Secukinumab shows superiority to etanercept

Recent head-to-head clinical trial results with secukinumab (Novartis) and etanercept (Enbrel, Amgen) show a significant superiority of secukinumab in the treatment and management of patients with moderate-to-severe plaque psoriasis, perhaps heralding a new standard of care for this patient population.

Novartis recently announced the new data from the phase 3 FIXTURE study, which compared the safety and efficacy of secukinumab (an interleukin-17A inhibitor) and etanercept (a tumor necrosis factor inhibitor) using two dosing regimens in patients with plaque psoriasis, at the 22^nd Congress of the European Association of Dermatology and Venereology (EADV) in Istanbul.

The randomized, double-blind, placebo-controlled, 52-week multicenter study included 1,036 patients, and compared two doses of secukinumab (300 mg and 150 mg) with etanercept 50 mg and placebo. The co-primary endpoints were assessed at week 12 and compared secukinumab efficacy versus placebo according to the Psoriasis Area and Severity Index 75 (PASI 75), and the Investigator’s Global Assessment.

The clinical trial met all primary and pre-specified key secondary endpoints. Both doses of secukinumab demonstrated improved efficacy to etanercept throughout the study, and results showed that secukinumab patients’ skin cleared faster and longer than etanercept patients, beginning as early as week two. Importantly, the data also showed that twice as many secukinumab patients experienced almost clear skin (PASI 90) and completely clear skin (PASI 100) by week 12, compared to patients on etanercept.

Patients on secukinumab also demonstrated a quicker resolution of their symptoms compared to those taking etanercept. Clinically relevant differences were observed as early as week two and on average, secukinumab 300 mg patients had their symptoms halved by week three, compared to week eight for etanercept patients. The study also showed that 72 percent of secukinumab 300 mg patients experienced at least a 90 percent reduction in erythema, thickness and scaling (PASI 90) by week 16 of the study.

The incidence of adverse events was similar between both 300 mg and 150 mg secukinumab treatment groups, and was comparable to those patients on etanercept. There were no deaths reported in the study, and the most common adverse events in any treatment group (including placebo) throughout the study were nasopharyngitis and headache.

“I think that the results of the clinical trial were no real surprise. Although secukinumab blocks only a very small part of the immune system, it evidently blocks the right part, resulting in the profound results we have seen. The data on secukinumab is excellent, and it appears to work dramatically well, and fast, achieving remissions that are durable, lasting out to one year,” says Mark Lebwohl, M.D., Sol and Clara Kest Professor and chairman of the department of dermatology at Mount Sinai School of Medicine, New York.

Secukinumab is an agent that selectively targets interleukin-17A (IL-17A), and research has shown that IL-17A plays a critical role in driving the body’s autoimmune response in diseases such as plaque psoriasis, making this cytokine one of the preferred targets for investigational therapies. According to Dr. Lebwohl, the positive results on secukinumab reflected in this clinical trial is very good news for patients suffering from plaque psoriasis.

“Etanercept’s main strength is that it has been around a long time and has an excellent safety profile. It is a drug that we know, and we have patients who are doing well on it, and stay on it, and I believe that it will continue to be used in that way. With this new trial data however, we now appear to have an excellent treatment alternative for our psoriasis patients,” Dr. Lebwohl says.

There are many different factors that the clinician will consider when contemplating appropriate therapy in plaque psoriasis patients and, according to Dr. Lebwohl, prime among those factors is what insurances companies will pay for.

“Just how much these drugs will ultimately cost our patients will play an important role in how we move forward in choosing therapy in our patients,” he says.

Patients with plaque psoriasis will often also have psoriatic arthritis and, Dr. Lebwohl says, the tumor necrosis factor (TNF) blockers such as etanercept and adalimumab have a proven track record in the treatment and management of patients with psoriatic arthritis.

“Both of these TNF blockers have been shown to prevent the X-ray progression of joint disease, which is very important in our psoriasis patients who have concomitant psoriatic arthritis. This is another important factor that will also impact our decision on what drug to use in our patients,” Dr. Lebwohl says. “Nevertheless, it must be said that secukinumab looks really good right now, as it has shown to work very quickly with a high efficacy, and can achieve remissions that are long lasting.”