Long-term Efficacy Of Ustekinumab Research Articles

Real-World Data on Short-Term and Long-Term Treatment Results of Ustekinumab in Patients with Steroid-Resistant/Dependent Ulcerative Colitis

Introduction: Ustekinumab is an IgG1 kappa monoclonal antibody directed against the common p40 subunit of interleukin-12 and interleukin-23, which activate Th1- and Th17-mediated immune responses, respectively. It has proven efficacy for the treatment of moderate to severe ulcerative colitis (UC) in the UNIFI phase III clinical trial; however, data on its efficacy in the real world are limited. In this study, we aimed to assess the real-world efficacy of ustekinumab. Methods: This observational study included 30 patients with UC who received ustekinumab from April 2020 to April 2022. We examined demographic information, disease type and activity (Mayo score, partial Mayo score [PMS]), use of biologics, concomitant use of predonisolone (PSL), 8-week ustekinumab clinical response rate, remission induction rate, 44- and 152-week remission maintenance rate, continuation rate, and 44-week steroid-free remission rate. The primary outcomes were the short- and long-term efficacy of ustekinumab. Results: Included patients (53% women; mean age: 41.2 years [16–80 years]) had an average disease duration of 86 weeks. The Mayo score (median) was 7.4 and the PMS was 5.4. Two (7%), 24 (80%), and four (13%) patients had a Mayo endoscopic subscore (MES) of MES1, MES2, and MES3, respectively. The median serum CRP was 1.0 mg/dL. Five patients had no history of biotherapy (naive), while eight and 17 had a history of one and two or more biologic agents, respectively. Eight patients were PSL-resistant and 22 were PSL-dependent. The 8-week clinical response rate was 73% and the clinical remission induction rate was 70%. The remission maintenance rates at 44 and 152 weeks were 67% and 63%, respectively. The ustekinumab retention rate was 67% (86-week mean follow-up period). Regarding biologic failure cases, the clinical response rate in the failure group with up to one biologic agent (including naive cases) was 84.6%, which was higher than the 58.0% rate in the failure group with two or more biologic agents (p = 0.06). Steroid-free remission rates at 44 and 152 weeks were 63% each. In the logistic regression analysis parameters for discontinuation of ustekinumab, only PMS remained significant after multivariate analysis (p = 0.018). Conclusion: Our study showed short-term and long-term ustekinumab effectiveness, especially with comparative low disease activity.

P420 Long term efficacy of ustekinumab in Crohn’s disease patients after vedolizumab failure

Abstract Background Ustekinumab (UST) and vedolizumab (VDZ) are approved biologic therapies for moderate-to-severe Crohn’s disease (CD). Data regarding their comparative efficacy in patients previously treated with anti-TNF agents are available. However, data is lacking regarding their long-term effectiveness after failure of a second or third-line biologic treatment. Our aim is to evaluate ustekinumab efficacy after swapping from vedolizumab therapy for primary or secondary failure. Methods We conducted a single-centre, retrospective study in CD patients treated with UST as third line biologic therapy who swapped from VDZ therapy upon failure between January, 2019 and October, 2021. We assessed clinical (HBI), laboratoristic (CRP), endoscopic (SES-CD) activity and use of steroids at the beginning of ustekinumab therapy and after, 12 months of treatment. We also collected data regarding previous biologic treatments. Clinical remission was defined as HBI <, 5, while clinical response was defined as a reduction of at least three points of HBI from baseline and/or the suspension of steroids. Results Of, 43 patients treated with UST after VDZ failure, 26 had a minimum follow up of, 12 months and were included in the study. All patients had previously been treated with antiTNF agents. After, 12 months, 4 patients have suspended treatment for failure; among patients still on treatment, clinical remission was evident in, 63% (n = 14) of cases, 13 of them were also in laboratoristic remission. Endoscopy at, 12 months was available in, 11/14 patients in clinical remission; of these, 6 (55%) were in endoscopic remission. In patients who did not achieve clinical remission, 18% (n = 4) obtained clinical response. The last, 18% (n = 4) of patients persisted on therapy. Conclusion Ustekinumab seems to be a viable and effective therapeutic option in patients with failure to multiple prior biologic therapies, obtaining deep remission after, 12 months of treatment in a large proportion of patients.

Long-Term Efficacy of Ustekinumab With and Without Concomitant Immunosuppressants for Crohnʼs Disease: Results From IM-UNITI Long-Term Extension Through 2 Years

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.

