Oral Glucocorticoids and Rates of Incident Diabetes Mellitus and Hypertension in Children with Juvenile Idiopathic Arthritis and Attention-Deficit/Hyperactivity Disorder

Daniel B. Horton¹, Fenglong Xie², Lang Chen², Melissa Mannion³, Brian L. Strom^4,5, Jeffrey Curtis⁶ and Timothy Beukelman⁷, ¹Pediatrics, Division of Pediatric Rheumatology, Rutgers Robert Wood Johnson Medical School, Rutgers Biomedical and Health Sciences, New Brunswick, NJ, ²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL, ³Pediatrics, University of Alabama at Birmingham, Birmingham, AL, ⁴Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, ⁵Rutgers Biomedical and Health Sciences, New Brunswick, NJ, ⁶Division Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL, ⁷Pediatric Rheumatology, University of Alabama at Birmingham, Birmingham, AL

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Diabetes, glucocorticoids, hypertension, juvenile idiopathic arthritis (JIA) and pediatrics

Session Information

Date: Sunday, November 13, 2016

Title: Pediatric Rheumatology – Clinical and Therapeutic Aspects - Poster I: Juvenile Idiopathic Arthritis, Uveitis

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Diabetes mellitus (DM) and hypertension (HTN) are well-known toxicities of glucocorticoids (GCs), but the risks of these complications are unclear in children with JIA. We studied rates of new-onset DM and HTN after oral GC exposure compared with non-users separately in children with JIA and children with attention-deficit/hyperactivity disorder (ADHD), a non-immune reference population.

Methods: Using Medicaid claims data (2000-2010), we identified children ages 1-18 diagnosed with JIA (based on diagnostic codes ± pharmacy claims) or ADHD (based on diagnostic codes). We studied oral GCs as time-varying exposures based on pharmacy claims after a ≥9-month GC-free baseline period. Incident DM was defined by new use of insulin or oral antidiabetic drugs; secondary type 2 DM definitions combined diagnoses and pharmacy claims. Incident HTN was defined by new use of antihypertensive drugs combined with diagnoses. We compared absolute rates of new DM and HTN in each cohort and used Cox regression to estimate hazard ratios (HRs) between GC-exposed and -unexposed children.

Results: Children with JIA contributed ~2,600 person-years (py) of GC-exposed time and ~38,000 py of unexposed time; children with ADHD had ~7,500 py exposed to GCs and ~1.6 million py unexposed. Compared with non-users, GC users were younger and more likely to be recently hospitalized before study entry. Within disease cohorts, exposed and unexposed groups were similar in terms of sex, race/ethnicity, and prior comorbidities. Compared with the unexposed, incremental rate differences of new DM drug use and type 2 diabetes were 10.4/1,000 py and 4.5/1,000 py in GC users with JIA, respectively, and 5.1/1,000 py and 1.7/1,000 py in GC users with ADHD, respectively (Table). The rate differences for new antihypertensive drug use were of similar magnitude: 15.4/1,000 py greater in GC users with JIA and 4.8/1,000 py greater in GC users with ADHD. After adjusting for age, sex, race/ethnicity, year of study entry, prior comorbidities and medications, and baseline healthcare utilization, GC exposure was associated with new DM drug use in children with JIA: current GC use, aHR 3.4 (95% CI 2.4, 4.8); any prior GC use, aHR 1.7 (95% CI 1.2, 2.4). The associations of GC use with type 2 DM in JIA, and with DM among children with ADHD, were similar (Table). The strength of association between GCs and HTN was even greater: current GC use, aHR 4.5 (95% CI 3.2, 6.2); any prior GC use, aHR 2.4 (95% CI 1.6, 3.6). Results for children with ADHD were also similar (Table).

Conclusion: In children with JIA, current oral glucocorticoid use is associated with a 3-fold increased rate of new treatment for diabetes mellitus and over 4-fold increased rate of new treatment for hypertension. These findings are similar among children with ADHD, but the absolute rates of these complications are higher in children with JIA. More work is needed to clarify how GC dose and duration relate to these toxicities.

