USA: FDA Approves First Once-Daily Oral Plaque Psoriasis Drug

From verywellhealth.com

Key Takeaways

• Regulators approved an oral once-daily drug, called Sotyktu (ducravacitinib) for treating moderate to severe plaque psoriasis.
• Clinical trials showed that the drug is more effective and better tolerated than the twice-daily oral psoriasis drug, Otezla (apremilast).
• An oral medication may be easier for patients to take than injectable biologics.
• 

  Lara Antal / Verywell

Last week, the FDA approved Sotyktu (deucravacitinib), a once-daily oral pill by Bristol Myers Squibb for people with moderate to severe plaque psoriasis—a chronic, systemic, immune-mediated disease.

The medication is meant to treat adults who have plaque psoriasis severe enough to make them candidates for systemic therapy and phototherapy.

Many of the drugs that are available to treat severe cases of plaque psoriasis are biologics that are injected or administered intravenously. These can be expensive and often require patients to routinely visit a provider to be treated and monitored. Even oral immunosuppressant options can increase the risk of infection and other undesirable side effects.

Deucravacitinib is the first oral treatment for plaque psoriasis that can be taken just once daily and the first oral medication approved for the disease in a decade. In clinical trials, the drug appeared to be more effective than the popular psoriasis drug, Otezla (apremilast).

More than 7.5 million U.S. adults live with psoriasis, according to the National Psoriasis Foundation. As many as 90% of those patients have plaque psoriasis, characterized by raised patches of inflamed and discoloured skin, and nearly a quarter of those have moderate to severe cases.

Unlike existing treatment for this population, deucravacitinib doesn’t require laboratory follow-up and seems to be well-tolerated, said April Armstrong, MD, MPH, professor of dermatology and associate dean of clinical research at the University of Southern California, who led the clinical trials.

“This is a breakthrough medication and, in my opinion, this drug will be the leading oral agent for our patients with psoriasis because of its robust efficacy and good safety profile,” Armstrong told Verywell. “I'm very excited to talk to my patients about this drug.”

Clinical Trials Show Significant Plaque Improvement

The FDA approved the drug based on two clinical trials, which compared deucravacitinib to apremilast in nearly 1,700 adults with a mean age of 46 years.

These participants all had moderate to severe plaque psoriasis. On average, they experienced psoriasis for 17 years on a quarter of their bodies. More than a fifth had clinically severe psoriasis and nearly 40% had used biological therapies to control their condition.

One group took a 6-milligram tablet of deucravacitinib once per day. Other participants took 30 milligrams of apremilast twice daily or received a placebo.

By month four, nearly 60% of patients achieved a meaningful benchmark: Psoriasis Area and Severity Index (PASI) 75. This is a measurement indicating 75% improvement in the amount of skin surface area covered by plaques. In comparison, fewer than 13% in the placebo group and 35% in the apremilast group reached PASI 75.

Additionally, plaques cleared or nearly cleared in more than half of the people treated with deucravacitinib. That’s in contrast to only about 7% of people in the control group.

Patients who took deucravacitinib continued to improve over time. After six months of treatment, 69% reached PASI 75 compared with 38% of those who took apremilast.

More Accessible, Fewer Side Effects

For people with moderate to severe plaque psoriasis, providers often prescribe injections or biologics which can alter the immune system to slow or stop disease progression. (Topical treatments are typically reserved for plaque psoriasis that only covers a small part of someone's body.)

There are some existing psoriasis treatments that can be given orally, such as Trexall (methotrexate) and Gengraf, Neoral, or Sandimmue (cyclosporine), but they tend to be less effective or lead to more serious side effects than the injectable options.

Biologic drugs are given by injection or intravenously and target specific portions of the immune system. These include Humira (adalimumab), Enbrel (etanercept), and Stelara (ustekinuman). These options can be expensive and may not be covered by insurance.

Both biologic and non-biologic immunosuppressant drugs often raise the risk of infection and other health problems. Patients who take them often need to be monitored routinely.

