Could guselkumab be a disease-modifying agent in plaque psoriasis? | MDedge Rheumatology

Could guselkumab be a disease-modifying agent in plaque psoriasis?

SAN DIEGO

– Could some of the monoclonal antibodies posting striking results in psoriasis trials be doing more than quelling symptoms?

At least some researchers think so, as evidenced by a brief discussion during AAD 2018 of the durable responses some guselkumab-treated patients achieved in the VOYAGE 2 trial.

"Isn't this amazing?" asked Kristian Reich, MD, after listening to several late-breaking, solidly positive trials of monoclonal antibodies for plaque psoriasis. "I think it's fantastic that we now have drugs that clear 50% or more of a patient's psoriasis. We should not be taking this for granted."

Dr. Reich, professor of dermatology at Georg-August-University in Gottingen, Germany, and a partner at the Dermatologikum Hamburg, then honed in on the durability of response numbers in the recently reported VOYAGE 2 trial of guselkumab, an anti–interleukin-23 antibody. Guselkumab (Tremfya) was approved by the Food and Drug Administration last July for treatment of adults with moderate to severe plaque psoriasis.

VOYAGE 2 was an active-comparator, placebo-controlled study that pitted guselkumab against adalimumab (Humira) and placebo in a crossover design. It enrolled about 900 patients with moderate to severe plaque psoriasis.

Patients were randomized to 28 weeks of treatment in three arms: guselkumab 100 mg (weeks 0 and 4, then every 8 weeks); placebo for 16 weeks, then guselkumab 100 mg at weeks 16 and 20; or adalimumab (80 mg at week 0, then 40 mg at week 1, and every 2 weeks through week 23).

At 28 weeks, a total of 375 Psoriasis Area and Severity Index (PASI) 90 treatment responders in the guselkumab arm were rerandomized to either stay on guselkumab (n = 193) or withdraw to placebo (n = 182) until they lost whatever response they had gained at that point.

Related

Interleukin-23 inhibition for psoriasis shows 'wow' factor 

Although PASI 90 responses were much better maintained in the guselkumab group that stayed on therapy, they did not fade quickly. The median time to loss of PASI 90 response was 15 weeks (23 weeks after last guselkumab dose) for patients randomized to the withdrawal group. And although 89% of the maintenance group maintained their PASI 90 response at 48 weeks, 37% of those in the withdrawal group had still maintained that 90% improvement over baseline by 48 weeks.

"Is this drug opening the door to disease modification? Is it doing something that allows disease control even if we stop the therapy? This is what we see happening when we stop the drug in PASI 90 responders. Yes, the disease is coming back, but the median time to recurrence is more than 3 months."

The cytokine profiles of these patients appear to support this idea, Dr. Reich contended.

"In the first 28 weeks, when they were all receiving the drug, their IL-23, IL-17A, and IL-17F levels were all going down rapidly. But this is the interesting part. In some patients who maintained their PASI response after withdrawal, those cytokines continued to be suppressed. They rose in patients who lost response. We need to do more tests to understand what's going on here, but I do think the door is opening to what I would call disease modification."

Not everyone agreed. Kim A. Papp, MD, who later presented results of bimekizumab in plaque psoriasis, took to the floor to dispute this claim.

"I admit, I did at one time believe this story about disease modification," said Dr. Papp, founder and president of Probity Medical Research in Waterloo, Ont. "But now I think we are simply seeing a pharmacokinetic effect. How can you reconcile what is clearly a pharmacologic and mechanistic perspective with this suggestion that you're modifying disease?"

Session moderator Hensin Tsao, MD, suggested that the answer might lie in some unknown in-between territory.

"We do see about 10%-20% of patients in whom drug-free remission is not explained by pharmacokinetics. In some patients, the drug is long gone, and they are still clear of disease – and we don't know how to talk about those patients yet. But we do need to study them because, for those people, clearly it is not a [pharmacokinetic] issue."

Dr. Reich disclosed financial relationships with numerous pharmaceutical companies, including Janssen, which manufactures guselkumab. Dr. Papp also disclosed multiple relationships with drug manufacturers.

