Efficacy and Safety of Ustekinumab in Asian Patients with Moderately to Severely Active Ulcerative Colitis: A Subpopulation Analysis of UNIFI Long-Term Extension through 4 Years

Ulcerative colitis (UC) is a chronic, relapsing, and remitting immune-mediated condition requiring long-term therapy. Moderate to severe disease is managed using steroids, sulfasalazine, thiopurines, biologicals [anti-tumor necrosis factor, anti-integrins, and anti-interleukin (IL) 12/23], and small molecules (janus kinase inhibitors, sphingosine-1-receptor modulators). Ustekinumab (UST) is an IgG1 monoclonal antibody acting on IL 12/23 recently authorized to treat moderate to severe UC that is not responsive to other biologic medicines. There remains an unmet need in the management of UC despite the growing availability of therapeutic agents. Current treatment algorithms use a standard approach for all patients, but targeted therapies are required for better outcomes. This systematic review aims to evaluate the safety and efficacy of UST in patients with moderate to severe UC. We also noted the clinical and endoscopic improvement with maintenance of clinical and steroid-free remission across multiple databases to strengthen reproducibility.This systematic review followed the Preferred Reporting Items for Systematic Review and Meta Analysis (PRISMA) 2020 guidelines. Relevant literature was retrieved from PubMed, PubMed Central, Cochrane Library, Science Direct, and Google Scholar. Articles published in English within the last five years (2020 to 2025) were included. Quality assessment tools were applied to ensure the quality of evidence-based medicine that will be utilized to develop a conclusion and direct future review.The studies analysed showed a superiority of UST in the induction and maintenance of remission in active, difficult-to-treat UC. Our findings indicate that a reduction in Mayo score with improvement in c-reactive protein (CRP) and fecal calprotectin (fCal) can be used to assess a reduction in inflammatory burden and response to treatment. Histo-endoscopic mucosal healing also provides a long-term clinical assessment of the reduction in disease burden. All safety events that led to drug discontinuation and malignancy were similar for UST therapy and placebo. UST, as a treatment option for moderate to severe UC, can provide an alternative avenue in the development of patient-centric targeted therapies. Further research targets should include the formulation of a standard dosing regimen and the evaluation of the long-term safety profile of the drug. There is also limited literature available for comparative analysis of UST treatment with other available therapeutic options, especially biologic agents, and its effect on extra-intestinal manifestations.

Background The UNIFI randomized-withdrawal maintenance study and long-term extension (LTE) evaluated the safety and efficacy of subcutaneous (SC) ustekinumab (UST) in patients with moderately to severely active ulcerative colitis (UC) who had responded to intravenous (IV) UST during induction. We evaluated the efficacy of UST dose adjustment through Week (Wk) 152 of the long-term extension (LTE). Methods 523 intravenous UST induction responders were randomized to SC maintenance therapy (SC placebo [PBO], n=175; UST 90mg every 12 weeks [q12w], n=172; or UST 90mg q8w, n=176). 284 UST patients who completed wk44 entered the LTE. PBO patients were discontinued after wk44 unblinding. Based on the investigator’s clinical judgement of their UC disease activity, patients in the LTE were eligible to receive dose adjustment starting at Wk 56: PBO to q8w, q12w to q8w, and q8w to q8w (sham adjustment). Patients in PBO or q8w groups were only eligible for dose adjustment or sham dose adjustment before unblinding. Patients were assessed for symptomatic remission, partial Mayo scores, and inflammatory markers ≥16 wks after dose adjustment. Results Overall, 60 patients (42.6%) in the q12w group and 40 patients (28.0%) in the q8w group underwent dose adjustment (or sham dose adjustment) prior to Wk 156 of the LTE; 51 and 39 patients in each group, respectively, had dose adjustment at Wk 136 or before, providing≥16 wks of data after dose adjustment (Table). At the first visit ≥16 weeks after dose adjustment, 70.6% of patients who adjusted from q12w to q8w and 61.5% who sham dose adjusted from q8w to q8w were in symptomatic remission. At the time of dose adjustment, 27/51 patients (52.9%) in the q12w group and 25/39 patients (64.1%) in the q8w group were in symptomatic remission. Of those who were in symptomatic remission at the time of dose adjustment, the majority (81.5% and 68.0%, respectively) were maintained in symptomatic remission at the first visit ≥16 wks after dose adjustment. Of those who were not in symptomatic remission at the time of dose adjustment, 58.3% and 50.0%, respectively, were in symptomatic remission at the first visit ≥16 wks after dose adjustment. Mean partial Mayo scores and CRP levels decreased after dose adjustment (Table). Conclusion Patients may benefit from UST dose adjustment to q8w.

