1. EFFICACY AND SAFETY OF HIGHER vs LOWER DOSE ADALIMUMAB MAINTENANCE THERAPY AS A FUNCTION OF DISEASE SEVERITY IN PEDIATRIC PATIENTS WITH CROHN’S DISEASE: SUBANALYSIS OF IMAgINE 1 Jeffrey Hyams 1, Wallace Crandall 2, Joel Rosh 3, Frank Ruemmele 4, Johanna Escher 5, Andreas Lazar 6, Yaqin Wang 7, Roopal Thakkar 7 1 Connecticut Children’s Medical Center, Hartford, CT, USA; 2 Nationwide Children’s Hospital, Columbus, OH, USA; 3 Goryeb Children’s Hospital/Atlantic Health, Morristown, NJ, USA; 4 Université Sorbonne Paris-Cité, Hôpital Necker Enfants Malades, Paris, France; 5 Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands; 6 AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany; 7 AbbVie Inc, North Chicago, IL, USA Advances in Inflammatory Bowel Diseases: Crohn’s & Colitis Foundation’s Clinical and Research Conference Hollywood, FL, December 12-14, 2013

2. F. Ruemmele: Speaker fees: Schering-Plough, Nestlé, MSD, Johnson & Johnson, Centocor; Board membership: Scientific advisory committee of DEVELOP study (Johnson & Johnson), invited to MSD France, Nestlé Nutrition Institute, Nestlé Health Science, Danone, and MeadJohnson, Biocodex W. Crandall: Consultant: AbbVie, Boehringer Ingelheim Pharma GmbH & Co KG; Financial support for research: AbbVie J Rosh: Consultant: AbbVie, Janssen, Soligenex; Speaker fees: Abbott Nutrition, Prometheus; Board Membership: GI Health Foundation; Financial support for research: AstraZeneca, AbbVie, Janssen, UCB J Escher: Consultant: Janssen Biologics; Speaker fees: MSD; Board membership: scientific advisory committee of DEVELOP study (Janssen Biologics); Financial support for research: MSD J Hyams: Consultant: Janssen Orthobiotech, AbbVie; Speaker fees and expert testimony: Janssen Orthobiotech; Financial support for research: AbbVie A Lazar, Y Wang, R Thakkar: Employees: AbbVie, may own AbbVie stock The authors and AbbVie scientists designed the study, and analyzed and interpreted the data. AbbVie funded the research. All authors contributed to the development of the content. The authors and AbbVie reviewed and approved the presentation. The authors maintained control over the final content. The authors thank Kristina Kligys, PhD, of AbbVie who prepared the first draft and assisted in production of the slides Disclosures 2CCFA 2013| Date 12-13-13

3. The treatment goal of Crohn’s disease (CD) in the pediatric population is to induce and maintain clinical remission and preserve and/or restore normal growth and pubertal development Adalimumab (ADA) has been shown to be an effective treatment for inducing and maintaining clinical remission and response in children with moderately to severely active CD 1 ADA has recently been approved in the EU for the treatment of severely active CD in pediatric patients (6 to 17 yrs old) who are refractory or intolerant to conventional therapy including primary nutrition therapy, a corticosteroid, and an immunomodulator Introduction 3 1 Hyams, et al. 2012. Gastroenterology. 143: 365-74 CCFA 2013| Date 12-13-13

4. IMAgINE 1: 52-wk randomized double-blind trial Children 6-17 years old (N=192) with a diagnosis of CD for at least 12 weeks, with a Pediatric Crohn’s Disease Activity Index (PCDAI) > 30 at Baseline – All patients had active disease despite concurrent therapy with stable dose of oral corticosteroid (for ≥ 2 weeks) and/or IMM for ≥ 8 weeks, with stable dose ≥ 4 weeks – Approximately 44% of patients received prior anti-TNF therapy Introduction 4CCFA 2013| Date 12-13-13

5. At Weeks 26 and 52, a numerically higher proportion of patients receiving higher-dose (HD) ADA than lower-dose (LD) ADA achieved clinical remission, but the differences were not statistically significant at each timepoint 1 – Remission Week 26: 38.7% HD vs 28.4% LD, p = 0.075 – Remission Week 52: 33.3% HD vs 23.2% LD, p = 0.100 In subgroup analyses at Week 52, a significantly higher remission rate was achieved in infliximab-naïve than infliximab-experienced patients with HD ADA 1 Introduction 5 1 Hyams, et al. 2012. Gastroenterology. 143: 365-74

