Presented at the 75 th Annual Meeting of the American Academy of Dermatology, Orlando, FL, March 3-7, 2017 METHODS INTRODUCTION OBJECTIVE

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1 Seven-Yer Interim Results from the ESPRIT 10-Yer Postmrketing Surveillnce Registry of Adlimumb for Moderte to Severe Psorisis Frncisco Kerdel, 1 Aln Menter, 2 Jshin J. Wu, 3 Mreike Bereswill, 4 Dilek Arikn, 5 Anne Cmez, 4 Arijit Gnguli, 5 nd Wendell C. Vldecntos 5 1 Florid Acdemic Dermtology Centers, Mimi, FL, USA; 2 Division of Dermtology, Bylor University Medicl Center, Dlls, TX, USA; 3 Kiser Permnente Los Angeles Medicl Center, Los Angeles, CA, USA; 4 AbbVie Deutschlnd GmbH & Co KG, Ludwigshfen, Germny; 5 AbbVie Inc., North Chicgo, IL, USA Presented t the 75 th Annul Meeting of the Americn Acdemy of Dermtology, Orlndo, FL, Mrch 3-7, INTRODUCTION Adlimumb (ADA), fully humn, recombinnt, monoclonl ntibody directed ginst tumor necrosis fctor-lph (TNF-α), is indicted for the tretment of moderte to severe chronic plque psorisis in dult ptients, who re cndidtes for systemic therpy or phototherpy. 1 ESPRIT is n ongoing, 10-yer interntionl, prospective observtionl registry evluting the long-term sfety nd effectiveness of origintor ADA (AbbVie) prescribed in in routine clinicl prctice ccording to locl product lbeling for dult ptients with chronic plque psorisis (NCT ). 2 OBJECTIVE To present sfety, effectiveness, nd ptient-reported outcomes (PROs) over 7-yer period (26 September 2008 through 30 November 2015) from n interim nlysis of dt collected from the ESPRIT registry. To view n electronic version of this poster, scn QR code or visit To obtin QR code reder, go to your device pp store nd serch for QR code reder. METHODS STUDY DESIGN AND PATIENTS Enrollment: Ptient enrollment ws initited on 26 September 2008 nd completed on 8 November As of 30 November 2015, 6066 ptients were enrolled in the ESPRIT registry. Study sites were locted in the United Sttes, Cnd, Austri, Czech Republic, Denmrk, Frnce, Germny, Greece, Irelnd, Netherlnds, Spin, Sweden, nd United Kingdom. Tretment: ADA ws dosed s recommended in the locl product lbel. Min Inclusion Criteri (Figure 1): Adult ptients ( 18 yers) with chronic plque psorisis who hve been prescribed ADA ccording to locl product lbeling nd meet one of the following criteri: Previously initited ADA therpy nd continued on ADA with no more thn 70 consecutive dys off drug. The initil ADA dose ws received either in pre-registry feeder clinicl tril or from n existing prescription outside of pre-registry feeder tril. Source documenttion of serious dverse events (SAEs), AEs of specil interest, nd dosing informtion since the initition of therpy cn be provided by the physicin. Newly initited ADA therpy within 4 weeks of registry entry. AbbVie Inc. funded this study nd prticipted in the study design; study reserch; collection, nlysis nd interprettion of dt; nd writing, reviewing nd pproving of this publiction. All uthors hd ccess to the dt, nd prticipted in the development, review, nd pprovl, nd in the decision to submit this publiction.

