Efficacy and Safety of Ixekizumab in Patients with Moderate-to-Severe Plaque Psoriasis: A Systematic Review and Meta-Analysis
Main Article Content
Plaque psoriasis is a chronic inflammatory skin disease affecting approximately 1% of adults worldwide. However, studies of Ixekizumab have shown mixed results. To evaluate the effectiveness and safety of Ixekizumab in patients with moderate to severe plaque psoriasis. This systematic review followed the PRISMA 2020 guidelines and was conducted on PubMed, ScienceDirect, and Google Scholar. Primary outcomes included PASI 75, PASI 90, PASI 100, and treatment-related adverse events. Secondary outcomes included sPGA (0/1), sPGA (0), DLQI (0/1), DLQI (0), NAPSI, and NRS itch score (?4). Proportions were used to convey the incidence of primary and secondary outcomes. Risk of bias was assessed using the RoB2 tool. Statistical analysis was performed using R version 4.4.2. This meta-analysis included 9 RCTs, with a low risk of bias in all studies. Analysis of PASI outcomes 75% shows the proportion of events of 81.1% (95% CI: 72.78%-87.32%; I2 = 85.5%). PASI 90% shows the proportion of events of 65.72% (95% CI: 49.87%- 78.70%; I2 = 95.4%) and PASI 100% of 38.98% (95% CI: 31.81%-46.65%; I² = 93.3%). Side effects caused by the intervention were 66.07% (95% CI: 58.23%–73.12%; I² = 88.9%). sPGA score ?1, DLQI ?1, NAPSI, NRS with a proportion of 71.15% (95% CI: 61.12%–79.47%), 59.68% (95% CI: 39.84%–76.79%), 28.44% (95% CI: 15.80%–45.71%), 47.91% (95% CI: 33.77%–62.40%). Ixekizumab demonstrated high efficacy in the treatment of moderate to severe plaque psoriasis, with adverse events occurring in more than half of participants consistently reported across studies.
Keywords:
efficacy, ixekizumab, safety, psoriasis, plaque
Abrouk, M., Nakamura, M., Zhu, T. H., Farahnik, B., Koo, J., & Bhutani, T. (2017). The impact of PASI 75 and PASI 90 on quality of life in moderate to severe psoriasis patients. The Journal of Dermatological Treatment, 28(6), 488–491. https://doi.org/10.1080/09546634.2016.1278198
Armstrong, A. W., Warren, R. B., Zhong, Y., Zhuo, J., Cichewicz, A., Kadambi, A., Junqueira, D., Westley, T., Kisa, R., Daamen, C., & Augustin, M. (2023). Short-, mid-, and long-term efficacy of deucravacitinib versus biologics and nonbiologics for plaque psoriasis: A network meta-analysis. Dermatology and Therapy, 13(11), 2839–2857. https://doi.org/10.1007/s13555-023-01034-7
Blauvelt, A., Leonardi, C., Elewski, B., Crowley, J. J., Guenther, L. C., Gooderham, M., Langley, R. G., Vender, R., Pinter, A., Griffiths, C. E. M., Tada, Y., Elmaraghy, H., Lima, R. G., Gallo, G., Renda, L., Burge, R., Park, S. Y., Zhu, B., & Papp, K. (2021). A head-to-head comparison of ixekizumab vs. guselkumab in patients with moderate-to-severe plaque psoriasis: 24-week efficacy and safety results from a randomized, double-blinded trial. The British Journal of Dermatology, 184(6), 1047–1058. https://doi.org/10.1111/bjd.19509
Blauvelt, A., Shi, N., Burge, R., Malatestinic, W. N., Lin, C.-Y., Lew, C. R., Zimmerman, N. M., Goldblum, O. M., Zhu, B., & Murage, M. J. (2020). Comparison of real-world treatment patterns among patients with psoriasis prescribed ixekizumab or secukinumab. Journal of the American Academy of Dermatology, 82(4), 927–935. https://doi.org/10.1016/j.jaad.2019.11.015
Carretero, G., Puig, L., Carrascosa, J. M., Ferrándiz, L., Ruiz-Villaverde, R., de la Cueva, P., Belinchón, I., Vilarrasa, E., Del Río, R., Sánchez-Carazo, J. L., López-Ferrer, A., Peral, F., Armesto, S., Eiris, N., Mitxelena, J., Vilar-Alejo, J., A Martín, M., & Soria, C. (2018). Redefining the therapeutic objective in psoriatic patients candidates for biological therapy. The Journal of Dermatological Treatment, 29(4), 334–346. https://doi.org/10.1080/09546634.2017.1395794
