1. What do we mean by opioid sparing and what are its potential individual and societal benefits? Eric C. Strain, M.D. Johns Hopkins University School of Medicine IMMPACT XXI , Washington, MD July 26, 2018

2. Disclosures
In the past year, I have served on advisory boards, received grant funding from, and/or consulted for: Alkermes, Analgesic Solutions, Caron, Indivior Pharmaceuticals, The Oak Group, OrphoMed, Pinney Associates, and the WHO. 1.

3. I am a fish out of water on much of this topic1.

4. Outline for this talk I. What do we mean by “opioid sparing”?
II. Why do we care about opioid sparing?
III. Does opioid sparing matter?
IV. Final thoughts 1.

5. Outline for this talk I. What do we mean by “opioid sparing”?
II. Why do we care about opioid sparing?
III. Does opioid sparing matter?
IV. Final thoughts 1.

6. Opioid sparing Strategies that accomplish one of the following:
1. Decrease in the acute dose of opioid that is taken
2. Decrease in the total number of doses of opioid taken
3. Decrease in some aspect of the opioid effect (e.g., side effect)
4. Not require the use of an opioid 1.

7. Opioid sparing Strategies that accomplish one of the following:
1. Decrease in the acute dose of opioid that is taken
2. Decrease in the total number of doses of opioid taken
3. Decrease in some aspect of the opioid effect (e.g., side effect)
4. Not require the use of an opioid
Underlying this is the assumption that there is at least no change in outcome with respect to the target clinical measure (analgesia) 1.

8. Outline for this talk I. What do we mean by “opioid sparing”?
II. Why do we care about opioid sparing?
III. Does opioid sparing matter?
IV. Final thoughts 1.

9. Why do we care about opioid sparing?
We have an opioid (abuse, misuse, addiction, dependence, use disorder) problem 1.

10. 1.

11. Why do we care about opioid sparing?
We have an opioid (abuse, misuse, addiction, dependence, use disorder) problem
Underlying assumption is that decreasing exposure to prescription opioids will decrease risk of developing problematic opioid use
Looking for both an individual and societal benefit 1.

12. Why do we care about opioid sparing?
How bad is the problem of opioid abuse in the U.S.? 1.

13. Opioid prescriptions dispensed

14. Opioid prescriptions dispensed

15. Opioid prescriptions dispensed

16. Opioid prescriptions dispensed

17. Opioid prescriptions dispensed

18. Opioid prescriptions dispensed
Steady
increase

19. Opioid prescriptions dispensed
Starting
to see
some
decrease?

20. Opioid abuse
Another problem with respect to opioid use is overdose deaths from use of opioids

21. Opioid overdoses 1.

22. Opioid overdoses 1.

23. Opioid overdoses 1.

24. Opioid overdoses 1.

25. Opioid overdoses
Slow steady rise in rx opioids (2000) 1.

26. Opioid overdoses
Sudden rise in heroin (2010) 1.

27. Opioid overdoses
Dramatic increase in fentanyl
(2014) 1.

28. Opioid overdoses – what I showed 2 years ago…1.

29. We have seen a change in the US death rate1.

30. We have seen a change in the US death rate1.

31. We have seen a change in the US death rate1.

32. We have seen a change in the US death rate
Different countries shown 1.

33. We have seen a change in the US death rate
US White non-Hispanic 1.

34. We have seen a change in the US death rate1.

35. We have seen a change in the US death rate
US Hispanic 1.

36. We have seen a change in the US death rate1.

37. We have seen a change in the US death rate1.

38. We have seen a change in the US death rate1.

39. We have seen a change in the US death rate
A greater
relative
increase 1.

40. Epidemiology of opioid abuse
We are very focused on opioid use and opioid overdoses, but we don’t have an opioid problem, we have a substance use problem – we are playing whack a mole so long as we focus on one drug type or drug class…

41. Taking our eyes off the cocaine ball…
Cocaine has doubled (and note MA) 1.

42. Epidemiology of opioid abuse
Where do people get opioids, and especially prescription opioids?

43. Epidemiology of opioid abuse
Where do people get opioids, and especially prescription opioids?
Varies as a function of whether have problematic use of prescription opioids…