2 METHODS (CONTINUED) Figure 1. Study Design And Ptient Popultion of ESPRIT Observtionl Registry Yers -6 All-Treted (All-Rx) ptients (N=6051) Ptients who received t lest one dose in the registry. Initited ADA in the pst Initil dose >4 weeks pre-registry Hs prticipted in pre-registry feeder tril (N=386) -5 Phse 3 M (N=1) Jun 2003 REVEAL M (N=3) Dec 2004 BELIEVE M (N=73) Nov 2007 Phse 3 M (N=1) Jun 2006 CHAMPION M (N=2) Jul 2005 PRIDE W (N=62) Sep 2007 OLE b M (N=196) My 2004 REACH M (N=23) Aug 2008 PROGRESS M (N=25) Jn 2008 Hs never prticipted in pre-registry feeder tril (N=3108) Newly initited ADA Initil dose <4 weeks pre-registry New prescription (New-Rx) ptients (N=2557) ESPRIT Registry (P10-023); Strt Dte: Sep 2008 Adlimumb tretment per locl product lbel * * * * * * * * * * * * * * * * * * * * * * Enrollment STATISTICAL ANALYSES Popultions (Figure 1): All-treted (All-Rx) ptient popultion: Ptients who received t lest one dose of ADA in the registry. New-prescription (New-Rx) ptient popultion: Ptients who newly initited ADA within 4 weeks prior to registry enrollment. New-Rx is subgroup of All-Rx ptient popultion. Descriptive sttistics re presented for bseline ptient demogrphics nd disese chrcteristics. ADA Exposure: Overll exposure to ADA (outside of nd within the registry) ws clculted s time from the initil (first ever) ADA dose to 14 dys fter the lst ADA dose in the registry, excluding the totl number of dys of tretment interruption in the registry. Registry exposure to ADA (within the registry) ws clculted s time from first ADA dose in registry to 14 dys fter the lst ADA dose in registry, excluding the totl number of dys of tretment interruption in the registry. A tretment interruption (TI) is defined s >70 dys without ny ADA dose; TI strts t dy 71 fter ADA ws stopped.. Strt dtes re shown for clinicl trils. b. REVEAL nd CHAMPION were mong the feeder trils for the OLE; the number of ptients in these trils were counted seprtely from OLE s 196 ptients. *Ptients were evluted 3 nd 6 months post enrollment, then every 6 months for up to 10 yers. Ptients re followed t intervls determined by routine clinicl prctice or s recommended by ntionl guidelines. Sfety dt re cptured during the entire study period. Ptients who discontinue registry drug re encourged to remin in the registry. ADA=dlimumb.

3 METHODS (CONTINUED) Sfety: All tretment-emergent dverse events (All-TEAEs) were events occurring from the dte of initil (first ever) ADA dose through 70 dys fter the dte of lst ADA dose in the registry, excluding AEs occurring during TIs. Incidence rtes for All-TEAEs re reported s events per 100 ptient yers of overll exposure to ADA (E/100PY) nd presented in subgroups of overll exposure to ADA. In ddition, the incidence of All-TEAEs is presented by time periods, i.e. the number of ptients with new occurrence of the specific AE divided by the number of ptients t risk. Ptients t risk hd t lest n overll exposure to ADA up to nd including the respective time period nd did not hve the specific AE in ny period before. Stndrdized mortlity rtio (SMR): SMR ws clculted s the rtio of observed to expected tretment-emergent deths using the 2006 country-specific World Helth Orgniztion (WHO) mortlity rtes. A SMR of <1.0 indictes tht the observed number of deths is lower thn expected rte in n ge-, sex-, nd country-mtched generl popultion. Effectiveness: Proportion of ptients chieving Physicin s Globl Assessment (PGA) of cler or miniml were nlyzed s observed during registry prticiption (ptients were not necessrily receiving ADA t the time of ssessment). Ptient-Reported Outcomes (US ptients only): Chnge from bseline in Dermtology Life Qulity Index (DLQI) nd Work Productivity Activity Impirment (WPAI) scores were nlyzed s observed during registry prticiption. RESULTS This 7-yer interim nlysis used dt collected from 6051 ptients (2557 New-Rx ptients, 42.3%), who were enrolled nd dosed between 26 September 2008 nd 30 November The mjority of ptients in ESPRIT were from sites in the United Sttes (69.5%) nd Cnd (13.9%) (70.1%) All-Rx nd 1652 (64.6%) New-Rx ptients re continuing in the registry s of 30 November Of those, 3070 (50.7%) All-Rx nd 1061 (41.5%) New-Rx ptients hve not permnently discontinued ADA. Of those, 2150 (35.5%) All-Rx nd 674 (26.4%) New-Rx ptients never interrupted ADA tretment for >70 dys (29.9%) All-Rx nd 905 (35.4%) New-Rx ptients discontinued from the registry; the most frequent reson for discontinuing ws being lost to follow up (14.4%, All-Rx nd 19.2, New-Rx) (Tble 1).

