Pediatric gastroesophageal reflux disease and acid-related conditions: trends in incidence of diagnosis and acid suppression therapy

Abstract

Objective: To describe the incidence of diagnosis of gastroesophageal reflux disease and acid-related conditions (GERD/ARC) throughout childhood and characterize patterns of diagnosis and treatment with proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H₂RAs).

Methods: Cohorts of GERD/ARC children (age 0–18 years) were identified from a large US administrative claims database covering 1999–2005 using ICD-9 codes. Incidence, healthcare utilization (HCU), costs, therapy discontinuation and switching rates were compared between various age and patient groups.

Results: Between 2000 and 2005 annual incidence of GERD/ARC diagnosis among infants (age ≤1 year) more than tripled (from 3.4 to 12.3%) and increased by 30% to 50% in other age groups. Patients diagnosed by GI specialists (9.2%) were more likely to be treated with PPIs compared to patients diagnosed by primary care physician (PCP). PPI-initiated patients doubled (from 31.5% in 1999 to 62.6% in 2005) and, when compared with H₂RA-initiated patients, were associated with 30% less discontinuation and 90% less therapy switching in the first month, and with higher comorbidity burden and pre-treatment total HCU and costs when diagnosed by GI specialists.

Limitations: The use of an exploratory definition for GERD/ARC, administrative claims data and potential coding errors in diagnosis codes used in selection process may limit the generalizability of the results.

Conclusions: GERD/ARC incidence increased for children of all ages between 2000 and 2005. PCPs made the majority of diagnoses. PPI initiations have now surpassed H₂RA initiations.

Key words::

• claims database
• gastroesophageal reflux disease (GERD) and acid-related conditions (ARC)
• histamine-2 receptor antagonists (H₂RA)
• incidence; proton pump inhibitor (PPI)

Introduction

Symptoms of gastroesophageal reflux (GER) are common during infancy and childhood^1,2 and include regurgitation, heartburn, epigastric pain, and respiratory difficulties³. Frequent regurgitation alone affects over half of newborns¹, but generally resolves with age, affecting fewer than 5% of children after their first year^1,2. However disruptive GER symptoms may constitute GER disease (GERD)³.

Despite the high prevalence of pediatric GER symptoms, the frequency of pediatric GERD diagnosis has not been widely studied. The prevalence of GER varies substantially depending on age and symptom^1,2. For the prevalence of GERD, however, little is known. Chitkara et al⁴ estimate the annual incidence of GERD among children aged less than 5 years to be 0.09%. Anecdotal evidence suggests that the incidence of diagnosis of GERD is increasing among children, and increasing rates of GERD have been documented in hospitalized infants⁵. These trends parallel a more thoroughly documented increase in GERD diagnoses among adults⁶.

The goal of treatment for pediatric GERD/acid- related conditions (ARC) is to eliminate symptoms, allow healing of esophageal mucosa and prevent or manage complications³. Pharmacological therapies for the treatment of GERD/ARC include promotility agents (metoclopramide and bethanechol) and acid suppression with histamine-2 receptor antagonists (H₂RAs) or proton pump inhibitors (PPIs). Promotility agents are not recommended for routine use. Both H₂RAs and PPIs have been shown to be efficacious in children and are widely prescribed in pediatric practice^3,7. However, no evidence-based guidance is available regarding the choice between H₂RAs and PPIs, and patterns of H₂RA and PPI use in infants and children have not been fully characterized. Pediatric PPI prescriptions for all indications have risen sharply in recent years, quadrupling for infants between 2000 and 2003⁸ and tripling for children aged 12–17 years between 1997 and 2000⁹. However, the extent to which this increase in pediatric PPI prescriptions represents an increasing preference for PPIs over H₂RAs, as described in adults¹⁰, versus an increasing incidence of the diagnosis of pediatric GERD/ARC remains unclear.

