DeEscalation of IBD Meds - ACG 2016

A talk in 2016 about the risks and opportunities to de-escalate IBD medications

Transcript

1. De-escalation of IBD Therapy: Who, When, and Why? Peter D.R. Higgins, MD, PhD, MSc Director, IBD Program University of Michigan
2. Austin • 21 y/o male, diagnosed with Crohn’s at age 12 – Ileal Strictures, perianal abscesses – Several years on Pentasa, 2 resections • Now in deep remission on ADA + MTX • Decides to stop meds, use marijuana instead • Does “fine” for 6 months, misses clinic appt – Turns up in ER in month 7 – Perianal abscess, active inflammation, new SB stricture – + Antibodies to adalimumab
3. Maintenance Therapy • ACG Guideline on Management of CD – Maintenance of remission reduces hospitalizations and surgery and improves patients’ quality of life – The word “maintenance” appears 63 times in the guideline – The words “de-escalation” or “step down” do not appear at all. – “Stay with what Got you to Remission” approach Lichtenstein, G., et al. AJG 3 104:465–483 2009.
4. The Mild IBD Patient • A happy but small minority – Never steroids – Never hospitalized – Never significant endoscopic disease or complications • The ileal CD discovered at screening colonoscopy – May not need any therapy • The mild proctitis patient who uses 5-ASA suppositories for 8 weeks a year
5. Agenda • De-escalation • Why De-Escalate? • Why is De-escalation Difficult to Discuss? • Who and When to De-Escalate • How to De-escalate
6. De-Escalation • Combination Therapy • Biologic Monotherapy • Immunomodulators • 5-ASA/SSZ • Unproven or no therapy Efficacy Disease Danger Zone Why would anyone choose to do this?
7. De-Escalation I haven’t crashed recently, so I am going to stop wearing my seat belt (maintenance therapy). If not - Minimize risk! - Monitor for near misses - Go back to seat belts if/when he has a near miss Your patients are thinking this right now. Try to talk them out of it.
8. Why De-Escalate? Some people like to live on the edge Patient Factors Am I cured? Did I even really have IBD? Do I still need this therapy? Magical Thinking Some don’t want to self- identify as a sick person
9. Why De-Escalate? Denial: I wasn’t that sick. Surgery wasn’t so bad. It won’t happen again. Patient Factors
10. Why De-Escalate? People have a lot of fear of adverse events Patients Doctors
11. Why De-Escalate? Brinksmanship Patient Factors I have decided to stop taking this medication, and you can’t make me take it anymore. But I want you to be responsible for the outcome of my decision. A cry for help – can we renegotiate Rx?
12. Why Not De-escalate? • Disease Risk >> Therapy risk • Flares disrupt life, hurt QoL – Are family, spouse supportive of this risk-taking? • Steroid rescue AE Rate >> therapy AE rate • Antibodies: Biologic may not work if stop/restart – Anti-biologic antibodies could be result
13. Why De-Escalate? Financial Factors Will coverage end? Will co-pay explode? The high deductible The January Lottery
14. Why De-Escalate? Medical Factors Cancers Infections Risks of Therapy Become Real
15. Why De-Escalate • Patients in deep biologic remission can take a drug holiday, and do well, for a while. • Reduce risk of infection • Save money spent on meds • Possibly reduce risk of cancer
16. How Much Time Can You Buy? • CD patients on azathioprine can take a thiopurine holiday – 53% had clinical flare by 3 years – Lower risk if CRP <2 mg/L, Hgb >12, ANC <4.0 • CD patients on IFX/Aza can step down to Aza – 43% had clinical flare by 1 year – CRP >5 mg/L or FCP >300 mg/g predicted flare 3-6 months before Treton, CGH 7: 80-85, 2009. Louis, Gastro, 142: 63-79, 2012.
17. Who is Likely to Do Well? • Patients in Deep Biologic Remission – Low CRP and FCP, high hemoglobin, no ulcers • Willing and able to do frequent monitoring of inflammation – Every 12 weeks – NPV for flare w/FCP<167: 100% Gisbert, IBD 15: 1190-98, 2009.
18. Why Is De-Escalation Such a Difficult Conversation?
19. Discounting the Future ≠ IBD Patient Physician Think Different They really do
