Table 2. Published dose finding studies (allergen immunotherapy) carried out in line with the German Therapy Allergen Ordinance (TAV) or independently thereof.
| Application/Ref. | Allergen source | Allergen preparation | Model | Result(s) | Comment |
|---|---|---|---|---|---|
| TAV allergens | |||||
| SLIT [14] | Birch pollen | Drops (non-modified) | NPT | With highest doses, statistically significant improvement compared to placebo after 5 months | Marked placebo effect (approx. 30%); no plateau formation, largest difference to placebo with highest dose |
| SCIT [15] | Birch pollen | Allergoid with adjuvant | CPT | 2 dose finding studies (comparison of cumulative dose) with symptom reduction | Absolute and relative differences significantly better compared to placebo with plateau formation with highest dose |
| SCIT [15] | House dust mite | Allergoid | NPT | With higher doses, statistically significant improvement compared to placebo after 12 months | Moderate differences due to marked placebo effect (approx. 30%) and considerable data scattering (Figure 3) |
| SLIT [16] | Grass pollen | Tablet (Allergoid) | CPT | No placebo group but 4 graduated actively treated groups. Significant superiority of marketed dosage according to patient assessment (secondary parameter) | No consistent dose-response relationship in primary endpoint. Interpretation of data difficult because no placebo was used. |
| SLIT [17] | House dust mite | Tablet (Allergoid) | CPT | Only one dose was statistically significantly superior to placebo | Small therapeutic window and only minor differences due to high placebo effect (approx. 50%) |
| Non-TAV allergens | |||||
| SLIT [18] | Bet v 1 | Tablet (recombinant, non-modified) | Field study | All 3 doses statistically significantly superior to placebo | No real dose-response relationship |
| SCIT [15] | Bet v 1 FV (folding variant) | Modified | Exposure chamber | All 4 doses statistically significantly superior to placebo | No real dose-response relationship |
| SCIT [20] | Bet v 1 peptides | Peptide immunotherapy | Field study | Only 2 concentrations tested against placebo; only smaller dose statistically significantly superior to placebo | Higher dose lower effect but more side effects; too few doses for real dose-response relationship |
| SCIT [21] | Lolium peptides | Peptide immunotherapy | CPT | Medium dose in responder analysis statistically significantly superior to placebo | Dose-response relationship with plateau reached in responder analysis |
| SCIT [22] | Timothy grass | Allergoid | IDT (LPR) | All doses statistically significantly superior to placebo | Significant improvement only in primary endpoint (IDT) without clear dose-response relationship; in exposure chamber, symptoms not significantly better compared to placebo |
The listed phase II studies to define the optimal dose for allergen immunotherapy illustrate the used products, models, results, and interpretations but may not be complete. Bet v 1 = birch pollen major allergen; CPT = conjunctival provocation test; IDT = intradermal test; LPR = late-phase reaction, delayed phase of immediate-type reaction; NPT = nasal provocation test; SLIT = sublingual immunotherapy; SCIT = subcutaneous immunotherapy.