Christopher Gasink

Ustekinumab Induction and Maintenance Therapy in Refractory Crohn's Disease

BACKGROUND In patients with Crohns disease, the efficacy of ustekinumab, a human monoclonal antibody against interleukin-12 and interleukin-23, is unknown. METHODS We evaluated ustekinumab in adults with moderate-to-severe Crohns disease that was resistant to anti-tumor necrosis factor (TNF) treatment. During induction, 526 patients were randomly assigned to receive intravenous ustekinumab (at a dose of 1, 3, or 6 mg per kilogram of body weight) or placebo at week 0. During the maintenance phase, 145 patients who had a response to ustekinumab at 6 weeks underwent a second randomization to receive subcutaneous injections of ustekinumab (90 mg) or placebo at weeks 8 and 16. The primary end point was a clinical response at 6 weeks. RESULTS The proportions of patients who reached the primary end point were 36.6%, 34.1%, and 39.7% for 1, 3, and 6 mg of ustekinumab per kilogram, respectively, as compared with 23.5% for placebo (P=0.005 for the comparison with the 6-mg group). The rate of clinical remission with the 6-mg dose did not differ significantly from the rate with placebo at 6 weeks. Maintenance therapy with ustekinumab, as compared with placebo, resulted in significantly increased rates of clinical remission (41.7% vs. 27.4%, P=0.03) and response (69.4% vs. 42.5%, P<0.001) at 22 weeks. Serious infections occurred in 7 patients (6 receiving ustekinumab) during induction and 11 patients (4 receiving ustekinumab) during maintenance. Basal-cell carcinoma developed in 1 patient receiving ustekinumab. CONCLUSIONS Patients with moderate-to-severe Crohns disease that was resistant to TNF antagonists had an increased rate of response to induction with ustekinumab, as compared with placebo. Patients with an initial response to ustekinumab had significantly increased rates of response and remission with ustekinumab as maintenance therapy. (Funded by Janssen Research and Development; CERTIFI ClinicalTrials.gov number, NCT00771667.).

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohns disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohns Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P=0.005 and P=0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohns disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329 , NCT01369342 , and NCT01369355 .).

O-001 A Multicenter, Double-Blind, Placebo-Controlled Phase3 Study of Ustekinumab, a Human IL-12/23P40 mAB, in Moderate-Service Crohn's Disease Refractory to Anti-TFNα: UNITI-1

