For Advisors Only BIOLOGIC THERAPY IN CROHN’S DISEASE ATILLA ERTAN, FACP, AGAF, MACG

Disclamer Grant/research support from Centocor, UCB Inc, Abbott Labs, Elan-Biogen Pharmaceuticals, Sucampo Pharmaceuticals, Genentech, Axcan, Barrx Inc & Salix Pharmaceuticals. Scientific advisory board member for Centocor, UCB Inc, Abbott Laboratories & Prometheus Labs.

THERAPEUTIC GOALS IN IBD Clinical improvement Clinical remission Corticosteroid weaning Maintenance of remission Maintained tissue healing Decrease in hospitalization & surgical interventions Prevention of complications Change natural course of the disease

Certolizumab pegol Humanized PEGylated Fab' fragment of an anti-TNF-α monoclonal antibody Single Fab' fragment –engineered for production in E.coli –no need for glycosylation of Fc portion 2 x 20 kD PEG – to extend half life of the Fab ' to a value comparable with a whole antibody product (approx. 2 weeks) –compatible with SC administration Site specific PEGylation –to hinge thiol –using proprietary linkage technology No monocyte or lymphocyte apoptosis, no complement activation, no ADCC Chapman A et al., Nature Biotech 1999; 17: Nesbitt and Henry, Abstract, ACG, Orlando FL, 2004 Molecular structure of certolizumab pegol. The chains of the Fab' fragments are shown in green/blue; the PEG is in yellow

Fully human monoclonal antibody (IgG 1 ) that specifically neutralizes TNF-  Half-life of 12 to 14 days Patient self-administered sc pen injection RA, PsA, and AS dose: single 40 mg injection every other week (eow) CD: starting dose 160/80 mg week 0, week 2 –Maintenance dose 40 mg eow week 4 Approved for RA, PsA, AS, CD with >190,000 patients currently being treated worldwide HUMIRA ® (adalimumab)

For Advisors Only Phase III Study of HUMIRA Induction of Remission in Anti-TNF Naïve Patients CLASSIC I (M02-403) Hanauer S, et al. Gastroenterol 2006;130:323–33 CLinical Assessment of Adalimumab Safety and Efficacy Studied as Induction Therapy in Crohn’s Disease

Results at Week 4 * p<0.05; † p=0.003; ‡ p=0.002 Clinical remission=CDAI<150 Clinical response  70 or  100=CDAI decrease from baseline ≥70 or ≥100 18% 24% 36% 12% 53% 55% 34% 32% 37% 49% Subjects (%) * ‡ 24% Placebo/placeboHUMIRA 40/20 HUMIRA 80/40HUMIRA 160/80 58% Clinical Remission Response,  70 Response,  100 * † * Humira Prescribing Information Feb 2007; Based on Hanauer, S. et al. Gastroenterol. 2006;130:323–33 CLASSIC I

For Advisors Only Phase III Study of HUMIRA Maintenance of Remission in Anti-TNF Naïve Patients CLASSIC II (M02-433) Sandborn WJ, et al. Gut Published Online First: 13 February 2007

Randomized Cohort: Clinical Remission (CDAI<150) LOCF; ITT population, n=55 *p<0.05 versus placebo * CLASSIC II Sandborn WJ, et al. Gut Published Online First: 13 February 2007

Open-label Cohort: Clinical Remission and Response LOCF (n=204) Remission CDAI  100 CDAI  70 Based on Sandborn, W. et al. 520, ACG 2005; CLASSIC II Sandborn WJ, et al. Gut Published Online First: 13 February 2007

Open-label Cohort: Conclusions HUMIRA administration led to long-lasting improvements in clinical response and remission –60% of patients achieved remission at week 56 with HUMIRA 40 mg EOW 64% of patients completed 56 weeks of therapy –54% of those patients maintained on 40 mg EOW Long-term administration of HUMIRA was well-tolerated in patients with Crohn’s disease –No new safety concerns CLASSIC II Sandborn WJ, et al. Gut Published Online First: 13 February 2007; Data on file.

