SUPPLEMENTARY APPENDIX...SUPPLEMENTARY APPENDIX 3 Figure S3A. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for comparing the proportion of patients in

SUPPLEMENTARY APPENDIX

1

PURSUIT-Maintenance Study Group .........................................................................................3

Page

Retrospective Efficacy Data Exclusion ......................................................................................12

Early Detection of Active Tuberculosis......................................................................................14

Placebo-Induction Responder Clinical Outcomes ....................................................................16

Corticosteroid carry-over effects ................................................................................................17

SUPPLEMENTAL TABLES AND FIGURES

Table S1. Association Between Prognostic Factors Identified by the Stepwise Selection

Method and Proportion of Patients in Clinical Remission at Both Week 30 and 54;

Primary Analysis Population .................................................................................19

Table S2. Endoscopy Mayo Subscores at the Time of Dose Adjustment; Randomized

Patients in PURSUIT-M Who Had a Dose Adjustment (Golimumab Induction

Responders)............................................................................................................20

Table S3. Major Secondary Efficacy Endpoints: Golimumab-Induction Responders by

Induction Study ......................................................................................................21

Table S4. Antibodies to Golimumab by Concomitant Immunomodulator Use: Treated

Patients ...................................................................................................................22

Table S5. Summary of Key Safety Findings Per Hundred Patient-Years of Follow-up

Through Week 54; Treated Patients Who Were Randomized ...............................23

Table S6. Safety Summary: Treated Patients .........................................................................24


2

Table S7. Hazard Ratios (95% Confidence Intervals) for Comparing the Time to First

Infection Between the Golimumab and Placebo Groups by Concomitant

Medication Use at Baseline; Randomized Patients in PURSUIT-M .....................26

Figure S1. Study medication dosage adjustments during the 54-week maintenance study ....27

Figure S2A. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for

comparing the proportion of patients in clinical response through week 54 in the

golimumab 100 mg group vs. the placebo group by demographic characteristics at

baseline of an induction study; golimumab induction-responders ........................28

Figure S2B. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for


golimumab 100 mg group vs. the placebo group by UC disease characteristics at

baseline of an induction study; golimumab-induction responders ........................29

Figure S2C. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for


golimumab 100 mg group vs. the placebo group by concomitant UC medication

history; golimumab-induction responders .............................................................30

Figure S2D. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for



usage; golimumab-induction responders ...............................................................31

Figure S2E. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for


golimumab 100 mg group vs. the placebo group by stratification factors;

golimumab-induction responders...........................................................................32


3

Figure S3A. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for


golimumab 50 mg group vs. the placebo group by demographic characteristics at


Figure S3B. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for


golimumab 50 mg group vs. the placebo group by UC disease characteristics at


Figure S3C. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for



history; golimumab-induction responders .............................................................35

Figure S3D. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for



usage; golimumab-induction responders ...............................................................36

Figure S3E. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for


golimumab 50 mg group vs. the placebo group by stratification factors;

golimumab-induction responders...........................................................................37


4

The participating investigators for the PURSUIT-Maintenance Study Group were:

Australia

S Brown, W Connell (former PI), St Vincent's Hospital, Fitzroy, VIC; HS Debinski, Melbourne Gastrointestinal Investigation Unit, Cabrini Hospital, Malvern, Victoria; TH Florin,University of Queensland, Department of Medicine, Mater Heath Services’ Adult Hospital, South Brisbane, Queensland; PR Gibson, Monash University, Alfred Hospital, Melbourne, VIC, M Sparrow (former PI), Box Hill Hospital Department of Gastroenterology, Box Hill, VIC; DJ Hetzel, Department of Gastroenterology & Hepatology, Q7 North Wing, Royal Adelaide Hospital, North Terrace, Adelaide; S Jakobovits, The Alfred Hospital Department of Gastroenterology, Prahran, VIC; VP Kwan, Westmead Hospital, Westmead, NSW; R Leong, Bankstown Lidcombe Hospital Department of Gastroenterology, Bankstown, NSW; F Macrae, Royal Melbourne Hospital Colorectal Medicine & Genetics, Parkville, VIC; B Mitchell, Launceston General Hospital, Launceston, TAS; G Radford-Smith, Royal Brisbane and Women's Hospital Department of Gastroenterology and Hepatology, Herston, QLD

Austria

A Kaser, Universitätsklinik fur Innere Medizin, Gastroenerologie & Hepatologie, Innsbruck; W Reinisch, Universitätsklinik für Innere Medizin III, Vienna

Belgium

M De Vos, U.Z. Gent Gastro-enterology, Gent; O De Wit, Cliniques Universitaires St-Luc Gastroenterology, Brussels;GR d’Haens, Imelda General Hospital, Bonheiden; PJ Rutgeerts, University Hospital Gasthuisberg, University of Leuven (Katholieke Universiteit Leuven- KUL), Department of Medicine, Division of Gastroenterology, Leuven

Bulgaria

T Dimitrova, NMH 'Tsar Boris III', Sofia; R Draganova, 4th MHAT Gastroenterology Unit at 1st Internal Department, Sofia; N Kostov, 5th MultiProf. ile Hospital for Active Treatment Gastroenterology Department with Hematology Sector, Sofia; IA Kotzev, Clinic of Gastroenterology, University Multifunctional Hospital for Active Treatment “St. Marina”, Varna; Z Krastev, UMHAT 'Sveti Ivan Rilsky' Clinic of Gastroenterolgy, Sofia; IP Marinova, UMHAT 'Dr. Georgi Stranski' - Pleven First Clinical Base Clinic of Gastroenterology, Pleven; D Nikolovska, Medical Institute-Central Clinical Base-Ministry of Interior Clinic of Gastroenterology, Sofia; A Petrov, 'Tokuda' Hospital Dept. of Internal Medicine, Division of Gastroenterology, Sofia; PM Petrov, Gastroenterology Unit at Department of Gastroenterology, Endocrinology, Nephrology and Hematology University, Multifunctional Hospital for Active Treatment, Sofia; S Stoinov, UMHAT 'Tzaritza Ioanna' Clinic of Gastroenterology, Sofia; D Takov, MMA MHAT Sofia, Sofia; K Tchernev, UMHAT 'Alexandrovska' Clinic of Internal Medicine - Gastroenterology Department, Sofia; GN Vasileva, MHAT Rousse AD 3rd Therapeutical Department - Gastroenterology & Hepatology, Rousse


5

Canada

FH Anderson, Liver and Intestinal Research Centre, Vancouver, BC; C Bernstein, Health Sciences Centre, Winnipeg, MB; B Bressler, GIRI Gastrointestinal Research Institute, Vancouver, BC; W Depew, Division of Gastroenterology, Kingston, ON; B Feagan, London Health Science Centre, University Hospital, London, ON; C Harnarine, Harnarine Carlton (Private Practice), Chatham, ON; D Hemphill, Barrie GI Associates, Barrie, ON; A Khalil, North Walkerville Medical Centre Attn: Biljana Basic-Panic, Windsor, ON; E Larkai, Edwin Larkai Medical Professional Corporation, Saskatoon, SK; F Saibil, Sunnybrook Health Sciences Centre, Toronto, ON; RA Singh, Victoria, BC; TA Sylwestrowicz, Medical Digestive, Saskatoon, SK

