case studies - Advances in Inflammatory Bowel Diseases

advertisement
Treating the Outpatient with Severe
IBD: Case Study
Alan C. Moss MD, FEBG, FACG, AGAF
Associate Professor of Medicine
Director of Translational Research
Disclosures
• Consultant; Janssen, Theravance, Bayer, Roche
• Research Support; Pfizer, NIDDK, Salix, Shire
Case - 42 yr old male patient
• Left-sided ulcerative colitis for 8 years
• Failed mesalamine 4.8g/day, azathioprine 100mg/day
• Recurrent flares responsive to prednisone
• Now steroid-dependent; gets more diarrhea /
abdominal pain / fevers when dose lowered to 20mg
• CRP 56 / ESR 80 / Hct 28 / Stool negative for C.difficile
• High-grade B-cell lymphoma 3 years ago – now in
remission
Sigmoidoscopy
What would you recommend?
A.
B.
C.
D.
E.
F.
G.
Colectomy
Infliximab
Vedolizumab
Methotrexate
Tacrolimus
Tofacitinib
Budesonide
‘Knowns & Unknowns’ in IBD Patients
Drug
Early “Response” Rate in UC#
Lymphoma Risk*
Infliximab
67%
(RCT, all)
Similar to IBD Population
Vedolizumab
49%
(RCT, on steroids)
None in clinical trials
Methotrexate
58%
(RCT, steroid-dependent)
Similar to General Population
Tacrolimus
60%
(OL, refractory)
Similar in Transplant Population
Tofacitinib
53%
(RCT, on steroids)
Case Reports
# week 6-8 clinical response
Sandborn W, N Engl J Med. 2012 Aug 16;367(7):616-24
Boschetti G, Dig Liver Dis. 2014 Oct;46(10):875-80
Mate-Jimenez J, Eur J Gastroenterol Hepatol. 2000 Nov;12(11):1227-33
Feagan B, N Engl J Med. 2013 Aug 22;369(8):699-710
* in patients without prior history of lymphoma
Lichtenstein, Am J Gastroenterol, 107 (2012), pp. 1409–1422
Mariette X, Blood, 99 (2002), pp. 3909–3915
Caillard S, Transplantation. 2005 Nov 15;80(9):1233-43
Lee B, N Engl J Med. 2014 Jun 19;370(25):2377-86
ECCO Recommendations
• Few data exist in using immunosuppressants (IS) in
IBD patients with prior cancer
• Recommended “waiting period” before IS starts ;
• 2 years for invasive cancers
• 5 years for aggressive cancers (lymphoma, melanoma,
breast, sarcomas, urinary tract cancers, and myeloma)
Beaugerie L, Dig Dis Vol. 31, No. 2, 2013
Magro F, J Crohns Colitis. 2014 Jan;8(1):31-44
Vedolizumab - Efficacy in Patients with UC on
Steroids
Feagan B, N Engl J Med. 2013 Aug 22;369(8):699-710
Treating the Outpatient with Severe IBD:
Case Study
Joshua Korzenik, MD
Director, BWH Crohn’s and Colitis Center
Brigham and Women’s Hospital
Boston, MA
Disclosures
• Consultation: Abbvie, Roche, Vithera, Shire
• Research support: Abbvie, Takeda, Pfizer,
Transparency
43 yo woman with Crohn’s
• Mid-jejunal, ileocolonic Crohn’s dx in 1994 at age 23
• Multiple resections:
– Ileocolonic in 2001
– Mid-jejunal resection 2003
– Poor response to 6-MP
• Perianal disease developed post-resection
–
–
–
–
Responded to infliximab then anaphylaxis
Rectovaginal fistula
Adalimumab- rash
Certolizumab
Psoriasis
• Paradoxical but not rare occurrence
• Report of 30 patients
–
–
–
–
–
Occurs on all anti-TNFs
Nearly half responded to topical therapy
17/30 no response to topical therapy
9/30 discontinued anti-TNF due to psoriasis
Eight patients were treated with an alternative antiTNF with recurrence in two (25%).
