Linda Stein Gold, M.D., on How Guselkumab Targets Psoriasis

Linda Stein Gold, M.D.

Credit: HMP Global Learning Network

In an interview with The Educated Patient, Linda Stein Gold, M.D., director of Dermatology Clinical Research at Henry Ford Health, discusses Johnson & Johnson’s SPECTREM study, which demonstrated treatment with guselkumab (Tremfya) led to significant skin clearance in patients with plaque psoriasis (PsO) with special-site involvement and low body surface area (BSA) whose disease had previously failed topical treatments.

What differentiated the SPECTREM study from other trials evaluating guselkumab in patients with PsO?

Linda Stein Gold, M.D.: PsO treatment decisions have historically been driven by BSA coverage of the disease rather than symptom burden. This means people with PsO lesions in special sites or high-impact areas (i.e., scalp, face, skin folds and genitals) that cover a smaller total area of their body are often prescribed topical treatments and are not considered as candidates for advanced therapies. In turn, many remain unable to successfully manage the symptoms of their disease and achieve skin clearance, as these special sites are often difficult-to-treat areas.

The SPECTREM study was the first prospective, large-scale, randomized-controlled, double-blind clinical study to measure skin clearance and other treatment outcomes in low-BSA moderate PsO with involvement across four special sites (scalp, face, skin folds and genitals) who had previous topical treatment failure. Results from the study show the majority of patients treated with guselkumab achieved high levels of skin clearance and improvement in quality-of-life impact.

The main difference between SPECTREM and other similar studies is that the trial enrolled participants who had lower BSA (2%-15% BSA), ensuring the study included PsO patients with moderate disease — in fact, most PsO patients’ [disease is] characterized as moderate. Other trials that have looked at lower-BSA PsO have required that 60% of participants have over 10% BSA, which is considered severe PsO, a less common form of the disease.

How does guselkumab differ from traditional topical treatments for psoriasis, especially for those who have not had success with other therapies?

LSG: Guselkumab is a biologic, which is a targeted, injectable treatment that helps regulate inflammatory factors that contribute to the development of PsO lesions. For many patients, biologics are a highly effective treatment for moderate to severe plaque PsO. It is important to make biologics available for patients with low-BSA but high-impact-area PsO, particularly because treatment for PsO in special sites like your scalp, nails, genitals, skin folds and face often needs to be tailored due to the sensitivity and unique characteristics of these areas.

For example, topical creams can be not only impractical or ineffective, but at times unsuitable for certain areas of the body. Additionally, special-site PsO is often difficult to treat, with many patients experiencing stubborn plaques that do not clear with topical or oral treatment. In these cases, I explore biologics like guselkumab for my patients.

What were the key findings of the study that patients should know about?
LSG: Results from the SPECTREM clinical trial showed statistical significance across all primary and secondary end points among participants who received guselkumab and could represent a new approach to care for people with low-BSA PsO in special sites.

There are three key takeaways that patients with this type of disease involvement should keep in mind:

• Guselkumab can offer you significant skin clearance, with 74.2% achieving the primary end point of an Investigator’s Global Assessment (IGA) score of cleared or minimal disease compared with 12.4% on placebo. These results were comparable irrespective of baseline BSA. 
• Guselkumab can completely clear PsO plaques from special sites, with complete clearance of each special site consistently achieved in the majority of patients who received guselkumab versus placebo: scalp (60.3% versus 9.3%); face (75.7% versus 23.9%); intertriginous (76.6% versus 24.2%); and genital (72.7% versus 32.7%).
• Guselkumab can lead to significant improvement in quality of life, based on self-reported outcomes from patients in the study, with 48.9% of patients achieving Dermatology Life Quality Index (DLQI) scores of 0/1 compared with patients receiving placebo (3.5%).

With these results in mind, I would encourage people living with low-BSA PsO in high-impact areas of involvement to talk to their doctor about whether a biologic like guselkumab may be right for them — especially those who are relying on topical creams and/or oral therapies that are not offering them skin clearance.

The SPECTREM study showed that guselkumab achieved significant skin clearance. What does “skin clearance” mean for someone living with psoriasis, and how might it impact their daily life?

LSG: Skin clearance in PsO means that there is a reduction in the plaques, scaling and redness on the skin. In some cases, the skin is cleared completely with no lesions. Many patients who take guselkumab are able to maintain clear skin and experience long-lasting disease control with a few injections per year.

Skin clearance is the primary goal for most patients with this disease, as living with a highly visible and chronic condition like PsO can take a significant emotional toll, beyond the physical symptoms. PsO often has a negative impact on quality of life and can even lead to anxiety, depression, isolation and other mental health challenges. People living with PsO may feel embarrassed, shame or have low self-esteem. For some, the disease may even influence aspects of daily life such as clothing choices and relationships.

While PsO is highly visible and skin clearance is important, it’s important to also remember that this disease is more than skin deep as it can lead to inflammation throughout the body. For example, up to 30% of people with PsO may develop psoriatic arthritis, which can cause joint pain, swelling, stiffness and even long-term disability if left untreated. The inflammation inside the body also increases the risk of cardiometabolic issues like diabetes, heart disease and stroke.

What are the potential benefits of using a biologic treatment like guselkumab for those with sensitive or difficult-to-treat areas?

LSG: People with PsO in high impact areas, such as the scalp, nails, genitals, skin folds and face may themselves overlook the severity of their disease when they only have lesions covering a smaller portion of their body. But in reality, these are special areas that deserve attention because outbreaks in these parts of the body can significantly impact a person’s quality of life, regardless of the overall size of their plaques.

Let’s use genital PsO as an example. The impact of this form of PsO can be tremendous — my patients often struggle with social anxiety, discomfort triggered by friction from clothing, challenges with sexual activity and intimacy, and more. As you can imagine, treatment with a topical cream in this area would be difficult and uncomfortable. Some patients may alternatively be on oral treatments, but these therapies may not be as effective in clearing these plaques. Treatment with a biologic like guselkumab would be my recommendation for a patient in this scenario, as they would likely achieve more significant skin clearance, and the treatment can be administered in a way that is more convenient when compared with a topical cream. These patients do meet the new criteria for systemic medication that was set forth by the International Psoriasis Council.

Is there anything else you would like our patient audience to know?

LSG: If a therapy doesn’t fit your lifestyle, isn’t effective or has stopped working, advocate for yourself. For example, if traditional treatments like topicals or light therapy aren’t effective, ask your doctor about more advanced therapies, like biologics, which are highly effective for moderate to severe PsO. If you’ve exhausted treatment options, you can also consider exploring clinical trials for newer therapies.

And finally, lean on others for support. Mental health is health, and it’s common to feel isolated living with a chronic and highly visible condition like PsO. Connecting with others who understand and share your lived experience can help you cope with the ups and downs of this condition.