A 6-month, multicenter, open-label study of fixed dose naproxen/esomeprazole in adolescent patients with juvenile idiopathic arthritis

Daniel J. Lovell, Jason A. Dare, Megan Francis-Sedlak, Julie Ball, Brian D. LaMoreaux, Emily Von Scheven, Adam Reinhardt, Rita S Jerath, Oral Alpan, Ramesh Gupta, Donald Goldsmith, Andrew Zeft, Henry Naddaf, Beth Gottlieb, Lawrence Jung, Robert J. Holt

Research output: Contribution to journalArticle

Abstract

Background: Juvenile idiopathic arthritis (JIA) is an inflammatory arthritis of unknown etiology, which lasts for greater than 6 weeks with onset before 16 years of age. JIA is the most common chronic rheumatic disease in children. NSAIDs have been the mainstay of initial management with naproxen (NAP) being commonly used, but they may cause serious side effects such as gastric ulcers which can be reduced by concomitant administration of proton pump inhibitors, such as esomeprazole (ESO). Methods: Primary objective was to evaluate the safety and tolerability of 3 fixed doses of NAP/ESO in JIA patients aged 12 to 16 years. Forty-six children and adolescents with JIA by International League of Associations for Rheumatology criteria, mean age of 13.6 years, from 18 US sites were prospectively enrolled over 2 years and followed for up to 6 months. Doses of the NAP/ESO fixed combination were based on baseline weight. The exploratory efficacy outcome was assessed with the ACR Pediatric-30, - 50, - 70, - 90 Response and the Childhood Health Assessment Questionnaire (CHAQ) discomfort and functional scores at months 1, 3, and 6 as change from baseline. Occurrence and causality were assessed for treatment emergent AEs (TEAEs) and discontinuations were monitored monthly. Results: Forty-six patients received at least 1 dose of naproxen/esomeprazole and 36 completed the trial. Thirty-seven (80.4%) had at least 1 treatment emergent adverse event (TEAE) and, with the exception of 2 events in one patient, all of the TEAEs were mild or moderate. Frequent TEAEs (≥5% of patients) were upper respiratory tract and gastrointestinal related. Eleven (23.9%) had at least 1 TEAE considered to be related to study drug. Four patients (8.7%) discontinued due to a TEAE with one of these being the only serious AE reported, acute hepatitis. Mean number of active joints at baseline was 3.1. Improvement in JIA signs and symptoms occurred at most assessments and by month 6, the percentage of patients with an ACR Pediatric-30, - 50, - 70, and - 90 Response was 47.1, 38.2, 32.4, and 17.6%, respectively. The percent of patients achieving ACR Pediatric response increased over time. CHAQ discomfort improved at each assessment and functional scores improved at all assessments for 'Arising, Walking, and Activities' with several improved for 'Dressing and Grooming, Eating, Hygiene, and Grip'. There was no indication of a dose-related efficacy effect. Conclusion: NAP/ESO was well tolerated in JIA patients aged 12 to 16 years with high levels of response to ACR criteria. No new safety signals were identified for the well-characterized components of this fixed dosed JIA treatment, which was developed to reduce the risk of gastric ulcers.

LanguageEnglish (US)
Article number41
JournalPediatric Rheumatology
Volume16
Issue number1
DOIs
StatePublished - Jun 26 2018
Externally publishedYes

Fingerprint

Esomeprazole
Naproxen
Juvenile Arthritis
Stomach Ulcer
Pediatrics
Therapeutics
Safety
Grooming
Upper Gastrointestinal Tract
Proton Pump Inhibitors
Health
Rheumatology
Hand Strength
Non-Steroidal Anti-Inflammatory Agents
Bandages
Rheumatic Diseases
Hygiene
Causality
Respiratory System
Hepatitis

Keywords

  • Esomeprazole
  • Juvenile idiopathic arthritis
  • Naproxen
  • Non-steroidal anti-inflammatory drugs (NSAIDs)

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Rheumatology
  • Immunology and Allergy

