Effect of First-Line Biologic Initiation on Glucocorticoid Exposure Initiation in Children Hospitalized with New-Onset Systemic Juvenile Idiopathic Arthritis: Emulation of a Pragmatic Trial Using Observational Data
Background: Glucocorticoid exposure is a significant driver of morbidity in children with systemic juvenile idiopathic arthritis (sJIA). We determined the effect of early initiation of biologic therapy (IL-1 or IL-6 inhibition) on glucocorticoid exposure in hospitalized patients with new-onset sJIA.
Methods: We emulated a pragmatic sequence of trials (“pseudo-trials”) of biologic initiation in children (≤ 18 years) hospitalized with new-onset sJIA utilizing retrospective data from an administrative database from 52 tertiary care children’s hospitals from 2008-2019. Eligibility window, treatment assignment and start of follow-up between biologic and non-biologic study arms were aligned for each pseudo-trial. Patients in the source population could meet eligibility criteria at several timepoints. Mixed-effects logistic regression was used to determine the effect of biologic initiation on in-hospital glucocorticoid exposure.
Results: 468 children met eligibility criteria, of which 19% received biologic therapy without preceding or concomitant initiation of immunomodulatory medications. This proportion significantly increased over time during the study period (p < 0.01). 1451 trial subjects were included across 4 pseudo-trials with 71 assigned to the biologic arm and 1409 assigned to the non-biologic arm. After adjustment, there was a trend toward decreased odds of glucocorticoid initiation in the biologic arm compared to the non-biologic arm (OR 0.39, 95% CI [0.13, 1.15]).
Conclusion: Biologic initiation in children hospitalized with new-onset sJIA significantly increased over time and may be associated with reduced glucocorticoid exposure. The increasing use of first-line biologic therapy may lead to clinically relevant reductions in treatment-related adverse effects of glucocorticoid-reliant therapeutic approaches.
Figure 1
Posted 28 Dec, 2020
On 08 Feb, 2021
On 08 Feb, 2021
Received 08 Feb, 2021
Received 08 Feb, 2021
On 07 Feb, 2021
On 07 Feb, 2021
Received 05 Feb, 2021
Received 05 Feb, 2021
Received 04 Feb, 2021
On 24 Jan, 2021
On 23 Jan, 2021
On 23 Jan, 2021
On 23 Jan, 2021
Invitations sent on 22 Jan, 2021
On 16 Dec, 2020
On 16 Dec, 2020
On 16 Dec, 2020
On 15 Dec, 2020
Effect of First-Line Biologic Initiation on Glucocorticoid Exposure Initiation in Children Hospitalized with New-Onset Systemic Juvenile Idiopathic Arthritis: Emulation of a Pragmatic Trial Using Observational Data
Posted 28 Dec, 2020
On 08 Feb, 2021
On 08 Feb, 2021
Received 08 Feb, 2021
Received 08 Feb, 2021
On 07 Feb, 2021
On 07 Feb, 2021
Received 05 Feb, 2021
Received 05 Feb, 2021
Received 04 Feb, 2021
On 24 Jan, 2021
On 23 Jan, 2021
On 23 Jan, 2021
On 23 Jan, 2021
Invitations sent on 22 Jan, 2021
On 16 Dec, 2020
On 16 Dec, 2020
On 16 Dec, 2020
On 15 Dec, 2020
Background: Glucocorticoid exposure is a significant driver of morbidity in children with systemic juvenile idiopathic arthritis (sJIA). We determined the effect of early initiation of biologic therapy (IL-1 or IL-6 inhibition) on glucocorticoid exposure in hospitalized patients with new-onset sJIA.
Methods: We emulated a pragmatic sequence of trials (“pseudo-trials”) of biologic initiation in children (≤ 18 years) hospitalized with new-onset sJIA utilizing retrospective data from an administrative database from 52 tertiary care children’s hospitals from 2008-2019. Eligibility window, treatment assignment and start of follow-up between biologic and non-biologic study arms were aligned for each pseudo-trial. Patients in the source population could meet eligibility criteria at several timepoints. Mixed-effects logistic regression was used to determine the effect of biologic initiation on in-hospital glucocorticoid exposure.
Results: 468 children met eligibility criteria, of which 19% received biologic therapy without preceding or concomitant initiation of immunomodulatory medications. This proportion significantly increased over time during the study period (p < 0.01). 1451 trial subjects were included across 4 pseudo-trials with 71 assigned to the biologic arm and 1409 assigned to the non-biologic arm. After adjustment, there was a trend toward decreased odds of glucocorticoid initiation in the biologic arm compared to the non-biologic arm (OR 0.39, 95% CI [0.13, 1.15]).
Conclusion: Biologic initiation in children hospitalized with new-onset sJIA significantly increased over time and may be associated with reduced glucocorticoid exposure. The increasing use of first-line biologic therapy may lead to clinically relevant reductions in treatment-related adverse effects of glucocorticoid-reliant therapeutic approaches.
Figure 1