Best Treatment Options for Uncontrolled Psoriasis

Failing to find relief for your psoriasis symptoms can be painful and frustrating. But treatment-resistant psoriasis, sometimes called uncontrolled psoriasis, is common. 

In fact, treatment failure is one of the major challenges facing psoriasis treatment today. Many people with the condition have to try many different treatments or treatment combinations before finding an effective approach for their symptoms. 

Thankfully, multiple effective treatments for psoriasis exist. Working with your team of healthcare providers to get a personalized approach to your treatment plan is crucial to finding the right treatments and lifestyle modifications to mitigate your symptoms.

Options for treatment-resistant psoriasis include systemic treatments, biologic therapies, or combination therapies, including a combination of topical and systemic therapies or rotating treatments.   

Once you find the right treatment approach for your psoriasis, it’s important that your providers continue to monitor your symptoms in case any changes occur.

In this article, we’ll explain the signs of uncontrolled psoriasis and what treatment options are available. We’ll also cover effective lifestyle changes and complementary approaches that can support your treatment and long-term remission. 

What is Uncontrolled Psoriasis?

Though not a medical term, uncontrolled psoriasis is a term used to describe psoriasis that doesn’t respond to treatment. Some may also refer to it as treatment resistant psoriasis.

There are two main types of uncontrolled psoriasis or treatment failure:

• Primary treatment failure: When your symptoms fail to resolve or improve after initial treatment as recommended by your healthcare provider. ‍
• Secondary treatment failure: When a previously effective treatment loses its efficacy and symptoms return or worsen. 

In some cases, uncontrolled psoriasis can be a sign of severe psoriasis.

Signs Current Psoriasis Treatment Isn’t Working

There are several signs that can indicate your psoriasis is uncontrolled or not responding to treatment, including:

• Your symptoms aren’t getting better, including continued or worsening itchiness or redness and plaques that won’t go away.
• Your symptoms improve or resolve initially, only to come back while you’re still following the same treatment protocol.
• Your psoriasis symptoms affect your ability to accomplish daily tasks, like working, driving, sleeping, or socializing.
• Joints become stiff, swollen, or painful. This could be a sign of psoriatic arthritis, a condition associated with psoriasis. 
• You experience a change in your mental health, including an increase in depression or anxiety or a reduced interest in socializing.  
• Side effects make it difficult or impossible for you to follow or continue your treatment as recommended by your healthcare provider.

If you experience any new or unchanged symptoms like the examples listed above, reach out to your provider to see if a change in treatment is needed.

Risk Factors for Uncontrolled Psoriasis

There isn’t a wealth of data examining potential risk factors for uncontrolled psoriasis, but some researchers have found a few shared characteristics among people who experience treatment failure, including:

• Having at least one difficult-to-treat area, like the scalp, face, nails, foot soles, genitals and palms
• Being born female
• Being 51-64 years of age
• Having previously used a targeted immune modulator (TIM)

Systemic Psoriasis Treatments

Systemics, also called systemic immune modulators, have been used to treat people with moderate-to-severe psoriasis for decades. Today, a provider may recommend systemics for those who try topical therapies but fail to find relief or for those who prefer non-injectable medication.

Most systemic therapies work by targeting the immune system. They are still widely used either as standalone treatment or in combination with biologic medications. 

Compared with biologics, systemic treatments are relatively low-cost and easier to access and administer. 

Methotrexate

Approved by the Food and Drug Administration (FDA) in 1972, Methotrexate was originally used to treat cancer. It works to treat psoriasis by binding to and inhibiting an enzyme that supports the rapid growth and division of skin cells.

Methotrexate is usually administered orally in a single dose ranging from 7.5mg to 25mg weekly, though some people divide the dose into three over a 24-hour period. Splitting the dose can help some people reduce the gastrointestinal (GI) side effects associated with the medication. 

Other possible side effects of methotrexate include:

• Dizziness
• Drowsiness
• Headache
• Swollen, tender gums
• Reddened eyes 
• Hair loss

Supplementing methotrexate therapy with folic acid is recommended to reduce the rate of side effects. Be sure to take folic acid every day except for the days you take methotrexate.

You should not take methotrexate if you are pregnant or planning to become pregnant. Rare but serious risks include liver damage, liver scarring, lung damage, decrease in blood cells, and an increased risk of developing certain cancers.

Cyclosporine

Cyclosporine was approved by the FDA to treat psoriasis in 1997. It works by binding to a family of proteins that helps to block proinflammatory signaling. 

Most providers recommend starting at a dose of 2.5-5 mg/kg/day for one month before gradually increasing the dose by 0.5mg per day until sustainable improvement in symptoms is achieved. Gradually increasing the dose can also help to identify side effects if and when they appear. 

