Efficacy of Risankizumab versus Secukinumab in Patients with Moderate-to-Severe Psoriasis: Subgroup Analysis from the IMMerge Study

Jeffrey J Crowley, Richard G Langley, Kenneth B Gordon, Andreas Pinter, Laura K Ferris, Simone Rubant, Huzefa Photowala, Zhenyi Xue, Tianshuang Wu, Tianyu Zhan, Stefan Beeck, Megha Shah, Richard B Warren, Jeffrey J Crowley, Richard G Langley, Kenneth B Gordon, Andreas Pinter, Laura K Ferris, Simone Rubant, Huzefa Photowala, Zhenyi Xue, Tianshuang Wu, Tianyu Zhan, Stefan Beeck, Megha Shah, Richard B Warren

Abstract

Introduction: Patients with moderate-to-severe plaque psoriasis who experience poor clinical outcomes, including patients with obesity or prior treatment, need improved treatment options. Risankizumab specifically inhibits interleukin 23 and has demonstrated superior efficacy in active-comparator studies in patients with moderate-to-severe plaque psoriasis. We compared the efficacy of risankizumab with that of secukinumab across patient subgroups.

Methods: Subgroup analyses using data from the phase 3 IMMerge study (NCT03478787) were performed. Efficacy in adults with moderate-to-severe psoriasis treated with risankizumab 150 mg and secukinumab 300 mg was assessed as the proportion of patients who achieved ≥ 90% improvement in Psoriasis Area Severity Index (PASI 90) at week 52 across demographics and disease characteristics. Post hoc analyses evaluated the proportion of patients who achieved PASI 90 and the least-squares mean percent PASI improvement from baseline at week 52 by body weight and body mass index (BMI), PASI 90 by prior treatment, and clinical response [PASI 90, PASI 100, and/or static Physician's Global Assessment (sPGA) score of clear (0) or almost clear (1)] at week 16 and maintained particular response at week 52. Logistic regression analyses examined the effect of covariates (age, sex, BMI, baseline PASI, treatment) and potential interactions on PASI 90 at week 52.

Results: More patients who received risankizumab (n = 164) compared with secukinumab (n = 163) achieved PASI 90 at week 52, regardless of demographics and disease characteristics (BMI, prior treatment, disease duration, and maintenance of clinical response at week 52). Improvements in PASI were greater in patients taking risankizumab than those taking secukinumab, regardless of weight or BMI. Results from logistic regression analysis showed treatment type had a significant impact on PASI 90 (risankizumab versus secukinumab, p < 0.0001).

Conclusion: Risankizumab showed consistently greater efficacy compared with secukinumab across different patient subgroups, and this was maintained through 52 weeks.

Trial registration: ClinicalTrials.gov identifier; NCT03478787.

Keywords: Biologics; Prior psoriasis treatment; Psoriasis; Risankizumab; Secukinumab; Subgroup analysis; Weight.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Proportion of patients who achieved PASI 90 at week 52 by baseline demographics and disease characteristic subgroups (intent-to-treat population). BMI body mass index, PASI Psoriasis Area and Severity Index; PASI 90 ≥ 90% improvement in PASI, sPGA static Physician’s Global Assessment, 95% CI 95% confidence interval. aDuration of plaque psoriasis was not prespecified in the statistical analysis plan
Fig. 2
Fig. 2
Proportion of patients who achieved PASI 90 at week 52 by BMI categories, weight categories, and weight quartiles (NRI) (a), and with improvement in PASI 90 as LS mean percent change from baseline at week 52 (LOCF) (b). *p < 0.05, **p < 0.01,***p < 0.001 versus secukinumab. BMI body mass index, LS least squares, LOCF last observation carried forward, NRI nonresponder imputation, PASI 90 ≥ 90% improvement in Psoriasis Area and Severity Index, 95% CI 95% confidence interval
Fig. 3
Fig. 3
Proportion of patients who achieved PASI 90 at week 52 by prior treatment history (NRI) (a), type of treatment (b), and prior biologic treatment failure (c). IL interleukin, NRI nonresponder imputation, PASI 90 ≥ 90% improvement in Psoriasis Area and Severity Index, TNF tumor necrosis factor
Fig. 4
Fig. 4
Clinical response maintenance at week 52 for patients who achieved PASI 90 at week 16 and maintained their clinical response at week 52 (NRI). NRI nonresponder imputation, PASI 90/100 ≥ 90%/100% improvement in Psoriasis Area and Severity Index, sPGA 0/1 static Physician’s Global Assessment of clear (0) or almost clear (1)