Using an administrative claims database, the present study examines: (1) the incidence of diagnosis of pediatric GERD or acid-related conditions (ARC) across age groups and over time between 2000 and 2005, and (2) diagnosis and treatment patterns of pediatric GERD/ARC patients between 1999 and 2005. Pre-diagnosis demographics, comorbidity profiles and healthcare resource use are also compared between children diagnosed by primary care physicians (PCPs) and those diagnosed by gastrointestinal (GI) specialists. Acid-related conditions is an exploratory category created for this study to ensure that potential ICD-9-CM codes are captured that could potentially be used to diagnose GERD. For the purpose of this study, ‘diagnosis’ refers to the ICD-9-CM diagnosis codes available in the claims data to represent GERD/ARC.

Methods

Data

Study samples of children (aged 0–17 years) were drawn from a HIPAA-compliant, de-identified in-house administrative claims database, which includes over 5 million lives (of which approximately 1.2 million were under 18 years of age) from 31 large, privately-insured companies across the US. The businesses of these Fortune 500 companies span a wide spectrum of industries, including financial services, energy, telecommunications, and food and beverages. Beneficiaries include employees, retirees, spouses and dependents. The database contains information on all beneficiaries’ demographics, monthly enrollment history, medical service utilization, and prescription drug dispenses available from 1999 through 2005. All visits to medical professionals (i.e., doctors, nurse practitioners, physician assistants, etc.) are included. While this database does not contain Medicaid claims it is a large dataset that is well representative of the population. Different samples of children were selected for the study of (1) incidence rates to examine the occurrence of selected ICD-9 codes that represent pediatric GERD/ARC, (2) diagnosis patterns to identify what physician specialties were involved in the diagnosis of GERD/ARC in pediatric population, and (3) treatment patterns uses to treat pediatric GERD/ARC.

Incidence rates analysis: sample selection criteria

Annual incidence rates of GERD/ARC were calculated for each year between 2000 and 2005. To be included in the incidence rate calculation for a particular year children were required to be (a) younger than 18 years of age in the year in question, (b) continuously enrolled in their health plans for at least the entire year in question, and (c), for children older than 1, to be continuously enrolled in their health plan and free of GERD/ARC diagnosis during the 6 months prior to the year in question (washout period). To calculate the annual incidence rate, the individuals meeting all selection criteria above during calendar years and age groups of interest were first identified (denominator). Then, for each year–age-group combination of interest, the incidence rate was defined as the number of such individuals who had been diagnosed with GERD (numerator) divided by the denominator. The defining list of ICD-9 codes for GERD/ARC was developed based on discussions with experts in pediatric GERD. Because there were multiple potential codes for GERD/ARC only those that were highly specific for the intent to diagnose a child with GERD/ARC were included. The ICD-9 codes for GERD included 530.81 (Esophageal reflux) and for ARC 530.1x (Esophagitis), 535.xx (Gastritis and duodenitis), 787.1 (Heartburn) and 789.06 (Epigastric pain).

Diagnosis patterns analysis: sample selection criteria and diagnosis definition

Children included in the diagnosis pattern analysis were required to be (a) younger than age 18 years at the time of receiving their first diagnosis of GERD/ARC symptoms (index date), (b) diagnosed by a PCP (family practice, internal medicine, general preventive medicine and pediatrician) or a GI specialist (gastroenterologist and pediatric gastroenterologist), and (c) continuously enrolled in their health plan for the 6 months prior to the index date (pre-diagnosis baseline period).

Treatment patterns analysis: sample selection criteria and pattern definitions

Prescriptions for H₂RAs (cimetidine, famotidine, nizatidine, ranitidine) and PPIs (esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole) were identified based on 9-digit National Drug Codes (NDC). Children with initial prescriptions for an H₂RA or PPI were identified irrespective of the dosage form (e.g., tablets, melt tablets). The index date and the index therapy were defined to be the date and type (H₂RA or PPI) of the initial therapy. To be included in the analyses, children must have (a) been continuously enrolled in their health plans during the 6 months prior to the index date (the pre-treatment baseline period), (b) been continuously enrolled during the 6 months following the index date (the study period), (c) received a GERD/ARC diagnosis during either the pre-treatment baseline period or the month following the index date, (d) been free of H₂RA or PPI prescriptions during the pre-treatment baseline period and (e) been free of combination H₂RA-PPI prescriptions within 1 week following the index date.