20. The Discount Rate Thinks about the now - Focused on pain, symptoms - Can’t plan for future, can’t count on the future Wants relief NOW, wants low risk NOW Thinks about the future - Invested years of training (pain now) for future benefits - Can plan for future, can count on the future Willing to take small risks now for future benefits Discount Rate 3-5% 55% Waljee, AK, et al. Inflamm Bowel Dis. 2011:1328-32.
21. Who To De-Escalate? • Patients who – Have well-controlled disease in the past • Low rate of bowel damage, complications, surgeries – Have been in BIOLOGIC remission for >1 year – Willing to do q 12 week monitoring – Have proven reliable in the past
22. When To De-Escalate? • Patients who are – Willing to wait, think about consequences • Consider worst-case scenarios • NOT a one-visit decision – At a stable, low-risk time in life
23. How to De-Escalate • Understand potential consequences • Family is supportive • Shared decision with doctor
24. Questions to Ask • Are you (and your family) prepared for a big flare? – Could cost you time from work/home – Time in hospital, unable to support family • Are you willing to take big steroids when you flare? • Understand it could take months to return to remission? • Are you prepared for risk that we may not be able to get you back in remission, and you may need surgery? • Will you agree to more frequent testing in place of meds? • When you flare, are you willing to go back on medication?
25. How to De-Escalate • Monitor inflammation q 12 weeks • Have a clear plan to restart maintenance if/when needed – Bridge with prednisone or budesonide if needed
26. HOW TO DE-ESCALATE
27. How to De-Escalate Biologics • Minimize risk of anti-biologic antibodies – Full dose immunomodulator for at least 12 weeks before stopping a biologic – Continue IMM for at least 12 weeks after discontinuing the biologic – Prevent Abs to allow restart later (88%) – Confirm plan with patient Louis, Gastro, 142: 63-79, 2012.
28. How to De-escalate from Combo • Can choose (after 6-12 m in remission): – Stop IMM / Reduce IMM dose – Stop Biologic • Can stop immunomodulators without taper – No IMM – more rapid drug clearance • Check inflammatory markers at 12 weeks • Check biologic level at 12 weeks – Less worry about anti-biologic Abs (most ATB in first 6m) Yarur AJ,et al. Clin Gastroenterol Hepatol 2015;13:1118–24.Van Assche G.et al. Gastroenterology 2008; 134: 1861–1868.
29. Monitoring Plan for De-Escalation • Document monitoring plan for return of inflammation – Does CRP identify flares in this patient? – Does fecal calprotectin? – If not, scope and scan • Practical? Does patient really want this? – Plan on an objective measure every 12 weeks – Document biologic remission with scope at 6 months after step down
30. De-Escalation of Immunomodulators • Don’t need to taper • No worries about anti-drug antibodies • Do need to monitor closely – Biomarkers q 12 weeks • Documented plan to restart if inflammation returns • Confirm remission with scope at 6 m Higgins, PDR, AJG 106: 556-8, 2011.
31. De-Escalation of 5-ASA Therapy • Long-term SSZ and 5-ASA adherence is poor • 41% with low-to-zero measurable drug – Often despite claiming adherence • 5.5x risk of flare in non-adherent – Increased risk of hospitalization – Dramatically increased costs Van Hees, PA, J Clin Gast, 4: 333-6, 1982. Kane, SV, APT 23: 577-585, 2006.
32. De-Escalation of 5-ASA Therapy in UC • Discuss and plan – No need to taper - stop – Don’t use sub-therapeutic doses • Monitor inflammation q 12 weeks • Restart (+/- rectal) when inflammation returns
33. Take Home Points • Always ask about missed doses of medication – Pre-emptively start the difficult conversation – Detect patients experimenting with skipped doses • Consider the consequences before de-escalation – Respect the disease! – Maintenance = Standard of Care • Make it a shared decision • Have a clear plan to: – Avoid anti-drug antibodies – Objectively monitor inflammation q 12 weeks – Step up therapy when inflammation returns
34. Thank You
37. Discounting the Future IBD Patient Physician Think Different They really do Which would you choose? $100 today $7,000 10 years from now Waljee, AK, et al. Inflamm Bowel Dis. 2011:1328-32.