For Advisors Only CHARM Fistula Outcomes

Complete Healing of Draining Fistulas at Last 2 Visits, Total Randomized Patients Healing = no draining fistulas for at least their last 2 post-baseline evaluations Patients with fistulas: draining fistulas at both screening and baseline PBO40 mg EOW40 mg weeklyboth HUMIRA groups 6/47 11/30 12/40 23/70 Patients Completely Healed (%) p= 0.016, combined HUMIRA groups vs placebo Colombel JF et al. T686d, DDW 2006 CHARM

Maintenance of Healing of Draining Fistulas: Weeks 26 and 56; All Randomized Patients Healing = no draining fistulas Patients with fistulas: draining fistulas at both screening and baseline Week 26Week 26 and 56 PBO40 mg EOW40 mg weeklyboth HUMIRA groups Patients Completely Healed (%) 6/47 10/30 11/40 21/70 6/47 10/30 11/40 21/70 p= Colombel JF, et al. Gastroenterol. 2007;132 (1):52-65 CHARM

Conclusions HUMIRA maintained remission in patients with moderately to severely active Crohn’s disease –There was no significant difference between the 40mg eow and 40mg weekly maintenance doses –HUMIRA was effective regardless of previous anti-TNF exposure Patients treated with HUMIRA discontinued steroids and remained in remission more frequently than patients receiving placebo HUMIRA treatment significantly increased the proportion of patients with complete healing of draining fistulas HUMIRA was well tolerated –Significantly lower rate of SAEs with HUMIRA maintenance compared to placebo –No new safety concerns compared to experience in RA and previous Crohn’s studies Colombel JF, et al. Gastroenterol. 2007;132 (1):52-65 CHARM

For Advisors Only Gauging Adalimumab Efficacy in Infliximab Non-Responders Phase III Study of HUMIRA Induction in Infliximab Failure Patients GAIN (M04-691) Sandborn WJ, et al. Ann Intern Med 2007;146(12):829-38

Response Rate  70-Point CDAI Decrease (CR-70) *p<0.005, † p<0.001, both vs. placebo. * † Week † % of Patients Sandborn WJ, et al. Ann Intern Med 2007;146(12): GAIN

Conclusions HUMIRA was effective in inducing clinical remission and response in subjects with moderate to severe Crohn’s disease who had lost response or had adverse reactions to infliximab –Effect was observed as early as Week 1 (CR-70) HUMIRA was well-tolerated with overall lower incidence of adverse events compared to placebo and with an AE profile similar to previous studies in Crohn’s and RA Sandborn WJ, et al. Ann Intern Med. 2007;146(12): GAIN

Summary: HUMIRA in Crohn’s Disease HUMIRA rapidly induces remission and response in patients with moderately to severely active disease HUMIRA is effective as a maintenance therapy –Remission and response –Steroid discontinuation –Healing of draining fistulas HUMIRA is effective in a broad patient population –Anti-TNF naïve –Anti-TNF experienced Across clinical studies, HUMIRA was well tolerated, with a safety profile consistent with RA Recommended dose: –Starting Dose: 160 mg week 0, 80 mg week 2 –Maintenance Dose: 40 mg EOW beginning week 4

For Advisors Only CLASSIC II Immunogenicity data

Immunogenicity 7/269 patients (2.6%) were positive for AAAs % AAA+ + Immunosuppressants0% - Immunosuppressants3.8% CLASSIC II 3/7 AAA+ patients (43%) in remission at Week 24 2/7 AAA+ patients (29%) in remission at Week 56 Sandborn WJ, et al. Gut Published Online First: 13 February 2007

THERAPEUTIC GOALS IN IBD Clinical improvement Clinical remission Corticosteroid weaning Maintenance of remission Maintained tissue healing Decrease in hospitalization & surgical interventions Prevention of complications Change natural course of the disease

For Advisors Only CHARM Safety Data

Adverse Events of Interest: All Exposure Adverse events (AE), n=1459E (E/100-PYs) Any AE12,124 (805.0) Any serious AE487 (32.3) Any AE leading to discontinuation326 (21.6) Infectious AE2,146 (142.5) Serious infections90 (6.0) Malignant neoplasms17 (1.1) Injection-site related AE552 (36.7) Opportunistic infections32 (2.1) Congestive heart failure (CHF)1 (<0.1) Demyelinating disease2 (0.1) Any fatal AE1 (<0.1) Colombel JF, et al. Gastroenterology 2007;132(4 Suppl 2):A-504.

