Browsing by Author "Ebach, Dawn R."

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    Comparative Effectiveness of Anti-TNF in Combination With Low-Dose Methotrexate vs Anti-TNF Monotherapy in Pediatric Crohn's Disease: A Pragmatic Randomized Trial
    (Elsevier, 2023-07) Kappelman, Michael D.; Wohl, David A.; Herfarth, Hans H.; Firestine, Ann M.; Adler, Jeremy; Ammoury, Rana F.; Aronow, Jeanine E.; Bass, Dorsey M.; Bass, Julie A.; Benkov, Keith; Berenblum Tobi, Catalina; Boccieri, Margie E.; Boyle, Brendan M.; Brinkman, William B.; Cabera, Jose M.; Chun, Kelly; Colletti, Richard B.; Dodds, Cassandra M.; Dorsey, Jill M.; Ebach, Dawn R.; Entrena, Edurne; Forrest, Christopher B.; Galanko, Joseph A.; Grunow, John E.; Gulati, Ajay S.; Ivanova, Anastasia; Jester, Traci W.; Kaplan, Jess L.; Kugathasan, Subra; Kusek, Mark E.; Leibowitz, Ian H.; Linville, Tiffany M.; Lipstein, Ellen A.; Margolis, Peter A.; Minar, Phillip; Molle-Rios, Zarela; Moses, Jonathan; Olano, Kelly K.; Osaba, Lourdes; Palomo, Pablo J.; Pappa, Helen; Park, K. T.; Pashankar, Dinesh S.; Pitch, Lisa; Robinson, Michelle; Samson, Charles M.; Sandberg, Kelly C.; Schuchard, Julia R.; Seid, Michael; Shelly, Kimberly A.; Steiner, Steven J.; Strople, Jennifer A.; Sullivan, Jillian S.; Tung, Jeanne; Wali, Prateek; Zikry, Michael; Weinberger, Morris; Saeed, Shehzad A.; Bousvaros, Athos; Medicine, School of Medicine
    Background & Aims Tumor necrosis factor inhibitors, including infliximab and adalimumab, are a mainstay of pediatric Crohn’s disease therapy; however, nonresponse and loss of response are common. As combination therapy with methotrexate may improve response, we performed a multicenter, randomized, double-blind, placebo-controlled pragmatic trial to compare tumor necrosis factor inhibitors with oral methotrexate to tumor necrosis factor inhibitor monotherapy. Methods Patients with pediatric Crohn’s disease initiating infliximab or adalimumab were randomized in 1:1 allocation to methotrexate or placebo and followed for 12–36 months. The primary outcome was a composite indicator of treatment failure. Secondary outcomes included anti-drug antibodies and patient-reported outcomes of pain interference and fatigue. Adverse events (AEs) and serious AEs (SAEs) were collected. Results Of 297 participants (mean age, 13.9 years, 35% were female), 156 were assigned to methotrexate (110 infliximab initiators and 46 adalimumab initiators) and 141 to placebo (102 infliximab initiators and 39 adalimumab initiators). In the overall population, time to treatment failure did not differ by study arm (hazard ratio, 0.69; 95% CI, 0.45–1.05). Among infliximab initiators, there were no differences between combination and monotherapy (hazard ratio, 0.93; 95% CI, 0.55–1.56). Among adalimumab initiators, combination therapy was associated with longer time to treatment failure (hazard ratio, 0.40; 95% CI, 0.19–0.81). A trend toward lower anti-drug antibody development in the combination therapy arm was not significant (infliximab: odds ratio, 0.72; 95% CI, 0.49–1.07; adalimumab: odds ratio, 0.71; 95% CI, 0.24–2.07). No differences in patient-reported outcomes were observed. Combination therapy resulted in more AEs but fewer SAEs. Conclusions Among adalimumab but not infliximab initiators, patients with pediatric Crohn’s disease treated with methotrexate combination therapy experienced a 2-fold reduction in treatment failure with a tolerable safety profile. ClinicalTrials.gov, Number: NCT02772965.
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    High Body Mass Index and Response to Anti-Tumor Necrosis Factor Therapy in Pediatric Crohn's Disease
    (Wolters Kluwer, 2024) Ebach, Dawn R.; Jester, Traci W.; Galanko, Joseph A.; Firestine, Ann M.; Ammoury, Rana; Cabrera, Jose; Bass, Julie; Minar, Phillip; Olano, Kelly; Margolis, Peter; Sandberg, Kelly; Linnville, Tiffany M.; Kaplan, Jess; Pitch, Lisa; Steiner, Steven J.; Bass, Dorsey; Moses, Jonathan; Adler, Jeremy; Gulati, Ajay S.; Wali, Prateek; Pashankar, Dinesh; Ivanova, Anastasia; Herfarth, Hans; Wohl, David A.; Benkov, Keith J.; Strople, Jennifer; Sullivan, Jillian; Tung, Jeanne; Molle-Rios, Zorela; Saeed, Shehzad A.; Bousvaros, Athos; Kappelman, Michael D.; Pediatrics, School of Medicine
    Introduction: Obesity is common among patients with pediatric Crohn's disease (PCD). Some adult studies suggest obese patients respond less well to anti-tumor necrosis factor (TNF) treatment. This study sought compares anti-TNF response and anti-TNF levels between pediatric patients with normal and high body mass index (BMI). Methods: The COMBINE trial compared anti-TNF monotherapy with combination therapy with methotrexate in patients with PCD. In this secondary analysis, a comparison of time-to-treatment failure among patients with normal BMI vs BMI Z -score >1, adjusting for prescribed anti-TNF (infliximab [IFX] or adalimumab [ADA]), trial treatment assignment (combination vs monotherapy), and relevant covariates. Median anti-TNF levels across BMI category was also examined. Results: Of 224 participants (162 IFX initiators and 62 ADA initiators), 111 (81%) had a normal BMI and 43 (19%) had a high BMI. High BMI was associated with treatment failure among ADA initiators (7/10 [70%] vs 12/52 [23%], hazard ratio 0.29, P = 0.007) but not IFX initiators. In addition, ADA-treated patients with a high BMI had lower ADA levels compared with those with normal BMI (median 5.8 vs 12.8 μg/mL, P = 0.02). IFX trough levels did not differ between BMI groups. Discussion: Overweight and obese patients with PCD are more likely to experience ADA treatment failure than those with normal BMI. Higher BMI was associated with lower drug trough levels. Standard ADA dosing may be insufficient for overweight children with PCD. Among IFX initiators, there was no observed difference in clinical outcomes or drug levels, perhaps due to weight-based dosing and/or greater use of proactive drug monitoring.