Safety Of Ustekinumab Research Articles

P1063 Comparison of all paediatric patients and young adults with Crohn’s Disease treated with ustekinumab in the REALITI Real-World Evidence Effectiveness Study

Abstract Background Treatment of paediatric patients (pts) with Crohn’s disease (CD) can offer some challenges to providers. There is an urgent need to inform prescribers about paediatric efficacy, safety, and dosing. REALITI evaluated the effectiveness and safety of ustekinumab (UST) routine clinical care in paediatric pts (age 2 to <18) regardless of disease severity or baseline corticosteroid use. Reference data are shown for young adults (age 18 to 25) with CD, for whom UST is approved. Data were obtained from the ImproveCareNow (ICN) Registry. Methods Data from pts from ICN with CD initiating treatment with UST between 10 January 2010 and 29 February 2020 were evaluated. A supplemental, retrospective chart review collected data not in ICN. The primary endpoint was clinical remission (Short Paediatric CD Activity Index [sPCDAI] score ≤10) at Week (Wk) 52. Data were summarized descriptively, and the proportion of pts achieving clinical remission and associated 2-sided 95% confidence intervals (CI) were calculated along with rates of inflammatory bowel disease (IBD)-related hospitalization and surgeries and serious/opportunistic infections. Results Overall, 479 pts in ICN with CD were treated with UST. We report an analysis of paediatric pts (n=348) compared to young adults (n=131). Most paediatric pts (98.9%) and young adults (95.4%) had received prior biologic therapy, with approximately half (47.1% and 50.4%, respectively) receiving corticosteroids at baseline. Slightly higher proportions of pts had moderate to severe disease (sPCDAI ≥30) among paediatric pts (49.7%) vs young adults (44.8%). Clinical remission at Wk52 was achieved in 30.2% of paediatric pts (105/348; 95% CI: [25.6%, 35.2%]) vs 28.2% of young adults (37/131; 95% CI: [21.2%, 36.5%]) (Figure 1A). Clinical remission rates decreased slightly over time from Wk 20-52 (Figure 1B); discontinuation rates through WK 52 remained low and were similar between groups (21.0%, 22.9%, respectively). Overall, 31.9% of paediatric pts and 19.8% of young adults had IBD-related hospitalizations; IBD-related surgery was reported in 16.1% and 9.2% of pts, respectively. Serious infections occurred in 7.5% of paediatric pts and 3.8% of young adults. Rates of opportunistic infections were low (1.4%, 0%, respectively). No events of tuberculosis, malignancy, or anaphylaxis requiring UST discontinuation occurred. One death, deemed by investigators as unrelated to IBD or UST treatment, was reported among paediatric pts; no deaths were reported among young adults. Conclusion Using real-world data from the ICN Registry, the remission rates for using UST to treat CD were found to be generally comparable between paediatric pts and young adults. No new safety signals were identified.

P958 Comparison of Paediatric Patients and Young Adults with Moderately to Severely Active Crohn’s Disease Treated with Ustekinumab in the REALITI Real-World Evidence Effectiveness Study

