Table 1.
Double-blind, randomized studies (versus placebo, comparator) selected in this systematic review involving either adult or both pediatric and adult patients.
| Ref* | Age† | Cohort size | Diagnosis | Allergen | Administration type | Study duration | Efficacyα | Safety |
|---|---|---|---|---|---|---|---|---|
| Mäkelä et al.21 | 12–65 | 637 | RC | Birch pollen | Pre-/coseasonal | 16 weeks (pre) + 6 months during birch and tree seasons | 30–33% reduction in DSS for 7DU | 68 SAEs No Ax |
| Pfaar et al.33 | 19–59 | 269 | R/RC | Birch pollen | Outside season | 5 months | Stepwise improvement in SS, significant in 20,000 AUN/mL and 40,000 AUN/mL doses | - |
| Voltolini et al.73 | 44±9 | 24 | R | Birch pollen | Pre-/coseasonal | 4 months over 2 consecutive seasons | Rhinorrhea and nasal obstruction decreased | No SAEs No Ax |
| Khinchi et al.111 | 20–58 | 71 | R | Standardized birch pollen | Coseasonal | 1 baseline year + 2 years treatment | 0.36/0.29 improvement in SS/MS in first season | No SAEs No Ax |
| Didier et al.41,65 | 18–50 | 633 | RC | 300 IR 5-grass pollen | Pre-/coseasonal | 2 or 4 months (pre) until end of season 1–3 years of treatment + 2 years of follow-up |
34.5–36.0% reduction in AASS at season 3 25.3–31.1% reduction in AASS after 1 year of follow-up 28.1% reduction in AASS after 2 years of follow-up |
3 SAEs at year 1 No Ax |
| Maloney et al.47 | 5–65 | 1501 | R/RC | MK-7243 grass | Pre-/coseasonal | 12 weeks (pre) until end of season | 23/29% improvement in TCS in entire/peak season 20% improvement in DSS in entire-season 35% improvement in DMS in entire-season |
No SAEs No Ax |
| Durham et al.60 | 18–65 | 634 | RC | SQ-grass pollen | Pre-/coseasonal | 4–8 months (pre) until end of season 3 years of treatment + 2 years of follow-up |
25–36% reduction in DSS after 5 seasons 20–45% reduction in DMS for 1–4 seasons 27–41% reduction in TCS after 5 seasons |
No SAEs No Ax |
| Horak et al.81 | 19–50 | 89 | RC | 300 IR 5-grass pollen | Pre-/coseasonal | 4 months | 33% improvement in TSS Effect since first and second month of treatment |
No SAEs No Ax |
| Mösges et al.86 | 18–50 | 105 | RC | Grass and rye pollen | Out of season | 9 months | Reduced TSC | No SAEs No Ax |
| Moreno-Ancillo et al.87 | 14–55 | 105 | R ± Asthma | Grass and olive pollen | Pre-/coseasonal | 6 months (pre) until end of season | Reduction in SS and MS No differences in SS and MS between groups |
No SAEs No Ax |
| de Blay et al.88 | 12–41 | 127 | RC | Standardized 3-grass pollen | Pre-/coseasonal | 10 months (pre) until end of season | Trend of improvement in clinical score | No SAEs No Ax |
| Didier et al.89 | 18–45 | 628 | RC | Standardized 5-grass pollen | Pre-/coseasonal | 4 months (pre) until end of season | Reduction in TSS with 300 IR and 500 IR | No SAEs No Ax |
| Smith et al.107 | 18–60 | 186 | R | 5-grass pollen | Continuous | 1 baseline year + 1–2 years of treatment | Improvement in SS in years 1 and 2 6.8 and 2.4 times to show reduced nose running and sneezing |
7 SAEs No Ax |
| Clavel et al.127 | 8–55 | 136 | R | Standardized 5-grass-pollen |
Coseasonal | 6 months | Lower MS during first 6 weeks of the season | No SAEs No Ax |
| Pfaar et al.84 | 18–59 | 185 | R/RC | 6-grass pollen | Continuous | 2 years | Improvement in TCS during a 42-day period in season | No SAEs No Ax |
| Palma-Carlos et al.98 | 19–43 | 33 | R | Grass pollen | Pre-/coseasonal | 2 years | Reduction in SS between first and second year, and after 2 years of treatment | No SAEs No Ax |
