High dose pollen intralymphatic immunotherapy: two RDBPC trials question
the benefit of dose increase
Abstract
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 one month in between was evaluated. Results Doses up to
10 000 SQ-U was 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 ILIT 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 3 000 SQ-U should be avoided.