Czech Republic

V Compel, Ordinace pro gastroenterologii a internu, Ceske Budejovice; P Klvana, Fakultni nemocnice Ostrava Revmatologicka ambulance, Ostrava-Poruba; O Sterba, Gastroenterologicka a Hepatologicka ambulance, Litomerice; M Volfova, Hepato-Gastroenterologie HK s.r.o., Hradec Kralove

Denmark

J Dahlerup, Aarhus Kommunehospital Medicinsk Afdeling V, Århus C; J Fallingborg, Aalborg Sygehus Syd Medicinski Gastroenterologisk Ambulatorium, Aalborg; K Lauritsen, Odense Universitetshospital Medicinsk Gastroenterologisk Afd. S, Odense; A Nielsen, Hvidovre Hospital Medicinsk Gastroenterologisk Afd. 439, Hvidovre

France

M Allez, M Lemann (former PI), Hôpital Saint-Louis Service de Gastro-entérologie, Paris Cedex 10; Y Bouhnik, Hopital Beaujon, Service de Gastro-entérologie, Clichy; JF Colombel, Centre Hospitalier Universitaire de Lille - Hôpital Claude H Service des Maladies de l'Appareil Digestif, Lille Cedex; JL Dupas, Centre Hospitalier Universitaire d Amiens Hopital Nord Service d'Hepato-Gastroenterologie, Amiens Cedex 1; X Hebuterne, Hopital de l’Archet 2, Service de Gastro-entérologie et de nutrition, Nice Cedex 3; F Zerbib, Hôpital Saint André CHU de Bordeaux Service d'Hepato-Gastro-Enterologie, Bordeaux

Germany

V Aldinger, Aldinger Volker Praxis fuer Innere Medizin Gastroenterologie, Hassloch, RP; B Bokemeyer, Gastroenterologische Praxis Minden, Minden, NW; C Buening, H Lochs (former PI), Charité Universitaetsmedizin Berlin - Campus Charité Mitte, Berlin, BE; H Kellner, Kellner Herbert, Muenchen, BY; JW Konturek, Elbe-Kliniken Stade-Buxtehude GmbH Gastroenterologie Stoffwechsel- und Infektionskrankheiten, Stade, NI; T Krummenerl, Gastroenterologische Gemeinschaftspraxis Praxis am Germania Campus, Muenster, NW; A Raedler, Asklepios Westklinikum Abt. fuer Innere Medizin / Gastroenterologie, Hamburg, HH; W Schmidt, Universitaetsklinikum Bochum - St. Josef-Hospital, St. Josef-Hospital, Bochum, NW; S Schreiber, Universitaetsklinikum Schleswig-Holstein Campus Kiel, Kiel, SH; U Seidler, Medizinische Hochschule Hannover Gastroenterologie und Hepatologie, Hannover, NI; A Sturm, Charité - Campus Virchow Klinikum Med. Klinik (Hepatologie/Gastroenterologie), Berlin, BE;


6

Hungary

I Altorjay, Debreceni Egyetem Orvos- és Egeszsegtudomanyi Centrum 2nd Dept. of Internal Medicine Division of Gastroenterology, Debrecen; L Bene, Peterfy S. u. Hospital, Dept. "E" of Internal Medicine, Gastroenterology, Budapest; Z Dobronte, Vas County Markusovszky Hospital, Dept. of Internal Medicine, Gastroenterology, Szombathely; I Fazekas, Bekes County Pándy Kálmán Hospital 1st Dept. of Medicine and Gastroenterology, Gyula; J Fiók, Sopron Medical SMO, Sopron; A Kiraly, University of Pecs, Faculty of Medicine, 3rd Dept. of Internal Medicine, Pécs; L Lakatos, Veszprem Megyei Csolnoky Ferenc Korhaz 1st Department of Internal Medicine, Veszprém; L Madacsy, Fejer County Szt. Gyorgy Hospital, 1st Dept. of Internal Medicine, Székesfehérvár; L Mádi-Szabó, Clinexpert SMO Gastroenterology, Budapest; F Nagy, Szeged University of Science Medical Science Center 1st Dept. of Internal Medicine, Szeged; P Orosz, Borsod-Abauj Zemplen County University and Teaching Hospital, 2nd Dept. of Internal Medicine, Gastroenterology, Miskolc; G Pecsi, Karolina Hospital Department of Internal Medicine Gastroenterology, Mosonmagyarovar; E Peterfai, DRC Gyogyszervizsgalo Kozpont Kft, Balatonfured; I Racz, Petz Aladar County and Teaching Hospital, 1st Dept. of Medicine and Gastroenterology, Györ; A Salamon, Clinfan Kft. Division of Gastroenterology, Szekszárd; Z Tulassay, Semmelweis University 2nd Dept. of Internal medicine, Budapest; L Ujszaszy, Miskolci Semmelweis Ignac Egeszegugyi Kozpont es Egyetemi Oktato Korhaz Nonprofit Kft., 1st Dept. of Medicine, Gastroenterology, I. Belgyogyaszat, Gasztroenterologia, Miskolc; M Varga, Réthy Pál Hospital Department of Internal Medicine, Békéscsaba; L Varga-Szabó, Szt. Pantaleon County Hospital 1st Dept. of Medicine Gastroenterology, Dunaujvaros

India

P Boddu, Osmania General Hospital Department of Gastroenterology, Hyderabad, ANDH PRAD; A Chandra, Department of Surgical Gastroenterology, Chatrapati Shahuji Maharaj Medical University, Lucknow, Uttar Pradesh; H Devarbhavi, St John’s Medical College Hospital, Gastroenterology, Bangalore, KARNA; M Kalla, S. R. Kalla Memorial Gastro and General Hospital, Jaipur; PM Krishna, EP Veerraju (former PI), Andhra Medical College Department of Gastroenterology, Vishakapatnam, ANDH PRAD; G Makharia All India Institute of Medical Sciences (AIIMS), Department of Gastroenterology, New Delhi, DELHI; GC Pai, Kasturba Hospital Department of Gastroenterology, Manipal, KARNA; NV Pai, Frant Medical Foundation, Ruby Hall Clinic, Pune, Maharashtra; JS Rajkumar, Lifeline Multispeciality Hospital Department of Gastroenterology, Chennai, TAMILNADU; DN Reddy, Asian Institute of Gastroenterology, Hyderabad, Andhra Praddesh; SC Samal, Department of Gastroenterology, Apollo Hospitals Education and Research Foundation, Jubilee Hills, Hyderabad; LV Shimpi, Jehangir Clinical Development Centre Pvt. Ltd., Jehangir Hospital Premises, Pune, Maharashtra; A Sood, Dayanand Medical College & Hospital, Department of Gastroenterology, Ludhiana, Punjab; DV Sreenivas, Care Hospital Department of Gastroenterology, Hyderabad, ANDH PRAD; V Thorat, Poona Hospital and Research Centre Department of Gastroenterology, Pune, MAHARA; G Verma, Kamineni Wockhardt Heart Hospital Gastroenterology, Hyderabad, ANDH PRAD