Egeberg, A., Merola, J. F., Schäkel, K., Puig, L., Mahar, P. D., Wang, I. Y., Pavo, I., Schuster, C., & Griffiths, C. E. M. (2022). Efficacy of ixekizumab in patients with moderate-to-severe plaque psoriasis and prediabetes or type 2 diabetes. Frontiers in Medicine, 9, 1092688. https://doi.org/10.3389/fmed.2022.1092688
Egeberg, A., Wu, J. J., Korman, N., Solomon, J. A., Goldblum, O., Zhao, F., et al. (2018). Ixekizumab treatment shows a neutral impact on cardiovascular parameters in patients with moderate-to-severe plaque psoriasis: results from UNCOVER-1, UNCOVER-2, and UNCOVER-3. Journal of the American Academy of Dermatology, 79(1), 104–109. https://doi.org/10.1016/j.jaad.2018.02.045
Eisen, M., Hartmane, I., Kingo, K., Mikazans, I., Toomson, T., Toomela, K., & Valiukeviciene, S. (2025). The real-world burden of moderate-to-severe psoriasis in patients under systemic treatment from Baltic countries: Data from the CRYSTAL observational study. Medicina, 61(3). https://doi.org/10.3390/medicina61030397
Gordon, K. B., Blauvelt, A., Papp, K. A., Langley, R. G., Luger, T., Ohtsuki, M., et al. (2016). Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. The New England Journal of Medicine, 375(4), 345–356. https://doi.org/10.1056/NEJMoa1603532
Gorelick, J., Shrom, D., Sikand, K., Renda, L., Burge, R., Dworkin, C., et al. (2019). Understanding treatment preferences in patients with moderate to severe plaque psoriasis in the USA: results from a cross-sectional patient survey. Dermatologic Therapy, 9(4), 785–797. https://doi.org/10.1007/s13555-019-00324-3
Hartmane, I., Ivdra, I., Mikaž?ns, I., & Bondare-ansberga, V. (2021). Immunopathogenic treatment options for psoriasis patients under a restrictive reimbursement environment. Pro Litteris et Scientia, 75(3), 158–166. https://doi.org/10.2478/prolas-2021-0025
Honma, M., Cai, Z., Burge, R., Zhu, B., Yotsukura, S., & Torisu-Itakura, H. (2020). Relationship between rapid skin clearance and quality of life benefit: Post hoc analysis of Japanese patients with moderate-to-severe psoriasis treated with ixekizumab (UNCOVER-J). Dermatology and Therapy, 10(6), 1397–1404. https://doi.org/10.1007/s13555-020-00441-4
Langley, R. G., Papp, K., Gooderham, M., Zhang, L., Mallinckrodt, C., Agada, N., Blauvelt, A., Foley, P., & Polzer, P. (2018). Efficacy and safety of continuous every-2-week dosing of ixekizumab over 52 weeks in patients with moderate-to-severe plaque psoriasis in a randomized phase III trial (IXORA-P). The British Journal of Dermatology, 178(6), 1315–1323. https://doi.org/10.1111/bjd.16426
Leonardi, C., Matheson, R., Zachariae, C., Cameron, G., Li, L., Edson-Heredia, E., et al. (2012). Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. The New England Journal of Medicine, 366(13), 1190–1199. https://doi.org/10.1056/NEJMoa1109997
Leonardi, C., Reich, K., Foley, P., Torii, H., Gerdes, S., Guenther, L., et al. (2020). Efficacy and safety of ixekizumab through 5 years in moderate-to-severe psoriasis: Long-term results from UNCOVER-1 and UNCOVER-2. Dermatology and Therapy, 10(3), 431–447. https://doi.org/10.1007/s13555-020-00367-x
Li, X., Zheng, J., Pan, W.-L., Zheng, M., Lu, Y., Li, F.-Q., et al. (2022). Efficacy and safety of ixekizumab in Chinese patients with moderate-to-severe plaque psoriasis: 60-week results from a phase 3 study. International Journal of Dermatology and Venereology, 5(4).