44. Source of prescription opioids
From Han et al.,
Ann Int Med, 2017
Used NSDUH data
from 2015

45. Source of prescription opioids

46. Source of prescription opioids

47. Source of prescription opioids
No Use Disorder,
getting for free
from family (two-
fold difference)

48. Source of prescription opioids
Use Disorder,
buying from friend/
relative

49. Source of prescription opioids
Use Disorder,
buying from others
(a lot more)

50. Why do we care about opioid sparing?
To summarize why we care about opioid sparing (I of II):
Increased exposure to opioids has resulted in more problematic use (although why people use opioids is complicated, and just getting opioids is not the reason people misuse them)
This exposure has been related, in part, to increased prescribing
Increased opioid overdose deaths 1.

51. Why do we care about opioid sparing?
To summarize why we care about opioid sparing (II of II):
Some proportion of people exposed to an opioid go on to develop problematic use of it (although we really don’t know what that is)
Even for those who don’t directly develop a problem after exposure, the availability of opioids may result in diversion to others who then develop misuse of opioids 1.

52. Outline for this talk I. What do we mean by “opioid sparing”?
II. Why do we care about opioid sparing?
III. Does opioid sparing matter?
IV. Final thoughts 1.

53. Does opioid sparing matter?
If sparing means no exposure to an opioid, then likely that sparing matters – we decrease the denominator under the circumstances of what is probably some relatively stable ratio of people who run the risk of developing an opioid use disorder (so we eventually decrease the number with problem use)
On the other hand, if we decrease the amount of exposure (but not the experience of being exposed to an opioid), then this probably gets more complicated… 1.

54. Does opioid sparing matter?
Things to consider if we decrease the amount of exposure:
1. Exposure to an opioid induces some immediate changes (e.g., acute physical dependence, shown in humans)
- So, maybe doesn’t really matter for the individual
- Clinical experience of first dose by people who go on to develop opioid use disorder (like it from the start) 1.

55. Does opioid sparing matter?
Things to consider if we decrease the amount of exposure:
2. Certainly more typical physical dependence with repeated (chronic) exposure, depending upon the 3Ds – drug, dose, days
- Decreased risk of physical dependence if decrease total amount of exposure (but physical dependence is not problematic use…) 1.

56. Does opioid sparing matter?
Things to consider if we decrease the amount of exposure:
3. More doses “out there” runs risk of more potential for diversion, misuse
- Note that decreasing availability of prescription opioids appears to be shifting use to heroin and fentanyl
- May have a long-term value to decrease available doses of rx opioids, but shorter term may actually be increasing individual and societal cost (deaths) 1.

57. Does opioid sparing matter?
Opioid sparing could also have other repercussions:
1. Alternative could be more expensive to health care system
2. Use of another substance could have more downstream problems (individual, societal – e.g., is cannabis really the solution?)
3. Individual efficacy may be lower 1.

58. Does opioid sparing matter?
The bottom line:
Opioid sparing can have value for individual prescribed, and for society 1.

59. Does opioid sparing matter?
The bottom line:
Opioid sparing can have value for individual prescribed, and for society
However, important to note that as we decrease prescription opioid use/exposure, we are seeing a backfilling with illicit opioid use (e.g., fentanyl) – sparing by itself won’t solve the opioid problem, and may be actually producing more societal pain and individual suffering 1.

60. Outline for this talk I. What do we mean by “opioid sparing”?
II. Why do we care about opioid sparing?
III. Does opioid sparing matter?
IV. Final thoughts 1.

61. Final thoughts
The value of opioid sparing likely depends upon the approach used to spare the opioid
The drive to “spare” opioid use is good and reasonable, and likely could decrease further development of opioid use problems (but we may have passed the prescription opioid use phase of the crisis)
The problem did not develop overnight, and the solution will not be equally quick as a fix (despite desires to do so and good intentions) 1.

62. Thank you 1.

63. Opioid sparing
What do we mean by “opioid sparing”? 1.

64. Opioid sparing What do we mean by “opioid sparing”?
So I will figure this out by googling the term (because what else do we do these days?) 1.

65. 1.

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68. What are the forces that are pushing the concept of ”opioid sparing”?1.