7

Israel

A Fich, Soroka Medical Center Department of Gastroenterology, Beer Sheva; Z Fireman, Gastroenterology Department, Hillel-Yaffe Medical Center, Hadera; S Fishman, Z Halpern (former PI), Tel Aviv Sourasky Medical Center, Institute of Gastroenterology and Liver Diseases, Tel Aviv; G Fraser, Rabin Medical Center Gastroenterology, Petah-Tikva; E Goldin, Hadassah University Hospital - Ein Kerem Services of Gastroenterology, Jerusalem; D Keret, Clalit Health Services Gastroenterology, Jerusalem; FM Konikoff, Sapir Medical Center Meir Hospital Gastroenterology Institute, Kfar Sava; A Lavy, Bnai Zion Medical Center Gastroenterology, Haifa; E Melzer, Kaplan Medical Center Gastroenterology Inst., Rechovot; E Nussinson, Ha’Emek Medical Center, Gastroenterology Unit, Afula; D Rachmilewitz, Shaare Zedek Medical Center Gastroenterology, Jerusalem; R Safadi, Holy Family Hospital Liver Unit, Nazareth; E Scapa, Assaf Harofeh Medical Center, Institute of Gastroenterology, Hepatology and Nutrition, Beer Yaakov

Japan

T Ando, Nagoya University Hospital Shoukakinaika, Nagoya-shi; Y Araki, Medical corp. Takano group Kurume Coloproctology Center Ichoka, Kurume-shi; T Ashida, Tokushukai Sapporo Higashi Tokushukai Hospital EnshoseiChosikkanseiCenter, Sapporo-shi; T Hisamatsu, Keio University Hospital Shokakinaika, Shinjuku-ku; J Kato, Okayama University Hospital, Okayama-shi; T Matsui, Fukuoka University Chikushi Hospital Shokakika, Chikushino-shi; T Matsumoto, Kyushu University Hospital Shokakannaika, Fukuoka-shi; K Mitsuyama, Kurume University Hospital ShokakibyoCenter, Kurume-shi; S Motoya, JA-Hokkaido Sapporo-Kosei General Hospital Daiichishokakika, Sapporo-shi; M Nagahori, Tokyo Medical and Dental University Hospital, Faculty of Medi Shokakinaika, Bunkyo-ku; S Nakamura, T Matsumoto (former PI), The Hospital of Hyogo College of Medicine Shokakinaika, Nishinomiya-shi; Y Sameshima, Sameshima Hospital Ichoka/Naika, Kagoshima-shi; A Shiotani, K Haruma (former PI), Kawasaki Medical School Hospital, Kurashiki-shi; Y Suzuki, Toho University Sakura Medical Center ShokakiCenter, Sakura-shi; M Takazoe, Social Insurance Central General Hospital Shokakinaika, Shimjuku-ku; S Tanaka, Hiroshima University Hospital Shoukakinaika, Hiroshima-shi; K Tatemoto, Tokyo Women's Medical University Hospital ShokakiNaika, Shinjuku-ku; S Umegae, Yokkaichi Shakai Hoken Hospital Geka/Daicho/Komonbyo(IBD)Center, Yokkaichi-shi; K Watanabe, Osaka City University Hospital Shokakinaika, Osaka-shi; S Watanabe, Juntendo University Hospital Department of Gastroenterology, Bunkyo-ku; S Yazumi, H Ito (former PI), Kitano Hospital The Tazuke Kofukai Med Research Shokakinaika, Osaka-shi

Latvia

A Danilans, P. Stradina Clinical University Hospital, Riga; G Delmans, Daugavpils Regional Hospital, Daugavpils

Lithuania

A Irnius, Mykolo Marcinkeviciaus hospital Department of Gastroenterology, Vilnius; L Kupcinskas, Kaunas Medical University Hospital Department of Gastroenterology, Kaunas


8

The Netherlands

DJ Bac, Gelderse Vallei Ziekenhuis Ede Internal Medicine and Gastroenterology, Ede; G Dijkstra, Universitair Medisch Centrum Groningen secretariaat maag-darm en leverziekten huispostcode, Groningen; DW Hommes, Leids Universitair Medisch Centrum Afdeling MDL, Leiden; CY Ponsioen, PCF Stokkers (former PI), Academisch Medisch Centrum, Amsterdam; AA van Bodegraven, VU Medisch Centrum MDL, Amsterdam; CJ van der Woude, Department of Gastroenterology and Hepatology, Erasmus MC Rotterdam, Rotterdam

New Zealand

MM Arnold, Hawkes Bay Hospital, Hastings; M Barclay, Christchurch Hospital Gastroenterology, Christchurch; J Brooker, Waikato Hospital Respiratory / Renal / Gastroenterology, Hamilton; S Parry, Department of Gastroenterology and Hepatology, Middlemore Hospital, Otahuhu, Auckland; M Schultz, Dunedin Hospital Gastroenterology, Dunedin; ID Wallace, Shakespeare Specialist Group, Milford, Auckland

Poland

A Bochenek, Centrum Badawcze Wspolczesnej Terapii Prywatny Gabinet Lekarski Anna Bochenek, Warszawa; M Chelstowska, Szpital Specjalistyczny Sw.Wojciecha SPZOZ Poradnia Gastroenterologiczna, Gdansk; J Chojnacki, SPZOZ Uniwersytecki Szpital Klinicczny nr 5 im., Gen. Dyw. B. Szareckiego, Uniwersytetu Medycznego w Lodzi, Klinika Gastroenterologii i Chorob Wewnetrznych, Lodz; I Ciecko-Michalska, Szpital Uniwersytecki w Krakowie Klinika Gastroenterologii Hepatologii oraz Chor. Zakaznych, Krakow; Z Hebzda, 5 Wojskowy Szpital Kliniczny z Poliklinika SPZOZ Klinika Chorob Wewnetrznych, Krakow; D Henzler, Szpital Wojewodzki w Opolu Oddzial Chorob Wewn. Pododdzial Gastroenterologii i Hematol, Opole; Z Jamrozik-Kruk, Wojewodzki Szpital Specjalistyczny im.NMP Oddz. Gastroenterol. i Chorob Wewn., Czestochowa; D Kleczkowski, Endoskopia Sp. z. o.o., Sopot; A Kopon, NZOZ Nasz Lekarz Praktyka Grupowa Lekarzy Rodzinnych z Przychodnia Specj., Torun; W Laszewicz, Samodzielny SPZOZ Wojewodzki Szpital, Zespolony im. J. Sniadeckiego w Bialymstoku, III Oddzial Chorob Wewnetrznych I Gastroenterologii, Bialystok; A Mamos, Med-Gastr Specjalistyczne Gabinety Lekarskie, Lodz; J Marecik, SPZOZ Wojewodzki Szpital Specjalistyczny im. L. Rydygiera Zaklad Endoskopii, Krakow; K Niezgoda, 110 Szpital Wojskowy Oddzial Chorob Wewnetrznych, Elblag; J Rudzinski, 10 Wojskowy Szpital Kliniczny z Poliklinika Kliniczny Oddzial Gastroenterologii, Bydgoszcz; G Rydzewska, Centralny Szpital Kliniczny MSWiA Klinika Chorob Wewn. i Gastroenterologii, Warszawa; M Slomka, Samodz.Publi.Szpital Kliniczny nr 4 w Lublinie Klinika Gastroenterologii z Pracownia Endoskopowa, Lublin; M Szura, Specjalistyczne.Centrum Diagnostyczno.-Zabiegowe Medicina Sp. z.o.o., Krakow; A Wiechowska-Kozlowska, NZOZ Sonomed, Szczecin


