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Immunomodulators for Atopic Dermatitis

Medically Reviewed by Stephanie S. Gardner, MD on March 01, 2022

Atopic dermatitis (AD) is a type of eczema, a condition that makes skin dry, red, and itchy. There are many ways to tame its symptoms, from creams that control itching to light therapy. But about half of people with AD don't find enough relief from these treatments alone.

That's when your doctor might prescribe a medicine called an immunomodulator. It relieves atopic dermatitis symptoms by dialing down your immune system.

What Are Immunomodulators?

In atopic dermatitis, your immune system reacts too strongly to normally harmless substances such as dust or pet fur. That overactive immune response is what causes symptoms like dryness and itching.

Immunomodulators, also called immunosuppressants, reduce the activity of your immune system. You can take these medicines as a pill, by injection, or as a topical that you rub onto your skin.

Injected and oral immunomodulators reduce the immune response throughout your body. Topical ones control the immune response in your skin.

Immunomodulators come in a few different types.

Calcineurin Inhibitors

Calcineurin inhibitors prevent immune cells in your skin from reacting to allergens like dust mites, pollen, and pet fur. Two of these medicines are approved to treat atopic dermatitis:

  • Tacrolimus ointment (Protopic) is for moderate to severe atopic dermatitis.
  • Pimecrolimus cream (Elidel) is for mild to moderate atopic dermatitis.

Calcineurin inhibitors are second-line treatments. That means you take them after other topical medicines haven't cleared your skin.

How to use them: Rub a thin layer of the medicine onto affected areas of your skin twice a day. Keep using the medicine until your symptoms improve.

What to expect: Tacrolimus should start to clear your skin in about a week. If you don't see any improvement in 2 weeks, ask your doctor about other treatment options.

Use pimecrolimus for the shortest amount of time needed to clear your skin. If you don't see any improvement in 6 weeks, stop using it and talk to your doctor.

Once your skin has cleared, you can drop down to using these topicals twice a week. This maintenance therapy helps prevent atopic dermatitis from coming back.

Side effects:

  • Burning, stinging, redness, or itching in the area where you apply them
  • Tingling skin
  • Change in skin color
  • Cold sores or warts

These medicines carry a warning because a very small number of people who used them got skin cancer or lymphoma afterward. It's not clear whether calcineurin inhibitors caused the cancer. Talk to your doctor about this risk, and follow the directions to make sure you use these medicines safely.

Stay out of the sun as much as possible while you take calcineurin inhibitors. When you do have to be outside, protect your skin by wearing sunscreen and sun-protective clothes.

Your doctor might recommend avoiding calcineurin inhibitors if you:

  • Have a skin condition called Netherton's syndrome
  • Are pregnant or breastfeeding, or you plan to get pregnant
  • Have had a skin disease such as chickenpox, shingles, or herpes

PDE4 Inhibitors

Crisaborole (Eucrisa) is a PDE4 inhibitor. It works by blocking a substance that causes inflammation in your skin. Crisaborole is approved to treat mild to moderate atopic dermatitis.

How to use it: Apply a thin layer of ointment to your skin twice a day. Dermatologists recommend using it after you take a shower or bath.

What to expect: One in three people who used crisaborole in studies had clear or almost clear skin within a month. Tell your doctor if you don't see an improvement after you've taken this medicine for 4 weeks.

Side effects: The most common side effect is burning or stinging in the area where you applied the ointment. These side effects should go away after you've used crisaborole for a while.

Biologics

Dupilumab (Dupixent) and tralokinumab (Adbry) are biologic drugs. They block chemicals called interleukins that are involved in triggering inflammation.

How to use them: Dupilumab comes as a shot. Adults get one 600-milligram dose, followed by a 300-milligram dose every other week. Tralokinumab comes in four 150-milligram injections followed by two 150-milligram injections every other week. Patients who weigh under 100 kilograms (about 220 pounds) who achieve clear or almost clear skin can decrease their dose to two 150-milligram injections every 4 weeks.

What to expect: More than one-third of people who used dupilumab in studies had clear or almost clear skin after 4 months. People who had clear or improved skin at 16 weeks with tralokinumab maintained their results at a year with continued use.

Side effects: The most common side effects for dupilumab are infections at the injection site, pinkeye, and cold sores. The most common side effects for tralokinumab are eye and eyelid redness and inflammation, injection-site reactions, and elevated levels of certain white blood cells (eosinophilia).

