Guselkumab front and center at EADV Congress

Due to the combination of efficacy, safety, and convenience, the interleukin (IL)-23 inhibitors will represent a “significant broadening” of the therapeutic armamentarium for moderate-to-severe psoriasis, according to Prof. Dr. Kristian Reich of Dermatologikum Hamburg in Hamburg, Germany.

Dr. Reich spoke on how IL-23 inhibitors fit into the psoriasis treatment armamentarium in a special melanoma session here at 26th European Academy of Dermatology and Venereology (EADV) Congress in Geneva.

“If you think of how we can treat psoriasis today, it's a perfect time to make sure that we get almost all of our patients under nice control,” Dr. Reich said in an interview with Dermatology Times. That optimism stems from the fact that, with the July 2017 approval of guselkumab by the U.S. Food and Drug Administration (FDA), IL-23 inhibitors now join TNF-alpha inhibitors and IL-17 inhibitors as very effective and available options for patients with psoriasis.  

On one hand, the IL-23 inhibitors represent one more very effective strategy for controlling psoriasis, with PASI rates that according to Dr. Reich are at least comparable to what can be achieved with other biologics. On the other hand, the IL-23 inhibitor data to date suggests a unique safety profile and convenience factor that could help define the role of these new agents in the therapeutic armamentarium.

Guselkumab, the first and so far only FDA-approved biologic to selectively block IL-23, is being discussed in detail at this and other EADV sessions, due in part to its recent U.S. approval. Dr. Reich said he anticipates the treatment might also be available to patients in the European Union (EU) by the end of the year.

“There will be more than one drug specifically antagonizing IL-23,” Dr. Reich said. “The first in class is guselkumab … there is great interest to understand what these drugs are, their profile, and where are they probably even better than the best drugs we had up to now.”

How does IL-23 compare?

Although head-to-head comparisons are needed, Dr. Reich said the IL-23 blockers “join the IL-17 blockers in bringing more patients to a high level of response … they are at least as good as the (IL-17 blockers) in bringing more patients to PASI 90 and PASI 100.”

Dr. Reich was also first author of the phase III VOYAGE 2 trial. In this double-blind, placebo- and active comparator-controlled study, Dr. Reich and colleagues found that guselkumab was an effective and well-tolerated maintenance therapy in patients with moderate to severe psoriasis, including those patients who had not previously responded to adalimumab. In particular, guselkumab was superior to adalimumab in the co-primary endpoints of Investigator Global Assessment (IGA) score of cleared/minimal (84.1% vs 8.5%) and PASI 90 response (70.0% vs 2.4%) at week 16. The PASI 100 rate at week 16 was 34.1%.

Moreover, the safety profile of guselkumab appears favorable. Whereas Candida infections are associated with IL-17 treatment and tuberculosis risk may be elevated in psoriasis patients on anti-TNF agents, no such “target-specific” safety signals have been identified to date for IL-23 inhibitors: “"they seem to be very clean in this aspect," Dr. Reich said.

Another point in favor of IL-23 inhibitors is convenience, Dr. Reich emphasized in his EADV presentation. Whereas biologics may require dosing on intervals as short as 2 weeks, the recommended dose of guselkumab is 100 mg at Week 0, Week 4, and every 8 weeks thereafter; moreover Dr. Reich said injection intervals of every 12 weeks are possible. With most other biologics, “we do not seem to be able to go to these long injection intervals,” he told Dermatology Times.

Patient profiles and psoriatic arthritis

Patient profiling is possible to determine the appropriate biologic agent for a patient with moderate to severe psoriasis, Dr. Reich said. Factors that he considers may include presence of nail disease or psoriatic arthritis, or frequent travel to a region where tuberculosis could be a risk.

For patients with prominent psoriatic arthritis, Dr. Reich said the data is strongest now for anti-TNF or IL-17 directed agents. However, some “promising” data are emerging for guselkumab. In a randomized, double-blind, placebo-controlled phase 2a study, investigators reported that guselkumab significantly improved joint symptoms, physical function, psoriasis, quality of life and other factors in patients with active psoriatic arthritis and at least 3% body surface area (BSA) of plaque psoriasis despite standard therapy.

“It's quite a complex process where you try to match the profile of a given drug with the profile of a specific patient,” he said. “But I see good reasons that in many of my patients that have moderate to severe plaque psoriasis, guselkumab could actually become my first biologic of choice because of the efficacy, safety, and convenience profile.”

Summary

Although data are still emerging, IL-23 inhibition appears to be an effective, safe, and convenient option for patients with moderate-to-severe plaque psoriasis.

Guselkumab, the first and so far only FDA-approved biologic to selectively block IL-23, was effective and well-tolerated in patients with moderate to severe psoriasis, including patients who had not previously responded to adalimumab.

With so many biologics available, patient profiling can be helpful to determine an appropriate treatment strategy for an individual patient.

Disclosures
Dr. Reich reports that he has served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Amgen, Biogen, Boehringer Ingelheim Pharma, Celgene, Covagen, Eli Lilly, Forward Pharma, GlaxoSmithKline, Janssen, Leo, Medac, Merck Sharp & Dohme, Novartis, Ocean Pharma, Pfizer, Regeneron, Takeda, UCB Pharma, and Xenoport.