Cite this

Lovell, D. J., Dare, J. A., Francis-Sedlak, M., Ball, J., LaMoreaux, B. D., Von Scheven, E., ... Holt, R. J. (2018). A 6-month, multicenter, open-label study of fixed dose naproxen/esomeprazole in adolescent patients with juvenile idiopathic arthritis. Pediatric Rheumatology, 16(1), [41]. https://doi.org/10.1186/s12969-018-0260-y

A 6-month, multicenter, open-label study of fixed dose naproxen/esomeprazole in adolescent patients with juvenile idiopathic arthritis. / Lovell, Daniel J.; Dare, Jason A.; Francis-Sedlak, Megan; Ball, Julie; LaMoreaux, Brian D.; Von Scheven, Emily; Reinhardt, Adam; Jerath, Rita S; Alpan, Oral; Gupta, Ramesh; Goldsmith, Donald; Zeft, Andrew; Naddaf, Henry; Gottlieb, Beth; Jung, Lawrence; Holt, Robert J.

In: Pediatric Rheumatology, Vol. 16, No. 1, 41, 26.06.2018.

Research output: Contribution to journalArticle

Lovell, DJ, Dare, JA, Francis-Sedlak, M, Ball, J, LaMoreaux, BD, Von Scheven, E, Reinhardt, A, Jerath, RS, Alpan, O, Gupta, R, Goldsmith, D, Zeft, A, Naddaf, H, Gottlieb, B, Jung, L & Holt, RJ 2018, 'A 6-month, multicenter, open-label study of fixed dose naproxen/esomeprazole in adolescent patients with juvenile idiopathic arthritis' Pediatric Rheumatology, vol. 16, no. 1, 41. https://doi.org/10.1186/s12969-018-0260-y
Lovell, Daniel J. ; Dare, Jason A. ; Francis-Sedlak, Megan ; Ball, Julie ; LaMoreaux, Brian D. ; Von Scheven, Emily ; Reinhardt, Adam ; Jerath, Rita S ; Alpan, Oral ; Gupta, Ramesh ; Goldsmith, Donald ; Zeft, Andrew ; Naddaf, Henry ; Gottlieb, Beth ; Jung, Lawrence ; Holt, Robert J. / A 6-month, multicenter, open-label study of fixed dose naproxen/esomeprazole in adolescent patients with juvenile idiopathic arthritis. In: Pediatric Rheumatology. 2018 ; Vol. 16, No. 1.
@article{70f3f12041d24e419cd0cba836cb335f,
title = "A 6-month, multicenter, open-label study of fixed dose naproxen/esomeprazole in adolescent patients with juvenile idiopathic arthritis",
abstract = "Background: Juvenile idiopathic arthritis (JIA) is an inflammatory arthritis of unknown etiology, which lasts for greater than 6 weeks with onset before 16 years of age. JIA is the most common chronic rheumatic disease in children. NSAIDs have been the mainstay of initial management with naproxen (NAP) being commonly used, but they may cause serious side effects such as gastric ulcers which can be reduced by concomitant administration of proton pump inhibitors, such as esomeprazole (ESO). Methods: Primary objective was to evaluate the safety and tolerability of 3 fixed doses of NAP/ESO in JIA patients aged 12 to 16 years. Forty-six children and adolescents with JIA by International League of Associations for Rheumatology criteria, mean age of 13.6 years, from 18 US sites were prospectively enrolled over 2 years and followed for up to 6 months. Doses of the NAP/ESO fixed combination were based on baseline weight. The exploratory efficacy outcome was assessed with the ACR Pediatric-30, - 50, - 70, - 90 Response and the Childhood Health Assessment Questionnaire (CHAQ) discomfort and functional scores at months 1, 3, and 6 as change from baseline. Occurrence and causality were assessed for treatment emergent AEs (TEAEs) and discontinuations were monitored monthly. Results: Forty-six patients received at least 1 dose of naproxen/esomeprazole and 36 completed the trial. Thirty-seven (80.4{\%}) had at least 1 treatment emergent adverse event (TEAE) and, with the exception of 2 events in one patient, all of the TEAEs were mild or moderate. Frequent TEAEs (≥5{\%} of patients) were upper respiratory tract and gastrointestinal related. Eleven (23.9{\%}) had at least 1 TEAE considered to be related to study drug. Four patients (8.7{\%}) discontinued due to a TEAE with one of these being the only serious AE reported, acute hepatitis. Mean number of active joints at baseline was 3.1. Improvement in JIA signs and symptoms occurred at most assessments and by month 6, the percentage of patients with an ACR Pediatric-30, - 50, - 70, and - 90 Response was 47.1, 38.2, 32.4, and 17.6{\%}, respectively. The percent of patients achieving ACR Pediatric response increased over time. CHAQ discomfort improved at each assessment and functional scores improved at all assessments for 'Arising, Walking, and Activities' with several improved for 'Dressing and Grooming, Eating, Hygiene, and Grip'. There was no indication of a dose-related efficacy effect. Conclusion: NAP/ESO was well tolerated in JIA patients aged 12 to 16 years with high levels of response to ACR criteria. No new safety signals were identified for the well-characterized components of this fixed dosed JIA treatment, which was developed to reduce the risk of gastric ulcers.",
keywords = "Esomeprazole, Juvenile idiopathic arthritis, Naproxen, Non-steroidal anti-inflammatory drugs (NSAIDs)",
author = "Lovell, {Daniel J.} and Dare, {Jason A.} and Megan Francis-Sedlak and Julie Ball and LaMoreaux, {Brian D.} and {Von Scheven}, Emily and Adam Reinhardt and Jerath, {Rita S} and Oral Alpan and Ramesh Gupta and Donald Goldsmith and Andrew Zeft and Henry Naddaf and Beth Gottlieb and Lawrence Jung and Holt, {Robert J.}",
year = "2018",
month = "6",
day = "26",
doi = "10.1186/s12969-018-0260-y",
language = "English (US)",
volume = "16",
journal = "Pediatric Rheumatology",
issn = "1546-0096",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - A 6-month, multicenter, open-label study of fixed dose naproxen/esomeprazole in adolescent patients with juvenile idiopathic arthritis