Background:Interleukins 12&23 are implicated in the pathophysiology of Crohns disease (CD). These pro-inflammatory cytokines are blocked by ustekinumab (UST). In a previous Phase 2b study (CERTIFI),1 UST IV induction followed by SC maintenance was shown effective in moderate-severe CD refractory to anti-TNF therapy. This Phase 3 study examined the efficacy and safety of IV UST induction in these patients. Methods:Patients with moderate-severely active CD (CDAI 220–450) who previously failed or were intolerant to at least 1 TNF-antagonist were randomized (1:1:1) at Week (Wk) 0 to a single dose of IV placebo (PBO), UST 130 mg, or weight-based tiered UST dosing approximating 6 mg/kg (260mg [weight ⩽55 kg], 390mg [weight >55 kg and ⩽85 kg], 520mg [weight >85 kg]). The primary endpoint was clinical response at Wk6, defined as reduction from baseline in the CDAI score of >100 points; patients with baseline CDAI score >220 to <248 points were considered in clinical response if a CDAI score of <150 was present. At Wk8, patients either transitioned to the IM-UNITI maintenance study or were followed to Wk20. Results:The 741 randomized patients had a history of TNF-antagonist failure, with baseline median CDAI of 317, CRP of 9.9 mg/L, and prior disease duration of 10.1 years. Of these, 51% had previously failed ≥2 anti-TNFs with 29.1%, 69.4%, and 36.4% of patients, respectively, satisfying protocol criteria for primary non-response, secondary non-response, or intolerance to at least one TNF antagonist. Statistical significance was demonstrated for the primary and all 4 major secondary endpoints at both IV doses. Clinical response at Wk6 (primary endpoint) was observed in 33.7% of the ∼6 mg/kg and 34.3% of the 130 mg UST groups versus 21.5% in PBO (P = 0.003 and 0.002, respectively). Clinical remission (CDAI <150) at Wk8 was observed in 20.9% of the ∼6 mg/kg group and 15.9% of the 130 mg UST group versus 7.3% on PBO (P < 0.001, P = 0.003, respectively). Clinical response at Wk8 was seen in 37.8% of the ∼6 mg/kg and 33.5% of the 130 mg UST groups, versus 20.2% on PBO (each P ⩽ 0.001). Proportion of patients with 70pt CDAI response at Wk6 was 43.8% of the ∼6 mg/kg and 46.1% of the 130 mg UST groups versus 30.4% in PBO (P = 0.002 and <0.001, respectively) and at the first post-baseline Wk3 visit, 40.6% in ∼6 mg/kg and 38.4% in the 130 mg UST groups versus 27.1% in PBO (P = 0.001 and P = 0.009, respectively), the final major secondary endpoint. Both IV UST induction doses additionally resulted in significant improvements in CDAI, IBDQ, CRP, fecal lactoferrin and calprotectin versus IV PBO. Proportions of patients with AEs, SAEs, and infections were similar in the UST and PBO groups. One opportunistic infection (listeria meningitis) was reported in the ∼6 mg/kg UST group. No malignancies, deaths, major adverse cardiovascular events, or TB occurred in UST-treated patients through Wk20. Conclusions:In a population of moderate-severe CD patients refractory to one or more prior TNF-antagonists, IV UST induced clinical response and remission and was well-tolerated throughout induction, confirming the previous positive induction data from the Phase 2b CERTIFI study.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase2b Study of Ustekinumab, a Human Monoclonal Antibody to IL-12/23p40, in Patients With Moderately to Severely Active Crohn's Disease: Results Through Week 22 From the Certifi Trial

Early Use of Azathioprine Has a Steroid Sparing Effect on Recently Diagnosed Crohns Disease Patients Miquel Sans, Antonio Lopez-San Roman, Maria Esteve, Fernando Bermejo, Valle GarciaSanchez, Yolanda Torres, Eugeni Domenech, Marta Piqueras, Montserrat Aceituno, Maria Gomez-Garcia, Carlos Taxonera, Javier P. Gisbert, Ana Gutierrez, Fernando Gomollon, Daniel Ginard, Antonio Bernal, Antonio Z. Gimeno-Garcia, Carmen Munoz, Fermin Mearin, Miguel Minguez, Manuel Barreiro-de Acosta, Xavier Calvet, Juan Buenestado, Olga Merino, Maria Barrachina, Luis Bujanda, Miriam Manosa, Maria M. Calvo, Esther Garcia, Miguel A. Montoro, Jose Manuel Herrera Justiniano, Montserrat Andreu, Vicent Hernandez, Joaquin Hinojosa, Julian Panes

Sa1211 Assessment of Sleep Impairment in Patients With Crohn's Disease: Results From the Ustekinumab Certifi Study

