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

Abstract

Table 2 Patient Disposition Number (%) of Patients Naproxen/Esomeprazole Magnesium 250 mg/20 mg Naproxen/Esomeprazole Magnesium 375 mg/20 mg Naproxen/Esomeprazole Magnesium 500 mg/20 mg Total Enrolled 51 Not assigned treatment (eligibility criteria not fulfilled) 5 Assigned treatment 4 20 22 46 -Received study drug 4 (100) 20 (100) 22 (100) 46 (100) -Completed study and received 6 mo of study drug 3 (75.0) 16 (80.0) 17 (77.3) 36 (78.3) -Discontinued prematurely 1 (25.0) 4 (20.0) 5 (22.7) 10 (21.7) -Adverse event 1 (25.0) 1 (5.0) 2 (9.1) 4 (8.7) -Lost to follow-up 0 2 (10.0) 0 2 (4.3) -Severe non-compliance with protocol 0 1 (5.0) 0 1 (2.2) -Withdrew consent 0 0 3 (13.6) 3 (6.5) Table 3 Demographics and Baseline Characteristics Naproxen/Esomeprazole Magnesium 250 mg/20 mg (N = 4) Naproxen/Esomeprazole Magnesium 375 mg/20 mg (N = 20) Naproxen/Esomeprazole Magnesium 500 mg/20 mg (N = 22) Total (N = 46) Age (years) Mean 12.8 13.6 13.8 13.6 SD 0.96 1.47 1.33 1.37 Median 12.5 13.0 13.5 13.0 Min, Max 12, 14 12, 16 12, 16 12, 16 Sex, n (%) Female 3 (75.0) 15 (75.0) 15 (68.2) 33 (71.7) Male 1 (25.0) 5 (25.0) 7 (31.8) 13 (28.3) Race, n (%) White 4 (100) 15 (75.0) 17 (77.3) 36 (78.3) Black or African American 0 3 (15.0) 2 (9.1) 5 (10.9) Asian 0 0 2 (9.1) 2 (4.3) Other 0 2 (10.0) 1 (4.5) 3 (6.5) Weight (kg) Mean 39.3 53.8 59.4 55.2 SD 2.63 9.37 8.27 10.07 Median 38.5 50.5 58.0 54.5 Min, Max 37, 43 42, 76 49, 76 37, 76 Height (cm) Mean 157.5 158.6 162.5 160.4 SD 4.73 8.78 7.70 8.14 Median 156.0 156.5 159.5 158.5 Min, Max 154, 164 144, 175 152, 176 144, 176 BMI (kg/m2) Mean 15.86 21.34 22.56 21.45 SD 1.579 2.797 3.476 3.534 Median 15.41 20.42 21.69 20.75 Min, Max 14.5, 18.1 16.8, 26.6 17.3, 32.0 14.5, 32.0 No. of Joints With Active Arthritisa N 4 19 21 44 Mean 1.0 4.1 2.5 3.1 SD 1.15 10.56 3.84 7.39 Median 1.0 1.0 1.0 1.0 Min, Max 0, 2 0, 46 0, 16 0, 46 BMI body mass index, max maximum, min minimum, SD standard deviation aA joint was considered to have active arthritis if the patient had any of the following: swelling, loss of motion and pain on motion, and/or loss of motion and tenderness. Table 4 TEAEs occurring in at least 2 patients Number (%) of Patients MedDRA System Organ Class Preferred Term NAP/ESO 250 mg/20 mg (N = 4) NAP/ESO 375 mg/20 mg (N = 20) NAP/ESO 500 mg/20 mg (N = 22) Total (N = 46) Patient with any TEAE 4 (100) 16 (80.0) 17 (77.3) 37 (80.4) Gastrointestinal disorders 1 (25.0) 8 (40.0) 8 (36.4) 17 (37.0) Abdominal pain upper 0 3 (15.0) 2 (9.1) 5 (10.9) Diarrhea 0 2 (10.0 2 (9.1) 4 (8.7) Nausea 0 3 (15.0) 1 (4.5) 4 (8.7) Abdominal discomfort 0 2 (10.0) 0 2 (4.3) Dyspepsia 0 0 2 (9.1) 2 (4.3) Vomiting 0 1 (5.0) 1 (4.5) 2 (4.3) Infections and infestations 2 (50.0) 4 (20.0) 9 (40.9) 15 (32.6) Upper respiratory tract infection 1 (25.0) 2 (10.0) 6 (27.3) 9 (19.6) Sinusitis 0 1 (5.0) 4 (18.2) 5 (10.9) Gastroenteritis viral 0 0 2 (9.1) 2 (4.3) Tooth infection 0 1 (5.0) 1 (4.5) 2 (4.3) Musculoskeletal and connective tissue disorders 2 (50.0) 2 (10.0) 2 (9.1) 6 (13.0) Back pain 1 (25.0) 1 (5.0) 0 2 (4.3) Pain in extremity 0 1 (5.0) 1 (4.5) 2 (4.3) Injury, poisoning and procedural complications 0 2 (10.0) 3 (13.6) 5 (10.9) Ligament sprain 0 0 3 (13.6) 3 (6.5) Nervous system disorders 2 (50.0) 1 (5.0) 2 (9.1) 5 (10.9) Headache 1 (25.0) 1 (5.0) 2 (9.1) 4 (8.7) General disorders and administration site conditions 0 0 2 (9.1) 2 (4.3) Fatigue 0 0 2 (9.1) 2 (4.3) Immune system disorders 0 1 (5.0) 1 (4.5) 2 (4.3) Hypersensitivity 0 1 (5.0) 1 (4.5) 2 (4.3) Neoplasms benign, malignant and unspecified (incl. cysts and polyps) 1 (25.0) 1 (5.0) 0 2 (4.3) Skin papilloma 1 (25.0) 1 (5.0) 0 2 (4.3) Respiratory, thoracic and mediastinal disorders 0 1 (5.0) 1 (4.5) 2 (4.3) Cough 0 1 (5.0) 1 (4.5) 2 (4.3) Secondary outcomes- pharmacokinetics Forty patients supplied samples for esomeprazole and 41 provided samples for naproxen. Competing interests D.J.L. receives grant / research support from the National Institutes of Health, NIAMS; Cincinnati Children’s Hospital Medical Center receives funds for DJL consulting from AstraZeneca, Bristol-Myers Squibb, AbbVie, Pfizer, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, GlaxoSmithKline, Boehringer Ingelheim, Celgene, and Janssen for consulting; He is on the speaker bureaus of Genentech and Bristol Meyers Squibb. (DOCX 54 kb) Authors’ Affiliations (1) Cincinnati Children’s Hospital Medical Center, Cincinnati, USA (2) University of Cincinnati School of Medicine, Cincinnati, USA (3) Arkansas Children’s Hospital, Little Rock, USA (4) Horizon Pharma USA, Inc, Lake Forest, USA (5) University of California San Francisco Pediatric Rheumatology, San Francisco, USA (6) University of Nebraska Medical Center/Children’s Hospital and Medical Center, Omaha, USA (7) Augusta University Medical Center, Augusta, USA (8) O & O Alpan, LLC, Fairfax, USA (9) Rheumatology and Immunology Private Practice, Memphis, USA (10) St. Christopher’s Hospital for Children, Philadelphia, USA (11) The Cleveland Clinic, Cleveland, USA (12) Toledo Clinic Inc, Toledo, USA (13) Cohen Children’s Medical Center of New York, New Hyde Park, USA (14) Children’s National Medical Center, Washington, DC, USA (15) Department of Pharmacy Practice, College of Pharmacy, University of Illinois-Chicago, Vernon Hills, USA Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al.