| Condition; author | Intervention | Anaphylaxis | Death |
|---|---|---|---|
| Allergic asthma | |||
| Normansell et al.,17 2015 | SLIT v. placebo | NR | "None of the included studies reported any deaths." |
| Calderón et al.,6 2013 | SCIT v. placebo | "Several serious TEAEs (some of which required epinephrine) were reported. Pichler et al.(56) mentioned use but did not state whether this concerned an active treatment or placebo group participant. The 4 incidents reported by Bousquet et al.(25) (3 of which required epinephrine) all concerned the active treatment group during the rush updosing phase" | NR |
| Lu et al.,18 2015 | SCIT v. placebo | NR | NR |
| Abramson et al.,1 2010 | SCIT v. placebo | "Systemic adverse reactions were reported by 32 studies. Systemic reactions were defined as any of anaphylaxis, asthma, rhinitis or urticaria, or any combination of these. The pooled relative risk was 2.45 (95% CI 1.91 to 3.13) in the 26 reporting reactions per patient and this was relatively homogeneous (I2 = 27%)."Incidence of near-fatal reactions estimated to be 1 per 1 million reactions | Incidence of fatal reactions estimated to be 1 per 2.5 million |
| Liao et al.,16 2015 | SLIT v. placebo | NR | NR |
| Calderón et al.,6 2013 | SLIT v. placebo | "The only serious adverse event (AE) reported was a severe exacerbation of asthma in 1 patient in the placebo group in the study by Pham-Thi et al.(55)" | "The only serious adverse event (AE) reported was a severe exacerbation of asthma in 1 patient in the placebo group in the study by Pham-Thi et al.(55)" |
| Tao et al.,19 2014 | SLIT v. placebo | "The main adverse reactions in our analysis were mild local reactions, such as mouth and/or throat itchiness, redness and swelling. The risk of adverse effects found in our meta-analysis was RR 2.23 (95% CI 1.17 to 4.24; p = 0.01) (Fig. 9). However, Tari et al. reported that severe asthma occurred in three patients attributing to the side effects of SLIT. (22)" | NR |
| Allergic rhinitis | |||
| Calderón et al.,34 2010 | SCIT v. placebo | "All studies reported a higher proportion of adverse events (AEs) in SIT groups than in placebo groups. Systemic AEs requiring administration of subcutaneous adrenaline were observed. (17, 21)" Both were in SCIT group. | NR |
| Calderón et al.,6 2013 | SCIT v. placebo | "The 2 earliest publications (23, 36) each featured 1 anaphylactic reaction caused by SCIT. More recent trials did not observe anaphylactic reactions." | NR |
| Meadows et al.,29 2013 | SCIT v. placebo | "Post-injection anaphylaxis was reported in only one small trial (159) (total n = 76) but was considerably more frequent following active treatment, occurring in approximately 10 of 39 patients (compared with 1 of 37 receiving placebo); 8 of the 10 patients were treated with adrenaline." | NR |
| Lin et al.,27 2013 | SCIT v. placebo | "Thirteen anaphylactic reactions were reported in four trials." None reported in control group. | "No deaths were reported." |
| Purkey et al.,30 2013 | SCIT v. placebo | "1 episode of anaphylaxis consisting of asthma and pruritus of the ear canal and oropharynx that required administration of epinephrine and oral corticosteroids.""In the patient who experienced anaphylaxis, symptoms developed 1 minute after administration of the 61st dose of treatment. Administration of subcutaneous epinephrine, intravenous methylprednisone, and nebulized salbutamol resulted in rapid resolution of symptoms. SCIT was discontinued in this patient." | "Local and systemic reactions (rare but with significant morbidity/mortality if they occur)." |
| Yang et al.,20 2016 | SLIT v. placebo | NR | NR |
| Di Bona et al.,21 2015 | SLIT v. placebo | No anaphylactic reactions reported in either SLIT or placebo groups. Nine events requiring epinephrine administration were reported in the SLIT group compared with 3 in the placebo group. | NR |
| Devillier et al.,24 2014 | SLIT v. placebo | NR | NR |
| CADTH,22 2014 | SLIT v. placebo | "In studies P05238, P05239, and P08067, it was mentioned that no participants experienced anaphylactic shock, and in studies GT-02, GT-07, GT-08, GT-12, and GT-14, there was no specific mention of anaphylactic shock. No incidence of anaphylaxis was reported in GT-02, GT-07, GT-08, and GT-12. In study P05238, one participant in the PPAE group received epinephrine due to an adverse event that occurred following the first administration of the study drug, and one placebo-treated patient used epinephrine in response to an anxiety attack, which the manufacturer stated was not an indicated (or medically appropriate) use for this medication." | "There were no deaths reported in studies GT-07, GT-02, GT-14, GT-12, and P05239. In studies GT-08, P05238, and P08067, one death was reported in each study … none were considered by the manufacturer to be treatment related." |
| Calderón et al.,6 2013 | SLIT v. placebo | "Bahceciler et al.(22) did not observe any AEs of note with a maintenance dose of 8 mg of 'Der p' allergens in children and adolescents. In contrast, de Bot et al.(31) studied a maintenance dose of 2 mg of Der p 1 allergen and reported that 96% of both active and placebo group patients experienced TEAEs (including a high proportion of nonlocal AEs). Nevertheless, no immunotherapy-dependent serious AEs were reported in any of the active groups." | NR |
| Lin et al.,27 2013 | SLIT v. placebo | "No life-threatening reactions, anaphylaxis, or deaths were reported in these trials." | "No life-threatening reactions, anaphylaxis, or deaths were reported in these trials." |
| Meadows et al.,29 2013 | SLIT v. placebo | "Anaphylaxis was reported in two trials (192, 195) and occurred in 4 of 427 patients receiving active treatment and in none of 282 patients receiving placebo." | NR |
| Manzotti et al.,28 2013 | SLIT(Grazax or Oralair)v. placebo | "However, it seems not advisable to use Grazax, that starts directly with the maintenance dose, in subjects with an history of systemic reactions to SCIT, because anaphylactic reactions at the first dose were reported in such subjects. (21)" | NR |
| Radulovic et al.,33 2010 | SLIT v. placebo | "None of the studies reported anaphylaxis." | NR |
| Calderón et al.,34 2010 | SLIT drops v. placebo | "No life-threatening AEs or fatalities were described." | "No life-threatening AEs or fatalities were described." |
| Calderón et al.,34 2010 | SLIT tablets v. placebo | "All seven studies reported on safety in detail; the principal AEs were mild, local and transient and none required adrenaline administration. Treatment-related SAEs were not observed." | "All seven studies reported on safety in detail; the principal AEs were mild, local and transient and none required adrenaline administration. Treatment-related SAEs were not observed." |
Note: AE = adverse event, CADTH = Canadian Agency for Drugs and Technologies in Health, CI = confidence interval, NR = not reported, RR = relative risk, SAE = systemic adverse event, SCIT = subcutaneous immunotherapy, SLIT = sublingual immunotherapy, TEAE = treatment-emergent adverse event.
*May include both children and adults.