AB1086 A 6-month, multicenter, open-label, exploratory study of fixed dose naproxen/esomeprazole in adolescent patients with juvenile idiopathic arthritis (JIA)
Authors: D.J. Lovell, J.A. Dare, J. Ball, M. Francis-Sedlak, B.D. LaMoreaux, R.J. Holt
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> JIA is an inflammatory arthritis of unknown etiology, which lasts for greater than 6 weeks with onset before 16 years of age.<sup>1 2</sup> Per the ACR guidelines, JIA is the most common chronic rheumatic disease in children.<sup>3</sup> NSAIDs have been the mainstay of initial management with naproxen being commonly used, but they can cause serious side effects such as gastritis. Herein, we report the results of a clinical trial in JIA patients receiving one of 3 fixed doses of naproxen/esomeprazole magnesium (nap/eso) given BID (table 1). <h3>Objectives</h3> To evaluate the signs/symptoms of JIA, safety and tolerability of nap/eso in adolescents age 12 to 16 years. <h3>Methods</h3> Forty-six children and adolescents with JIA by ILAR criteria, mean age of 13.6 years, from 18 US sites were prospectively enrolled over 2 years and treated for up to 6 months. Mean number of active joints at baseline was 3.1. Doses were based on baseline weight (table 1). Disease activity 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. <h3>Results</h3> Forty-six patients received at least 1 dose of study drug and 36 completed the trial. The% of patients achieving ACR Paediatric response increased over time (figure 1). 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. Thirty-seven (80.4%) had at least 1 TEAE. Frequent TEAEs (≥5%) were upper respiratory tract infection, upper abdominal pain, sinusitis, diarrhoea, headache, nausea, and ligament sprain. Eleven (23.9%) had at least 1 TEAE considered to be related to study drug. Most frequent study drug-related TEAE (≥5%) was upper abdominal pain. Four (8.7%) discontinued due to a TEAE. Note: the number above each bar represents the number of patients at that dose. The ACR Pediatric-30,–50, −70, and −90 responses were defined as an improvement of at least 30% (or 50%, 70%, 90% respectively) from baseline in at least 3 of the 6 signs and symptoms variables, with no more than 1 of the remaining variables worsening by &gt;30%. JIA signs and symptoms variables: physician's global assessment of disease activity, CHAQ disability index score, CHAQ global assessment of well-being, number of joints with active arthritis, number of joints with limited range of motion, serum CRP or ESR. <h3>Conclusions</h3> 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%. No new safety signals were identified for the well-characterised components of this fixed dosed JIA treatment, which was developed to reduce the risk of gastric ulcers. <h3>References</h3> [1] Petty RE, et al. J Rheumatol2004:31:390–392 [2] Rigante D, et al. Clinic Rev Allerg Immunol2015; 49:253–261 [3] Ringold S, et al. Arthritis Rheum2013; 65 (10):2499–2512 <h3>Disclosure of Interest</h3> D. Lovell Grant/research support from: National Institutes of Health, NIAMS. Cincinnati Childrens Hospital Medical Centre receives funds from AstraZeneca, Bristol-Myers Squibb, AbbVie, Pfizer, Roche, Novartis, UBC, Forest Research Institute, Horizon Pharma, Johnson and Johnson, Biogen, Takeda, Genentech, GlaxoSmithKline, Boehringer Ingelheim, Celgene, and Janssen for consulting, Speakers bureau: Genentech and Bristol Meyers Squibb, J. Dare Grant/research support from: AbbVie, AstraZeneca, Bristol-Myers Squibb, Horizon Pharma, Medac, Pfizer, Roche and UCB, J. Ball Shareholder of: Horizon Pharma USA, Inc., Employee of: Horizon Pharma USA, Inc., M. Francis-Sedlak Shareholder of: Horizon Pharma USA, Inc., Employee of: Horizon Pharma USA, Inc., B. LaMoreaux Shareholder of: Horizon Pharma USA, Inc., Employee of: Horizon Pharma USA, Inc., R. Holt Shareholder of: Horizon Pharma USA, Inc., Employee of: Horizon Pharma USA, Inc.