Characteristics associated with variation in corticosteroid exposure in children with steroid-sensitive nephrotic syndrome: Results from a Canadian longitudinal study

Background: Variation in dose and duration of corticosteroids for childhood-onset steroid-sensitive nephrotic syndrome occurs worldwide, likely reflecting the evolving evidence on optimal dosing and variable severity of the disease observed between patients. We conducted a study to determine the associations between site, physician, and patient factors and average daily corticosteroid dose and duration of therapy. Methods: Data were derived from the Canadian Childhood Nephrotic Syndrome (CHILDNEPH) Project, an observational longitudinal study from 2013 to 2019 of children with nephrotic syndrome involving pediatric nephrologists in 11 sites across Canada. Primary outcome was average daily corticosteroid dose prescribed per episode of proteinuria, reported as mg/m2 prednisone equivalents. Secondary outcome was duration of treatment for each episode of proteinuria in days. Exposure variables were categorized into site-, physician- and patient-level variables. Results: 328 children, median age at enrollment of 4.3 years old (Interquartile range [IQR]: 3.6), participated and were followed for a median time of 2.62 years (IQR: 2.61). The observed variability in average daily corticosteroid dose and in duration of therapy was mostly attributed to the site where the patient was treated. Accounting for between patient, physician and site differences, average daily corticosteroid dose decreased with increasing age (beta coefficient: -0.07 [95% Confidence interval (CI) -0.09, -0.05], p<0.001). African and Indigenous ethnicity was associated with longer treatment duration compared to Caucasian (beta coefficient: African 42.29 [95% CI 7.85, 76.73 p=0.016], Indigenous 29.65 [95% CI 2.79, 56.52 p=0.03]). Conclusions: We found practice variation with respect to corticosteroid prescriptions across 11 Canadian sites, and that variation is mostly explained at the site level. Age and ethnicity are important factors to be considered, as they are significantly associated with average corticosteroid dose and duration of therapy.

P11.04 Autonomy duration as analyzed by KPS≥70 cumulative time in patients with biopsy-only glioblastoma (BO-GBM). A sub-analysis of the Timone cohort

BACKGROUND Improvement or maintenance of autonomy is a crucial and understudied issue for glioblastoma (GBM) patients whose outcome is poor. Biopsy-only GBM (BO-GBM) is a situation where survival is short and independence is of particular importance. Our objective was to explore functional outcome in biopsy-only patients. MATERIAL AND METHODS A regional glioma SIRIC cohort was conducted at CHU Timone in 2014–2017 and we retrospectively reviewed the BO-GBM subgroup. We prospectively collected age, corticosteroid dose, tumoral surface, treatment allocated and completed, and survival outcome. Functional independence was analyzed as a cumulative time of Karnofsky performance status (KPS) ≥70 from the date of diagnosis until death. We analyzed potential factors associated to time with KPS ≥70. RESULTS Among 535 patients enrolled in the cohort, surgery was restricted to biopsy in 139 patients (BO-GBM). Mean tumoral surface measured on gadolinium-enhanced T1-weighted MRI was 1198mm2 (min: 65; max: 4515mm2). Mean steroid dose at diagnosis was 50mg prednisolone per day. Corticosteroid dose was ≥50mg prednisolone per day for 77 patients and &lt;50mg per day for 56 patients. Fifty-four patients (39%) were referred to radiotherapy-temozolomide (RT-TMZ), 68 (49%) considered unfitted for RT received chemotherapy upfront only (CT-UF), and 17 patients (12%) were referred to palliative care only. Median overall survival (OS) was 7.5 months (95%CI: 6.0–9.2), 14.0 months (95%CI: 9.7–18.7) and 6.0 months (95%CI: 4.6–7.7) for BO-GBM, RT-TMZ and CT-UF respectively. At diagnosis, 81 (58.3%) patients presented with self-care capacity (KPS ≥ 70%). For these patients, median time of autonomy preservation was 7.6 months (95%CI: 6.1–9.0). Median time of autonomy preservation differed according to treatment modalities: it was 8.6 months (95%CI: 5.9–11.3) versus 6.3 months (95%CI: 2.9–9.7) for RT-TMZ versus CT-UF group respectively (p&lt;0.001). In univariate analysis, time with KPS ≥ 70% was correlated with age (p=0.001), initial KPS (p&lt;0.001), tumoral surface measured on gadolinium-enhanced T1-weighted MRI (p=0.03) and corticosteroid dose (p=0.001). In multivariate analysis, time with KPS≥70 was correlated with age (p=0.001) and KPS at diagnosis (p&lt;0.001). CONCLUSION Patients with inoperable GBM referred to radiotherapy-temozolomide present a valuable duration of functional independence, although shorter in patients not referred to RT. Duration of functional independence could be considered in addition to PFS and OS for treatment evaluation in patients with GBM.

