But the interleukin-36-receptor inhibitor spesolimab may have sparked infections in up to 47% of volunteers over 12 weeks and antidrug antibodies were detected in nearly half of patients, researchers report in the New England Journal of Medicine.
"To put this into perspective, these are non-life-threatening infections that don't contribute to the demise of patients at all," versus a condition that can lead to deadly infections, senior author Dr. Mark Lebwohl of the Icahn School of Medicine at Mount Sinai, in New York City, told Reuters Health by phone. "There's really no contest there."
Pustular psoriasis is the rarest form of psoriasis, afflicting roughly one in 12,500 people worldwide. The autoinflammatory skin disease, with its erupting pustules, kills 2% to 16% of those afflicted with it because a flare can lead to septic shock and cardiorespiratory failure as the skin loses its integrity. A flare can last a few months.
There are no approved therapies. One challenge posed by the disease is that the pattern and extent of flares can vary widely from patient to patient, with a wide variety of triggers.
The study, known as Effisayil 1, was conducted at 37 sites in 12 countries. Thirty-five patients were assigned to receive spesolimab and 18 to receive placebo. Boehringer Ingelheim paid for the study and analyzed the data.
To gauge the effectiveness of the treatment, the team used the five-point Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore, where 0 meant clear, 1 indicated almost clear and 4 meant severe pustulation.
Before treatment, 83% of the 35 volunteers in the spesolimab group who were experiencing a flare had a score of 3 or 4 and at least 5% of their skin had erythema and some pustules.
One week after treatment, 54% had a score of 0. Among the 18 patients in the control group, 72% of whom started out with a rating of 3 or 4, only 6% improved enough after placebo infusions to be rated clear (P<0.001).
On a score that also factors in erythema and scaling - the GPPGA total score - 43% of spesolimab recipients had a score of 0 or 1 compared with 11% of those getting placebo (P=0.02).
"The beauty of it is how quickly it works," said Dr. Lebwohl, professor and dean for clinical therapeutics. "We see dramatic improvement in one week in the majority of patients."
On the eighth day, "anyone who didn't do well was able to get open-label treatment," he said. "The condition is so life-threatening, we thought it would be unethical to withhold a treatment that we knew from the earlier proof-of-concept study that it worked."
There was a 12-week follow-up period to assess side effects, during which four patients in the drug group and two in the control group received rescue treatment with spesolimab one week after the initial therapy.
Pyrexia was seen in 6% of spesolimab recipients versus 22% of placebo patients, so the fever was probably due to the pustular psoriasis. But the infection rate was nearly three times higher: 17% with the drug and 6% with placebo.
"There was no particular pathogen or affected organ," the researchers say.
None of the placebo patients had a serious adverse event but the rate was 6% - amounting to two patients - with spesolimab.
"Longer and larger trials are warranted to determine the effect and risks of spesolimab in patients with pustular psoriasis," the researchers write.
SOURCE: https://bit.ly/327cnEC The New England Journal of Medicine, online December 22, 2021.
By Gene Emery
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