INTRODUCTION: UNIFI is a phase 3, double-blind, PBO-controlled study that evaluated ustekinumab (UST) treatment in pts with moderate-severe UC who previously failed biologic or conventional therapy. Pts who completed safety and efficacy evaluations at maintenance Wk44 could enter the long-term extension (LTE) continuing the same treatment regimen (PBO or UST 90mg SC q8w or q12w). Starting at Wk56, pts could dose adjust: PBO to UST q8w, UST q12w to q8w, and UST q8w to q8w (sham adjustment). METHODS: PK, immunogenicity, and their relationships with efficacy and safety were evaluated among pts who received UST SC in the LTE. Serum UST concentrations (conc) through Wk92 and antibodies to UST (ATU) through Wk96 were determined using validated assays. Clinical efficacy was assessed with symptomatic and partial Mayo remission at Wk92; safety events were evaluated through Wk96. RESULTS: During the LTE, randomized pts who continued 90mg SC UST and did not dose adjust (n = 271) had median non-trough UST conc of 6.49−6.66 µg/mL, 4 wks after dosing in the q8w group, and 2.11−2.56 µg/mL, 8 wks after dosing in the q12w group. High proportions (≥80%) of pts were in symptomatic remission and partial Mayo remission at Wk92 in each serum UST conc quartile, thus no clear exposure-response was demonstrable; however, proportions of pts with normalized calprotectin and normalized CRP at Wk92 increased with increasing serum UST conc quartiles (Table). No trends were found between serum UST conc and incidence of infections, serious infection, or serious AEs through Wk96 (Table). Among 400 pts who received continuous UST in induction, maintenance, and the LTE, ATU were found in 22/400 (5.5%) and were often transient. Of these, most (18/22 pts) had titers at or below 1:800; 4 of the 22 pts were positive for neutralizing antibodies. Among pts randomized to UST, the proportions in symptomatic or partial Mayo remission at Wk92 were similar between pts who were positive (80.0%, 80.0%; respectively) and pts who were negative (81.0%, 82.2%; respectively) for ATU. No relationship was observed between ATU and injection site reactions. CONCLUSION: Following treatment with UST 90mg SC q12w or q8w during the LTE, sustained serum UST levels were observed through Wk92 and were generally consistent with serum UST levels observed for these treatment groups during the maintenance study. The incidence of ATU was low and often transient through Wk96, and anti-drug antibodies did not appear to affect efficacy or injection site reactions.Table 1

Background/AimsWe aimed to evaluate the efficacy and safety of ustekinumab (UST) in the East-Asian population with moderate to severely active ulcerative colitis (UC).MethodsThis sub-analysis was conducted on data from East-Asian patients included in the UNIFI program (NCT02407236). UNIFI consisted of two double-blind, placebo-controlled trials: an 8-week induction study and a 44-week randomized withdrawal maintenance study.ResultsOf 133 East-Asian patients (Japanese: 107, Korean: 26) who underwent randomization, 131 completed induction study and 111 entered maintenance study. In the maintenance study, 78 patients were randomized. Patients who received UST 130 mg and UST 6 mg/kg showed numerically higher clinical remission at week 8 in the induction study (5/44 [11.4%] and 5/45 [11.1%], respectively) compared with those who received placebo (0/44, 0%). The proportion of patients achieved clinical remission at week 44 was numerically higher in the UST 90 mg q12w group (10/21, 47.6%), but similar in the UST 90 mg q8w group (5/26, 19.2%) compared to placebo (7/31, 22.6%). Serious adverse events were reported in 1 patient in UST 130 mg group, but no patient in UST 6 mg/kg group through week 8 in the induction study, and 1 patient in UST 90 mg q12w group and 5 patients in the UST 90 mg q8w group in the maintenance study. No deaths were reported in East-Asian patients throughout the study.ConclusionsUST induction and maintenance treatments were effective in East-Asian patients with moderate to severe UC; the efficacy and safety profiles were consistent with the overall population.

