EVALUATION OF THREE ALLERGEN EVALUATION OF THREE ALLERGEN SPECIFIC IMMUNOTHERAPY SPECIFIC IMMUNOTHERAPY

METHODSMETHODSStandard Injection Standard Injection

RUSH Injection RUSH Injection SublingualSublingual

Abstract# 54Abstract# 54

Richard Herrscher M.D. FACAAIRichard Herrscher M.D. FACAAIClinical Faculty U.T. Southwestern Medical Center Dallas, Clinical Faculty U.T. Southwestern Medical Center Dallas,

TexasTexas

Medical Director AIR Care P.A.Medical Director AIR Care P.A.

BACKGROUNDBACKGROUND

• RUSH immunotherapyRUSH immunotherapy - - one day scheduleone day schedule– Started using RUSH in 2000 based on description by Started using RUSH in 2000 based on description by

Sharkey P, Portnoy J.Sharkey P, Portnoy J. Ann AllergyAnn Allergy 1996;76:175-80 1996;76:175-80

– Little is known how this schedule compares to Little is known how this schedule compares to standard immunotherapy in terms of efficacy.standard immunotherapy in terms of efficacy.

• SLIT (sublingual immunotherapy)SLIT (sublingual immunotherapy)– Started using SLIT in 2003 based on evidence from Started using SLIT in 2003 based on evidence from

European studies reviewed by Canonica and European studies reviewed by Canonica and Passalacqua Passalacqua JACI 2003;111:437-48JACI 2003;111:437-48

– Very little data using U.S. extracts.Very little data using U.S. extracts.

PURPOSE and METHODSPURPOSE and METHODS

• Purpose of StudyPurpose of Study– To evaluate how alternative schedules of To evaluate how alternative schedules of

RUSH and SLIT compare to standard RUSH and SLIT compare to standard injection immunotherapy (SCIT) in terms of:injection immunotherapy (SCIT) in terms of:

• Compliance - patient acceptanceCompliance - patient acceptance• Clinical efficacyClinical efficacy• SafetySafety

PURPOSE and METHODSPURPOSE and METHODS

• MethodsMethods– Observational study. Data collection began in 2005.Observational study. Data collection began in 2005.– Evaluated all patients starting immunotherapy from Evaluated all patients starting immunotherapy from

July 2003 through December 2004. July 2003 through December 2004. – Data collection is ongoing.Data collection is ongoing.

– Efficacy data collected prospectively with attempt to Efficacy data collected prospectively with attempt to collect 6, 12 and 24 month time points.collect 6, 12 and 24 month time points.

– Efficacy evaluated by patient questionnaire:Efficacy evaluated by patient questionnaire:

Symptom and Medication reductionSymptom and Medication reduction scoresscores

5 point scale 0% - 25% - 50% - 75% - 100%5 point scale 0% - 25% - 50% - 75% - 100%

RUSH INJECTION SCHEDULERUSH INJECTION SCHEDULE

• One - day RUSH protocolOne - day RUSH protocol– Very similar to previously described protocolsVery similar to previously described protocols

– Sharkey P, Portnoy J. Sharkey P, Portnoy J. Ann AllergyAnn Allergy 1996;76:175-80 1996;76:175-80

– Harvey SM, Laurie S, Hilton K, Khan DA. Harvey SM, Laurie S, Hilton K, Khan DA. Ann Ann Allergy Asthma and ImmunologyAllergy Asthma and Immunology 2004;92:414-9 2004;92:414-9• 38% systemic reaction rate during rush protocol38% systemic reaction rate during rush protocol

RUSH INJECTION SCHEDULERUSH INJECTION SCHEDULE

VialVial

DilutionDilution

Day 1Day 1 DilutionDilution 1:11:1 1:11:1

ScheduleSchedule Vial sizeVial size 10 ml10 ml 10 ml10 ml

Dose (ml)Dose (ml) ScheduleSchedule 1X wk1X wk monthlymonthly

1:10001:1000 0.070.07

0.150.15

0.300.30

Dose (ml)Dose (ml) 0.050.05

0.070.07

0.100.10

0.150.15

0.200.20

0.250.25

0.300.30

0.400.40

0.500.50

0.500.50

1:1001:100 0.070.07

0.150.15

0.30.3

1:101:10 0.070.07

0.150.15

0.300.30

1:11:1 0.050.05

SLIT SCHEDULESLIT SCHEDULE

DilutionDilution 1:10,0001:10,000 1:10001:1000 1:1001:100 1:101:10 1:11:1

Vial sizeVial size 5 ml5 ml 5 ml5 ml 5 ml5 ml 5 ml5 ml 15 ml15 ml

scheduleschedule qd.- qod.qd.- qod. qd.- qod.qd.- qod. qd.- qod.qd.- qod. qd.- qod.qd.- qod. 3X wk3X wk

