NONADHERENCE IN CHRONIC MYELOID LEUKEMIA RESULTS OF A

NON-ADHERENCE IN CHRONIC MYELOID LEUKEMIA: RESULTS OF A GLOBAL SURVEY OF 2546 CML PATIENTS IN 79 COUNTRIES EHA Abstract S 1104 - Stockholm, 16/6/2013 Giora Sharf, Verena Hoffmann, Felice Bombaci, Mina Daban, Fabio Efficace, Joëlle Guilhot, Jana Pelouchová, Euzebiusz J. Dziwinski, Jan de Jong , Anthony Gavin, Jan Geissler 1

CML Advocates Network: the global network of leukemia patient groups Connecting 77 organisations from 61 countries Key facts • Public directory of CML groups • “Social media platform” to have CML patient advocates collaborate • Build skills, coordinate campaigns, build partnerships, share knowledge Founded 2007 by 4 patient advocates 2 . http: //www. cmladvocates. net

Prior studies demonstrated non-adherence is key problem in CML (ADAGIO 2008, Hammersmith) – and has clear clinical impact (Bazeos 2009) Objectives of our patient-driven study: Understand patient behaviours associated with adherence Help identify the ‘true’ issues behind non-adherence Explore cultural influence and difference on adherence Support development of physician and patient tools to improve adherence and improve patient outcomes 3 .

Truly global research in 12 languages: 2546 CML patients from 79 countries participated Global reach Countries with >30 respondents Countries with base <30 respondents Sample: Total of 2546 respondents Online 2151 Paper 395 Methodology 4 • Online - Recruited by patient associations online & via other methods • Paper & Pen (France, Germany, Italy) – Recruited by physicians at consultations • CML patients over 18 years old, currently taking oral medication for CML • Fieldwork – Started on CML World Day, 22/9 2012 – 30 th January 2013.

We also used the validated Morisky Adherence Scale to classify patients into adherence levels Questions: Forget medication Miss for other reason Stopped because felt worse Adherence score classifies patients into adherence groups: Low: 21 % Forget when travelling Take yesterday? Stop when under control Inconvenience How often difficulty remembering Medium: 47 % High: 33 % F 1/ base = all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) - Please answer ‘yes’ or ‘no’ to each question based on your personal experience with your CML medication. F 2/ base = all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) - How often do you have difficulty remembering to take all your medications? 5. Use of the ©MMAS is protected by US copyright laws. Permission for use is required. A license agreement is available from: Donald E. Morisky, Sc. D, Sc. M, MSPH, Professor, Department of Community Health Sciences, UCLA School of Public Health, 650 Charles E. Young Drive South, Los Angeles, CA 90095 -1772.

The results presented are initial descriptive findings. In-depth analysis will follow, including specific countries. 6

29% have missed a dose accidentally in the last month. 11% have intentionally decided to miss a dose. Missed a dose intentionally in last month % Missed a dose accidentally in last month % + Yes: Ser. , USA, other Cen. & Lat. Am. 2 29 Yes No 68 Don't Know 3 average doses missed in last month 11 +Yes: Ser. , USA 8% Yes No 89 missed both accidently and on purpose in the last month C 2 a / base=all respondents (n=2546) - Patients sometimes are not able to take their medication as prescribed. In the last month, have you missed a dose accidentally or due to circumstances that were outside of your control? C 2 b / n=746 How many doses did you miss in the last month? C 2 c / base=all respondents (n=2546) – In the last year, have you missed a dose accidentally or due to circumstances that were outside of your control? C 2 b & C 2 cc / base=all respondents (n=2546) - How many doses did you miss in the last month/year? C 4 a / base=all respondents (n=2546) - Patients sometimes make a conscious decision to miss a dose of medication. In the last month, have you decided to miss a dose? C 4 b / n=2258 - In the last year, have you decided to miss a dose? 7.