JAK Inhibitors

JAK inhibitors block chemical signals that are involved in promoting inflammation. These medicines come in a cream and pills.

Ruxolitinib (Opzelura) cream is approved for mild to moderate atopic dermatitis that hasn't improved with other creams or ointments.

Abrocitinib (Cibinqo) and upadacitinib (Rinvoq) are pills. They're approved for people with moderate to severe and mild to moderate atopic dermatitis, respectively, that hasn't cleared up with other treatments.

How to use them: Apply a thin layer of ruxolitinib ointment twice a day to affected areas of your body. Take abrocitinib and upadacitinib by mouth once a day.

What to expect: You can use ruxolitinib for up to 8 weeks. If you don't see improvement after 2 months, check with your doctor. Between 25 percent and 60 percent of people get partially or totally clear skin after 3 to 4 months on abrocitinib or upadacitinib.

Side effects: JAK inhibitors carry a "black box warning" because they might increase the risk for serious infections, cancer, blood clots, heart attack, or stroke. Talk to your doctor about these risks before you start using ruxolitinib. Ask how your doctor will monitor you while you take this medication.

Other possible side effects from these drugs include:

  • Cold symptoms like a stuffy or runny nose or sore throat
  • Nausea and vomiting
  • Diarrhea
  • Headache
  • Cold sores

Traditional Immunomodulators

These medicines were originally designed to lower the immune system response to prevent organ rejection after a transplant or to treat diseases like cancer or arthritis. They're not approved for atopic dermatitis, but doctors sometimes prescribe them for severe atopic dermatitis that hasn't improved with other treatments.

These medications include:

How to use them: They come as a pill or an injection.

What to expect: You take these immunomodulators only for a short period of time to get your atopic dermatitis under control. Once your symptoms have improved, you can switch to a topical or taper off.

Side effects:

  • Increased risk for infections and certain cancers
  • Vomiting
  • High blood pressure
  • Kidney or liver damage

Ask your doctor which tests you'll need while taking these medicines to monitor for problems.

Steroids

Steroids are one of the most common treatments for atopic dermatitis. They bring down swelling, relieve itching, and help skin heal.

Doctors rarely prescribe oral steroids because of their side effects. But you might take a steroid pill for a few days to get a severe flare-up under control.

Topical steroids come in many forms, including as a:

  • Lotion
  • Gel
  • Cream
  • Ointment
  • Spray

These medicines range in strength from mild to very strong. You can buy some mild steroids over the counter. For stronger topical steroids or oral steroids, you'll need a prescription from your doctor.

How to use it: Rub a thin layer of the steroid on affected areas of your skin. Most people take topical steroids once or twice a day for 1 to 2 weeks.

What to expect: Use steroids for the shortest possible time needed to clear your skin. If you take a high-dose steroid, you may need to lower the dose a little bit at a time to come off the medicine. This is called a "step down." It helps prevent your symptoms from coming back, or rebounding.

Side effects:

  • Thinning skin
  • Stretch marks or spider veins
  • Skin irritation called contact dermatitis
  • Acne
  • Rash
  • Changes in skin color

It can take time to find the right medicine or combination of medicines to control atopic dermatitis flares. Let your doctor know if you don't see improvement within a few weeks of using these medications.

Show Sources

SOURCES:

American Academy of Dermatology: "Atopic dermatitis treatment: Crisaborole (Eucrisa) Ointment."

BioMed Research International: "Nonsteroidal Topical Immunomodulators on Allergology and Dermatology."

JAMA Dermatology: "Systemic Immunomodulatory Treatments for Patients with Atopic Dermatitis."

Mayo Clinic: "Atopic dermatitis (eczema)."

MedlinePlus: "Pimecrolimus Topical," "Ruxolitinib Topical," "Tacrolimus Topical."

Missouri Department of Social Services: "Atopic Dermatitis Agents."

National Eczema Association: "FAQ - Cibinqo (Abrocitinib)," "FAQ - Dupixent (Dupilumab)," "FAQ - Eucrisa (Crisaborole)," "FAQ- Opzelura (Ruxolitinib) Cream," "FAQ - Rainbow (Upadacitinib)," “FAQ - Adbry (Tralokinumab-Idrm),”"Immunosuppressants," "Prescription Oral," "Prescription Topicals."

National Eczema Society: "Topical Calcineurin Inhibitors," "Topical Steroids."

NHS: "Atopic eczema - treatment," "Topical Corticosteroids."

PLOS: "Just Skin Deep – Your Immune System at the Surface."

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