Better together

| Melissa Leavitt

You name it, Lisa Medlin has tried it.

Since being diagnosed with psoriasis as a child, her treatment regimen has run the gamut from topicals to biologics and everything in between, with detours through phototherapy, methotrexate and steroids. During college, her search for “the one” — the one treatment, that is — even took her to a dermatologist whom she says took an experimental approach to treatment, putting her on antibiotics to eradicate her psoriasis.

“Needless to say, I didn’t get better with that,” Medlin said. “I just got worse.”

Now 49, the Tennessee family nurse practitioner and associate professor of nursing has settled into a therapy routine of the biologic Cosentyx (secukinumab) and topicals, with short courses of cyclosporine to manage flares.

Medlin may have finally found “the one.” But for her — like many people living with psoriasis and psoriatic arthritis — “the one” is actually more than one.

Why two (or more) can be better than one

Doctors call the practice of combining two or more therapies into a single treatment plan “combination therapy.” It can be helpful for many diseases, including psoriatic disease.

For psoriasis, combinations might come in the form of one or more topicals, a topical plus a systemic treatment or even multiple systemic treatments. Topicals are applied directly to the skin, while systemic treatments affect the whole body and can be taken by mouth or injection.

According to a May 2013 article in the Journal of Drugs in Dermatology, combination therapy is the most common method of treating psoriasis in the United States. And those with psoriatic arthritis are no strangers to combination therapy either, with systemic medications often sharing space in the same medicine cabinet.

The reason for trying a combination therapy rather than just one treatment at a time is straightforward, said Dr. Steven Feldman, a dermatologist at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.

“The goals are improved efficacy and greater safety,” he said.

Many treatments for psoriatic disease affect the immune system, making them great candidates for calming the overactive immune reaction seen in patients with psoriasis and psoriatic arthritis. But that also caps how much of the drug a patient can safely take.

As noted in an April 2015 article in the journal JAMA Dermatology, in which the NPF Medical Board offered guidelines for combining biologics with other systemic treatments in psoriasis, increasing the dose is not always an option.

If a patient is not getting the desired result from one systemic treatment, for instance, he or she can’t always take more. So when that happens, doctors often prescribe an additional medication.

“None of the agents is absolutely perfect,” said Dr. Tina Bhutani, a dermatologist at the University of California, San Francisco. “Even if someone is having really good control on, let’s say, a biologic or another systemic agent, they might still have some stubborn plaques left over. They might still have some joint pain that’s occurring. So we add on the combination therapy as a way of getting them even better.”

For example, combining a topical with a systemic treatment can make the wait before a patient starts seeing results a little easier.

“Usually the systemic agent takes a little bit of time to start working. While we’re waiting for the systemic agent to take full effect, the topical can start to work very quickly,” Bhutani said.

Combining topicals can deliver better results as well, Feldman said.

Ointments, creams and foams, for instance, may all be suited to different parts of the body. And some formulations work better for different symptoms and locations.

“You might treat the scalp differently from the elbows, the elbows differently from the genitals,” Feldman said.

Combination therapy can be used to address multiple symptoms of psoriatic arthritis at the same time.

According to Dr. Evan Siegel, a rheumatologist in private practice in Maryland and a member of NPF’s Medical Board, a treatment may improve one symptom of psoriatic arthritis, such as joint inflammation, but not another manifestation of the disease, such as enthesitis (inflammation where the tendons and ligaments insert into the bone) or ongoing skin disease.

That’s when combination therapy comes into play.

“Almost always it would be methotrexate plus a biologic if we need two therapies” for psoriatic arthritis, Siegel said.

Taking methotrexate in addition to another systemic treatment — particularly a biologic — can be an effective treatment for psoriasis and psoriatic arthritis. Medlin has used methotrexate in combination with phototherapy, Enbrel (etanercept), Humira (adalimumab) and Remicade (infliximab), to name a few.

The nausea she experienced with methotrexate meant she didn’t always take it as directed, she said. But she often saw better results when she combined it with a biologic.

A June 2015 review published in the British Journal of Dermatology analyzed results from eight studies examining a biologic used in combination with methotrexate for the treatment of psoriasis. Overall, the study found that combining a biologic with methotrexate was more effective than the biologic alone and was not associated with a higher rate of adverse events.

