High-dose pollen intralymphatic immunotherapy: Two RDBPC trials question the benefit of dose increase

Allergy. 2022 Mar;77(3):883-896. doi: 10.1111/all.15042. Epub 2021 Aug 29.


Background: The same dosing schedule, 1000 SQ-U times three, with one-month intervals, have been evaluated in most trials of intralymphatic immunotherapy (ILIT) for the treatment of allergic rhinitis (AR). The present studies evaluated if a dose escalation in ILIT can enhance the clinical and immunological effects, without compromising safety.

Methods: Two randomized double-blind placebo-controlled trials of ILIT for grass pollen-induced AR were performed. The first included 29 patients that had recently ended 3 years of SCIT and the second contained 39 not previously vaccinated patients. An up-dosage of 1000-3000-10,000 (5000 + 5000 with 30 minutes apart) SQ-U with 1 month in between was evaluated.

Results: Doses up to 10,000 SQ-U were safe after recent SCIT. The combined symptom-medication scores (CSMS) were reduced by 31% and the grass-specific IgG4 levels in blood were doubled. In ILIT de novo, the two first patients that received active treatment developed serious adverse reactions at 5000 SQ-U. A modified up-dosing schedule; 1000-3000-3000 SQ-U appeared to be safe but failed to improve the CSMS. Flow cytometry analyses showed increased activation of lymph node-derived dendritic but not T cells. Quality of life and nasal provocation response did not improve in any study.

Conclusion: Intralymphatic immunotherapy in high doses after SCIT appears to further reduce grass pollen-induced seasonal symptoms and may be considered as an add-on treatment for patients that do not reach full symptom control after SCIT. Up-dosing schedules de novo with three monthly injections that exceeds 3000 SQ-U should be avoided.

Trial registration: ClinicalTrials.gov NCT02679105 NCT02975479.

Keywords: clinical immunology; immunotherapy and tolerance induction; pollen; rhinitis.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens
  • Desensitization, Immunologic / adverse effects
  • Double-Blind Method
  • Humans
  • Immunologic Factors
  • Immunotherapy
  • Poaceae
  • Pollen
  • Quality of Life
  • Rhinitis, Allergic* / therapy
  • Rhinitis, Allergic, Seasonal* / therapy
  • Treatment Outcome


  • Allergens
  • Immunologic Factors

Associated data

  • ClinicalTrials.gov/NCT02679105
  • ClinicalTrials.gov/NCT02975479