Efficacy of pidotimod in children: a systematic review based on 310 RCTs_Chinese Journal of Evidence-Based Medicine

Authors：

YI Qiusha ^1,2,3,4 , YANG Chunsong ^1,2,3 , ZENG Linan ^1,2,3 , CHEN Lina ⁶ , QIAO Lina ⁷ , HUANG Liang ^1,2,3 , SONG Haoxin ^1,2,3,5 , LIN Mao ^1,2,3,5 , LI Wenrui ^1,2,3,5 , MI Xue ^1,2,3,4 ,  ZHANG Lingli ^1,2,3

1. Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, 610041, P.R.China;
2. Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, 610041, P.R.China;
3. Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, 610041, P.R.China;
4. West China School of Medicine, Sichuan University, Chengdu, 610041, P.R.China;
5. West China School of Pharmacy, Sichuan University, Chengdu, 610041, P.R.China;
6. Department of Pediatric Respiratory Immunology, West China Second University Hospital, Sichuan University, Chengdu, 610041, P.R.China;
7. Department of Pediatric Intensive Care Unit, West China Second University Hospital, Sichuan University, Chengdu, 610041, P.R.China;

Corresponding?author：

ZHANG Lingli, Email: zhanglingli@scu.edu.cn

Keywords：

Children; Pidotimod; Meta-analysis; Systematic review; Randomized controlled trial

DOI：

10.7507/1672-2531.201810058

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Objective To systematically review the efficacy of pidotimod in children.Methods PubMed, The Cochrane Library, EMbase, CNKI, CBM, VIP and WanFang Data databases were searched online to collect randomized controlled trials (RCTs) on pidotimod in children from inception to January, 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software.Results A total of 310 RCTs involving 30 525 children were included. The results of meta-analysis showed that, compared with conventional therapy, conventional therapy combined with pidotimod could not improve the efficacy of children with respiratory infections (RR=1.78, 95%CI 0.99 to 3.20, P>0.05). However, pidotimod could significantly reduce the number of respiratory tract infection (MD=?2.79, 95%CI ?3.12 to ?2.46, P<0.05), shorten the time of respiratory tract infection (MD=?4.15, 95%CI ?4.72 to ?3.58, P<0.05), and the time of fever (MD=?1.47, 95%CI ?1.77 to ?1.17, P<0.05) in recurrent respiratory tract infection. Pidotimod could also reduce the time of fever (MD=?0.90, 95%CI ?1.60 to ?0.20, P<0.05) in children with mycoplasma pneumoniae pneumonia, the time of fever (MD=?1.51, 95%CI ?1.91 to ?1.11, P<0.05) in children with hand-foot-mouth disease, and reduce the incidence of anaphylactoid purpura followed up for 6 months (RR=0.42, 95%CI 0.30 to 0.61, P<0.05) in children with anaphylactoid purpura. However, there was no significant difference between two groups in the recurrence of asthma for 1 year follow-up (RR=0.80, 95%CI 0.60 to 1.06, P>0.05).Conclusion Current evidence shows that pidotimod may be effective for children with respiratory tract infection, asthma, hand-foot-mouth disease, could reduce disease relapse and relieve symptoms related to illness.

Citation： YI Qiusha, YANG Chunsong, ZENG Linan, CHEN Lina, QIAO Lina, HUANG Liang, SONG Haoxin, LIN Mao, LI Wenrui, MI Xue, ZHANG Lingli. Efficacy of pidotimod in children: a systematic review based on 310 RCTs. Chinese Journal of Evidence-Based Medicine, 2019, 19(5): 571-577. doi: 10.7507/1672-2531.201810058 Copy

