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An oral interleukin (IL)-23 inhibitor for psoriasis produced 16-week response rates as high as 79% in moderate-to-severe plaque psoriasis, a prospective phase II trial showed.

The drug (JNJ-77242113) achieved response rates of 37% to 79% across five dose levels. In contrast, patients treated with placebo had a 9% response rate at 16 weeks. The most common adverse events (AEs) were COVID-19 and nasopharyngitis, with no evidence of a dose-related increase in AEs.

"The level of reduction of psoriasis that was observed with higher doses of JNJ-77242113 at week 16 was similar in magnitude to the responses seen with several of the injectable biologics that are currently approved for psoriasis," reported Robert Bissonnette, MD, of Innovaderm Research in Montreal, and co-authors in the . "The percentage of patients who had a PASI [Psoriasis Area and Severity Index] 90 response with JNJ-77242113 100 mg twice daily at week 16 was 60%. In contrast, phase III trials of other available oral treatments showed that 27% to 36% of patients had a PASI 90 response after 16 weeks of treatment with deucravacitinib [Sotyktu] and 18% to 20% of patients had PASI 90 response with apremilast [Otezla] at week 16."

The study added to "stunning progress" made over the past two decades in the treatment of moderate-to-severe psoriasis, wrote Joel M. Gelfand, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, in an . If confirmed by larger studies, a PASI 90 response rate of 60% would be similar to the most effective injectable biologics.

"However, two occurrences of infection ... and a suicide attempt were reported as serious adverse events," Gelfand continued. "Larger trials will be needed to determine whether such events are attributable to chance, psoriasis itself, or inhibition of interleukin-23 signaling. Furthermore, JNJ-77242113 needs to be taken on an empty stomach, and therefore, effectiveness may be lower in real-world settings."

Treatment effect also might be influenced by body weight, he added. In the highest dose group, for example, 100% of patients with a body mass index (BMI) <25 achieved a PASI 75 response, as compared with 68% of patients with a BMI ≥30.

IL-23 plays a critical role in pathogenic T-cell activation in psoriasis, and multiple biologic agents that target IL-23 in psoriasis have been approved, Bissonnette and co-authors noted in their introduction. Biologics have limitations, one being the requirement for intravenous or subcutaneous administration. Many patients prefer oral medications over injections, which can be especially problematic for children and adult patients who fear needles.

Two oral therapies have approval for psoriasis, apremilast (a phosphodiesterase 4 inhibitor) and deucravacitinib (a tyrosine kinase 2 inhibitor), but apremilast has relatively modest efficacy as compared with biologics, and long-term safety data on tyrosine kinase 2 inhibitors remain limited, the authors continued. JNJ-77242113 "selectively and potently" blocks IL-23 and production of downstream cytokines, such as IL-17. The drug was evaluated in the phase II dose-finding trial.

Investigators enrolled 255 patients with a mean baseline PASI score of 19.1 and mean psoriasis duration of 18.2 years. Almost 80% of the patients had received prior systemic therapies. Patients were randomly assigned to placebo or to one of five doses of JNJ-77242113: 25 mg QD, 25 mg BID, 50 mg QD, 100 mg QD, or 100 mg BID. The primary endpoint was the proportion of patients who had a PASI 75 response after 16 weeks.

The results demonstrated a statistically significant increase in PASI 75 rates (P<0.001) across the five doses of JNJ-77242113 versus a 9% response rate in the placebo group:

• 25 mg QD - 37%
• 25 mg BID - 51%
• 50 mg QD - 58%
• 100 mg QD - 65%
• 100 mg BID - 79%

A similar response pattern emerged from an analysis of PASI 90 responses (a secondary endpoint), as JNJ-77242113 treatment groups had response rates of 26% to 60%, increasing with each higher dose. The placebo group had a PASI 90 response rate of 2%. PASI 100 response rates ranged from 10% to 40% across the JNJ-77242113 dose groups versus 0% in the placebo group. The proportion of patients achieving an investigator global assessment score of 0-1 (clear/nearly clear) ranged from 40% to 64% in the JNJ-77242113 groups, as compared with 12% in the placebo group.

For all five JNJ-77242113 dose groups combined, the most common all-grade adverse events (AEs) were COVID-19 (11%), nasopharyngitis (7%), and diarrhea (5%). Serious AEs occurred in 1% of all dose groups combined.

"The data from this trial are limited by the small number of patients in each trial group and the short duration of treatment," the authors added. "In addition, no corrections for multiplicity were made, so definitive effects of JNJ-77242113 for particular dose groups or for secondary endpoints cannot be inferred."

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