What’s Next When Creams for Psoriasis Aren’t Working?

If you have psoriasis but your skin isn’t getting better with creams or lotions, you’re probably frustrated. The rashes are still there, and you wish they weren’t. Don’t worry: You have options, and clear skin is possible. 

When psoriasis doesn’t go away with topical treatments (like creams, lotions, or shampoos), there are many different systemic options to try. Systemic medications go inside the body — like pills, injections, or infusions. Which option is best for you depends on many factors, including your personal preferences. Learn about the systemic treatment options for psoriasis, their possible side effects, and when you may want to consider using one.

How to tell when psoriasis creams aren’t working

For many people, psoriasis symptoms can be managed with medicated creams and lotions alone. But, sometimes stronger medications, like pills and injections, are needed. 

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• The cost of treating psoriasis: Read how one woman used health insurance and manufacturer copay savings programs to help pay for her psoriasis medications.

This may be the case if: 

• Prescription creams are no longer keeping your symptoms under control. 

• You have psoriasis on large areas of skin and applying cream isn’t practical.

• You also have a diagnosis of psoriatic arthritis.

In 2024, we have over 20 systemic medications for psoriasis that you can use when topicals just aren’t doing the trick. And there are many more on the way. In many situations, these can also be used in combination with topicals to address psoriasis from both the inside and out. 

Though it might take some time to find the best psoriasis medication that works for you, there’s one out there that can help. Here are the different options. 

Which oral medications treat psoriasis?

There are several oral medications that can help when psoriasis doesn’t respond to creams alone. Oral medications are pills you take by mouth. 

Methotrexate

Methotrexate (Trexall) has been around for almost 50 years. You take 3 to 10 (depending on the dose) tiny pills at the same time once a week. It’s also available as an oral liquid (Jylamvo) if you have difficulty swallowing pills. While taking methotrexate, you also take a daily vitamin called folic acid to prevent side effects. 

Possible side effects: Nausea, diarrhea, or fatigue the day after taking the medication. Methotrexate is not a good choice if you have liver disease or you’re trying to get pregnant.

Acitretin

Acitretin (Soriatane) is a retinoid, which is a form of vitamin A. It’s the only oral retinoid medication that’s FDA-approved to treat psoriasis. You take acitretin once daily with a meal.   

Possible side effects: Dry skin and mouth, hair loss, and higher cholesterol levels. Acitretin is also not a good choice if you’re trying to get pregnant.

Apremilast

Apremilast (Otezla) is FDA-approved to treat psoriasis and psoriatic arthritis. You take it twice a day, with or without food. Over the first 5 days, you’ll gradually increase the dose of apremilast until you reach the recommended dose. 

Possible side effects: Nausea, diarrhea, and headache. Apremilast isn’t a good choice if you have a history of suicidal thoughts or severe depression.

Tofacitinib

Tofacitinib (Xeljanz) is FDA-approved for psoriatic arthritis, but not psoriasis. You take it once or twice daily. In certain situations, tofacitinib may still be a good option for psoriasis (off-label use). 

Possible side effects: A higher risk of shingles, inflammation of the nose and sinuses, and blood test abnormalities. Tofacitinib is not a good choice if you have a history of blood clots, cancer, or heart disease.

Cyclosporine

Cyclosporine (Neoral, Gengraf) is FDA-approved to treat severe psoriasis in adults with a healthy immune system. It comes as a pill or liquid that you take twice daily. 

Possible side effects: Higher blood pressure, kidney damage, and headache. Cyclosporine is not a good choice if you have kidney disease. Healthcare professionals typically recommend cyclosporine only after other options haven’t worked, since the possible side effects can be more severe.

Psoriasis injection treatments

Biologics are advanced medications that turn off a piece of the immune system that’s too active. Biologics are divided into categories based on which part of the immune system they turn off:

• Tumor necrosis factor (TNF) alpha-blockers, like Humira (adalimumab) and Enbrel (etanercept) 

• Interleukin (IL)-17A blockers, like Cosentyx (secukinumab) or Taltz (ixekizumab), and 

IL-17A/17F blockers, like Bimzelx (bimekizumab)

• IL-12/23 and IL-23 blockers, like Stelara (ustekinumab) or Tremfya (guselkumab)

• IL-36 blockers, like Spevigo (spesolimab)

How do you take biologic medications?