Introduction To describe the extent of sleep impairment reported in CERTIFI (Ph2 evaluating UST in inducing & maintaining clinical response & remisison)using Jenkins Sleep Evaluation Questionnaire (JSEQ) & establish a clinically meaningful improvement threshold for JSEQ. Methods Pts with moderate-to-severe CD(CDAI ≥220 & ≤450) who had previously failed or were intolerant to ≥1 anti-TNF were randomised to PBO/UST induction at wk0. Primary endpt was clinical response (≥100-pt reduction in CDAI from BL) at wk6. Sleep impairment assessed using JSEQ (total score 0–20; higher scores indicate greater sleep impairment) at BL&wk6. Relationships between BL sleep impairment, clinical disease activity (CDAI), & HRQoL impact(IBDQ) evaluated using Pearson correlation. Clinically meaningful improvement threshold of JSEQ was established with the anchor-based [clinical response by reduction in CDAI of ≥70-pt or clinically meaningful improvement (≥16-pt) in IBDQ] & distribution-based (change by one-half of the standard deviation [SD] of BL JSEQ score) methods. Prop of pts who achieved clinically meaningful improvements in JSEQ at wk6 was determined & compared. Results At BL,both grps(n = 526) experienced similar degree of moderate sleep impairment, with JSEQ scores (mean±SD) of 11.0 ± 4.30(PBO)&11.0 ± 4.59(UST),resp. About 60% were “waking up feeling tired and worn out”; about 30–35% of pts had trouble falling asleep, staying asleep,& woke up several times during the night for 15–30 days in the previous month. At BL, JSEQ was correlated with CDAI (r = 0.19, p 2 or > 3 points from BL JSEQ score at wk6) were derived. More pts who received UST induction achieved both thresholds at wk6(Table). Conclusion Pts experience significant sleep problems as measured by JSEQ; magnitude of impairment correlates with disease activity. Both anchor- &distribution-based methods derive similar thresholds representative of clinically meaningful improvements in JSEQ. UST induction resulted in a greater proportion of pts achieving clinically meaningful improvements in sleep impairments. Disclosure of Interest C. Gasink Employee of: Janssen R&D, LLC, D. Chan Employee of: Janssen R&D, LLC, L.-L. Gao Employee of: Janssen R&D, LLC, B. Schenkel Employee of: Janssen Scientific Affairs, LLC, C. Han Employee of: 3. Janssen Pharmaceutical Services

Long-term efficacy and safety of ustekinumab for Crohn's disease through the second year of therapy

In Phase 3 studies of ustekinumab, a fully human monoclonal IL‐12/23p40 antibody approved for moderate‐to‐severe Crohns disease, patients entered a long‐term extension after completing 8 weeks of induction and 44 weeks of maintenance treatment. Efficacy through 92 weeks and safety through 96 weeks of IM‐UNITI maintenance are reported.

Challenges in longitudinal exposure-response modeling of data from complex study designs: a case study of modeling CDAI score for ustekinumab in patients with Crohn’s disease

Informative exposure-response modeling of clinical endpoints is important in drug development to identify optimum dose and dosing regimens. Despite much recent progress in mechanism-based longitudinal modeling of clinical data, challenges remain in clinical trials of diseases such as Crohn’s disease, where a commonly used composite endpoint Crohn’s Disease Activity Index (CDAI) has considerable variation in its administration and scoring between different assessors and complex study designs typically include maintenance phases with randomized withdrawal re-randomizations and other response driven dose adjustments. This manuscript illustrates the complexities of exposure-response modeling of such composite endpoint data through a latent-variable based Indirect Response model framework for CDAI scores using data from three phase III trials of ustekinumab in patients with moderate-to-severe Crohn’s Disease. Visual predictive check was used to evaluate model performance. Potential impacts of the study design on model development and evaluation of the E–R relationship in the induction and maintenance phases of treatment are discussed. Certain biases appeared difficult to overcome, and an autocorrelated residual error model was found to provide improvement.

Long-Term Efficacy and Safety of Ustekinumab for Crohn’s Disease: Results From Im-Uniti Long-Term Extension Through two Years