Overview of Opportunistic Infections: All Exposure System organ class, n (%) Any HUMIRA n=1459 Any AE29 (2.0) Oral Candidiasis22 (1.5) Esophageal Candidiasis4 (0.3) Coccidioidomycosis1 (<0.1) Nocardiosis1 (<0.1) Tuberculosis3 (0.2) Colombel JF, et al. Gastroenterology 2007;132(4 Suppl 2):A-504.

Conclusions HUMIRA was generally safe and well-tolerated in the treatment of patients with moderately to severely active Crohn’s disease No clinically meaningful differences during the induction period in patients treated with HUMIRA vs placebo When normalized for exposure, patients who received placebo experienced generally higher rates of adverse events than patients treated with maintenance HUMIRA The safety profile of HUMIRA is consistent over more than 10 years of clinical experience Colombel JF, et al. Gastroenterology 2007;132(4 Suppl 2):A-504.

THERAPEUTIC GOALS IN IBD Clinical improvement Clinical remission Corticosteroid weaning Maintenance of remission Maintained tissue healing Decrease in hospitalization & surgical interventions Prevention of complications Change natural course of the disease

For Advisors Only DDW 2007 HUMIRA Data Update

For Advisors Only An Evaluation of Adalimumab on the Risk of Hospitalization in Patients With Crohn’s Disease, Data from CHARM BG Feagan 1, R Panaccione 2, WJ Sandborn 3, GR D’Haens 4, S Schreiber 5, PJ Rutgeerts 6, EV Loftus 3, KG Lomax 7, EQ Wu 8, PM Mulani 9 1 Department of Medicine, Epidemiology and Biostatistics, University of Western Ontario, London Health Sciences Centre, London, ON, Canada; 2 Inflammatory Bowel Disease Clinic, University of Calgary, Calgary, AB, Canada; 3 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; 4 Department of Gastroenterology, Imelda GI Clinical Research Center, Bonheiden, Belgium; 5 Department of Medicine, Christian-Albrechts University, Kiel, Germany; 6 Gastro-Enterologie, University Hospital of Gasthuisberg, Leuven, Belgium; 7 Immunology Development, Abbott, Parsippany, NJ, USA; 8 Analysis Group Inc., Boston, MA, USA; 9 Global Health Economics & Outcomes Research, Abbott, Abbott Park, IL, USA BG Feagan 1, R Panaccione 2, WJ Sandborn 3, GR D’Haens 4, S Schreiber 5, PJ Rutgeerts 6, EV Loftus 3, KG Lomax 7, EQ Wu 8, PM Mulani 9 1 Department of Medicine, Epidemiology and Biostatistics, University of Western Ontario, London Health Sciences Centre, London, ON, Canada; 2 Inflammatory Bowel Disease Clinic, University of Calgary, Calgary, AB, Canada; 3 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; 4 Department of Gastroenterology, Imelda GI Clinical Research Center, Bonheiden, Belgium; 5 Department of Medicine, Christian-Albrechts University, Kiel, Germany; 6 Gastro-Enterologie, University Hospital of Gasthuisberg, Leuven, Belgium; 7 Immunology Development, Abbott, Parsippany, NJ, USA; 8 Analysis Group Inc., Boston, MA, USA; 9 Global Health Economics & Outcomes Research, Abbott, Abbott Park, IL, USA Feagan BG, et al. Gastroenterology 2007;132(4 Suppl 2):A-513.

