Superior treatment persistence with ustekinumab in Crohn’s disease and vedolizumab in ulcerative colitis compared with anti‐TNF biological agents: real‐world registry data from the Persistence Australian National IBD Cohort (PANIC) study

2021 ◽  
Author(s):  
Yanna Ko ◽  
Sudarshan Paramsothy ◽  
Yunki Yau ◽  
Rupert W. Leong
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Real World ◽  
Biological Agents ◽  
Registry Data ◽  
Treatment Persistence

scholarly journals P361 The effect of immunomodulators and other factors on the persistence of biological agents for Crohn’s disease and ulcerative colitis: data from the Australian population-based registry

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S342-S343 ◽  
Author(s):  
Y Ko ◽  
S Paramsothy ◽  
R Leong
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Real World ◽  
Population Based ◽  
Biological Agents ◽  
Treatment Persistence ◽  
Persistence Rate ◽  
Third Line ◽  
Population Based Registry

Abstract Background Treatment persistence (duration of medication use) provides real-world evidence on therapeutic effectiveness, tolerability and prescriber and patient preferences. Biological agent persistence in Crohn’s disease (CD) and ulcerative colitis (UC) was compared from a national population-based registry with no hierarchical prescribing order. We hypothesised immunotherapy co-therapy would increase persistence for anti-TNF agents, but not for non-anti-TNF agents due to reduced immunogenicity. Methods A randomly selected ten per cent subgroup of the prospectively collected population-based registry from the Australian Pharmaceutical Benefits Scheme between June 2005 and June 2019 was analysed. Treatment persistence of adalimumab (ADA), infliximab (IFX), vedolizumab (VDZ) and ustekinumab (UST) was compared. Factors affecting discontinuation were evaluated using multivariate proportional hazard regression. Results 886 patients consisting of 1294 lines of therapy (992 CD, 302 UC, 2778 person-years of follow-up) were included. In CD, UST had the highest overall persistence rate (median persistence rate was > 74.6% where 24.6 months is the maximum follow-up time recorded), followed by VDZ, IFX and ADA (p = 0.03) (Figure 1). UST had the highest persistence as first, second and third-line therapies (p < 0.05). In UC, VDZ had the highest persistence rate (median persistence rate was >50.3% where 47.4 months is the maximum follow-up time recorded), followed by IFX and ADA (p < 0.001) (Figure 2). VDZ had the highest persistence rates as first-line therapy (p < 0.001), while second and third-line therapies did not demonstrate significant differences. Persistence of biological agents correlated with immunomodulator co-therapy in CD (R2: 0.65 p < 0.001) and UC (R2: 0.50 p < 0.001). Thiopurine co-therapy significantly increased persistence for IFX and ADA in CD and UC (p < 0.001) (Figures 3 and 4) but was not significant for UST and VDZ. Methotrexate decreased persistence for VDZ in UC and had no effects on UST, IFX and ADA in UC and CD. In acute-severe UC, there were no significant differences between IFX as monotherapy vs. co-therapy. On multivariate analysis, higher persistence was seen in males (HR: 0.75 95% CI: 0.59–0.94) and with immunomodulator co-therapy (HR 0.77 95% CI: 0.61–0.97, p = 0.03). Conclusion This real-world data reflecting treatment effectiveness, tolerability and patient and prescriber preferences supports the use of UST and VDZ over anti-TNF agents in CD and UC, respectively, to achieve high treatment persistence which is independent of immunomodulator co-therapy, possibly secondary to differing immunogenicity rates. It also highlights the substantial increase in anti-TNF therapy persistence with thiopurine co-therapy, but not with methotrexate.

scholarly journals A Comparison of the Randomized Clinical Trial Efficacy and Real-World Effectiveness of Tofacitinib for the Treatment of Inflammatory Bowel Disease: A Cohort Study

2019 ◽  
Author(s):  
Vivek A. Rudrapatna ◽  
Benjamin S. Glicksberg ◽  
Atul J. Butte
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Trials ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Real World ◽  
Controlled Trials ◽  
Real World Data ◽  
Eligibility Criteria ◽  
Primary Endpoints ◽  
Three Phase