INTRODUCTION: The UNIFI induction study evaluated the efficacy and safety of ustekinumab (UST) in patients with moderately to severely active ulcerative colitis (UC) after a single intravenous infusion. In this analysis, we evaluated the rapidity of the onset of the treatment effect. METHODS: Eligible patients were randomly assigned to placebo (PBO) or UST 130 mg or ∼6 mg/kg. Patients recorded stool frequency and categorized rectal bleeding daily for the 7 days before each visit. Partial Mayo scores were calculated at baseline and Week 2 using the average of the stool frequency and rectal bleeding scores from the most recent consecutive 3-day period before the visit and the physician's global assessment score recorded at the visit. C-reactive protein (CRP) and fecal biomarkers were measured at baseline and Day 14. RESULTS: At baseline, the mean 3-day average daily stool frequency was 7.0 in the PBO group, 6.9 in the UST 130-mg group, and 7.0 in the UST ∼6-mg/kg group. Patients receiving UST showed greater reductions in the daily number of stools compared with PBO as soon as the first assessment time point at Day 7. Mean changes from baseline in daily stool frequency were -0.7 for PBO, -1.0 for UST 130-mg (P = 0.098), and -1.2 for UST ∼6-mg/kg group (P = 0.018) by Day 7, respectively, and -0.9, -1.6 (P < 0.001), and -1.9 (P < 0.001) by Day 13, respectively (Figure 1). Rectal bleeding scores at baseline and Week 2 are summarized in Figure 2. Patients receiving UST showed significantly greater improvement from baseline to Day 14 in partial Mayo score and CRP (Table, P < 0.001 for all comparisons of UST vs PBO). Differences between the UST and PBO treatment groups in mean changes from baseline to Day 14 in fecal calprotectin did not reach significance (PBO -33.96 mg/kg, UST 130 mg 79.12 mg/kg [P = 0.875], UST ∼6 mg/kg -412.68 mg/kg [P = 0.152]). However, patients receiving UST showed significantly greater improvement in fecal calprotectin at Week 4 (mean changes from baseline: PBO -226.78 mg/kg, UST 130 mg -881.22 mg/kg [P = 0.013], UST ∼6 mg/kg -802.75 mg/kg [P < 0.001]). Similar results were observed for fecal lactoferrin. CONCLUSION: The effect of UST began rapidly after induction, with symptomatic improvement and reduction of systemic inflammation seen as early as the first assessments at Days 7 and 14, respectively.

INTRODUCTION: The UNIFI randomized-withdrawal maintenance study evaluated the safety & efficacy of subcutaneous (SC) ustekinumab (UST) in patients (pts) with moderately to severely active ulcerative colitis (UC) who had responded to intravenous (IV) UST induction. Pts who completed the maintenance study could enter a long-term extension (LTE) through 220 weeks (wks). We evaluated the effect of UST maintenance therapy on stool frequency & rectal bleeding through 92wks in pts who were treated in the LTE. METHODS: All pts who completed Wk44 were eligible to enter & continue in the LTE at the investigator’s discretion. PBO pts were discontinued from the LTE after maintenance study unblinding. During the LTE, pts were eligible to receive dose adjustment (PBO to q8w or q12w to q8w or q8w to q8w [sham dose adjustment]) starting at Wk56 based on investigator assessment of pts’ UC disease activity. Dose adjustment was considered part of the treatment experience & not considered a treatment failure for these analyses. Pts recorded the number of stools & rectal bleeding symptoms for 7 days before each visit. The proportions of pts with Mayo stool frequency subscores of 0 (normal number of stools) or 1 (1 to 2 stools more than normal) or rectal bleeding subscores of 0 (no blood seen) were evaluated. Absolute stool number was also summarized. RESULTS: Pts who were randomized & treated in the LTE were included in these analyses (UST 90 mg q12w: n = 141; UST 90 mg q8w: n = 143). Absolute stool numbers in the UST q12w and q8w groups were 6.6 and 6.5 stools per day, respectively, at induction baseline (BL) & decreased to 2.8 and 2.7, respectively, by maintenance BL. Reductions achieved at maintenance BL were maintained at Wk92 (2.7 & 2.2, respectively). At induction BL, only 12.8% & 18.2% of pts, respectively, had Mayo stool frequency subscores of 0 or 1. By maintenance BL, 80.9% & 80.4%, respectively, had Mayo stool frequency subscores of 0 or 1, & these percentages were maintained through Wk92 (79.4% & 86.7% at Wk92, respectively). At induction BL, 9.2% & 7.0%, respectively, had no blood seen in the stool. By maintenance BL, 87.2% & 84.6%, respectively, had no blood seen in the stool, & these percentages were maintained through Wk92 (86.5% & 88.8%). CONCLUSION: Among pts who were treated in the LTE, reductions in stool frequency & rectal bleeding that had been achieved after IV UST induction were maintained through 2 yrs of UST SC maintenance. These data support the durability of response to UST in UC.Table 1