Cox Regression: CD-Related Hospitalization All Randomized Patients (n=778) *The hospitalization risk for HUMIRA patients is calculated using the Kaplan-Meier estimate of the hospitalization risk for placebo patients and the hazards ratio from the Cox regression model. The following formula was used: 4.1% = 1– (1–9.5%) Treatment Group Parameter Estimates Hazards Ratio (95% CI)P-value HUMIRA– (0.244–0.727) Placebo (reference group) – All Randomized Patients Multivariate Cox regression results: Given a 3-month CD-related hospitalization risk of 9.5% for a patient on placebo, the hospitalization risk would reduce to 4.1% if the patient was treated with HUMIRA* CHARM

Conclusions HUMIRA treatment resulted in statistically significant reductions of both all-cause and CD-related hospitalization risks in patients with moderate-to severe Crohn’s disease –For randomized responders, the relative risk reductions of CD-related hospitalization for HUMIRA compared to placebo were 78% and 57% at 3 months and 1 year, respectively –Even after controlling for potential confounding variables, HUMIRA had a statistically significant impact on reduction of all-cause and CD-related hospitalization risk compared to placebo This risk reduction associated with HUMIRA implies significant benefits to patients in terms of absenteeism and improving patient quality of life The lowering of hospitalization risk with HUMIRA could also reflect in significant costs savings to payers CHARM Feagan BG, et al. Gastroenterology 2007;132(4 Suppl 2):A-513.

For Advisors Only Early Crohn’s Disease Shows High Levels of Remission to Therapy With Adalimumab: Sub-analysis of CHARM S Schreiber 1 *, W Reinisch 2 *, JF Colombel 3, WJ Sandborn 4, DW Hommes 5, J Li 6, JD Kent 7, PF Pollack 6 1 Medicine, Christian Albrechts University, Kiel, Germany; 2 Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; 3 Hepatogastroenterology, CHU Lille, Lille, France; 4 Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; 5 Gastroenterology and Hepatology, Leiden Medical Center, Leiden, Netherlands; 6 Abbott, Parsippany, NJ, USA; 7 Abbott, Abbott Park, IL, USA; *Co-lead authors S Schreiber 1 *, W Reinisch 2 *, JF Colombel 3, WJ Sandborn 4, DW Hommes 5, J Li 6, JD Kent 7, PF Pollack 6 1 Medicine, Christian Albrechts University, Kiel, Germany; 2 Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; 3 Hepatogastroenterology, CHU Lille, Lille, France; 4 Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; 5 Gastroenterology and Hepatology, Leiden Medical Center, Leiden, Netherlands; 6 Abbott, Parsippany, NJ, USA; 7 Abbott, Abbott Park, IL, USA; *Co-lead authors Schreiber S, et al. Gastroenterology 2007;132(4 Suppl 2):A-147.

*p=0.002, **p<0.001, † p=0.014, ‡ p=0.001 all vs placebo Clinical Remission at Weeks 26 and 56 by Disease Duration: RR Week 26 Week 56 Placebo All HUMIRA † ‡ <2 years: PBO n=23 HUMIRA n=39; 2 to <5 years: PBO n=36, HUMIRA n=57;  5 years: PBO n=111, HUMIRA n=233 <2 years 2 to <5 years  5 years CHARM Schreiber S, et al. Gastroenterology 2007;132(4 Suppl 2):A-147.

*p=0.008, **p<0.001, † p=0.017, ‡ p=0.002 vs placebo Clinical Response (CR-100) at Weeks 26 and 56 by Disease Duration: RR Placebo All HUMIRA † ‡ <2 years: PBO n=23 HUMIRA n=39; 2 to <5 years: PBO n=36, HUMIRA n=57;  5 years: PBO n=111, HUMIRA n=233 <2 years 2 to <5 years  5 years CHARM Week 26 Week 56 Schreiber S, et al. Gastroenterology 2007;132(4 Suppl 2):A-147.

