a global retrospective and physician-based analysis of...
TRANSCRIPT
introduction
• Tyrosinekinaseinhibitors(TKIs)haveproventobehighlyeffectiveinthetreatmentofvariousphasesofPh+CML
• SeveralstudieshavedemonstratedthatadherencetoTKItherapyisapredictorofachievingoptimaloutcomes1-3
- Marinandcolleagues1reportedastrongcorrelationbetweenadherencerate(<90%or≥90%)andthe6-yearprobabilityofamajormolecularresponse(MMR;28.4%vs94.5%;P<.001)andcompletemolecularresponse(CMR;0%vs43.8%;P=.002)
- Noensandcolleagues3demonstratedpatientswithsuboptimalresponseshadsignificantlyhighermeanpercentagesofmissedimatinibdoses(23.2%±23.8%)thandidthosewithoptimalresponses(7.3%±19.3%,P=.005)
• Sincechronicphase(CP)CMLisnowalong-termdiseaseinmostpatients,itiscriticalthatpatientsunderstandtheimportanceofadheringtotheirprescribeddrugregimentomaximizeandsustainefficacyovermanyyears
1. Marin D, Bazeos A, Mahon FX, et al. J Clin Oncol. 2010;28:2381-2388. 2. Larson RA , et al. Blood. 2009;114(22):872 [abstract 2213]. 3. Noens L, van Lierde MA, De Bock R, et al. Blood. 2009;113(22):5401-5411.
objective
• Toestablishthekeydeterminantsofdrugadherence,andtoestablishatypicaladherenceratetobeusedasabaselineforfuturecomparison
methods
• 405CML-treatingphysiciansfrom5countriesparticipatedinanonlinequantitativesurveyandprovidedpatienttreatmenthistories
- Physicianswereaskedtoratestatementsonascaleof1-7,with7beinginfullagreement
• 1,155patienttreatmenthistoriesandcompliancerecordswereretrospectivelyanalyzed
- PatientswithPh+CML-CPincludedintheanalysishadreceivedtherapywithnilotinib,dasatinib,orimatinib
- Alloftheindividualpatientrecordsanalyzedincludedthedatesofallinitialandrefillprescriptions,aswellasinformationregardingthedosingandquantityofdrugsupplied
• Adherencewasdefinedbyphysicianassessmentofpatientrecordsandrecordedintheirsurveyresponse
- Efficacydatawasalsocollectedaccordingtophysicianassessmentoftheresponse
countries included in research: Physician respondents total records
Brazil 48 111
France 103 311
Italy 105 317
Spain 106 300
Russia 43 116
Project totals: 405 1,155
results
table 1: Patient characteristicsFrance
(n = 311)italy
(n = 317)spain
(n = 300)brazil
(n = 111)russia
(n = 116)
Average age, years 56 58 58 49 48
Patients with comorbidities, % 32 36 28 25 11
Patients on non-CML medications, % 32 32 32 23 10
Patients in chronic phase at diagnosis, % 91 88 93 84 80
Average time between diagnosis and frontline treatment, months
2.1 1.9 3.1 4.3 4.7
results
Figure 1: Percentage of Patient treatment based on the line of therapy*
0
20
40
60
80
100
120
Frontline Second-line Third-line
Dasatinib Nilotinib Imatinib
% o
f P
atie
nts
Bei
ng T
reat
ed
1.5
43
52
5
21
70
9
1.5
97
* Based on physician responses (n = 314) from France, Italy, and Spain.