Abstract Background Few approved treatment options exist for paediatric patients (pts) with Crohn’s disease (CD). Paediatric inflammatory bowel disease (IBD) medication approvals are delayed nearly 7 years after adult approvals,1 resulting in off-label use and potential for incorrect dosing. The REALITI Study evaluated the effectiveness and safety of ustekinumab (UST) in routine clinical care in paediatric pts (age 2-<18) and young adults (age 18-25) with moderately to severely active CD (Short Paediatric CD activity [sPCDAI] score ≥30) using data from the ImproveCareNow (ICN) Registry. Methods Effectiveness data from pts with CD treated with UST were extracted from the ICN Registry between 10 January 2010 and 29 February 2020. A supplemental, retrospective chart review was conducted to collect data not in the ICN Registry. The primary endpoint was clinical remission (sPCDAI≤10) at Week (Wk) 52. All data were summarized descriptively, and the proportion of pts achieving clinical remission and associated 2-sided 95% confidence interval were calculated across multiple populations. Rates of discontinuations, IBD-related hospitalizations, surgeries, and serious infections were also calculated. Results A total of 479 CD pts in ICN were treated with UST, including 348 paediatric pts and 131 young adults. We report an analysis of 114 paediatric pts who weighed >40 kg and had a sPCDAI ≥30. All pts were treatment refractory; 99.1% had not responded to prior biologic therapies, with less than 1% biologic naïve. Results were compared to 51 ICN young adults with moderately to severely active CD, a population for which UST is approved. Clinical remission at Wk 52 was achieved in 22.8% (26/114; 95% CI: 16.1%, 31.3%) of paediatric pts vs 21.6% (11/51; 95% CI:12.5%, 34.6%) of young adults (Figure 1A). Discontinuation rates through Wk 52 were similar between paediatric pts (25.4%) and young adults (25.5%; Figure 1B). Overall, 36.0% of paediatric pts and 21.6% of young adults had IBD-related hospitalizations. IBD-related surgery was reported in 14.0% of paediatric pts and 11.8% of young adults. Serious infections occurred in 9.6% of paediatric pts and 3.9% of young adults. Opportunistic infections occurred in 1.8% of paediatric pts and 0% of young adults. No events of tuberculosis, malignancy, or anaphylaxis requiring UST discontinuation occurred in either group. No deaths were reported. Conclusion This study of real-world data from the ICN Registry found similar remissions rates in paediatric pts and young adults with CD treated with UST, suggesting comparable effectiveness of UST in both age groups. No new safety signals were identified. (Crowley E, et al. J Crohns Colitis. 2022 Feb 23;16(2):331-335.)

P834 Choosing wisely: Ustekinumab in Elderly Crohn’s Patients – A Comparative Study

Abstract Background The burden of Inflammatory Bowel Disease (IBD) in elderly patients derives from background comorbidities and the elevated risk associated with immunosuppressive treatments. In the present study, we aimed to assess the efficacy and safety of ustekinumab (UST) in elderly patients with Crohn's disease (CD). Methods This study was designed as a retrospective-cohort study including patients ≥ 60 years old (elderly) and patients < 60 years (non-elderly) who commenced UST for CD at a large, tertiary medical center. Outcomes were assessed by clinical response evaluation through parameters such as physician global assessment (PGA) and the Harvey-Bradshaw index (HBI), alongside assessment of clinical biomarkers, hospitalization rates, treatment persistence, and the necessity for surgical interventions. A secondary analysis was conducted of elderly patients treated with UST compared to elderly patients treated with vedolizumab (VDZ). Results In total, the primary analysis included 99 patients treated with UST (34 elderly patients and 65 non-elderly patients). Duration of follow-up was a median of 12 months (IQR 0). Elderly patients had predominantly an isolated ileal disease (68%) compared to an ileo-colonic disease (36%) in non-elderly patients (p = 0.017). The median age of onset was 68 years (IQR 64-75), and 34 years (IQR 28-42), respectively. Furthermore, elderly individuals were more likely to receive corticosteroids as their initial treatment (44% vs. 14%, <0.001). No differences were demonstrated in disease duration, EIM, phenotype, or previous biological therapy. Following six months of therapy, elderly patients were more likely to achieve complete clinical remission (31% vs. 12%, p = 0.035) as assessed by PGA. The elderly group experienced higher hospitalization rates during the 6-month (21% vs 4.6%, p = 0.029) and the 12-month follow-up period (15% vs. 3.1%, p = 0.045), while surgery rates were comparable between non-elderly and elderly groups (table 1). Concerning elderly UST vs elderly VDZ patients (n=69), no significant differences were observed in clinical response and remission rates between the groups after 6 and 12 months of follow up. In addition, no significant differences were shown in regard to safety (hospitalizations, surgery or therapy cessation rates). Conclusion UST is an effective treatment option in elderly CD patients. However, this population had higher hospitalization rates compared to non-elderly patients, greatly owing to age and comorbidities.

