Risk Factors and Treatment Outcomes for Oral Immunotherapy-Induced Gastrointestinal Symptoms and Eosinophilic Responses (OITIGER)

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.

Keywords: Cow's milk allergy; Eosinophilic esophagitis; Oral immunotherapy.