Michael R Goldberg1, Liat Nachshon2, Michael B Levy3, Arnon Elizur2, Yitzhak Katz4. 1. Allergy, Immunology and Pediatric Pulmonary Institute, Shamir Medical Center, Zerifin, Israel. Electronic address: goldbergsm@yahoo.com. 2. Allergy, Immunology and Pediatric Pulmonary Institute, Shamir Medical Center, Zerifin, Israel; Department of Pediatrics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 3. Allergy, Immunology and Pediatric Pulmonary Institute, Shamir Medical Center, Zerifin, Israel. 4. Department of Pediatrics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Abstract
BACKGROUND: We recently described that oral immunotherapy (OIT)-induced gastrointestinal symptoms were associated with peripheral eosinophilic responses (termed OITIGER). OBJECTIVE: To identify treatment outcomes after dose modification and risk factors for developing OITIGER. METHODS: Treatment modifications in patients with OITIGER (n = 65) including cumulative dose reductions or treatment suspension were individualized and based on the severity of symptoms and an associated absolute eosinophil count (AEC, eosinophils/μL) of more than 900. Multivariate analysis for risk factors associated with OITIGER was performed in milk-OIT subjects. RESULTS: Treatment modifications reduced the cumulative daily dosage load by a median of 50% (interquartile range, 50%-67%) in 43 of 65 (66.1%) patients, deferred dose increases in 2 of 65 (3.1%) patients, or temporarily suspended treatment in 18 of 65 (27.7%) patients. Two patients (3.1%) had no treatment intervention. Symptoms and eosinophilia abated on dosage modification, allowing for resumption of dose increases (n = 34) or reinitiation of treatment (n = 9) after a median of 29 (interquartile range, 20-56) and 19 (interquartile range, 17-44) days, respectively. OITIGER reoccurred during treatment in 10 of 54 (18.5%) patients, which resolved after further dose modification. In long-term follow-up (>3-26 months), 31 of 32 patients were asymptomatic with stable AECs. Patients with OITIGER had a higher OIT failure rate (P = .004) and were less likely to reach full desensitization (P < .001), as compared with asymptomatic patients (n = 684). Multivariate analysis identified several risk factors for OITIGER: starting dose more than 120 mg (P < .001; odds ratio, 7.14), second-month dose more than 4-fold over the starting dose (P = .037; odds ratio, 2.18), and baseline AEC more than 600/μL (P = .002; odds ratio, 3.2). CONCLUSIONS: OITIGER is transient or reversible in most subjects, and its occurrence is related to OIT starting dose, its rate of increase, and baseline AECs.
BACKGROUND: We recently described that oral immunotherapy (OIT)-induced gastrointestinal symptoms were associated with peripheral eosinophilic responses (termed OITIGER). OBJECTIVE: To identify treatment outcomes after dose modification and risk factors for developing OITIGER. METHODS: Treatment modifications in patients with OITIGER (n = 65) including cumulative dose reductions or treatment suspension were individualized and based on the severity of symptoms and an associated absolute eosinophil count (AEC, eosinophils/μL) of more than 900. Multivariate analysis for risk factors associated with OITIGER was performed in milk-OIT subjects. RESULTS: Treatment modifications reduced the cumulative daily dosage load by a median of 50% (interquartile range, 50%-67%) in 43 of 65 (66.1%) patients, deferred dose increases in 2 of 65 (3.1%) patients, or temporarily suspended treatment in 18 of 65 (27.7%) patients. Two patients (3.1%) had no treatment intervention. Symptoms and eosinophilia abated on dosage modification, allowing for resumption of dose increases (n = 34) or reinitiation of treatment (n = 9) after a median of 29 (interquartile range, 20-56) and 19 (interquartile range, 17-44) days, respectively. OITIGER reoccurred during treatment in 10 of 54 (18.5%) patients, which resolved after further dose modification. In long-term follow-up (>3-26 months), 31 of 32 patients were asymptomatic with stable AECs. Patients with OITIGER had a higher OIT failure rate (P = .004) and were less likely to reach full desensitization (P < .001), as compared with asymptomatic patients (n = 684). Multivariate analysis identified several risk factors for OITIGER: starting dose more than 120 mg (P < .001; odds ratio, 7.14), second-month dose more than 4-fold over the starting dose (P = .037; odds ratio, 2.18), and baseline AEC more than 600/μL (P = .002; odds ratio, 3.2). CONCLUSIONS: OITIGER is transient or reversible in most subjects, and its occurrence is related to OIT starting dose, its rate of increase, and baseline AECs.
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