Long-term efficacy of ustekinumab and absolute PASI response in patients with moderate-to-severe psoriasis in a dermatology department of a university hospital

Long-term efficacy of ustekinumab and absolute PASI response in patients with moderate-to-severe psoriasis in a dermatology department of a university hospital

The Clinical and Cost Effectiveness of Ustekinumab for the Treatment of Psoriatic Arthritis: A Critique of the Evidence.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of ustekinumab (Janssen) to submit evidence for the clinical and cost effectiveness of ustekinumab for the treatment of active psoriatic arthritis (PsA) as part of the Institute's single technology appraisal (STA) process. The Centre for Reviews and Dissemination and the Centre for Health Economics Technology Appraisal Group at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the ERG review of the manufacturer's evidence submission, and summarises the NICE Appraisal Committee's final guidance (TA340) issued in June 2015. The manufacturer presented evidence on ustekinumab for two patient populations: (1) a tumour necrosis factor-α (TNFα)-inhibitor-naïve population who had not previously received any TNFα inhibitors (biologics); and (2) a TNFα-inhibitor-exposed population who had previously received at least one TNFα inhibitor. The clinical evidence for ustekinumab was derived from two randomised controlled trials (PSUMMIT 1 and 2), in which a total of 927 patients who had not responded to previous disease-modifying antirheumatic drug therapies received ustekinumab 45 mg, ustekinumab 90 mg, or placebo. These data suggested that ustekinumab is more effective than placebo over 16-24 weeks in terms of both joint and skin response. In the absence of head-to-head comparisons between different biologics (ustekinumab, golimumab, etanercept, adalimumab and infliximab), the manufacturer conducted a network meta-analysis to estimate the relative efficacy of treatments for the TNFα-inhibitor-naïve population. Results of this analysis were marked as academic in confidence and are therefore not reported. For the TNFα-inhibitor-exposed population, the clinical analysis was limited to ustekinumab versus conventional management only, and was based on a subgroup of 180 patients from the PSUMMIT 2 trial. The ERG raised concerns relating to the lack of data on the long-term efficacy of ustekinumab, the limited data available for the exposed population, and the lack of consideration of the sequential use of treatments. Based on the manufacturer's original model, the ERG found ustekinumab to be dominated by golimumab in the anti-TNF-inhibitor-naïve population, and had an incremental cost-effectiveness ratio (ICER) of £29,843/quality-adjusted life-years versus conventional management in the exposed population. The ERG's analyses highlighted the fact that there is significant uncertainty around the model results. In addition, the ERG's exploratory cost-effectiveness analysis, which incorporated the sequential use of TNFα inhibitors, suggested that ustekinumab would not be cost effective if it were used as second-line treatment. The initial NICE recommendations asserted that ustekinumab was not recommended for treating active PsA. However, the manufacturer submitted a post-consultation model that included a Patient Access Scheme (PAS), halving the unit cost of ustekinumab 90 mg to £2147 (the same as a 45 mg dose). The NICE final recommendations were that, dependent on the inclusion of the PAS, ustekinumab is recommended as an option, along or in combination with methotrexate, for treating active PsA in adults only when treatment with TNFα inhibitors is contraindicated but would otherwise be considered, or the person has previously had treatment with one or more TNFα inhibitors, which has failed.

Long-term efficacy of ustekinumab in patients with moderate-to-severe psoriasis: results from the PHOENIX 1 trial through up to 3 years

An unmet need remains for safe and effective long-term treatments of psoriasis. To evaluate ustekinumab efficacy and safety for up to 3 years in the PHOENIX 1 trial. Patients (n = 766) with moderate-to-severe psoriasis were randomized to ustekinumab 45 mg or 90 mg at weeks 0 and 4, and then every 12 weeks, or placebo at weeks 0 and 4, with crossover to ustekinumab at week 12. Ustekinumab responders [≥ 75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at weeks 28 and 40] were re-randomized at week 40 to continue or withdraw from treatment until psoriasis recurrence. Partial responders (week 28: PASI 50-74; week 40: < PASI 75) switched to dosing every 8 weeks. Clinical efficacy was assessed by PASI, the Physician's Global Assessment (PGA), and the Dermatology Life Quality Index (DLQI) measures. Overall, 79·8% of the ustekinumab-treated patients remained in the study for 3 years. PASI 75 response rates (45 mg: 61·2%; 90 mg: 72·4%) at week 76 were maintained through year 3 (45 mg: 62·7%; 90 mg: 72·2%); PGA response was similarly durable. At year 3, 80·9% (45 mg) and 82·7% (90 mg) of week 40 responders continuing treatment every 12 weeks achieved a PASI 75 response, while 42·6% (45 mg) and 58·0% (90 mg) achieved a PASI 90 response. Among partial responders adjusted to dosing every 8 weeks, 50·9% (45 mg) and 52·0% (90 mg) had a PASI 75 response at year 3. DLQI responses paralleled the PASI responses. Through year 3, no dose response was observed in rates of adverse events (AEs), overall infections, serious AEs, or AEs leading to discontinuation; nor was there evidence of cumulative organ toxicity. CONCLUSIONS; Continuous, stable, maintenance dosing with ustekinumab was generally well tolerated and sustained durable efficacy for up to 3 years of treatment.