Table. Absolute and relative (hazard) rates of new diabetes mellitus and hypertension among GC-exposed and -unexposed children with JIA and ADHD
	Diabetes mellitus				Hypertension
	New DM drug use¹		New type 2 DM²		New HTN drug use³
	JIA	ADHD	JIA	ADHD	JIA	ADHD
No. of outcomes/ person-years
Never GC-unexposed⁴	163 / 38,323	3,423 / 1,579,778	78 / 38,538	1,230 / 1,583,059	140 / 37,864	2,129 / 1,577,660
Ever GC-exposed⁴	40 / 2,730	56 / 7,691	18 / 2,759	19 / 7,712	49 / 2,561	46 / 7,463
Incidence per 1,000 py (95% CI)
Never GC-unexposed⁴	4.3 (3.7, 5.0)	2.2 (2.1, 2.2)	2.0 (1.6, 2.5)	0.8 (0.7, 0.8)	3.7 (3.1, 4.4)	1.4 (1.3, 1.4)
Ever GC-exposed⁴	14.7 (10.8, 20.0)	7.3 (5.6, 9.5)	6.5 (4.1, 10.4)	2.5 (1.6, 3.9)	19.1 (14.5, 25.3)	6.2 (4.6, 8.2)
Rate difference	10.4 (5.8,15.0)	5.1 (3.2, 7.0)	4.5 (1.5,7.5)	1.7 (0.6, 2.8)	15.4 (10.0, 20.8)	4.8 (3.0, 6.6)
Model 1⁵:
No current GC exposure (ref)	1.0	1.0	1.0	1.0	1.0	1.0
Any current GC exposure,⁴ aHR (95% CI)	3.4 (2.4, 4.8)	3.4 (2.6, 4.4)	3.2 (1.9, 5.4)	3.1 (2.0, 4.9)	4.5 (3.2, 6.2)	4.3 (3.2, 5.8)
Model 2⁵:
Never GC exposure (ref)	1.0	1.0	1.0	1.0	1.0	1.0
Ever GC exposure,⁴ aHR (95% CI)	1.7 (1.2, 2.4)	1.4 (1.3, 1.5)	1.9 (1.1, 3.2)	1.4 (1.2, 1.6)	2.4 (1.6, 3.6)	1.7 (1.6, 1.9)
ADHD, attention-deficit/hyperactivity disorder; aHR, adjusted hazard ratio; CI, confidence interval; DM, diabetes mellitus; GC, oral glucocorticoid; HTN, hypertension; py, person-years; ref, reference. ¹Insulin or oral antidiabetic drugs ²Type 2 diabetes diagnosis based on combination of diagnosis claims and antidiabetic drug pharmacy claims ³Because of their decreased specificity to hypertension diagnoses, beta-blockers and clonidine needed to be accompanied by ICD-9 code for hypertension within ± 4 months ⁴Exposure status during the study period; exposure was reclassified in time-varying fashion; some subjects contributed time to both exposure cohorts ⁵ Models adjusted for age, sex, race/ethnicity, year of cohort entry, prior comorbidities (for DM: hypertension, obesity; for HTN: diabetes, obesity), prior medications (for DM: antipsychotics, non-steroidal anti-inflammatories; for HTN: non-steroidal anti-inflammatories, stimulants), recent healthcare utilization (hospitalization, number of baseline medications, number of clinical encounters)

Disclosure: D. B. Horton, None; F. Xie, None; L. Chen, None; M. Mannion, None; B. L. Strom, AstraZeneca, 5,Bayer, 5,Boehringer Ingelheim, 5,GSK, 5,Eli Lilly and Company, 5,Roche Pharmaceuticals, 5,Sanofi-Aventis Pharmaceutical, 5,Takeda, 5,UCB, 5; J. Curtis, None; T. Beukelman, Novartis Pharmaceutical Corporation, 5,UCB, 5.

To cite this abstract in AMA style:

Horton DB, Xie F, Chen L, Mannion M, Strom BL, Curtis J, Beukelman T. Oral Glucocorticoids and Rates of Incident Diabetes Mellitus and Hypertension in Children with Juvenile Idiopathic Arthritis and Attention-Deficit/Hyperactivity Disorder [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/oral-glucocorticoids-and-rates-of-incident-diabetes-mellitus-and-hypertension-in-children-with-juvenile-idiopathic-arthritis-and-attention-deficithyperactivity-disorder/. Accessed .

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