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.

scholarly journals The Safety Profile of Vedolizumab in Ulcerative Colitis and Crohn’s Disease: 4 Years of Global Post-marketing Data

2019 ◽  
Vol 14 (2) ◽  
pp. 192-204 ◽  
Author(s):  
Russell D Cohen ◽  
Fatima Bhayat ◽  
Aimee Blake ◽  
Simon Travis
Keyword(s):  
Ulcerative Colitis ◽  
Adverse Event ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Real World ◽  
Safety Profile ◽  
Safety Data ◽  
Real World Data ◽  
Safety Database ◽  
Post Marketing

Abstract Background and Aims Vedolizumab is a gut-selective antibody to α 4  β 7 integrin, approved to treat moderate-to-severe ulcerative colitis and Crohn’s disease in adults. Clinical trial data on patients meeting protocol-specified criteria may not reflect real-world clinical practice. This is a descriptive analysis of 4 years of post-marketing safety data on vedolizumab. Methods The Vedolizumab Global Safety Database contains all adverse event reports collated by Takeda Pharmaceutical Company Ltd since vedolizumab approval [May 20, 2014]. Adverse event reports received between approval and May 19, 2018 were identified using Medical Dictionary for Regulatory Activities version 21.0 Preferred Terms. Adverse event frequencies were calculated and categorised. Results In approximately 208 050 patient-years of vedolizumab exposure, 32 752 patients reported 80 218 events. In patients with Crohn’s disease or ulcerative colitis, 37 662 and 34 259 events occurred in 14 191 and 14 042 patients, respectively, and 8297 events occurred in 4519 individuals with other [off-label] or unreported indications. Overall, 5230 [14%; Crohn’s disease] and 3580 [10%; ulcerative colitis] events were serious. Most frequently reported were gastrointestinal events (Crohn’s disease, 6156 [16%]; ulcerative colitis, 5701 [17%]). Patients with Crohn’s disease or ulcerative colitis reported 251 malignancies [<1%], 402 hepatobiliary events [<1%], and 5876 infections (1137 serious [19%], 301 opportunistic [5%]). Patients aged ≥70 years [2326 patients] reported <10% of events. Conclusions Adverse event patterns were consistent with clinical trials, with no new safety concerns. Most reported events were non-serious and event frequency was low, considering patient-years of exposure. Although limitations of post-marketing safety reports require acknowledgement, these real-world data support a favourable safety profile of vedolizumab.

scholarly journals Real-world effectiveness of vedolizumab in inflammatory bowel disease: week 52 results from the Swedish prospective multicentre SVEAH study

2021 ◽  
Vol 14 ◽  
pp. 175628482110233
Author(s):  
Carl Eriksson ◽  
Sara Rundquist ◽  
Vyron Lykiardopoulos ◽  
Ruzan Udumyan ◽  
Per Karlén ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Real World ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Real World Data ◽  
Inflammatory Bowel

Background: Prospectively and systematically collected real-world data on vedolizumab are scarce. We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD). Methods: This study was a prospective, observational, multicentre study. Overall, 286 patients with active IBD were included (Crohn’s disease, n = 169; ulcerative colitis, n = 117). The primary outcomes were clinical response at week 12 and clinical remission at week 52, based on the Harvey Bradshaw Index and the partial Mayo Clinic score. Secondary outcomes included clinical remission at week 12, clinical response at week 52, corticosteroid-free clinical remission at week 52, changes in biochemical measures, and health-related quality of life (HRQoL). Results: At baseline, 88% of the patients were exposed to anti-TNF and 41% of the patients with Crohn’s disease had undergone ⩾1 surgical resection. At week 12, clinical response was 27% and remission 47% in Crohn’s disease; corresponding figures in ulcerative colitis were 52% and 34%. Clinical response, remission and corticosteroid-free remission at week 52 were 22%, 41% and 40% in Crohn’s disease and 49%, 47% and 46% in ulcerative colitis, respectively. A statistically significant decrease in median faecal-calprotectin and C-reactive protein was observed at 12 and 52 weeks in patients with Crohn’s disease and ulcerative colitis. The HRQoL measures Short Health Scale and EuroQol 5-Dimensions improved in both Crohn’s disease and ulcerative colitis patients ( p < 0.001). Clinical disease activity at baseline was inversely associated with clinical remission at week 52. Conclusion: Vedolizumab proved effective for the treatment of refractory IBD in clinical practice.