P698 Effectiveness and Safety of Ustekinumab for Ulcerative Colitis: A Brazilian Multicentre Real-World Observational Study

Abstract Background Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicentre cohort of Brazilian patients with UC. Methods We conducted a multicentre retrospective observational cohort study, including patients with moderate to severe UC (Total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of zero) within one year from baseline. Secondary endpoints included clinical response between weeks 12-16, endoscopic response within one year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety. Results A total of 50 patients were included (female, n=36, 72.0%), with a median disease duration of 9.2 years (1-27). Most patients had extensive colitis (n=38, 76.0%), and 43 (86.0%) were steroid-dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n=31; vedolizumab [VDZ], n=27). The co-primary endpoints of clinical remission and endoscopic remission at 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12-16 was 56.0%, endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 67.4%, and 50.0%, respectively. The UST treatment persistence rates at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and three patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-six adverse events (AEs) were reported, 15 of which were considered as serious AEs. Conclusion This is the first real-world experience study to report the effectiveness and safety of UST specifically in a Latin American population. In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST.

P280 Comparative responsiveness of disease activity indices in moderately-to-severely active Ulcerative Colitis: a post-hoc analysis of the UNIFI trial

Abstract Background Clinical, endoscopic, histological, and composite instruments are used to measure disease activity in ulcerative colitis (UC). We compared responsiveness of the Mayo Clinic Score (MCS), modified Mayo Clinic Score (mMS), partial Mayo Clinic Score (pMS), Robarts Histopathology Index (RHI), and UC-100 score after treatment with ustekinumab in patients with moderately-to-severely active UC. Methods Publicly available data from the phase 3 UNIFI induction trial (NCT02407236) comparing the efficacy and safety of ustekinumab versus placebo in patients with moderate-to-severe UC were obtained from Vivli (Vivli ID #7549) and Yale University Open Data Access Project (#2021-4848). Post-hoc analyses were performed on patient level data to ascertain outcomes of interest. Treatment assignment was the criterion for change in evaluation of responsiveness, which was quantified using the probability of a treated patient having a larger change than a placebo patient (win probability [WinP]) and estimated using nonparametric methods. Extent of responsiveness was interpreted according to Cohen’s benchmarks as very small (WinP<0.56); small (0.56≤ WinP<0.64); medium (0.64≤ WinP<0.71); and large (WinP≥0.71). Results Data from 961 patients with moderately-to-severely active UC randomised in UNIFI were included. At baseline, 319 patients received placebo and 624 patients received ustekinumab. A total of 912 (94.9%) patients completed the induction trial. Overall mean baseline index scores were: MCS 8.9 (±1.6), mMS 6.6 (±1.3), pMS 6.2 (±1.4), RHI 16.6 (±8.1), and UC-100 score 71.4 (±16.5) (Table). The UC-100 demonstrated a large degree of responsiveness (WinP 0.72 [95% CI: 0.66, 0.78]). The MCS (0.68 [0.62, 0.73]), mMS (0.69 [0.63, 0.75]), and pMS (0.65 [0.59, 0.71]) demonstrated similar, medium effect sizes (all comparisons p>0.05) (Figure). The RHI alone had a relatively small effect size (WinP 0.63 [0.56-0.70]). Among individual UC-100 components (Mayo Clinic stool frequency subscore, Mayo Clinic endoscopic subscore, and RHI), the endoscopic score was most responsive (WinP 0.59 [0.36-0.82]). The combination of endoscopy and RHI was associated with a medium degree of responsiveness (WinP 0.69 ([0.34, 1.00]). Conclusion UC disease activity indices are similarly responsive to change. Depending on trial design and measurement feasibility, different instruments can be considered optimal for evaluation of efficacy. The mMS is similarly responsive to the MCS without including the physician global assessment and may be more appropriate for determining trial eligibility and defining primary endpoint, whereas the UC-100 may be more appropriate for measuring treatment effect when an objective continuous measure is needed.