74% believe they take their CML medication exactly as prescribed, but 19% of them missed a dose last month Self rated adherence (rated 1 -5) % 1 - Rarely take exactly as prescribed 113 21% 2 3 4 5 - Always take exactly as prescribed 74% - always stick to therapy as prescribed + Neth. , Slov. , Thai. , It. (paper) BUT: 19% of those who claim to always take medicine as prescribed, had in fact missed a dose accidently in the last month. Gap between perception & reality. C 1 / base=all respondents (n=2546) - In general, to what extent do you think you are able to stick to your CML therapy schedules and dosage, as prescribed by your CML doctor? C 1 / C 2 a / base (n=1886) - Patients sometimes are not able to take their medication as prescribed. In the last month, have you missed a dose accidentally or due to circumstances that were outside of your control? 8 .

USA and Serbia stand out through the proportion missing doses, both accidentally & intentionally % Missed on Purpose in last year Global Average “Above global average for missed doses” Global Average “Below global average for missed doses” % Missed Accidentally / Due to Circumstance in last year C 2 a / base=all respondents (n=2546) - Patients sometimes are not able to take their medication as prescribed. In the last month, have you missed a dose accidentally or due to circumstances that were outside of your control? C 2 c / base=all respondents (n=2546) – In the last year, have you missed a dose accidentally or due to circumstances that were outside of your control? C 4 a / base=all respondents (n=2546) - Patients sometimes make a conscious decision to miss a dose of medication. In the last month, have you decided to miss a dose? C 4 b / n=2258 - In the last year, have you decided to miss a dose? 9.

Forgetting & routine interruption are primary reasons for accidental, (gastro) SE for intentional non-adherence Reason for missing accidentally % (n=1283) Forgot 41 Interrupted routine 27 Reason for deciding to miss % (n=491) 35 Not feeling well Reduce side effects 26 Attending special occasion Travelling 17 Too ill 15 Fell asleep 9 Ran out of medication 7 Medication not ready at pharmacy 6 Reminder failed 4 11 Wanted to socialise 10 Interfered with travel 10 Feeling down 9 Dr said could miss 9 CML under control 7 Interfered with work 4 Didn't want to be reminded 4 Feeling better Couldn't swallow 1 Dosing schedule complicated 1 To save money Friend/partner said could miss 2 1 Side effects aiming to reduce: Gastro (79%) Dermatolog ical (17%) Mental (21%) 0 Whilst accidental missing is more linked to memory, purposeful missing of doses is more related to physical symptoms C 2 d / n=1283 - Which circumstances led to a missed dose of your medication? C 5 / n=491 - Why did you decide to miss a dose of your medication? C 6 / n=126 - Which side effect(s) were you hoping to avoid by intentionally missing one or more doses of your medication? 10 .

In fact, those with better adherence are particularly tied to their routines Helpfulness of routine amongst adherence groups % Routine helps greatly +Israel, Leb. , Mex. , USA, Ger. (online), Italy (paper) 56 69 71 L 76 L Routine helps moderately Routine helps little 23 13 13 7 3 1 6 2 21 13 13 12 13 Total Low Medium High 2 1 Routine does not help I do not have a routine E 1 base = all respondents (n=2546), Low (n=528), Medium (n=1185), High (n=833) In order to remember to take their medication, patients sometimes try to follow a routine. Does having a daily routine help you remember to take your medication? 11 .

Patients in the low adherence group are usually of lower age Age / Gender % Total adherence Low Medium High 21 14 11 H H 20 12 M, H Younger Male / 18 -40 Female / 18 -40 14 12 7 Older H Male / 41 -55 18 Female / 41 -55 17 15 20 19 17 L Male / 56+ Female / 56+ 20 18 10 14 18 16 L, M 19 28 L L 19 20 A 1 / base=all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) – How old are you? A 2 / base=all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) – What is your gender? 12 .

Imatinib seems to be linked with higher adherence, Nilotinib more prevalent in low adherence group (on Morisky Scale, so all motivations for non-adherence regarded!) Current medication vs. levels of adherence % + Nilotinib 25 36 33 46 19 Imatinib 27 Nilotinib High 48 46 + Medium Low 21 Dasatinib B 3 a / base-all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) - Which medication do you take for your CML currently? 13 .