Cullen et al, IBD Journal, 2011
FDA Adverse Event Reporting System
(FAERS)
• 5,432 reports (2004-2011)1
– Infliximab 1789
– Adalimumab 3475
– Certolizumab 168
• British Society for Rheumatology Biologics Register2
– 9826 anti-TNF-treated
– 2880 DMARD-treated patients
• 25 cases of psoriasis in anti-TNF/ 0 in DMARD-treated
• 1.04 (95% CI 0.67 to 1.54) per 1000 person years
1) Kip et all, IBD, 2013 2) Harrison, Ann Rheum Dis, 2009
Other Auto-Immune Diseases
Provoked by Anti-TNF Agents
•
•
•
•
•
•
•
•
Drug-induced lupus
Psoriasis
Alopecia areata/totalis
Autoimmune hepatitis
Sjogren’s syndrome
Demylinating diseases
Vasculitis
IBD
Treatment options?
A)
B)
C)
D)
E)
Surgery
Methotrexate
Golimumab
Ustekinumab
Cyclosporine
CERTIFI: Ustekinumab Phase IIb for
Response Induction in CD
Sandborn WJ et al. N Engl J Med 2012;367:1519-28
CASE #2
Crohn’s disease
• 27 yo man with a hx of ileocolonic Crohn’s
disease for 6 years
• 6-MP partial response, infliximab added
• Sustained remission for 4 years on dual
therapy
• He wants to discontinue all medications
• CRP/ESR normal
• All other routine labs are normal
You recommend:
A) Discontinue 6-MP
B) Discontinue Infliximab
C) Discontinue both
D) Colonoscopy or imaging
1) If normal:
a. Discontinue 6-MP
b. Discontinue Infliximab
c. Discontinue both
2) If not normal:
a. Discontinue 6-MP
b. Discontinue Infliximab
“STORI”: What happens when IFX is withdrawn?
• Prospective multi-center study: GETAID
• Patients with luminal CD, >17 y.o., who received at least
1 year of IFX plus AZA/6-MP/MTX
• At least 2 infusions of IFX administered in preceding 6
months. Final IFX no more than 2 weeks after accrual.
• Outcome: Steroid-free remission >6 months, CDAI <150.
• CDAI at recruitment: 37 (19-61)
Louis E et al. Gastroenterology 2012; 142 (1): 63-70.
“STORI”: What happens when IFX is withdrawn?
Louis E et al. Gastroenterology 2012; 142 (1): 63-70.
What do these data mean for this patient?
• Low-to-Intermediate risk of relapse
– Male, no previous surgery
– On immunomodulator
– Normal CRP, hemoglobin
• Options:
– Stop IFX, continue 6-MP
– Continue 6-MP, then stop IFX
• Louis et al.: Re-treatment with IFX induced remission in
36/40 (96%)
Treating the Outpatient with Severe
IBD: Case Studies
Corey A. Siegel, MD, MS
Geisel School of Medicine at Dartmouth
Dartmouth-Hitchcock Medical Center
CCFA Advances
December 5th, 2014
Case: 67 year old gentleman with UC
• 67 year old gentleman with recent onset of diarrhea
with bleeding
• 10-12x/day, up at night
• Stool studies (including C. diff) negative
• Colonoscopy and biopsies consistent with moderately
active extensive ulcerative colitis
Past medical history
• Hip osteoarthritis, s/p hip replacement
• Pneumonia 3 months prior
• Admitted to ICU, intubated
• Quit smoking at that time
Current meds: none other than occasional naproxen
Case: 67 year old gentleman with UC
• First treatment options in new diagnosis of moderately
active UC?
• Does “top down” apply to UC also?
• Initiated on prednisone 40mg daily + 4.8 grams of 5ASA, Rowasa nightly
• Unable to taper down below 20mg
• Now what?






