New IL-23-targeted biologic approved in Canada for Tx of plaque psoriasis


Guselkumab, a biologic therapy that is part of a new class of agents targeting interleukin (IL)-23 without blocking IL-12, was approved in Nov. 2017 by Health Canada for the treatment of moderate to severe plaque psoriasis in adults.

The new therapy is more precisely targeted than some earlier biologics, Dr. Melinda Gooderham said during an interview with DERM.city.She was a researcher involved in clinical trials of guselkumab.

“It does not block interleukin12, only interleukin-23, through binding the p19 subunit.” This results in a different sideeffect profile, she said, while producing the same high level of psoriasis clearance of many of the other biologics.

Dr. Gooderham is a dermatologist and the medical director at the SKiN Centre for Dermatology in Peterborough, Ont.

>50% of patients clear at 48 months

Results from the VOYAGE 1 (J Am Acad Dermatol2017; 76(3):405–417) and VOYAGE 2 (J Am Acad Dermatol 2017; 76(3):418–431) clinical trials of guselkumab were very good, said Dr. Gooderham. Approximately 70% of patients treated with the new biologic achieved Psoriasis Area and Severity Index (PASI) scores of 90.

“I like to look out a bit longer in the treatment,” Dr. Gooderham said. “If you look at the 48-week results [of guselkumab treatment], patients are achieving very high levels of clearance— more than half of patients were completely clear.” This compares to treatment with adalimumab, which results in approximately 30% of patients achieving PASI-100 by week 48, she said.

In the VOYAGE 1 trial, patients were randomized into one of three study arms study arms—329 were treated with guselkumab 100 mg at weeks zero and four, then every eight weeks;

174 received acebo at weeks zero, four, and 12, then guselkumab at weeks 16 and 20, then every eight weeks; and 334 were treated with adalimumab 80 mg at week zero, 40 mg at week one, and 40 mg every two weeks through week 47.

That trial found guselkumab to be superior to placebo at week 16 (p<0.001) both in reaching an Investigator’s Global Assessment (IGA) score of cleared or minimal (85.1% vs 6.9%, respectively), and in improvement in PASI score from baseline (PASI 90, 73.3% vs. 2.9%, respectively). The new biologic also showed superior IGA and PASI 90 results compared to adalimumab (p<0.001) at week 16 (85.1% vs. 65.9% and 73.3% vs. 49.7%), 24 (84.2% vs. 61.7% and 80.2% vs. 53.0%), and 48 (80.5% vs. 55.4% and 76.3% vs. 47.9%). The three arms had similar rates of adverse events.

A new option for patients

The VOYAGE 2 trial was similar in design to VOYAGE 1, but also examined interrupted treatment and switching patients who did not respond to adalimumab therapy to guselkumab. From weeks 28 to 48, better response persistence was seen among patients in the study arm that persisted in guselkumab maintenance compared to groups to a placebo for a withdrawal period (p<0.001). Among the patients who did not respond to adalimumab who switched to guselkumab, 66.1% achieved PASI 90 at week 48.

Having a new class of biologics for psoriasis will benefit patients, said Dr. Wayne Gulliver, a dermatologist in practice in St. John’s, N.L., and a professor of medicine (dermatology) at Memorial University in St. John’s.

“[Guselkumab] has a good safety profile, and the fact that it is a totally new class of biologic means we now have another option for patients who fail TNF inhibitors, IL-12/23 biologics, IL-17 biologics, or oral systemics.”

Guselkumab may also be a preferred choice for patients who desire or need a less frequent dosing schedule, said Dr. Gulliver. “Doctors administer a dose at day zero, at one month, and then every two months. So for people who are travelling, people working off-shore, it is convenient that they can take it every two months.”

Dr. Gulliver also emphasized the significance of the high rate of PASI-100 clearance among patients treated with guselkumab, and mentioned that practitioners should also recognize that many patients who achieve PASI-100 on this treatment have their clearance persist even with interrupted treatment.

Having a new biologic option will also be of benefit to patients who may have other comorbidities that preclude the use of other therapies, said Dr. Gooderham. “For example, if there is a history of multiple sclerosis then a doctor would not want to prescribe a TNF inhibitor. Or if the patient has a history of inflammatory bowel disease, their doctor may not want to prescribe IL-17 inhibitors.

Even patients who have inadequately responded to or failed ustekinumab, which targets IL-12/23 through the p40 subunit, appear to sometimes benefit from switching to guselkumab, Dr. Gooderham said. “They showed that in the NAVIGATE trial where, at week 16, they took patients who were not clear or almost clear with ustekinumab, and switched them to guselkumab.”

In that trial, a greater proportion of the patients in the study arm in which patients inadequately responding to ustekinumab were switched to guselkumab achieved IGA 0/1 and at least a two-grade improvement at week 28 (31.1% vs. 14.3%; p=0·001) and week 52 (36.3% vs. 17.3%; p<0·001) compared to the patients who continued on ustekinumab. As well, in the NAVIGATE trial (Br J Dermatol2018; 178(1):114–123) greater proportions of patients treated with guselkumab achieved PASI 90, PASI 100 and DLQI 0/1 at week 52.

Not indicated for psoriatic arthritis

At this time, guselkumab may not be the ideal psoriasis therapy for a patient who also has psoriatic arthritis, Dr. Gooderham said. “It is not indicated for the arthritis portion of their psoriasis. Which might steer you toward another agent such as a TNF inhibitor or an IL-17 inhibitor, or ustekinumab, which works on a similar part of the pathway.”

#Guselkumab #PlaquePsoriasis #Adalimumab #IL1223

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