Background The UNIFI randomised-withdrawal maintenance study evaluated the safety and efficacy of subcutaneous (SC) ustekinumab (UST) in patients (patients) with moderately to severely active ulcerative colitis (UC) who had responded to intravenous (IV) UST during induction. We evaluated the efficacy of UST dose adjustment during the long-term extension (LTE). Methods At Week (Week) 0 of the 44 weeks maintenance study, 523 patients who had responded to IV UST induction were randomly assigned in a 1:1:1 ratio to placebo (PBO) SC, UST SC 90 mg q12w, or 90 mg q8w. Patients who completed the maintenance study were eligible to enter the LTE if the investigator thought they would benefit from continued treatment. PBO patients were discontinued from the LTE after the maintenance study was unblinded and the analysis was complete. Based on investigator’s clinical judgement of UC disease activity, patients in the LTE were eligible to receive dose adjustment starting at Week 56: PBO to q8w, q12w to q8w, and q8w to q8w (sham adjustment). PBO patients were only eligible for dose adjustment before unblinding. Patients were assessed for symptomatic remission (SR), partial Mayo scores, and inflammatory markers ≥16 weeks after dose adjustment. Results Symptomatic remission was maintained through Week 92 among patients treated with UST regardless of dose adjustment in the LTE (Figure). Overall, 40 (28.4%) and 37 (25.9%) patients in the q12w and q8w groups, respectively, underwent dose adjustment (or sham dose adjustment) prior to Week 92 of the LTE. Among patients who received dose adjustment at Week 76 or before and had data ≥16 weeks after dose adjustment, symptomatic remission was observed in 70.0% in the q12w-to-q8w group and 71.4% in the q8w-to-q8w group, the majority of whom were in symptomatic remission at the time of the dose adjustment (Table). The safety profile of UST in patients who received dose adjustment was generally consistent with the overall safety profile of UST. Conclusion Patients may benefit from UST dose adjustment to q8w. However, the majority of UST-treated patients were in SR at the time of dose adjustment in this study. No new safety signals were observed among patients who dose adjusted.

The ongoing UNIFI long-term extension evaluates subcutaneous ustekinumab for moderate-to-severe ulcerative colitis (UC) from weeks 44 through 220. To assess efficacy (through week 92) and safety (through week 96) during the long-term extension METHODS: Overall, 399 responders to intravenous ustekinumab induction and who were randomised to maintenance therapy were treated in the long-term extension (115 received subcutaneous placebo, 141 received ustekinumab 90mg every 12weeks [q12w], and 143 received ustekinumab 90mg q8w). Placebo treatment was discontinued at unblinding after week 44. Partial Mayo scores were collected every 12weeks and at each dosing visit after unblinding. Safety was evaluated throughout. Among all patients randomised in maintenance, symptomatic remission rates (stool frequency=0/1; rectal bleeding=0) at week 92 were, 64.5% and 67.6% in the ustekinumab q12w and q8w groups, respectively. Among randomised patients treated in the long-term extension, 78.7% and 83.2% of patients receiving q12w and q8w, respectively, attained symptomatic remission at week 92; >95% of patients in symptomatic remission at week 92 were corticosteroid-free. Both ustekinumab groups maintained efficacy through week 92. From weeks 44 to 96, adverse events (AEs) per hundred patient-years (PY) of follow-up for combined ustekinumab vs placebo were: 255.68 vs 267.93; serious AEs, 9.34 vs 12.69; malignancies (including non-melanoma skin cancers), 0.93 vs 1.49; and serious infections, 2.33 vs 2.99. One patient with multiple comorbidities who received one ustekinumab dose after dose adjusting from placebo experienced a fatal cardiac arrest. The efficacy of ustekinumab in patients with UC was sustained through 92weeks. No new safety signals were observed (ClinicalTrials.gov number, NCT02407236).