Discontinuation of index therapy was defined as a supply gap of 30 or more days of the index drug (H₂RA or PPI). Among patients discontinuing their index therapy, therapy switching was defined as receiving a drug from the alternative class (i.e., changing from PPI to H₂RA or vice versa) within 14 days following the last supply day of index drug prior to discontinuation.

Baseline cost calculations

Drug costs were defined as the costs for all prescription drugs identified using NDC codes (GERD/ARC related or not). Medical costs were defined as all non-drug costs, including inpatient and outpatient hospital visits, physician office visits, emergency room (ER) visits and all lab tests. Total healthcare costs were defined as the sum of drug and medical costs. All of the costs were calculated using the reported payments made by the insurance companies. Other costs such as co-payment, coinsurance or deductibles (e.g., third party costs) were not included in the calculation of costs.

Statistical methods

Incidence Rate Analysis: The annual incidence of the diagnosis of GERD/ARC was computed separately for different age groups in each year. GERD/ARC patients were further classified as to whether they received prescriptions for H₂RAs or PPIs during the year of diagnosis.

Diagnosis Patterns Analysis: GERD/ARC patients diagnosed by PCPs were compared to those diagnosed by GI specialists in terms of pre-diagnosis baseline characteristics, including comorbidities, prescriptions for H₂RAs or PPIs, healthcare resource use and total healthcare costs. Chi-squared tests were used to compare categorical variables and Wilcoxon rank sum tests were used to compare continuous variables. Among patients free of H₂RA or PPI prescriptions during the pre-diagnosis baseline, the proportions prescribed H₂RAs or PPIs in the first month following diagnosis were computed for PCPs and GI specialists.

Treatment Patterns Analysis: Rates of discontinuation and switching and median days on index therapy were estimated using the Kaplan–Meier method for patients initiated with H₂RAs or PPIs. Using the same methods as in the analysis of diagnosis patterns, patient characteristics measured during the pre-treatment baseline period, including comorbidities, all-cause and GERD-related healthcare utilization and healthcare costs, were compared between H₂RA patients and PPI patients. Trends in prescription H₂RA vs. PPI use over time were estimated using ordinary least squares (OLS) regression. Logistic regression was used to identify pre-treatment baseline characteristics associated with the use of PPIs vs. H₂RAs as the first line therapy in pediatric GERD/ARC patients. All analyses were conducted in SAS Version 9.1 (SAS Institute, Cary, NC, USA).

Results

Incidence rates

The annual incidence of the diagnosis of GERD/ARC increased between 2000 and 2005 for children of all ages (Table 1). Infants (ages 0 and 1) experienced the largest increase (262%) from an annual incidence of diagnosis of 3.4% in 2000 to 12.3% in 2005. During the same period, the annual incidence of the diagnosis of GERD/ARC among the other children of different age groups (i.e., 2, 3–5, 6–11 and 12–17), increased by 34% to 50%. Among the children older than age 1, those in the 12–17 group experienced the highest incidence rate (1.26%) in 2005, an increase from 0.94% in 2000. Similar conclusions can be drawn from the analysis of incidence rates of pediatric patients with subsequent prescription treatment with either H₂RAs or PPIs (Table 1).

Table 1. Annual incidence rate of the diagnosis of GERD/ARC in pediatric patients by age group.

All pediatric patients (ages 0–17)
Year*	0–1	2	3–5	6–11	12–17
2000	3.40	0.75	0.62	0.79	0.94
2005	12.30	1.11	0.93	1.09	1.26
% Change	262	48	50	38	34
Pediatric patients treated with H2RAs or PPIs
Year*	0–1	2	3–5	6–11	12–17
2000	1.50	0.17	0.10	0.13	0.29
2005	8.10	0.33	0.28	0.40	0.46
% Change	440	94	180	208	59

*Incidence rates for each year-age group combination were calculated as the number of individuals diagnosed with GERD divided by the total number of individuals in each year-age group category.