Effect of Low-Dose Corticosteroid Use on HBV Reactivation in HBsAg-positive Rheumatoid Arthritis Patients

Background: It is well known that the use of corticosteroids (CS) results in increased viral replication and elevated alanine aminotransferase in hepatitis B virus (HBV) patients. However, only a few studies have investigated the effect of low-dose CS on HBV reactivation. In addition, there are few studies on the effects of synthetic disease-modifying anti-rheumatic drugs on HBV reactivation. Objective: We investigated the reactivation of HBV in rheumatoid arthritis (RA) patients treated with long-term low-dose corticosteroids. In addition, we analyzed factors affecting HBV reactivation, including disease-modifying anti-rheumatic drugs. Methods: We retrospectively reviewed medical records and analyzed the incidence of HBV reactivation in RA patients who were hepatitis B surface antigen (HBsAg) positive and who were receiving ≤10 mg of prednisolone over 4 weeks. Logistic regression analysis was performed to investigate the factors that increase the risk of HBV reactivation. Results: A total of 141 patients were included in the study, out of which 24 (17.0%) patients had HBV reactivation. The administration of low-dose corticosteroids did not affect HBV reactivation in HBsAg-positive RA patients (odds ratio: 0.807, 95% confidence interval: 0.143–4.546, p = 0.808), nor did the duration of corticosteroid administration, average daily corticosteroid dose, and cumulative corticosteroid dose. Administration of leflunomide was found to significantly increase the risk of HBV reactivation (odds ratio: 3.851, 95% confidence interval: 1.026–14.459, p = 0.046). Conclusion: The administration of low-dose corticosteroids did not affect the rate of HBV reactivation, suggesting that it can be used safely. Leflunomide may increase the risk of HBV reactivation; therefore, HBV patients should be carefully monitored when receiving this drug.

Schweres Asthma: Vergleich einer Typ-2-Biomarkerstrategie mit einem Symptom-basierten Algorithmus zur Steuerung der Kortisondosis

<b>Background:</b> Asthma treatment guidelines recommend increasing corticosteroid dose to control symptoms and reduce exacerbations. This approach is potentially flawed because symptomatic asthma can occur without corticosteroid responsive type-2 (T2)-driven eosinophilic inflammation, and inappropriately high-dose corticosteroid treatment might have little therapeutic benefit with increased risk of side-effects. We compared a biomarker strategy to adjust corticosteroid dose using a composite score of T2 biomarkers (fractional exhaled nitric oxide [FENO], blood eosinophils, and serum periostin) with a standardised symptom-risk-based algorithm (control). <b>Methods:</b> We did a single-blind, parallel group, randomised controlled trial in adults (18–80 years of age) with severe asthma (at treatment steps 4 and 5 of the Global Initiative for Asthma) and FENO of less than 45 parts per billion at 12 specialist severe asthma centres across England, Scotland, and Northern Ireland. Patients were randomly assigned (4:1) to either the biomarker strategy group or the control group by an online electronic case-report form, in blocks of ten, stratified by asthma control and use of rescue systemic steroids in the previous year. Patients were masked to study group allocation throughout the entirety of the study. Patients attended clinic every 8 weeks, with treatment adjustment following automated treatment-group-specific algorithms: those in the biomarker strategy group received a default advisory to maintain treatment and those in the control group had their treatment adjusted according to the steps indicated by the trial algorithm. The primary outcome was the proportion of patients with corticosteroid dose reduction at week 48, in the intention-to-treat (ITT) population. Secondary outcomes were inhaled corticosteroid (ICS) dose at the end of the study; cumulative dose of ICS during the study; proportion of patients on maintenance oral corticosteroids (OCS) at study end; rate of protocol-defined severe exacerbations per patient year; time to first severe exacerbation; number of hospital admissions for asthma; changes in lung function, Asthma Control Questionnaire-7 score, Asthma Quality of Life Questionnaire score, and T2 biomarkers from baseline to week 48; and whether patients declined to progress to OCS. A secondary aim of our study was to establish the proportion of patients with severe asthma in whom T2 biomarkers remained low when corticosteroid therapy was decreased to a minimum ICS dose. This study is registered with ClinicalTrials.gov, NCT02717689 and has been completed. <b>Findings:</b> Patients were recruited from Jan 8, 2016, to July 12, 2018. Of 549 patients assessed, 301 patients were included in the ITT population and were randomly assigned to the biomarker strategy group (n = 240) or to the control group (n = 61). 28.4% of patients in the biomarker strategy group were on a lower corticosteroid dose at week 48 compared with 18.5% of patients in the control group (adjusted odds ratio [aOR] 1.71 [95% CI 0.80–3.63]; p = 0.17). In the per-protocol (PP) population (n = 121), a significantly greater proportion of patients were on a lower corticosteroid dose at week 48 in the biomarker strategy group (30.7% of patients) compared with the control group (5.0% of patients; aOR 11.48 [95% CI 1.35–97.83]; p = 0.026). Patient choice to not follow treatment advice was the principle reason for loss to PP analysis. There was no difference in secondary outcomes between study groups and no loss of asthma control among patients in the biomarker strategy group who reduced their corticosteroid dose. <b>Interpretation:</b> Biomarker-based corticosteroid adjustment did not result in a greater proportion of patients reducing corticosteroid dose versus control. Understanding the reasons for patients not following treatment advice in both treatment strategies is an important area for future research. The prevalence of T2 biomarker-low severe asthma was low. <b>Funding</b>: This study was funded, in part, by the Medical Research Council UK.