1.	Auteri A, Pasqui AL, Bruni F, et al. Effect of Pidotimod, a new immunostimulating agent, on some aspects of immune response. In vitro study. Pharmacol Res, 1992, 26(Suppl 2): 196-197.
2.	Migliorati G, Nicoletti I, Riccardi C. Immunomodulating activity of pidotimod. Arzneimittelforschung, 1994, 44(12A): 1421-1424.
3.	Migliorati G, D'Adamio L, Coppi G, et al. Pidotimod stimulates natural killer cell activity and inhibits thymocyte cell death. Immunopharmacol Immunotoxicol, 1992, 14(4): 737-748.
4.	Giagulli C, Noerder M, Avolio M, et al. Pidotimod promotes functional maturation of dendritic cells and displays adjuvant properties at the nasal mucosa level. Int Immunopharmacol, 2009, 9(12): 1366-1373.
5.	Zuccotti GV, Mameli C, Trabattoni D, et al. Immunomodulating activity of Pidotimod in children with Down syndrome. J Biol Regul Homeost Agents, 2013, 27(1): 253-258.
6.	Carta S, Silvestri M, Rossi GA. Modulation of airway epithelial cell functions by Pidotimod: NF-kB cytoplasmatic expression and its nuclear translocation are associated with an increased TLR-2 expression. Ital J Pediatr, 2013, 39(1): 29.
7.	徐小軍, 趙志剛, 徐建中. 匹多莫德(萬適寧)的藥理作用及其臨床應用. 中國醫院用藥評價與分析, 2003, 3(2): 115-117.
8.	Mameli C, Pasinato A, Picca M, et al. Pidotimod for the prevention of acute respiratory infections in healthy children entering into daycare: A double blind randomized placebo-controlled study. Pharmacol Res, 2015, 97: 79-83.
9.	Namazova-Baranova LS, Alekseeva AA, Kharit SM, et al. Efficacy and safety of pidotimod in the prevention of recurrent respiratory infections in children: a multicentre study. Int J Immunopathol Pharmacol, 2014, 27(3): 413-419.
10.	曲建平. 匹多莫德對預防反復呼吸道感染兒童療效觀察. 內蒙古醫學雜志, 2009, 41(S7): 85-86.
11.	季偉, 趙德育, 沈照波, 等. 酪酸梭菌588預防嬰幼兒反復呼吸道感染多中心隨機對照研究. 兒科藥學雜志, 2015, 21(4): 13-17.
12.	中華醫學會兒科學分會呼吸學組《中華兒科雜志》編輯委員會. 反復呼吸道感染的臨床概念和處理原則. 中華兒科雜志, 2008, 46(2): 108-110.
13.	中華醫學會兒科學分會呼吸學組《中華兒科雜志》編輯委員會. 兒童支氣管哮喘診斷與防治指南(2016年版). 中華兒科雜志, 2016, 54(3): 167-181.
14.	Schaad UB, Esposito S, Razi CH. Diagnosis and management of RRTIs in children: a practical guide. Arch Pediatr Infect Dis, 2016, 4(1): e31039.
15.	王曉川, 申昆玲. 反復呼吸道感染臨床診治路徑. 中國實用兒科雜志, 2016, 31(10): 721-725.
16.	食品藥品監管總局. 總局關于修訂匹多莫德制劑說明書的公告(2018年第30號), 2018. Available at: http://samr.cfda.gov.cn/WS01/CL1706/226085.html.
17.	食品藥品監管總局. 總局關于匹多莫德口服液啟動臨床有效性試驗的通知(藥監藥化管函〔2018〕31號), 2018. Available at: http://samr.cfda.gov.cn/WS01/CL0844/226712.html.
18.	食品藥品監管總局. 總局關于匹多莫德制劑有關事宜的通知(食藥監藥化管函〔2018〕32號), 2018. Available at: http://samr.cfda.gov.cn/WS01/CL0844/226713.html.
19.	The Cochrane Collaboration. The Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0(Updated March 2011). Available at: http://handbook-5-1.cochrane.org/.
20.	de la Torre González C, Pacheco Ríos A, Escalante Domínguez AJ, et al. Comparative meta-analysis of immunoestimulant agents used in pediatric patients in Mexico. Rev Alerg Mex, 2005, 52(1): 25-38.
21.	Del-Rio-Navarro BE, Espinosa Rosales F, Flenady V, et al. Immunostimulants for preventing respiratory tract infection in children. Cochrane Database Syst Rev, 2006, (4): CD004974.
22.	Manikam L, Reed K, Venekamp RP, et al. Limited evidence on the management of respiratory tract infections in Down's syndrome: A Systematic Review. Pediatr Infect Dis J, 2016, 35(10): 1075-1079.
23.	鄭麗麗, 姚莉, 范芳芳, 等. 免疫佐劑治療兒童呼吸道感染臨床療效的Meta分析. 中國現代醫學雜志, 2016, 26(16): 81-87.
24.	Aivazis V, Hatzimichail A, Papachristou A, et al. Clinical evaluation and changes of the respiratory epithelium function after administration of Pidotimod in Greek children with recurrent respiratory tract infections. Minerva Pediatr, 2002, 54(4): 315-319.
25.	Ferrario BE, Garuti S, Braido F, et al. Pidotimod: the state of art. Clin Mol Allergy, 2015, 13(1): 8.