Liu, L., Lu, J., Allan, B. W., Tang, Y., Tetreault, J., Chow, C.-K., et al. (2016). Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A. Journal of Inflammation Research, 9, 39–50. https://doi.org/10.2147/JIR.S100940
Lockshin, B., Cronin, A., Harrison, R. W., McLean, R. R., Anatale-Tardiff, L., Burge, R., et al. (2021). Drug survival of ixekizumab, TNF inhibitors, and other IL-17 inhibitors in real-world patients with psoriasis: The Corrona Psoriasis Registry. Dermatologic Therapy, 34(2), e14808. https://doi.org/10.1111/dth.14808
Mahil, S. K., Wilson, N., Dand, N., et al. (2020). Psoriasis treat to target: defining outcomes in psoriasis using data from BADBIR. The British Journal of Dermatology, 182(5), 1158–1166. https://doi.org/10.1111/bjd.18333
Morita, A., Okubo, Y., Morisaki, Y., et al. (2022). Ixekizumab 80 mg every 2 weeks treatment beyond week 12 for generalized pustular psoriasis and erythrodermic psoriasis. Dermatology and Therapy, 12(2), 481–494. https://doi.org/10.1007/s13555-021-00666-x
Paller, A. S., Seyger, M. M. B., Magariños, G. A., et al. (2020). Ixekizumab in pediatric patients (IXORA-PEDS). The British Journal of Dermatology, 183(2), 231–241. https://doi.org/10.1111/bjd.19147
Papp, K. A., Leonardi, C. L., Blauvelt, A., et al. (2018). Integrated efficacy analysis of UNCOVER studies. The British Journal of Dermatology, 178(3), 674–681. https://doi.org/10.1111/bjd.16050
Reich, K., Augustin, M., Thaçi, D., et al. (2020). Ixekizumab vs fumaric acid esters and methotrexate. The British Journal of Dermatology, 182(4), 869–879. https://doi.org/10.1111/bjd.18384
Saeki, H., Nakagawa, H., Nakajo, K., et al. (2017). Ixekizumab in Japanese psoriasis patients. Journal of Dermatology, 44(4), 355–362. https://doi.org/10.1111/1346-8138.13800
Strober, B., Leonardi, C., Papp, K. A., et al. (2017). Safety outcomes with ixekizumab. Journal of the American Academy of Dermatology, 76(3), 432–440. https://doi.org/10.1016/j.jaad.2016.09.037
Wasel, N., Thaçi, D., French, L. E., et al. (2020). IXORA-S nail psoriasis study. Dermatology and Therapy, 10(4), 663–670. https://doi.org/10.1007/s13555-020-00383-x
Ying, L., Suyun, J., Yanhua, L., et al. (2023). Observational study ixekizumab in Chinese adults. Advances in Therapy, 40(12), 5464–5474. https://doi.org/10.1007/s12325-023-02672-1
Armstrong, A. W., Warren, R. B., Zhong, Y., Zhuo, J., Cichewicz, A., Kadambi, A., Junqueira, D., Westley, T., Kisa, R., Daamen, C., & Augustin, M. (2023). Short-, mid-, and long-term efficacy of deucravacitinib versus biologics and nonbiologics for plaque psoriasis: A network meta-analysis. Dermatology and Therapy, 13(11), 2839–2857. https://doi.org/10.1007/s13555-023-01034-7
Blauvelt, A., Leonardi, C., Elewski, B., Crowley, J. J., Guenther, L. C., Gooderham, M., Langley, R. G., Vender, R., Pinter, A., Griffiths, C. E. M., Tada, Y., Elmaraghy, H., Lima, R. G., Gallo, G., Renda, L., Burge, R., Park, S. Y., Zhu, B., & Papp, K. (2021). A head-to-head comparison of ixekizumab vs. guselkumab in patients with moderate-to-severe plaque psoriasis: 24-week efficacy and safety results from a randomized, double-blinded trial. The British Journal of Dermatology, 184(6), 1047–1058. https://doi.org/10.1111/bjd.19509
