Sublingual Immunotherapy For Environmental and Food Allergies Is Safe in Real-World Telemedicine Care: Evidence from 23,118 Patient-Years

Technical Summary: Sublingual Immunotherapy Safety in Real-World Telemedicine Care

Problem Statement
Sublingual immunotherapy (SLIT) is a recognized disease-modifying treatment for allergic respiratory disease, generally considered safer than subcutaneous immunotherapy (SCIT). While randomized controlled trials (RCTs) have established a safety profile characterized by mild, localized adverse events, these findings often rely on highly selected populations managed under controlled conditions. There is a significant gap in large-scale safety data regarding SLIT delivered through fully remote, telemedicine-based care models. In such settings, treatment is prescribed and monitored without direct clinical supervision, potentially altering patterns of adverse event reporting, adherence, and treatment persistence. Existing real-world evidence has largely been confined to conventional clinical pathways rather than end-to-end telemedicine platforms.

Methodology
This study is a retrospective, longitudinal, observational analysis of a large real-world registry derived from the Curex telemedicine platform.

• Cohort: The study included 15,409 patients who received personalized SLIT formulations for environmental and food allergies between 2020 and 2025. Eligibility required at least three months of treatment supply and the completion of at least one follow-up survey.
• Exposure: The total treatment exposure amounted to 23,118 patient-years. The median treatment duration was 16.3 months, with patients receiving a median of five treatment shipments.
• Data Collection: Adverse events (AEs) were captured via the Allergy Response Tracker (ART), a structured longitudinal survey. Events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, graded from I (mild) to V (death).
• Statistical Analysis: Safety outcomes were summarized as patient-level proportions and exposure-adjusted event rates per 100 patient-years. Kaplan–Meier methods were employed to evaluate the time to the first adverse event. Sensitivity analyses were conducted to assess the impact of treatment duration and calendar cohorts on AE reporting.

Key Results

• Overall Safety Profile: Adverse events were infrequent and predominantly mild. At the patient level, 6.87% reported at least one Grade I event, 1.72% reported Grade II, 0.08% reported Grade III, and 0.01% (one patient) reported a Grade IV event. No Grade V events (deaths) were reported.
• Event Rates: The overall adverse event rate was 6.40 events per 100 patient-years, driven primarily by Grade I events (5.10 per 100 patient-years).
• Nature of Events: The most frequently reported AEs involved the upper respiratory tract (e.g., nasal congestion, sneezing, throat irritation) and were mild. Systemic reactions were rare.
• Severe Reactions:
  • Anaphylaxis: Two cases (0.01%) were identified; only one was considered treatment-related.
  • Eosinophilic Esophagitis (EoE): Five new diagnoses (0.03%) and three exacerbations of pre-existing disease (0.02%) were observed. Notably, none of the patients with new EoE diagnoses or exacerbations were receiving food-allergen SLIT formulations; all were treated for environmental allergies.
  • Cardiovascular Events: One Grade IV event (cardiac arrest) occurred approximately 12 months after initiation in a patient with a pre-existing arrhythmia disorder and was deemed unrelated to SLIT.
• Temporal Analysis: Kaplan–Meier analysis showed a gradual accumulation of adverse events over time without evidence of increasing risk relative to treatment duration. Sensitivity analyses found no evidence that adverse events were associated with premature treatment discontinuation.

Key Contributions

• Scale and Setting: This study provides one of the largest real-world evaluations of SLIT safety to date, specifically within a fully remote telemedicine model, encompassing over 23,000 patient-years of exposure.
• Real-World Generalizability: It characterizes the safety profile of SLIT in a heterogeneous population outside of traditional supervised clinical environments, addressing the limitation of RCTs where populations are often highly selected.
• Specific Safety Signals: The study offers detailed data on rare but critical safety concerns, including anaphylaxis and EoE, within a large telemedicine cohort, noting that EoE cases were not associated with food-allergen formulations in this dataset.

Significance and Claims
The paper claims that home-administered SLIT delivered via telemedicine demonstrates a favorable safety profile, characterized by predominantly mild adverse events and exceptionally low rates of severe reactions. The authors assert that serious systemic reactions, anaphylaxis, and EoE are rare despite the massive scale of exposure. These findings support the safety of SLIT in routine clinical practice and suggest that telemedicine-based delivery models can safely facilitate long-term allergen immunotherapy at scale. The study concludes that the safety outcomes observed in this remote setting are comparable to those reported in traditional clinical practice, supporting the expansion of telemedicine-enabled immunotherapy programs.

The authors maintain a modest tone regarding causal inferences, acknowledging limitations such as the reliance on patient-reported data, potential misclassification of symptoms overlapping with underlying allergic disease, and the lack of a concurrent SCIT comparator group within the study design. However, they position the results as consistent with the broader literature suggesting SLIT offers a substantially more favorable safety profile than SCIT.