9

Romania

DE Dobru, Spitalul Clinic Judetean Mures Medicala IV - Gastroenterologie II, Targu Mures; LS Gheorghe, Inst. Cl. Boli Digestive Transplant Hepatic Fundeni Clinica de Gastroenterologie si Hepatologie, Bucuresti; A Goldis, S.C. Cabinet Particular Policlinic Algomed, Timisoara; F Ionita-Radu, Spitalul Clinic de Urgenta Militar Central Dr. Carol Davila Clinica de Gastroenterologie si Hepatologie, Bucuresti; O Pascu, Spitalul Clinic de Urgenta "Prof. . Dr. Octavian Fodor" Clinica Medicala III - Medicina Interna II, Cluj-Napoca; C Stanciu, Institutul de Gastroenterologie si Hepatologie Iasi Clinica Medicala II – Gastroenterologie, Iasi; R Voiosu, Spitalul Clinic Colentina Medicina Interna, Bucuresti

Russian Federation

B Alikhanov, 7 Central Military Clinical Aviation Hospital of Ministry of Chair of Therapy, Moscow; I Kholina, SPb SHI "City Hospital #9" Cardiology, St. Petersburg; O Khrustalev, Yaroslavl Regional Clinical Hospital, Yaroslavl; M Livzan, SEI of HPE “Omsk State Medical Academy of RosZdrav”, Omsk; O Sablin, Center of Emergency and Radiation Medicine Gastroenterology, St. Petersburg; V Simanenkov, City Hospital #26, St. Petersburg; E Valuyskich, SI SRI of Physiology SB RAMS Gastroenterology, Novosibirsk

Serbia

M Cvetkovic, N Milinic (former PI), Clinical Hospital Center Bezanijska Kosa, Department of Gast, Belgrade; G Golubovic, Clinical Center Zemun Gastroenterology, Zemun; G Jankovic, Clinical Center of Serbia, Clinic for Gastroenterology and Hepatology, Belgrade; N Jojic, Clinical Hospital Center Zvezdara Clinic for Gastroenterology and Hepatology, Belgrade; A Nagorni, Clinical Center of Nis Clinic for gastroenterology and hepatology, Nis; D Tarabar, Military Medical Academy Clinic for Gastroenterology, Belgrade

Slovak Republic

I Bunganic, MUCO, Gastroenterologicka ambulancia, Presov; M Gregus, NZZ-KM Management s.r.o., Gastroenterologicke oddelenie, Nitra

Slovakia

D Balaz, PIGEAS s.r.o., Sucany; I Bunganic, Gastro I s.r.o., Presov; S Cernok, NsP Nove Mesto nad Vahom n.o. Gastroenterologicka ambulancia, Nove Mesto nad Vahom; M Gregus, KM Management spol. s. r.o. ZZ-Gastroenterologicke a hepatologicke centrum Nitra, Nitra; T Hlavaty, FNsP Bratislava - Nemocnica Ruzinov 5. Interna klinika, Bratislava

South Africa

O Mwantembe, Clinical Research Unit, University Prestoria, Pretoria; KE Pettengell, Parklands Hospital, Overport, KZ-Natal; C van Rensburg, Louis Leipoldt Medical Centre, Cape Town, W Cape; JP Wright, Kingsbury Hospital, Claremont, W Cape


10

Sweden

R Befrits, Karolinska Universitetssjukhuset Solna Gastrocentrum Medicin, Stockholm; P Karlen, Södersjukhuset Gastroenterologi / Hepatologi, Stockholm

Ukraine

O Datsenko, Kharkiv Med. Acad.of Post-graduate Educ.City Clin. Hosp.#2, Kharkiv; A Dorofeyev, Central City Clinical Hospital #3, Department of Gastroenterology, Donetsk State Medical University named after M.Gorkyy, Chair of Internal Medicine #2, Donetsk; AI Golovchenko, Military Medical Center of the Air Force of Ukraine, National Center of Health, Clinic of Gastroenterology, Vynnytsya; N Gubergrits, Donetsk State Medical University n.a.M.Gorkyy Chair of Internal Diseases # 1.b.on the DRTMC, Donetsk; N Kharchenko, P.L.Shupyk NMA of Post -graduate Educ. City Clin.Hosp.#8 Dept. of Gastroenterology and Dietology, Kyiv; V Klymenko, Zaporizhzhia Medical University DCH st Zap2 SI "Pridnipr railw."Dept.of surg., Zaporizhzhya; V Neyko, Central City Clinical Hospital, Therapeutic Department, Ivano-Frakovsk State Medical University, Chair of Propedeutics of Internal Diseases, Ivano-Frankovsk; A Petrov, Crimean St.Med.Uni.b.on Repub.clin.hosp. n.Semashko chair of ther.# 1 with the c. in endocrinology, Simferopol;Y Zakharash, Hospital of Military Medical division of Security Service of Ukraine, National Medical University named after O.O.Bogomolets, Chair of Faculty Surgery #1, Kyiv

USA

M Avila, Research Consultants Group, Hialeah, FL; C Barish, Wake Research Associates LLC, Raleigh, NC; R Bhandari, Bhandari Baj Raj, Monroe, LA; R Bloomfeld, Wake Forest University Baptist Medical Center, Internal Medicine/Gastroenterology, Winston Salem, NC; VD Bohman Jr, Northern Utah Gastroenterology, Logan, UT; SD Bologna, Center for Digestive Health, Troy, MI; M Bukhari, Gastroenterology Specialist, Morganton, NC; T Chami, Florida Medical Clinic P.A. Clinical Research Division, Zephyrhills, FL; W Chey, Rochester Institute for Digestive Diseases & Sciences Inc, Rochester, NY; L Cohen, Research Associates of New York, New York, NY; J Collins, Oregon Health & Science University, Portland, OR; A Coppola Jr, Little Rock Diagnostic Clinic, Little Rock, AR; I Crespo, Advanced Research Institute, Trinity, FL; W deVilliers, University of Kentucky Medical Center, Lexington, KY; W Emlich Jr, Remington-Davis Inc., Columbus, OH; A Ertan, Ertan Atilla (private practice), Huston, TX; JM Fields, Center for Clinical Studies, Inc., Dearborn, MI; M Filippone, Christiana Care Research Institute, Newark, DE; F Fowler, Carolina Digestive Health Associates, Harrisburg, NC; W Futch, Southern Gastroenterology Associates, New Bern, NC; J Goff, Rocky Mountain Clinical Research, Denver, CO; GL Gordon, Center for Digestive and Liver Diseases, Inc., Mexico, MO; N Grandhi, Gastroenterology Research Consultants of Greater Cincinnati, Cincinnati, OH; D Grunkemeier, G Koval (former PI), The Oregon Clinic-West Hills Gastroenterology, Portland, OR; JW Hamilton, Dean and St. Mary's Outpatient Center, Madison, WI; S Hanauer, University of Chicago Hospitals, Chicago, IL; RN Hansen, Arapahoe Gastroenterology, PC, Littleton, CO; JS Hanson, Charlotte Gastroenterology and Hepatology, P.L.L.C., Charlotte, NC; W Harlan, Asheville Gastroenterology Associates P.A. The Endoscopy Center, Asheville, NC; A Hemaidan, Advanced Medical Research Center, Port Orange, Fl; P Higgins, University of Michigan Office of Dr. Higgins, Ann Arbor, MI; J Hoekstra, National Clinical Research Inc.-Richmond Jim McKenney, Richmond, VA; R Holbrook, Central Sooner Research, Norman, OK; W Holderman, Digestive Health Specialists, Tacoma, WA;


