2016 Section 5 Green Book

LI ET AL

J ALLERGY CLIN IMMUNOL nnn 2015

TABLE III. Randomized trials comparing the clinical effects of SCIT and SLIT

Allergen (duration)

Patients enrolled/dropouts

Age range (y)

Study, year

Main results

Piazza et al, 15 1993

SCIT 5 17/0 SLIT 5 14/0 LNIT 5 12/0 Control 5 14/0 SCIT 5 10/0 SLIT 5 15/0 SCIT 5 15/0 SLIT 5 10/0 Placebo 5 11/0 SCIT 5 24/5 SLIT 5 23/9 Placebo 5 24/9

Mite (2 y)

15-60 SLIT: decrease in symptoms at 3 mo but not 12-24 mo

SCIT: decrease in symptoms at 3, 12, and 24 mo; IgE, IgG, and IgG 4 changed only in SCIT. No change at all in LNIT.

Quirino et al, 16 1996 *

Grass (1 y)

18-60 Significant reduction in symptom and drug intake score in both

groups vs baseline. No change in IgE level. Increase in IgG level and reduction of skin reactivity only in the SCIT group.

Mungan et al, 17 1999

Mite (1 y)

18-65 Reduction in rhinitis score for SLIT and SCIT. Asthma score

reduction only for SCIT. Reduction in drug score for both SLIT and SCIT. Reduction in SPT diameter only in the SCIT group.

Khinchi et al, 18 2002 *

Birch (2 y)

18-60 Reduction in rhinitis score in SLIT and SCIT. No significant difference between the 2 treatments, both superior to placebo.

Medication scores SLIT and SCIT decreased vs placebo. No change in QoL.

Mauro et al, 19 2007 Antunez et al, 20 2007 Tahamiler et al, 21 2008 Ventura et al, 22 2009

Birch (4 mo) SCIT 5 23/8 SLIT 5 24/5

18-65 During pollen season, no SLIT-SCIT difference in symptoms plus drug scores. Specific IgG 4 levels significantly increased with SCIT only. 8-17 Improvement in subjective evaluation and VAS in both groups. Increase in IgG 4 levels only for SCIT. Decreases IgE/IgG 4 levels in both. NR (adults) Decrease in symptom score and nasal provocation scores in both groups after 3 y of treatment (greater in SCIT). Improvement maintained after 3 y only in SCIT. 18-65 Decrease in symptom scores in both groups (no value given): decrease in nasal eosinophil counts in SLIT. 5-12 Significant reduction in total rhinitis and asthma scores, medication scores, VAS scores, and skin reactivity for both SCIT and SLIT. No difference between routes of administration. 7-14 Significant reduction in symptom and medication score vs baseline with both treatments. SCIT is better than SLIT vs placebo. 5-12 Decreased asthma attacks and use of steroids at 4, 12, and 18 mo for SCIT and SCIT plus SLIT at 12 mo only for SLIT. No change in VAS score for asthma with SCIT or SIT alone.

SCIT 5 12/1 SLIT 5 11/1

Mite (2 y)

Mite (3 1 3 y) SCIT 5 96/NR SLIT 5 97/NR Cypress (1 y) SCIT 5 10 SLIT 5 10

Eifan et al, 23 2010

SCIT 5 16/2 SLIT 5 16/1 Drug 5 16/2 SCIT 5 10/1 SLIT 5 11/1 Placebo 5 11/0

Mite (1 y)

Yukselen et al, 24 2011

Mite (1 y)

Keles et al, 25 2011 *

SCIT 5 15/2 SLIT 5 15/2 SCIT 1 SLIT 5 15/1 Drugs 5 15/3

Mite (1 y)

QoL , Quality of life; NR , not reported; SCIT , subcutaneous immunotherapy; SLIT , sublingual immunotherapy; SPT , skin prick test; VAS , visual analog scale. *Double-blind double-dummy.

TABLE IV. Optimal maintenance doses of allergen based on available dose-ranging studies

Author, year

Total patients randomized

Allergen/preparation

Optimal maintenance dose

Durham et al, 34 2006 Didier et al, 35 2007 Creticos et al, 30 2014 Bergmann et al, 31 2014

855 628

Timothy grass/tablets 5-Grass mix tablets

15 m g of Phl p 5/d 25 m g/mL group 5/d 12 m g of Amb a 1/d

784 AR/ARC

Ragweed tablets

AR/ARC

Dust mite

28 m g of Der p 1, 120 m g of Der f 1 (500 IR)

Mosbech et al, 2014 32 and 2015 36

Asthma 604 AR 204

Dust mite tablet

6 SQ-HDM 6 SQ-HDM

Nolte et al, 33 2015

124

Dust mite tablets

12 DU *

AR , Allergic rhinitis; ARC , allergic rhinoconjunctivitis; HDM , house dust mite. *Same product as the Mosbech et al studies but different dosing units.

studies suggest that dual administration of SLIT products can be well tolerated. However, there are no published data on the concomitant use of the 3 products approved in the United States with each other or with SCIT, and the PIs state that concomitant dosing might increase the likelihood of local or systemic adverse reactions to either SCIT or SLIT.

scheduled time the next day. If you don’t take [the product] for more than one day, contact your health provider before restarting.’’ 2,3,40

CAN SLIT ALLERGENS BE COMBINED? The European experience suggests that distinct SLIT tablets (grass and ragweed) can be administered separately to the same patient. One open-label, controlled, 4-parallel-group, randomized study showed favorable results in patients sensitized to grass and birch with 2 SLIT products 14 ; another reported favorable results in patients given SLIT with grass plus olive extract. 27 Ongoing

WHAT ADVERSE EVENTS CAN OCCUR WITH SLIT? Adverse reactions associated with SLIT can be local or systemic. Local reactions, such as oral or mild gastrointestinal symptoms, are fairly common, affecting up to

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