Immuntherapy Guide Increases Dsing Accuracy Jared Darveaux, MD
Disclsures Nne ON TARGET
Backgrund Immuntherapy (IT) is a therapeutic tl used t treat allergic rhinitis and allergic asthma fr decades In 2011, practice parameters were published n the practice f IT Within these practice parameters are recmmendatins n IT dses fr standardized and nn-standardized antigens These recmmendatins are meant t ptimize therapeutic results while minimizing the risk f adverse sht reactins
Backgrund In general, administratin f higher dses increases the likelihd f clinical effectiveness Lw dses are less likely t be effective, and very lw dses usually are ineffective
Recmmended Dses Multiple studies demnstrate that the efficacius dse fr allergen immuntherapy is between 5-20 μg f the majr allergen per injectin Based n clinical trials invlving single antigens Using recmmended dses is shwn t: Prvide early imprvement in symptms Alng with the duratin f treatment, imprves lngterm benefit
QI Prject Backgrund Many f the physicians in ur clinic utilized a chart created t simplify the IT rdering prcess Cncentratins f each antigen were based n the number f different antigens included in each vial While this chart was useful, it was created several years befre the recent practice parameters were released As such, utilizatin f this chart had the ptential t under r verdse IT prescriptins
Prject Aims T align the prcess f rdering IT with current practice parameter guidelines Simplify the IT rdering prcess Determine the effect f prviding a new dsing guide that adheres t practice parameters n dsing accuracy
Measures Review f the last 10 new IT rders (excluding venm) 55 allergen data pints Determined if prescribed dse fit within practice parameter guidelines Prescriptins were categrized as Very high: 2x the highest recmmended dse High: > recmmended maximum dse, < 2x recmmended maximum dse Apprpriate: within recmmended dse range Lw: < recmmended minimum dse, > 1/2 recmmended minimum dse Very Lw: 1/2 recmmended minimum dse N/A: nt applicable, n recmmendatins n dse
Lw 9% Dsing Accuracy All Antigens Apprpriate 25% Very lw 35% High 13% Very high 9% N/A 9% N = 55 antigen prescriptins
Lw 10% All Antigens (excluding mlds) Apprpriate 28% High 14% Very lw 38% Very high 10% N = 50 antigen prescriptins
Dsing Accuracy Standardized Antigens Apprpriate 46% Very lw 8% Very high 21% High 25% N = 24 antigen prescriptins Standardized extracts include cat, dust mite, grass, and ragweed
40 35 Accuracy by Schedule 30 % Accurate Dse 25 20 15 10 *Animal schedule 0% accurate 5 0 0.25 ML/SHOT 0.5 ML/SHOT 1 ML/SHOT ANIMAL (0.2 ML/SHOT)
Measures Cmmn Themes Prescriptins that were High and Very High were exclusively Grass and Ragweed Very few f the trees were dsed within the recmmended range Under-dsed All prescriptins in the "very lw" grup were either n a 0.25 ml/sht schedule r received a mix r bth All f the Rx written fr mixes (6 tree r cmmn weed) were very lw fr the individual antigens cntained in the mix
Mixes The maintenance cncentrate shuld be frmulated t deliver a dse cnsidered t be therapeutically effective fr each f its cnstituent cmpnents Eastern 6 tree mix recmmendatins fr pllens are within the range f 1:200 w/v 1:100 w/v Stck cncentratin = 20,000 PNU/ml = 1:46 w/v Cncentratin fr each f these unrelated allergens is nly 1/6 f this = 3,333 PNU/ml = 1:276 w/v Therefre, even at ur stck cncentratin n a 0.5 ml/sht schedule, a patient wuld receive 1,667 PNU per injectin = 1:552 w/v/antigen = majr underdse!
Interventin/Methds Created a new chart t be used as a guide fr IT dsing based ff f practice parameter recmmendatins New chart uses a 0.5 ml/sht schedule nly Mst IT Rx can achieve therapeutic dse with a 0.5 ml injectin 0.25 ml/injectin difficult t prvide sufficient dse in injectin amunt fr mst antigens