SOURCE: Gordon K et al. AAD 2018Abstract 6748.

msullivan@frontlinemedcom.com

https://www.mdedge.com/rheumatology/article/159383/psoriasis/could-guselkumab-be-disease-modifying-agent-plaque-psoriasis

Could guselkumab be a disease-modifying agent in plaque psoriasis?

SAN DIEGO

– Could some of the monoclonal antibodies posting striking results in psoriasis trials be doing more than quelling symptoms?

At least some researchers think so, as evidenced by a brief discussion during AAD 2018 of the durable responses some guselkumab-treated patients achieved in the VOYAGE 2 trial.

"Isn't this amazing?" asked Kristian Reich, MD, after listening to several late-breaking, solidly positive trials of monoclonal antibodies for plaque psoriasis. "I think it's fantastic that we now have drugs that clear 50% or more of a patient's psoriasis. We should not be taking this for granted."

Dr. Reich, professor of dermatology at Georg-August-University in Gottingen, Germany, and a partner at the Dermatologikum Hamburg, then honed in on the durability of response numbers in the recently reported VOYAGE 2 trial of guselkumab, an anti–interleukin-23 antibody. Guselkumab (Tremfya) was approved by the Food and Drug Administration last July for treatment of adults with moderate to severe plaque psoriasis.

VOYAGE 2 was an active-comparator, placebo-controlled study that pitted guselkumab against adalimumab (Humira) and placebo in a crossover design. It enrolled about 900 patients with moderate to severe plaque psoriasis.

Patients were randomized to 28 weeks of treatment in three arms: guselkumab 100 mg (weeks 0 and 4, then every 8 weeks); placebo for 16 weeks, then guselkumab 100 mg at weeks 16 and 20; or adalimumab (80 mg at week 0, then 40 mg at week 1, and every 2 weeks through week 23).

At 28 weeks, a total of 375 Psoriasis Area and Severity Index (PASI) 90 treatment responders in the guselkumab arm were rerandomized to either stay on guselkumab (n = 193) or withdraw to placebo (n = 182) until they lost whatever response they had gained at that point.

Related

Interleukin-23 inhibition for psoriasis shows 'wow' factor

Although PASI 90 responses were much better maintained in the guselkumab group that stayed on therapy, they did not fade quickly. The median time to loss of PASI 90 response was 15 weeks (23 weeks after last guselkumab dose) for patients randomized to the withdrawal group. And although 89% of the maintenance group maintained their PASI 90 response at 48 weeks, 37% of those in the withdrawal group had still maintained that 90% improvement over baseline by 48 weeks.

"Is this drug opening the door to disease modification? Is it doing something that allows disease control even if we stop the therapy? This is what we see happening when we stop the drug in PASI 90 responders. Yes, the disease is coming back, but the median time to recurrence is more than 3 months."

The cytokine profiles of these patients appear to support this idea, Dr. Reich contended.

"In the first 28 weeks, when they were all receiving the drug, their IL-23, IL-17A, and IL-17F levels were all going down rapidly. But this is the interesting part. In some patients who maintained their PASI response after withdrawal, those cytokines continued to be suppressed. They rose in patients who lost response. We need to do more tests to understand what's going on here, but I do think the door is opening to what I would call disease modification."

Not everyone agreed. Kim A. Papp, MD, who later presented results of bimekizumab in plaque psoriasis, took to the floor to dispute this claim.

"I admit, I did at one time believe this story about disease modification," said Dr. Papp, founder and president of Probity Medical Research in Waterloo, Ont. "But now I think we are simply seeing a pharmacokinetic effect. How can you reconcile what is clearly a pharmacologic and mechanistic perspective with this suggestion that you're modifying disease?"

Session moderator Hensin Tsao, MD, suggested that the answer might lie in some unknown in-between territory.

"We do see about 10%-20% of patients in whom drug-free remission is not explained by pharmacokinetics. In some patients, the drug is long gone, and they are still clear of disease – and we don't know how to talk about those patients yet. But we do need to study them because, for those people, clearly it is not a [pharmacokinetic] issue."

Dr. Reich disclosed financial relationships with numerous pharmaceutical companies, including Janssen, which manufactures guselkumab. Dr. Papp also disclosed multiple relationships with drug manufacturers.

SOURCE: Gordon K et al. AAD 2018 Abstract 6748.

msullivan@frontlinemedcom.com

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Skin Care Physicians of Costa Rica

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