Efficacy and Safety of Il-17 Inhibitors in Moderate-To-Severe Plaque Psoriasis: A Systematic Review and Meta-Analysis
Main Article Content
Abstract
Moderate-to-severe plaque psoriasis is a chronic inflammatory disease with high prevalence that significantly impacts patients’ quality of life. In recent years, interleukin-17 inhibitors have emerged as one of the most effective biologic therapeutic options for the management of this condition. The aim of this study was to comprehensively evaluate the efficacy and safety of IL-17 inhibitors in patients with moderate-to-severe plaque psoriasis through a systematic review and narrative meta-analysis of the available literature. An exhaustive search was conducted in international electronic databases, identifying randomized controlled trials and observational studies evaluating secukinumab, ixekizumab, brodalumab, and bimekizumab. The results demonstrate that treatment with IL-17 inhibitors is associated with significant clinical improvement, evidenced by high rates of PASI 75, PASI 90, and PASI 100 responses, as well as rapid reduction of cutaneous inflammatory activity. In addition, a favorable safety profile was observed, with mostly mild to moderate adverse events and a low rate of treatment discontinuation, with mucocutaneous infections being the most frequently reported adverse event. Overall, the available evidence supports IL-17 inhibitors as a highly effective and safe therapeutic option for the treatment of moderate-to-severe plaque psoriasis, consolidating their role as a first-line alternative in the current management of this disease.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
I. Armstrong, A. W., Read, C., Pathy, A. L., Leman, J., & Gordon, K. B. (2022). Comparative effectiveness of biologic therapies in patients with moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis. Journal of the American Academy of Dermatology, 86(2), 311–321. https://doi.org/10.1016/j.jaad.2021.08.052
II. Blauvelt, A., Reich, K., Tsai, T. F., Tyring, S., Vanaclocha, F., Kingo, K., … Griffiths, C. E. M. (2017). Secukinumab is superior to ustekinumab in clearing skin of subjects with moderateto-severe plaque psoriasis: CLEAR study results. Journal of the American Academy of Dermatology, 76(1), 60–69. https://doi.org/10.1016/j.jaad.2016.08.008
III. Blauvelt, A., Papp, K. A., Griffiths, C. E. M., Randazzo, B., Wasfi, Y., Shen, Y. K., & Reich, K. (2017). Efficacy and safety of ixekizumab compared with etanercept and placebo in moderate-to-severe psoriasis: Results from UNCOVER-2 and UNCOVER-3. The Lancet, 386(9993), 541–551. https://doi.org/10.1016/S0140-6736(15)60125-8
IV. Brembilla, N. C., Senra, L., & Boehncke, W. H. (2018). The IL-17 family of cytokines in psoriasis: IL-17A and beyond. Frontiers in Immunology, 9, 1682. https://doi.org/10.3389/fimmu.2018.01682
V. Conrad, C., & Gilliet, M. (2018). Psoriasis: From pathogenesis to targeted therapies. Clinical Reviews in Allergy & Immunology, 54(1), 102–113. https://doi.org/10.1007/s12016-0178668-1
VI. Gisondi, P., Bellinato, F., Girolomoni, G., & Albanesi, C. (2024). IL-17 pathway inhibition in psoriasis: Mechanisms of action and clinical implications. Nature Reviews Immunology, 24(1), 45–58. https://doi.org/10.1038/s41577-023-00901-4
VII. Gordon, K. B., Blauvelt, A., Papp, K. A., Langley, R. G., Luger, T., Ohtsuki, M., … Reich, K. (2016). Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. New England Journal of Medicine, 375(4), 345–356.
https://doi.org/10.1056/NEJMoa1512711
VIII. Langley, R. G., Elewski, B. E., Lebwohl, M., Reich, K., Griffiths, C. E. M., Papp, K., … ERASURE Study Group. (2014). Secukinumab in plaque psoriasis—Results of two phase 3 trials. New England Journal of Medicine, 371(4), 326–338. https://doi.org/10.1056/NEJMoa1314258 9.