References

    1. World Health Organization. Global report on psoriasis. Geneva, Switzerland: World Health Organization; 2016. Accessed May 6, 2020. .
    1. Warren RB, Kleyn CE, Gulliver WP. Cumulative life course impairment in psoriasis: patient perception of disease-related impairment throughout the life course. Br J Dermatol. 2011;164(suppl 1):1–14. doi: 10.1111/j.1365-2133.2011.10280.x.
    1. Bremmer S, Van Voorhees AS, Hsu S, Korman NJ, Lebwohl MG, Young M, et al. Obesity and psoriasis: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2010;63(6):1058–1069. doi: 10.1016/j.jaad.2009.09.053.
    1. Armstrong AW, Harskamp CT, Armstrong EJ. The association between psoriasis and obesity: a systematic review and meta-analysis of observational studies. Nutr Diabetes. 2012;2:e54. doi: 10.1038/nutd.2012.26.
    1. Mazzotta A, Esposito M, Costanzo A, Chimenti S. Efficacy and safety of etanercept in psoriasis after switching from other treatments: an observational study. Am J Clin Dermatol. 2009;10(5):319–324. doi: 10.2165/11310770-000000000-00000.
    1. Papp KA, Gordon KB, Langley RG, Lebwohl MG, Gottlieb AB, Rastogi S, et al. Impact of previous biologic use on the efficacy and safety of brodalumab and ustekinumab in patients with moderate-to-severe plaque psoriasis: integrated analysis of the randomized controlled trials AMAGINE-2 and AMAGINE-3. Br J Dermatol. 2018;179(2):320–328.
    1. Chiricozzi A, Gisondi P, Girolomoni G. The pharmacological management of patients with comorbid psoriasis and obesity. Expert Opin Pharmacother. 2019;20(7):863–872. doi: 10.1080/14656566.2019.1583207.
    1. Takeshita J, Grewal S, Langan SM, Mehta NN, Ogdie A, Van Voorhees AS, et al. Psoriasis and comorbid diseases: epidemiology. J Am Acad Dermatol. 2017;76(3):377–390. doi: 10.1016/j.jaad.2016.07.064.
    1. Lebwohl M, Yeilding N, Szapary P, Wang Y, Li S, Zhu Y, et al. Impact of weight on the efficacy and safety of ustekinumab in patients with moderate to severe psoriasis: rationale for dosing recommendations. J Am Acad Dermatol. 2010;63(4):571–579. doi: 10.1016/j.jaad.2009.11.012.
    1. Menter A, Papp KA, Gooderham M, Pariser DM, Augustin M, Kerdel FA, et al. Drug survival of biologic therapy in a large, disease-based registry of patients with psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR) J Eur Acad Dermatol Venereol. 2016;30(7):1148–1158. doi: 10.1111/jdv.13611.
    1. Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2) Lancet. 2008;371(9625):1675–1684. doi: 10.1016/S0140-6736(08)60726-6.
    1. Puig L. The role of IL 23 in the treatment of psoriasis. Expert Rev Clin Immunol. 2017;13(6):525–534. doi: 10.1080/1744666X.2017.1292137.
    1. Gooderham MJ, Papp KA, Lynde CW. Shifting the focus—the primary role of IL-23 in psoriasis and other inflammatory disorders. J Eur Acad Dermatol Venereol. 2018;32(7):1111–1119. doi: 10.1111/jdv.14868.
    1. Gaffen SL, Jain R, Garg AV, Cua DJ. The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing. Nat Rev Immunol. 2014;14(9):585–600. doi: 10.1038/nri3707.
    1. Krueger JG, Ferris LK, Menter A, Wagner F, White A, Visvanathan S, et al. Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2015;136(1):116–24.e7. doi: 10.1016/j.jaci.2015.01.018.