Infant Ustekinumab Clearance, Risk of Infection, and Development After Exposure During Pregnancy

Background and aimEvidence on ustekinumab safety in pregnancy is gradually expanding, but its clearance in the postnatal period is unknown. The aim of this study was to investigate ustekinumab concentrations in umbilical cord blood and rates of clearance after birth, as well as how these correlate with maternal drug concentrations, risk of infection, and developmental milestones during the first year of life. MethodsPregnant women with inflammatory bowel disease were prospectively recruited from 19 hospitals in Denmark and the Netherlands between 2018 and 2022. Infant infections leading to hospitalization/antibiotics, and developmental milestones were assessed. Serum ustekinumab concentrations were measured at delivery and specific time-points. Non-linear regression analysis was applied to estimate clearance. ResultsIn 78 live-born infants from 76 pregnancies, we observed a low risk of adverse pregnancy outcomes and normal developmental milestones. At birth, the median infant:mother ustekinumab ratio was 2.18 (95%CI,1.69-2.81). Mean time to infant clearance was 6.7 (95%CI,6.1-7.3) months. One-in-four infants at 6 months had an extremely low median concentration of 0.015 μg/ml (range:0.005-0.12) . No variation in median ustekinumab concentration was noted between infants with (2.8μg/ml; range,0.4-6.9) and without (3.1μg/ml; range,0.7-11.0) infections during the first year of life (p=0.41). ConclusionsNo adverse signals after intrauterine exposure to ustekinumab were observed with respect to pregnancy outcome, infections, or developmental milestones during the first year of life. Infant ustekinumab concentration was not associated with risk of infections. With the ustekinumab clearance profile, live attenuated vaccination from 6 months of age seems of low risk.

Efficacy and Safety of Ustekinumab for Ulcerative Colitis Through 4 Years: Final Results of the UNIFI Long-Term Maintenance Study.

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.

Role of ustekinumab in treatment of ulcerative colitis: a narrative review.

The therapeutic armamentarium for gastroenterologists in treating ulcerative colitis (UC) has been rapidly growing since the introduction of monoclonal antibodies directed against anti-TNFs. Ustekinumab is a monoclonal antibody binding the shared p40 subunit of IL-12and IL-23, and the inhibition of these two cytokines, implicated in host response to microbial pathogens, has demonstrated clinical efficacy in different immune-mediated diseases, including moderate-to-severe UC. This narrative review summarizes the newest clinical evidence regarding the efficacy, effectiveness and safety of ustekinumab in moderate-to-severe UC, including specific situations (pregnancy, breastfeeding, elderly/pediatric populations, extraintestinal manifestations, acute severe UC, pouchitis anddual biological therapy). Finally, positioning is discussed in light of the existing evidence.

Use of ustekinumab after other biological therapies in moderate-severe psoriasis: Real long-term data

ObjectiveUstekinumab is used in moderate-severe plaque psoriasis with inadequate response to anti-tumour necrosis factor a drugs. Recent studies support the need to assess real long-term data. The aim of this study was to evaluate the real long-term effectiveness and safety of ustekinumab in moderate-severe plaque psoriasis refractory to 2 anti-tumour necrosis factor a drugs. MethodRetrospective descriptive study from January 2010 to March 2019. The study included patients with moderate-severe plaque psoriasis previously treated with at least 2 anti-tumour necrosis factor a biologic drugs. The effectiveness endpoints were Psoriasis Area and Severity Index 90 and 75 response rates at weeks 24, 48, 72, and 96. Safety was assessed using adverse effects and treatment withdrawal. ResultsA total of 36 patients were included (men, 61%). Ustekinumab was used after treatment with 2 anti-tumour necrosis factor a drugs in 88.9% of patients. The biologic drugs most frequently administered prior to ustekinumab were infliximab (94.4%) and etanercept (91.7%). It was observed that at least 66.7% of patients reached Psoriasis Area and Severity Index 90 at weeks 24, 48, 72, and 96. Adverse effects were recorded in 6 patients. There were no treatment withdrawals. ConclusionsUstekinumab showed real long-term effectiveness and safety in moderate-severe plaque psoriasis with inadequate response to 2 previous anti-tumour necrosis factor a drugs.

