BenefitRisk of Crohns Disease Therapeutics

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Benefit-Risk of Crohns Disease Therapeutics

• William Sandborn, MD
• Mayo Clinic and Mayo College of Medicine
• Rochester, MN, USA

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Back up slides shown
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CD303 Response and Remission at Month 6
P 0.001
P 0.016
P 0.001
P 0.006
Percent
N40 N32
N40 N32
N171 N168
N171 N168
Response
Remission
CD303
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CD303 Response and Remissionat Month 12
P 0.001
P 0.006
P 0.001
P 0.006
Percent
N171 N168
N171 N168
N40 N32
N40 N32
Response
Remission
CD303
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CD307 Response by Varying CRP Cut-Point
CD307
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CD301 ?CRP - Response in patients with disease
confined to the ileum
Patients ()
Time (weeks)
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CD301 Week 10 Response by Baseline CRP ITT
population - LOCF
Patients in Response ()
plt0.05 for all thresholds but CRP9, 11
C-Reactive Protein Baseline Threshold Level (mg/L)
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Pulmonary Aspergillosis

• 75-year-old male with Crohns disease had
  received 10 infusions of natalizumab
• Concomitant NSAID use and high-dose steroids in
  tapering regimen
• Perforated duodenal ulcer, severe GI hemorrhage,
  and peritonitis 1 month following last dose of
  natalizumab
• Spent several weeks in hospital, including ICU
• CT of lungs showed bilateral infiltrates
• Sputum culture revealed Aspergillus sp
• Patient developed multi-organ failure and died 3
  months after last dose of natalizumab

CD301 / 303 / 351
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Pneumocystis carinii Pneumonia

• 69-year-old male with Crohns disease had
  received 34 infusions of natalizumab
• History of cirrhosis due to nonalcoholic
  steatohepatitis with varices, portal
  hypertension, splenomegaly, and ascites
• Developed hepatic encephalopathy 1 month after
  last dose of natalizumab
• Natalizumab stopped patient treated and
  recovered
• Hospitalized 1 month later with hepatic
  encephalopathy, acute renal failure, and anemia
• Treated in ICU, intubated, and transfused
• Sputum culture revealed PCP
• Developed multi-organ failure and died

CD301 / 303 / 351
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Burkholderia cepacia Pneumonia

• 62-year-old woman with CD, type II DM, HT, and
  tobacco use
• Received 3 infusions of natalizumab
• Developed non-productive cough with dyspnea
• Cardiomegaly, hydrothorax, pulmonary vessel
  congestion with atelectasis
• Diagnosed and treated as CHF
• Bronchoscopic lavage revealed Burkholderia
  cepacia
• Treated with antibiotics

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Table 13 Efficacy of Natalizumab Effect of
Concomitant Immunosuppressants
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CD303 Response and Remission at Months 6 and
12Tertiary Endpoints
Response
Remission
P 0.001
P 0.001
P 0.001
P 0.001
Patients ()
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CD307 Response in Anti-TNF Failure
Subgroups(Weeks 8 12)
Favors Placebo
Favors Natalizumab
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CD301 ?CRP - Response for Patients with No
response to initial TNF? therapy
Patients ()
Time (weeks)