Introduction Ustekinumab (UST) is a fully human mAB to IL–12/23 p40 approved for treatment of moderate-severe active Crohn’s disease (CD). The IM-UNITI long-term extension (LTE) evaluates efficacy and safety of subcutaneous (SC) UST through approximately 5 years of treatment, with wk96 results reported herein. Method 1281 patients (pts) entered the maintenance study, including 397 UST induction responders in the primary IM-UNITI population. PBO induction responders continued on PBO, PBO induction non-responders received UST 130 mg IV then UST 90 mg SC q12w if in clinical response at wk8, and UST induction non-responders received UST 90 mg SC and if in clinical response at wk8 continued on UST 90 mg q8w. All pts completing wk44 were eligible to enter LTE continuing their treatment regimen, including 567 UST pts. Results Table 1 presents analyses for randomised pts where pts missing data/discontinued are assumed not to be in response/remission at wk92, with 72.6% of q12w pts and 74.4% of q8w pts achieving remission at wk92. Baased on observed data analyses, among randomised pts who continued to receive UST through wk96, 79.2% of q12w and 87.1% of q8w pts were in remission and 90.9%–94.3% were in response at wk92, respectively. Among all UST treated pts who continued to receive UST through wk96, remission and response rates at wk92 were 70.7%–84.7%. Safety events were not higher among UST treated pts vs PBO through wk96, including overall AE’s (82.9 vs 91), SAE’s (14.16 vs 18.2), and serious infections (3.73 vs 4.33). Among UST treated pts, there were 2 deaths (sudden death, asphyxia). Two non-NMSC malignancies were reported, a seminoma (UST) and a papillary thyroid cancer (PBO only). Conclusion SC UST maintained clinical response and remission through two years. No new safety signals were observed. Disclosure of Interest None Declared

OC-007 A Multicenter, Double-Blind, Placebo (PBO)-Controlled Ph3 Study of Ustekinumab (UST), AHuman MAB to IL-12/23P40, IN PTS with Moderately-Severely Active Crohn’s Disease (CD) Who are Naïve or not Refractory to anti-TNFΑ: UNITI-2