Blauvelt, A., Shi, N., Burge, R., Malatestinic, W. N., Lin, C.-Y., Lew, C. R., Zimmerman, N. M., Goldblum, O. M., Zhu, B., & Murage, M. J. (2020). Comparison of real-world treatment patterns among patients with psoriasis prescribed ixekizumab or secukinumab. Journal of the American Academy of Dermatology, 82(4), 927–935. https://doi.org/10.1016/j.jaad.2019.11.015
Carretero, G., Puig, L., Carrascosa, J. M., Ferrándiz, L., Ruiz-Villaverde, R., de la Cueva, P., Belinchón, I., Vilarrasa, E., Del Río, R., Sánchez-Carazo, J. L., López-Ferrer, A., Peral, F., Armesto, S., Eiris, N., Mitxelena, J., Vilar-Alejo, J., A Martín, M., & Soria, C. (2018). Redefining the therapeutic objective in psoriatic patients candidates for biological therapy. The Journal of Dermatological Treatment, 29(4), 334–346. https://doi.org/10.1080/09546634.2017.1395794
Egeberg, A., Merola, J. F., Schäkel, K., Puig, L., Mahar, P. D., Wang, I. Y., Pavo, I., Schuster, C., & Griffiths, C. E. M. (2022). Efficacy of ixekizumab in patients with moderate-to-severe plaque psoriasis and prediabetes or type 2 diabetes. Frontiers in Medicine, 9, 1092688. https://doi.org/10.3389/fmed.2022.1092688
Egeberg, A., Wu, J. J., Korman, N., Solomon, J. A., Goldblum, O., Zhao, F., et al. (2018). Ixekizumab treatment shows a neutral impact on cardiovascular parameters in patients with moderate-to-severe plaque psoriasis: results from UNCOVER-1, UNCOVER-2, and UNCOVER-3. Journal of the American Academy of Dermatology, 79(1), 104–109. https://doi.org/10.1016/j.jaad.2018.02.045
Eisen, M., Hartmane, I., Kingo, K., Mikazans, I., Toomson, T., Toomela, K., & Valiukeviciene, S. (2025). The real-world burden of moderate-to-severe psoriasis in patients under systemic treatment from Baltic countries: Data from the CRYSTAL observational study. Medicina, 61(3). https://doi.org/10.3390/medicina61030397
Gordon, K. B., Blauvelt, A., Papp, K. A., Langley, R. G., Luger, T., Ohtsuki, M., et al. (2016). Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. The New England Journal of Medicine, 375(4), 345–356. https://doi.org/10.1056/NEJMoa1603532
Gorelick, J., Shrom, D., Sikand, K., Renda, L., Burge, R., Dworkin, C., et al. (2019). Understanding treatment preferences in patients with moderate to severe plaque psoriasis in the USA: results from a cross-sectional patient survey. Dermatologic Therapy, 9(4), 785–797. https://doi.org/10.1007/s13555-019-00324-3
Hartmane, I., Ivdra, I., Mikaž?ns, I., & Bondare-ansberga, V. (2021). Immunopathogenic treatment options for psoriasis patients under a restrictive reimbursement environment. Pro Litteris et Scientia, 75(3), 158–166. https://doi.org/10.2478/prolas-2021-0025
Honma, M., Cai, Z., Burge, R., Zhu, B., Yotsukura, S., & Torisu-Itakura, H. (2020). Relationship between rapid skin clearance and quality of life benefit: Post hoc analysis of Japanese patients with moderate-to-severe psoriasis treated with ixekizumab (UNCOVER-J). Dermatology and Therapy, 10(6), 1397–1404. https://doi.org/10.1007/s13555-020-00441-4
Langley, R. G., Papp, K., Gooderham, M., Zhang, L., Mallinckrodt, C., Agada, N., Blauvelt, A., Foley, P., & Polzer, P. (2018). Efficacy and safety of continuous every-2-week dosing of ixekizumab over 52 weeks in patients with moderate-to-severe plaque psoriasis in a randomized phase III trial (IXORA-P). The British Journal of Dermatology, 178(6), 1315–1323. https://doi.org/10.1111/bjd.16426
