Targeted biologic therapies have greatly improved the safety and efficacy of treatment for plaque psoriasis, and therapeutic advances continue in this area. Newer and emerging biologic agents were discussed in several presentations at the 2024 Fall Clinical Dermatology Conference.

Following these presentations, featured expert Steven R. Feldman, MD, PhD, was interviewed by Conference Reporter Associate Editor-in-Chief Rick Davis. Dr Feldman’s clinical perspectives on this topic are presented here.

The newest biologic agents for plaque psoriasis are the IL-17 and IL-23 inhibitors, both of which were discussed at the 2024 Fall Clinical Dermatology Conference. The most recent US Food and Drug Administration (FDA)–approved IL-17 inhibitor is bimekizumab, which has a different target than the other available IL-17 inhibitors. While bimekizumab binds to both IL-17A and IL-17F, secukinumab and ixekizumab bind only to IL-17A. IL-17A and IL-17F are very important in psoriasis, as are the IL-17AA and IL-17FF homodimers and the IL-17A/F heterodimers that can form. Since secukinumab and ixekizumab target IL-17A, they therefore neutralize IL-17AA dimers and inhibit IL-17A/F dimers, but they do not affect IL-17FF dimers. IL-17FF dimers appear to be important in psoriasis, based on the efficacy of bimekizumab, which may be more effective than the older IL-17 inhibitors and could be highly effective for psoriatic arthritis. This was discussed by April W. Armstrong, MD, MPH, during a session at the conference. However, there is an increased risk of oral candidiasis with IL-17 inhibitors because IL-17 is important in controlling fungal infections. The risk of oral candidiasis is further increased with bimekizumab vs secukinumab or ixekizumab, but it is easily managed with antifungal lozenges.

IL-23 inhibitors really seem to hit a “sweet spot” in psoriasis management, and I am not surprised, because the genes for both IL-23 subunits and the IL-23 receptor are associated with psoriasis. Data from the phase 3b SPECTREM study evaluating the IL-23 inhibitor guselkumab for moderate plaque psoriasis with low body surface area and special site involvement (eg, the face, genitals, scalp, and skin folds) were presented at the 2024 Fall Clinical Dermatology Conference in a poster by Linda F. Stein Gold, MD, and colleagues. The special areas are typically not more resistant to treatment than other areas of skin, although sometimes they may seem like they are. Regardless, psoriasis in these areas has an effect on patient quality of life. The improvement in severity scores that we saw in the SPECTREM study seems to be similar to the excellent improvement that was seen in other areas of skin with guselkumab in a previous study.

JNJ-77242113, a novel oral peptide IL-23 inhibitor in development, was also discussed at the conference in presentations by Mark Lebwohl, MD, and Andrea T. Murina, MD. It is unclear if it has the same level of efficacy as guselkumab or risankizumab, as guselkumab and risankizumab get approximately 85% of patients to a Psoriasis Area and Severity Index (PASI) score of 75% or greater, whereas JNJ-77242113 gets up to 78.6% of patients there, depending on the dose. So, JNJ-77242113 is more effective than adalimumab and ustekinumab and about as effective as secukinumab.

Since this is an oral drug, I wonder if patients could be missing some doses and if that is affecting the efficacy. Adherence is not perfect with biologics, but I think that it is better than it is with oral drugs. If a patient misses doses of an oral drug, that could potentially reduce the efficacy further compared with the injectable agents, even though they all target cytokine signaling.

Finally, I think that it is key to understand that biologics are generally so large and complex that it is hard to duplicate them to create biosimilars. This means that the biosimilars are not identical to the originally patented drug, and some people worry that the biosimilars will not provide the same results. However, even the original manufacturer of a patented biologic cannot necessarily perfectly duplicate it, so every batch can be different from every other batch. A biosimilar is basically like another batch of the original product, only you get more data on the similarities than you do for different batches of the originally patented product.