4 RESULTS (CONTINUED) Tble 1. Resons for Discontinution from Registry nd from Registry Drug (All-Rx nd New-Rx Ptient Popultion) Reson for Discontinution (in >1% ptients) All-Rx, N=6051 n (%) New-Rx, N=2557 n (%) From registry, ny reson 1809 (29.9) 905 (35.4) Lost to follow-up 874 (14.4) 491 (19.2) Lck of efficcy 89 (1.5) 56 (2.2) Withdrew consent 355 (5.9) 156 (6.1) Deth 70 (1.2) 25 (1.0) Non-complince 86 (1.4) 49 (1.9) Other 333 (5.5) 116 (4.5) From registry drug b, ny reson 2981 (49.3) 1496 (58.5) AE 170 (2.8) 87 (3.4) SAE or SAE of interest 101 (1.7) 40 (1.6) Lost to follow-up 399 (6.6) 226 (8.8) Lck of efficcy 1101 (18.2) 610 (23.9) Intolernce 44 (0.7) 35 (1.4) Withdrew consent 117 (1.9) 59 (2.3) Other 445 (7.4) 220 (8.6) Unknown reson 668 (11.0) 268 (10.5). Resons for registry discontinutions in 1% of ptients were AE, intolernce, ptient moved, SAE or SAE of interest, stisfctory improvement, pregnncy, or unknown resons. b. Resons for registry drug discontinutions in 1% of ptients were ptient deth, stisfctory improvement, or required dditionl therpy. All-Rx=ll-treted ptient popultion; New-Rx=new prescription ptient popultion; AE=dverse event; SAE=serious dverse event. Ptient demogrphics nd disese chrcteristics t registry entry re presented in Tble 2. Tble 2. Ptient Demogrphics nd Disese Chrcteristics t Registry Entry (All-Rx nd New-Rx Ptient Popultion) Demogrphic or Chrcteristic All-Rx, N=6051 New-Rx, N=2557 Sex, n (%) Mle 3489 (57.7) 1380 (54.0) Femle 2562 (42.3) 1177 (46.0) White 5268 (87.3) 2223 (87.1) Blck 178 (2.9) 65 (2.5) Asin 259 (4.3) 106 (4.2) Rce, n (%)* Americn Indin/ Alsk ntive 16 (0.3) 7 (0.3) Ntive Hwiin or other pcific islnder 40 (0.7) 25 (1.0) Other 253 (4.2) 115 (4.5) Multi-rce 22 (0.4) 12 (0.5) Psoritic Arthritis, n (%)* Not nlyzed b 867 (34.0) c Fmily history of psorisis, n (%)* Not nlyzed b 1067 (41.9) d Cler 731 (12.1) 53 (2.1) Miniml 1177 (19.5) 141 (5.5) PGA e, n (%)* Mild 1149 (19.1) 310 (12.2) Moderte 1781 (29.6) 1118 (44.0) Severe 973 (16.2) 749 (29.4) Very severe 213 (3.5) 172 (6.8) Age, yers, medin (rnge) 47.0 (18 94) 46.0 (18 91) Weight, kg, medin (rnge) 87.0 (41 252) f 86.0 (41 218) g BMI, kg/m 2, medin (rnge) 29.4 (16 77) h 29.4 (16 70) i Durtion of psorisis j, yers, medin (rnge) Not nlyzed b 13.4 (0 68) k *Percentges clculted on non-missing vlues. Missing dt: All-Rx: n=15; New-Rx: n=4. b Not nlyzed becuse not ll dt were cptured in the registry dtbse. c Missing dt: New-Rx: n=7. d Missing dt: New-Rx: n=9. e Mny ptients hd received ADA prior to entering the registry, demonstrted by the number of ptients entering the registry with PGA of cler or miniml. Missing dt: All-Rx: n=27; New-Rx: n=14. f N=5927; g N=2497; h N=5909; i N=2492; k N=2548. j Clculted t registry entry. All-Rx=ll-treted ptient popultion; New-Rx=new prescription ptient popultion; PGA=physicin s globl ssessment; BMI=body mss index.

