen while you are asleep.
Folic acid goes on the other days, as prescribed. It is not a substitute for a missed methotrexate dose.
With the weekly injection, keep to the same day and rotate the site.
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 if it is within about two days of your usual day. If longer, skip it and take the next on your usual day. Never take two weekly doses close together to catch up, and never take a daily dose to make up for a missed week.
If you have taken more than one weekly dose, or taken it several days in a row, contact a doctor or a poison center straight away. Do not wait to see how you feel. This overdose is treatable caught early and dangerous when it is not.
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
Methotrexate is watched by blood test, and the schedule is not optional. The problems it causes are silent until they are advanced.
Before starting: Full blood count, liver tests, kidney function, and a pregnancy test where relevant. Hepatitis B, hepatitis C, HIV and tuberculosis screening is standard, because the drug damps the immune system. A chest x-ray if there is any history of lung disease.
Early on: Blood counts and liver tests within a week or two of starting, and again after each dose increase. This is when a sudden drop in blood counts would show.
Once stable: Full blood count, liver tests and kidney function every one to three months, depending on the dose and what else you take, for as long as you are on the drug.
The liver over the long term: Years of methotrexate can scar the liver, and the risk rises with total lifetime dose, heavy alcohol use, obesity, diabetes and fatty liver disease. Biopsy used to be the check; most clinics now use a blood marker of scarring and a scan of liver stiffness.
The lungs: A rare but serious lung inflammation can occur. A new dry cough, breathlessness or fever means being seen, not waiting for the next appointment.
What to report between tests: Mouth ulcers, unexplained bruising or bleeding, sore throat or fever, dark urine, yellowing of the eyes or skin, severe nausea, any new cough or breathlessness.
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.
● Methotrexate
● Skyrizi
First dose
First doseTaking it: Once a week, not daily, with folic acid on the other days. Nausea, tiredness or mouth soreness in the day or two after each dose is common early on; folic acid usually blunts it.
Weeks 1 to 2
Weeks 1 to 2Settling in: Nothing visible in the skin yet.
Weeks 4 to 8
Weeks 4 to 8Working: Plaques thin and spread less, thickness and scale first. Joint pain from psoriatic arthritis often improves in the same window, one reason it is chosen over a skin-only treatment.
About 3 months
About 3 monthsJudge it here: Substantial improvement is the realistic target.
Beyond 3 months
Beyond 3 monthsLong term: Where it suits, the result holds while the dose continues, with regular blood tests. Some stay on it for years.
Many months
Many monthsNails: Nail psoriasis can improve, but slowly. Nails always lag behind the skin.
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.
Methotrexate
Skyrizi
Common
Common
- Nausea or tiredness the day after the dose
- Mouth sores
- Mild hair thinning
Common
- Colds and upper respiratory infections
- Headache, tiredness
- Injection-site reactions
Tell your doctor
Tell your doctor
- Cough or breathlessness
- Fever, sore throat or unusual bruising
Tell your doctor
- Persistent cough or night sweats
Stop and get care
Stop and get care
- Taking it daily by mistake
- Yellowing skin or dark urine
Stop and get care
- Fever with serious infection
- Swelling of face or throat
Safety and who should avoid it
Pregnancy
Never
Both partners avoid conception during and for 3 months after.
Use care
Discuss with your clinician.
Breastfeeding
Never
Not compatible.
Use care
Discuss with your clinician.
Children
Specialist only
Used in children with monitoring.
Not used
Adults for psoriasis.
Monitoring
Required
Blood counts, liver and kidney tests; every 3 months once stable.
Sometimes
TB test before starting; liver tests for Crohn's dosing.
Key interactions
Check
Trimethoprim-sulfamethoxazole, NSAIDs, some antibiotics; limit alcohol.
Check
Avoid live vaccines.
Other cautions
Avoid
Liver disease, heavy drinking, kidney disease, active infection.
Avoid
Active TB or serious infection.
Cost and getting it
Getting it and cost
Generic methotrexate tablets are among the least expensive systemic treatments in dermatology. Folic acid is cheap too.
The weekly auto-injector pens cost considerably more, and coverage usually requires showing that tablets caused nausea or did not work well enough. Plain injectable vials are cheaper than the pens.
The real cost is the monitoring, repeated blood tests and periodically a liver scan or blood marker. Usually covered, but they are appointments and not optional.
Insurers frequently require a trial of methotrexate before approving a biologic, one reason it is still so often the first systemic drug tried.
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 months.
Psoriasis returns slowly, often over many months.
Taper needed?
Usually not, but plan the next step first.
No.
After the last dose
Wait at least 3 months before trying to conceive — applies to both partners.
Restarting usually works again.
Common questions
Methotrexate:How often do I take it?
Once a week, on the same day. Never daily. Daily dosing by mistake is the most dangerous error with this drug and it has been fatal. Get medical help the same day if it happens.
Methotrexate:Why do I also have to take folic acid?
Methotrexate blocks folate, and the mouth ulcers, nausea and low blood counts come from that. Folic acid on the other days restores enough folate to reduce them without stopping the treatment working.
Methotrexate:Do I really need all the blood tests?
Yes. Liver damage and falling blood counts cause no symptoms until they are advanced. The tests are the only early warning.
Methotrexate:Can I drink alcohol?
The concern is regular drinking, not a single glass, because alcohol and methotrexate both stress the liver. Agree an actual limit with your doctor.
Methotrexate:Can I take it if I want to have a baby?
No. It must be stopped well before trying to conceive, and the advice covers both partners. It causes miscarriage and serious birth defects. Ask your own doctor how far in advance.
Methotrexate:How long before I know if it is working?
Give it about three months. First changes often show at four to eight weeks, but three months on a tolerated dose is the fair point to judge.
Methotrexate:Is it chemotherapy?
It is chemotherapy at much higher doses. At psoriasis doses it acts as an immune-calming drug, and the experience is not comparable.
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.
Keep exploring.
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Skyrizi
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Methotrexate
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