Emerging Therapies In Psoriasis: A Systematic Review
Many new biologics are being studied for use in psoriasis. In this review, we evaluate and summarize findings about emerging biologic therapies for psoriasis. We reviewed published data from phase 2 and 3 clinical trials of 2 IL-17 inhibitors (ixekizumab and brodalumab); 3 IL-23 inhibitors (guselkumab, tildrakizumab, and risankizumab); and 1 tumor necrosis factor (TNF) inhibitor (certolizumab pegol). Janus kinase inhibitors were not included in our review, as they currently are not approved by the US Food and Drug Administration (FDA) and there are no plans to further develop this class for treatment of psoriasis. Overall, the clinical improvement provided by and the safety profiles of these agents are promising; they may be equal to or more efficacious than available therapeutic options for treating the symptoms of psoriasis. Long-term studies are still needed, however, to further establish safety and efficacy profiles for these biologic agents.
Practice Points
- Tumor necrosis factor α, IL-23, and IL-17A are key targets for psoriasis therapy based on an understanding of the key role that these cytokines play in the pathophysiology of disease.
- The biologic agents secukinumab and ixekizumab are approved for use in the management of psoriasis. Other biologics—brodalumab, bimekizumab, guselkumab, tildrakizumab, risankizumab, and certolizumab pegol—have been (and some continue to be) the focus of phase 2 and phase 3 clinical trials.
- Findings of several of those trials support the idea that therapies targeting IL-23, specifically its p19 subunit, but that spare IL-12 are effective against psoriasis.
- Longer-term studies are needed to determine whether the agents reviewed here, including those approved for clinical use, are suitable for prolonged administration.
IL-23 Inhibitors Guselkumab, Tildrakizumab, and Risankizumab
Making comparisons among the IL-23 inhibitors also is difficult; studies were not head-to-head comparison trials, and the VOYAGE and reSURFACE studies used different time points for primary end points. Furthermore, only phase 2 trial data are available for risankizumab. Despite these limitations, results of these trials suggest that guselkumab and risankizumab may be slightly more efficacious than tildrakizumab. However, future studies, including head-to-head studies, would ultimately provide further information on how these agents compare.
Guselkumab was shown to remain efficacious at 48 weeks, though patients on maintenance dosing had better results than those who were re-treated.12 Moreover, guselkumab was found to be effective in hard-to-treat areas, such as the scalp,11 and in patients who did not respond to adalimumab. Guselkumab may therefore benefit patients who have experienced limited clinical improvement on other biologics.12
Tildrakizumab was shown to improve PASI 75 and PGA scores through week 28 of treatment. Moreover, a higher percentage of patients taking tildrakizumab scored 0 or 1 on the dermatology life quality index, suggesting that the drug improves quality of life.14 No specific safety concerns arose in either reSURFACE trial; however, long-term studies are needed for further evaluation.
Risankizumab appears to be a promising new therapy based on phase 2 trial results. Improvements also were seen in dermatology life quality index scores, scalp and fingernail symptoms, and palmoplantar psoriasis.15 Of note, neutralizing antidrug antibodies were found in 3 patients during this study,15 which may present potential problems for long-term efficacy. However, preliminary data from 3 phase 3 trials—ultIMMa-1, ultIMMa-2, and IMMvent—are promising.17
CONCLUSION
Advances in the understanding of psoriasis have led to new targeted therapies. Ongoing clinical trials have shown encouraging results for treating physical and psychological symptoms of psoriasis. The findings of these trials support the idea that therapies targeting IL-23, specifically its p19 subunit, are effective against psoriasis while sparing IL-12. Long-term data from open-label extension studies would help guide clinical recommendations regarding the safety profiles of these agents and determine their long-term utility.
