VIT Schedules


Practice Parameter (2011)
  • Approved by FDA
Traditional schedule (Hollister-Stier)
  • Weekly injections
Modified rush schedule (Alk-Abello)
  • 2–3 doses/day at 30 min intervals for each of the first 8 weeks----
Week No.
Concentration (μg/mL)
Volume (mL)----
Week No.
Concentration (μg/mL)
Volume (mL)
1
1.0
0.05
1
0.01
0.1




0.1
0.1




1.0
0.1
2
1.0
0.1
2
1.0
0.1




1.0
0.5




10
0.1
3
1.0
0.2
3
10
0.1




10
0.5




10
1.0
4
1.0
0.4
4
100
0.1




100
0.2
5
10
0.05
5
100
0.2




100
0.3
6
10
0.1
6
100
0.3




100
0.3
7
10
0.2
7
100
0.4




100
0.4
8
10
0.4
8
100
0.5




100
0.5
9
100
0.05
9
100
1.0
10
100
0.1
Monthly
100
1.0
11
100
0.2



12
100
0.4



13
100
0.6



14
100
0.8



15
100
1.0



16
100
1.0



18
100
1.0



21
100
1.0



Monthly
100
1.0



When the maintenance dose is achieved, the interval may be advanced from weekly to monthly.

EAACI Venom Allergy Monograph (2009)
eaaci_vit_schedule.png

BSACI Guidelines (2011)
BSACI_Venom_conv_IT.png
BSACI_venom_rush_IT.png
BSACI_venom_ultrarush_IT.png

Notes
  • Starting dose - often 0.01 μg but 1 μg probably safe
    • Johns Hopkins standard regimen begins with 1-6 μg on the first day
  • Maintenance dose (for almost all cases) = 1 mL of 100 μg/mL venom extract
    • Clinical efficacy is dose-dependent, with complete protection from systemic reaction occuring in 98% treated with mixed vespid venoms (300 μg total dose), 90-95% with single vespid venoms, and 75-85% with honey bee venom
      • Efficacy lower in patients with mastocytosis (75%)
      • Sting challenge studies show that protection against systemic reactions is achieved when the maintenance dose is reached after an 8-week build-up
    • 100 μg is approximately equal to 1-2 bee stings and to many more Vespula stings
    • The maintenance dose should be achieved, regardless of large local reactions or temporary delays caused by systemic reactions during VIT
      • BSACI: if there are severe systemic reactions to 100 μg, the dose should be reduced and if further reactions occur, VIT discontinued
    • 2 studies have provided evidence that a 50 μg maintenance dose in children is effective using bee and yellow jacket venom
    • Higher maintenance doses (150-200 μg or more) are recommended for bee-keepers, who may be stung by several insects at the same time and in treatment failures or incomplete treatment success (e.g. sting reaction while on maintenance VIT)
      • Further testing might be needed to determine whether there is a new or untreated venom sensitivity before considering an increase in the venom dose
  • Multiple venoms - Treatment often requires multiple venoms, which can be administered on the same day
    • Do not mix venoms together (e.g., wasps or honeybee with yellow jacket), even though yellow jacket and hornet venom are available premixed as a mixed-vespid extract
    • Some recommend that if 2 or more venoms are required, they should be given in separate protocols a few days apart
  • Accelerated schedules - In the case of VIT, adverse reactions are not more common with modified-rush and rush regimens than with traditional regimens, and these schedules are not considered experimental
    • Maintenance dose can be routinely achieved in 8 weeks, and even 2 or 3-day rush schedules can be used without an increased risk of systemic reactions
  • Maintenance injection interval - 4 weeks is recommended for indefinite treatment in the FDA–approved product package inserts
    • In Europe, general consensus is that the maintenance interval should be 4 weeks for the 1st year, extended to 6 weeks in the 2nd year, and then to 8 weeks if VIT is continued over 5 years
    • Practice parameter: "experts in the field support the regimen of a 4-week maintenance interval for 12 to 18 months followed by a 6-week interval for 12 to 18 months and then 8-week intervals"
    • Maintenance intervals have been effectively increased to 3 months after a few years (but a 6 month interval was not found to be effective)
  • Premedication
    • Antihistamine premedication during build-up phase has been shown to reduce local reactions and mild systemic reactions and might improve the efficacy of VIT
    • Montelukast premedication may reduce local reactions to VIT
  • Dose adjustment for new vial
    • Lieberman: once a patient has reached the maintenance dose of VIT, we keep that dose intact, we do not lower the dose with a new vial
  • Pre-VIT injection assessment



Fire Ant IT Schedules


Conventional
  • Conventional dosing schedules for Solenopsis invicta or a mixture of S. invicta/S. richteri whole-body extract (Insect Allergy Practice Parameter 2011):
fire_ant_it_sched.png

