Real-world safety of personalized telemedicine-delivered sublingual immunotherapy: reported adverse events across 18,398 patient-years

Tharpe, C., Mardaga, K., Davidson, J. et al.  Allergy Asthma Clin Immunol (2026). https://doi.org/10.1186/s13223-026-01079-1

Abstract

Background

Sublingual immunotherapy (SLIT) is an effective disease-modifying treatment for allergic respiratory disease. Despite its increased utilization in the United States, Real-world safety data for personalized SLIT delivered through fully remote care remain limited.

Methods

This retrospective longitudinal study evaluated patients receiving personalized SLIT through a US telemedicine platform between 2020 and 2026. Patients who completed at least one survey after shipment receipt were included. Reported adverse events were graded using CTCAEv5.0. Shipment-derived exposure, capped at the administrative cutoff, was adjusted for self-reported adherence.

Safety outcomes were summarized as patient-level proportion and exposure-adjusted event rates per 100 patient-years. Time to first reported adverse event was assessed (Kaplan–Meier). Cumulative incidence of adverse event-related discontinuation was compared between included and excluded cohorts (Gray’s test), with other reasons as competing events.

Results

Of 29,675 patients receiving SLIT, 13,584 (45.8%) were included, contributing 18,398 adherence-adjusted patient-years. Overall, 28.1% of requested surveys were completed. Median treatment duration was 17.1 months (IQR 11.1–25.4). Grade I, II, III, and IV events were reported by 7.76%, 1.95%, 0.09%, and 0.01% (unrelated to SLIT) of patients, respectively. No deaths (Grade V) were recorded. Eight adverse events per 100 patient-years were reported (95% CI [7.60–8.42]), driven primarily by Grade I (6.37 per 100 patient-years [6.01–6.75]). The most frequently reported symptoms were predominantly mild and involved the upper respiratory tract. Five confirmed or suspected cases of eosinophilic esophagitis (EoE) were identified without a prior diagnosis; three with pre-existing EoE reported exacerbations. Two patients reported anaphylaxis or severe allergic reactions, one considered treatment-related. Reported adverse events gradually accumulated over time. At 36 months, cumulative incidence of discontinuation due to adverse events among included and excluded patients was 1.8% (95% CI [1.5–2.1]) and 3.1% (95% CI [2.8–3.5]; Gray’s test p < 0.001).

Conclusion

In this real-world telemedicine cohort, across 18,000 patient-years, reported adverse events were predominantly mild. Severe events, including anaphylaxis and EoE, were rare. These findings suggest that SLIT may be administered and monitored at home using telemedicine (fully remote) with low rates of reported serious adverse events. Incomplete survey participation and higher adverse-event-related discontinuation among excluded patients may limit generalization.

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