Comparison between brodalumab, secukinumab and ixekizumab effectiveness and drug survival: A real‐life experience on 638 patients with psoriasis

Psoriasis is an inflammatory skin disease with an important impact worldwide; its treatment comprises biological therapies targeting specific immune cytokines, such as interleukin-17.1, 2 Three molecules targeting this cytokine have been used over the years. Differences in pharmacodynamics and pharmacokinetics are responsible for differences in therapeutic efficacy. Studies directly comparing the long-term efficacy of the three available anti-IL17 agents is still lacking.3-5 We performed a retrospective real-life study to compare the effectiveness and drug survival (DS) of brodalumab, secukinumab, ixekizumab in patients with moderate-to-severe psoriasis attending the Dermatology Clinic of the Turin University Hospital, from 1 January 2015 to 1 June 2022. Severity of disease was measured by the psoriasis area severity index (PASI). PASI improvement of 90%, 100% and PASI <3 was registered for each on-treatment patient at 12, 24 and 48 weeks. DLQI response rates were collected at baseline and after 48 weeks of treatment. Survival curves were evaluated using Kaplan–Meier curves and compared using log-rank tests only for patients at risk of discontinuation. Statistical analysis of observed cases was conducted without imputation of therapeutic discontinuation. Data are presented as mean and standard deviation for continuous variables and as percentage and number for categorical variables. Statistical analysis was carried out using ANOVA model for continuous variables, followed by Bonferroni's test and chi-square test for comparison of categorical variables with significance at p < 0.05. Fisher's exact test was used as appropriate for comparison of categorical variables. Analysis of effectiveness was conducted on observed cases for each timepoint (i.e. only surviving subjects) without imputation of discontinuations. We then conducted a multivariate analysis with logistic regression model for achievement of PASI90, <3 and 100 according to treatments, mean BMI, mean age, mean baseline PASI, sex, joint involvements and bio-naïve status. Table 1 summarises the characteristics of the cohort. Of 638 patients, 255 were treated with secukinumab, 189 with ixekizumab and 194 with brodalumab. Significant differences were found in mean DLQI and PASI at T0; the ixekizumab subgroup showed the lowest DLQI (p < 0.001), and brodalumab the lowest PASI at baseline (p < 0.001), which could have reduced the interpretation of data for PASI <3 achievements. No differences in terms of overall PASI improvement were found at Week 12 among the three groups, while at Week 24 brodalumab showed a significantly lower PASI compared to the other subgroups (p < 0.003). DS analysis shows no difference in the three treatment groups (p = 0.159) (Figure 1, Figure S1). At the analysis of the standardised response rates (Table 1), ixekizumab was superior to secukinumab for PASI100, PASI <3 and PASI90 at Week 12 (p = 0.012, 0.005, 0.001), at Week 24 it was superior for PASI <3 and PASI90 (p = 0.009 and 0.022), and at Week 48 it was superior for PASI100, PASI <3 and PASI90 (p = 0.008, 0.046, 0.017). Brodalumab was superior to secukinumab at Week 12 for PASI100, PASI <3 and PASI90 (p = 0.019, <0.001, <0.001, respectively) and superior to secukinumab at Week 24 for PASI100, PASI <3 and PASI90 (p = 0.019, <0.001, 0.001, respectively). No significant differences between brodalumab and ixekizumab were observed (Table 1). DLQI reduction from baseline to Week 48 is higher for the ixekizumab group than the secukinumab one (p: 0.04). At Week 48, 76% of patients on brodalumab showed a DLQI≤1 versus 65% of patients on ixekizumab and 57% of patients on secukinumab (p = 0.037). The subanalysis of the bio-naïve population in Table 1 confirms the trend that brodalumab is superior to ixekizumab and secukinumab in achieving PASI<3 at 12 weeks (88% vs. 76% and 63%, p = 0.027 and p = <0.001, respectively), with superiority maintained up to Week 24 compared to secukinumb and then progressively lost. Ixekizumab appears to be superior to secukinumab at Weeks 12 and 48 and superior to brodalumab for PASI<3 at Week 48 (95% vs. 83% p = 0.031). (Table 1). At multivariate analysis of achieving PASI100, PASI90 and PASI <3 at Week16, considering the three treatments, age, gender, BMI, associated arthropathy and naïve status, brodalumab was superior to secukinumab in all outcomes (odds ratio [OR] 1.56, CI 1.03–2.35; OR 2.31, CI 1.51–3.53; OR 2.32, CI 1.46–3.53, respectively), ixekizumab was superior for PASI100 (OR 1.75, CI 1.18–2.6), PASI90 (OR 1.76, CI 1.18–2.62) and PASI <3 (OR 1.96, CI 1.28–3.02) (Table S1). To our knowledge, this is one of the few studies comparing these three IL-17 inhibitors indirectly in terms of effectiveness and DS. The data on effectiveness is in line with the few indirect comparisons in the literature.1, 6 The same consideration can be made on the quality of life with brodalumab, achieving DLQI 0/1 more frequently than the other two treatments, although with only 51 patients observed. Different mean PASI at baseline among the treatments limits the evidence on achievement of PASI <3 at earlier time points, and the analysis of observed cases reduces the strength of evidence. Concerning DS, the nature of a retrospective real-life analysis for only patients at risk of discontinuation for each timepoint also reduces the strength of evidence. Nonetheless, these inherent limitations are shared with other similar studies.7-9 Our data are in line with the few studies in the literature except for the recent work by Torres et al. which showed the superiority of ixekizumab over secukinumab only at 48 months, a timepoint that was not recorded in our study.7-9 LM wrote the paper, performed the research, designed the research study, analysed the data, SS, CC, NS, AV, ES, MO performed the research, PQ contributed essential reagents tools, PD contributed essential reagents tools and performed the research, SR designed the research study, analysed the data and contributed essential reagents tools. None. None. The authors have declared no conflicts of interest. All patients signed written consent. Data available upon reasonable request. Figure S1. Drug survival of secukinumab, ixekizumab, and brodalumab with Kaplan–Meier curves only for patients at risk for each timepoint, with the number of patients at risk for each treatment at each time point. Table S1. Multivariate analysis for PASI100, 90 and <3 at 16 weeks according to biological treatments, mean age, sex, mean BMI, difficult-site-involvement, PsA, bio-naïve status, mean baseline PASI. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.