Background Ustekinumab (UST) is an interleukin-12/23 p40 antagonist approved for the treatment of moderately to severely active ulcerative colitis (UC). Here, we report the final efficacy and safety results of UST in the Asian subpopulation in the UNIFI long-term extension (LTE) through 4 years (Week [WK] 200). Methods Overall, 87 intravenous (IV) UST induction WK8 responders were randomised to subcutaneous (SC) maintenance therapy: 34 placebo (PBO); 24 UST 90 mg every 12 weeks (q12w); 29 UST 90 mg q8w. The nonrandomised patients (pts) included 22 IV UST induction nonresponders who received SC UST at WK8, responded at WK16, and continued on SC UST q8w; and 12 responders to IV PBO induction who received SC PBO.1,2 Pts who completed WK44 continued on SC UST q8w or PBO treatment in the LTE, and PBO pts were discontinued after unblinding. Starting at WK56, randomised pts with UC worsening could adjust to SC UST 90 mg q8w. Efficacy was evaluated in UST-randomised pts (n=53) using symptomatic remission (Mayo stool frequency subscore of 0 or 1 and rectal bleeding subscore of 0). Safety was evaluated for all pts treated in the LTE, including randomised and nonrandomised populations until WK220. Results Among all UST-randomised pts at maintenance baseline WK0 (intent-to-treat population with nonresponder imputation for missing data and treatment failure criteria), 49.1% were in symptomatic remission at WK200 (biologic naïve 77.8.%; failures 34.4%); 49.1% of pts were in corticosteroid-free symptomatic remission at WK200 (Table 1; Fig. 1-2). Overall, 43.5% of biologic failure and 0% of biologic naïve pts who were randomised to UST and treated in the LTE discontinued treatment between WK44 and WK200. Among randomised pts who continued UST in the LTE, 63.4% were in symptomatic remission at WK200; 78.6% of pts with observed data at WK200 were in symptomatic remission (Table 1; Fig. 3); and 80.0% of those in clinical remission at WK44 were in symptomatic remission at WK200. Safety events were similar among UST-treated pts compared with PBO. From maintenance baseline WK0 through WK220, pts receiving UST (combined UST) and PBO had 241.8 and 56.5 total pt-years of follow-up, respectively. Safety events per 100 pt-years of follow-up for combined UST vs PBO were AEs: 222.48 vs 320.29, SAEs: 11.58 vs 7.08, and serious infections: 1.65 vs 1.77. During the final year of the LTE, no deaths or major cardiovascular events were reported in UST-treated Asian pts. Conclusion Consistent with the overall study population in UNIFI LTE1,2, Asian pts receiving SC UST generally maintained clinical benefit through 4 years. No new safety signals were observed. 1Afif W, et al. UEGW. Vienna, Austria, October 8-11, 2022. 2Sands BE, et al. ACG. Charlotte, NC, October 21-26, 2022

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 90 mg q12w, n = 132; or UST 90 mg q8w, n = 132. Additional nonrandomized pts were assigned to receive UST 90 mg q12w (PBO induction non-responder), UST 90 mg 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). CONCLUSION: 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 1Table 2

Introduction: Ustekinumab (UST) is a fully human immunoglobulin G1 kappa mAB to human IL 12/23p40 approved for the treatment of moderate to severe active Crohn's disease (CD). The continuing IM-UNITI long-term extension (LTE) evaluates the efficacy and safety of subcutaneous (SC) UST through approximately 5 years of treatment. Results through maintenance week 44 previously demonstrated no apparent benefit of concomitant immunosuppressant (IMM) use on efficacy, drug levels or immunogenicity of UST. Results through 2 years are reported herein. Methods: 1281 patients entered the maintenance study, including 397 UST induction responders in the primary population (randomized to placebo (PBO) SC; n=133, UST 90mg SC q12w (q12w); n=132, or UST 90mg SC q8w (q8w); n=132). A one-time dose adjustment to UST 90mg SC q8w occurred in randomized patients who met loss of response (LOR) criteria between weeks 8 & 32. All patients completing week 44 were eligible to enter the LTE continuing the treatment they were on at week 44. This analysis included the 82 patients on UST q8w from the primary population who did not meet LOR criteria for dose adjustment and entered the LTE. Clinical remission at each study visit, serum UST concentrations from maintenance weeks 44 to 92, and immunogenicity were assessed in patients taking vs. not taking concomitant IMMs. Results: Baseline use of concomitant IMMs in the randomized UST q8w LTE population was 35.4% (29/82). Patients that were not on IMMs at baseline (64.6%, 53/82), all remained off IMMs through week 92. Rates of remission in the q8w group were not higher among patients with baseline IMM use and were similar through week 92 (Table 1). Furthermore, concomitant use of immunomodulators did not appear to have any notable or consistent effect on serum UST concentrations or antidrug- antibody formation at any timepoint examined (Table 1). Conclusion: Data through 2 years of UST treatment (90mg q8w maintenance) in the IM-UNITI LTE study suggest that concurrent use of immunomodulators does not increase remission efficacy. Further supporting the notion that concomitant use of IMM with UST is not necessary, no effect on serum UST concentrations or antidrug antibodies was seen across all timepoints, in contrast to findings with other biologic agents.573 Figure 1 No Caption available.