    1. Singh S, Kroe-Barrett RR, Canada KA, Zhu X, Sepulveda E, Wu H, et al. Selective targeting of the IL23 pathway: generation and characterization of a novel high-affinity humanized anti-IL23A antibody. MAbs. 2015;7(4):778–791. doi: 10.1080/19420862.2015.1032491.
    1. SKYRIZI. Prescribing information. AbbVie Inc.; 2021. . Accessed July1, 2021.
    1. Gordon KB, Strober B, Lebwohl M, Augustin M, Blauvelt A, Poulin Y, et al. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet. 2018;392(10148):650–661. doi: 10.1016/S0140-6736(18)31713-6.
    1. Ohtsuki M, Fujita H, Watanabe M, Suzaki K, Flack M, Huang X, et al. Efficacy and safety of risankizumab in Japanese patients with moderate to severe plaque psoriasis: results from the SustaIMM phase 2/3 trial. J Dermatol. 2019;46(8):686–694. doi: 10.1111/1346-8138.14941.
    1. Thaçi D, Eyerich K, Pinter A, Sebastian M, Unnebrink K, Rubant S, et al. Direct comparison of risankizumab and fumaric acid esters in systemic-therapy-naive patients with moderate to severe plaque psoriasis: a randomized controlled trial. Br J Dermatol. 2021 doi: 10.1111/bjd.20481.
    1. Reich K, Gooderham M, Thaçi D, Crowley JJ, Ryan C, Krueger JG, et al. Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial. Lancet. 2019;394(10198):576–586. doi: 10.1016/S0140-6736(19)30952-3.
    1. Ruggiero A, Fabbrocini G, Cinelli E, Megna M. Guselkumab and risankizumab for psoriasis: a 44-week indirect real-life comparison. J Am Acad Dermatol. 2021;85(4):1028–1030. doi: 10.1016/j.jaad.2021.01.025.
    1. Gkalpakiotis S, Cetkovska P, Arenberger P, Dolezal T, Arenbergerova M, Velackova B, et al. Risankizumab for the treatment of moderate-to-severe psoriasis: real-life multicenter experience from the Czech Republic. Dermatol Ther (Heidelb) 2021;11(4):1345–1355. doi: 10.1007/s13555-021-00556-2.
    1. Hansel K, Zangrilli A, Bianchi L, Peris K, Chiricozzi A, Offidani A et al. A 52-week update of a multicentre real-life experience on effectiveness and safety of risankizumab in psoriasis. J Eur Acad Dermatol Venereol. 2021.
    1. Blauvelt A, Reich K, Tsai T-F, Tyring S, Vanaclocha F, Kingo K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: results from the CLEAR study. J Am Acad Dermatol. 2017;76(1):60–9.e9. doi: 10.1016/j.jaad.2016.08.008.
    1. Warren RB, Blauvelt A, Poulin Y, Beeck S, Kelly M, Wu T, et al. Efficacy and safety of risankizumab vs secukinumab in patients with moderate-to-severe plaque psoriasis (IMMerge): results from a phase III, randomized, open-label, efficacy-assessor-blinded clinical trial. Br J Dermatol. 2021;184(1):50–59. doi: 10.1111/bjd.19341.
    1. Strober B, Menter A, Leonardi C, Gordon K, Lambert J, Puig L, et al. Efficacy of risankizumab in patients with moderate-to-severe plaque psoriasis by baseline demographics, disease characteristics and prior biologic therapy: an integrated analysis of the phase III UltIMMa-1 and UltIMMa-2 studies. J Eur Acad Dermatol Venereol. 2020;34(12):2830–2838. doi: 10.1111/jdv.16521.
    1. Dmitrienko A, D'Agostino RB., Sr Multiplicity considerations in clinical trials. N Engl J Med. 2018;378(22):2115–2122. doi: 10.1056/NEJMra1709701.
    1. Gordon K, Korman N, Frankel E, Wang H, Jahreis A, Zitnik R, et al. Efficacy of etanercept in an integrated multistudy database of patients with psoriasis. J Am Acad Dermatol. 2006;54(3 Suppl 2):S101–S111. doi: 10.1016/j.jaad.2005.11.1088.