Prebiotics and Probiotics in Inflammatory Bowel Disease: Where are we now and where are we going?

2020 ◽  
Vol 15 (3) ◽  
pp. 216-233 ◽  
Author(s):  
Maliha Naseer ◽  
Shiva Poola ◽  
Syed Ali ◽  
Sami Samiullah ◽  
Veysel Tahan
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Clinical Trials ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Effects ◽  
Bowel Disease ◽  
Relapse Prevention ◽  
Remission Induction ◽  
Inflammatory Bowel

The incidence, prevalence, and cost of care associated with diagnosis and management of inflammatory bowel disease are on the rise. The role of gut microbiota in the causation of Crohn's disease and ulcerative colitis has not been established yet. Nevertheless, several animal models and human studies point towards the association. Targeting intestinal dysbiosis for remission induction, maintenance, and relapse prevention is an attractive treatment approach with minimal adverse effects. However, the data is still conflicting. The purpose of this article is to provide the most comprehensive and updated review on the utility of prebiotics and probiotics in the management of active Crohn’s disease and ulcerative colitis/pouchitis and their role in the remission induction, maintenance, and relapse prevention. A thorough literature review was performed on PubMed, Ovid Medline, and EMBASE using the terms “prebiotics AND ulcerative colitis”, “probiotics AND ulcerative colitis”, “prebiotics AND Crohn's disease”, “probiotics AND Crohn's disease”, “probiotics AND acute pouchitis”, “probiotics AND chronic pouchitis” and “prebiotics AND pouchitis”. Observational studies and clinical trials conducted on humans and published in the English language were included. A total of 71 clinical trials evaluating the utility of prebiotics and probiotics in the management of inflammatory bowel disease were reviewed and the findings were summarized. Most of these studies on probiotics evaluated lactobacillus, De Simone Formulation or Escherichia coli Nissle 1917 and there is some evidence supporting these agents for induction and maintenance of remission in ulcerative colitis and prevention of pouchitis relapse with minimal adverse effects. The efficacy of prebiotics such as fructooligosaccharides and Plantago ovata seeds in ulcerative colitis are inconclusive and the data regarding the utility of prebiotics in pouchitis is limited. The results of the clinical trials for remission induction and maintenance in active Crohn's disease or post-operative relapse with probiotics and prebiotics are inadequate and not very convincing. Prebiotics and probiotics are safe, effective and have great therapeutic potential. However, better designed clinical trials in the multicenter setting with a large sample and long duration of intervention are needed to identify the specific strain or combination of probiotics and prebiotics which will be more beneficial and effective in patients with inflammatory bowel disease.

scholarly journals Real-World Data for Planning Eligibility Criteria and Enhancing Recruitment: Recommendations from the Clinical Trials Transformation Initiative

2021 ◽  
Author(s):  
Scott R. Evans ◽  
Dianne Paraoan ◽  
Jane Perlmutter ◽  
Sudha R. Raman ◽  
John J. Sheehan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Real World Data ◽  
Eligibility Criteria ◽  
World Data ◽  
Study Planning ◽  
Efficiency And Effectiveness ◽  
Multi Stakeholder ◽  
Functional Teams ◽  
Data Driven Decisions

AbstractThe growing availability of real-world data (RWD) creates opportunities for new evidence generation and improved efficiency across the research enterprise. To varying degrees, sponsors now regularly use RWD to make data-driven decisions about trial feasibility, based on assessment of eligibility criteria for planned clinical trials. Increasingly, RWD are being used to support targeted, timely, and personalized outreach to potential trial participants that may improve the efficiency and effectiveness of the recruitment process. This paper highlights recommendations and resources, including specific case studies, developed by the Clinical Trials Transformation Initiative (CTTI) for applying RWD to planning eligibility criteria and recruiting for clinical trials. Developed through a multi-stakeholder, consensus- and evidence-driven process, these actionable tools support researchers in (1) determining whether RWD are fit for purpose with respect to study planning and recruitment, (2) engaging cross-functional teams in the use of RWD for study planning and recruitment, and (3) understanding patient and site needs to develop successful and patient-centric approaches to RWD-supported recruitment. Future considerations for the use of RWD are explored, including ensuring full patient understanding of data use and developing global datasets.

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