*p<0.001, **p=0.017, † p=0.004 vs placebo Clinical Response (CR-70) at Weeks 26 and 56 by Disease Duration: RR Placebo All HUMIRA † <2 years: PBO n=23 HUMIRA n=39; 2 to <5 years: PBO n=36, HUMIRA n=57;  5 years: PBO n=111, HUMIRA n=233 <2 years 2 to <5 years  5 years CHARM Week 26 Week 56 Schreiber S, et al. Gastroenterology 2007;132(4 Suppl 2):A-147.

Disease Duration <2 years Disease Duration 2–5 years Disease Duration  5 years Adverse Event, % PBO N=23 All HUMIRA N=39 PBO N=36 All HUMIRA N=57 PBO N=111 All HUMIRA N=233 Any AE AEs leading to discontinuation of drug * Infectious AE * Any SAE * Infectious SAE Injection-site reaction * Deaths *p<0.05 vs placebo Adverse Events by Disease Duration: All HUMIRA-Treated Patients CHARM Schreiber S, et al. Gastroenterology 2007;132(4 Suppl 2):A-147.

Conclusions HUMIRA maintained remission through Week 56 in patients with active CD, regardless of disease duration –Maintenance of clinical remission and response through Week 56 was greater in HUMIRA-treated patients with early Crohn’s disease (<2 years) Long-term maintenance of remission rates suggest that early disease modification with HUMIRA would be beneficial to early CD patients Schreiber S, et al. Gastroenterology 2007;132(4 Suppl 2):A-147. CHARM

For Advisors Only GAIN Rapid Response to Adalimumab in Crohn’s Disease Patients who Have Failed Infliximab GR D’Haens 1, RA Enns 2, G Van Assche 3, JD Kent 4, J Li 5, PF Pollack 5, DT Rubin 6 1 Gastroenterology, Imelda GI Clinical Research Center, Bonheiden, Belgium; 2 Gastroenterology, University of British Columbia, Vancouver, BC, Canada; 3 Gastroenterology, University of Leuven, Leuven, Belgium; 4 Abbott, Abbott Park, IL, USA; 5 Abbott, Parsippany, NJ, USA; 6 Gastroenterology, University of Chicago, Chicago, IL, USA GR D’Haens 1, RA Enns 2, G Van Assche 3, JD Kent 4, J Li 5, PF Pollack 5, DT Rubin 6 1 Gastroenterology, Imelda GI Clinical Research Center, Bonheiden, Belgium; 2 Gastroenterology, University of British Columbia, Vancouver, BC, Canada; 3 Gastroenterology, University of Leuven, Leuven, Belgium; 4 Abbott, Abbott Park, IL, USA; 5 Abbott, Parsippany, NJ, USA; 6 Gastroenterology, University of Chicago, Chicago, IL, USA D’Haens GR, et al. Gastroenterology 2007;132(4 Suppl 2):A-502.

Rationale Significant responses to HUMIRA in rheumatoid arthritis have been observed as early as one day after the first injection 1 A previous multicenter study in CD patients found significant correlation with 3 patient-reported diary components of the Crohn’s disease activity index [CDAI] (number of stools, abdominal pain, and general well-being) and the overall CDAI score (r=0.87, p<0.001) 2 1. Wolfe F, et al. Arthiritis Rheum 2006;54(9) (Suppl):S424; 2. Sandler RS, et al. J Clin Epi 1988;41:451–58 GAIN D’Haens GR, et al. Gastroenterology 2007;132(4 Suppl 2):A-502.

Objective and Methods To assess the time to symptomatic response to HUMIRA in CD patients who have failed prior treatment with infliximab Endpoints: CDAI diaries –Summation of 3 patient-reported components extracted from 7-day CDAI diaries collected at baseline, Weeks 1, 2, and 4  Abdominal pain—sum of 7 daily ratings (0=none, 1=mild, 2=moderate, 3=severe)  Frequency of loose stools—number of liquid or very soft stools in 1 week  General well-being—sum of 7 daily ratings (0=generally well, 1=slightly under par, 2=poor, 3=very poor, 4=terrible) –Days 1–7 summed; 9–15; 23–29 GAIN D’Haens GR, et al. Gastroenterology 2007;132(4 Suppl 2):A-502.