Low adherence group more likely to take their medication 2 x day or in the evening How many times take medication % / Av. 1. 3 27 Av. 1. 4 M, H 35 M, Av. H 1. 3 H H H 29 Time of day that take medication % 46 Av. 1. 3 Morning 51 2 x a day 20 Midday 1 x a day 61 68 21 21 19 L, M 76 40 41 34 Low Medium H, M 49 Evening Total Medium L, M High 3 x a day L Low 45 21 4 x a day 69 Total 40 H Low adherers are also aware that the doses they miss most are their evening doses (34%) High B 4 a / base=all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) - How many times a day do you take your CML medication? B 4 b / base=all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) - When during the day do you usually take your CML medication? 14 .

Low adherence group worries more about Qo. L and long term side effects, and is not clear about consequences Attitudes towards CML treatment by adherence groups (top 3 box%) 0 10 20 30 40 50 60 70 My health depends on my CML medication H, M I have been told I need to take every dose of my CML treatment or the treatment may not work 80 90 100 L I worry if I miss a dose of my CML medication Low H, M I worry about the long term effects of my CML medication H Having to take my CML medication worries me H H My CML medication impacts my work life H My CML medication impacts my social life H My CML medication disrupts my life It is ok to miss a few doses of my CML medication every now and then H I find it difficult to swallow my CML medication H, M Medium High H, M H, M I find it difficult to open / close the CML medication packages C 8 / base=all respondents (n=2546). Low (n=528), Medium (n=1185), High (n=833) When thinking about your CML medication, please indicate the extent to which you agree with each of the following statements? (Please indicate for each item below on a scale of 1 -7 where 1=strongly disagree and 7=strongly agree) 15 .

Importance of relationship of doctors and patients 16

Adherence is strongly influenced on relationship of CML patient with physician High adherence group is more likely to discuss missing a dose with their physicians Accidentally HIGH LOW Intentionally HIGH LOW „Yes always“ 83 % 47 % „Yes always“ 85 % 48 % High adherence group is more satisfied with info received from HCPs & HCPs is perceived to be approachable Info received HIGH LOW HCP is approachable HIGH LOW „Very satisfied“ 69 % 45 % „Very approachable“ 73 % 53 % 4% 16 % „Not very approachable“ 7% 14 % „Not satisfied at all“ / „Somewhat dissatisfied“ 17 .

Tools to drive Adherence 18

Reminders from family members & pill dispensers are primary tools used, followed by electronic reminders Tool Usage (%) I would not use I would use if available Reminders from fam. members 44 9 Med. box/pill dispenser 43 14 E-reminders via mobiles (SMS/alarms) 54 40 10 60 + Under 30 yrs 24 Reminders from dr. s or nurses at apps 75 Possible future niche in mobile applications for over ¼ of patients Smart phone / mobile applications + Under 30 yrs 43 19 67 Alarm clock I already use + Under 30 yrs 19 10 10 + Under 30 yrs 9 + Under 30 yrs 26 Phone call reminders 79 12 5 Refrigerator magnet reminders 78 13 5 Email reminders 83 9 + Under 30 yrs 3 E 2 base = all respondents (n=2546) Below is a list of tools that could help you to remember to take your CML medication. For each item, please indicate whether you already use such a tool, or if you would use the tool if it were available 19 .

Conclusions & Recommendations 20

Conclusions Haematologists… • should not take the patients adherence assessment for granted • have a central role in driving adherence – what tools would help? • should discuss impact of medication on patients lives more (side effects & quality of life) to drive adherence • should highlight impact of routines in taking the drug Particular attention paid to more “at adherence risk” groups: • Younger patients • Longer time on treatment • Twice daily regimen, strong side effects There is future potential for tools to support adherence… Priority is on change of mindset of low adherers… …in partnership with us! 21 .

Thank you! To the CML patients in 79 countries that participated. To the CML patient organisations supporting the survey. The Workgroup: Giora Sharf, Verena Hoffmann, Felice Bombaci, Mina Daban, Fabio Efficace, Joëlle Guilhot, Jana Pelouchová, Euzebiusz J. Dziwinski, Jan de Jong, Anthony Gavin, Jan Geissler Our Partners: German CML Study Group – GIMEMA Italy – French FI LMC Group 22

Disclosures Giora Sharf: • Research support from Ariad, BMS, Novartis, Pfizer • Patient Advisor of Ariad, Novartis, BMS, Pfizer 23