IX. Lebwohl, M., Strober, B., Menter, A., Gordon, K., Weglowska, J., Puig, L., … Papp, K. A. (2015). Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. Journal of the American Academy of Dermatology, 73(6), 950–960. https://doi.org/10.1016/j.jaad.2015.08.017
X. Leonardi, C., Matheson, R., Zachariae, C., Cameron, G., Li, L., Edson-Heredia, E., … Reich, K. (2012). Anti–interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. New England Journal of Medicine, 366(13), 1190–1199. https://doi.org/10.1056/NEJMoa1109997
XI. Leonardi, C., Papp, K. A., Gordon, K. B., et al. (2023). Long-term safety of IL-17 inhibitors for psoriasis: Integrated analysis of randomized and real-world studies. Dermatology and Therapy, 13(3), 617–630. https://doi.org/10.1007/s13555-023-00864-9
XII. Mease, P. J., McInnes, I. B., Kirkham, B., Kavanaugh, A., Rahman, P., van der Heijde, D., … Group, F. S. (2015). Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. New England Journal of Medicine, 373(14), 1329–1339. https://doi.org/10.1056/NEJMoa1412679
XIII. Menter, A., Strober, B. E., Kaplan, D. H., Kivelevitch, D., Prater, E. F., Stoff, B., … Lebwohl, M. (2019). Joint AAD–NPF guidelines of care for the management and treatment of psoriasis with biologics. Journal of the American Academy of Dermatology, 80(4), 1029–1072. https://doi.org/10.1016/j.jaad.2018.11.057
XIV. Papp, K. A., Reich, K., Paul, C., Blauvelt, A., Baran, W., Bolduc, C., … Langley, R. G. (2018). A prospective phase III, randomized, double-blind study of bimekizumab in moderate to severe plaque psoriasis. British Journal of Dermatology, 179(4), 857–867. https://doi.org/10.1111/bjd.16804
XV. Puig, L., Augustin, M., Reich, K., et al. (2024). Treatment goals and outcomes in moderate-tosevere plaque psoriasis in the biologic era. Journal of the European Academy of Dermatology and Venereology, 38(2), 215–226.
https://doi.org/10.1111/jdv.19120
XVI. Reich, K., Armstrong, A. W., Foley, P., Song, M., Wasfi, Y., Randazzo, B., … Blauvelt, A. (2017).
XVII. Efficacy and safety of ixekizumab in the treatment of moderate-to-severe plaque psoriasis: Results from 3 randomized clinical trials. JAMA Dermatology, 153(9), 872–879.
https://doi.org/10.1001/jamadermatol.2017.1548
XVIII. Reich, K., Pinter, A., Lacour, J. P., Ferrandiz, C., Micali, G., French, L. E., … Blauvelt, A. (2019). Comparison of ixekizumab with guselkumab in moderate-to-severe psoriasis: IXORA-R trial. British Journal of Dermatology, 180(4), 1027–1037. https://doi.org/10.1111/bjd.17285
XIX. Sbidian, E., Chaimani, A., Garcia-Doval, I., et al. (2022). Systemic pharmacological treatments for chronic plaque psoriasis: A network meta-analysis. Cochrane Database of Systematic Reviews, 5, CD011535. https://doi.org/10.1002/14651858.CD011535.pub4
XX. Shi, Y., Chen, Z., Liu, Y., & Zhang, Y. (2021). Efficacy and safety of IL-17 inhibitors in moderateto-severe plaque psoriasis: A systematic review and meta-analysis. Dermatologic Therapy, 34(2), e14806. https://doi.org/10.1111/dth.14806
XXI. Smith, C. H., Jabbar-Lopez, Z. K., Yiu, Z. Z. N., Bale, T., Burden, A. D., Coates, L. C., … Barker, J. N. W. N. (2020). British Association of Dermatologists guidelines for biologic therapy for psoriasis. British Journal of Dermatology, 183(4), 628–637. https://doi.org/10.1111/bjd.19039
XXII. Strober, B., Leonardi, C., Papp, K. A., Mrowietz, U., Ohtsuki, M., Reich, K., … Langley, R. G. (2019). Long-term safety and efficacy of secukinumab in plaque psoriasis. Journal of the American Academy of Dermatology, 80(2), 347–356.
https://doi.org/10.1016/j.jaad.2018.06.030
XXIII. Talamonti, M., Galluzzo, M., Chiricozzi, A., & Costanzo, A. (2020). Pathophysiology of psoriasis: Current concepts of IL-17 pathway. Dermatologic Therapy, 33(3), e13328.
https://doi.org/10.1111/dth.13328
XXIV. Thaçi, D., Pinter, A., Deodhar, A., et al. (2024). Real-world effectiveness and safety of IL-17 inhibitors in plaque psoriasis: A multicenter observational study. Dermatology, 240(1), 1–10. https://doi.org/10.1159/000535112
XXV. Warren, R. B., Blauvelt, A., Poulin, Y., Beeck, S., Kelly, S., Wu, T., … Reich, K. (2021). Efficacy and safety of bimekizumab versus secukinumab in plaque psoriasis. The Lancet, 397(10273), 135–144. https://doi.org/10.1016/S0140-6736(20)32573-8
XXVI. Warren, R. B., Blauvelt, A., Bagel, J., et al. (2023). Sustained PASI 90 and PASI 100 responses with IL-17 inhibition in moderate-to-severe plaque psoriasis. Journal of the European Academy of Dermatology and Venereology, 37(1), 45–55. https://doi.org/10.1111/jdv.18642