Restricted accessResearch articleFirst published online 2024-03
A Bayesian Network Meta-Analysis of the Effect of Targeted Therapies on the Total Length of Hospital Stay in Children with Drug-Induced Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis Syndrome
Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare potentially life-threatening hypersensitivity disorders characterized by widespread skin and mucosal involvement. However, there is no standardized evidence-based treatment to reduce the complications of SJS/TEN. This article aims to compare the efficacy of different treatments for pediatric SJS/TEN in terms of length of hospital stay (LOS) using a Bayesian network meta-analysis (NMA). A Bayesian NMA is used to compare and combine evidence from multiple studies and allows clinicians to estimate the relative effectiveness of different treatments/interventions while accounting for heterogeneity in the available evidence.
Methods:
We conducted a comprehensive electronic database search for studies compatible with our inclusion criteria. Six studies with 103 patients were included in the NMA; of them, 37 patients were treated with intravenous immunoglobulin (IVIG), 37 with systemic corticosteroids (CS), 23 with IVIG + CS, and 3 with Etanercept (ET) + CS. Patients with a median age of 10 years were included in the study.
Results:
CS had the highest probability of being the most optimal treatment for SJS/TEN in terms of shorter LOS based on the Surface Under the Cumulative Ranking curve levels, and CS + IVIG was associated with a statistically nonsignificant trend toward shorter LOS than IVIG alone. Remarkably, none of the treatments showed a significant benefit over the other interventions in terms of LOS.
Conclusion:
Current evidence suggests that coadministration of CS and IVIG may be associated with a shorter LOS than IVIG alone. Further research with larger randomized controlled trials is needed to reach a definitive conclusion about the efficacy of specific therapy on LOS in pediatric SJS/TEN and to establish more definitive treatment guidelines.
Get full access to this article
View all access options for this article.
References
1.
AntoonJW, GoldmanJL, LeeB, et al.Incidence, outcomes, and resource use in children with Stevens–Johnson syndrome and toxic epidermal necrolysis. Pediatr Dermatol, 2018; 35(2):182–187; doi: 10.1111/pde.13383
2.
OwenCE, JonesJM. Recognition and management of severe cutaneous adverse drug reactions (including drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis). Med Clin North Am, 2021; 105(4):577–597; doi: 10.1016/j.mcna.2021.04.001
3.
RamienML, GoldmanJL, BellónTet al.Pediatric SJS-TEN: Where are we now?. F1000Res, 2021; 9:1–11; doi: 10.12688/f1000research.20419.1
4.
ButtGF, HassanA, WallaceGR, et al.Human leukocyte antigen B*0702 is protective against ocular Stevens–Johnson syndrome/toxic epidermal necrolysis in the UK population. Sci Rep, 2021; 11(1):1–8; doi: 10.1038/s41598-021-82400-3
5.
FrimpongA, ThiamLG, Arko-BohamB, et al.Safety and effectiveness of antimalarial therapy in sickle cell disease: A systematic review and network meta-analysis. BMC Infect Dis, 2018; 18(1):1–10; doi: 10.1186/s12879-018-3556-0
6.
PatelTK, PatelPB, ThakkarS. Comparison of effectiveness of interventions in reducing mortality in patients of toxic epidermal necrolysis: A network meta-analysis. Indian J Dermatol Venereol Leprol, 2021; 87(5):628–644; doi: 10.25259/IJDVL_605_19
7.
HoltzM, GrimstadF, HigginsJet al.Vulvovaginal involvement in pediatric Stevens−Johnson syndrome: A case series. J Pediatr Adolesc Gynecol, 2021; 34(5):745–748; doi: 10.1016/j.jpag.2021.03.011
8.
WangY, RaoR, JacobsDS, et al.Prosthetic replacement of the ocular surface ecosystem treatment for ocular surface disease in pediatric patients with Stevens–Johnson syndrome. Am J Ophthalmol, 2019; 201:1–8; doi: 10.1016/j.ajo.2019.01.006
9.
ChatproedpraiS, WutticharoenwongV, TemparkT, et al.Clinical features and treatment outcomes among children with Stevens–Johnson syndrome and toxic epidermal necrolysis: A 20-year study in a tertiary referral hospital. Dermatol Res Pract, 2018; 7;2018:3061084; doi: 10.1155/2018/3061084
10.
FooteCJ, ChaudhryH, BhandariMet al.Network meta-analysis: Users' guide for surgeons: Part I – Credibility. Clin Orthop Relat Res, 2015; 473(7):2166–2171; doi: 10.1007/s11999-015-4286-x
11.
RouseB, ChaimaniA, LiT. Network meta-analysis: an introduction for clinicians. Intern Emerg Med, 2016; 12:103–111; doi: 10.1007/s11739-016-1583-7
12.
ToninFS, RottaI, MendesAM, et al.Network meta-analysis: A technique to gather evidence from direct and indirect comparisons. Pharm Pract (Granada), 2017; 15(1):943; doi: 10.18549/PharmPract.2017.01.943
13.
HackenbergerBK. Bayes or not Bayes, is this the question?. Croat Med J, 2019; 60(1):50–52; doi: 10.3325/cmj.2019.60.50
14.
