1 NON-ADHERENCE IN CHRONIC MYELOID LEUKEMIA: RESULTS OF A GLOBAL SURVEY OF 2546 CML PATIENTS IN 79 COUNTRIES EHA Abstract S 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

. 2 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

. 3 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

. 4 Truly global research in 12 languages: 2546 CML patients from 79 countries participated Sample: Total of 2546 respondents Global reach Methodology 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/ – 30 th January Paper Online Countries with >30 respondents Countries with base <30 respondents

. 5 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 Forget when travelling Take yesterday? Stop when under control Inconvenience How often difficulty remembering Low: 21 % Medium: 47 % High: 33 % Adherence score classifies patients into adherence groups: F1/ 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. F2/ 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? Use of the ©MMAS is protected by US copyright laws. Permission for use is required. A license agreement is available from: Donald E. Morisky, ScD, ScM, MSPH, Professor, Department of Community Health Sciences, UCLA School of Public Health, 650 Charles E. Young Drive South, Los Angeles, CA

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

. 7 29% have missed a dose accidentally in the last month. 11% have intentionally decided to miss a dose. Missed a dose accidentally in last month % 3 average doses missed in last month Missed a dose intentionally in last month % C2a / 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? C2b / n=746 How many doses did you miss in the last month? C2c / 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? C2b & C2cc / base=all respondents (n=2546) - How many doses did you miss in the last month/year? C4a / 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? C4b / n= In the last year, have you decided to miss a dose? 8% missed both accidently and on purpose in the last month + Yes: Ser., USA, other Cen. & Lat. Am. + Yes: Ser., USA

. 8 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) % C1 / 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? C1 / C2a / 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? + 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.

. 9 USA and Serbia stand out through the proportion missing doses, both accidentally & intentionally % Missed on Purpose in last year % Missed Accidentally / Due to Circumstance in last year “Above global average for missed doses” Global Average “Below global average for missed doses” C2a / 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? C2c / 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? C4a / 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? C4b / n= In the last year, have you decided to miss a dose?

. 10 Forgetting & routine interruption are primary reasons for accidental, (gastro) SE for intentional non-adherence Reason for missing accidentally % (n=1283) C2d / n= Which circumstances led to a missed dose of your medication? C5 / n=491 - Why did you decide to miss a dose of your medication? C6 / n=126 - Which side effect(s) were you hoping to avoid by intentionally missing one or more doses of your medication? Reason for deciding to miss % (n=491) Side effects aiming to reduce: Gastro (79%) Dermatolog ical (17%) Mental (21%) Whilst accidental missing is more linked to memory, purposeful missing of doses is more related to physical symptoms

. 11 In fact, those with better adherence are particularly tied to their routines Helpfulness of routine amongst adherence groups % +Israel, Leb., Mex., USA, Ger. (online), Italy (paper) LL LL E1 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?

. 12 Patients in the low adherence group are usually of lower age Age / Gender % A1 / base=all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) – How old are you? A2 / base=all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) – What is your gender? Total adherenceHigh Medium Low  M, H  H HH HH LL LL  L, M LL Younger Older

. 13 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!) B3a / base-all respondents (n=2546) Low (n=528), Medium (n=1185), High (n=833) - Which medication do you take for your CML currently? Current medication vs. levels of adherence % + Nilotinib +

. 14 Low adherence group more likely to take their medication 2x day or in the evening Time of day that take medication % B4a / 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? B4b / 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? Low adherers are also aware that the doses they miss most are their evening doses (34%) How many times take medication % / Av. Av. 1.3 Av. 1.4 Av. 1.3  M, H HH HH  L, M LL  H, M HH HH

. 15 My health depends on my CML medication I have been told I need to take every dose of my CML treatment or the treatment may not work I worry if I miss a dose of my CML medication I worry about the long term effects of my CML medication Having to take my CML medication worries me My CML medication impacts my work life My CML medication impacts my social life My CML medication disrupts my life It is ok to miss a few doses of my CML medication every now and then I find it difficult to swallow my CML medication I find it difficult to open / close the CML medication packages Low adherence group worries more about QoL and long term side effects, and is not clear about consequences Attitudes towards CML treatment by adherence groups (top 3 box%) C8 / 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)  H, M HH H, M  LL  HH HH HH HH HH

16 Importance of relationship of doctors and patients

. 17 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 High adherence group is more satisfied with info received from HCPs & HCPs is perceived to be approachable Accidentally HIGHLOW „Yes always“ 83 %47 % Intentionally HIGHLOW „Yes always“ 85 %48 % Info received HIGHLOW „Very satisfied“ 69 %45 % „Not satisfied at all“ / „Somewhat dissatisfied“ 4 %16 % HCP is approachable HIGHLOW „Very approachable“ 73 %53 % „Not very approachable“ 7 %14 %

18 Tools to drive Adherence

. 19 Reminders from family members & pill dispensers are primary tools used, followed by electronic reminders Tool Usage (%) Possible future niche in mobile applications for over ¼ of patients E2 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 + Under 30 yrs + Under 30 yrs

20 Conclusions & Recommendations

. 21 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!

22 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

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