Conclusions HUMIRA led to statistically significant rapid improvements in patient-reported CDAI measures as early as Day 4. Statistically significant differences between HUMIRA and placebo groups were maintained for the remainder of the study GAIN D’Haens GR, et al. Gastroenterology 2007;132(4 Suppl 2):A-502.

For Advisors Only Adalimumab Safety in Crohn’s Disease Clinical Trials JF Colombel 1, WJ Sandborn 2, W Reinisch 3, SB Hanauer 4, PJ Rutgeerts 5, BE Sands 6, W Lau 7, JD Kent 8, PF Pollack 9 1 Hepatogastroenterology, CHU Lille, Lille, Nord, France; 2 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; 3 Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; 4 Section of Gastroenterology, University of Chicago, Chicago, IL, USA; 5 Gastro-Enterologie, University Hospital of Gasthuisberg, Leuven, Belgium; 6 MGH Crohn’s and Colitis Center, Massachusetts General Hospital, Boston, MA, USA; 7 Biostatistics, Abbott, Parsippany, NJ, USA; 8 Immunology Development, Abbott, Abbott Park, IL, USA; 9 Immunology Development, Abbott, Parsippany, NJ, USA JF Colombel 1, WJ Sandborn 2, W Reinisch 3, SB Hanauer 4, PJ Rutgeerts 5, BE Sands 6, W Lau 7, JD Kent 8, PF Pollack 9 1 Hepatogastroenterology, CHU Lille, Lille, Nord, France; 2 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; 3 Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; 4 Section of Gastroenterology, University of Chicago, Chicago, IL, USA; 5 Gastro-Enterologie, University Hospital of Gasthuisberg, Leuven, Belgium; 6 MGH Crohn’s and Colitis Center, Massachusetts General Hospital, Boston, MA, USA; 7 Biostatistics, Abbott, Parsippany, NJ, USA; 8 Immunology Development, Abbott, Abbott Park, IL, USA; 9 Immunology Development, Abbott, Parsippany, NJ, USA Colombel JF, et al. Gastroenterology 2007;132(4 Suppl 2):A-504.

Objectives and Methods To assess overall HUMIRA safety across induction and maintenance datasets in Crohn’s disease clinical trials Clinical trial safety data of patients who received at least 1 open-label (OL) or randomized double-blind (DB) injection of HUMIRA were evaluated in 3 analysis sets: –Induction trials  CLASSIC I  GAIN  The OL 4-week induction phase of CHARM –DB Maintenance trials  CLASSIC II  CHARM Safety data collected through February 14, 2006, were included in this summary analysis –All Exposure  CLASSIC I  CLASSIC II  CHARM  GAIN  OL extension trial following CHARM and GAIN Colombel JF, et al. Gastroenterology 2007;132(4 Suppl 2):A-504.

Patient Exposure to HUMIRA in Crohn’s Clinical Trials The Crohn’s disease clinical trial database represents 1,506-PYs of exposure to HUMIRA *Includes induction and extension trials through February 14, 2006 ExposurePatients* Any 1,459 >6 months883 >1 year661 >2 years240 >3 years69 Colombel JF, et al. Gastroenterology 2007;132(4 Suppl 2):A-504.

Adverse Events of Interest: Induction Period *Statistically significant difference vs placebo (p<0.05) using Fisher’s Exact test Statistical testing was only performed for the pooled HUMIRA 160/80 mg and placebo groups No malignant neoplasm or congestive heart failure (CHF) occurred Adverse events (AE), n (%) Placebo n=240 HUMIRA 80/40 mg DB n=75 HUMIRA 80/40 mg OL n=854 HUMIRA 160/80 mg DB n=235 Any AE176 (73)51 (68)508 (60)148 (63)* Any serious AE11 (5)1 (1)45 (5)5 (2) Any AE leading to discontinuation6 (3)1 (1)54 (6)2 (1) Infectious AE51 (21)12 (16)130 (15)38 (16) Serious infections4 (2)010 (1)2 (1) Injection-site related AE29 (12)16 (21)109 (13)41 (17) Opportunistic infections001 (0.1)1 (0.4) Demyelinating disease001 (0.1)0 Any fatal AE001 (0.1)0 Colombel JF, et al. Gastroenterology 2007;132(4 Suppl 2):A-504.