Background Ustekinumab (UST) is an IL12/23 blocker approved for use in Crohn’s disease and ulcerative colitis (UC). In the UNIFI maintenance study of patients (pts) with moderate-severe UC, >90% of the pts who achieved clinical response or remission at week (wk) 44 were able to eliminate corticosteroids, an important goal of therapy. In this analysis, we describe the corticosteroid-sparing effects of UST treatment through 3 years among pts who were treated in the UNIFI long-term extension (LTE). Methods 523 intravenous UST induction responders were randomized to SC maintenance therapy (SC placebo [PBO], n=175; UST 90mg every 12 wks [q12w], n=172; or UST 90mg q8w, n=176). 284 UST pts who completed wk44 entered the LTE. PBO pts were discontinued after wk44 unblinding. Based on the investigator’s clinical judgement of their UC disease activity, pts in the LTE were eligible to receive dose adjustment starting at wk56: PBO to q8w, q12w to q8w, and q8w to q8w (sham adjustment). Pts in PBO or q8w groups were only eligible for dose adjustment or sham dose adjustment before unblinding. Efficacy was evaluated in randomized pts using symptomatic remission (Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0). During the maintenance study, all pts receiving corticosteroids at maintenance baseline were required to initiate tapering. Through wk152 of the LTE, symptomatic remission endpoints were calculated with treatment failure and missing data nonresponder imputation, and dose adjustment was not considered to be a treatment failure. Missing corticosteroid dose data was managed using last observation carried forward. Results Of the 284 pts in the randomized population who were treated with UST in the LTE, 139 were receiving corticosteroids at maintenance baseline. Of these, 91.4% (n=127) were no longer receiving corticosteroids at wk152. The average prednisone-equivalent corticosteroid dose among pts receiving corticosteroids at maintenance baseline in the q8w group was 15.4 mg/day at maintenance baseline and 1.7 mg/day at wks44 & 152. In the q12w group, average prednisone-equivalent doses were 15.4, 1.0, and 4.6 mg/day, respectively (Table 1). Corticosteroid-free symptomatic remission rates through wk152 are summarized in Table 2. Results were similar for the q8w and q12w maintenance doses. Of the UST-treated pts who were in symptomatic remission at wk152, 94.6% (88/93) in the q12w group and 98.0% (97/99) in the q8w group were corticosteroid-free. Conclusion UST maintenance therapy, with both q8w and q12w dosing regimens, was effective in reducing and eliminating the use of corticosteroids in pts with UC through 3 years. Through 3 years of treatment with UST, the majority of pts in symptomatic remission were corticosteroid free.

