乌鸦传媒

MADRID -- The anti-interleukin (IL)-23 monoclonal antibody guselkumab was effective in relieving multiple disease domains of psoriatic arthritis, a phase IIa study found.

In a cohort of 149 patients with active disease, the primary endpoint -- a 20% response according to the criteria of the American College of Rheumatology (ACR20) -- was achieved at week 24 by 58% of those receiving guselkumab compared with 18.4% of those given placebo (P<0.001), according to Atul Deodhar, MD, of Oregon Health & Science University in Portland.

In addition, 78.6% of those receiving guselkumab had 75% improvement on the Psoriasis Area and Severity Index (PASI75) compared with 12.5% of those on placebo (P<0.001), he reported at the here.

"Guselkumab targets the p19 subunit of IL-23, whereas IL-12 and IL-23 share the p40 subunit, which is blocked by ustekinumab (Stelara). Guselkumab has previously demonstrated efficacy in three phase III trials," Deodhar said at the meeting.

"This agent is completely new, and opens up an additional choice for our patients," he said during a press briefing. "With all the drugs we have for psoriatic arthritis, about 40% of patients don't have an ACR20 response. So we are always trying to find newer drugs with different mechanisms of action," he said.

Patients enrolled in the study had to have at least 3% body surface area affected by psoriasis despite standard-of-care treatment, 3 or more tender and swollen joints, and C-reactive protein above 0.3 mg/dL.

They were randomized 2:1 to receive 100 mg of subcutaneous guselkumab at baseline and week 4 and then every 8 weeks thereafter.

At week 16, patients who had less than 5% improvement in tender and swollen joint counts were allowed early escape with open-label ustekinumab (which is approved for psoriatic arthritis).

And at week 24, all patients still receiving placebo were crossed over to subcutaneous guselkumab, 100 mg every 8 weeks.

At baseline, patients' mean age was 44, and the gender distribution was equal. On average, they had nine swollen and 16 to 18 tender joints. About 10% had previously received a tumor necrosis factor (TNF) inhibitor.

At week 24, ACR50 responses were seen in 34% of the guselkumab group compared with 10.2% of the placebo group (P=0.002), while ACR70 responses were seen in 14% and 2% (P=0.023).

For the skin, PASI90 responses were seen in 66.3% versus 6.3% (P<0.001) and PASI100 responses were seen in 40% versus 6% (P<0.001).

"The skin data were quite impressive. So for someone with significant involvement of the skin as well as of the joints, this could be a game-changer," he said.

On the Health Assessment Questionnaire Disability Index, changes from baseline at week 24 were -0.42 versus -0.06 (P<0.001).

For both enthesitis and dactylitis, the mean changes from baseline were -100% versus -33% (P=0.009 and P<0.001).

Quality of life was assessed on the Short Form-36 physical and mental component scores. For the physical component, mean change from baseline was 6.59 in the guselkumab group versus 0.46 in the placebo group (P<0.001), and for the mental component, the changes were 4.95 versus 0.42 (P=0.002).

A total of 23% of patients receiving guselkumab achieved a state of minimal disease activity by week 24, compared with 2% of those given placebo (P=0.001).

"Safety was similar to what we have seen in the psoriasis studies," Deodhar said.

A total of 36% of patients in the guselkumab group reported any adverse event, as did 32.7% of those in the placebo group. For serious adverse events, there was one knee injury in a patient on placebo and one myocardial infarction in a patient on guselkumab. Another patient also had grade 3 neutropenia, which resolved when guselkumab was discontinued.

There were no deaths, malignancies, serious or opportunistic infections, or injection site reactions.

"Guselkumab significantly improved joint symptoms, physical function, psoriasis, enthesitis, dactylitis, and quality of life. It was well tolerated with no unexpected safety findings," he concluded.

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