| Nelson et al.66 | 18–63 | 439 | RC | Timothy grass pollen | Pre-/coseasonal | 16 weeks (pre) until end of season | 18 and 20% improvement in DSS and TCS 26% improvement in DMS |
No SAEs No Ax |
| Durham et al.103 | 18–65 | 855 | RC | Timothy grass pollen | Pre-/coseasonal | 8 weeks (pre) and season (10 weeks) | 16/28% reduction in SS/MS during season with 75,000 SQ-T 21/29% efficacy increased with pre-seasonal (≤8 weeks) |
No SAEs No Ax |
| Lima et al.116 | 18– | 56 | RC | Timothy grass pollen | Continuous | 12–18 months | No differences between groups in SS and MS | No SAEs No Ax |
| Creticos et al.48 | 18–55 | 429 | R/RC | Ragweed pollen | Pre-/coseasonal | 8–16 weeks (pre) until end of season | 43% decrease in TCS in entire season 42/41% decrease in DSS in entire/peak season |
No SAEs No Ax |
| Creticos et al.54 | 18–50 | 784 | R/RC | Ragweed pollen | Pre-/coseasonal | 12–16 weeks (pre) until end of season | 9–24% reduction in TCS in peak season (1.5, 6, 12 Amb a 1-U) 12–27% reduction in DCS in entire season (same doses) |
12 SAEs No Ax |
| Skoner et al.71 | 18–50 | 115 | RC | Ragweed pollen | Pre-/coseasonal | 8–10 weeks (pre) until end of season | 15% reduction in rhinoconjunctivitis SS in entire season DSS and DMS reduced in 48 mg Amb a 1/d (same period) |
18 SAEs No Ax |
| Bowen et al.105 | 6–58 | 83 | RC | Ragweed pollen | Pre-/coseasonal | 1–2 weeks (pre) and season (3 months) | No differences between groups in SS and MS | No SAEs No Ax |
| André et al.114 | 7–55 | 110 | R | Standardized ragweed pollen | Pre-/coseasonal | 28 days + 30 days (pre) and co-seasonal 6.5 months with maintenance treatment | Lower SS and MS during the season Highest doses showed highly response for TSS than lower ones |
No SAEs No Ax |
| Okamoto et al.42 | 12–64 | 531 | RC | Japanese cedar pollen | Continuous | 4 months (pre) until end of second consecutive season | 18 and 30% lower TNSMS in first and second seasons | No SAEs No Ax |
| Okubo et al.83 | 40±15 | 61 | RC | Japanese cedar pollen | Pre-/coseasonal | 6 weeks (pre) until end of season | Lower TSS for some days | No SAEs No Ax |
| Horiguchi et al.85 | 20–37 | 77 | RC | Japanese cedar pollen | Pre-/coseasonal | 4 months (pre) until end of season | Lower SS | No SAEs No Ax |
| Vervloet et al.93 | 19–60 | 76 | RC | Juniperus ashei pollen | Coseasonal | 2 seasons | 40–60% reduction in TMS No differences between groups in TSS |
No SAEs No Ax |
| Tonnel et al.110 | 7–45 | 120 | R | House-dust mite | Continuous | 24 months | SS decreased after 1 year and persisted | No SAEs No Ax |
| Bousquet et al.123 | 7–42 | 85 | Asthma | House-dust mite | Continuous | 25 months | Reduction in SS | No SAEs No Ax |
| Guo et al.27 | 18±9 | 48 | R | House-dust mite | Continuous | 12 months | Improvement in individual nasal SS and TNSS after 11–12 months of treatment | No SAEs No Ax |
| Okubo et al.28 | 12–64 | 946 | R | House-dust mite | Continuous | 12 months | 19 and 22% reduction in TCRS with 20,000 and 10,000 JAU 18 and 22% improvement in SS with same respective doses |
No SAEs No Ax |
| Zieglmayer et al.34 | 18–58 | 106 | R/RC ± Asthma | SQ-House-dust mite | Continuous | 12 months | Improvement of symptoms in patients with 12 SQ-HDM Reduction in 65% in TASS |
No SAEs No Ax |
| Nolte et al.35 | 12–85 | 1482 | R/RC | SQ-House-dust mite | Continuous | Up to 52 weeks | 17% improvement in TCRS 16% reduction in DSS |
No SAEs One Ax |
| Okamoto et al.29 | 12–64 | 968 | R ± Asthma | House-dust mite | Continuous | 52 weeks | 18 and 13% improvement in AASS in the weeks 44–52 for 300 IR and 500 IR | No SAEs No Ax |