Uceris
Anti-TNF
Immunomodulator
Vedolizumab
Some combination of above
Surgery
Case: 67 year old gentleman with UC
• Initiated on infliximab monotherapy (with prednisone 40mg
daily)
• Start to taper prednisone
• Week 14 infliximab concentration = 11, negative antibody
• But unable to taper below prednisone 20mg
• Repeat colonoscopy with moderately active extensive
colitis (no significant change)
• Now what?





Increase infliximab dose
Add immunomodulator
Change to vedolizumab
Start smoking
Surgery
Cigarette Smoking in UC: Immunology
• Immunologic mechanisms for the protective effect of
cigarette smoking in UC remain unclear
• Immunologic and clinical studies in IBD have focused
on nicotine
• Therapeutic trial experience in UC with nicotine gum,
transdermal nicotine, enemas has been inconclusive
One component of cigarette smoke, carbon monoxide
(CO), possesses potent anti-inflammatory effects in
numerous models of acute inflammation
Otterbein L et al, Nat Med 2000;6:422-8
ALERT: “BAD AIR”
CO as a Therapeutic?
Other delivery vehicles?
Iskander H, et al. IBD LIVE case series. Inflamm Bowel Dis 2014.
Lee, S, et al. E-cigarettes as salvage therapy for medically refractory
ulcerative colitis. Presented at Advances in IBD, 2013.
Case: 67 year old gentleman with UC
•
•
•
•
•
Started to smoke ½ pack per day
Within 2 weeks started to taper prednisone
OFF ALL prednisone 4 weeks later
Continues infliximab 5mg/kg every 8 weeks
Follow-up colonoscopy with near complete
mucosal healing!!!!
Case: 41 year old woman with Crohn’s
disease
(2 scenarios)
• Diagnosed with ileal and perianal Crohn’s disease
• At diagnosis started on 6MP + Infliximab + Cipro
• Elevated LFTs – shunting with 6MP (despite
heterozygous TPMT – with half dosing!)
• Infliximab monotherapy – did GREAT
• Complete mucosal healing
• No further perianal lesions
• Asymptomatic
41 year old woman with Crohn’s disease
(2 scenarios)
• One year later – performed therapeutic drug monitoring
• Prometheus ANSER assay
• Infliximab trough concentration = 0
• Antibody level = 24
• Options?






Ignore
Repeat the test with a different assay
Increase infliximab dose
Add back an immunomodulator
Switch to another anti-TNF
Switch class of biologic
BRIDGe “anti-TNF optimizer”
• RAND appropriateness panel
• Evaluated two aspects of therapeutic
drug monitoring
1. When to test?
2. What to do with the results
• When to test?
•
•
•
•
At end of induction, primary nonresponse
Secondary non-response
During maintenance, responding
Restarting after drug holiday
Melmed GY, et al. Presented at ACG and UEGW 2014
BRIDGe “anti-TNF optimizer”
www.BRIDGeIBD.com
BRIDGe “anti-TNF optimizer”
www.BRIDGeIBD.com
BRIDGe “anti-TNF optimizer”
www.BRIDGeIBD.com
BRIDGe “anti-TNF optimizer”
www.BRIDGeIBD.com
BRIDGe “anti-TNF optimizer”
www.BRIDGeIBD.com
41 year old woman with Crohn’s disease
(scenario #2)
• Recurrent perianal disease, mild-moderate ileal
recurrence
• One year later – performed therapeutic drug monitoring
• ANSER assay
• Infliximab trough concentration = 2
• Antibody level = 4
• Options?






Ignore
Repeat the test with a different assay
Increase infliximab dose
Add back an immunomodulator
Switch to another anti-TNF
Switch class of biologic
BRIDGe “anti-TNF optimizer”
www.BRIDGeIBD.com
BRIDGe “anti-TNF optimizer”
www.BRIDGeIBD.com
BRIDGe “anti-TNF optimizer”
www.BRIDGeIBD.com
BRIDGe “anti-TNF optimizer”
www.BRIDGeIBD.com
BRIDGe “anti-TNF optimizer”
www.BRIDGeIBD.com
Can you make antibodies go away?
IFX levels closed squares
ATI open squares
Ben-Horin S, et al. Clin Gastroenterol Hepatol. 2013; 11:444-447.
Download
Related flashcards

Emergency medicine

24 cards

Security

27 cards

Surgery

42 cards

Traumatology

37 cards

Hygiene

25 cards

Create Flashcards