Possible side effects of cyclosporine include:

• Diarrhea
• Heartburn
• Headache
• Gas
• Increased hair growth on face, arms or back
• Acne
• Uncontrollable shaking of a part of the body
• Changes in vision
• Rash, itching, or hives

You should not take cyclosporine if you are pregnant, breastfeeding or planning to become pregnant or breastfeed. Rare but serious risks include an increased risk of infection and developing certain cancers, particularly skin cancer and lymphoma.

Apremilast

Apremilast is the one of the more recent oral psoriasis medications to emerge to market, receiving FDA approval in 2014. It is a phosphodiesterase 4 inhibitor and can also be used to treat psoriatic arthritis.

Some providers recommend starting with an initial dose of 10 mg daily that is titrated by 10 mg per day for the first five days. This can help to lower the risk of GI side effects. Maintenance dosing for apremilast is 30 mg twice daily.

Possible side effects of apremilast include:

• Diarrhea
• Nausea
• Stomach pain
• Headache
• Vomiting
• Weight loss
• Flu-like symptoms

Apremilast can cause some people to feel depressed or suicidal. If you experience any changes to your mental health while taking the medication, reach out to your healthcare provider as soon as possible.

Research shows that apremilast may be particularly effective at treating psoriasis of the scalp and palms. Additional data suggests that apremilast may be especially effective at treating psoriasis when combined with other treatments, including phototherapy the biologic adalimumab. 

Efficacy Rates and Risks of Systemic Treatments

Compared with biologics, the efficacy of oral systemic treatments is generally low, except for cyclosporine. 

A large systematic review of ten randomized controlled trials, prospective studies and case series found that a cyclosporine dose of 5 mg/kg/day produced a 75% reduction in psoriasis symptoms in 50-97% of people, while a dose of 2.5 mg/kg/day per day achieved a 75% reduction in symptoms in 28-85% of people taking the medication.

Because each systemic treatment carries its own side effects, contraindications, and precautions, it’s important to speak with your provider about which systemic treatment may be best for you. 

Biologic Therapies

The first biologics developed to treat psoriasis were approved by the FDA in 2003. Since then, the continued development of this class of medicines has significantly improved the treatment of psoriasis. 

Biologics are injectable medicines made from living sources. They are used to treat moderate-to-severe psoriasis and psoriatic arthritis and work by targeting specific immune pathways. 

However, there are serious risks to consider when taking biologics, including an increased risk of respiratory, urinary, and skin infections. Biologics can also blunt vaccine responses.

Biologics are generally more expensive than systemics. 

TNF Inhibitors

TNF inhibitors are biologics that use antibodies to the cytokine tumor necrosis factor-alpha, a cytokine involved in inflammation. 

Three of the most commonly used TNF-a inhibitors include: 

• Humira (adalimumab)
• Enbrel (etanercept)
• Remicade (infliximab)

It typically takes 12-16 weeks of continuous treatment of either Humira or Enbrel before a marked improvement in symptoms can be observed. With Remicade, you may see an improvement after just 8-10 weeks.

All three TNF-a inhibitors have demonstrated efficacy and long-term safety in the treatment of moderate-to-severe psoriasis, but severe side effects are possible. These include:

• Serious infections
• Reactivation of hepatitis B and C
• Tuberculosis
• Drug-induced lupus
• Rare central nervous system disorders

IL-17 Inhibitors

Interleukin (IL)-17 and IL-23 inhibitors are both part of a newer class of drugs sometimes referred to as newer biologics.

Examples of IL-17 inhibitors include: 

• Cosentyx (secukinumab)
• Taltz (ixekizumab)

IL-inhibitors work by targeting interleukin-17A, a key cytokine in psoriasis inflammation. 

One review from 2021 suggests that both Cosentyx (secukinumab) and Taltz (ixekizumab)

were more effective than older biologics like Humira (adalimumab) or Enbrel (etanercept) in helping people reach 90% or 100% skin clearance as defined by the Psoriasis Area Severity Index (PASI).

Another meta-analysis from 2020 found that Taltz (ixekizumab) was the most effective biologic in achieving a 90% reduction in symptoms according to the PASI.

The risk of side effects of newer biologics like IL-17 inhibitors was similar to older biologics. Possible side effects of IL-17 inhibitors include:

• Injection site reactions
• Upper respiratory tract infections

IL-23 Inhibitors

IL-23 inhibitors are another class of new biologics that work by blocking a protein called IL-23. Blocking IL-23 helps to calm an overactive immune system to reduce psoriasis symptoms 

Examples of IL-23 inhibitors include:

• Skyrizi (risankizumab)
• Tremfya (guselkumab)

A meta-analysis comparing the efficacy and safety of biologics in treating moderate-to-severe plaque psoriasis found that both Skyrizi (risankizumab) and Tremfya (guselkumab) had better safety profiles than the other biologic drugs evaluated.

Still, side effects are possible. Common IL-23 side effects include:

• Common cold, or other upper respiratory tract infections
• Headache
• Fatigue

Combination Therapies

Guidelines from the U.S. and Europe recommend combination therapies for treating moderate-to-severe psoriasis that doesn’t respond well to topical therapies alone.