Introduction In the Ph2b CERTIFI study, a single intravenous (IV) UST induction dose was effective & safe in CD pts previously failing anti-TNFs,1 but efficacy in pts only failing conventional therapy is unknown. We evaluated 2 IV UST induction dose regimens in a CD population not refractory to anti-TNFs. Methods Pts with moderate-severely active CD (CDAI 220–450) who failed conventional therapy but were not refractory to anti-TNFs were randomised to a single dose of IV PBO, UST 130 mg, or weight-based tiered UST dosing ~6  mg/kg. Primary endpoint was clinical response at Wk6 (reduction in CDAI score of ≥100 pts). At Wk8, pts transitioned to IM-UNITI maintenance study or had safety follow-up through Wk20. Results Of 628 pts randomised, median disease duration was 6.4 yrs; baseline (BL) mean CDAI was 303; 39% & 35% were receiving steroids & immunomodulators, respectively at BL; 69% were naïve to anti-TNFs. At Wk6, 55.5% & 51.7% in ~6 mg/kg & 130 mg UST grps were in clinical response vs 28.7% PBO (p < 0.001). At Wk8, 40.2% & 30.6% of pts in ~6 mg/kg & 130 mg UST grps were in clinical remission vs 19.6% PBO (p ≤ 0.009). Both UST doses showed significant improvements vs PBO in CDAI, IBDQ, CRP, & faecal lactoferrin & calprotectin. Proportions of AEs, SAEs, & infections were similar in UST & PBO grps. No malignancies, deaths, opportunistic infections or TB occurred in UST-treated pts.Abstract OC-007 Table 1 PBO(n = 209) UST 130 mg(n = 209) UST ~6 mg/kgcc (n = 209) Clinical Responsea Wk 3 45 (21.5) 68 (32.5)p = 0.010 81 (38.8)p < 0.001 *Wk 6 60 (28.7) 108 (51.7)Delta =23%p < 0.001 116 (55.5)Delta =26.8%p < 0.001 Wk 8 67 (32.1) 99 (47.4)p < 0.001 121 (57.9)p < 0.001 Clinical Remissionb Wk 3 24 (11.5) 33 (15.8)p = 0.199 48 (23.0)p = 0.002 Wk 6 37 (17.7) 60 (28.7)p = 0.007 73 (34.9)p < 0.001 Wk 8 41 (19.6) 64 (30.6)Delta =11.0%p = 0.009 84 (40.2)Delta =20.6%p < 0.001 N (%); a ≥ 100 pt reduction in CDAI; bCDAI <150; cweight-range based UST doses ~6 mg/kg: 260 mg (weight ≤55 kg), 390 mg (weight >55 kg and ≤85 kg), 520 mg (weight >85 kg); *primary endpoint Conclusion IV UST induced clinical response & remission in pts with moderate-severe CD not previously failing anti-TNFs & was well-tolerated through induction. Reference 1 Sandborn WJ, et al. N Engl J Med 2012;367:1519–1528. Disclosure of Interest B. Feagan Grant/research support from: Abbott/AbbVie, Amgen, Astra Zeneca, Bristol-Myers Squibb (BMS), Janssen Biotech (Centocor), JnJ/Janssen, Roche/Genentech, Millennium, Pfizer, Receptos, Santarus, Sanofi, Tillotts, UCB Pharma, Consultant for: Abbott/AbbVie, Actogenix, Akros, Albireo Pharma, Amgen, Astra Zeneca, Avaxia Biologics Inc., Avir Pharma, Axcan, Baxter Healthcare Corp., Biogen Idec, Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, GiCare Pharma, Gilead, Given Imaging Inc., GSK, Ironwood Pharma, Janssen Biotech (Centocor), JnJ/Janssen, Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nektar, Nestles, Novonordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist, Receptos, Salix Pharma, Serono, Shire, Sigmoid Pharma, Synergy Pharma Inc., Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharma, VHsquared Ltd., Warner-Chilcott, Wyeth, Zealand, Zyngenia, Speaker bureau with: Abbott/AbbVie, JnJ/Janssen, Takeda, Warner-Chilcott, UCB Pharma, Conflict with: Patent holder; Member Scientific Advisory board, Abbott/AbbVie, Amgen, Astra Zeneca, Avaxia Biologics Inc., Bristol-Myers Squibb, Celgene, Centocor Inc., Elan/Biogen, Ferring, JnJ/Janssen, Merck, Nestles, Novartis, Novonordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Takeda, Teva, TiGenix, Tillotts Pharma AG, UCB Pharma; Member, Board of Directors Officer – Robarts Clinical Trials Inc, C. Gasink Shareholder of: Janssen, Employee of: Janssen, Y. Lang Shareholder of: Janssen, Employee of: Janssen, J. Friedman Shareholder of: Janssen, Employee of: Janssen, J. Johanns Shareholder of: Janssen, Employee of: Janssen, L.-L. Gao Shareholder of: Janssen, Employee of: Janssen, B. Sands Grant/research support from: Janssen, Consultant for: Janssen, S. Hanauer Grant/research support from: Janssen, Consultant for: Janssen, Conflict with: Lecturer for Janssen, P. Rutgeerts Grant/research support from: J&J, Merck, UCB, AbbVie, Consultant for: J&J, Merck, UCB, AbbVie, Millenium/Takeda, Genentech/Hoffman LaRoche, Medimmune/AstraZeneca/Amgen, Merck/Serono, Bristol Myers Squibb, Robarts, Tillotts Pharma, Conflict with: Lectures for J&J, Merck, AbbVie, S. Targan Grant/research support from: Cedars-Sinai Medical Centre, Consultant for: Janssen, NuMedii, Inc., Conflict with: Advisory board for the Seaver Foundation; Scientific Advisory Board Member Symbiotix, S. Ghosh Grant/research support from: Abbvie, Conflict with: International Steering Committees: Janssen, Abbvie, Pfizer, Receptos, BMS, Aerpio; Advisory Committees: Takeda, Abbvie, Janssen, Pfizer, Allergan, W. de Villiers Conflict with: member of steering committee, active participant as investigator, J.-F. Colombel Consultant for: Pfizer, Takeda, Protagonist Therapies, Celgene, Genentech, Second Genome, Vertex, Amgen, Merck Sharp Dohme, Janssen, Nestle, AbbVie, Tigenix, Receptos, Conflict with: Speaker for AbbVie, Ferring, Shire, Takeda, Z. Tulassay: None Declared, U. Seidler Conflict with: Local continuing medical education seminars for MSD, W. Sandborn Grant/research support from: Receptos, Exact Sciences, Amgen, the American College of Gastroenterology, Broad Foundation, Prometheus Laboratories, AbbVie, Boehringer Ingelheim, Takeda, Atlantic Pharmaceuticals, Janssen, Bristol-Myers Squibb, Genentech, Pfizer, and Nutrition Science Partners, Conflict with: Personal fees from Receptos, Prometheus Laboratories, AbbVie, Boehringer Ingelheim, Takeda, Atlantic Pharmaceuticals, Janssen, Bristol-Myers Squibb, Genentech, Pfizer, Nutrition Science Partners, Kyowa Hakko Kirin, Millennium Pharmaceuticals, Celgene Cellular Therapeutics, Santarus, Salix Pharmaceuticals, Catabasis Pharmaceuticals, Vertex Pharmaceuticals, Warner Chilcott, Gilead Sciences, Cosmo Pharmaceuticals, Ferring Pharmaceuticals, Sigmoid Biotechnologies, Tillotts Pharma, Am Pharma BV, Dr. August Wolff, Avaxia Biologics, Zyngenia, Ironwood Pharmaceuticals, Index Pharmaceuticals, Nestle, Lexicon Pharmaceuticals, UCB Pharma, Orexigen, Luitpold Pharmaceuticals, Baxter Healthcare, Ferring Research Institute, Amgen, Novo Nordisk, Mesoblast Inc., Shire, Ardelyx Inc., Actavis, Seattle Genetics, MedImmune (AstraZeneca), Actogenix NV, Lipid Therapeutics Gmbh, Eisai, Qu Biologics, Toray Industries Inc., Teva Pharmaceuticals, Eli Lilly, Chiasma, TiGenix, Adherion Therapeutics, Immune Pharmaceuticals, Celgene, Arena Pharmaceuticals, Ambrx Inc., Akros Pharma, Vascular Biogenics, Theradiag, Forward Pharma, Regeneron, Galapagos, Seres Health, Ritter Pharmaceuticals, Theravance, Palatin, Biogen, and the University of Western Ontario (owner of Robarts Clinical Trials); non-financial support from Receptos