• Atthetimeofthisstudy,imatinib,nilotinib,anddasatinibwereapprovedbytheEuropeanMedicinesAgencyforthetreatmentofCMLinthefollowingpatientpopulations:
- Imatinib:newlydiagnosedPh+CML-CPandinterferon-alpha-failedPh+CML-CP,-AP,and-BC
- Nilotinib:imatinib-failedPh+CML-CPand-AP - Dasatinib:imatinib-failedPh+CML-CP,-AP,and-BC
Figure 2: Physician Attitudes regarding the Ability of Achieving a milestone to Predict durable responses to therapy
FR
CHR is a predictor of durable response*
CCyR is a predictor of durable response*
MMR is a predictor of durable response*
IT ES BR RU FR IT ES BR RU FR IT ES BR RU0
102030405060708090
100
Strong Predictor Neutral Weak Predictor
% o
f P
hysi
cian
s
Please rate the following response levels by their ability to predict a durable response:
16 20 1533
4255
7157 60 65
83 86 8271
8447
5858
40
44
4427
43 40 3516 12 18
2916
3722 27 27
14
1 2 0 0 0 1 2 0 0 0
* Note: 1-7 Scale, 1-2 Weak Predictor, 3-5 Neutral, 6-7 Strong Predictor.Fr, France (n = 103); it, Italy (n = 105); es, Spain (n = 106); br, Brazil (n = 43); ru, Russia (n = 48).
• Approximately80%ofphysiciansbelievedMMRwasastrongpredictorofdurableresponse
• Fewer(~60%)believedCCyRwasastrongpredictorofdurableresponse
Figure 3: Physician Attitudes toward Patient Adherence
% o
f P
hysi
cian
s
% o
f P
hysi
cian
s
I would like to have a better sense of whether or not my
patients are adherent to therapy*
I discuss adherence with my patients at every appointment*
FR IT ES BR RU FR IT ES BR RUAgree Neutral Disagree Agree Neutral Disagree
53
25
42 42
79
40
6849 44
217 8 9 15
5344
58
8391
4252
39
179
50 34 0 0
0
20
40
60
80
100
120
0
20
40
60
80
100
120
* Note: 1-7 Scale, 1-2 Disagree, 3-5 Neutral, 6-7 Agree.Fr, France (n = 103); it, Italy (n = 105); es, Spain (n = 106); br, Brazil (n = 43); ru, Russia (n = 48).
• Themajorityofphysiciansagreedthattheydiscussadherencewiththeirpatientsateveryappointment
Figure 4: Physician Attitudes towards Patient Adherence
Sufficient evidence exists that, for patients with CML, better
adherence improves outcomes*
Non-adherence is a major driver of disease progression*
FR IT ES BR RU
% o
f P
hysi
cian
s
FR IT ES BR RU
% o
f P
hysi
cian
s
0
20
40
60
80
100
120
0
20
40
60
80
100
120
74
5463
85 88
25
4436
15 12
1 12 0 0
52
19
58
38
74
43
68
39
58
26
5 13 4 03
Agree Neutral Disagree Agree Neutral Disagree
* Note: 1-7 Scale, 1-2 Disagree, 3-5 Neutral, 6-7 Agree.Fr, France (n = 103); it, Italy (n = 105); es, Spain (n = 106); br, Brazil (n = 43); ru, Russia (n = 48).
• Themajorityofphysiciansfromthe5countriesagreedthereisalinkbetweenadherenceandimprovedoutcomes
• PhysiciansfromFrance,Spain,andRussiaagreedthatnon-adherencewasadriverofprogression,whilethemajorityofphysiciansfromItalyandBrazilhadneutralfeelingsaboutthisstatement
table 2: Percent of Patients with missed doses by country% Patients France italy spain brazil russia
No missed doses 43 46 46 52 53
1%-5% missed doses 40 36 35 32 17
5%-10% missed doses 7 7 7 8 7
≥ 10% missed doses 10 11 12 8 23
• Overall,47%-57%ofpatientshadsomemisseddoses• Onaverage,>10%ofpatientsmissed≥10%oftheirprescribed
dailydose• AlthoughpatientsinRussiahadthehighestpercentageofpatients
whodidnotmissadose,patientsinRussiahadthehighestpercentageof≥10%oftheirdosesbeingmissed
Figure 5: Percent of missed doses in Patients with Known response levels*
CHR PCyR CCyR MMR CMR
% o
f P
atie
nts
Wit
h M
isse
d D
ose
s
60 19 70 87 127n =
7.5
8.5
5.2
4.1
2.5
0
1
2
3
4
5
6
7
8
9
10
* Includes 363 patient records from France, Italy, and Spain.