Based on available data in 2015, NPF’s Medical Board recommendations expressed the highest preference for combining methotrexate with biologics over combining methotrexate with other systemics such as acitretin, phototherapy and cyclosporine. Methotrexate can also be effective as a standalone treatment, but in combination with a biologic, it can make the biologic more effective.

When a rheumatologist told her why that was, Medlin said it made her more willing to take it. Many people who take biologics find that they deliver dramatic improvement up front but slowly lose effectiveness because the body has a tendency to develop antibodies against biologics. But methotrexate can stop the formation of antibodies because it affects the part of the immune system that makes them.

In contrast to biologics, which target specific parts of the immune system, “methotrexate does more of what we call ‘blanket immunosuppression,’ calming down all aspects of the immune system,” said Bhutani.

Combinations to control flares

Taking more than one drug at the same time isn’t the only type of combination therapy.

An article in the March 2004 issue of the Journal of the American Academy of Dermatology described several different combination therapy approaches. One is taking multiple drugs concurrently.

Another is called “sequential therapy.” This involves taking a powerful, fast-acting drug to begin with, then gradually transitioning to a different drug for long-term therapy.

Medlin knows firsthand about transitioning from powerful short-term fixes to a therapy she could live with in the long run.

About a year ago, a trip to the hospital for a flare of pustular psoriasis unfolded into a five-week stay. During that time, she said she took steroids intravenously as well as other treatments, including acitretin and Cosentyx. Today, Cosentyx is her mainstay although breakthrough flares still require her to take cyclosporine for shorter periods of time. “It’s working really well,” she said.

While she was in the hospital, Medlin said she was carefully monitored to make sure that the treatments were not causing dangerous side effects. Acitretin, for example, can cause liver damage.

“They could take my blood any time they wanted to, to make sure my liver was OK,” she said.

At one point, she did develop an elevation in liver enzymes that can be a sign of liver damage.

Does double the treatment double the risk?

One advantage of combination therapy is that it can reduce the risk of side effects from medications, Bhutani said.

“Instead of using a really high dose of a medication and possibly getting side effects from it, we can use a lower dose of two medications and minimize the side effects of both of them,” she said.

Being aware of the risks associated with your combination therapy plan is essential to managing multiple therapies safely, and many individual treatments or combinations require monitoring for specific side effects.

Siegel explained what that means, for instance, for someone taking a biologic-methotrexate combination.

“What you’ve done is combined the individual risks of each therapy,” Siegel said. “Methotrexate has one set of toxicities, the biologics have a different set of toxicities. For example, a particular biologic that a patient is on may not have much in the way of liver toxicity. Adding methotrexate would mean that you have to be much more vigilant for problems with the liver.”

Managing multiple treatments

In addition to developing elevated liver enzymes, Medlin also experienced hyperglycemia when she was in the hospital, she said.

Hyperglycemia, otherwise known as high blood sugars, is a symptom of diabetes. Diabetes can be a comorbidity (a health condition that has been linked to another disease) of psoriatic disease, and having psoriasis or psoriatic arthritis can be associated with a higher risk of developing diabetes, something Medlin works hard to avoid.

“I have to keep a pretty close eye on my blood sugars. I have to keep a close watch on my weight. I do have a healthy lifestyle. But if I didn’t, I’m convinced I would either be or become diabetic within a year,” she said.

Being aware of how psoriatic disease treatments may interact with treatments for comorbidities — or the comorbidities themselves — is an important part of managing multiple treatments.

Siegel, Feldman and Bhutani said there are some therapies and combinations that may not be the best option for people with certain comorbidities.

“We are always, always, always thinking about the entire patient — and all of the ways that their various comorbidities would interact with their underlying psoriatic arthritis and with the medication that we’re going to give them,” Siegel said.

“If someone is diabetic, for example, you want to be very careful about adding prednisone, a steroid,” because of potential effects on blood sugar or blood pressure, he explained.

Adding a nonsteroidal anti-inflammatory drug (NSAID) to a patient’s treatment plan can also require extra care, he said.

NSAIDs can help with persistent joint pain and swelling, but if a patient also has cardiovascular disease or high blood pressure, Siegel said, “I’m going to be very careful about adding nonsteroidal anti-inflammatory drugs.”