There are two ways you can take a biologic medication: Subcutaneously (injected into the fat below the skin) or intravenously (infused directly into the vein). The way you take the medication depends on the type of medication you’re prescribed. How often you take the biologic depends on the medication — anywhere from twice a week to once every 3 months. 

Here’s some more information: 

• Subcutaneous injections: Most biologics come in an “injector pen,” so you never see a needle. You squeeze an area of fat on your belly or thigh and push a button. Prefilled syringes and vials are other available forms. You may choose to inject yourself or ask a friend or family member to help. A healthcare professional or pharmacist might also be able to help you inject. Medication companies also have great resources with “how-to-inject” videos online and phone numbers that you can call to help you troubleshoot. Some will even send a nurse to your home to teach you how to do it.

• Intravenous infusions: A few biologics come in infusion form. This means that you have to drive to an infusion center and get an IV placed in your arm. Infusions can take 30 minutes to 2 hours to complete, depending on the biologic. Nurses keep a close eye on you while you are there to watch for side effects. For some, this might be more convenient.

What are the side effects of biologics?

Specific side effects will depend on the individual and the medication you’re taking. But, certain side effects are common to all biologics:

• Injection site reactions: Some redness of the skin after injection is normal. But if the skin is red and swollen after every injection and the redness and swelling is getting bigger and lasting longer after each shot, this could be a sign of an allergy. A healthcare professional might suggest some tricks to help with the reactions, but if those don’t help, you might need a different medication. 

• Risk of infections: Since biologics turn off pathways in your immune system, this means that they increase your risk of getting infections. The most common infections are the common cold and flu. But sometimes, biologics can lead to severe infections that need hospitalization. 

To protect you from infection while taking biologics, your health team will take some precautions, for example:

• Testing you for hepatitis, HIV, and tuberculosis infections before starting biologics

• Making sure that you are up to date on recommended vaccinations

• Holding off taking your biologic if you are sick

You might feel scared about possible side effects, and that’s understandable. But know that all medications can cause side effects — even over-the-counter ones. Choosing the right medication is all about balancing the risks and benefits. You and your dermatology care team will choose a medication together. Then, you’ll have an ongoing conversation about how well the medication is working and how you feel while taking it. 

Which medication works best for psoriasis?

The American Academy of Dermatology and National Psoriasis Foundation published guidelines in 2019 for the treatment of psoriasis with biologics. But they don’t list or name the best medication, since there really isn’t one. Why is that? 

First, everyone is different, and you have your own version of psoriasis. A medication that works well for one person might not work best for you.

Second, there aren’t many studies that directly compare one medication to another. In other words, it’s hard to put medications in a foot race and see who wins. Sometimes, researchers compare study results to get an idea of which medication works best. For example, an ongoing study is comparing trials of systemic psoriasis medications. So far, it includes 179 different trials. Most recent data shows that medications in the IL-17 and IL-23 blocker family might work best. Remicade, an infusion in the TNF-alpha blocker family, also works well.

How to choose the right medication for your psoriasis

With so many options available, it’s normal to feel a bit overwhelmed. Some factors that you and your health team will consider when choosing a medication include: 

• The type of psoriasis you have

• The severity of your psoriasis

• Your other health problems

• Medication side effects

• Your insurance coverage 

If you don’t have insurance or your insurance doesn’t cover the medication you need, there are  programs that can help. This includes manufacturer copay cards if you have private insurance and different assistance programs if you have Medicare. 

How long will it take for the medication to work?

Generally speaking, oral medications take about 2 to 3 months to start working. Biologics take about 3 to 6 months to kick in, though some people see improvement faster.

Sometimes, the first medication you try will work great. Other times, it will take a little trial and error to find the medication that clears your skin. It can be frustrating to wait for a medication to work and then find out that it doesn’t. But there’s a medication out there for you. 

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Written by:

Samantha C. Shapiro, MD

Samantha Shapiro, MD, is a board-certified rheumatologist and internist with expertise in autoimmune and inflammatory conditions. She founded the division of rheumatology at Dell Medical School at The University of Texas at Austin.

Reviewed by:

Maria Robinson, MD, MBA

Maria Robinson, MD, MBA, is a board-certified dermatologist and dermatopathologist who has practiced dermatology and dermatopathology for over 10 years across private practice, academic, and telehealth settings. She is a fellow of the American Academy of Dermatology and the American Society of Dermatopathology.

Reviewed by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

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