Benign intracranial hypertension associated with inhaled corticosteroids in a child with asthma

A 13-year-old male asthmatic presented to the general paediatric clinic with papilloedema identified following a check-up with his optician due to blurred vision. His asthma was well controlled on a moderate dose of inhaled corticosteroid and there had been no recent increase or decrease in the dose. A diagnosis of benign intracranial hypertension (BIH) was made based on a raised cerebrospinal fluid opening pressure, papilloedema, a normal neurological examination and normal neuroimaging. The only associated risk factor was his inhaled corticosteroids. He was commenced on acetazolamide and the inhaled corticosteroid dose was reduced, resulting in resolution of his papilloedema. This case serves to highlight that steroid side effects including BIH may occur at moderate doses of inhaled corticosteroids and that inhaled corticosteroid dose should be regularly reviewed and decreased to the lowest dose that maintains asthma control.

DOP86 Corticosteroid-sparing effects of ustekinumab therapy for Ulcerative Colitis through 3 years: UNIFI long-term extension

Background Ustekinumab (UST) is an IL12/23 blocker approved for use in Crohn’s disease and ulcerative colitis (UC). In the UNIFI maintenance study of patients (pts) with moderate-severe UC, &gt;90% of the pts who achieved clinical response or remission at week (wk) 44 were able to eliminate corticosteroids, an important goal of therapy. In this analysis, we describe the corticosteroid-sparing effects of UST treatment through 3 years among pts who were treated in the UNIFI long-term extension (LTE). Methods 523 intravenous UST induction responders were randomized to SC maintenance therapy (SC placebo [PBO], n=175; UST 90mg every 12 wks [q12w], n=172; or UST 90mg q8w, n=176). 284 UST pts who completed wk44 entered the LTE. PBO pts were discontinued after wk44 unblinding. Based on the investigator’s clinical judgement of their UC disease activity, pts in the LTE were eligible to receive dose adjustment starting at wk56: PBO to q8w, q12w to q8w, and q8w to q8w (sham adjustment). Pts in PBO or q8w groups were only eligible for dose adjustment or sham dose adjustment before unblinding. Efficacy was evaluated in randomized pts using symptomatic remission (Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0). During the maintenance study, all pts receiving corticosteroids at maintenance baseline were required to initiate tapering. Through wk152 of the LTE, symptomatic remission endpoints were calculated with treatment failure and missing data nonresponder imputation, and dose adjustment was not considered to be a treatment failure. Missing corticosteroid dose data was managed using last observation carried forward. Results Of the 284 pts in the randomized population who were treated with UST in the LTE, 139 were receiving corticosteroids at maintenance baseline. Of these, 91.4% (n=127) were no longer receiving corticosteroids at wk152. The average prednisone-equivalent corticosteroid dose among pts receiving corticosteroids at maintenance baseline in the q8w group was 15.4 mg/day at maintenance baseline and 1.7 mg/day at wks44 & 152. In the q12w group, average prednisone-equivalent doses were 15.4, 1.0, and 4.6 mg/day, respectively (Table 1). Corticosteroid-free symptomatic remission rates through wk152 are summarized in Table 2. Results were similar for the q8w and q12w maintenance doses. Of the UST-treated pts who were in symptomatic remission at wk152, 94.6% (88/93) in the q12w group and 98.0% (97/99) in the q8w group were corticosteroid-free. Conclusion UST maintenance therapy, with both q8w and q12w dosing regimens, was effective in reducing and eliminating the use of corticosteroids in pts with UC through 3 years. Through 3 years of treatment with UST, the majority of pts in symptomatic remission were corticosteroid free.