    1. Naldi L, Addis A, Chimenti S, Giannetti A, Picardo M, Tomino C, et al. Impact of body mass index and obesity on clinical response to systemic treatment for psoriasis. Evidence from the Psocare project. Dermatology. 2008;217(4):365–373. doi: 10.1159/000156599.
    1. Clark L, Lebwohl M. The effect of weight on the efficacy of biologic therapy in patients with psoriasis. J Am Acad Dermatol. 2008;58(3):443–446. doi: 10.1016/j.jaad.2007.11.011.
    1. Papp KA, Langley RG, Sigurgeirsson B, Abe M, Baker DR, Konno P, et al. Efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase II dose-ranging study. Br J Dermatol. 2013;168(2):412–421. doi: 10.1111/bjd.12110.
    1. Singh S, Facciorusso A, Singh AG, Vande Casteele N, Zarrinpar A, Prokop LJ, et al. Obesity and response to anti-tumor necrosis factor-alpha agents in patients with select immune-mediated inflammatory diseases: a systematic review and meta-analysis. PLoS ONE. 2018;13(5):e0195123. doi: 10.1371/journal.pone.
    1. Papp KA, Reich K, Blauvelt A, Kimball AB, Gooderham M, Tyring SK, et al. Efficacy of tildrakizumab for moderate-to-severe plaque psoriasis: pooled analysis of three randomized controlled trials at weeks 12 and 28. J Eur Acad Dermatol Venereol. 2019;33(6):1098–1106. doi: 10.1111/jdv.15400.
    1. Lee JE, Wang J, Florian J, Wang YM, Kettl D, Marcus K, et al. Effect of body weight on risk-benefit and dosing regimen recommendation of secukinumab for the treatment of moderate to severe plaque psoriasis. Clin Pharmacol Ther. 2019;106(1):78–80. doi: 10.1002/cpt.1478.
    1. Reich K, Puig L, Szepietowski JC, Paul C, Lacour JP, Tsianakas A, et al. Secukinumab dosing optimization in patients with moderate-to-severe plaque psoriasis: results from the randomized, open-label OPTIMISE study. Br J Dermatol. 2020;182(2):304–315. doi: 10.1111/bjd.18143.
    1. Feldman SR, Zhao Y, Navaratnam P, Friedman HS, Lu J, Tran MH. Patterns of medication utilization and costs associated with the use of etanercept, adalimumab, and ustekinumab in the management of moderate-to-severe psoriasis. J Manag Care Spec Pharm. 2015;21(3):201–209.
    1. Menter A, Strober BE, Kaplan DH, Kivelevitch D, Prater EF, Stoff B, et al. Joint AAD–NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol. 2019;80(4):1029–1072. doi: 10.1016/j.jaad.2018.11.057.
    1. Warren RB, Smith CH, Yiu ZZN, Ashcroft DM, Barker J, Burden AD, et al. Differential drug survival of biologic therapies for the treatment of psoriasis: a prospective observational cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR) J Invest Dermatol. 2015;135(11):2632–2640. doi: 10.1038/jid.2015.208.
    1. Megna M, Fabbrocini G, Ruggiero A, Cinelli E. Efficacy and safety of risankizumab in psoriasis patients who failed anti-IL-17, anti-12/23 and/or anti IL-23: preliminary data of a real-life 16-week retrospective study. Dermatol Ther. 2020;33(6):e14144.
    1. A study of the safety and efficacy of risankizumab in adult participants with plaque psoriasis who have had a suboptimal response to secukinumab or ixekizumab. identifier: NCT04102007 [Internet]. Available from: . Cited 10 Dec 2021.

Source: PubMed

3
Iratkozz fel