1. Auteri A, Pasqui AL, Bruni F, et al. Effect of Pidotimod, a new immunostimulating agent, on some aspects of immune response. In vitro study. Pharmacol Res, 1992, 26(Suppl 2): 196-197.
2. Migliorati G, Nicoletti I, Riccardi C. Immunomodulating activity of pidotimod. Arzneimittelforschung, 1994, 44(12A): 1421-1424.
3. Migliorati G, D'Adamio L, Coppi G, et al. Pidotimod stimulates natural killer cell activity and inhibits thymocyte cell death. Immunopharmacol Immunotoxicol, 1992, 14(4): 737-748.
4. Giagulli C, Noerder M, Avolio M, et al. Pidotimod promotes functional maturation of dendritic cells and displays adjuvant properties at the nasal mucosa level. Int Immunopharmacol, 2009, 9(12): 1366-1373.
5. Zuccotti GV, Mameli C, Trabattoni D, et al. Immunomodulating activity of Pidotimod in children with Down syndrome. J Biol Regul Homeost Agents, 2013, 27(1): 253-258.
6. Carta S, Silvestri M, Rossi GA. Modulation of airway epithelial cell functions by Pidotimod: NF-kB cytoplasmatic expression and its nuclear translocation are associated with an increased TLR-2 expression. Ital J Pediatr, 2013, 39(1): 29.
7. 徐小軍, 趙志剛, 徐建中. 匹多莫德(萬適寧)的藥理作用及其臨床應用. 中國醫院用藥評價與分析, 2003, 3(2): 115-117.
8. Mameli C, Pasinato A, Picca M, et al. Pidotimod for the prevention of acute respiratory infections in healthy children entering into daycare: A double blind randomized placebo-controlled study. Pharmacol Res, 2015, 97: 79-83.
9. Namazova-Baranova LS, Alekseeva AA, Kharit SM, et al. Efficacy and safety of pidotimod in the prevention of recurrent respiratory infections in children: a multicentre study. Int J Immunopathol Pharmacol, 2014, 27(3): 413-419.
10. 曲建平. 匹多莫德對預防反復呼吸道感染兒童療效觀察. 內蒙古醫學雜志, 2009, 41(S7): 85-86.
11. 季偉, 趙德育, 沈照波, 等. 酪酸梭菌588預防嬰幼兒反復呼吸道感染多中心隨機對照研究. 兒科藥學雜志, 2015, 21(4): 13-17.
12. 中華醫學會兒科學分會呼吸學組《中華兒科雜志》編輯委員會. 反復呼吸道感染的臨床概念和處理原則. 中華兒科雜志, 2008, 46(2): 108-110.
13. 中華醫學會兒科學分會呼吸學組《中華兒科雜志》編輯委員會. 兒童支氣管哮喘診斷與防治指南(2016年版). 中華兒科雜志, 2016, 54(3): 167-181.
14. Schaad UB, Esposito S, Razi CH. Diagnosis and management of RRTIs in children: a practical guide. Arch Pediatr Infect Dis, 2016, 4(1): e31039.
15. 王曉川, 申昆玲. 反復呼吸道感染臨床診治路徑. 中國實用兒科雜志, 2016, 31(10): 721-725.
16. 食品藥品監管總局. 總局關于修訂匹多莫德制劑說明書的公告(2018年第30號), 2018. Available at: http://samr.cfda.gov.cn/WS01/CL1706/226085.html.
17. 食品藥品監管總局. 總局關于匹多莫德口服液啟動臨床有效性試驗的通知(藥監藥化管函〔2018〕31號), 2018. Available at: http://samr.cfda.gov.cn/WS01/CL0844/226712.html.
18. 食品藥品監管總局. 總局關于匹多莫德制劑有關事宜的通知(食藥監藥化管函〔2018〕32號), 2018. Available at: http://samr.cfda.gov.cn/WS01/CL0844/226713.html.
19. The Cochrane Collaboration. The Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0(Updated March 2011). Available at: http://handbook-5-1.cochrane.org/.
20. de la Torre González C, Pacheco Ríos A, Escalante Domínguez AJ, et al. Comparative meta-analysis of immunoestimulant agents used in pediatric patients in Mexico. Rev Alerg Mex, 2005, 52(1): 25-38.
21. Del-Rio-Navarro BE, Espinosa Rosales F, Flenady V, et al. Immunostimulants for preventing respiratory tract infection in children. Cochrane Database Syst Rev, 2006, (4): CD004974.
22. Manikam L, Reed K, Venekamp RP, et al. Limited evidence on the management of respiratory tract infections in Down's syndrome: A Systematic Review. Pediatr Infect Dis J, 2016, 35(10): 1075-1079.
23. 鄭麗麗, 姚莉, 范芳芳, 等. 免疫佐劑治療兒童呼吸道感染臨床療效的Meta分析. 中國現代醫學雜志, 2016, 26(16): 81-87.
24. Aivazis V, Hatzimichail A, Papachristou A, et al. Clinical evaluation and changes of the respiratory epithelium function after administration of Pidotimod in Greek children with recurrent respiratory tract infections. Minerva Pediatr, 2002, 54(4): 315-319.
25. Ferrario BE, Garuti S, Braido F, et al. Pidotimod: the state of art. Clin Mol Allergy, 2015, 13(1): 8.

Chinese Journal of Evidence-Based Medicine

Efficacy of pidotimod in children: a systematic review based on 310 RCTs

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