Leonardi, C., Matheson, R., Zachariae, C., Cameron, G., Li, L., Edson-Heredia, E., et al. (2012). Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. The New England Journal of Medicine, 366(13), 1190–1199. https://doi.org/10.1056/NEJMoa1109997
Leonardi, C., Reich, K., Foley, P., Torii, H., Gerdes, S., Guenther, L., et al. (2020). Efficacy and safety of ixekizumab through 5 years in moderate-to-severe psoriasis: Long-term results from UNCOVER-1 and UNCOVER-2. Dermatology and Therapy, 10(3), 431–447. https://doi.org/10.1007/s13555-020-00367-x
Li, X., Zheng, J., Pan, W.-L., Zheng, M., Lu, Y., Li, F.-Q., et al. (2022). Efficacy and safety of ixekizumab in Chinese patients with moderate-to-severe plaque psoriasis: 60-week results from a phase 3 study. International Journal of Dermatology and Venereology, 5(4).
Liu, L., Lu, J., Allan, B. W., Tang, Y., Tetreault, J., Chow, C.-K., et al. (2016). Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A. Journal of Inflammation Research, 9, 39–50. https://doi.org/10.2147/JIR.S100940
Lockshin, B., Cronin, A., Harrison, R. W., McLean, R. R., Anatale-Tardiff, L., Burge, R., et al. (2021). Drug survival of ixekizumab, TNF inhibitors, and other IL-17 inhibitors in real-world patients with psoriasis: The Corrona Psoriasis Registry. Dermatologic Therapy, 34(2), e14808. https://doi.org/10.1111/dth.14808
Mahil, S. K., Wilson, N., Dand, N., et al. (2020). Psoriasis treat to target: defining outcomes in psoriasis using data from BADBIR. The British Journal of Dermatology, 182(5), 1158–1166. https://doi.org/10.1111/bjd.18333
Morita, A., Okubo, Y., Morisaki, Y., et al. (2022). Ixekizumab 80 mg every 2 weeks treatment beyond week 12 for generalized pustular psoriasis and erythrodermic psoriasis. Dermatology and Therapy, 12(2), 481–494. https://doi.org/10.1007/s13555-021-00666-x
Paller, A. S., Seyger, M. M. B., Magariños, G. A., et al. (2020). Ixekizumab in pediatric patients (IXORA-PEDS). The British Journal of Dermatology, 183(2), 231–241. https://doi.org/10.1111/bjd.19147
Papp, K. A., Leonardi, C. L., Blauvelt, A., et al. (2018). Integrated efficacy analysis of UNCOVER studies. The British Journal of Dermatology, 178(3), 674–681. https://doi.org/10.1111/bjd.16050
Reich, K., Augustin, M., Thaçi, D., et al. (2020). Ixekizumab vs fumaric acid esters and methotrexate. The British Journal of Dermatology, 182(4), 869–879. https://doi.org/10.1111/bjd.18384
Saeki, H., Nakagawa, H., Nakajo, K., et al. (2017). Ixekizumab in Japanese psoriasis patients. Journal of Dermatology, 44(4), 355–362. https://doi.org/10.1111/1346-8138.13800
Strober, B., Leonardi, C., Papp, K. A., et al. (2017). Safety outcomes with ixekizumab. Journal of the American Academy of Dermatology, 76(3), 432–440. https://doi.org/10.1016/j.jaad.2016.09.037
Wasel, N., Thaçi, D., French, L. E., et al. (2020). IXORA-S nail psoriasis study. Dermatology and Therapy, 10(4), 663–670. https://doi.org/10.1007/s13555-020-00383-x
Ying, L., Suyun, J., Yanhua, L., et al. (2023). Observational study ixekizumab in Chinese adults. Advances in Therapy, 40(12), 5464–5474. https://doi.org/10.1007/s12325-023-02672-1
