Calprotectin-Directed Humira® Maintenance Therapy (CADHUM)

Patients frequently discontinue maintenance medications in Crohn's disease, particularly
when in remission. Patients want to know that they truly need to take a medication, yet they
don't want to have flares. As a biomarker, fecal calprotectin < 167 has a 100% negative
predictive value for flare within the next 12 weeks (Gisbert, 2009). Adalimumab has low
antigenicity, and can be safely stopped and restarted later with good clinical effect
(Colombel, 2007). Patients want intermittent therapy, if it can be delivered in a timely
fashion when pre-clinical inflammation starts, in order to avoid clinically-significant
flares. This study will combine monitoring for pre-clinical inflammation with fecal
calprotectin and as-needed dosing with Adalimumab to maintain remission in patients who have
obtained remission with Adalimumab. This will be compared to two comparator arms: standard
maintenance therapy and complete cessation of therapy (Step-Down approach).

Inclusion Criteria:

1. Men or women 18 years of age or older at the time of informed consent.

2. Crohn's disease confirmed by endoscopy with biopsies.

3. On maintenance Adalimumab at a dose of 40 mg SC q 2 weeks without concomitant
immunosuppressive therapy.

4. Must be in clinical remission (CDAI <150) at the baseline/randomization (Week 0)
visit and biologic remission (both CRP <0.8 and FCP <167)at Week 0.

5. Prior medication for Crohn's disease may include one of the following and must have
been stopped with wash out periods: Methotrexate, Azathioprine, 6-Mercaptopurine,
Tacrolimus, Steroids.

6. Negative for TB, Hepatitis B-negative, and negative stool for Clostridium difficile.

Exclusion Criteria

1. Unable to consent for themselves.

2. Are prisoners, students or employees of the investigators, or mentally incapacitated.

3. Are unwilling to complete this 48 week study, provide stool samples throughout, or
unwilling to undergo multiple venipunctures.

4. Have a current infection with Clostridium difficile, clinically-significant
intestinal stricture, history of allergy, or adverse reaction, to Adalimumab, history
of sensitivity to latex.

5. Are currently using steroids or systemic immunomodulators (MTX, AZA, 6-MP, or
Tacrolimus), or have used another biologic medication in the past 12 weeks other than
Adalimumab, or have current or past use of Kineret® (Anakinra) or Tysabri®
(natalizumab).

6. Have received any live bacterial or viral vaccinations ≤ 12 weeks prior to Week 0 and
must not receive 12 months after study as well as BCG vaccination

7. Are known to have congestive heart failure.

8. Have a history of, or ongoing chronic or recurrent infectious disease, including but
not limited to chronic renal, chest infection (i.e. bronchiectasis) or urinary tract
infection (i.e. recurrent pyelonephritis) or open, draining, or infected skin wounds
or ulcers.

9. Have evidence of current clinically active and important infection.

10. Have or ever had a non-tuberculous mycobacterium infection or serious opportunistic
infection (i.e. cytomegalovirus, Pneumocystis carinii, aspergillosis).

11. Are known to be infected with HIV, Hepatitis B, or Hepatitis C.

12. Have severe, progressive, or uncontrolled renal, hepatic, hematological, endocrine,
pulmonary, cardiac, neurologic, cerebral, or psychiatric disease, or signs and
symptoms thereof.

13. Have a known history of lymphoproliferative disease including lymphoma. Have a
history of certain malignancies within five years of screening.