AU - Lovell, Daniel J.

AU - Dare, Jason A.

AU - Francis-Sedlak, Megan

AU - Ball, Julie

AU - LaMoreaux, Brian D.

AU - Von Scheven, Emily

AU - Reinhardt, Adam

AU - Jerath, Rita S

AU - Alpan, Oral

AU - Gupta, Ramesh

AU - Goldsmith, Donald

AU - Zeft, Andrew

AU - Naddaf, Henry

AU - Gottlieb, Beth

AU - Jung, Lawrence

AU - Holt, Robert J.

PY - 2018/6/26

Y1 - 2018/6/26

N2 - Background: Juvenile idiopathic arthritis (JIA) is an inflammatory arthritis of unknown etiology, which lasts for greater than 6 weeks with onset before 16 years of age. JIA is the most common chronic rheumatic disease in children. NSAIDs have been the mainstay of initial management with naproxen (NAP) being commonly used, but they may cause serious side effects such as gastric ulcers which can be reduced by concomitant administration of proton pump inhibitors, such as esomeprazole (ESO). Methods: Primary objective was to evaluate the safety and tolerability of 3 fixed doses of NAP/ESO in JIA patients aged 12 to 16 years. Forty-six children and adolescents with JIA by International League of Associations for Rheumatology criteria, mean age of 13.6 years, from 18 US sites were prospectively enrolled over 2 years and followed for up to 6 months. Doses of the NAP/ESO fixed combination were based on baseline weight. The exploratory efficacy outcome was assessed with the ACR Pediatric-30, - 50, - 70, - 90 Response and the Childhood Health Assessment Questionnaire (CHAQ) discomfort and functional scores at months 1, 3, and 6 as change from baseline. Occurrence and causality were assessed for treatment emergent AEs (TEAEs) and discontinuations were monitored monthly. Results: Forty-six patients received at least 1 dose of naproxen/esomeprazole and 36 completed the trial. Thirty-seven (80.4%) had at least 1 treatment emergent adverse event (TEAE) and, with the exception of 2 events in one patient, all of the TEAEs were mild or moderate. Frequent TEAEs (≥5% of patients) were upper respiratory tract and gastrointestinal related. Eleven (23.9%) had at least 1 TEAE considered to be related to study drug. Four patients (8.7%) discontinued due to a TEAE with one of these being the only serious AE reported, acute hepatitis. Mean number of active joints at baseline was 3.1. Improvement in JIA signs and symptoms occurred at most assessments and by month 6, the percentage of patients with an ACR Pediatric-30, - 50, - 70, and - 90 Response was 47.1, 38.2, 32.4, and 17.6%, respectively. The percent of patients achieving ACR Pediatric response increased over time. CHAQ discomfort improved at each assessment and functional scores improved at all assessments for 'Arising, Walking, and Activities' with several improved for 'Dressing and Grooming, Eating, Hygiene, and Grip'. There was no indication of a dose-related efficacy effect. Conclusion: NAP/ESO was well tolerated in JIA patients aged 12 to 16 years with high levels of response to ACR criteria. No new safety signals were identified for the well-characterized components of this fixed dosed JIA treatment, which was developed to reduce the risk of gastric ulcers.

