The Health Canada approval of a new biologic provides more options for patients with moderate-to-severe psoriasis to achieve clear or almost clear, according to Canadian dermatologists.
Secukinumab—the first approved human monoclonal antibody (mAb) that selectively binds to interleukin 17A (I L- 17A)—was approved for use in Canada in March after safety and efficacy was demonstrated in 10 Phase II and Phase III studies that included over 3,430 adults with moderate- to severe plaque psoriasis. The trials found that secukinumab resulted in clear or almost clear skin in the majority of patients. Some of the studies were conducted at 12 sites in Canada, with a total of 116 Canadian participants.
A novel and exciting therapy “This is quite a novel and exciting [therapy] for psoriasis,” Dr. Charles Lynde, director of the Lynde Institute for Dermatology in Markham, Ont., and an associate professor at the University of Toronto, told DERM.city.
“[It takes a] newer pathway. The previous pathways have been TNF blockers—that is [adalimumab] and [infliximab]. Then we had also [ustekinumab], which is an [IL-12] and IL-23 blocker. There are severalnew IL-17s [coming] but [secukinumab] is the firstone.” Dr. Lynde, who participated in the Canadian clinical trials, noted that two other IL-17 antagonists are in the clinical trial phase and expected to be released for use in Canada in the next few years.
They potentially could have a better efficacy and safety profile than what is currently on the market. An abnormal cytokine IL-17A can hyperproliferate in the skin, causing redness, inflammation, and itchiness,according to Dr. Lynde.
“By blocking [IL-17A] you kindof normalize it. You do not block it 100 per cent, so it cannot function well in the body. But, you are dampening it down so it is functioning the way it should in the body.”
The monoclonal antibodies block a portion of thecytokine IL-17A and develop what Dr. Lynde described asthe “‘sweet spot,’ where you have quite a high efficacy,without having a lot of side effects.”
Biologics raising the bar in psoriasis therapy
Dr. Lynde said the introduction of this therapy, and other biologics, “raises the bar” for treatment, because not many years ago Psoriasis Area Severity Index (PASI) 50, a 50% reduction after 12 weeks of treatment, was considered the target goal for psoriasis treatment.
“Literally, only five years ago, we were talking about PASI 75, which meant 75 per cent improvement and patients were quite happy at these levels because theyhad not attained these levels before,” said Dr. Lynde. “We are now talking about a significant number of people, if they take this drug, [who] are going to be clear or almost clear [PASI 90 or 100].”
He said the response from patients treated with secukinumab has been a “wow factor”—a good shock. “It is giving further options for patients and ultimately as dermatologists we are trying to make our patients' lives better and we can certainly do that with this particular drug,” said Dr. Lynde.
Secukinumab superior to ustekinumab
A study, Comparison to assess Long-term Efficacy, sAfetyand toleRability of secukinumab vs. ustekinumab (CLEAR), that was presented at the 73rd annual meeting of the American Academy of Dermatology in San Francisco in March, found that secukinumab was superior to ustekinumab. The CLEAR Phase IIIb study met the primary end point of showing superiority to ustekinumab as assessed by PASI 90 response at week 16 (79. 0% vs. 57. 6%,p<0. 0001).
In addition, PASI 100 at week 16 was achieved by significantly more patients treated with secukinumab than those receiving ustekinumab (44.3%vs. 28.4%, p<0.0001). “I think that the important thing about this study is that [it shows] there is another option available for moderate-to-severe psoriasis that works quickly and safely,” Dr. Ron Vender, associate clinical professor of medicine at McMaster University in Hamilton, told DERM.city.
“There is always a need for new treatments, for different approaches for the treatment of moderate-to-severe psoriasis because of the variability of response that is observed when treating these patients.” Recommendation is to optimize current biologic before considering switching therapies Secukinumab can be used in biologic naive patients or patients who have failed other biologics and who are looking for a new approach, according to Dr. Vender.
He noted, however, that clinicians should optimize the patient’s current biologic treatment before switching to a new biologic. “There are various approaches to [optimization]. So it could mean decreasing frequency of dosing, it could be increasing dosing, it could be adding concomitant systemic therapy, and it could be adding concomitan ttopical therapy, as well as adding phototherapy,” said Dr.Vender.
The safety profile is no different from other biologics currently on the market, noted Dr. Vender. Biologics are considered to have a good safety profile with only minor adverse events observed in some patients. “They are relatively safe, with no unsuspected safety issues,” he said.
Another benefit of secukinumab, according to Dr.Vender, is that it has a convenient maintenance dose of only once per month. The loading dose is weekly for five weeks.
Non-proprietary and brand names of therapies: secukinumab(Cosentyx, Novartis Pharmaceuticals Canada); ustekinumab (Stelara, Janssen Inc. ), adalimumab (Humira, Abbvie Corporation); infliximab (Remicade, Janssen Inc.).
Originally published in the Aug. 2015 issue of The Chronicle of Skin & Allergy