• Greateradherencetotherapywassignificantlycorrelatedwithachievementofbettertherapeuticmilestones(P=.04)
• ThepatientswiththelowestadherencerateachievedabestresponserateofPCyR;over20%ofpatientswithaPCyRmissed≥10%oftheirdoses
• Patientswhohadthehighestlevelsofadherencewerealsoreportedashavingdeeperresponselevels(MMRandCMR)
Figure 6: modeled estimate of the Percentage of Patients With cml remaining on therapy based on Patient records and us claims data*
0%
25%
50%
75%
European Region Record Review Data
US Healthcare Claims Data (24 month Enrollment†)
100%
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Months After Imatinib Initiation
% o
f Pat
ient
s W
ith C
ML
Rem
aini
ng o
n Th
erap
y
European region, n = 386 patient records with ≥ 24 months of therapy
80%
80%
* Includes 363 patient records from France, Italy, and Spain.† PharMetrics Data (2001-2008); unlimited gaps in therapy allowed. Minimum enrollment approach requires at least
3 months continuous eligibility prior to first imatinib claim and at least 24 months of continuous eligibility following first imatinib claim
• DatafrompatientsrecordswithintheEuropeanregioncloselymatchedtheUSHealthcareclaimsdataanalysis,suggestingthereweresimilarratesofdiscontinuationfromtherapyamongtheEuropeandtheUSregions
table 3: Potential Factors that influence Patient AdherenceAll 5 countries France, italy, and spain only
Patient records
(n)
missed doses
(%)
P value missed doses
Patient records
(n)
missed doses
(%)
P value missed doses
Healthcare providers involved in patient adherence counseling
Hematologist only 125 4
.100
65 3.2
.027
Nurse but no hematologist 41 9.6 38 10.0
Both nurse and hematologist 114 6.1 82 2.5
Neither nurse nor hematologist 233 4.7 185 5.4
Patient co-morbidities
No significant co-morbidities 374 4.9
.344281 4.2
.093
≥ 1 co-morbidities 139 6.2 122 6.6
Patient age < 60 years 301 5.0.533
214 4.7.704
≥ 60 years 212 5.7 189 5.2
Concomitant medication
No 363 5.0.519
270 4.4.209
Yes 150 5.9 189 5.2
• PatientrecordreviewofthesubsetofpatientsinFrance,ItalyandSpaindemonstratedpatientsadheredtotheirtherapysignificantlybetterifindividuallycounseledonadherencebyanurseand/orhematologist
• Highernumericalratesofnon-adherencewereobservedinpatientswithcomorbiditiesandconcomitantmedications,thoughthedifferencesdidnotreachstatisticalsignificance
Figure 7: Adherence support roles healthcare Providers currently Play vs roles Physicians believe they should Play*
71
36
41 40
6467
4940
54
36
0
10
20
30
40
50
60
70
80
90
100
Physici
ans
Nurses
Pharm
acist
s
Physici
ans
Nurses
Physici
ans
Nurses
Pharm
acist
s
Adherence supportoutside of office visit
71
3641 40
6467
49
40
5457
36
Pharm
acist
s
% o
f P
hysi
cian
Res
po
nses
Current role Roles they should play
Identify non-adherent patients
Respond regardingtolerability issues
13
29
14
25 27
11
25
* Includes 363 patient records from France, Italy, and Spain. Responses to the survey questions could include that more than one healthcare professional was currently being used or that they should play a larger role; therefore, the sum of responses in each category may not have a sum of 100%.