AB - Background: Juvenile idiopathic arthritis (JIA) is an inflammatory arthritis of unknown etiology, which lasts for greater than 6 weeks with onset before 16 years of age. JIA is the most common chronic rheumatic disease in children. NSAIDs have been the mainstay of initial management with naproxen (NAP) being commonly used, but they may cause serious side effects such as gastric ulcers which can be reduced by concomitant administration of proton pump inhibitors, such as esomeprazole (ESO). Methods: Primary objective was to evaluate the safety and tolerability of 3 fixed doses of NAP/ESO in JIA patients aged 12 to 16 years. Forty-six children and adolescents with JIA by International League of Associations for Rheumatology criteria, mean age of 13.6 years, from 18 US sites were prospectively enrolled over 2 years and followed for up to 6 months. Doses of the NAP/ESO fixed combination were based on baseline weight. The exploratory efficacy outcome was assessed with the ACR Pediatric-30, - 50, - 70, - 90 Response and the Childhood Health Assessment Questionnaire (CHAQ) discomfort and functional scores at months 1, 3, and 6 as change from baseline. Occurrence and causality were assessed for treatment emergent AEs (TEAEs) and discontinuations were monitored monthly. Results: Forty-six patients received at least 1 dose of naproxen/esomeprazole and 36 completed the trial. Thirty-seven (80.4%) had at least 1 treatment emergent adverse event (TEAE) and, with the exception of 2 events in one patient, all of the TEAEs were mild or moderate. Frequent TEAEs (≥5% of patients) were upper respiratory tract and gastrointestinal related. Eleven (23.9%) had at least 1 TEAE considered to be related to study drug. Four patients (8.7%) discontinued due to a TEAE with one of these being the only serious AE reported, acute hepatitis. Mean number of active joints at baseline was 3.1. Improvement in JIA signs and symptoms occurred at most assessments and by month 6, the percentage of patients with an ACR Pediatric-30, - 50, - 70, and - 90 Response was 47.1, 38.2, 32.4, and 17.6%, respectively. The percent of patients achieving ACR Pediatric response increased over time. CHAQ discomfort improved at each assessment and functional scores improved at all assessments for 'Arising, Walking, and Activities' with several improved for 'Dressing and Grooming, Eating, Hygiene, and Grip'. There was no indication of a dose-related efficacy effect. Conclusion: NAP/ESO was well tolerated in JIA patients aged 12 to 16 years with high levels of response to ACR criteria. No new safety signals were identified for the well-characterized components of this fixed dosed JIA treatment, which was developed to reduce the risk of gastric ulcers.

KW - Esomeprazole

KW - Juvenile idiopathic arthritis

KW - Naproxen

KW - Non-steroidal anti-inflammatory drugs (NSAIDs)

UR - http://www.scopus.com/inward/record.url?scp=85049091401&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049091401&partnerID=8YFLogxK

U2 - 10.1186/s12969-018-0260-y

DO - 10.1186/s12969-018-0260-y

M3 - Article

VL - 16

JO - Pediatric Rheumatology

T2 - Pediatric Rheumatology

JF - Pediatric Rheumatology

SN - 1546-0096

IS - 1

M1 - 41

ER -