H₂RA, histamine-2 receptor antagonists; PPI, proton pump inhibitor.

Diagnosis patterns

The majority of the 21,471 children identified with GERD/ARC between 1999 and 2005 were diagnosed by PCPs (90.8%) with the remaining 9.2% diagnosed by GI specialists. Compared to PCP-diagnosed patients, GI specialist-diagnosed patients had a higher prevalence of comorbid symptoms and conditions, used more healthcare resources and incurred higher total healthcare costs at baseline (Table 2). The most common co-morbid conditions were abdominal pain (excluding epigastric pain) and pharyngitis. Pre-diagnosis H₂RA treatment was more prevalent than PPI treatment in PCP-diagnosed patients (4.3 vs. 2.6%), whereas GI specialist-diagnosed patients were more likely to have baseline use of PPIs than H₂RAs (19.1 vs. 15.5%). For patients free of H₂RA or PPI prescriptions during the pre-diagnosis baseline period, those diagnosed by a GI specialist were more likely to be prescribed PPIs vs. H₂RAs (30 vs. 9%) within the first month following diagnosis whereas those diagnosed by PCPs were less likely to be prescribed PPIs vs. H₂RAs (10 vs. 14%).

Table 2. Baseline characteristics of pediatric GERD/ARC patients diagnosed by GI specialists and primary care physicians (PCPs).

Baseline characteristics*	GI specialist	PCP^†	p-value^‡
Sample size, n	1,985	19,486
Female, %	51.8%	52.5%	0.534
Age, mean (SD)	10.5 (5.1)	9.9 (5.2)	<0.001^§
Number of comorbid conditions, mean (SD)	1.78 (1.50)	1.01 (1.22)	<0.001^§
Healthcare utilization, %
Hospitalization	9.0%	3.7%	<0.001^§
ER visit	21.2%	14.6%	<0.001^§
Outpatient visit	51.4%	26.8%	<0.001^§
Number of outpatient visits, mean (SD)	1.51 (3.54)	0.58 (1.78)	<0.001^§
Relevant medication use, %
H2 antagonists	15.5%	4.3%	<0.001^§
PPIs	19.1%	2.6%	<0.001^§
Promotility agents	2.9%	0.6%	<0.001^§
Healthcare costs, mean (SD)
Total drug cost	$400 ($1,497)	$169 ($962)	<0.001^§
Total medical cost	$4,091 ($25,835)	$1,268 ($11,200)	<0.001^§
Total healthcare cost	$4,492($26,299)	$1,437 ($11,330)	<0.001^§

*Baseline characteristics were measured over the 6 months prior to the first GERD/ARC diagnosis.

^†PCP (primary care physician) included family practice, internal medicine, general preventive medicine and pediatrician.

^‡Wilcoxon tests were used for comparing continuous variables; chi-squared tests were used for comparing categorical variables.

^§Significant at 5% level.

GERD, gastroesophageal reflux disease; ARC, acid-related conditions; H₂RA, histamine-2 receptor antagonists; PPI, proton pump inhibitor; GI specialist, gastrointestinal specialist.

Treatment patterns

Of the 9,329 GERD/ARC patients initiated on an H₂RA or PPI between 1999 and 2005, 4,729 (50.7%) were initiated on an H₂RA. Compared to patients initiated on H₂RAs, patients initiated on PPIs (Table 3) had a significantly higher prevalence of comorbid symptoms and conditions, upper respiratory infections, otitis media and abdominal pain being the most common, during the pre-treatment baseline period and significantly higher healthcare resource use and total healthcare costs ($4,431 vs. $3,887). Between 1999 and 2005, the proportion of PPI patients followed an increasing trend in all age groups (p-value for trend <0.001), with the overall proportion of PPI-initiated patients nearly doubling from 31.5% to 62.6% (Figure 1). In addition, older patient groups had a higher percentage of PPI use than the younger groups (data not shown).