Real-world effectiveness and safety of ustekinumab in bio-naive patients with moderate-to-severe Crohn's disease: A Canadian multi-center study

BackgroundClinical practice guidelines recommend ustekinumab as a first-line biological treatment option for moderately-to-severely active Crohn's disease (CD). However, there is limited real-world effectiveness and safety data in bio-naïve patients. AimsTo assess ustekinumab effectiveness and safety in bio-naïve CD patients. MethodsMedical charts were reviewed retrospectively at seven Canadian centers. The primary outcome was the proportion of patients achieving clinical remission at Month 6 following ustekinumab initiation. Secondary outcomes included clinical, biochemical, and endoscopic response, and remission at Months 4, 6 and 12. Ustekinumab safety was assessed over the one-year follow-up period. Results158 charts were reviewed. Clinical remission was achieved by 50.0% (36/72), 67.7% (105/155), and 73.7% (84/114) of patients at Months 4, 6, and 12, respectively. At these study timepoints, biochemical remission was observed in 65.2% (43/66), 71.6% (63/88), and 73.9% (68/92) of patients. At Months 6 and 12, endoscopic remission was observed in 40.5% (15/37) and 56.3% (27/48) of patients, respectively. Most participants (93.5%; 145/155) persisted on ustekinumab through Month 12. No serious adverse drug reactions were reported. ConclusionIn this real-world study, ustekinumab presents as an effective first-line biologic for induction and maintenance of remission among bio-naïve Canadian patients with moderately-to-severely active CD.

O09 Long-term safety of ustekinumab in paediatric patients with moderate-to-severe plaque psoriasis: results from an ongoing observational study

Abstract The European Medicines Agency approved ustekinumab for psoriasis treatment in adolescents (12–17 years) in 2015 (CADMUS trial), and children (6–11 years) in 2020. Interim results are reported from a post-authorization study (NCT03218488) evaluating the long-term safety profile of ustekinumab. This ongoing, prospective, observational, multicentre study enrolled patients (6–17 years) diagnosed with moderate-to-severe plaque psoriasis initiating ustekinumab. Clinical data and all adverse events (AEs) through approximately 54 months (data cut-off) are reported. Younger children (6–11 years) were included later in the study. Data are reported by age (younger cohort, 6–11; older cohort, 12–17). At data cut-off, 85 patients, 10 younger (median follow-up, 0.24 years) and 75 older (median follow-up, 1.69 years), had been enrolled. Ustekinumab therapy was discontinued in 11 (12.9%) patients, all from the older cohort. Overall, 50/85 (58.8%) patients reported 290 AEs and 27 (31.8%) reported 96 AEs considered related to ustekinumab. The most commonly reported AEs were nasopharyngitis (n = 8, 9.4%), fatigue (n = 7, 8.2%) and headache (n = 7, 8.2%). Most AEs were mild and did not result in treatment change. Nine (10.6%) patients reported 13 serious AEs; one (appendicitis) was considered related to ustekinumab. One younger patient reported two AEs considered related to ustekinumab, although neither was serious and therapy continued. No malignancies or deaths were reported in either cohort. These findings revealed no new safety concerns and are generally consistent with the known safety profile for ustekinumab in paediatric patients.

Effectiveness and safety of ustekinumab for the treatment of psoriasis; six years of clinical experience

BackgroundThis work aimed to investigate the long-term clinical experience with ustekinumab in cases with psoriasis.Materials and methodsThis retrospective cohort research group consisted of cases who presented to the dermatology outpatient clinics between January 2015 and January 2021, diagnosed with psoriasis, and were treated with ustekinumab. Data including gender, age, weight, disease duration, naïve and non-naïve status, psoriasis type, duration of medication, comorbidities, psoriasis area and severity index scores, the causes of treatment discontinuation, and previous treatments were retrospectively reviewed and analyzed.Results160 cases with psoriasis were treated with ustekinumab during the research period. Twenty-four patients were excluded. Among 136 cases, 84 (61.8%) were male and 52 (38.2%) were female. We determined 80.55% of the non-naïve cases responded to ustekinumab.ConclusionUstekinumab can be a suitable treatment option for non-naïve and resistant patients. Our data suggest the positive effect persists in cases with favorable responses to the first or second dose of ustekinumab. Also, we determined male cases gave more rapid and more robust responses than female cases, and patients were more willing about continuing the treatment.

Phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group study of ustekinumab in Japanese patients with active polymyositis and dermatomyositis who have not adequately responded to one or more standard-of-care treatments

ObjectivesTo evaluate the efficacy and safety of ustekinumab (UST) in a multicentre, randomised, double-blind, placebo-controlled trial in adult Japanese patients with active polymyositis (PM) and dermatomyositis (DM).MethodsFifty-one Japanese adults diagnosed...

Real-world effectiveness and safety of ustekinumab and vedolizumab in elderly patients with Crohn's disease.

Studies report favorable efficacy and safety profiles of ustekinumab (UST) and vedolizumab (VDZ) in Crohn's disease (CD), but effectiveness and safety data in elderly patients with CD is lacking. We retrospectively analyzed 78 elderly patients (39 each UST and VDZ) and found that patients on UST and VDZ experienced similar rates of clinical response, remission and mucosal healing despite high proportion of prior biologic exposure. Both UST and VDZ appear to be effective and safe in this at-risk CD population. Further large studies are needed to validate our findings.

Comparison of Effectiveness and Safety of Ustekinumab and Adalimumab As Induction or Maintenance Therapy in Patients With Moderate to Severe Crohn's Disease: A Systematic Review and Meta-Analysis.

This meta-analysis has been conducted to compare ustekinumab and adalimumab as induction or maintenance therapy in patients with moderate to severe Crohn's disease (CD).The current meta-analysis was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).Two investigators independently searched online databases including PubMed, Cumulated Index to Nursing and Allied Health Literature (CINAHL), and Cochrane Library for relevant articles published up to April 2023. The initial search terms were "ustekinumab," "adalimumab," and "Crohn's disease". Three studies (with a total of 612 patients) were included in the present meta-analysis. Wedid not find any significant difference in clinical remission (OR: 1.31, 95% CI: 0.68-2.52), clinical response (OR: 1.39, 95% CI: 0.39-4.91),endoscopic remission (OR: 1.56, 95% CI: 0.66-3.64), and steroid-free remission(OR: 0.98, 95% CI: 0.67-1.42) between patients who received ustekinumab and patients who received adalimumab.In conclusion, this meta-analysis provides valuable insights into the efficacy and safety of ustekinumab and adalimumab in the treatment of moderate to severe CD. Our findings indicate that both drugs have similar effectiveness in achieving clinical remission, clinical response, radiological remission and steroid-free remission.

A critical review of ustekinumab for the treatment of active ulcerative colitis in adults

ABSTRACT Introduction Ustekinumab is a humanized monoclonal antibody, targeting the p40 subunit common to both human interleukin 12 and 23, approved by the European Medicines Agency and US Food and Drug Administration for the treatment of moderate-to-severe ulcerative colitis. Areas covered In this review, the results of the phase 3 UNIFI and the real-world studies assessing the efficacy and safety of ustekinumab in moderate-to-severe ulcerative colitis are discussed, as well as limitations of these studies. Predictive factors of response, the interest of therapeutic drug monitoring and the positioning of ustekinumab in specific situations are also addressed. Finally, in the light of data presented, the positioning of ustekinumab in the therapeutic algorithm of ulcerative colitis will also be considered. Expert opinion Ustekinumab has been shown to be effective to induce and maintain clinical, endoscopic and histologic remission in moderate-to-severe ulcerative colitis both in phase 3 and real-world studies, with a favorable safety profile. Overall, its favorable risk–benefit ratio, its efficacy on extra-intestinal manifestations and in biologics failure patients make ustekinumab an ideal candidate as first, second, or third-line therapy in ulcerative colitis.