Feldman urges caution against someone with liver disease taking methotrexate, and he also noted that acitretin can elevate lipid levels, which are linked to high cholesterol and other signs of heart disease.

Sometimes a treatment can have a negative effect on psoriatic disease itself. For example, beta blockers are drugs commonly prescribed to lower blood pressure. But, according to Bhutani, “Beta blockers are actually infamous for worsening psoriasis. If that’s the only option, then we have to work through it. But if at all possible, we try to avoid treating psoriasis patients’ blood pressure and cardiovascular disease with a beta blocker.”

Avoiding dangerous drug interactions

Regardless of health conditions, some treatments aren’t meant to be taken together because they can lead to dangerous drug-drug interactions. For example, Feldman said that giving patients an antibiotic called Septra (trimethoprim and sulfamethoxazole) when they’re already on methotrexate can be very dangerous.

“That can make methotrexate toxicity much worse,” he said.

A study published in the journal Dermatology in February 2010 examined the frequency of drug-drug interactions in people with psoriasis in the United States taking either methotrexate or cyclosporine.

Of nearly 8,000 patients, researchers found that more than half also had prescriptions for drugs that could interact in a potentially dangerous way with their psoriasis treatment, leading to problems with the kidneys or gastrointestinal system, for example.

Interactions can occur when someone takes multiple drugs that are processed the same way in the body, such as oral treatments that are processed in the liver, Bhutani said.

However, an advantage of biologics is that, because they are injected or given intravenously, they are processed in a different way, said Bhutani.

She advised patients who think they may be experiencing a drug interaction to call their physician as soon as possible. And if the problem is urgent, take immediate action.

“If you have trouble breathing or some more serious signs, just stop the medication and [go] to urgent care or the emergency room,” Bhutani said.

Many resources are available to help ensure people with psoriatic disease avoid dangerous drug interactions and are on a treatment plan that takes their total health into account.

For example, NPF offers patients booklets that discuss treatment options and the potential risks of particular therapies or combinations. Feldman said he always keeps them in his coat pocket to give to patients when he’s discussing potential medications.

NPF’s Patient Navigation Center can answer your questions about treatments. Another resource to help make sure your treatments are as safe and effective as possible might be right around the corner — or at your local shopping center.

“The pharmacist is a great option for patients to not only manage their medication but also to manage their disease,” said Dr. Renee Baiano, a pharmacist and NPF medical professional member.

Physicians can sometimes be difficult to reach, she said, while pharmacists are available most of the day, and in some cases, 24 hours a day. They are trained to review medications prescribed by different doctors and make sure everything can be safely taken together.

“We are on the front lines,” Baiano said.

Juggling medications from different providers

Many people with psoriasis or psoriatic arthritis see multiple physicians — a dermatologist, rheumatologist and primary care physician, for example. Because it can be difficult for every member of the care team to interact, it’s often up to the patient to keep everyone informed of medication changes and any health issues that have arisen.

Bhutani recommends patients keep a card in their wallet that lists all of their medications, including the name of the drug, the dose and how often it’s taken.

“Having all of that information is very, very helpful and probably the most efficient way of making sure that everyone is on the same page,” she said.

Siegel also urges patients to make sure that, if they’re on a biologic, every member of their care team knows about it.

For Medlin, staying healthy is a team effort. She has an internist, a dermatologist and a nutritionist she sees regularly. But she knows that she’s the most valuable player on her team.

“I have to tell them when I know something is wrong. I listen to my body, and I call them. And I think that’s my responsibility,” Medlin said.


Driving discovery, creating community

For more than 50 years, we’ve been driving efforts to cure psoriatic disease and improve the lives of those affected. But there’s still plenty to do! Learn how you can help our advocacy team shape the laws and policies that affect people with psoriasis and psoriatic arthritis – in your state and across the country. Help us raise funds to support research by joining Team NPF, where you can walk, run, cycle, play bingo or create your own fundraising event. If you or someone you love needs free, personalized support for living a healthier life with psoriatic disease, contact our Patient Navigation Center. And keep the National Psoriasis Foundation going strong by making a donation today. Together, we will find a cure.

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