11

USA (cont.)

R Huey, E Williams (former PI), Digestive Health Specialists Clinical Research, Tupelo, MS; IE Ibegbu, Kingston, NC; D James, Tulsa, OK; J Katz, Case Medical Center Gastroenterology, Cleveland, OH; B Kaufman, Atlantic Gastroenterology Associates Atlantic Gastroenterology Associates P.A., Egg Harbor Twp., NJ; M Kestell, Spokane Digestive Disease Center, Spokane, WA; RK Kottoor, University of Florida, Jacksonville, FL; S Lawrence, R Hansen (former PI), Arapahoe Gastroenterology Associates P.C., Littleton, CO; B Leman, Iowa Digestive Disease Center, Clive, IA; D Lewis, Arkansas Primary Care Clinic PA, Little Rock, AR; S Lichtiger, Simon Lichtiger MD, New York, NY; E Loftus, W Sandborn (former PI), Mayo Clinic – Rochester, Rochester, MN; J Lowe, Advanced Research Institute, Ogden, UT; P Malik, Gastroenterology Associates of Tidewater, Chesapeake, VA; P Mannon, University of Alabama Medical Center Clinical Research Program, Birmingham, AL; J Marion Jr, Present Chapman Marion Steinlau Lisl Huffaker-research, New York, NY; R Matsuyama, Capital Gastroenterology Consultants of Sacramento, Roseville, CA; A McNair Jr, Digestive Health Center PA, Pascagoula, MS; PB Miner, Oklahoma Foundation for Digestive Research, Oklahoma City, OK; K Mirkin, Gastroenterology Associates of Northern Virginia, Fairfax, VA; F Nammour, Odyssey Research Services Odyssey Research, Fargo, ND; F Opper, Hanover Medical Specialists P.A., Wilmington, NC; WM Pandak, McGuire DVAMC, Richmond, VA; L Perera, Medical College Of Wisconsin Division of GI & Hepatology, Milwaukee, WI; R Phillips, Gastroenterology Group of Naples, Naples, FL; V Pratha, Clinical Applications Laboratories Inc., San Diego, CA; E Rock, PMA Medical Specialists, Limerick, PA; M Safdi, Consultants for Clinical Research Inc., Cincinnati, OH; B Salzberg, Atlanta Gastroenterology Specialist PC, Suwanee, GA; PL Schroeder, Cotton-O’Neil Clinical Research Center, Digestive Health, Topeka, KS; DA Schwartz, Vanderbilt University Medical Center, Nashville, TN; J Schwartz, Northwest Gastroenterologists S.C., Arlington Heights, IL; I Shafran, Shafran Gastroenterology Center, Winter Park, FL; I Stein, Frist Clinic, Nashville, TN; D Suiter, Health Science Research Center, Pratt, KS; RE Tepper, Long Island Clinical Research Associates, LLP, Great Neck, NY; C Thomson, Digestive and Liver Specialists SMO Management for Dr. Thomson- Medicus Alliance, Sugar Land, TX; J Valentine, University of Florida Shands Endoscopy Center, Gainesville, FL; R Vasudeva, Consultants in Gastroenterology, Columbia, SC; R Wanamaker, Center for Digestive and Liver Health, Savannah, GA; RA Wohlman, Northwest Gastroenterology Associates, Bellevue, WA; L Wruble, Memphis Gastroenterology Group PC, Germantown, TN; ZH Younes, Gastroenterology Center of the Mid South, PC, Germantown, TN; A Zwick, Zwick Andrew M.D. (Private Practice), Boca Raton, FL


12

Retrospective Efficacy Data Exclusion

During review of the Biological Licensing Application for golimumab as treatment for ulcerative

colitis, a routine Food and Drug Administration (FDA) audit identified discrepancies at a

PURSUIT-SC study site in Poland that were not considered to be significant Good Clinical

Practice violations.

A subsequent follow-up audit conducted by Janssen Research & Development, LLC on June 13

and 14, 2013 raised additional concerns about discrepancies at this site. After informing all

relevant Health Authorities (FDA, European Medicines Evaluation Agency, etc.) and

Institutional Review Boards/International Ethics Committees on July 2, 2013, Janssen Research

& Development, LLC made the decision to exclude patient efficacy data from this site.

Golimumab-induction responders comprise the primary analysis population in this study. Based

on the design of the clinical program, golimumab-induction responders who completed

PURSUIT-SC were eligible for continued therapy and were randomized in this maintenance

study. Among the patients enrolled at this site, seven golimumab-induction responders

participated in PURSUIT-M. The efficacy results summarized in the present paper exclude data

for these seven patients. An updated CONSORT figure of the primary efficacy analysis

population (N=456) is shown below.

As noted in the manuscript, the exclusion of data from this site had a minimal impact on the

efficacy results and does not alter the conclusions of the study.


13


14

Early Detection of Active Tuberculosis

To aid in the early detection of tuberculosis reactivation or new tuberculosis infection during trial

participation, patients must be evaluated for signs and symptoms of active tuberculosis at

scheduled visits or by telephone contact approximately every 8 to 12 weeks. The following

series of questions is suggested for use:

• “Have you had a new cough of > 14 days’ duration or a change in a chronic cough?”

• “Have you had any of the following symptoms:

− Persistent fever?

− Unintentional weight loss?

− Night sweats?”

• “Have you had close contact with an individual with active tuberculosis?” (If there is

uncertainty as to whether a contact should be considered “close,” a physician specializing

in tuberculosis should be consulted.)

If the evaluation raises suspicion that a patient may have tuberculosis reactivation or new

tuberculosis infection, an immediate and thorough investigation should be undertaken, including,

where possible, consultation with a physician specializing in tuberculosis. During this period of

evaluation treatment with study agent will be interrupted until the investigator is sure no active

infection is present.