Efficacy and safety of ustekinumab in Russian bionaive patients with moderately to severely active ulcerative colitis: a subanalys is of global phase 3 induction and maintenance studies (UNIFI) up to 3 years

AIM: to evaluate efficacy and safety of ustekinumab in Russian patients with ulcerative colitis in UNIFI study. PATIENTS AND METHODS: the UNIFI program (CNTO1275UCO3001) consisted of two randomized placebo-controlled trials: an 8-week induction study and a 44-week maintenance study and long-term period. This analysis included patients from 14 Russian centers.RESULTS: the induction study of the UNIFI program enrolled 74 patients from Russia, 89.2% patients (n = 66) were bionaive. The paper presents the results of bionaive patients. Sixty-six are included in the induction phase: 18 received ustekinumab 130 mg IV, 25 received ustekinumab 6 mg/kg IV, and 23 received a placebo. At week 8 in the groups of patients treated with ustekinumab at doses of 6 mg/kg and 130 mg, clinical remission was achieved in 24.0% and 16.7%, respectively, in the placebo group, the rate was 17.4%. The proportion of patients with clinical responses at week 8 was 68.0%, 50.0% and 39.1% in the ustekinumab 6 mg/kg, 130 mg and placebo groups, respectively. Mucosal healing at week 8 was achieved in 48.0% in the ustekinumab 6 mg/kg group, in 33.3% of patients in the ustekinumab 130 mg group, and in 21.7% of patients in the placebo group. Histoendoscopic mucosal healing at week 8 developed in 27.8% of patients in the ustekinumab 130 mg group, in 24.0% of patients in the ustekinumab 6 mg/kg group, and in 21.7% of patients in the placebo group. Forty bionaive patients were re-randomized for further participation in the maintenance phase: 13 patients received ustekinumab 90 mg subcutaneously every 12 weeks, 12 received ustekinumab every 8 weeks, and 15 received a placebo. At week 44, clinical remission was achieved in 46.2% of ustekinumab every 12 weeks, 75.0% of ustekinumab every 8 weeks (p = 0.054 compared with placebo), and 33.3% of placebo. Mucosal healing achieved in 46.2% of patients in the ustekinumab once every 12 weeks group, in 75.0% of patients in the ustekinumab once every 8 weeks group (p = 0.054 compared with. placebo), and in 33.3% of patients in the placebo group. Histoendoscopic mucosal healing achieved in 46.2% of patients in the ustekinumab once every 12 weeks group, while in the ustekinumab once every 8 weeks group, the percentage of such patients was 75.0% (p = 0.021 compared with placebo) and in the placebo group — 26.7%. Symptomatic remission at week 152 developed in 83.3% in the ustekinumab every 12 weeks group, 81.8% in the ustekinumab every 8 weeks group. In the induction phase decrease of CRP and FCP median levels detected in patients treated with ustekinumab, in the maintenance phase, median levels of laboratory inflammatory markers after induction were sustained by ustekinumab treatment. The rate of steroid-free symptomatic remission at week 152 was consistent with the rate of symptomatic remission. The safety profile of ustekinumab was generally consistent with placebo during all follow up period.CONCLUSION: subanalysis confirmed shortand long-term efficacy and safety in Russian patients with moderate to severe active ulcerative colitis. The results of subanalysis are consistent with previously obtained data in the population of patients participating in the global UNIFI program.

Ustekinumab Versus Anti-tumour Necrosis Factor Alpha Agents as Second-Line Biologics in Crohn's Disease