BéliveauA, GustafsonP. A theoretical investigation of how evidence flows in bayesian network meta-analysis of disconnected networks. Bayesian Anal, 2021; 16(3):803–823; doi: 10.1214/20-BA1224
15.
DiasS, SuttonAJ, AdesAE, et al.Evidence synthesis for decision making 2: A generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. Med Decis Making, 2013; 33(5):607–617; doi: 10.1177/0272989X12458724
16.
GrecoT, Biondi-ZoccaiG, SalehOet al.The attractiveness of network meta-analysis: A comprehensive systematic and narrative review. Heart Lung Vessel, 2015; 7(2):133–142.
17.
HoaglinDC, HawkinsN, JansenJP et al. Conducting indirect-treatment-comparison and network-meta-analysis studies: Report of the ISPOR task force on indirect treatment comparisons good research practices: Part 2. Value Health, 2011; 14(4):429–437; doi: 10.1016/j.jval.2011.01.011
18.
KibretT, RicherD, BeyeneJ. Bias in identifcation of the best treatment in a Bayesian network meta-analysis for binary outcome: A simulation study. Clin Epidemiol, 2014; 6:451–460; doi: 10.2147/CLEP.S69660
19.
LitwinowiczK, ChoroszyM, OrnatM, et al.Bayesian network meta-analysis of face masks' impact on human physiology. Sci Rep, 2022; 12(1):1–11; doi: 10.1038/s41598-022-09747-z
20.
PhillippoDM, DiasS, AdesAE, et al.Sensitivity of treatment recommendations to bias in network meta-analysis. J R Stat Soc Ser A Stat Soc, 2018; 181(3):843–867; doi: 10.1111/rssa.12341
21.
WuY, HuH, CaiJet al.Applying latent class analysis to risk stratification of incident diabetes among Chinese adults. Diabetes Res Clin Pract, 2021; 174:108742; doi: 10.1016/j.diabres.2021.108742
22.
HuD, O'ConnorAM, WangC, et al.How to conduct a Bayesian network meta-analysis. Front Vet Sci, 2020; 7(271):1–14; doi: 10.3389/fvets.2020.00271
23.
KibretTC.A Bayesian Network Meta-Analysis for Binary Outcome: A Simulation Study. [Dissertation]. Canada: University of Canada; 2013.
24.
SinghJ, GsteigerS, WheatonL, et al.Bayesian network meta-analysis methods for combining individual participant data and aggregate data from single arm trials and randomised controlled trials. BMC Med Res Methodol, 2022; 22(1):186; doi: 10.1186/s12874-022-01657-y
25.
CarneyN, CheneyT, TottenAM, et al.Prehospital airway management: A systematic review. Prehosp Emerg Care, 2022; 26(5):716–727; doi: 10.1080/10903127.2021.1940400
26.
SatoS, KanbeT, TamakiZet al.Clinical features of Stevens–Johnson syndrome and toxic epidermal necrolysis. Pediatr Int, 2018; 60(8): 697–702; doi: 10.1111/ped.13613
27.
AhluwaliaJ, WanJ, LeeDH, et al.Mycoplasma-associated Stevens–Johnson syndrome in children: Retrospective review of patients managed with or without intravenous immunoglobulin, systemic corticosteroids, or a combination of therapies. Pediatr Dermatol, 2014; 31(6):664–669; doi: 10.1111/pde.12481
28.
ChiMH, ChungWH, HuiRCY, et al.Clinical features and outcomes in children with Stevens–Johnson syndrome and toxic epidermal necrolysis. J Dermatol, 2022; 49(9):895–902; doi: 10.1111/1346-8138.16476
29.
KohMJA, TayYK. Stevens–Johnson syndrome and toxic epidermal necrolysis in Asian children. J Immunol Res, 2010; 62(1):54–60; doi: 10.1016/j.jaad.2009.06.085
30.
SibbaldC, PuttermanE, MichelettiR, et al.Retrospective review of drug-induced Stevens–Johnson syndrome and toxic epidermal necrolysis cases at a pediatric tertiary care institution. Pediatr Dermatol, 2020; 37(3):461–466; doi: 10.1111/pde.14118
31.
WilliamsV, ReddyM, BansalA, et al.Intensive care needs and long-term outcome of pediatric toxic epidermal necrolysis: A 10-year experience. Int J Dermatol, 2021; 60(1):44–52; doi: 10.1111/ijd.15054
32.
ChangWC, AbeR, AndersonP, et al.SJS/TEN 2019: From science to translation. J Dermatol Sci, 2020; 98(1):2–12; doi: 10.1016/j.jdermsci.2020.02.003
ChangH, WangTJ, LinMH, et al.A review of the systemic treatment of Stevens–Johnson syndrome and toxic epidermal necrolysis. Biomedicines, 2022; 10(9):2105; doi: 10.3390/biomedicines10092105
35.
CharltonOA, HarrisV, PhanK, et al.Toxic epidermal necrolysis and Steven–Johnson syndrome: A comprehensive review. Adv Wound Care (New Rochelle), 2019; 9(7):426–439; doi: 10.1089/wound.2019.0977
36.