Drop doseDrop dose

q.d.- q.o.d.q.d.- q.o.d.Build-upBuild-up

3X weekly3X weeklymaintenancemaintenance

1 (0.05ml)1 (0.05ml)

22

33

44

55

66

77

88

99

10 (0.5ml)10 (0.5ml)

11

22

33

44

55

66

77

88

99

1010

11

22

33

44

55

66

77

88

99

1010

11

22

33

44

55

66

77

88

99

1010

11

22

33

44

55

66

77

88

99

1010

ALLERGEN EXTRACTS/DOSEALLERGEN EXTRACTS/DOSEAllergenAllergen TreeTree GrassGrass WeedWeed MoldMold MiteMite

strengthstrength 1:20w/v1:20w/v 100k 100k BAU/mlBAU/ml

1:20w/v1:20w/v 1:20w/v1:20w/v 10k 10k BAU/mlBAU/ml

Major allergenMajor allergen GREERGREER

N/AN/A N/AN/A 488 488 ggAmb a1/mlAmb a1/ml

40 40 ggAlt a1/mlAlt a1/ml

166 166 ggDer p1f1/mlDer p1f1/ml

Std. SCITStd. SCIT0.5 ml /month0.5 ml /month

.05.05 ml ml 6.0k6.0k BAUBAU

0.06 0.06 mlml

29 29 gg

0.06 0.06 mlml

2.4 2.4 gg

1.0k1.0k BAUBAU

17.3 17.3 gg

RUSH SCITRUSH SCIT0.5 ml /month0.5 ml /month

.05.05 ml ml 5.5k5.5k BAUBAU

0.06 0.06 mlml

29 29 gg

0.06 0.06 mlml

2.4 2.4 gg

980980 BAUBAU

16.3 16.3 gg

SLITSLIT6.0 ml /month6.0 ml /month

.83 .83 mlml 89.0k89.0k BAUBAU

0.83 0.83 mlml

405 405 gg

1.1 1.1 mlml

44 44 gg

18k18k BAUBAU

299 299 ggSLIT increaseSLIT increase

Monthly doseMonthly dose1515XX 1515XX 1414XX 1717XX 1717XX

SCHEDULE PERFORMANCESCHEDULE PERFORMANCE% Patients Achieving Maintenance Doses% Patients Achieving Maintenance Doses

1:11:1 1:101:10 1:1001:100 1:10001:1000Vial dilutionVial dilution

6 6 monthsmonths

12 12 monthsmonths

24 24 monthsmonths

100%100%

50%50%

100%100%

50%50%

100%100%

50%50%

Std. SCITStd. SCIT

RUSH SCITRUSH SCIT

SLITSLIT

SCHEDULE PERFORMANCESCHEDULE PERFORMANCECumulative Allergen DoseCumulative Allergen Dose

6 6 monthsmonths

12 12 monthsmonths

24 24 monthsmonths

Std. SCITStd. SCIT RUSH RUSH SLITSLITAmb a1Amb a1 9.3 9.3 gg 200 200 gg 976 976 gg

Effective dose increaseEffective dose increase (22X)(22X) (105X)(105X)

Amb a1Amb a1 234 234 gg 395 395 gg 3.8 mg3.8 mg

Effective dose increaseEffective dose increase (1.7X)(1.7X) (16X)(16X)

Amb a1Amb a1 610 610 gg 683 683 gg 8.5 mg8.5 mg

Effective dose increaseEffective dose increase (1.1X)(1.1X) (14X)(14X)

• All patients starting IT July-03 thru Dec-04All patients starting IT July-03 thru Dec-04