Figure 1. Distribution of pediatric GERD/ARC patients initiated on H₂RAs and PPIs (1999–2005). GERD, gastroesophageal reflux disease; ARC, acid-related conditions; H₂RA, histamine-2 receptor antagonists; PPI, proton pump inhibitors.

Table 3. Baseline characteristics of pediatric GERD/ARC patients initiated on H₂RAs and PPIs.

Baseline characteristics*	H2RAs	PPIs	p-value^†
Sample size, n	4,729	4,600
Female, %	51.6%	52.9%	0.218
Age, mean (SD)	9.3 (5.5)	11.5 (4.8)	<0.001^‡
Number of comorbid conditions, mean (SD)	1.4 (3.2)	1.7 (4.1)	<0.001^‡
Healthcare utilization, %
Hospitalization, GERD related	2.5%	4.0%	<0.001^‡
Hospitalization, any cause	8.4%	10.0%	0.007^‡
ER visit, GERD related	3.7%	3.8%	0.921
ER visit, any cause	21.9%	22.4%	0.608
Outpatient visit, GERD related	11.6%	21.5%	<0.001^‡
Outpatient visit, any cause	41.4%	53.2%	<0.001^‡
Number of outpatient visits, mean (SD)	1.0 (2.9)	1.5 (3.7)	<0.001^‡
Healthcare costs, mean (SD)
Total drug cost	$201 ($1,239)	$309 ($1,221)	<0.001^‡
Total medical cost	$3,686 ($38,518)	$4,122 ($24,976)	<0.001^‡
Total healthcare cost	$3,887 ($38,585)	$4,431 ($25,190)	<0.001^‡

*Baseline characteristics were measured over the 6 months prior to the initiation of H₂RAs or PPIs.

^†Wilcoxon tests were used for comparing continuous variables; chi-squared tests were used for comparing categorical variables.

^‡Significant at 5% level.

GERD, gastroesophageal reflux disease; ARC, acid-related conditions; H₂RA, histamine-2 receptor antagonists; PPI, proton pump inhibitor.

The median time on index therapy during the first year was also twice as long for patients initiated on PPIs compared to those initiated on H₂RAs (Table 4). PPI patients were 30% less likely to discontinue the index therapy and 90% less likely to switch during the first month following index therapy initiation.

Table 4. Treatment pattern of pediatric GERD/ARC patients initiated on H₂RAs and PPIs.

Treatment pattern	H2RAs	PPIs
Sample size, n	4,729	4,600
Discontinuation of index therapy*
1-month discontinuation rate^† (%)	71.0%	51.7%
Median days on index therapy during first year^‡	30	60
Switching of index therapy^§
1-month switching rate^† (%)	4.6%	0.5%

*Discontinuation was defined as having a 30-day gap between index drug (H₂RA or PPI) supplies.

^†Kaplan–Meier method was used to estimate rates of discontinuation and switching.

^‡Patients were required to be continuously enrolled for the first year after index date.

^§Switching was defined as having a prescription for alternative drug (i.e., H₂RAs for PPI patients, and PPIs for H₂RA patients) within 14 days from the end of last index drug supply. Switching patients were required to discontinue index therapy.

GERD, gastroesophageal reflux disease; ARC, acid-related conditions; H₂RA, histamine-2 receptor antagonists; PPI, proton pump inhibitor.

In a multivariate logistic regression model, initiation with PPIs rather than H₂RAs was associated with older age, more recent treatment initiation, asthma, abdominal pain, depression, dysphagia, noncardiac chest pain, underweight, failure to thrive (FTT), absence of GERD-related ER visits, GERD-related outpatient visits, visits to an otolaryngologist or pulmonologist, diagnosis by upper endoscopy and use of promotility agents during the pre-treatment baseline period (Table 5).

Table 5. Selected predictors of PPIs vs. H₂RAs as first line therapy for pediatric GERD/ARC Patients*,^†.

