Interleukin-17 (IL-17) and IL-23 are key drivers of psoriasis pathogenesis and are the primary targets of psoriasis biologics therapy. At present, four IL-17 inhibitors (secukinumab, brodazumab, ixekizumab, bimegizumab) and three IL-23 inhibitors (guselkumab, tirelizumab, ressacizumab) have been approved for marketing by the European Medicines Agency and the US Food and Drug Administration, and clinical trials have shown good efficacy. Drug survival is often used to assess drug performance, but there is a lack of reviews on drug survival for newer biologics (IL-17 and IL-23 inhibitors). Therefore, this review and meta-analysis aimed to assess drug survival after the use of IL-17 and IL-23 inhibitors in patients with psoriasis.
Research Methods:
The authors conducted a comprehensive search of relevant articles in PubMed, Embase, the Cochrane Library and Web of Science (last search date 27 December 2023). Relevant studies were screened using Rayyan software and the inclusion criteria were: (1) cohort studies, (2) patients with plaque psoriasis ≥ 18 years of age, and (3) at least one IL-17 or 23 inhibitor, including: secukinumab, ixekizumab, brodalumab, risalizumab, guselkumab, and tirelizumab. Exclusion criteria were: (1) studies primarily of people with psoriatic arthritis, (2) fewer than 10 participants, and (3) use of a language other than English.
The primary endpoint of the study was drug survival, and the subgroup analyses were: registration/electronic health record data and pharmacy/claims data-. According to different reasons for discontinuation, the summary curves of drug survival of different biologics were mainly divided into three categories: (1) drug survival due to discontinuation due to ineffective treatment-, (2) drug survival due to discontinuation due to adverse events, and (3) the total drug survival of the above two combined. Biologics-naïve treatment is an important factor affecting drug survival, so drug survival data from patients who have not been treated with biologics and who have experience with biologics were extracted for analysis. In addition, the overall drug survival and treatment-ineffective drug survival of different biologics at 1, 2 and 3 years were directly compared and expressed as differences in drug survival estimates and 95% CIs.
Findings:
Sixty-nine studies with 48,704 patients were included. Among them, 47 articles reported secukinumab (n=23960), 31 articles reported ixekizumab (n=12446), 13 articles reported brodalumab (n=2353), 24 articles reported guselkumab (n=8174), 7 articles reported risakizumab (n=1427), and 4 articles reported tirelizumab (n=304).
Registration/electronic health record data
The extracted register/electronic health record data were obtained from medical records (42 studies; 11,365 patients) and patient registries (13 studies; 10,154 patients) from 29 different countries (mainly in Europe). Drug survival estimates (SSEs) were higher for overall drug survival for all included biologics (e.g., SSE ≥ 0.8 at year 1). (See Table 1, Figures 1 and 2). Drug survival estimates were higher in patients who had not been treated with biologics than in patients with the same-biologics experience. Risakizumab showed the highest SSE in terms of overall drug survival at 1, 2, and 3 years (0.86 for all SSE>s). Guselkumab had the highest SSE for almost all drug survival outcomes.
Table 1: Total drug survival estimates (95% confidence interval) for each drug survival outcome
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Figure 1: Nonparametric random-effects total drug survival curves, 95% confidence intervals for overall survival
Note: Blue is the total drug survival curve, gray is the individual study, A: secukinumab, B: ixekizumab, C: brodazumab, D: guselkumab, E: risalizumab, F: tirelizumab
Figure 2: Non-parametric random-effects total drug survival curve, 95% confidence interval for ineffective related drug survival
Note: Blue is the total drug survival curve, gray is the individual study, A: secukinumab, B: ixekizumab, C: brodalumab, D: guselkumab, E: risalizumab
Pharmacy/claims data
Data were obtained from 14 pharmacy/claims database studies (27,521 patients) in 9 different countries, mostly in North America. The SSE for pharmacy/claims data in years 1 and 2 is lower compared to SSE for registration/electronic health record data.
Research Discussion
Previous systematic reviews and meta-analyses of the efficacy of biologics for psoriasis were conducted at specific time points (e.g., 1 and 2 years), which resulted in under-represented studies reporting drug survival at other time points. To overcome this limitation, this study used the Combescure method, which allows for the inclusion of a complete drug survival curve.
Efficacy-related survival estimates (including those related to treatment failure) were similar for secukinumab, ixekizumab, and brodalumab, but the survival of treatment-related drugs was significantly higher with ixekizumab than with secukinumab at year 3, suggesting that patients taking ixekizumab were less likely to discontinue due to ineffectiveness than those taking secukinumab. Risakizumab had the highest SSE in terms of overall drug survival at 1 year, 2 years, and 3 years. Compared with other biologics, guselkumab had the highest SSE for overall drug survival at 1 year, 2 years, and 3 years. Drug survival was higher in biologic-naïve patients than in biologics-treated patients. The estimates for the pharmacy/claims databases are significantly lower compared to the total drug survival estimates in the registered/electronic health record databases.
Conclusions of the study
Psoriasis patients had higher drug survival after the use of IL-17 and IL-23 inhibitors, with guselkumab and risalizumab having the highest drug survival.
Bibliography:
Thomas SE, Barenbrug L, Hannink G, Seyger MMB, de Jong EMGJ, van den Reek JMPA. Drug Survival of IL-17 and IL-23 Inhibitors for Psoriasis: A Systematic Review and Meta-Analysis. Drugs. 2024 Apr 17. doi: 10.1007/s40265-024-02028-1. Epub ahead of print. PMID: 38630365.