JacobsenA, OlabiB, LangleyA, et al.Systemic interventions for treatment of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome. Cochrane Database Syst Rev, 2022; 3(3):CD013130; doi: 10.1002/14651858.CD013130.pub2
37.
FrantzR, HuangS, AreA, et al.Stevens–Johnson syndrome and toxic epidermal necrolysis: A review of diagnosis and management. Medicina, 2021; 57(9):895; doi: 10.3390/medicina57090895
38.
HiraharaK, KanoY, SatoY, et al.Methylprednisolone pulse therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis: clinical evaluation and analysis of biomarkers. J Am Acad Dermatol, 2013; 69(3):496–498; doi: 10.1016/j.jaad.2013.04.007
39.
YeLP, ZhangC, ZhuQX. The effect of intravenous immunoglobulin combined with corticosteroid on the progression of Stevens–Johnson syndrome and toxic epidermal necrolysis: A meta-analysis. PLoS One, 2016; 11:1–17; doi: 10.1371/journal.pone.0167120
40.
ViardI, WehrliP, BullaniR, et al.Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science, 1998; 282(5388):490–493; doi: 10.1126/science.282.5388.490
41.
JacobiC, ClausM, WildemannB, et al.Exposure of NK cells to intravenous immunoglobulin induces IFN gamma release and degranulation but inhibits their cytotoxic activity. Clin Immunol, 2009; 133(3):393–401; doi: 10.1016/j.clim.2009.09.006
42.
HuangYC, LiYC, ChenTJ. The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis. Br J Dermatol, 2012; 167(2):424–432; doi: 10.1111/j.1365-2133.2012.10965.x
43.
AoS, GaoX, ZhanJ, et al.Inhibition of tumor necrosis factor improves conventional steroid therapy for Stevens–Johnson syndrome/toxic epidermal necrolysis in a cohort of patients. J Am Acad Dermatol, 2022; 86(6):1236–1245; doi: 10.1016/j.jaad.2022.01.039
Pozzo-MaganaBRD, Lazo-LangnerAL, CarletonB, et al.A systematic review of treatment of drug-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in children. J Popul Ther Clin Pharmacol, 2011; 18(1):121–133.
46.
AntoonJW, GoldmanJL, ShahSS, et al.A retrospective cohort study of the management and outcomes of children hospitalized with Stevens–Johnson syndrome or toxic epidermal necrolysis. J Allergy Clin Immunol Pract, 2019; 7(1):244–250; doi: 10.1016/j.jaip.2018.05.024
47.
KrajewskiA, Maciejewska-MarkiewiczD, JakubczykK, et al.Impact of multiple medical interventions on mortality, length of hospital stays and reepithelialization time in toxic epidermal necrolysis, Steven–Johnsons syndrome, and TEN/SJS overlap: Metanalysis and metaregression of observational studies. Burns, 2022; 48(2):263–280; doi: 10.1016/j.burns.2021.11.004
48.
WangYM, TaoYH, FengT, et al.Beneficial therapeutic effects of hemoperfusion in the treatment of severe Stevens–Johnson syndrome/toxic epidermal necrolysis: Preliminary results. Eur Rev Med Pharmacol Sci, 2014; 18(23):3696–3701
49.
Ferrándiz-PulidoC, García-FernándezD, Domínguez-SampedroP, et al.Stevens–Johnson syndrome and toxic epidermal necrolysis in children: A review of the experience with paediatric patients in a University Hospital. J Eur Acad Dermatol Venereol, 2011; 25(10):1153–1159; doi: 10.1111/j.1468-3083.2010.03935.x
50.
LiottiL, CaimmiS, BottauP, et al.Clinical features, outcomes and treatment in children with drug induced Stevens–Johnson syndrome and toxic epidermal necrolysis. Acta Biomed, 2019; 90(3):52–60; doi: 10.23750/abm.v90i3-S.8165
51.
Torres-NavarroI, Briz-RedónA, Botella-EstradaR. Systemic therapies for Stevens–Johnson syndrome and toxic epidermal necrolysis: A SCORTEN-based systematic review and meta-analysis. J Eur Acad Dermatol Venereol, 2021; 35(1):159–171; doi: 10.1111/jdv.16685
52.
ParadisiA, AbeniD, BergamoF, et al.Etanercept therapy for toxic epidermal necrolysis. J Am Acad Dermatol, 2014; 71(2):278–283; doi: 10.1016/j.jaad.2014.04.044
53.
BalcıS, BaydemirC. Meta analysis in medical sciences. KOU Sag Bil Derg, 2015; 1(1):9–11; doi: 10.30934/kusbed.349511
54.
ShiQ, TanL, ChenZ, et al.Comparative efficacy of pharmacological and nonpharmacological interventions for acne vulgaris: A network meta-analysis. Front Pharmacol, 2020; 11:592075; doi: 10.3389/fphar.2020.592075
55.
JansenJP, FleurenceR, DevineB, et al.Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: Report of the ISPOR task force on indirect treatment comparisons good research practices: Part 1. Value Health, 2011; 14(4):417–428; doi: 10.1016/j.jval.2011.04.002
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
