PMID- 35799700
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2296-2360 (Print)
IS  - 2296-2360 (Electronic)
IS  - 2296-2360 (Linking)
VI  - 10
DP  - 2022
TI  - Value of Literature Review to Inform Development and Use of Biologics in Juvenile 
      Idiopathic Arthritis.
PG  - 909118
LID - 10.3389/fped.2022.909118 [doi]
LID - 909118
AB  - BACKGROUND: Juvenile idiopathic arthritis (JIA) is one of the most common 
      pediatric inflammatory rheumatic diseases (PiRDs). Uncontrolled disease activity 
      is associated with decreased quality of life and chronic morbidity. Biologic 
      disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors 
      (JAKi) have considerably improved clinical outcomes. For optimized patient care, 
      understanding the efficacy-safety profile of biologics in subgroups of JIA is 
      crucial. This systematic review based on published randomized controlled trials 
      (RCTs) aims to assess efficacy and safety data for bDMARDs and JAKi with various 
      JIA subgroups after 3 months of treatment. METHODS: Data for American College of 
      Rheumatology (ACR) pediatric (Pedi) 30, 50, and/or 70 responses after 3 months of 
      treatment were selected from RCTs investigating bDMARDs or JAKi in JIA according 
      to predefined inclusion/exclusion criteria. Treatment and control arms were 
      compared by calculating risk ratios (RRs) with 95% confidence intervals (CIs), 
      and proportions of overall, serious adverse events (AEs) and infections were 
      analyzed. Forest plots were generated to summarize efficacy and safety endpoints 
      across studies, JIA subgroups, and type of biologics. RESULTS: Twenty-eight out 
      of 41 PiRD RCTs investigated bDMARD or JAKi treatments in JIA. 9 parallel RCTs 
      reported ACR Pedi 30, 50, and/or 70 responses 3 months after treatment 
      initiation. All treatment arms showed improved ACR Pedi responses over controls. 
      RRs ranged from 1.05 to 3.73 in ACR Pedi 30, from 1.20 to 7.90 in ACR Pedi 50, 
      and from 1.19 to 8.73 in ACR Pedi 70. An enhanced effect for ACR Pedi 70 was 
      observed with infliximab combined with methotrexate in PJIA vs. methotrexate 
      monotherapy. A slightly higher risk of gastrointestinal AEs and infections was 
      observed with treatment arms compared to placebo or methotrexate monotherapy. 
      CONCLUSION: Investigated bDMARDs and JAKi showed superior treatment responses 
      compared to controls after 3 months of treatment, which were more pronounced in 
      ACR Pedi 50 and 70 than in ACR Pedi 30. Higher susceptibility to infections 
      associated with bDMARDs or JAKi vs. control arms must be weighed against 
      efficacious treatment of the underlying disease and prevention of disease-related 
      damage. Additional RCTs are warranted to further inform development and 
      utilization of biologics in JIA.
CI  - Copyright (c) 2022 Golhen, Winskill, Yeh, Zhang, Welzel and Pfister.
FAU - Golhen, Klervi
AU  - Golhen K
AD  - Pediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel 
      (UKBB), University of Basel, Basel, Switzerland.
FAU - Winskill, Carolyn
AU  - Winskill C
AD  - Integrated Drug Development, Certara LP, Princeton, NJ, United States.
FAU - Yeh, Cynthia
AU  - Yeh C
AD  - Integrated Drug Development, Certara LP, Princeton, NJ, United States.
FAU - Zhang, Nancy
AU  - Zhang N
AD  - Integrated Drug Development, Certara LP, Princeton, NJ, United States.
FAU - Welzel, Tatjana
AU  - Welzel T
AD  - Pediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel 
      (UKBB), University of Basel, Basel, Switzerland.
AD  - Pediatric Rheumatology, University Children's Hospital Basel (UKBB), University 
      of Basel, Basel, Switzerland.
FAU - Pfister, Marc
AU  - Pfister M
AD  - Pediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel 
      (UKBB), University of Basel, Basel, Switzerland.
AD  - Integrated Drug Development, Certara LP, Princeton, NJ, United States.
LA  - eng
PT  - Systematic Review
DEP - 20220621
PL  - Switzerland
TA  - Front Pediatr
JT  - Frontiers in pediatrics
JID - 101615492
PMC - PMC9253535
OTO - NOTNLM
OT  - JAK inhibitors
OT  - bDMARDs
OT  - efficacy
OT  - juvenile idiopathic arthritis
OT  - literature review
OT  - randomized controlled trials
OT  - safety
OT  - systematic review
COIS- CW, CY, NZ, and MP were employed by Certara LP. The remaining authors declare 
      that the research was conducted in the absence of any commercial or financial 
      relationships that could be construed as a potential conflict of interest.
EDAT- 2022/07/09 06:00
MHDA- 2022/07/09 06:01
PMCR- 2022/06/21
CRDT- 2022/07/08 02:36
PHST- 2022/04/05 00:00 [received]
PHST- 2022/05/24 00:00 [accepted]
PHST- 2022/07/08 02:36 [entrez]
PHST- 2022/07/09 06:00 [pubmed]
PHST- 2022/07/09 06:01 [medline]
PHST- 2022/06/21 00:00 [pmc-release]
AID - 10.3389/fped.2022.909118 [doi]
PST - epublish
SO  - Front Pediatr. 2022 Jun 21;10:909118. doi: 10.3389/fped.2022.909118. eCollection 
      2022.