Topical + Systemic Combinations

Topical treatments are typically used as a first-line treatment for mild-to-moderate psoriasis. But if your psoriasis is moderate-to-severe, or if topical treatments don’t resolve your symptoms, your provider may recommend a combination of topical and systemic treatments.

Phototherapy Combinations

Light therapy, sometimes called phototherapy, can also be used in combination therapy. 

Research suggests that narrowband UVB (NB-UVB) phototherapy can be used alongside methotrexate and that this combination has greater efficacy at lower doses than using either therapy as a standalone treatment.

Rotating Treatments

Rotating available therapies can help to reduce long-term toxicity risk when treating moderate-to-severe psoriasis. 

Rotating therapies like methotrexate, cyclosporine, acitretin, and UVB phototherapy may help to extend the lifespan and efficacy of your treatment by reducing cumulative toxicity, especially hepatic and renal effects.

Lifestyle and Complementary Approaches

Several types of lifestyle and complementary approaches can help to treat and manage psoriasis symptoms long-term.

Stress Management

One review from 2018 suggests that stress may act as a principal trigger in 31-88% of psoriasis cases. Different forms of stress management, including relaxation, hypnosis, biofeedback and behavioral and cognitive stress management therapies have been shown to be effective in people with psoriasis. 

Diet Modifications

Research shows that diet modifications can improve symptoms and the quality of life of people with psoriasis.

Nutritional therapy for psoriasis includes recommendations such as:

• Reducing intake of saturated fats (limit foods like red meat and dairy)
• Replacing saturated fat intake with polyunsaturated fats from the omega-3 family (including fatty fish and nuts)
• Incorporating foods with antioxidants like vitamin A, vitamin E and selenium
• Increasing fiber intake (think leafy greens and berries)
• Tailoring your diet to pharmacological treatment

Exercise Recommendations

Some people with moderate-to-severe psoriasis may experience barriers to exercise as a result of their symptoms. In fact, large observational cross-sectional and cohort studies show that people with psoriasis are less active than people without the disease. 

Because heart disease is a comorbidity of psoriasis, experts believe that exercise may help to reduce the risk of developing heart disease while also helping to improve psoriasis symptoms.

However, a limited amount of research suggests that regular exercise may be an effective standalone treatment. One randomized trial suggests that exercise at least three times a week for a total of 20 weeks may help improve symptoms and PASI scores in people with psoriasis who are overweight or obese. However, more research is needed to determine these effects long-term and in lower BMI patients.

If your physical mobility is limited due to discomfort or pain from your psoriasis symptoms, reach out to your healthcare provider about what’s best for your body.

Working with Your Healthcare Team

Having a trusted healthcare team is essential to ensuring that your psoriasis treatment is tailored to your changing health needs and lifestyle.

Working with a primary care physician (PCP), a dermatologist, and any other specialists recommended can help to support your physical and mental health in the long-run.

When to Switch Treatments

Not all psoriasis treatments work for everybody. And some treatments may work initially, but then fail to provide relief in the long-term or as your health circumstances change. For these reasons, your provider may recommend switching treatments. 

Though switching psoriasis therapies and opening yourself up to a new set of possible side effects may sound daunting, this practice is very common. The American Academy of Dermatology (AAD) recommends switching therapies if you experience a lack of treatment efficacy or safety or tolerability issues. 

Always consult with your provider before switching treatments, but if you’re experiencing a resurgence or worsening of symptoms it’s a good idea to reach out to them for guidance. They will also monitor your progress and help you set realistic expectations for this transition.

Cost and Insurance Considerations

The cost of your psoriasis treatment can vary widely depending on the type of treatment or combination of treatments and your insurance coverage. 

Generally, biologics are the more expensive psoriasis treatment option, with yearly out-of-pocket costs ranging between $39,000-$53,000. 

If your insurance covers some or all of your treatment, your expenses will be much lower. Keep in mind that opting for generic brands over brand-name options can also help to reduce pharmacological costs.

Still, one survey from 2022 of people with psoriasis reflects that the majority of people with the condition needed a more cost-effective option for treatment.

If you need assistance paying for a treatment recommended by your healthcare provider, ask them about any available patient assistance programs. 

Finally, some psoriasis therapies may require prior authorization, which can involve documentation of your disease severity, medical history, and response to previous treatments.

Conclusion & Next Steps  

Finding the right treatment for your psoriasis may take some trial and error. But if you’ve been suffering with uncontrolled symptoms, know that there are many effective options available.

Whether a systemic, biologic, or combination therapy is right for you, you can get unlimited virtual access to expert, specialized care for psoriasis through Zest. Make an appointment within days or use our 24/7 chat messaging service to find relief that lasts and suits your personalized health needs.

To find safe and effective relief from your symptoms, book a virtual appointment within days.