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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蔡呈芳(Tsen Fang Tsai) | |
| dc.contributor.author | Tzu Chui | en |
| dc.contributor.author | 崔慈 | zh_TW |
| dc.date.accessioned | 2021-06-16T05:28:40Z | - |
| dc.date.available | 2020-08-26 | |
| dc.date.copyright | 2020-08-26 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-07-30 | |
| dc.identifier.citation | Bilal, J., Berlinberg, A., Bhattacharjee, S., Trost, J., Riaz, I. B., Kurtzman, D. J. B. (2018). A systematic review and meta-analysis of the efficacy and safety of the interleukin (IL)-12/23 and IL-17 inhibitors ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab and tildrakizumab for the treatment of moderate to severe plaque psoriasis. J Dermatolog Treat, 29(6), 569-578. doi:10.1080/09546634.2017.1422591 Blauvelt, A., Papp, K. A., Griffiths, C. E., Randazzo, B., Wasfi, Y., Shen, Y. K., . . . Kimball, A. B. (2017). Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol, 76(3), 405-417. doi:10.1016/j.jaad.2016.11.041 Gordon, K. B., Strober, B., Lebwohl, M., Augustin, M., Blauvelt, A., Poulin, Y., . . . et al. (2018). 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 (london, england), 392(10148), 650‐661. doi:10.1016/S0140-6736(18)31713-6 Gottlieb, A. B., Saure, D., Wilhelm, S., Dossenbach, M., Schuster, C., Smith, S. D., . . . Thaci, D. (2020). Indirect comparisons of ixekizumab versus three interleukin-23 p19 inhibitors in patients with moderate-to-severe plaque psoriasis - efficacy findings up to week 12. J Dermatolog Treat, 1-8. doi:10.1080/09546634.2020.1747592 Harden, J. L., Krueger, J. G., Bowcock, A. M. (2015). The immunogenetics of Psoriasis: A comprehensive review. J Autoimmun, 64, 66-73. doi:10.1016/j.jaut.2015.07.008 Howell, S. T., Cardwell, L. A., Feldman, S. R. (2018). Treating Moderate-to-Severe Plaque Psoriasis With Guselkumab: A Review of Phase II and Phase III Trials. Ann Pharmacother, 52(4), 380-387. doi:10.1177/1060028017743268 Hsu, S. H., Tsai, T. F. (2020). Evolution of the inclusion/exclusion criteria and primary endpoints in pivotal trials of biologics and small oral molecules for the treatment of psoriasis. Expert Rev Clin Pharmacol. doi:10.1080/17512433.2020.1743175 Huang, P. H., Liao, Y. H., Wei, C. C., Tseng, Y. H., Ho, J. C., Tsai, T. F. (2008). Clinical effectiveness and safety experience with alefacept in the treatment of patients with moderate-to-severe chronic plaque psoriasis in Taiwan: results of an open-label, single-arm, multicentre pilot study. J Eur Acad Dermatol Venereol, 22(8), 923-930. doi:10.1111/j.1468-3083.2007.02575.x Kolli, S. S., Gabros, S. D., Pona, A., Cline, A., Feldman, S. R. (2019). Tildrakizumab: A Review of Phase II and III Clinical Trials. Ann Pharmacother, 53(4), 413-418. doi:10.1177/1060028018809522 Kurd, S. K., Gelfand, J. M. (2009). The prevalence of previously diagnosed and undiagnosed psoriasis in US adults: results from NHANES 2003-2004. J Am Acad Dermatol, 60(2), 218-224. doi:10.1016/j.jaad.2008.09.022 Langley, R. G. (March, 2019). Efficacy and Safety of Continuous Q12W Risankizumab versus Treatment Withdrawal: Results from the Phase 3 IMMhance Trial Ohtsuki, M., Fujita, H., Watanabe, M., Suzaki, K., Flack, M., Huang, X., . . . Igarashi, A. (2019). Efficacy and safety of risankizumab in Japanese patients with moderate to severe plaque psoriasis: Results from the SustaIMM phase 2/3 trial. J Dermatol, 46(8), 686-694. doi:10.1111/1346-8138.14941 Ohtsuki, M., Kubo, H., Morishima, H., Goto, R., Zheng, R., Nakagawa, H. (2018). Guselkumab, an anti-interleukin-23 monoclonal antibody, for the treatment of moderate to severe plaque-type psoriasis in Japanese patients: Efficacy and safety results from a phase 3, randomized, double-blind, placebo-controlled study. J Dermatol, 45(9), 1053-1062. doi:10.1111/1346-8138.14504 Papp, K., Thaci, D., Reich, K., Riedl, E., Langley, R. G., Krueger, J. G., . . . Shames, R. (2015). Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br J Dermatol, 173(4), 930-939. doi:10.1111/bjd.13932 Papp, K. A., Blauvelt, A., Bukhalo, M., Gooderham, M., Krueger, J. G., Lacour, J. P., . . . Padula, S. J. (2017). Risankizumab versus Ustekinumab for Moderate-to-Severe Plaque Psoriasis. N Engl J Med, 376(16), 1551-1560. doi:10.1056/NEJMoa1607017 Reich, K., Armstrong, A. W., Foley, P., Song, M., Wasfi, Y., Randazzo, B., . . . Gordon, K. B. (2017). Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol, 76(3), 418-431. doi:10.1016/j.jaad.2016.11.042 Reich, K., Papp, K. A., Blauvelt, A., Tyring, S. K., Sinclair, R., Thaci, D., . . . Kimball, A. B. (2017). Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. Lancet, 390(10091), 276-288. doi:10.1016/s0140-6736(17)31279-5 Tsai, T. F., Wang, T. S., Hung, S. T., Tsai, P. I., Schenkel, B., Zhang, M., Tang, C. H. (2011). Epidemiology and comorbidities of psoriasis patients in a national database in Taiwan. J Dermatol Sci, 63(1), 40-46. doi:10.1016/j.jdermsci.2011.03.002 Tsai, T. F., 乾癬與皮膚疾病的免疫生物製劑治療. 景福醫訊第35卷第9期 2018 年 9月 Tzellos, T., Kyrgidis, A., Trigoni, A., Zouboulis, C. C. (2012). Association of ustekinumab and briakinumab with major adverse cardiovascular events: An appraisal of meta-analyses and industry sponsored pooled analyses to date. Dermatoendocrinol, 4(3), 320-323. doi:10.4161/derm.23100 WHO. (2016). Global report on psoriasis <9789241565189_eng.pdf>. Xu, S. S., Zhang, X. Y., Pan, M. J., Shuai, Z. W., Xu, S. Q., Pan, F. M. (2019). Treatment of plaque psoriasis with IL-23p19 blockers: A systematic review and meta-analysis. International Immunopharmacology, 75. doi:10.1016/j.intimp. 2019.105841 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/56439 | - |
| dc.description.abstract | 目的: 使用介白素23p19抑制劑在中度至重度斑塊型乾癬病患的感染副作用之統合分析。 研究方法: 藉由先定義的標準進行文獻回顧.使用介白素-23 抑制劑之雙盲、 隨機並使用安慰劑做為控制組的臨床試驗，收集並分析不良事件中的感染事件集合的數據來自於Risankizumab、Guselkumab 和 Tildrakizumab這些文獻利用數據資料計算風險比 與其95 %信賴區間和0.05 的雙尾統計。 統計分析基本上是以積極治療為原則 ，比較治療組 (IL23p19)與安慰劑組之間的感染事件並使用CMA 3.0版 的軟體 做為分析工具。 結果: 共有八篇文獻中的十個 隨機, 安慰劑控制的臨床試驗被納入這個統合分析。就不良事件的發生率 (RR:0.961, 95% CI: 0.899- 1.027, P=0.237) 和嚴重不良事件(RR: 0.782, 95% CI: 0.479-1.276, P=0.325) 而言， 介白質-23p19 抑制劑與安慰劑具有相似的安全性.但是若比較介白質-23p19 抑制劑與安慰劑之感染與主要心血管事件的不良事件, 使用介白質-23p19 抑制劑之感染的風險比是1.136 (RR: 1.136, 95% CI 0.999- 1.291, P=0.051) 。使用生物制劑 (IL23p19 inhibitors之主要心血管事件的風險比是0.890 ( RR: 0.890, 95% CI 0.181- 4.389, P=0.887) 。 分別分析個別介白素-23 抑制劑相較於安慰劑組有關之嚴重不良事件的數據發現: Guselkumab，相較其他兩組IL23抑制劑有較高的風險, (RR 1.463, 95% CI 0.599~3.074, P=0.404) ，因不良事件導致受試者退出臨床試驗相較安慰劑組的風險比例為 RR: 0.242, (RR 0,242, 95% CI 0.105~0.559, P: 0.001) ，使用IL23抑制劑雖然有較高的感染風險，但相較於安慰劑組卻也有效的減少大約76%受試者因不良事件退出試驗的風險。 結論: 當比較斑塊型乾癬病患使用 IL23抑制劑與安慰劑16 週後發現 ，IL23 生物製劑可能與14%增加感染風險有關。雖然兩者的主要心血管事件的風險並無統計學上的意義，但是IL23抑制劑的長期安全仍有待評估。 | zh_TW |
| dc.description.abstract | Objective: To systematically analyze the safety of Interleukin (IL)-23p19 blockers in patient with moderate to severe plaque psoriasis. Method: The literature review was performed on the predefined criteria. The searching keywords included Guselkumab, Risankizumab, and Tildrakizumab. The Interleukin (IL)-23 blocker double blind, randomization and placebo control trials were collected and the infection events in the adverse events were identified. The pooled data were from clinical trials of Guselkumab, Risankizumab, and Tildrakizumab. The Risk Ratio with 95% confidence interval (CI) and 2-sided statistical significance level of 0.05 were calculated. The statistical analysis was basically used on intend to treat; it compared the infection events between treated group and placebo group with the software of Comprehensive Meta-analysis (CMA) version 3.0. Result: A total of 10 randomized placebo-controlled trials from 8 papers were included in this meta-analysis. The IL23p19 inhibitor had similar safety results with placebos in the incidence of adverse event (AE) (RR:0.961, 95% CI: 0.899- 1.027, P=0.237) and severe adverse event (SAE) (RR: 0.782, 95% CI: 0.479-1.276, P=0.325). But the comparison of the adverse events in infection and Major Cardio-Vascular Event (MACE) between the IL23 blockers and placebo group shows that Risk Ratio (RR) of infection is 1.136 (RR: 1.136, 95% CI 0.999- 1.291, P= 0.051) in participants treated with IL23 blockers versus the placebo group. The calculated RR of MACE among the biologics is 0.890 (RR: 0.890, 95% CI 0.181- 4.389, P=0.887) in participants treated with IL23 blockers, compared to the placebo group. Separately analyzing the data of SAE on each IL 23 blockers versus placebo groups revealed that Guselkumab, with a RR of 1.463, (RR 1.463, 95% CI 0.599~3.074, P=0.404) is the highest, compared to others. The subjects discontinuing from the studies due to adverse event had RR of 0.242, (RR 0,242, 95% CI 0.105~0.559, P: 0.001). Conclusion: While comparing IL-23 blockers and placebo within 16 weeks in plaque psoriasis participants treated with IL23 biologics, they may associate with 14% increased risk of infection. Although the RR of MACE is non-statistically significant, long-term safety remains to be determined. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T05:28:40Z (GMT). No. of bitstreams: 1 U0001-2607202023094800.pdf: 3201636 bytes, checksum: 0c77668b900b17da9ead160d5c25f1b6 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 口試委員會審定書 I 致謝 II 目錄 III 中文摘要 IX SYNOPSIS XI THE INFECTIOUS COMPLICATION OF IL-23P19 BLOCKERS FOR PLAQUE PSORIASIS: A META-ANALYSIS PROTOCOL 1 1. Introduction 1 2. Method: 3 3. Result 5 4. Discussion 7 5. Conclusion 9 6. PROSPECTIVE: PLEASE REFER TO PROTOCOL (APPENDIX A.) 9 7. REFERENCE: 10 8. TABLE 14 Table1. 14 9. FIGURE 15 FIG. 1. PSORIASIS PATHOGENESIS 15 FIG.2. 15 Fig 3. 16 Fig. 4. 17 Fig. 5. 17 Fig. 6. 18 Fig. 7. 18 Fig. 8. 19 Fig. 9. 20 Fig. 10. 20 Fig. 11. 21 Fig.12 21 Fig. 13. 22 Fig. 14 22 APPENDIX A. PROTOCOL 23 1.0 Synopsis 25 2.0 TABLE OF CONTENTS 34 3.0 INTRODUCTION 37 3.1 Differences Statement 40 3.2 Benefits and Risks 40 4.0 STUDY OBJECTIVE 41 5.0 INVESTIGATIONAL PLAN 41 5.1 Overall Study Design and Plan: Description 41 Screening Visit 42 Treatment Period 42 End of Observation Visit 43 5.2 Selection of Study Population 43 5.2.2 Exclusion Criteria 44 5.2.3 Prohibited Therapy 45 5.2.4 Contraception Recommendations and Pregnancy Testing 45 5.3 Efficacy and Safety assessments/ variables 47 5.3.1.1 Study Procedures 47 Inclusion/Exclusion Criteria 47 Demographics 47 Medical and Surgical History 48 Physical Examination 48 Vital Signs Assessment 48 Body Weight 48 12-Lead Electrocardiogram (ECG) 49 Psoriasis Area and Severity Index (PASI) Evaluation 49 Static Physician Global Assessment (sPGA) 49 Psoriasis Scalp Severity Index (PSSI) 50 Dermatology Life Quality Index (DLQI) 50 Pregnancy Testing 50 Laboratory Testing 51 Table 1. Clinical Laboratory Tests 52 Tuberculosis Testing 54 Monitoring Adverse Events 54 Prior and Concomitant Therapy Assessment 54 Local Tolerability Assessment 55 Study Drug Administration 55 Monitoring for Hypersensitivity Reactions 56 5.3.2 Sample Managements 56 5.3.2.1 Handling/Processing of Samples 56 