Investigators should be aware that tuberculosis reactivation in immunocompromised patients

may present as disseminated disease or with extrapulmonary features. Patients with evidence of

active tuberculosis must immediately discontinue study agent and should be referred for

appropriate treatment.

Patients who experience close contact with an individual with active tuberculosis during the

conduct of the trial must have a repeat chest radiograph, a repeat diagnostic tuberculosis test


15

(consisting of both a tuberculin skin test and a QuantiFERON-tuberculosis Gold test), and, if

possible, referral to a physician specializing in tuberculosis to determine the patient’s risk of

developing active tuberculosis and whether treatment for latent tuberculosis is warranted.

During this period of evaluation treatment with study agent will be interrupted until the

investigator is sure no active infection is present. For the purposes of this trial, a positive result

from either the tuberculin skin test or

For patients at investigative sites in South Africa, a yearly QuantiFERON-tuberculosis Gold test

is required.

the QuantiFERON-tuberculosis Gold test should be

considered detection of latent tuberculosis. A patient whose initial QuantiFERON-tuberculosis

Gold test result is indeterminate should have the test repeated. The results of the test should be

discussed by the investigator and medical monitor. If treatment for latent tuberculosis is

recommended and the patient continues in the trial, treatment must be initiated prior to or

simultaneously with the administration of further study agent. Patients who discontinue

treatment for latent tuberculosis prematurely or who are noncompliant with therapy must

immediately discontinue further administration of study agent and be encouraged to return for all

subsequent scheduled study visits.


16

Placebo-Induction Responder Clinical Outcomes

Clinical response, clinical remission, and mucosal healing, all at Week 30 and at Week 54, were

evaluated in patients who were enrolled into this maintenance study but were not randomized (ie,

nonrandomized placebo-induction responders, placebo- induction nonresponders, and

golimumab-induction nonresponders in PURSUIT-IV or PURSUIT-SC).

Among the 764 nonrandomized patients who received maintenance therapy, 129 patients were in

clinical response to placebo at Week 6 in an induction study (ie, placebo-induction responders)

and continued to receive placebo. A total of 14.7% (19 patients) of placebo-induction responders

terminated study participation. The most common reason was “Other”, reported by 8.5% (11

patients). Overall, 123 placebo-induction responders (6 patients from 3 sites were excluded due

to site’s noncompliance with good clinical practice) were evaluable for efficacy of clinical

response, clinical remission, and mucosal healing, all at Week 30 and at Week 54. Among

placebo-induction responders, 45.5% and 36.6% were in clinical response at Week 30 and at

Week 54, respectively. Among placebo-induction responders, 30.1% and 25.2 % were in clinical

remission at Week 30 and at Week 54, respectively. Among placebo-induction responders,

46.3% and 34.1% had mucosal healing at Week 30 and at Week 54, respectively.


17

Corticosteroid carry-over effects

Patients entering either induction trial had to be receiving a stable dose of corticosteroids for at

least 2 weeks and the dose remained stable for the duration of the induction trial. As mandated

by the protocol, patients who increased their corticosteroid dose during induction were not

eligible for the maintenance trial. The median average daily prednisone equivalent corticosteroid

dose (excluding budesonide) at Week 0 of this maintenance trial was 20.00 mg/day for the 100

mg (IQ range, 15.00 to 30.00), 50 mg (IQ range: 12.50 to 25.00), and placebo (IQ range, 13.65 to

30.00) groups.

A prespecified subgroup analysis (odds ratio and the associated 95% confidence interval of each

golimumab dose group versus placebo based on the logistic regression model that includes

factors for treatment group, clinical remission status at baseline and induction dose factor) was

performed (see table below). Subgroups of patients who received <20 mg/day, 20 mg/day or

greater, budesonide, and no corticosteroids (Supplemental Appendix Figures S2D [golimumab

100 mg] and S3D [golimumab 50 mg]) were included in these analyses. The sample size of the

subgroup of patients receiving budesonide was too small for evaluation. For the golimumab 100

mg maintenance group, patients receiving <20 mg/day (odds ratio, 3.2) and those not receiving

corticosteroids (odds ratio, 3.4) were slightly more likely to maintain clinical response through

week 54 compared with the overall efficacy analysis population (odds ratio 2.2); whereas,

patients receiving 20 mg/day or greater (odds ratio, 1.4) were slightly less likely to achieve the

primary endpoint. On the contrary, for the golimumab 50 mg maintenance group, compared

with the primary analysis population (odds ratio, 2.0), patients receiving <20 mg/day (odds ratio,

1.0) and those not receiving corticosteroids (odds ratio, 1.7) were slightly less likely to maintain


18

clinical response through week 54; whereas, patients receiving 20 mg/day or greater (odds ratio,

3.7) were slightly more likely to achieve the primary endpoint.

The results of subgroup analyses for those who received ≥30 mg/day prednisone-equivalent and

those who received ≥40 mg/day prednisone-equivalent are shown in Table 1. Please note that the

number of patients receiving ≥40 mg/day prednisone-equivalent is limited because eligible

patients for this maintenance trial could not be receiving more than 40 mg/day prednisone-

equivalent

Table 1. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for comparing the proportion of patients in clinical response through week 54 in the golimumab 50 mg and 100 mg groups vs. the placebo group by corticosteroid subgroup

---Placebo--- ------------------Golimumab 50 mg------------------ ----------------Golimumab 100 mg------------------

n % n % Odds ratio (95% CI) P-value n %

Odds ratio (95% CI) P-value

All patients 154 31.2 151 47.0 2.0 (1.2, 3.2) .010 151 49.7 2.2 (1.4, 3.6) <.001

None 66 30.3 71 43.7 1.7 (0.8, 3.4) .167 69 59.4 3.4 (1.6, 7.0) .001

<20 mg/day 24 33.3 24 29.2 1.0 (0.2, 3.8) .817 24

50.0 3.2 (0.8, 12.3) .101

≥20 mg/day 59 32.2 51 60.8 3.7 (1.6, 8.7) .023 54 37.0 1.4 (0.6, 3.2)

.723

≥30 mg/day 28 46.4 18 61.1 2.9 (0.59, 13.81) .429 26 34.6 0.7 (0.20, 2.37) .569

≥40 mg/day 17 47.1 8 62.5 NE (NE, NE) NE 12 33.3 NE (NE, NE) NE

Key: CI, confidence interval

The inconsistency of these efficacy results makes it difficult to draw definitive conclusions on

any corticosteroid carry-over effects.


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Table S1. Association Between Prognostic Factors Identified by the Stepwise Selection Method and Proportion of Patients in Clinical Remission at Both Week 30 and 54; Primary Analysis Population

Baseline Measurements

Odds Ratioa,b

95% Confidence

Intervala

p-Valuea Mayo score 0.750 (0.635, 0.885) <.001 Log- transformed fecal lactoferrin 0.779 (0.614, 0.988) .040 Albumin 4.152 (1.828, 9.428) <.001 a Based on a logistic regression model with clinical remission at both week 30 and week 54 as

the response variable and treatment group and prognostic factors identified by the stepwise selection method as covariates.

b Odds ratio per unit increase. An odds ratio of less than 1 indicates that lower baseline measurement is associated with higher proportion of patients in clinical remission.