5 RESULTS (CONTINUED) Medin durtion of overll exposure to ADA ws 1398 ( ) dys nd 714 ( ) dys for All-Rx nd New-Rx ptient popultion, respectively. Medin durtion of registry exposure to ADA ws 1132 ( ) dys nd 714 ( ) dys for All-Rx nd New-Rx ptient popultion, respectively. The number of ptients ccording to durtion of overll exposure to ADA nd registry exposure to ADA re shown in Figure 2. Figure 2. Number of Ptients Bsed on Durtion of ADA Exposure (All-Rx nd New-Rx Ptient Popultion) The time to discontinution from the registry nd from registry drug in All-Rx nd New-Rx ptients re shown in Figure 3. Figure 3. Time to Discontinution from the Registry nd from Registry Drug (ADA), (All-Rx nd New-Rx Ptient Popultion) ADA=dlimumb; All-Rx=ll-treted ptient popultion; New-Rx=new prescription ptient popultion. Time of observtion (first dy to lst dy of registry prticiption) for time to registry discontinution; Registry exposure to ADA for time to registry drug discontinution. ADA=dlimumb; All-Rx=ll-treted ptient popultion; New-Rx=new prescription ptient popultion.

6 RESULTS (CONTINUED) SAFETY An overview of incidence rtes (E/100PY of overll exposure to ADA) of ll tretment-emergent dverse events (All-TEAEs) in All-Rx ptients by subgroups of overll exposure to ADA is presented in Tble 3. A mjority of the rollover ptients from feeder studies hve overll exposure to ADA of >7 yers nd their AEs from feeder studies re included in the All-TEAE nlyses. The incidence of All-TEAEs by time periods of overll exposure to ADA, i.e. the occurrence of new cses of specific AE, in All-Rx ptients remined stble over time nd is shown in Figure 4. Tble 3. Incidence Rtes of All-TEAE of Interest in Subgroups of Overll Exposure to ADA (All-Rx Ptient Popultion) AE of Interest E (E/100PY) N= PY= Subgroups of Overll Exposure to ADA 1 yr >1 3 yrs >3 5 yrs >5 7 yrs >7 yrs b Overll All-Rx AE 301 (51.1) 527 (22.3) 791 (15.4) 1207 (13.1) 2334 (36.6) 5160 (21.8) AE leding to discontinution of ADA 143 (24.3) 134 (5.7) 85 (1.7) 39 (0.4) 8 (0.1) 409 (1.7) Serious AE 125 (21.2) 197 (8.3) 232 (4.5) 290 (3.2) 191 (3.0) 1035 (4.4) Serious infection 40 (6.8) 52 (2.2) 53 (1.0) 58 (0.6) 44 (0.7) 247 (1.0) Orl Cndidisis 1 (0.2) 3 (0.1) 2 (<0.1) 0 3 (<0.1) 9 (<0.1) Active tuberculosis 2 (0.3) 2 (<0.1) 2 (<0.1) (<0.1) Opportunistic infection, other c 0 1 (<0.1) 1 (<0.1) 1 (<0.1) 0 3 (<0.1) Mlignncy 19 (3.2) 35 (1.5) 43 (0.8) 83 (0.9) 67 (1.0) 247 (1.0) Congestive hert filure 2 (0.3) 0 5 (<0.1) 3 (<0.1) 1 (<0.1) 11 (<0.1) Lupus-like rections nd systemic lupus 5 (0.8) 0 1 (<0.1) 1 (<0.1) 1 (<0.1) 8 (<0.1) Demyelinting disorder 2 (0.3) 1 (<0.1) 1 (<0.1) 1 (<0.1) 0 5 (<0.1) AE leding to deth 8 (1.4) 12 (0.5) 7 (0.1) 2 (<0.1) 2 (<0.1) 31 (0.1) Intolernce to initil ADA therpy nd subsequent discontinutions most likely occurred during the first yer of ADA nd mjority of these events were summrized s TEAEs within the 1 yr subgroup. b The higher incidence