Antigen Target Dse Starting Cnc. Prescriptin Dse Apprx. Vl. (ml/10 ml vial) Lw Medium High Lw Medium High Ragweed Mix 6 12 AgE U 1:20 w/v 1:200 w/v 1:160 w/v 1:100 w/v 1 1.25 2 Pllen 1:200 1:100 w/v Cmmn Weed Mix a 20,000 PNU/ml 15,500 PNU/ml 20,000 PNU/ml 20,000 PNU/ml 7.75 10 10 Eastern 6 Tree Mix b 20,000 PNU/ml 20,000 PNU/ml 20,000 PNU/ml 20,000 PNU/ml 10 10 10 Eastern Oak Mix 20,000 PNU/ml 4,000 PNU/ml 5,000 PNU/ml 6,666 PNU/ml 2 2.5 3.33 Elm Mix 1:20 w/v 1:200 w/v 1:160 w/v 1:100 w/v 1 1.25 2 Birch Mix 20,000 PNU/ml 3,333 PNU/ml 5,000 PNU/ml 6,000 PNU/ml 1.66 2.5 3 Western Walnut Mix 20,000 PNU/ml 3,333 PNU/ml 5,000 PNU/ml 6,000 PNU/ml 1.66 2.5 3 Ash Mix 1:20 w/v 1:200 w/v 1:160 w/v 1:100 w/v 1 1.25 2 Maple/Bx Elder Mix 1:20 w/v 1:200 w/v 1:160 w/v 1:100 w/v 1 1.25 2 Hickry Mix 20,000 PNU/ml 4,000 PNU/ml 5,000 PNU/ml 6,666 PNU/ml 2 2.5 3.33 Willw/Black Salix Nigra 1:20 w/v 1:200 w/v 1:160 w/v 1:100 w/v 1 1.25 2 7 grass mix c 1,000 4,000 BAU 100,000 BAU/mL 2,000 BAU/ml 5,000 BAU/ml 8,000 BAU/ml 0.2 0.5 0.8 KORT 300 1500 BAU 10,000 BAU/ml 750 BAU/ml 1,500 BAU/ml 3,000 BAU/ml 0.75 1.5 3 Dust mite mix, Dp, r Df 500 2,000 AU 10,000 AU/ml 1,000 AU/ml 2,500 AU/ml 4,000 AU/ml 1 2.5 4 Cat hair/cat pelt 1,000 4,000 BAU 10,000 BAU/ml 2,000 BAU/ml 5,000 BAU/ml 8,000 BAU/ml 2 5 8 Dg 15 μg Can f 1 1:100 w/v 1:250 w/v 1:250 w/v 1:250 w/v 4 4 4 Fungi Highest Tlerated Alternaria Tenuis 20,000 PNU/ml 2,500 PNU/mL 5,000 PNU/ml 10,000 PNU/ml 1.25 2.5 5 Cladsprium Herbarum 20,000 PNU/ml 2,500 PNU/mL 5,000 PNU/ml 10,000 PNU/ml 1.25 2.5 5 Penicillium Mix 20,000 PNU/ml 2,500 PNU/mL 5,000 PNU/ml 10,000 PNU/ml 1.25 2.5 5 Aspergillus Fumigatus 20,000 PNU/ml 2,500 PNU/mL 5,000 PNU/ml 10,000 PNU/ml 1.25 2.5 5 Hrmdendrum Hrdei 1:20 w/v 1:160 w/v 1:80 w/v 1:40 w/v 1.25 2.5 5 Biplaris 20,000 PNU/ml 2,500 PNU/mL 5,000 PNU/ml 10,000 PNU/ml 1.25 2.5 5 Fusarium Mllinifrme 20,000 PNU/ml 2,500 PNU/mL 5,000 PNU/ml 10,000 PNU/ml 1.25 2.5 5 Insects d HTD Can mix dust mite and mlds. Cannt mix pllens with mlds Hney Bee Venm 100 μg/ml 100 μg/ml a Individual antigen cncentratin in mix is 1/5 f ttal PNUs Yellw Jacket Venm 100 μg/ml 100 μg/ml b Individual antigen cncentratin in mix is 1/6 f ttal PNUs Yellw Hrnet Venm 100 μg/ml 100 μg/ml c Kentucky Blue/June, Meadw Fescue, Orchard, Perennial Rye, Redtp, Wasp Venm 100 μg/ml 100 μg/ml Sweet vernal, Timthy Mixed Vespid Venm 300 μg/ml 300 μg/ml d Insects are n a REGULAR schedule (1 ml/injectin) ON TARGET
Methds New dsing guides were used ver the curse f 4 mnths with ccasinal minr mdificatins Unknwn whether the rdering prvider used the new dsing guide Educatin was prvided in the frm f 1:1 caching, didactic training sessins and real time guidance At the end f 4 mnths the 10 mst recent IT prescriptins were evaluated 58 allergen data pints Results cmpared t thse btained prir t initiatin f the new guide
Lw 9% All Antigens Pre Implementatin Apprpriate 25% Very lw 35% High 13% N/A 9% Very high 9% All Antigens Pst Implementatin Relative imprvement = 128% Abslute imprvement = 32% Apprpriate 57% High 10% Lw 7% Very lw 7% N/A 16% Very high 3% N = 58
All Antigens Excluding Mlds (Pre) Lw 10% Very lw 38% Apprpriate 28% High 14% Very high 10% All Antigens Excluding Mlds (Pst) Relative imprvement = 143% Abslute imprvement = 40% p = < 0.0001 Apprpriate 68% Lw 8% Very lw 8% 4% High 12% N = 49
Standardized Antigens (Pre) Apprpriate 46% High 25% Very Lw 8% Very high 21% Standardized Antigens (Pst) n Relative imprvement = 74% Abslute imprvement = 34% p = < 0.0001 Apprpriate 80% High 20% N = 20
Cnclusins Implementatin f the new dsing guide significantly imprves the accuracy f dsing IT Using antigen mixes fr SCIT rarely prvides sufficient amunts f each individual antigen t dse within practice parameter guidelines Mst antigens can reach a sufficient dse using a 0.5 ml/sht schedule alne
Future Directins Lk at sht reactin rates befre and after implementatin f the dsing guide Review charts frm thse with previus sht reactins t see if verdsed
Special Thanks Sameer Mathur, MD, PhD 1 Sujani Kakumanu, MD 1 Diane Dierdrff, CPhT 2 University f Wiscnsin Hspitals and Clinics Divisin f allergy and Immunlgy 1 Pharmacy 2