5.3.2.2 Disposition of Samples 56 5.3.3 Safety Variables 56 5.3.4 Efficacy Variables 56 5.3.4.2 Additional Variables 57 5.4 Removal of Subjects from Therapy or Assessment 57 5.5 Treatments 59 5.5.2 Identity of Investigational Product (IP) 60 Table 2. Identity of Investigational Product 60 5.5.2.2 Storage and Disposition of Study Drug 61 5.5.3 Method of Assigning Subjects to Treatment Groups 61 5.5.4 Selection and Timing of Dose for Each Subject 61 5.5.5 Drug Accountability 62 5.6 Discussion and Justification of Study Design 63 5.6.2 Appropriateness of Measurements 63 5.6.3 Suitability of Subject Population 63 6.0 COMPLAINTS 63 6.1 Medical Complaints 64 6.1.1 Definitions 64 6.1.1.2 Serious Adverse Events 65 6.1.1.3 Adverse Events of Special Interest 67 6.1.2 Adverse Event Severity 68 6.1.3 Relationship to Study Drug 68 Reasonable Possibility 68 6.1.4 Adverse Event Collection Period 69 Figure 2. Adverse Event Collection 69 6.1.6 Pregnancy 70 6.2 Reporting 70 7.0 PROTOCOL DEVIATIONS 71 8.0 STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE 71 8.1 Statistical and Analytical Plans 71 8.1.1 Analysis Populations 72 8.1.2 Planned Methods of Statistical Analysis 72 8.1.3 Demographics and Baseline Characteristics 72 8.1.4 Safety Analysis 72 i. Data Monitoring Committee 73 ii. Major Cardio-Vascular Event Committee 73 8.1.5 Statistical Analysis of Efficacy 74 8.1.6 a. Interim Analysis 75 b. Determination of Sample Size 75 9.0 ETHICS 77 9.1 Independent Ethics Committee (IEC) or Institutional Review Board (IRB) 77 9.2 Ethical Conduct of the Study 77 9.3 Subject Information and Consent 78 9.3.1 Informed Consent Form and Explanatory Material 78 10.0 SOURCE DOCUMENTS AND CASE REPORT FORM COMPLETION 79 10.1 Source Documents 79 10.2 Case Report Forms 79 11.0 DATA QUALITY ASSURANCE 80 12.0 USE OF INFORMATION 80 13.0 COMPLETION OF THE STUDY 81 14.0 Responsibilities of the Clinical Investigator 82 15.0 Reference List 83 Appendix A. Study Activities Flow Chart 86 Appendix B Study Procedures 89 Tuberculosis Screening 89 Appendix C. Psoriasis Area and Severity Index (PASI) 90 Appendix D. Static Physician Global Assessment (sPGA) 93 Appendix E. Psoriasis Scalp Severity Index (PSSI) 95 | |
| dc.language.iso | en | |
| dc.subject | 介白素23p19抑制劑 | zh_TW |
| dc.subject | Guselkumab | zh_TW |
| dc.subject | Risankizumab | zh_TW |
| dc.subject | Tildrakizumab | zh_TW |
| dc.subject | 斑塊型乾癬 | zh_TW |
| dc.subject | 安全性概況 | zh_TW |
| dc.subject | 感染 | zh_TW |
| dc.subject | 重大心血管事件 | zh_TW |
| dc.subject | 統合分析 | zh_TW |
| dc.subject | plaque psoriasis | en |
| dc.subject | IL23 Inhibitors | en |
| dc.subject | cardiovascular events | en |
| dc.subject | safety profile | en |
| dc.subject | Guselkumab | en |
| dc.subject | meta-analysis | en |
| dc.subject | infection | en |
| dc.subject | Risankizumab | en |
| dc.subject | Tildrakizumab | en |
| dc.title | 使用介白素23p19抑制劑治療斑塊型乾癬其感染副作用之統合分析 | zh_TW |
| dc.title | The infectious complication of IL-23p19 blockers for plaque psoriasis: A meta-analysis protocol | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林家齊(Chia Chi Lin),李婉若(Woan Ruoh Lee) | |
| dc.subject.keyword | 介白素23p19抑制劑,Guselkumab,Risankizumab,Tildrakizumab,斑塊型乾癬,安全性概況,感染,重大心血管事件,統合分析, | zh_TW |
| dc.subject.keyword | IL23 Inhibitors,Guselkumab,Risankizumab,Tildrakizumab,plaque psoriasis,safety profile,cardiovascular events,infection,meta-analysis, | en |
| dc.relation.page | 95 | |
| dc.identifier.doi | 10.6342/NTU202001878 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-07-31 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 臨床醫學研究所 | zh_TW |
| 顯示於系所單位： | 臨床醫學研究所 | |
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