6. Screening Baseline Week 4 Week 26 Primary Endpoint * Week 52 Open-label induction Baseline/Week 2 ≥40 kg: 160/80 <40 kg: 80/40 Randomization stratified by: Week 4 body weight Week 4 responder status Prior infliximab use Higher-Dose Lower-Dose ≥40 kg: 40 mg eow <40 kg: 20 mg eow ≥40 kg: 20 mg eow <40 kg: 10 mg eow Double-Blind Maintenance Dose escalation for flare or non-response beginning at Week 12 Week 2 * Potential dose adjustment by body weight Study Design-IMAgINE 1 6CCFA 2013| Date 12-13-13

7. Aim To evaluate the efficacy and safety of the two maintenance ADA dosing regimens based on Baseline disease severity in children with moderately to severely active CD Disease severity was classified based on the median of Basline PCDAI observed for the study population – Moderate CD = BL PCDAI < 40 – Severe CD = BL PCDAI ≥ 40 7CCFA 2013| Date 12-13-13

8. Endpoints Clinical remission (PCDAI ≤ 10) at Week 52 Clinical response (PCDAI decrease ≥ 15 points from Baseline) at Week 52 Clinical remission and response at Week 52 by prior infliximab use 8CCFA 2013| Date 12-13-13

9. Chi-square test to compare treatment groups including subgroup analysis by prior infliximab use Non-responder imputation (NRI) was applied, whereby patients were considered as non-responders for:  Missing data  Premature discontinuation  Switch to weekly therapy Data Analysis 9CCFA 2013| Date 12-13-13

10. Clinical Remission = PCDAI ≤ 10 Clinical Remission - Week 52 10CCFA 2013| Date 12-13-13

11. Clinical Response = decrease in PCDAI ≥ 15 points from BL Clinical Response - Week 52 11CCFA 2013| Date 12-13-13

12. By Prior Infliximab use Infliximab-experiencedInfliximab-naive LD ADAHD ADA Median BL PCDAI Clinical Remission - Week 52 12CCFA 2013| Date 12-13-13

13. By Prior Infliximab use Infliximab-experiencedInfliximab-naive LD ADAHD ADA Median BL PCDAI Clinical Response - Week 52 13CCFA 2013| Date 12-13-13

14. Safety BL PCDAI < 40BL PCDAI ≥ 40 Lower-Dose ADA 20/10mg N=41, 22.7 PY Events (E/100PY) Higher-Dose ADA 40/20mg N=39, 25 PY Events (E/100PY) Lower-Dose ADA 20/10mg N=54, 24.8 PY Events (E/100PY) Higher-Dose ADA 40/20mg N=54, 29.2 PY Events (E/100PY) Any AE223 (982.4)235 (940.0)241 (971.8)272 (931.5) Serious AE4 (17.6)8 (32.0)16 (64.5)16 (54.8) AE leading to discontinuation 2 (8.8)3 (12.0)11 (44.4)17 (58.2) Serious infections1 (4.4)1 (4.0)2 (8.1)4 (13.7) Malignancy0000 Opportunistic infection (excl TB) 001 (4.0)1 (3.4) Injection site rxn6 (26.4)9 (36.0)18 (72.6)16 (54.8) Hematologic AE4 (17.6)4 (16.0)1 (4.0)7 (24.0) Deaths0000 14CCFA 2013| Date 12-13-13

15. Conclusions At Week 52, higher-dose maintenance ADA was a more effective therapy than lower-dose ADA for children with severe CD; patients with moderate CD benefitted equally from either dose Infliximab-naïve patients achieved the greatest remission and response rates SAEs were slightly more frequent in patients with moderate CD receiving higher-dose than lower-dose ADA. The overall safety profile was similar for higher-dose and lower-dose ADA treatment 15CCFA 2013| Date 12-13-13

16. BACK-UP SLIDES

17. Clinical Remission = PCDAI ≤ 10 Clinical Remission - Week 26 CCFA 2013| Date 12-13-13

18. Clinical Response = decrease in PCDAI ≥ 15 points from BL Clinical Response - Week 26 CCFA 2013| Date 12-13-13