Potential risk factors^‡	Coefficient	Odds ratio	95% confidence limits		p-value
Age group
Age 0 year	–1.78	0.17	0.12	0.25	<0.001**
Age 1 year	–1.67	0.19	0.15	0.24	<0.001**
Age 2 years	–1.22	0.30	0.22	0.40	<0.001**
Age 3–5 years	–1.00	0.37	0.31	0.44	<0.001**
Age 6–11 years	–0.52	0.59	0.53	0.66	<0.001**
Age 12–17 years as reference
Female	–0.05	0.95	0.87	1.04	0.280
Index year^§
Index year 1999	–1.48	0.23	0.15	0.34	<0.001**
Index year 2000	–1.42	0.24	0.19	0.30	<0.001**
Index year 2001	–1.19	0.30	0.26	0.36	<0.001**
Index year 2002	–0.97	0.38	0.33	0.44	<0.001**
Index year 2003	–0.72	0.49	0.42	0.56	<0.001**
Index year 2004	–0.38	0.69	0.60	0.79	<0.001**
Index year 2005 as reference
Deyo Charlson Comorbidity Index	0.00	1.00	0.88	1.13	0.986
Healthcare utilization
Hospitalization, GERD related	–0.16	0.85	0.63	1.15	0.291
ER visit, GERD related	–0.43	0.65	0.51	0.83	0.001**
Outpatient visit, GERD related	0.30	1.35	1.17	1.57	<0.001**
Allergist visit	0.34	1.41	1.00	2.00	0.053
ENT – otolaryngologist visit	0.56	1.75	1.44	2.12	<0.001**
Pulmonologist visit	0.40	1.50	1.09	2.06	0.014**
Relevant medication use
Promotility agents	0.51	1.67	1.14	2.45	0.009**

*A subset of covariates are shown in this table.

†Based on logistic regression.

^‡Risk factors were measured on the index date or over the 6-month baseline period.

^§Index year referred to the calendar year in which the index date falls.

**Significant at 95% level.

GERD, gastroesophageal reflux disease; ARC, acid-related conditions; H₂RA, histamine-2 receptor antagonists; PPI, proton pump inhibitor.

Discussion

Using a large US claims database, this study described an increasing incidence of diagnosis of pediatric GERD/ARC between 2000 and 2005 across all age groups, with the greatest increase occurring among infants. Patients in this study encompass different areas of the country and different types of health insurance and thus the results are representative of the actual pediatric GERD/ARC population in the US. The incidence rates of diagnosis observed in this study are higher than the estimate of Chitkara et al⁴ for children aged younger than 5 years born between 1976 and 1982. The difference in incidence rates of diagnosis may be explained by several factors.

The broader definition of GERD/ARC used in the present study and the use of only a 6-month washout period to define incident cases of diagnosis of GERD/ARC would be expected to yield higher incidence rates than counting first-ever diagnoses of GERD alone. Given the increasing incidence of diagnosis of GERD/ARC over time, the more current cohort investigated in the present study would be expected to have a higher incidence of diagnosis of GERD/ARC than the historical cohort studied by Chitkara et al⁴. Finally, the nationwide patient population investigated in the present study is more diverse than the largely Caucasian sample from Rochester, Minnesota, studied by Chitkara et al⁴.

A limitation of the present study is that diagnosis codes for GERD/ARC could not be validated against clinical records, as in Chitkara et al⁴. The definition of ARC used in this study is an exploratory category that was defined by the authors for the purpose of this study only. Also, ICD-9 coding can be subjective to the individual doing the actual coding. For example, in clinical practice a child with pain in the upper abdomen might be coded as epigastric pain, GERD, or gastritis depending on the practitioner. Since no tests are usually done it is impossible to know what is, in fact, the true source of the child's pain. The differences in our methodology and patient populations make comparisons with the Chitkara et al⁴ difficult. Interestingly, both studies found no difference in the incidence of the diagnosis of GERD/ARC between males and females.

The annual incidence rates of diagnosis of pediatric GERD/ARC observed in this study in 2000 (0.6–1.0%) are comparable in magnitude to the 0.45% annual incidence rate for GERD in patients of any age in the UK in 1996¹¹ and the 0.54% annual incidence that can be estimated for Georgia Medicaid patients in 1998 using the data reported by Kotzan et al¹². The slightly higher incidence rates of diagnosis observed in this study, compared to patients of any age in 1996 and 1998, are consistent with a higher prevalence of GER symptoms among children compared to adults and with the trend towards increasing rates of GERD diagnosis observed in this study.