20

Table S2. Endoscopy Mayo Subscores at the Time of Dose Adjustment; Randomized Patients in PURSUIT-M Who Had a Dose Adjustment (Golimumab Induction Responders)

Placebo

Golimumab

Total 50 mg 100 mg

Randomized patients in C0524T18 who had a dose adjustment, n 75 51 43 169

Endoscopy subscore at the time of dose adjustment, n (%)

na 73 50 42 165

0 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

1 7 (9.6) 7 (14.0) 1 (2.4) 15 (9.1)

2 44 (60.3) 23 (46.0) 20 (47.6) 87 (52.7)

3 22 (30.1) 20 (40.0) 21 (50.0) 63 (38.2)

a Patients who had an endoscopy subscore at the time of dose adjustment.


21

Table S3. Major Secondary Efficacy Endpoints: Golimumab-Induction Responders by Induction Study

PURSUIT-IV PURSUIT-SC Golimumab Golimumab Placebo 50 mg 100 mg Placebo 50 mg 100 mg Variable (N=30) (N=28) (N=31) (N=124) (N=123) (N=120) Clinical remissiona,b, n (%)

at both weeks 30 and 54 6 (20.0) 10 (35.7) 10 (32.3) 18 (14.5) 25 (20.3) 32 (26.7)

Mucosal healinga,b, n (%)

at both weeks 30 and 54 10 (33.3) 14 (50.0) 16 (51.6) 31 (25.0) 49 (39.8) 48 (40.0)

Maintained remission through week 54a,b,c, n (%) 8 12 8 46 40 46

2 (25.0) 7 (58.3) 3 (37.5) 11 (23.9) 12 (30.0) 18 (39.1) Corticosteroid-free remission at week 54 a,b,d

Receiving corticosteroids at PURSUIT-M baseline, n 19 15 20 68 63 62

Maintained clinical remission through week 54 and corticosteroid-free at week 54 6 (31.6) 5 (33.3) 5 (25.0) 10 (14.7) 17 (27.0) 14 (22.6)

a. Patients who had a prohibited change in ulcerative colitis medication, an ostomy or colectomy, a dose adjustment, or discontinued study agent due to lack of therapeutic effect prior to the designated analysis timepoint are considered not to be in clinical remission, corticosteroid-free clinical remission, or have mucosal healing.

b. Patients who had all 4 Mayo subscores missing at week 30 (or at week 54) are considered not to be in clinical remission at week 30 (or at week 54). Patients who had a missing endoscopy subscore at week 30 or week 54 are considered to not have mucosal healing.

c. Includes patients who were in clinical remission at baseline of this maintenance trial. d. Patients who had a missing value in corticosteroid use at week 54 had their last value carried forward. Key: PURSUIT-IV, Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment-Intravenous; PURSUIT-SC,

Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment-Subcutaneous; PURSUIT-M, Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment-Subcutaneous


22

Table S4. Antibodies to golimumab by concomitant immunomodulator use: Treated Patients

Placeboa Golimumab Placebob

(Randomized) 50 mg 100 mg Combined

(Nonrandomized) Golimumab

100 mg Total Patients receiving immunomodulators, n 52 47 258 305 15 372

Patients with appropriate samples, n 52 47 248 295 15 362 Patients positive for antibodies to golimumab at any time, n (%) 1 (1.9) 1 (2.1) 2 (0.8) 3 (1.0) 0 (0) 4 (1.1) Patients negative for antibodies to golimumab, n (%) 51 (98.1) 46 (97.9) 246 (99.2) 292 (99.0) 15 (100) 358 (98.9)

Patients not receiving immuno-modulators, n 104 107 531 638 41 783

Patients with appropriate samples, n 103 105 492 597 41 741 Patients positive for antibodies to golimumab at any time, n (%) 10 (9.7) 3 (2.9) 13 (2.6) 16 (2.7) 2 (4.9) 28 (3.8) Patients negative for antibodies to golimumab, n (%) 93 (90.3) 102 (97.1) 479 (97.4) 581 (97.3) 39 (95.1) 713 (96.2)

a. Patients who were in clinical response to golimumab induction dosing and were randomized to placebo on entry into this maintenance trial. b. Patients who were in nonresponders to placebo induction dosing and received golimumab 100 mg on entry into this maintenance trial.


23

Table S5. Summary of Key Safety Findings Per Hundred Patient-Years of Follow-up Through Week 54; Treated Patients Who Were Randomized

Placeboa

Golimumaba

50 mg

100 mg

Treated patients who were randomized 156 154 154

Mean duration of follow-up (weeks) 32.7 44.3 46.3

Mean exposure (number of administrations) 8.2 11.1 11.3

Number of specified events per hundred patient-years of follow-up Adverse events 211.22 187.16 172.68 Serious adverse events 12.62 10.41 17.09 Infections 55.09 61.06 60.39 Serious infections 3.08 3.88 3.73 Adverse events leading to discontinuation of study agent 10.43 6.16 10.44

a Includes data up to the time of dose adjustment for those who increased dose.


24

Table S6. Safety Summary: Treated Patients

Golimumab

Placeboa,b (N=285)

50 mga (N=154)

100 mga, c,d (N=946)

200 mgd,e (N=14)

All Golimumabf

(N=1075) Mean duration of follow-up, weeks 34.4 44.3 39.7 27.5 41.6 Mean exposure, no. of injections 8.5 11.1 9.2 6.9 9.8

≥1 Adverse event, n (%) 182 (63.9) 112 (72.7) 699 (73.9) 9 (64.3) 801 (74.5) Frequent adverse eventsg

Ulcerative colitis 48 (16.8) 27 (17.5) 175 (18.5) 1 (7.1) 203 (18.9)

Nasopharyngitis 16 (5.6) 14 (9.1) 90 (9.5) 3 (21.4) 104 (9.7)

Headache 20 (7.0) 12 (7.8) 73 (7.7) 1 (7.1) 86 (8.0)

Arthralgia 19 (6.7) 11 (7.1) 58 (6.1) 1 (7.1) 70 (6.5) Upper respiratory tract infection 10 (3.5) 8 (5.2) 58 (6.1) 1 (7.1) 66 (6.1)

Abdominal pain 9 (3.2) 11 (7.1) 46 (4.9) 0 (0.0) 56 (5.2)

Rash 5 (1.8) 9 (5.8) 28 (3.0) 1 (7.1) 38 (3.5)

Pharyngitis 4 (1.4) 8 (5.2) 20 (2.1) 1 (7.1) 29 (2.7)

Infections, n (%) 76 (26.7) 60 (39.0) 341 (36.0) 4 (28.6) 398 (37.0) Required antimicrobial therapy 43 (15.1) 39 (25.3) 206 (21.8) 1 (7.1) 245 (22.8)

Discontinued study agent due to ≥1 Adverse event,h n (%) 16 (5.6) 8 (5.2) 121 (12.8) 0 (0.0) 129 (12.0)

Serious adverse events, n (%) 19 (6.7) 13 (8.4) 139 (14.7) 1 (7.1) 152 (14.1)

Infections 3 (1.1) 5 (3.2) 28 (3.0) 0 (0.0) 33 (3.1) Neoplasms benign, malignant, and unspecified (including cysts and polyps), n (%) 2 (0.7) 4 (2.6) 11 (1.2) 0 (0.0) 15 (1.4)


25

Table S6. Safety Summary: Treated Patients (Cont.)

