Real-Life Safety of Japanese Cedar Pollen Sublingual Immunotherapy Tablets: A Post-Marketing Survey

Abstract

Background: Japanese cedar (JC) pollen sublingual immunotherapy (SLIT)-tablets (5000 Japanese allergy units [JAU]) are licensed for the treatment of JC-pollinosis with no age restriction on the basis of the results of a 5-year clinical trial. However, there have been no large-scale surveys of 5000 JAU in an actual clinical setting.

Methods: This was a multicenter observational prospective study. We assessed the safety and effectiveness of the long-term use of 5000 JAU in patients with JC-pollinosis, with an observation period of two seasons of JC pollen dispersal, at clinical sites in Japan.

Results: Our safety analysis included 516 patients and the effectiveness analysis included 469 patients. Adverse drug reactions (ADRs) occurred in 68 patients (13.18%) and mainly comprised administration site-related events that occurred during the early phase of administration. Treatment discontinuation due to ADRs occurred in 18 patients (3.49%). No deaths, anaphylactic shock, or serious ADRs occurred. Regarding effectiveness, the severity of JC-pollinosis was rated as "almost asymptomatic + mild" in 82.19% of patients in Season 1 and 92.58% in Season 2. Quality of life was rated as "score 0 (Fine) + 1" in 75.83% of patients in Season 1 and 86.09% in Season 2. Overall improvement was rated as "improved + slightly improved" in 95.68% of patients in Season 1 and 96.38% in Season 2 following the initiation of JC pollen SLIT-tablets. Nasal and ocular symptom scores also decreased with increasing treatment duration. Treatment continuation rates were 89.53% in Season 1 and 78.29% in Season 2.

Conclusion: The JC pollen SLIT-tablets appear to be safe and effective in an actual clinical setting during two seasons. No new safety or effectiveness issues were identified, and no additional safety or effectiveness precautions were required.

Keywords: Japanese cedar pollen; SLIT; allergic rhinitis; post‐marketing surveillance; sublingual immunotherapy tablets.

FIGURE 1

Patient disposition.

FIGURE 2

Most common ADRs (occurred in ≥ 1% of patients administered 5000 JAU) stratified by age (A) and onset of ADRs stratified by SOC classification (B) using the Japanese version of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use Medical Dictionary for Regulatory Activities (MedDRA/J 26.0) in the safety analysis set (n = 516). ADR, adverse drug reaction; JAU, Japanese Allergy Units; SOC, system organ class.

FIGURE 3

JC‐pollinosis symptom severity (A), JRQLQ general state (B), and overall improvement (C) over time in the effectiveness analysis set (n = 469). JC‐pollinosis symptom severity was based on a five‐point scale (data show the proportion of each scale). The JRQLQ general state was based on the face scale (data show the proportion of each score on the face scale). Overall improvement was based on a five‐point scale (data show the proportion of each score on the scale). A paired t‐test was used to assess the rhinitis symptom severity scores and JRQLQ general state at each timepoint corresponding to the baseline (p < 0.001 at all timepoints). JC, Japanese cedar; JRQLQ, Japanese Rhinoconjunctivitis Quality of Life Questionnaire.

FIGURE 4

Cumulative incidence of “almost asymptomatic” (A, B) and “at least one level of improvement (C, D) status for JC‐pollinosis symptom severity after receiving JC pollen SLIT‐tablets. Regarding “almost asymptomatic,” (A) shows the results for all patients and (B) shows the stratified results by JC‐pollinosis symptom severity at baseline. Regarding “at least one level of improvement,” (C) shows the results for all patients and (D) shows the stratified results by JC‐pollinosis symptom severity at baseline. A log‐rank test was performed to stratify by severity of JC‐pollinosis symptoms at baseline in (B) and (D). JC, Japanese cedar; SLIT, sublingual immunotherapy.