BackgroundThere are little data on positioning biologics in Crohn's disease (CD).AimsWe aimed to assess the comparative effectiveness and safety of ustekinumab vs tumour necrosis factor-alpha (anti-TNF) agents after first-line treatment with anti-TNF in CD.MethodsWe used Swedish nationwide registers to identify patients with CD, exposed to anti-TNF who initiated second-line biologic treatment with ustekinumab or second-line anti-TNF therapy. Nearest neighbour 1:1 propensity score matching (PSM) was used to balance the groups. The primary outcome was 3-year drug survival used as a proxy for effectiveness. Secondary outcomes included drug survival without hospital admission, CD-related surgery, antibiotics, hospitalization due to infection and exposure to corticosteroids.ResultsSome 312 patients remained after PSM. Drug survival at 3 years was 35% (95% CI 26–44%) in ustekinumab compared to 36% (95% CI 28–44%) in anti-TNF-treated patients (p = 0.72). No statistically significant differences were observed between the groups in 3-year survival without hospital admission (72% vs 70%, p = 0.99), surgery (87% vs 92%, p = 0.17), hospital admission due to infection (92% vs 92%, p = 0.31) or prescription of antibiotics (49% vs 50%, p = 0.56). The proportion of patients continuing second-line biologic therapy did not differ by reason for ending first-line anti-TNF (lack of response vs intolerance) or by type of first-line anti-TNF (adalimumab vs infliximab).ConclusionBased on data from Swedish routine care, no clinically relevant differences in effectiveness or safety of second-line ustekinumab vs anti-TNF treatment were observed in patients with CD with prior exposure to anti-TNF.

Predictive factors of the clinical efficacy of ustekinumab in patients with refractory Crohn's disease: tertiary centers experience in Japan.

Therapeutic efficacy of ustekinumab in the real-world data is limited in patients with refractory Crohn's disease (CD). In addition, factors predictive of better therapeutic efficacy of ustekinumab remains unsolved in CD. We aimed to evaluate therapeutic efficacy of ustekinumab in patients with refractory CD and to identify the factors associated with the efficacy of ustekinumab. We retrospectively analyzed the clinical data of 72 patients treated with ustekinumab for refractory CD. Therapeutic efficacy was assessed at weeks 8, 26, 52, and 104 on the basis of dual remission, defined as the combination of Crohn's Disease Activity Index < 150 and CRP < 0.3mg/dL, and factors predictive of the induction and maintenance of dual remission were investigated. The cumulative continuation rates and safety of ustekinumab were assessed. The dual remission rates at weeks 8, 26, 52, and 104 were 31.9%, 37.9%, 47.5%, and 42.6%, respectively. A short disease duration (≤ 2years) and higher baseline serum albumin levels (≥ 3.1g/dL) were positively associated with dual remission at weeks 8 and 52. Meanwhile, higher serum CRP levels (≥ 1.19mg/dL) were negatively associated with dual remission at week 8. The cumulative ustekinumab continuation rate was favorable, and no severe adverse events were found. A short disease duration and higher baseline serum albumin levels might be predictive of favorable therapeutic efficacy of ustekinumab in refractory CD. Induction efficacy appears to be lower in patients with higher serum CRP levels.

Systematic Review and Meta-Analysis of Observational Studies on the Effectiveness and Safety of Ustekinumab among Patients with Inflammatory Bowel Disease in Eastern and Western Countries.

Ustekinumab (UST) is an IL12/23 inhibitor utilized for altering inflammatory responses in inflammatory bowel disease (IBD). Clinical trials and case reports suggested that the effectiveness and safety of UST may differ among IBD patients in Eastern and Western countries. However, related data have not been systematically reviewed and analyzed. This systematic review and meta-analysis of the safety and effectiveness of UST in IBD included relevant literature from the Medline and Embase databases. The main outcomes were clinical response, clinical remission, endoscopic response, endoscopic remission, and adverse events in IBD. We analyzed 49 real-world studies, most of which included patients with biological failure (89.1% CD and 97.1% UC). In UC patients, clinical remission rates were 34% at 12 weeks, 40% at 24 weeks, and 37% at 1 year. In CD patients, clinical remission rates were 46% at 12 weeks, 51% at 24 weeks, and 47% at 1 year. Clinical remission rates of CD patients were 40% at 12 weeks and 44% at 24 weeks in Western countries, versus 63% and 72% in Eastern countries, respectively. UST is an effective drug for IBD with a promising safety profile. Although no RCTs have been performed in Eastern countries, the effectiveness of UST on CD patients is not inferior to that in Western countries based on the existing data.