FA conventional IT schedule.png



Accelerated Schedules
FA 2 day rush IT schedule.png
FA 1 day rush IT schedule.png



General Notes
  • Maintenance dose = 0.5 mL of 1:100 (5 mg) fire ant whole body extract
  • After the maintenance dose of 0.5 mL of 1:100 wt/vol is administered safely several times, the dosage interval can be advanced to every 2 then every 4 weeks
  • As with non-fire ant VIT, accelerated schedules seem to be safe and effective


Reactions during VIT

  • Systemic reaction rate is up to 10-15% in most patients and 15-25% in those with mastocytosis

Risk Factors

  • IT with bee venom (14.2% reaction rate vs. 2.8% for vespid VIT)
  • Pre-existing allergic rhinitis
  • Mastocytosis, elevated tryptase level
  • Age is not a risk factor
  • Maybe ACE inhibitors and beta-blockers
    • Unknown whether the risk with beta 1-selective beta-blockers is less than that observed with the nonselective beta-blockers

Management of Large Local Reactions

  • BSACI: a dose reduction to the previous tolerated dose in the initial course is recommended. In patients with recurrent LLR, premedication with an antihistamine should be considered or the dosage split between different sites
  • Montelukast premedication may reduce local reactions to VIT

Management of Systemic Reactions

  • BSACI: subsequent dose should be reduced (depending upon the severity of the reaction) followed by careful dose escalation and premedication with antihistamine considered
  • For recurrent reactions, consider:
    • Limit treatment to a single venom initially and to give several small doses at 30 min intervals to achieve a higher total dose for each visit
    • Rush VIT
    • Small number of reported cases using omalizumab pretreatment for patients previously unable to tolerate VIT; in most such cases the omalizumab therapy could be safely discontinued after 6 months


Duration of VIT

  • Duration is controversial, but should be at least 3-5 years
    • Golden: demonstrable advantages to 5 years vs 3, but some patients (especially children) seem to do well with only 3 years (children with 3.5 years had only 5% relapse rate during the following 10-15 years)
    • BSACI:
      • In UK practice, a duration of 3 years is recommended
      • There is no evidence to support indefinite VIT in mastocytosis and this cannot be recommended in the UK without further evaluation
    • Ledford:
      • If anaphylaxis occurs during treatment (either to stings OR allergy injections), or if the original sting reaction was severe/life threatening, VIT should probably not be stopped until at least the skin test becomes negative
      • Stopping after 3-5 years (with or without a decrease in skin test reactivity) can be considered with milder anaphylactic history
  • Some recommend indefinite immunotherapy for patients with severe anaphylaxis with loss of consciousness due to reports that some of these patients (after several years of VIT) with negative in vitro test or skin tests experienced systemic reactions (some fatal) to subsequent stings after stopping VIT
  • Skin test to venom becomes negative in 25% after 5 years of VIT; 60-70% are negative after 7-10 years
    • When both skin and sIgE are negative, VIT has been discontinued with no systemic reactions to subsequent stings
    • Some recommend repeat testing every 2-3 years during VIT, although negative results are uncommon until 5 years of VIT or longer.
    • Repeat sIgE testing is not required for consideration of discontinuing VIT
  • After 5 years of VIT, there is still a 10% risk of a systemic reaction (but most reactions are mild)
    • Risk factors for having a sting reaction after VIT done: adults > children, honey bee > vespidae, more severe initial reaction or reaction to VIT, unchanged skin test during VIT, elevated tryptase level or mastocytosis

Duration of Fire Ant IT

  • A definitive recommendation about the duration of immunotherapy for fire ants cannot be made
  • Recommendations range from 3 years to indefinitely, with some stopping when skin tests are negative
    • Lieberman: my personal choice is usually to stop in 5 years if the reaction was not severe



Epinephrine Injector

  • Chance of needing epinephrine for a sting reaction is almost 1% in random adults, 2-3% in large local reactors, children with cutaneous systemic reactions, patients undergoing VIT, and those who discontinue VIT after 5 years and have no high-risk factors
  • Lieberman: it is my personal practice to tell a patient who has had an immediate hypersensitivity reaction to hymenoptera sting to continue carrying their epinephrine injector with them lifelong (even after a successful course of VIT)
  • BSACI: in addition to all patients during VIT up-dosing, the following groups are provided with epinephrine even after successful VIT course:
    • Those at continuing risk of multiple stings, for example a gardener with an occupational risk of multiple wasp stings or a beekeeper after bee VIT
    • If during immunotherapy the patient continued to experience allergic reactions
    • Patients with an elevated baseline tryptase or mastocytosis




References