Several factors could explain an increasing incidence of pediatric GERD/ARC diagnosis. Awareness of pediatric GERD/ARC may have been increased by marketing campaigns following new labels for pediatric GERD. Given the dramatic increase in the incidence of diagnosis, particularly among infants, it is of concern that some of the increase in GERD/ARC diagnosis may represents over-diagnosis. However, a true modest increase in the incidence of GERD is supported by the world-wide increase in the incidence of Barrett's esophagus and esophageal cancers^13,14, both which are thought to be related to GERD^15,16. Changes in children's lifestyles, especially an increased intake of fats, sugars, and caffeine from fast food and soda¹⁷, as well as an increasing incidence of childhood obesity¹⁸, could contribute to an increased risk of GERD/ARC. It is also possible that some of the increase in GERD/ARC diagnoses could be explained by mis-diagnoses of eosinophilic esophagitis, which is also increasing in incidence¹⁹.

This study found that most infants and children diagnosed with GERD/ARC are diagnosed by PCPs rather than GI specialists. Though a limitation of this study is that prescription treatments for GERD/ARC could not be linked to the prescribing physician's specialty, the preponderance of diagnoses by PCPs suggests that most treatment for GERD/ARC also takes place in a primary care setting. This finding has implications for the design and interpretation of clinical studies of GERD/ARC therapies in pediatrics, as most published studies were conducted in the tertiary care setting.

This study also indicates that less than half of the children identified with GERD/ARC were subsequently prescribed acid-suppression therapy. There is a possibility that these children may be prescribed lifestyle modification or may be using over-the-counter (OTC) H₂RAs or PPIs. Such use of OTC H₂RAs or PPIs by children may be limited especially since these OTC medications are not labeled for pediatric use. Also, the OTC medications would probably be used by older children since they are generally available only in solid dosage forms which may be difficult for infants and younger children to swallow. Since the present study used claims data the authors could not examine lifestyle modifications and to what extent written prescriptions were not filled or if prescriptions that were actually filled were not consumed.

The increase in PPI prescriptions observed in this study is consistent with the increase described by Barron et al⁸. The current study further shows that the increase in pediatric PPI prescriptions is due to two trends: an increasing incidence of diagnosis of pediatric GERD/ARC treated with acid-suppression therapy and an increasing preference for prescription PPIs vs. H₂RAs. The increase use in PPIs in infancy is surprising since PPIs are not FDA approved in this age group and recent infant placebo-controlled trials have not be able to demonstrate efficacy.

The majority of pediatric prescriptions for acid suppression therapy observed in this study were continued for less than 2 months, with patients initiated on H₂RAs tending to discontinue earlier than patients initiated on PPIs. Longer treatment durations with PPIs could arise from PPI patients being generally sicker, in terms of having a higher comorbidity burden and higher healthcare resource utilization at baseline. The durations of use for both PPI and H₂RA treatment observed among pediatric patients in this study are much shorter than durations of use reported in adults²⁰.

Conclusion

The annual incidence of diagnosis of GERD/ARC diagnosis increased for children of all ages between 1999 and 2005, more than tripling among infants, with the majority of diagnoses made by PCPs. Initiation of prescription therapy with PPIs has become increasingly common for pediatric GERD/ARC, and is now more common than initiation with prescription H₂RAs.

Acknowledgment

Declaration of interest: This study was sponsored by Takeda Pharmaceuticals North America, Inc., Deerfield, IL, USA.

S.P.N. has disclosed that she is on the Speakers’ Bureau and serves as a consultant for Takeda Pharmaceuticals North America; S.K. and O.H.D. have disclosed they are employed by Takeda Pharmaceuticals North America; E.Q.W., J.M.M. and N.B. have disclosed they are employed by Analysis Group, Inc. and received consulting fees from Takeda Pharmaceuticals North America.