• Acrossthecountries,physiciansbelievedtheytakeonanappropriateamountofresponsibilityonadherenceeducationandthatnursesandpharmacistscouldplayamoreactiveroleinadherencemanagement
• Physiciansbelievedamulti-disciplinaryapproachtoaddressingpatientadherencemaybebeneficial
Figure 8: Patient enrollment in Adherence Programs* (n = 623 Patient records)
Percent of Patients
Pill Organizerfor Patient Use
Patient Medication Diary
24 Hour Nurse Hot-Lines
Informational Calendar
Pamphlets ExplainingMedication Regimens
Nurse Specialist Calls Patients
Refill Reminder Calls
Patient Buddy Programs
Pharmacy Refill Reports
No Programs
6%
6%
8%
15%
16%
18%
55%
1%
1%
3%
0% 100%
* Enrollment of patients from France, Italy, and Spain in compliance programs (n = 623 patient records).
• Physiciansaregenerallyreactivewhenutilizingadherenceinterventions,ratherthanproactive
• ThesurveyofCML-treatingphysiciansdemonstratedthattheirperceptionsofadherencecloselymatchedtheactualratesofadherence
Figure 9: Physician monitoring of non-adherence*
6053 57
4130
41
11
36 41
7 514
7 7
26
2837
23
3450 28
47
4427
59
4842
4840
45
8 714
1715
1928
1525 31
3637 38
40
24
4 3 6 9 612 15
5 7 311 7 8
135
0
10
20
30
40
50
60
70
80
90
100
FR IT ES FR IT ES FR IT ES FR IT ES FR IT
Pharmacy datareported to me shows
non-adherence
Blood level monitoringresults suggestnon-adherence
Frequency of writingprescription refills shows
non-adherence
Patient proactivelymentions theirown adherence
Discussions with thepatient suggestnon-adherence
ES
% o
f Ph
ysic
ian
s
Never Sometimes Usuallly Always
* Includes responses from physicians in France, Italy, and Spain. Fr, France (n = 103); it, Italy (n = 105); es, Spain (n = 106).
• Physiciansrespondedtheymostfrequentlylearnaboutpatientnon-adherencethroughconversationswithpatients,ratherthanthroughothermeans,suchasthefrequencyofwritingprescriptionrefills
• Additionally,physiciansstatedtheybelievedpatientforgetfulnesswasthemajorreasonbehindnon-adherence(42%-73%ofrespondents)
conclusions
• Only43%-53%ofpatientswerefullyadherenttotherapyacrossall5countriesthatparticipatedinthisstudy
- Overall,>10%ofpatientsmissed≥10%oftheirprescribeddailydose
• Addressingnon-adherencebymultiplehealthcareprofessionalsresultedinpatientsmissingsignificantlyfewerdoses(P=.027)
• Greateradherencetotherapywassignificantlycorrelatedwithachievementofbettertherapeuticmilestones(P=.04),whichmayhaveanimpactonthelong-termoutcomesofpatients
• Thisstudyimpliesthatadherencecanbeimprovedthroughamulti-disciplinaryteaminvolvementandprovidesstrongsupportfortheimplementationofearly,proactiveandfocusedinterventionsincombatingnon-adherencetomaximizepatientoutcomes
-= disclosures
Guilhot: Novartis: Equity Ownership, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding. coombs: Novartis: Employment, Equity Ownership. Zernovak: Novartis: Employment, Equity Ownership. szczudlo: Novartis: Employment, Equity Ownership. rosti: Novartis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau; Roche: Speakers Bureau.
-= AcKnoWledGment
The authors would like to thank Marc Paolantonio of Novartis for his support with these data.
A Global Retrospective and Physician-Based Analysis of Adherence to Tyrosine Kinase Inhibitor (TKI) Therapies for Chronic Myeloid Leukemia (CML)
François Guilhot1, John Coombs2, Oleg Zernovak2, Tomasz Szczudlo2 and Gianantonio Rosti3
1Clinical Investigation Centre P 802 INSERM, CHU de Poitiers, Poitiers, France; 2Novartis Pharmaceuticals Corporation, East Hanover, NJ; 3Department of Hematology/Oncology, “L. and A. Seràgnoli”, St Orsola University Hospital, Bologna, Italy
Poster Presentation at the 52nd ASH Annual Meeting and Exposition, December 4-7, 2010, Orlando, Florida [abstract 1514].