COMPLIANCE DATACOMPLIANCE DATAupdatedupdated

RUSHRUSH Std. SCITStd. SCIT SLITSLIT

Age yrs.Age yrs. (range)(range) 32.5 32.5 (6-60)(6-60) 24.4 24.4 (3-67)(3-67) 18.2 18.2 (4-71)(4-71)

Total startsTotal starts (M/F)(M/F) 8484 (44/40)(44/40) 146 146 (74/72)(74/72) 97 97 (56/41)(56/41)

Current on Current on therapytherapy

62 62 (74%)(74%) 9292 (63%)(63%) 5858 (60%)(60%)

Total evaluatedTotal evaluated 6262 9292 5858

UPDATED EFFICACY DATAUPDATED EFFICACY DATAPatient starts July 2003 - Dec 2004Patient starts July 2003 - Dec 2004

75%75%

25%25%

50%50% 43.1%43.1%

28.1%28.1%21.4%21.4%

50%50%

34.9%34.9% 34.7%34.7%

< 12 months therapy< 12 months therapy > 12 months therapy> 12 months therapy

No. patientsNo. patients 2929 4949 3131 3333 4343 2727Mean monthsMean months 9.29.2 8.58.5 7.87.8 17.917.9 17.317.3 15.015.0

Std.Std.SCITSCIT

RUSHRUSH SLITSLIT

Med/ SxMed/ Sx

Me

dic

atio

n/ S

ymp

tom

Me

dic

atio

n/ S

ymp

tom

Re

duc

tion

Sco

reR

ed

uctio

n S

core

P=.001P=.001 P=.03P=.03

EFFICACY DATAEFFICACY DATAPatient starts July 2003 - May 2005Patient starts July 2003 - May 2005

75%75%

25%25%

50%50%39.9%39.9%

28.4%28.4%23.2%23.2%

43.1%43.1%

29.2%29.2% 33.9%33.9%

6 months6 months 12 months12 months

No. patientsNo. patients 2121 6060 4141 3838 4242 3434 1919 2828 1313Mean mo’sMean mo’s 7.27.2 7.37.3 6.96.9 12.812.8 12.412.4 12.912.9 21.221.2 20.920.9 19.119.1

Std.Std.SCITSCIT

RUSHRUSH SLITSLIT

Med/ SxMed/ Sx

Me

dic

atio

n/ S

ymp

tom

Me

dic

atio

n/ S

ymp

tom

Re

duc

tion

Sco

reR

ed

uctio

n S

core

56.0%56.0%

46.5%46.5%41.4%41.4%

24 months24 months

P=.025P=.025 P=.015P=.015

SAFETY DATASAFETY DATA

SYSTEMIC REACTIONSSYSTEMIC REACTIONSmoderate - severemoderate - severe

Total patientsTotal patients 9999 201201 142142

Post Rush 1st or Post Rush 1st or 2nd injection2nd injection

1111 N/AN/A N/AN/A

Total otherTotal other 5 (5%)5 (5%) 12 (6%)12 (6%) 1 (0.7%)1 (0.7%)

Total w/reactionTotal w/reaction 16 (16%)16 (16%) 12 (6%)12 (6%) 1 (0.7%)1 (0.7%)

Total number of Total number of reactionsreactions

2222 1212 11

Immediate/ Immediate/ <30min<30min 1414 88 11

Delayed / Delayed / >30min>30min 88 44

Std.SCITStd.SCITRUSHRUSH SLITSLIT

• SLITSLIT– Much safer than injection therapy.Much safer than injection therapy.– Making it feasible for home administration.Making it feasible for home administration.

– Extends immunotherapy to group unable to Extends immunotherapy to group unable to comply with office injectionscomply with office injections

– Is not a completely benign therapyIs not a completely benign therapy

SUMMARYSUMMARY

• SLITSLIT– Efficacy appears equal to standard Efficacy appears equal to standard

injections.injections.– Optimal dosing? 15X cumulative injection Optimal dosing? 15X cumulative injection

dose performed well in our patients.dose performed well in our patients.

• RUSHRUSH– More efficacious early on (0-18 months), More efficacious early on (0-18 months),

higher compliance, more systemic higher compliance, more systemic reactions.reactions.

SUMMARYSUMMARY