The efficacy and safety profile of ustekinumab (UST) in Crohn's disease (CD) is favorable; however, data in elderly patients are lacking. We aimed to assess the safety and efficacy of UST in elderly CD. We performed a retrospective cohort study of CD patients classified as elderly (age ≥ 65years at UST initiation) or nonelderly (<65years) treated at a large, tertiary referral center. Outcomes assessed were clinical (measured by physician global assessment [PGA]) and steroid-free response, remission, adverse events, and postsurgical complications were compared by age category. Multivariable regression modeling and survival analysis was also performed. In total, 117 patients (elderly n = 39, nonelderly n = 78) were included in the study. Elderly patients had predominantly moderate disease (87.2%), while nonelderly had a higher proportion of severe disease activity (44.9%) (p = 0.001), though no differences in baseline endoscopic activity, prior biologic use, or steroid or immunomodulator use at baseline existed (p > 0.05 all). While nearly 90% patients in both groups experienced clinical response to UST, compared to nonelderly, elderly patients were less likely to achieve complete clinical remission (28.2% vs. 52.6%, p = 0.01). On regression modeling, age was not associated with clinical outcomes (p > 0.05 all). Mucosal healing was achieved in 26% elderly and 30% nonelderly patients (p = 0.74). There were no significant differences in infusion reactions (2.6% vs. 6.4%, p = 0.77), infection (5.2% vs. 7.7%, p = 0.7), or postsurgical complications (p = 0.99) by age category. UST is safe and effective in elderly CD. Although limited by sample size and retrospective design, such real-world data can inform biologic positioning in this IBD population.

Background The UNIFI Jr study (NCT04630028) evaluated efficacy and safety of ustekinumab in paediatric patients with moderately-to-severely-active ulcerative colitis (UC). Methods 112 patients (2 to &amp;lt; 18 years; weight ≥10kg); moderately-to-severely active UC (baseline Mayo score ≥6, Mayo endoscopy subscore ≥2 and inadequate response or intolerant to conventional/biologic therapy or corticosteroid-dependent) received a single open-label, IV ustekinumab induction (I) dose. At Week (W)8, 109 patients were randomized in a 1:1 ratio stratified by weight (&amp;lt;40kg/≥40kg) and W8 clinical response status (decrease from baseline [BL] in Modified Mayo score ≥30% and ≥2 points with decrease from BL rectal bleeding subscore ≥1 or rectal bleeding subscore ≤1) to receive blinded SC ustekinumab maintenance therapy Q8W/Q12W for 44-weeks. Ustekinumab dosing was based on body-surface-area (&amp;lt;40kg) or weight-tier (≥40kg). Primary endpoints were clinical remission (Mayo subscores: stool ≤1 without an increase from BL, rectal bleeding 0, endoscopy 0-1 with no friability present) at W8 and at W52 in those with induction response at W8. Results Among 112 patients (median [IQR] age 14.0 [11.0-15.5] years; 54.5% female; 60.7% biologic-naive); median (IQR) PUCAI score 55.0 (45.0-60.0), 91.7% moderate UC, median (IQR) Mayo score 8.0 (7.0-9.0), and 67.0% extensive UC. At W8, 79 patients achieved clinical response (induction responders). At Week 52, 32 of 79 (40.5% [95% CI: 30.4%-51.5%]) clinical responders achieved clinical remission, 52 (65.8%) achieved symptomatic remission, 51 (64.6%) were in clinical remission by PUCAI (score &amp;lt;10), 32 (40.5%) achieved endoscopic improvement, 32 (40.5%) were corticosteroid-free for ≥90 days, and 29 (36.7%) had histologic-endoscopic mucosal improvement (Figure 1). Remission rate was higher in patients without prior biologic failures (25 [47.2%; 95% CI: 34.4%-60.3%]) compared to those with biologic failure (7 [26.9%; 95% CI: 13.7%-46.1%])(Figure 2). Not having previously failed biologic therapy was associated with higher W52 remission rates. Remission rates were similar from W8 to W52 in all weight subgroups (Figure 2). Both Q8W and Q12W maintenance regimens were efficacious. During maintenance therapy, serious adverse events (SAE) occurred in 6.4% (7/109) of patients, most commonly reported SAEs were GI disorders (UC). AE rates were similar between Q8W/Q12W groups and treatment-emergent SAEs occurred in 9.3% (5/54) and 3.6% (2/55) of patients in Q8W/Q12W groups, respectively. Conclusion Ustekinumab induction and maintenance therapy was effective in treating paediatric patients aged 2 to &amp;lt; 18 years with moderate-to-severe paediatric UC. Ustekinumab was well-tolerated with no new safety signals. Conflict of interest: De Greef, Elisabeth: Advisory Board Johnson &amp; Johnson. Received medical writing assistance funded by Johnson &amp; Johnson. Turner, Dan: Consultation fee: Janssen, Pfizer, Ferring, Abbvie, Takeda, Prometheus Biosciences, Lilly, SorrisoPharma, Boehringer Ingelheim, Galapagos, BMS, AlfaSigma, Merck, Genentech Research support: Janssen, Abbvie, Takeda, Pfizer Received medical writing assistance funded by Johnson &amp; Johnson Royalties: Shaare Zedek Medical Center, Hospital for Sick Children Russell, Richard K.: Grant: Nestec Other: Abbvie, Celltrion, Janssen, Lilly, Nestle, Pharmacosmos, Pfizer Received medical writing assistance funded by Johnson &amp; Johnson Griffiths, Anne: Grant: Abbvie Personal Fees: Abbvie, Alfasigma, Amgen, Janssen, Lilly, Merck, Pfizer, Roche, Takeda Received medical writing assistance funded by Johnson &amp; Johnson Kierkuś, Jarosław: Grant: Nestle Other: Nutricia, Abbvie, Nestle Received medical writing assistance funded by Johnson &amp; Johnson Korczowski, Bartosz: A grant was received from Johnson &amp; Johnson and Takeda to conduct scientific research. Received medical writing assistance funded by Johnson &amp; Johnson. Meglicka, Monika: Received consultation fees, royalties from Sandoz and Ferring Received medical writing assistance funded by Johnson &amp; Johnson Cohen, Stanley: Consultant, Janssen, Kate Farms Research grants last 3 years, Janssen, Abbvie, Principal, Nutrition4Kids, LLC Received medical writing assistance funded by Johnson &amp; Johnson Hyams, Jeffrey: Abbvie: Advisory Board Janssen: Advisory Board Roche/Genentech: Consultant Takeda: Consultant Received medical writing assistance funded by Johnson &amp; Johnson Rosh, Joel: Advisor/Consultant: AbbVie, Janssen, Mesoblast. Received medical writing assistance funded by Johnson &amp; Johnson. Strauss, Richard: Employee of Johnson &amp; Johnson and may own stock or have stock options in Johnson &amp; Johnson. Received medical writing assistance funded by Johnson &amp; Johnson. Adedokun, Omoniyi: Employee Johnson &amp; Johnson and may own stock or have stock options in Johnson &amp; Johnson Received medical writing assistance funded by Johnson &amp; Johnson Salas, Jose: Employee of Johnson &amp; Johnson and may own stock/have stock options in Johnson &amp; Johnson. Received medical writing assistance funded by Johnson &amp; Johnson. Wang, Yuhua: Employee of Johnson &amp; Johnson and hold Johnson &amp; Johnson stocks and options. Received medical writing assistance funded by Johnson &amp; Johnson. Dr. Ufberg, Paul: Employee of Johnson &amp; Johnson and may hold stock or stock options in Johnson &amp; Johnson. Received medical writing assistance funded by Johnson &amp; Johnson. Van Limbergen, Els: Employee of Johnson &amp; Johnson and may own/have stock options in Johnson &amp; Johnson. Received medical writing assistance funded by Johnson &amp; Johnson.