of All-TEAEs in the subgroup with highest overll exposure to ADA (>7 yers), which includes mjority of rollover ptients from feeder studies, is likely due to closer AE documenttion in feeder studies compred with registry AE collection nd retroctive collection of AEs for ptients who initited ADA therpy outside of n AbbVie clinicl tril before the registry. c Excluding orl cndidisis nd tuberculosis. TEAE=tretment-emergent dverse event; ADA=dlimumb; All-Rx=ll-treted ptient popultion; AE=dverse event; E=event; PY=ptient yers; yr=yer.

7 RESULTS (CONTINUED) Figure 4. Incidence of All-TEAEs of Interest by Time Periods of Overll Exposure to ADA (All-Rx Ptient Popultion) Stndrdized mortlity rtio ws 0.27 (95%CI, ) for All-Rx nd 0.28 (95% CI, ) for New-Rx, indicting tht the observed number of deths ws below expected for ge-, sex- nd country-mtched popultion (Figure 5). Figure 5. Stndrdized Mortlity Rtios (SMR), Overll nd by Gender (All-Rx nd New-Rx Ptient Popultion) The AEs collected from rollover ptients during feeder studies hve most likely occurred in the first yer of overll exposure to ADA. b Ptients with 7 yers of overll exposure to ADA re selected subgroup from the overll popultion who hd longest exposure to ADA nd potentilly hd longer durtion of disese. N = number of ptients who hd t lest n overll exposure to ADA up to nd including the respective time period. Incidence is defined s the number of ptients with new occurrence of the specific AE divided by the number of ptients t risk, i.e. ptients who hd t lest n overll exposure to ADA up to nd including the respective time period nd who did not hve the specific AE in ny period before. TEAE=tretment-emergent dverse event; All-Rx=ll-treted ptient popultion; AE=dverse event; ADA=dlimumb; d/c=discontinution. All-Rx=ll-treted ptient popultion; New-Rx=new prescription ptient popultion; PY=ptient yers; CI=confidence intervls.

8 P tie n ts (% ) C h n g e fr o m B s e lin e in D L Q I (M e n, S D ) RESULTS (CONTINUED) EFFECTIVENESS % of All-Rx nd % of New-Rx ptients chieved PGA cler or miniml during yers 1 7 of registry prticiption (Figure 6). Figure 6. Proportion of Ptients (s Observed) Achieving PGA Cler or Miniml (All-Rx nd New-Rx Ptient Popultion) PATIENT-REPORTED OUTCOMES (US ptients only) Improvement in DLQI scores nd WPAI subscores from bseline were mintined through the first 7 yers of registry prticiption (Figures 7 nd 8). Figure 7. Chnge from Bseline (s Observed) in DLQI Scores (All-Rx nd New-Rx Ptient Popultion) A ll-r x (N = ) N e w -R x (N = ) 5 A ll-r x (N = ) N e w -R x (N = ) n = N = R e g is tr y p r tic ip tio n (m o n th s ) R e g is tr y p r tic ip tio n (m o n th s ) N = PGA=physicin s globl ssessment; All-Rx=ll-treted ptient popultion; New-Rx=new prescription ptient popultion. Decrese in DLQI score denotes improvement. DLQI=dermtology life qulity index; All-Rx=ll-treted ptient popultion; New-Rx=new prescription ptient popultion.