Adverse Events of Interest: Double-Blind Maintenance Period (E/100-PYs) EOW = every other week; W = weekly; E = Events; E/100-PYs = Events/100-patient-years No congestive heart failure (CHF), Lupus-like illness, demyelinating disease, or fatal AE occurred Adverse events (AE) Placebo n=279, PYs HUMIRA 40 mg eow n=279, PYs HUMIRA 40 mg weekly n=275, PYs Any AE Any serious AE Any AE leading to discontinuation Infectious AE Serious infections954 Malignant neoplasm200 Injection-site related AE Opportunistic infections213 Colombel JF, et al. Gastroenterology 2007;132(4 Suppl 2):A-504.

Adverse Events of Interest: All Exposure Adverse events (AE), n=1459E (E/100-PYs) Any AE12,124 (805.0) Any serious AE487 (32.3) Any AE leading to discontinuation326 (21.6) Infectious AE2,146 (142.5) Serious infections90 (6.0) Malignant neoplasms17 (1.1) Injection-site related AE552 (36.7) Opportunistic infections32 (2.1) Congestive heart failure (CHF)1 (<0.1) Demyelinating disease2 (0.1) Any fatal AE1 (<0.1) Colombel JF, et al. Gastroenterology 2007;132(4 Suppl 2):A-504.

Overview of Malignant Neoplasms: All Exposure Three events were coded as neoplasms but were not confirmed as malignant: 1 Lung nodule, 2 Lymphoid tissue regrowth, 3 Bowen’s keratosis System organ class, n (%)Patients (n=1,459) Any AE16 (1.1) Acute Myeloid Leukemia1 (<0.1) Basal Cell Carcinoma3 (0.2) Bladder1 (<0.1) Breast1 (<0.1) Lung Neoplasm 1 1 (<0.1) Neoplasm 2 1 (<0.1) Neoplasm Skin 3 1 (<0.1) Non-Hodgkin’s Lymphoma1 (<0.1) Ovarian1 (<0.1) Thyroid2 (0.1) Prostate1 (<0.1) Skin1 (<0.1) Squamous Cell Carcinoma2 (0.1) Colombel JF, et al. Gastroenterology 2007;132(4 Suppl 2):A-504.

Overview of Opportunistic Infections: All Exposure System organ class, n (%) Any HUMIRA n=1459 Any AE29 (2.0) Oral Candidiasis22 (1.5) Esophageal Candidiasis4 (0.3) Coccidioidomycosis1 (<0.1) Nocardiosis1 (<0.1) Tuberculosis3 (0.2) Colombel JF, et al. Gastroenterology 2007;132(4 Suppl 2):A-504.

Conclusions HUMIRA was generally safe and well-tolerated in the treatment of patients with moderately to severely active Crohn’s disease No clinically meaningful differences during the induction period in patients treated with HUMIRA vs placebo When normalized for exposure, patients who received placebo experienced generally higher rates of adverse events than patients treated with maintenance HUMIRA The safety profile of HUMIRA is consistent over more than 10 years of clinical experience Colombel JF, et al. Gastroenterology 2007;132(4 Suppl 2):A-504.

For Advisors Only HUMIRA Safety Data Across Indications

Rates of AEs of Interest (E/100-PYs) in HUMIRA Global Clinical Trials Indication RAPsAASPsJIACD Exposure (PYs) 12, ,506 Patients 10, ,459 Serious Infections Tuberculosis Lymphomas Demyelinating disease SLE/Lupus-like syndrome CHF Schiff MH, et al. Ann Rheum Dis. 2006;65: Burmester G, et al. EULAR 2006, Amsterdam. #THU0214. Burmester GR, et al. ACR, Washington DC, 2006, #467. Colombel JF, et al. Gastroenterology 2007;132(4 Suppl 2):A-504.