The Effects of Ustekinumab on Health-related Quality of Life in Patients With Moderate to Severe Crohn’s Disease

Background and Aims We assessed the effect of ustekinumab on health-related quality of life [HRQOL] in adults with Crohns disease [CD]. Methods Patients with moderately to severely active CD and inadequate response or intolerance to tumour necrosis factor antagonists [UNITI-1, n = 741], or conventional therapy [UNITI-2, n = 627] were randomised to placebo, ustekinumab 130 mg, or 6 mg/kg intravenous induction therapy. At Week 8, ustekinumab-treated responders (Crohns Disease Activity Index [CDAI] reduction ≥100 or CDAI <150 points) were re-randomised to subcutaneous maintenance therapy [IM-UNITI, n = 388] with placebo, ustekinumab 90 mg every 12 weeks [q12w], or ustekinumab 90 mg every 8 weeks [q8w], for 44 additional weeks. Inflammatory Bowel Disease Questionnaire [IBDQ] and 36-item Short Form Health Survey [SF-36] physical component summary [PCS] and mental component summary [MCS] scores were completed at induction baseline and Week 8, and at maintenance Weeks 20 and 44. Clinically meaningful improvement in IBDQ and PCS and MCS scores were evaluated. For all HRQOL outcomes, each ustekinumab dose and placebo were compared. Results Induction baseline mean values of IBDQ, PCS, and MCS were similar across groups, but impaired relative to general population norms. At Week 8, ustekinumab induced greater improvement than placebo in both HRQOL scores. Significantly greater proportions of patients receiving ustekinumab 6 mg/kg or 130 mg had clinically meaningful IBDQ improvement [UNITI-1: 54.8%, 46.9% versus 36.5%, respectively; UNITI-2: 68.1%, 58.7% versus 41.1%, respectively; p <0.05, all comparisons]. Similarly, greater proportions of ustekinumab-treated patients in both studies had clinically meaningful improvements in PCS and MCS as compared with placebo. At Week 44, improvements in IBDQ, PCS, and MCS scores were maintained with ustekinumab. Conclusions Ustekinumab improved HRQOL in patients with moderately to severely active CD.