From the Journals

In psoriasis, risankizumab outperforms adalimumab

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IL-23 inhibitor expands psoriasis arsenal

Until recently, TNF-alpha inhibitors have been the most commonly prescribed biologic agents for psoriasis. They are more targeted than small molecules like cyclosporine or methotrexate, but still are associated with immune side effects like infection and malignancy. Drugs that specifically target IL-23 home in on the pathogenicity of psoriasis, and they are not associated with infection and malignancy. The results of this study offer evidence that IL-23 inhibitors represent another effective and convenient option for the treatment of psoriasis. Physicians can select from IL-23 inhibitors, IL-17 inhibitors, and TNF-alpha inhibitors to determine the optimal treatment for patients based on patient weight, childbearing status, age, and comorbid conditions.

Mark Lebwohl, MD, is in the department of dermatology at Icahn School of Medicine at Mount Sinai, New York.



In a phase 3, active comparator controlled trial, treatment with risankizumab led to better skin clearance than treatment with adalimumab in patients with moderate-to-severe plaque psoriasis. Results of the IMMvent trial were published online ahead of print July 4 in the Lancet.

Risankizumab targets the p19 subunit of the cytokine IL-23. Selectivity for p19 has the potential to be safer than some other approaches that target the p40 subunit, because p19 is specific to IL-23, and many immune defense processes can function without IL-23. The p40 subunit is shared with IL-12, and blocking it can therefore lead to off-target effects.

Risankizumab was previously shown to have superior safety and efficacy over ustekinumab, which inhibits a subunit shared by IL-23 and IL-12 (Gordon KB et al. Lancet. 2018;392[10148]:650-61). Adalimumab is a TNF-alpha inhibitor that is frequently used to treat psoriasis, and which became available in biosimilar form in Europe in 2018.

The researchers randomized 605 adult patients from 66 sites in 11 countries to receive either risankizumab or adalimumab. The first phase (Part A) of the trial lasted up to 16 weeks, and tested the general superiority of risankizumab over adalimumab. The second phase (Part B), from week 16 to 44, evaluated the efficacy of risankizumab in participants who experienced an intermediate response, defined as Psoriasis Area and Severity Index (PASI) score of 50-90.

At the start of Part B, subjects initially receiving adalimumab who had at least a 90% improvement in PASI stayed on adalimumab (PASI 90), while those who had less than 50% improvement in PASI were switched to risankizumab. The remaining intermediate responders (PASI 50-90) were re-randomized to continue adalimumab or switch to risankizumab. All subjects initially randomized to risankizumab continued risankizumab during part B.

At the end of Part A, 72% of the risankizumab group achieved PASI 90, compared with 47% in the adalimumab group (p < 0.0001). A total of 84% in the risankizumab group had a static Physician’s Global Assessment (sPGA) score of 0 or 1 at the end of Part A, compared with 60% in the adalimumab group (p < 0.0001).

During Part B, among intermediate adalimumab responders, 66% of those switched to risankizumab achieved PASI 90, compared with 21% of continued on adalimumab (p < 0.0001).

In Part A, 56% of patients taking risankizumab experienced an adverse event, as did 57% of those taking adalimumab. Among adalimumab intermediate responders, 75% of those who switched to risankizumab during Part B had an adverse event, compared with 66% of those who continued adalimumab.

SOURCE: Reich K, et al. Lancet 2019, July 4 .

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