Is Combination Therapy Right for You?

Written by Hallie Levine
Medically Reviewed by Stephanie S. Gardner, MD on August 19, 2026

There are many good treatments available for atopic dermatitis (AD). But if you have moderate-to-severe AD, also known as eczema, you may have to try different medications before your symptoms get better. Sometimes, your doctor may even suggest that you take more than one. This is known as combination therapy.

“Combination therapy can be very effective because it targets several different pathways that cause atopic dermatitis,” explains Paul Yamauchi, MD, PhD, a clinical assistant professor of dermatology at the David Geffen School of Medicine at UCLA in Los Angeles. About three-quarters of people with AD who use biologics or JAK inhibitors — medications generally reserved for patients with more severe symptoms — use combination therapy.

But it’s not for everyone, and the more medications you take, the more at risk you are for side effects. Here’s what people with moderate-to-severe AD need to know.

Combination therapy combines at least two prescription medications for AD. Most people with moderate-to-severe AD require advanced targeted treatments, such as biologics, which are given as injections every two to four weeks, or JAK inhibitors, which are taken daily as a pill, says Matthew Zirwas, MD, a dermatologist at Bexley Dermatology in Bexley, Ohio.

These drugs work well for most patients, but they aren’t always enough. “These medicines block certain cytokines, or inflammatory substances in the body that can trigger AD,” Zirwas explains. “But sometimes, patients have elevated levels of more than just one cytokine, so they need more than one drug to get symptoms under control.”

 

There are many types of combination therapy for AD. Here are some of the most common pairings:

Topical therapy with a biologic. If you’re already on a topical prescription cream such as a steroid or calcineurin inhibitor, your doctor may decide to keep you on them while you start biologic treatment. “We usually have them take both until we feel confident that they are responding to the newer medication,” says Yamauchi.

A biologic with an immunosuppressant. This combines a biologic with a drug, such as cyclosporine or methotrexate, that helps slow down your immune system to better manage your AD symptoms. These may be given for just three to four months to help manage a flare, or long term.

A biologic with a biologic. If you are already on a biologic, your doctor may prescribe a second one to see if you get a better response. “There aren’t published studies, but there are case reports where we’ve found that the combination is safe and works well, especially to relieve extreme itching,” says Yamauchi.

A biologic with a JAK inhibitor. JAK inhibitors are a new class of drugs that also work to block immune signals that can trigger AD. “Biologics block inflammatory pathways outside cells, while JAK inhibitors block pathways inside cells,” explains JiaDe Yu, MD, chair of the Department of Dermatology for the VCU School of Medicine in Richmond, Virginia. “The theory is that if you combine the two, you’ll get a broader effect than if you just use one alone.” One small study of nine patients found that about two-thirds responded to this type of combination therapy.

A biologic or JAK inhibitor with phototherapy. Phototherapy, or ultraviolet light therapy, can help control moderate-to-severe AD. “It’s not as effective as either a biologic or a JAK, but anecdotally I’ve found that when I add it onto treatment, patients often have a better response,” says Yu. While you can take a biologic or JAK inhibitor at home, you’ll need to go to your doctor’s office two to three times a week for phototherapy.

Over-the-counter (OTC) combination therapy for AD

Combination therapy for AD isn’t just for prescription medications. Some OTC treatments can also help you manage your AD.

Zirwas often suggests his patients with moderate-to-severe AD try an OTC supplement along with their medications. Some research suggests that adults with AD who take 10 milligrams of melatonin daily see improvement in AD symptoms such as itching, as well as better sleep quality.

Another option is a topical probiotic that contains a bacteria called Roseomonas mucosa. It’s present on healthy skin that’s been shown to ease AD symptoms in both adults and kids. “It won’t replace prescription treatments, but it can complement them,” says Zirwas.

There’s also a form of OTC combination therapy most dermatologists recommend: regular moisturizer along with your regular treatment. “Moisturizer is important to maintain a healthy skin barrier,” says Yamauchi. It can also help seal in topical medications, he adds. The best types of moisturizers for people with AD are thick creams, such as Cetaphil or Eucerin, or even ointments like Vaseline. Apply them at least twice a day, including right after you take a bath or shower.

Your doctor won’t suggest combination therapy until you’ve tried at least two to three other medications. “If a patient has tried a couple of the biologics and a couple of the JAK inhibitors, I might consider combining both to see if we get a better response,” says Yamauchi. 

The combination therapy your doctor suggests may be based on what’s covered by insurance. Biologics and JAK inhibitors are very expensive, so insurance may be less likely to let you use both of them. “We often start with a biologic plus an older immunosuppressant like cyclosporine, to get it covered by insurance, and if that doesn’t work, try a biologic and a biologic, or a biologic and a JAK inhibitor,” says Zirwas. 

There hasn’t been a lot of research on the use of combination therapy for AD. “We don’t have exact statistics on how effective it is, although there are published case reports to show that they can be helpful,” points out Zirwas. Here are some things to keep in mind if your doctor does suggest combination therapy:

Side effects. The more drugs you take, the more likely you are to get side effects. For biologics, the most common side effects are redness and itching at the injection site, along with facial redness and conjunctivitis (red, inflamed eyes). Side effects of JAK inhibitors include:

Very rarely, they can cause blood clots, pneumonia, or tuberculosis. “The good news is anecdotally we haven’t seen a lot more side effects in patients who use both a biologic and a JAK inhibitor,” Zirwas says. 

Cost. Biologics and JAK inhibitors are both very costly, with out-of-pocket costs of up to $40,000 per year. “It can be very hard to get insurance to cover more than one of these drugs at a time,” Yu says. “Sometimes, we have no choice but to keep patients on free samples so that they can at least trial a combination for a couple months.” 

Time. Some combination treatments, such as a topical plus phototherapy or a biologic and phototherapy, work well but need more time. “Phototherapy is very helpful when it’s added to one of these drugs, but most patients don’t have the time to come into the office three times a week for 30-minute sessions,” Yu says. Also, it can be hard to remember or find time to administer more than one drug at home.

If you decide to start combination therapy, you must take medications exactly as prescribed. If you miss an injection or skip a pill, you may not get the results you want.

Your doctor will let you know what side effects to look for. If you are on more than one drug, you may need to be carefully monitored. If you’re on a JAK inhibitor, for example, your doctor may want you to have blood tests to check your complete blood count (CBC), liver function, and cholesterol levels every three to six months.

You can expect to see results faster when you are on combination therapy. “Most patients notice an improvement in their AD within a couple weeks, although it can take 8-12 weeks to get the complete effects,” Yu says. 

It’s not clear how long you’ll need to be on combination therapy for your AD. “Some patients are on it for just a few months to help get a flare under control, and some will stay on it indefinitely,” Yamauchi says. If your AD gets better completely, your doctor may try to lower your dose of either or both medicines and see how you respond, he adds.

Finally, if you’ve tried different combination options and they don’t help with your AD, talk to your doctor. “You may not have atopic dermatitis but another condition such as celiac disease, or even cutaneous T-cell lymphoma, which is a form of skin lymphoma,” Zirwas explains.

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