Deucravacitinib, meanwhile, more specifically targets a key enzyme rather than suppressing the immune system broadly. This approach, Armstrong said, makes it a safer alternative to the other available drugs.

How Does Deucravacitinib Work?

The drug is the first to target tyrosine kinase 2 (TYK2), an enzyme that is linked to susceptibility for psoriasis. 

TYK2 is a member of the Janus kinase (JAK) family. Many treatments for autoimmune disorders target JAKs, but most JAK inhibitors don’t do much to affect TYK2. By blocking this specific enzyme, the drug interrupts some of the cellular processes that are key for forming psoriatic lesions.

Plus, a TYK2 inhibitor drug could be safer because it has a narrow target, compared to other JAK inhibitors, which can have a broad effect on the immune system.  

“By having more specific targeting of the pathways that are involved in psoriasis, we avoid essentially hitting the other pathways that are important for our normal human functions,” Armstrong said. These include the effects on blood cell counts, lipid and other types of metabolism, and other types of immunity.

Deucravacitinib works similarly to the widely-used psoriasis biologic agent Stelara (ustekinumab). But that drug is a monoclonal antibody that needs to be injected in a hospital setting. Deucravacitinib, on the other hand, comes as an oral pill that patients can easily take at home or while travelling.

How to Take It

Deucravacitinib is much simpler to take than most of the other injectable biologic drugs currently on the market. The 6-milligram pill is taken once a day. It can be taken with or without food.

The drug should be most effective after five to six months of treatment, but most patients will start to see improvement within just a few weeks, Armstrong said.

There are no known drug-drug interactions, so patients can use deucravacitinib alongside treatments for other conditions.

In clinical trials, patients who took deucravacitinib were less likely to discontinuation the treatment than those taking apremilast.

“Patients—once they are on the medication—tend to stay on the medication," Armstrong said.

As with many chronic conditions, pausing or stopping treatment may allow the condition to re-emerge.  

Known Side Effects

In clinical trials, the most common adverse events associated with deucravacitinib were the common cold, upper respiratory tract infection, headache, diarrhoea, and nausea.

More than 1% of patients who took deucravacitinib experienced upper respiratory infection, increased levels of creatine phosphokinase (CK) in the blood, herpes simplex, mouth ulcers, acne, or inflammation of the hair follicles (folliculitis).

More people who took deucravacitinib experienced adverse events than those who took the placebo. However, only 2% of participants stopped the treatment due to serious adverse events compared with 4% in the placebo group.

Additionally, there were no herpes zoster infections, opportunistic infections, thromboembolic events, hematologic or lipid abnormalities that are characteristic of JAK1, JAK2, and JAK3 inhibitors.

Armstrong said people with severe liver disease should not take deucravacitinib. It should also not be taken along with other immunosuppressants.

What This Means For You

If you have moderate to severe plaque psoriasis, talk with a health provider about whether you should take deucravacitinib to control your condition.

https://www.verywellhealth.com/fda-approves-first-once-daily-oral-plaque-psoriasis-drug-6735912

Alisha Bridges: My Experience With Plaque Psoriasis

From verywellhealth.com

The first time I realized people viewed me differently was in middle school. There were times growing up that if I could have worn a full-body suit with a hood over my face, I would have.

I remember beauty becoming important to my peers around age 10. I started to notice the stares and whispers. At that time, my skin was about 90% covered with flares from plaque and guttate psoriasis. 

As a child, it was hard to embrace something that made me different from my classmates. I didn’t understand what it meant to have a chronic illness. All I knew was that I had dry skin that was itchy and unattractive, and I hated it. Not only did I have a disease that covered my body, but I also had the responsibility to explain it to my peers and the adults around me.

I grew up in the 1990s, during a time when people didn’t know much about psoriasis. I remember the awkward moments when my classmates asked what was on my skin. As I rambled to explain, I found it only led to more questions that I was uncomfortable answering or was unsure about.

While in school, I opted out of sports because I didn’t want to wear the uniforms required to play. These outfits required shorts and tank tops. I was more at peace with not participating than having to deal with the stress and insecurities that came with showing my skin.

