William J. Sandborn, MD, FACG1, Paul Rutgeerts, MD, PhD, FRCP2, John Lynch, MD, PhD3, Rory Rebuck, MSN, CRNP3, Yuhua Wang, PhD3, Bin Zou, PhD3, Christopher Gasink, MD4, Omoniyi Adedokun, MS, RPh3, Bruce E. Sands, MD, MS, FACG5, Stephen Hanauer, MD, FACG6, Stephan Targan, MD7, Subrata Ghosh, MD, FRCP, FRCPE, FRCPC8, Willem J. S. de Villiers, MD, PhD9, Jean-Frederic Colombel5, Brian G. Feagan, MD10; 1University of California San Diego, La Jolla, CA; 2University Hospital Gasthuisberg, Leuven, Brabant Wallon, Belgium; 3Janssen Research & Development, LLC, Spring House, PA; 4Janssen Scientific Affairs, LLC, Horsham, PA; 5Icahn School of Medicine at Mount Sinai, New York, NY; 6Northwestern University, Chicago, IL; 7Cedars-Sinai Medical Center, Los Angeles, CA; 8University of Birmingham, Birmingham, England, United Kingdom; 9University of Stellenbosch, Stellenbosch, Western Cape, South Africa; 10Robarts Clinical Trials Inc. / Academic Medical Center, Amsterdam, the Netherlands / Western University, London, ON, Canada
Introduction: Ustekinumab (UST) is approved for treatment of moderate-to-severely active Crohn’s disease (CD) and ulcerative colitis. Here we report final results of the IM-UNITI long-term extension (LTE) study, with efficacy and safety through 5 years (yrs) of subcutaneous (SC) UST treatment. Methods: 1281 patients (pts) entered the maintenance study, including 397 IV UST induction responders, randomized to either SC placebo [PBO], n=133; UST 90mg q12w, n=132; or UST 90mg q8w, n=132. Additional nonrandomized pts were assigned to receive UST 90mg q12w (PBO induction non-responder), UST 90mg q8w (delayed Wk16 responder to UST), or PBO (PBO induction responder). All pts who entered the LTE at Wk44 continued the same treatment regimen they were receiving at Wk44, including 567 UST-treated pts (237 randomized ). 151 PBO-treated pts terminated study participation after study unblinding and analysis of the Wk44 data. Results: Among all pts originally randomized in the maintenance study (ITT analysis), 28.7% and 34.4% of pts were in clinical remission 5 yrs later, at Wk252, on 90 mg UST q12w and q8w, respectively. Approximately half (51.1%) of the pts who entered the LTE completed their final dosing visit. Key results after 5 yrs among pts who entered the LTE, including response and remission overall and in anti-TNF therapy history subsets, are summarized in Table 1. Of the pts who were in clinical remission at wk252, 89.5% who received continuous q12w (34/38) and 93.3% who received continuous q8w (42/45) were not receiving steroids. Antibody to UST rates through Wk272 remained low, occurring in 5.8% (31/532) of randomized pts continuously receiving UST in the LTE (excluding randomized PBO dose adjusters). Safety events (per hundred pt-yrs) were not higher among all UST-treated pts entering the LTE compared with PBO from Wk0 through Wk272 (Table 2). No new deaths were reported after Wk156 (6 reported previously). Six pts had malignancies (excluding NMSC) between Wks156 and 272 (q12w: intraocular melanoma, renal cell carcinoma; q8w: endometrial adenocarcinoma, lentigo maligna melanoma, lobular breast cancer in situ, pancreatic carcinoma). Discussion: Pts receiving SC UST generally maintained clinical response and remission through 5 yrs. Nearly half of anti-TNF-naive pts who responded to UST IV induction were in remission after 5 yrs of SC q8w maintenance treatment. No new safety signals were observed.
Table 1.
Table 2.
Disclosures: William Sandborn: Janssen Research & Development, LLC – Advisory Committee/Board Member, Consultant, Speaker's Bureau, Other Financial or Material Support, This study was supported by Janssen Research & Development, LLC. Paul Rutgeerts: Janssen Research & Development, LLC – Advisory Committee/Board Member, Consultant, Speaker's Bureau, Other Financial or Material Support, This study was supported by Janssen Research & Development, LLC. John Lynch: Janssen Research & Development, LLC – Employee. Johnson & Johnson – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds). Rory Rebuck: Janssen Research & Development, LLC – Employee. Yuhua Wang: Janssen Research & Development, LLC – Employee. Bin Zou: Janssen Research & Development, LLC – Employee. Christopher Gasink: Janssen Research & Development, LLC – Employee. Johnson & Johnson – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds). Omoniyi Adedokun: Janssen Research & Development, LLC – Employee. Bruce Sands: Janssen Research & Development, LLC – Advisory Committee/Board Member, Consultant, Speaker's Bureau, Other Financial or Material Support, This study was supported by Janssen Research & Development, LLC. Stephen Hanauer: Janssen Research & Development, LLC – Advisory Committee/Board Member, Consultant, Speaker's Bureau, Other Financial or Material Support, This study was supported by Janssen Research & Development, LLC. Stephan Targan: Janssen Research & Development, LLC – Advisory Committee/Board Member, Consultant, Speaker's Bureau, Other Financial or Material Support, This study was supported by Janssen Research & Development, LLC. Subrata Ghosh: Janssen Research & Development, LLC – Advisory Committee/Board Member, Consultant, Speaker's Bureau, Other Financial or Material Support, This study was supported by Janssen Research & Development, LLC. Willem de Villiers: Janssen Research & Development, LLC – Advisory Committee/Board Member, Consultant, Speaker's Bureau, Other Financial or Material Support, This study was supported by Janssen Research & Development, LLC. Jean-Frederic Colombel: Janssen Research & Development, LLC – Advisory Committee/Board Member, Consultant, Speaker's Bureau, Other Financial or Material Support, This study was supported by Janssen Research & Development, LLC. Brian Feagan: Janssen Research & Development, LLC – Advisory Committee/Board Member, Consultant, Speaker's Bureau, Other Financial or Material Support, This study was supported by Janssen Research & Development, LLC.
