Persistence of the clinical effect of grass allergen peptide immunotherapy after the second and third grass pollen seasons

Abstract

Immunotherapy with grass allergen pep des provides long-las ng clinical benefit for up to 2 years a er treatment 25 days 14-week treatment period Follow-up assessments 42% symptom improvement P = .0346 Change in rhinoconjunc vi s symptoms over placebo were assessed in the Environmental Exposure Unit (EEU) over 4 rye grass pollen challenges 4 Post-treatment EEU challenges One 6 nmol pep de injec on every 2 weeks One 12 nmol pep de injec on every 4 weeks 24% symptom improvement P = .2597

Peptide allergen‐specific immunotherapy for allergic airway diseases—State of the art

“…48 Campbell and colleagues confirmed that this approach generates IL-10 + regulatory T cells capable of "linked" suppression of the response to distinct T cell epitopes within the same allergen. 66 Similar observations have been made in SP-AIT studies of bee venom, 67 grass allergen 39,40 and peanut allergy. 68 The induction of IL-10-secreting T cells in these SP-AIT studies is important since these Tr1 cells are known to promote IgG 4 production.…”

“…Phase 1-3 clinical trials have been conducted to investigate the efficacy and safety of peptide AIT for allergic airway diseases. These have mainly focussed on major allergens including birch pollen, 36,37 grass pollen [38][39][40][41][42][43][44] or cat. [45][46][47][48][49][50][51][52][53][54][55][56] The main approach taken in these studies has been to administer SPs or COPs over 4-6 weeks, either starting at a relatively low dose with structured escalation to reach a target cumulative dose or by delivering a fixed pre-determined dose administered weekly or fortnightly.…”

“…Recent studies have also shown a sustained clinical benefit at years 1-3 following a relatively short course of therapy, alongside persistent immunological signals as described above, albeit with a downward trend from immediate post-treatment metrics. 37,40 Ellis et al 39 reported a phenomenon of a bell-shaped pharmacological response rather than a linear dose-response association with grass pollen peptides, highlighting the importance of dose titration in early clinical trials to inform robust design of phase III trials and beyond. Whilst a cumulative dose of 48 nmol of grass peptides (4 or 8 injections) induced a significant therapeutic benefit, a similar (or expected dose-response benefit) response was not detected with a higher dose of 96 nmol.…”

“…Current recommendations with whole allergen extracts of SLIT and SCIT are that 3 years of treatment is recommended to achieve long-term efficacy. 4,5 Whilst there is preliminary and promising evidence that a short course of peptide AIT for 4-6 weeks confers sustained 37,40,48 clinical benefit at years 1-3, without additional treatment, further studies are clearly warranted to determine long-term efficacy with optimization of dosing regimens, route of administration (intradermal vs subcutaneous), duration of therapy and safety specifically in asthma. Further research is also needed in children in order to determine the role for peptide AIT not only in established allergic airway disease, but also with respect to prevention of asthma and newer sensitizations as reported with whole allergen AIT.…”

“…Importantly, no unexpected safety signals arose from administration of these SPs. It is interesting to note that a short course of treatment with SPs in ARC has been shown to induce long-term suppression of symptoms, 37,40 whereas the use of SPs produces only short-term benefit in autoimmune disease. 32,69 We propose that this is due to the continued exposure of allergic patients to strong antigens and the generation of memory B cells producing blocking antibodies.…”