High school is when my psoriasis started impacting my self-esteem the most. During my freshman year, I was cast in the school play, Pinocchio. During our very first dress rehearsal, our drama teacher brought makeup for the cast to use.

Excited and eager to do my makeup as Ms. Fire-Eater, the villain of the show, I began to pick out my hues. The drama teacher stopped me and, in front of everyone, said, “Oh no, you can’t use any of the makeup I bought. I don’t know what’s going on with your skin.” I was hurt and embarrassed, and I felt powerless.

However, there was a silver lining. There was an assistant teacher by the name of Ms. Dee, who I told what happened. The next day, Ms. Dee came to school with a bag of samples from MAC Cosmetics and gave them to me. That was the first time I had ever heard of MAC, and I still use it as my main source of makeup.

Turning Over a New Leaf

I started to come out of my shell and feel more comfortable with myself after college. Eventually, I found an online support group for people living with psoriasis. During this time I felt extremely frustrated with my skin.

I decided to share my frustrations on the support group with a blog entitled, "My Suicide Letter." The letter is not about physical death, but a metaphor about killing the parts of me that were ashamed to live, due to my psoriasis, so I could experience a better and happier life. At the end of the letter, I proclaim ridding of the shame might be a slow death, but eventually, it would be no more.

The support and love I received from that letter was unexpected. Followed by the outpour of support, someone sent the letter to the National Psoriasis Foundation, who then invited me to their annual volunteer conference. It was my first time meeting people living with the disease, and it was what catapulted me into advocacy work.

Courtesy of Alisha Bridges

The Ups and Downs of Treatment

I’ve tried every treatment under the sun, which ranges from phototherapy to topical treatments to oral medications to now biologics, which have proven to be the most effective for me. Biologics are injections that suppress a part of your immune system that is overactive and causing the psoriasis flares.

When the COVID-19 pandemic began, there was uncertainty about the safety of biologics due to it suppressing the immune system in those who use them. In early February 2020, my healthcare provider advised me to postpone use. However, after a thorough conversation with my healthcare provider about the risk, I came to the conclusion I still wanted to continue.

So far, I have used five different types of injections. Treatment is not one-size-fits-all. What may work for one person may not have any effect on the next. Each biologic is constructed to target different parts of the immune system. Unfortunately, there is no test that indicates what part of your immune system is causing psoriasis. The process is simply trial and error and seeing what works.

Humira and Enbrel don’t work for me. They are TNF-alpha inhibitors, meaning the drugs are fighting against the overproduction of TNF-alpha proteins. Since they didn’t work, that tells me that my immune system doesn’t have an issue with TNF-alpha.

However, Skyrizi is a biologic that bonds with excess interleukin (IL) inhibitors, specifically IL-23 proteins, and it works really well. It cleared my skin up about 90%. I also tried Waltz, which cleared me up 100%, but after a while, it started failing.

So it’s a trial and error. You have to put yourself at risk for potential side effects of treatment that you don’t even know will work.

My medicine costs $16,000 for two injections every three months. Biologics are expensive, but there are patient programs available that can help you pay for your treatment.

Side effects are typically a top concern for patients and can vary from person to person. A common side effect of biologics is upper respiratory conditions like the common cold. COVID has made this side effect increasingly difficult, because now every time I get sick, I fear I might have COVID-19.

In my experience, there are a lot of healthcare providers who aren’t well-versed in Black skin or our culture. For example, I have scalp psoriasis. I wash my hair maybe once a week. I was given a treatment that requires you to wash your hair three to four times a week. But all that water is damaging for my hair.

That treatment is constructed for someone who I can’t relate to, but I’m required to use it. It wasn’t women like me in those clinical trials, but I’m using the medicine.

I recommend finding a healthcare provider who has worked with Black skin and someone who is involved in research.

As Black women, we deal with a lot of cultural challenges, like not telling your business and keeping struggles to yourself, not trusting healthcare providers, socioeconomic issues of not having insurance, or even being able to get to the doctor.