Golimumab

Placeboa,b (N=285)

50 mga (N=154)

100 mga, c,d (N=946)

200 mgd,e (N=14)

All Golimumabf

(N=1075) Injection-site reactions, n (%)

Total no. of injections 6328 4392 22700 276 27368 Injections with reactions, n (%) 26 (0.4) 18 (0.4) 87 (0.4) 15 (5.4) 120 (0.4)

≥1 Injection-site reactions, n (%) 6 (2.1) 3 (1.9) 27 (2.9) 3 (21.4) 31 (2.9) a. Includes data up to the time of dose adjustment for those who increased dose from the indicated dose. b. Includes 1) patients who were in clinical response to golimumab induction dosing and were randomized to placebo on entry into this

maintenance trial; and 2) patients who were in clinical response to placebo induction dosing and received placebo on entry into this maintenance trial.

c. Includes 1) patients who were in clinical response to golimumab induction dosing and were randomized to golimumab 100 mg on entry into this maintenance trial; 2) patients who were not in clinical response to either placebo or golimumab induction dosing and received golimumab 100 mg on entry into this maintenance trial; and 3) patients who were dose adjusted to golimumab 100 mg from placebo (randomized or nonrandomized) or from golimumab 50 mg.

d. Includes data from the time of dose adjustment onward for those who increased to the indicated dose. e. Includes data from the time of dose decrease for patients who were dose adjusted to golimumab 200 mg from golimumab 100 mg and later

on had their dose decreased from 200 mg to 100 mg. f. Includes data from the time of the first golimumab dose onward. g. Most frequently reported adverse events are those that occurred at a frequency of ≥5% in any treatment group. h. Ulcerative colitis flares were the most frequently reported adverse event that led to discontinuation of study agent, in 1.8%, 3.9%, and 9.0%

of patients in the placebo, golimumab 50 mg, and golimumab 100 mg groups, respectively.


26

Table S7. Hazard Ratios (95% Confidence Intervals) for Comparing the Time to

First Infection Between the Golimumab and Placebo Groups by Concomitant Medication Use at Baseline; Randomized Patients in PURSUIT-M

Baseline Measurements

Hazard Ratioa

95% Confidence

Intervala

p-Valuea Immunomodulator use (Yes vs No) 1.106 (0.812, 1.506) 0.522 Corticosteroid use (Yes vs No) b 0.927 (0.661, 1.302) 0.663 a Based on a Cox proportional hazards mode that includes covariates for treatment group, baseline

corticosteroid use, and baseline immunomuodulator use. b Patients who were receiving oral corticosteroids on entry into this study were to begin tapering the daily

dose of corticosteroids beginning at Week 0.


27

Figure S1. Study medication dosage adjustments during the 54-week maintenance study

a. Following a protocol amendment, dose adjustment to golimumab 200 mg q4w was discontinued; patients initially randomized to

golimumab100 mg continued to receive golimumab 100 mg and patients who already had their dosage increased to golimumab 200 mg q4w had their dosage decreased to golimumab 100 mg q4w.

b. Fourteen patients increased their dose to 200 mg (three of these patients were still receiving 200 mg and had their dose decreased to 100 mg at the time of implementation of Protocol Amendment 3).


28

Figure S2A. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for comparing the proportion of patients in clinical response through week 54 in the golimumab 100 mg group vs. the placebo group by demographic characteristics at baseline of an induction study; golimumab-induction responders

CI, confidence interval; NE, not evaluable; yrs, years


29

Figure S2B. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for comparing the proportion of patients in clinical response through week 54 in the golimumab 100 mg group vs. the placebo group by UC disease characteristics at baseline of an induction study; golimumab-induction responders

CI, confidence interval; NE, not evaluable; UC, ulcerative colitis; yrs, years; CRP, C-reactive protein.


30

Figure S2C. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for comparing the proportion of patients in clinical response through week 54 in the golimumab 100 mg group vs. the placebo group by concomitant UC medication history; golimumab-induction responders

UC, ulcerative colitis; CI, confidence interval; 6-MP, 6-mercaptopurine; AZA, azathioprine; 5-ASA, 5-aminosalicylates.


31

Figure S2D. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for comparing the proportion of patients in clinical response through week 54 in the golimumab 100 mg group vs. the placebo group by concomitant UC medication usage; golimumab-induction responders

CI, confidence interval; P. Eq., prednisone equivalent; 6-MP, 6-mercaptopurine; AZA, azathioprine; 5-ASA, 5-aminosalicylates; MTX, methotrexate; NE, not evaluable.


32

Figure S2E. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for comparing the proportion of patients in clinical response through week 54 in the golimumab 100 mg group vs. the placebo group by stratification factors; golimumab-induction responders

CI, confidence interval; IV, intravenous; SC, subcutaneous; NE, not evaluable.


33

Figure S3A. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for comparing the proportion of patients in clinical response through week 54 in the golimumab 50 mg group vs. the placebo group by demographic characteristics at baseline of an induction study; golimumab-induction responders

CI, confidence interval; NE, not evaluable; yrs, years


34

Figure S3B. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for comparing the proportion of patients in clinical response through week 54 in the golimumab 50 mg group vs. the placebo group by UC disease characteristics at baseline of an induction study; golimumab-induction responders

CI, confidence interval; NE, not evaluable; yrs, years; UC, ulcerative colitis; CRP, C-reactive protein.


35

Figure S3C. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for comparing the proportion of patients in clinical response through week 54 in the golimumab 50 mg group vs. the placebo group by concomitant UC medication history; golimumab-induction responders

UC, ulcerative colitis; CI, confidence interval; 6-MP, 6-mercaptopurine; AZA, azathioprine; 5-ASA, 5-aminosalicylates


36

Figure S3D. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for comparing the proportion of patients in clinical response through week 54 in the golimumab 50 mg group vs. the placebo group by concomitant UC medication usage; golimumab-induction responders

UC, ulcerative colitis; CI, confidence interval; P. Eq., prednisone equivalent; 6-MP, 6-mercaptopurine; AZA, azathioprine; 5-ASA, 5-aminosalicylates; MTX, methotrexate; NE, not evaluable.


37

Figure S3E. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for comparing the proportion of patients in clinical response through week 54 in the golimumab 50 mg group vs. the placebo group by stratification factors; golimumab-induction responders

CI, confidence interval; IV, intravenous; SC, subcutaneous; NE, not evaluable.

Documents

SUPPLEMENTARY APPENDIX...SUPPLEMENTARY APPENDIX 3 Figure S3A. Odds ratios (vertical bars) and 95% confidence intervals (horizontal bars) for comparing the proportion of patients in