Results from a six-month, Phase 4 trial support a combination therapy of the anti-inflammatory naproxen together with an immediate-release form of esomeprazole to reduce the risk of gastric ulcers in adolescents with juvenile idiopathic arthritis (JIA).
The study, “A 6-month, multicenter, open-label study of fixed dose naproxen/esomeprazole in adolescent patients with juvenile idiopathic arthritis,” was published in the journal Pediatric Rheumatology.
The underlying causes of JIA remain largely unknown, and the main therapeutic strategy against the disease relies on the use of anti-inflammatory agents, such as naproxen (sold under several brand names). However, this type of treatment may lead to serious side effects, such as gastric ulcers.
In pediatric patients ages 12-16 with gastroesophageal reflux disease — when stomach contents come back up into the esophagus — treatment with delayed-release esomeprazole (brand name Nexium, by AstraZeneca) proved effective as a short-term treatment. Esomeprazole is a proton pump inhibitor that blocks acid production in the stomach.
Now, a team of researchers reported the results of a Phase 4 clinical trial (NCT01544114) that assessed the effectiveness of a combination therapy of naproxen with an immediate-release form of esomeprazole to reduce the risk of gastric ulcers in JIA patients.
They evaluated the safety and tolerability of three different concentrations of naproxen — 250 mg, 375 mg, or 500 mg — together with 20 mg of esomeprazole, given twice a day, 30 minutes before morning and evening meals. The treatment was administered for six months.
The study included 46 adolescents with JIA ages 12 to 16 (mean age 13.6), of which 36 completed the trial. The study’s primary objective (endpoint) was to evaluate the safety of the combo therapy by measuring the number of patients with treatment-emergent adverse events.
Effectiveness was assessed by measuring disease activity via the American College of Rheumatology (ACR) response criteria — ACR30, ACR50, ACR70, ACR90 — defined as improvements in a certain number of symptoms of at least 30%, 50%, 70%, or 90%, respectively, from the beginning of the study.
Additional parameters assessed included participants’ responses to the Childhood Health Assessment Questionnaire (CHAQ) discomfort and functional scores at months 1, 3, and 6.
CHAQ is a self-reported questionnaire that measures both disability and discomfort, and is one of the most commonly used in children and teens with JIA.
In total, 37 patients had at least one treatment-emergent adverse event (TEAE), with the most common including upper respiratory tract infection, upper abdominal pain, sinusitis, diarrhea, headache, nausea, and ligament sprain.
A total of 11 patients had at least one adverse effect that was related to the combo therapy, with four patients having to discontinue the treatment due to the development of hepatitis, numbness, abdominal pain, or worsening of JIA.
Concerning effectiveness, the combination therapy led to an improvement in JIA signs and symptoms, with the number of patients achieving ACR pediatric response increasing over time. By the end of the study (month six), 47.1% of the patients achieved ACR-30; 38.2% achieved ACR-50; 32.4%, ACR-70; and 17.6% achieved ACR-90.
The CHAQ discomfort scores also improved with the combo therapy, specifically in the functional parameters for rising, walking, and activities, as well as in dressing and grooming, eating, hygiene, and grip.
No link between a particular dose of naproxen and effectiveness was found.
“The fixed combination of NAP/ESO [naproxen/esomeprazole] was well tolerated in JIA patients aged 12 to 16 years,” researchers wrote. “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 in patients requiring chronic naproxen therapy.”
The research team believes the combo therapy of naproxen and esomeprazole could be an effective strategy to reduce the incidence of naproxen-related gastric ulcers in JIA patients.