Ulcerative colitis (UC) is a chronic condition that may require long-term treatment. We report the final efficacy and safety results of the UNIFI long-term extension study of ustekinumab in patients with UC through 4 years. Ustekinumab induction responders who completed 44 weeks of maintenance treatment and agreed to enter the long-term extension continued their subcutaneous maintenance therapy (90 mg ustekinumab every 8 or 12 weeks [q8w or q12w] or placebo). Starting at week 56, randomized patients could receive dose adjustment to 90 mg q8w. Symptoms and adverse events were assessed through the study; endoscopic assessment was conducted at week 200. Of the 348 patients randomized to subcutaneous ustekinumab at maintenance baseline (q8w and q12w combined), 55.2% were in symptomatic remission at week 200. A greater proportion of biologic-naive patients (67.2% [117/174]) were in symptomatic remission than those with a history of biologic failure (41.6% [67/161]). Among patients in symptomatic remission at week 200, 96.4% were corticosteroid-free. Of the 171 patients with endoscopic evaluation at week 200, 81.6% (71/87) in the q12w group and 79.8% (67/84) in the q8w group had endoscopic improvement. From weeks 156 to the final safety visit (up to week 220), no deaths, major adverse cardiovascular events, or tuberculosis occurred in patients receiving ustekinumab. Nasopharyngitis, UC worsening, and upper respiratory tract infections were the most frequently reported adverse events. The long-term efficacy of ustekinumab maintenance in patients with UC was confirmed through 4 years. No new safety signals were observed. ClinicalTrials.gov number NCT02407236.