Table 3. Immunotherapy trials comparing single extract to multiple extract immunotherapy.

References	Study objective	Design/participants	Intervention and outcome measures	Results	Possible study limitations
Henzgen et al. [60]	Comparison of SCIT with single tree pollen extract and a mixture of tree pollen extracts in tree pollen allergic patients	Open, randomized, Single centre N = 40 Intervention group 1: N = 18/20 completed Intervention group 2: N = 18/20 completed	Intervention: Intervention group 1: SCIT with birch pollen extract for 3 years Intervention group 2: SCIT with mixture of tree pollen extracts (hornbeam/oak/alder/hazel) Outcome measure: Symptom score Number of symptomatic days	Significant improvement in both groups No significant difference in outcome measures between both groups	No placebo No objective outcome measures
Petersen et al. [61] Wihl et al. [62] Ipsen et al. [63]	Comparison of SCIT with single tree pollen extracts and a mixture of tree pollen extracts in tree pollen allergic patients	Double-blind, matched pair, single centre N = 54 Intervention group 1: N = 23/27 completed Intervention group 2: N = 22/27 completed	Intervention: Intervention group 1: SCIT with standardized birch pollen extract for 3 years Intervention group 2: SCIT with a mixture of birch, alder and hazel extract for 3 years Outcome measure: Symptom score Medicine consumption score SPT Nasal Provocation Test Patients’ specific IgE	Significant improvement in both groups No significant difference in outcome measures between both groups	No placebo
Frostad et al. [64]	Comparison of SCIT with crude and refined timothy grass pollen extract and with a mixture of four grass pollen extracts in grass pollen allergic patients	Single-blind for treated groups, randomized, single centre N = 90 Intervention group 1: N = 14/17 completed Intervention group 2: N = 20/24 completed Intervention group 3: N = 16/19 completed Control Group: N = 30	Intervention: Intervention group 1: SCIT with crude aqueous timothy grass pollen extract for 3 years Intervention group 2: SCIT with refined aqueous timothy grass pollen extract for 3 years Intervention group 3: SCIT with crude aqueous extract from equal amounts of four grass pollens (Dactylis glomerata, Festuca elatior, Phleum pratense, Lolium perenne) Control group: No SCIT, but symptomatic medication Outcome measure: Symptom score and symptomatic medication score Patient self-evaluation Nasal Provocation Patients’ specific IgE	Significant improvement in all intervention groups compared to the control group Refined timothy grass pollen extract at least equally effective as crude pollen extract and grass pollen mixture	Crude extract possibly not stable in storage, No real placebo
Verstraeten and Verstraeten [65]	Comparison of SCIT with tyrosine-bound grass pollen mixture, aluminium hydroxide-adsorbed grass pollen mixture, purified timothy grass pollen extract for 4 years	Open, Randomized, single centre N = 60 Intervention group 1: N = 20 Intervention group 2: N = 17 Intervention group 3: N = 23	Intervention: Intervention group 1: SCIT with crude extract of 12 grass pollens adsorbed with aluminium hydroxide (bent, brome, cocksfoot, dogstail, fescue, foxtail, meadow, rye, vernal, timothy, false oat, Yorkshire fog) for 4 years Intervention group 2: SCIT with glutaraldehyde-pollen-tyrosine adsorbate of 12 grass pollens (bent, brome, cocksfoot, dogstail, fescue, foxtail, meadow, rye, vernal, timothy, false oat, Yorkshire fog) for 4 years Intervention group 3: SCIT with purified standardized timothy pollen extract for 4 years Outcome measure: Symptom score as correlated with pollen count Supplementary medication score Patient self-evaluation	Significant improvement in all intervention groups Timothy grass pollen extract at least equally effective as grass pollen mixture	No placebo