What Is Combination Therapy and Why Is It Needed?

The range of psoriasis treatment options has increased dramatically over the past few years. With the arrival of therapeutic biologic agents on the scene, many people with psoriasis and healthcare providers alike are excited about having an improved treatment toolbox. Even though biologics are powerful therapies that offer promise to people with psoriasis, they don’t work equally for everyone.  Because of this, there has been recent interest in clarifying the role of combination therapy for people with psoriasis.

For many people with psoriasis, there is significant frustration that comes with trying multiple treatment options for years, but not being able to find a single treatment that seems to work for them. Frustration with treatment options is understandable. Research has shown that healthcare providers may tend to minimize the severity of symptoms that patients identify and thus some symptoms are not taken into consideration when determining therapeutic options4.  Also, healthcare providers may present treatment options in a way that makes patients think there are either/or choices. For example, should you really have to choose between clear skin and or joint pain?  Talking about your treatment goals with your healthcare provider is an important way of making the treatment options more realistic, and combination therapy may be an option for expanding that range of choices.

Why is combination therapy needed?

While many people with psoriasis can find relief from traditional psoriasis therapies, many people are frustrated from not able to achieve long-term clearance of skin lesions without flare-ups or other symptoms. As well, higher dose administration of many medications can lead to toxicities resulting in organ damage.

Therapeutic biologics are generally believed to have improved treatment outcomes, yet they are not effective for all people with psoriasis.   Combining biologics with traditional psoriasis therapies may provide an important treatment option for people who do not adequately respond to monotherapy (a single drug used on its own).

The theory behind combination therapy is that it is possible to optimize treatment outcomes due to the potential for one medication to boost the efficacy (or minimize the side effects) of another drug. It is also often possible with combination therapy to use lower doses of the individual drugs so that overall toxicity may be reduced1. In addition, the patient may find the regimen to be more tolerable thus increasing their adherence to the prescribed treatment regimen.  In a recent research review, Cather and Crawley present the current evidence regarding the combination of biologics with systemic therapies1.

Those all-too-familiar treatment challenges!

The goal of systemic therapy is to eliminate the chronic inflammation experienced with psoriasis and to achieve skin clearance. Historically, conventional systemic treatment options for psoriasis have included methotrexate, cyclosporine, and oral retinoids such as acitretin. However, for many people with psoriasis, the use systemic medications is limited by safety concerns, limited efficacy, or both. Clinically, cyclosporine is often generally considered the most effective systemic medication, providing a rapid response. However, concerns with kidney disease, hypertension, and numerous drug interactions can be reasons why it is not used. Also, cyclosporine use is limited to 12 months continuous use for psoriasis. Methotrexate also has to be used with caution with people that have liver problems or in those who regularly consume alcohol. Both methotrexate and retinoids should not be used by women who are pregnant2.

Patient dissatisfaction with conventional systemic therapies has been well documented. People are often not satisfied with the inconvenience of administration of traditional psoriasis therapies as well as their related side effects3. Topical corticosteroids can be effective in clearing plaques, but have their own limitations and complications, and don’t work equally well on all affected body parts. Approximately 40% of patients on systemic therapy alone have expressed dissatisfaction with their treatment outcomes, and overall patient satisfaction has been found to be lower with systemic therapy than with biologic agents, biologic/methotrexate combinations, or phototherapy4. Dissatisfaction with treatment options often leads to discontinuation of treatment.  Obviously, if treatment is halted prematurely, symptoms will rebound and may become worse than they were prior to treatment.

Because the chronic inflammation associated with psoriasis may also be associated with other inflammatory co-morbid conditions, targeted biologic therapeutics may provide a treatment effect that goes beyond skin clearance. For example, a recent literature review found that methotrexate combined with a TNF-alpha inhibitor biologic may have the added benefit of reducing cardiovascular inflammation in people with psoriasis3.

When is combination therapy most appropriate?

In general, research has shown that your healthcare provider may want to consider combination therapy1:

    • When monotherapies have proven inadequate
    • When full dose of a monotherapy raises tolerance concerns
    • When a patient has complications or comorbidities and the use of an additional agent may help with the other condition
    • For patients that are switching therapies and the use of multiple therapies can serve a bridging function
    • When tailoring therapy to handle long-term treatment for flare-ups and relapsing disease

Combination therapy may be appropriate for people who are switching to a biologic agent and their healthcare provider has recommended tapering off of a previous systemic therapy in order to prevent a flare-up with discontinuation. Additionally, patients with complications or comorbid conditions may benefit from the use of combination therapy with biologics. Patients who have been on systemic therapy long-term and need to be concerned with potential toxicity may benefit from combination therapy. This is true for long-term methotrexate use and potential liver damage and cyclosporine and potential kidney damage3.

Additionally, combination therapy may help in the prevention or treatment of co-occurring diseases in certain patients (e.g., use of retinoids in a patient at risk of non-melanoma skin cancer, or anti-TNF therapy in a patient with comorbid Crohn’s disease). Patients who may benefit from lower dose treatment regimens and thus less aggressive therapy may also be candidates for combination therapy. In addition, there may be certain situations that are considered transitional where it would make sense to start combination therapy, such as in advance of times when flares-ups are known to occur for a patient (e.g., in the winter) or when a patient changes insurance and there are concerns about possible disruptions in therapy4.

Closing thoughts

Combination therapy also offers an opportunity for your healthcare provider to work with you to tailor a treatment in situations where there is a concern that traditional psoriasis treatments will be less effective. For example, people who also have psoriasis and psoriatic arthritis or those who are at risk of organ damage due to long-term use of systemic therapies, are most likely to be good candidates for combination therapy. People who have plaque psoriasis that is generally well controlled but is resistant to treatment in certain areas, like the scalp, might also be candidates for combination therapy.

Further research is needed to substantiate head-to-head comparisons of various treatment combinations versus monotherapy. In many ways, combination therapy offers hope for long-term treatment options, but there are many unknowns, and there is no predictable path for which combination therapies will work best for you. While your healthcare provider may be willing to start you on combination therapy, there is a need for additional research to determine which combinations are the most effective. As well, further research will help identify an evidence base that will allow healthcare providers to select combinations that will achieve the best results with the least amount of side-effects and that may confer additional benefits for better managing co-occurring health conditions.

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