9 C h n g e fr o m B s e lin e (% ) [M e n, S D ] RESULTS (CONTINUED) Figure 8. Chnge from Bseline (s Observed) in WPAI Subscores (All-Rx Ptient Popultion) b CONCLUSION In this 7-yer interim nlysis, no new sfety signls were observed nd sfety ws consistent with the known sfety profile of ADA. The number of tretment-emergent deths in the registry ws below the expected rte for comprble generl popultion. As-observed effectiveness of ADA nd improvement from bseline in PROs were mintined through 84 months REFERENCES HUMIRA [pckge insert]. North Chicgo, IL, USA, AbbVie Inc; Menter A, et l., J Am Acd Dermtol. 2015; 73(3): N = T W P I T A I P re s e n te e is m A b s e n te e is m W o rk P ro d u c tiv ity n d A c tiv ity Im p irm e n t M o n th 1 2 M o n th 2 4 M o n th 3 6 M o n th 4 8 M o n th 6 0 M o n th 7 2 M o n th 8 4 Decrese in WPAI subscores denotes improvement. b New-Rx ptients showed mintined improvement in WPAI subscores similr to All-Rx ptients (dt not shown). WPAI=work productivity nd ctivity impirment; TWPI=totl work productivity impirment; TAI=totl ctivity impirment; presenteeism=impirment while working; All-Rx=ll-treted ptient popultion; New-Rx=new prescription ptient popultion. ACKNOWLEDGEMENTS & DISCLOSURES F Kerdel hs received honorri from AbbVie, Amgen, Celgene, Jnssen, Leo, Pfizer, Eli Lilly, Novrtis, nd Stiefel for prticiption s speker; nd received grnts from AbbVie, Amgen, AstrZenec, Celgene, Jnssen, Eli Lilly, Novrtis, nd Pfizer, for prticiption s n investigtor. A Menter hs grnts nd honorri from AbbVie, Amgen, Jnssen Biotech, Inc., nd LEO Phrm for service on n dvisory bord, s consultnt, investigtor, nd speker; received grnts nd honorri from Allergn nd Eli Lilly for service on n dvisory bord, s consultnt nd investigtor; received grnts nd honorri from Boehringer Ingelheim for service on n dvisory bord nd s n investigtor; received grnts nd honorri from Novrtis, Pfizer, nd Xenoport for service s consultnt nd investigtor; received grnts from Ancor, Celgene, Dermir, Merck, Neothetics, Regeneron, nd Symbio/Mruho for service s n investigtor; nd received honorri from Glderm, nd Vite for service s consultnt. JJ Wu received reserch funding from AbbVie, Amgen, AstrZenec, Boehringer Ingelheim, Coherus Biosciences, Dermir, Eli Lilly, Jnssen, Merck, Novrtis, Pfizer, Regeneron, Sndoz, nd Sun Phrmceuticl Industries; he is consultnt for AbbVie, Amgen, Celgene, Dermir, Eli Lilly, Pfizer, Regeneron, Sun Phrmceuticl Industries, nd Vlent Phrmceuticls. M Bereswill, D Arikn, A Cmez, A Gnguli, nd WC Vldecntos re full-time slried employees of AbbVie nd my own stock/options. AbbVie funded the ESPRIT study (NCT ), contributed to its design nd prticipted in dt collection, nlysis nd interprettion of the dt, nd in writing, review, nd pprovl of the publiction. Medicl writing support ws provided by Deep Venkitrmni, PhD, of AbbVie.