AbstractBackgroundReal-world data are receiving attention from regulators, biopharmaceuticals and payors as a potential source of clinical evidence. However, the suitability of these data to produce evidence commensurate with randomized controlled trials (RCTs) and the best practices in their use remain unclear. We sought to compare the real-world effectiveness of Tofacitinib in the treatment of IBD against efficacy rates published by corresponding RCTs.MethodsElectronic health records at the University of California, San Francisco (UCSF) were queried and reviewed to identify 86 Tofacitinib-treated IBD patients through 4/2019. The primary endpoint was treatment effectiveness. This was measured by time-to-treatment-discontinuation and by the primary endpoints of RCTs in Ulcerative Colitis (UC) and Crohn’s Disease (CD). Endpoints were measured and analyzed following a previously published protocol and analysis plan.Findings86 patients (68 with UC, 18 with CD) initiated Tofacitinib for IBD treatment. Most of the data needed to calculate baseline and follow-up disease activity indices were documented within the EHR(77% for UC, 91% for CD). Baseline characteristics of the UCSF and RCT cohorts were similar, except for a longer disease duration and 100% treatment failure of Tumor Necrosis Factor inhibitors in the former. None of the UCSF cohort would have met the RCT eligibility criteria due to multiple reasons.The rate of achieving the RCT primary endpoints were highly similar to the published rates for both UC(16%, P=0·5) and CD (38%, P=0·8). However, treatment persistence was substantially higher: 69% for UC (week 52) and 75% for CD (week 26).InterpretationAn analysis of routinely collected clinical data can reproduce published Tofacitinib efficacy rates, but also indicates far greater treatment durability than suggested by RCTs including possible benefit in CD. These results underscore the value of real-world studies to complement RCTs.FundingThe National Institutes of Health and UCSF Bakar InstituteResearch in ContextEvidence before this studyTofacitinib is the most recently approved treatment for Ulcerative Colitis. Data related to treatment efficacy for either IBD subtype is generally limited, whether from controlled trials or real-world studies. A search of clinicaltrials.gov was performed in January 2019 for completed phase 2 or 3, interventional, placebo-controlled clinical trials matching the terms “Crohn’s Disease” OR “Ulcerative Colitis” in the conditions field, and matching “Placebo” AND “Tofacitinib” OR “CP-690,550”) in the Interventions field. We identified three Phase 3 trials for UC (OCTAVE trials, all initially reported in a single article in 2016) and three Phase 2 trials of CD (two published in the same article in 2017, one reported in 2014). The Phase 3 UC trials reported 57·6% pooled clinical response rate in the Tofacitinib-assigned groups after 8 weeks (induction), and a 37·5% pooled remission rate among eligible induction trial responders in the Tofacitinib-assigned groups at 52 weeks. The 2017 CD trial reported a 70·8% pooled rate of response or remission in the Tofacitinib-assigned groups after 8 weeks, and a 47·6% pooled rate of response or remission among enrolled induction-trial responders at 26 weeks. A bias assessment of both UC and CD trials indicated a high risk of attrition bias and unclear risk of bias related to conflicts of interest. We also performed a search of pubmed.gov in January 2019 using search terms (“Colitis” OR “Crohn’s”) AND (“Tofacitinib” OR “CP-690,550”) OR “real-world” to identify cohort studies of Tofacitinib efficacy in routine clinical practice. No studies meeting these criteria were identified.Added value of this studyThis is one of the early studies to closely compare the results of clinical trials with the continuously-updated data captured in the electronic health records, and the very the first to assess the efficacy-effectiveness gap for Tofacitinib. We found that none of the patients treated at our center thus far would have qualified for the clinical trial based on published eligibility criteria. We found that the drug appeared to perform similarly to its efficacy when using the endpoints reported in clinical trials, but treatment persistence was significantly greater than would have been expected from the reported trial outcomes: 69% for UC at week 52 and 75% for CD at week 26.Implications of all the available evidenceTofacitinib is an effective treatment for the Ulcerative colitis and may be efficacious for Crohn’s disease. Controlled trials may not be representative of real-world cohorts, may not be optimally designed to identify efficacious drugs, and may not accurately predict patterns of use in clinical practice. Further studies using real-world data as well as methods to enable their proper use are needed to confirm and continuously monitor the efficacy and safety of drugs, both for on- and off-label use.

UNDERSTANDING REAL-WORLD BIOLOGIC MAINTENANCE DOSING PATTERNS AMONG PEDIATRIC ULCERATIVE COLITIS AND CROHN’S DISEASE PATIENTS

2021 ◽  
Vol 160 (3) ◽  
pp. S30
Author(s):  
Wallace Crandall ◽  
Richard Colletti ◽  
Wendy Komocsar ◽  
Chunyan Liu ◽  
Jennifer Dotson ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Real World ◽  
Dosing Patterns

scholarly journals Real-World Experience With Acute Infusion Reactions to Ustekinumab at 2 Large Tertiary Care Centers

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Elizabeth A Spencer ◽  
Jami Kinnucan ◽  
Julie Wang ◽  
Marla C Dubinsky
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Real World ◽  
Tertiary Care ◽  
Retrospective Chart Review ◽  
Infusion Reaction ◽  
Large Tertiary Care ◽  
Infusion Reactions ◽  
Tertiary Care Centers

Abstract Background Ustekinumab is approved for Crohn’s disease and Ulcerative colitis with acute infusion reactions reported at a rate of 0.9%–4.5%. Methods A retrospective chart review was conducted on inflammatory bowel disease (IBD) patients experiencing an acute infusion reaction to ustekinumab at 2 large institutions. Results Acute ustekinumab infusion reactions occurred in 16 patients with Crohn’s disease (CD) and Ulcerative colitis (UC), at a rate of 0.8%–3%. Patients were all naïve to ustekinumab, receiving their initial IV induction. Ninety-three percent subsequently tolerated the injection without issues. Conclusions In this large, real-world study of acute infusion reactions to ustekinumab, the rate was similar to that seen in clinical trials—0.8%–3%.

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