<p><strong>BACKGROUND: </strong>The objective of this work was to describe magnetic resonance imaging (MRI) changes over time in inflammatory and structural lesions at the sacroiliac joint (SIJ) in children with spondyloarthritis (SpA) exposed and unexposed to tumor necrosis factor inhibitor (TNFi).</p>

<p><strong>METHODS: </strong>This was a retrospective, multicenter study of SpA patients with suspected or confirmed sacroiliitis who underwent at ≥2 pelvic MRI scans. Images were reviewed independently by 3 radiologists and scored for inflammatory and structural changes using the Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ inflammation score (SIS) and structural score (SSS). Longitudinal, quantitative changes in patient MRI scans were measured using descriptive statistics and stratified by TNFi exposure. We used an average treatment effects (ATE) regression model to explore the average effect of TNFi exposure over time on inflammatory and structural lesions, adjusting for baseline lesion scores.</p>

<p><strong>RESULTS: </strong>Forty-six subjects were evaluated using the SIS (n&nbsp;= 45) and SSS (n&nbsp;= 18). Median age at baseline imaging was 13.6 years, 63% were male and 71% were white. Twenty-three subjects (50%) were TNFi exposed between MRI studies. The median change in SIS in TNFi exposed and unexposed subjects with a baseline SIS ≥0 was - 20.7 and - 14.3, respectively (p&nbsp;= 0.09). Eleven (85%) TNFi exposed and 8 (89%) unexposed subjects with a baseline SIS ≥0 met the SIS minimal clinically important difference (MCID; ≥2.5). Using the ATE model adjusted for baseline SIS, the average effect of TNFi on SIS in patients with a baseline SIS ≥2 was - 14.5 (p&nbsp;&lt; 0.01). Unadjusted erosion change score was significantly worse in TNFi unexposed versus exposed subjects (p&nbsp;= 0.03) but in the ATE model the effect of TNFi was not significant.</p>

<p><strong>CONCLUSION: </strong>This study quantitatively describes how lesions in the SIJs on MRI change over time in patients exposed to TNFi versus unexposed. Follow-up imaging in TNFi exposed patients showed greater improvement than the unexposed group by most metrics, some of which reached statistical significance. Surprisingly, a majority of TNFi unexposed children with a baseline SIS≥2 met the SIS MCID. Additional studies assessing the short and long-term effects of TNFi on inflammatory and structural changes in juvenile SpA are needed.</p>

<p><strong>BACKGROUND: </strong>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.</p>

<p><strong>METHODS: </strong>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 to 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.</p>

<p><strong>RESULTS: </strong>Four hundred sixty-eight 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&nbsp;&lt; &nbsp;0.01). 1451 trial subjects were included across 4 pseudo-trials with 71 assigned to the biologic arm and 1380 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]).</p>

<p><strong>CONCLUSION: </strong>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.</p>

<p><strong>OBJECTIVE: </strong>Increasing evidence supports that early initiation of biologics may dramatically improve disease course and reduce glucocorticoid exposure for children with systemic juvenile idiopathic arthritis (JIA). We characterized variation in the use of first-line biologic and glucocorticoid therapy and identified drivers of variation in children hospitalized with new-onset systemic JIA.</p>

<p><strong>METHODS: </strong>We conducted a retrospective cohort study of children hospitalized with new-onset systemic JIA from 2008-2019 utilizing a comparative pediatric database from 52 tertiary care children's hospitals. Subjects and treatment receipt were identified using International Classification of Diseases (ICD)-9 and ICD-10 discharge diagnosis codes, pharmacy billing data and clinical transaction classification codes. Mixed-effects logistic regression was used to identify patient and hospital-level factors associated with receipt of glucocorticoids and biologics.</p>

<p><strong>RESULTS: </strong>534 children with new-onset systemic JIA hospitalized during the study period met inclusion criteria. Twenty-nine percent received biologics and 58% received glucocorticoids. Biologic use increased over time (p &lt; 0.001), methotrexate use decreased (p &lt; 0.01), and glucocorticoid use remained unchanged. Biologics and glucocorticoid use varied significantly between hospitals. High annual hospital volume, intensive care unit stay, and later discharge year were significantly associated with biologic exposure. Medium-high and high annual hospital volume were significantly associated with less glucocorticoid exposure.</p>

<p><strong>CONCLUSION: </strong>Despite increasing evidence demonstrating improved outcomes with first-line treatment with biologics, we found significant treatment variation across hospitals with many children not receiving biologics and a persistent high rate of glucocorticoid exposure. These results underscore the need for comparative efficacy studies and improved treatment standardization.</p>