All of these can make getting help more difficult. That’s why it’s important to find other women who you can relate to in online support groups. I also recommend getting involved with the National Psoriasis Foundation, no matter what your ethnicity is.

A Continuing Struggle

It’s easy to look at someone like me—a patient advocate openly speaking about their disease—and think that I’m always confident. I still have bad days. I still hate the fact that I have psoriasis.

I despise the moments I have to fight with insurance companies to obtain my treatment or attempt to be the middle person between insurance, the pharmacy, and healthcare providers. It’s always a real reminder that although I’m currently clear from psoriasis, I still have this disease and it will continue to impact my life.

Meet the Author

Alisha M. Bridges is an award-winning writer, public speaker, media consultant, and health activist. She advocates on behalf of patients to bridge the gap between the medical community and patients living with chronic disease. Alisha volunteers with the National Psoriasis Foundation, where she speaks openly about her own experience with psoriasis at conferences.

https://www.verywellhealth.com/alisha-bridges-my-experience-with-plaque-psoriasis-5204989

Q&A: Psoriasis, mental health care affected by socioeconomic burdens

From healio.com

In this issue’s cover story, experts discussed how reducing psoriasis in the patient is the best way to curb the negative impact on mental health that stems from disease stigma.

However, not everyone in the United States is offered the same level of care to do so.

Paul Wallace

Healio Psoriatic Disease spoke to Paul Wallace, MD, MPA, a Los Angeles-based, board-certified dermatologist and researcher, about how socioeconomic status can affect the level of care for patients with psoriasis.

Healio: How does socioeconomic status affect the stigma of psoriasis and the ability to receive care?

Wallace: There has always been a stigma regarding skin disease. It is something you cannot hide. Most patients with moderate to severe psoriasis want to be invisible, or like everyone else in regard to their skin.

People look at psoriasis and think it is contagious. It is red, it is inflamed, sometimes it can be bleeding.

For some with psoriasis it is an inconvenience, but it is something that can be worked through. But, say you are a blue-collar worker – not necessarily someone in the supervisor or corporate level – and you need light therapy. Here in the Los Angeles area, it could take an hour to get there, it is a 30-minute treatment, and then an hour to get back. And you need to do it three times a week. To miss 2.5 hours of work three times a week is unacceptable. As you move from one economic level to another you might not have the luxury to do the treatments.

This is a solvable, controllable problem and we have not been making this accessible to everyone in this country.

Healio: How do insurance companies and different levels of coverage affect psoriasis patients’ ability to get proper treatment?

Wallace: There is clearly a 2-tier, perhaps even a 3-tier, system in this country. If you have commercial or employment insurance and a PPO, you can get all of the FDA-approved biologics at no cost to you. But if you are on a government assisted program, you have to go through a tremendous number of hurdles to get the medication.

That is one of the most frustrating things for me as a physician. This is so far away from the practice of medicine in being dictated by insurance companies.

For example, we know the efficacy of methotrexate is far below the least-effective biologic. And there has been a number of studies that show it is cost effective to get these patients’ disease under control to improve their quality of life and their ability to be productive citizens. But many government programs mandate 3 months of methotrexate before moving on to biologic treatments.

There is a gap in the type of care some individuals get. It is not unusual that those on state insurance plans have as much as a 6 month wait before they can get into our office. They need to get approval by their insurance company and many times a referral from their primary care doctor before they see a specialist.

Healio: In this issue’s cover story we discuss the importance of mental health help for psoriasis patients who are suffering from the effects of stigma from their disease. How is the ability to receive mental health care impacted by socioeconomic status?

Wallace: If it is possible I send all of my patients to a psychologist to have either one-on-one or group sessions to help them understand they are not alone.

The problem is in 90% or more of insurance plans, especially those with government plans, counselling is not included.

Availability and accessibility for all in this country would be the best approach.

https://www.healio.com/news/dermatology/20211013/qa-psoriasis-mental-health-care-affected-by-socioeconomic-burdens?utm_source=selligent&utm_medium=email&utm_campaign=news&M_BT=6459271603417