| Roux et al.36 | 18–55 | 355 | R | House-dust mite | Continuous | 6 months | 33, 29, and 20% reduction in SS with 500 IR, 300 IR and 100 IR | No SAEs No Ax |
| Virchow et al.37 | 17–83 | 834 | R + Asthma | SQ-House-dust mite | Continuous | Up to 18 months | Both 6 SQ and 12 SQ doses reduced the risk of asthma exacerbation (moderate or severe, or with deterioration in asthma symptoms) | No SAEs No Ax |
| Demoly et al.39 | 18–66 | 992 | R/RC ± Asthma | SQ-House-dust mite | Continuous | 12 months | 18–22% reduction in TCS with 6 and 12 SQ Significant reduction in SS and MS with both doses |
No SAEs No Ax |
| Potter et al.40 | 18–60 | 60 | R ± Asthma | House-dust mite | Continuous | 24 months | Progressive improvement in TSS No differences between SLIT and placebo |
No SAEs No Ax |
| Nolte et al.44 | 18–58 | 124 | R/RC ± Asthma | House-dust mite | Continuous | 24 weeks | 27 and 49% reduction in TNSS at week 24 with 6 DU and 12 DU | No SAEs No Ax |
| Mosbech et al.45 | 14–73 | 604 | R + Asthma | House-dust mite | Continuous | 12 months | 29% improvement in TCRS with 6 SQ dose in the end of treatment | 4 SAEs No Ax |
| de Blay et al.49 | >14 | 108 | Asthma | House-dust mite | Continuous | 12 months | Significant reduction in ACQ at the end of study with 6 SQ | No SAEs No Ax |
| Wang et al.50 | 14–50 | 484 | Asthma | House-dust mite | Continuous | 12 months | 80.5 and 54.0% improvement in well-, or totally-controlled asthma in subjects with moderate, persistent asthma and SLIT | No SAEs No Ax |
| Bergmann et al.52 | 18–50 | 509 | R | House-dust mite | Continuous | 12 months + 12 months follow-up | 17.9 and 20.2% reduction in AASS with 300 IR and 500 IR maintained during the follow-up | 4 SAEs No Ax |
| Mosbech et al.53 | >14 | 604 | R + Asthma | SQ-House-dust mite | Continuous | 12 months | 42.0 and 50.0% relative mean and median reduction for 6 SQ | 2 SAEs No Ax |
| Wang et al.56 | 4–60 | 120 | R | House-dust mite | Continuous | 6 months | Significant reduction in TSS since week 14 | No SAEs No Ax |
| Cortellini et al.69 | 14–42 | 27 | R | Alternaria | Coseasonal | 10 months | Improvement in mean SS at the end of treatment Reduction in MS compared with run-in season and placebo |
No SAEs No Ax |
| Ariano et al.117 | 35±13 | 20 | RC | Cupressus arizonica | Coseasonal | 12 months | Lower SS and MS during the season | No SAEs No Ax |
| Passalacqua et al.120 | 19–47 | 30 | RC | Parietaria sp. | Pre-seasonal | 5 months | Decrease in SS and MS after therapy | No SAEs No Ax |
| Purello-D’Ambrosio et al.121 | 32±17 | 30 | RC ± Asthma | Parietaria judaica | Pre-/coseasonal | 1 season | Reduced SS and MS especially during the season | No SAEs No Ax |
*
Subanalyses (with redundant results), pooled studies, or references with not available full-text were not included in the table.
†
Age is shown as range (minimum–maximum) or mean ± standard deviation.
α
If not indicated, efficacy results are referred to the active treatment group. Comparisons are made with placebo. Only significant results are shown (p<0.05).
AASS, average adjusted symptoms score; ACQ, asthma control questionnaire; Ax, anaphylactic reaction; DMS, daily medication score; DSS, daily symptom score; DU, development units; IR, index of reactivity; JAU, Japanese allergy units; MS, medication score; R, rhinitis; RC, rhinoconjunctivitis; SAE, severe or serious adverse events (related to SLIT); SS, symptom score; TASS, total asthma symptom score; TCRS, total combined rhinitis score; TCS, total combined score; TMS, total medication score; TNSMS, total nasal symptom and medication score; TNSS, total nasal symptom score; TSS, total symptom score.