array(41) {
  ["project_title"]=>
  string(108) "A Comparison of the Rapidity of Clinical Response between Infliximab and Tofacitinib for Ulcerative Colitis."
  ["project_narrative_summary"]=>
  string(547) "Active ulcerative colitis (UC) is a disabling condition and rapid resolution of symptoms is a main concern of both patients and their physicians. There are many choices for initial treatment but very few studies have compared the speed at which remission is achieved between different agents. In this study, we are planning to compare the rapidity of response to infliximab (IFX), a chimeric monoclonal anti-TNF antibody, and tofacitinib (TOF), an oral small molecule JAK inhibitor. We will be using data from the ACT and OCTAVE induction studies."
  ["project_learn_source"]=>
  string(9) "colleague"
  ["project_learn_source_exp"]=>
  string(111) "New question comparing rapidity of response. We pool data from the YODA Project with other data sources (VIVLI)"
  ["project_key_personnel"]=>
  array(1) {
    [0]=>
    array(6) {
      ["p_pers_f_name"]=>
      string(6) "Shahin"
      ["p_pers_l_name"]=>
      string(5) "Merat"
      ["p_pers_degree"]=>
      string(2) "MD"
      ["p_pers_pr_affil"]=>
      string(0) ""
      ["p_pers_scop_id"]=>
      string(10) "6603772416"
      ["requires_data_access"]=>
      string(0) ""
    }
  }
  ["project_ext_grants"]=>
  array(2) {
    ["value"]=>
    string(68) "No external grants or funds are being used to support this research."
    ["label"]=>
    string(68) "No external grants or funds are being used to support this research."
  }
  ["project_funding_source"]=>
  string(0) ""
  ["project_assoc_trials"]=>
  array(2) {
    [0]=>
    object(WP_Post)#4701 (24) {
      ["ID"]=>
      int(1114)
      ["post_author"]=>
      string(4) "1363"
      ["post_date"]=>
      string(19) "2014-09-22 10:31:00"
      ["post_date_gmt"]=>
      string(19) "2014-09-22 10:31:00"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(159) "NCT00036439 - A Randomized, Placebo-controlled, Double-blind Trial to Evaluate the Safety and Efficacy of Infliximab in Patients With Active Ulcerative Colitis"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(4) "open"
      ["ping_status"]=>
      string(4) "open"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(155) "nct00036439-a-randomized-placebo-controlled-double-blind-trial-to-evaluate-the-safety-and-efficacy-of-infliximab-in-patients-with-active-ulcerative-colitis"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2024-05-13 12:54:39"
      ["post_modified_gmt"]=>
      string(19) "2024-05-13 16:54:39"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(204) "https://dev-yoda.pantheonsite.io/clinical-trial/nct00036439-a-randomized-placebo-controlled-double-blind-trial-to-evaluate-the-safety-and-efficacy-of-infliximab-in-patients-with-active-ulcerative-colitis/"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
    [1]=>
    object(WP_Post)#4700 (24) {
      ["ID"]=>
      int(1117)
      ["post_author"]=>
      string(4) "1363"
      ["post_date"]=>
      string(19) "2014-09-22 10:36:00"
      ["post_date_gmt"]=>
      string(19) "2014-09-22 10:36:00"
      ["post_content"]=>
      string(0) ""
      ["post_title"]=>
      string(159) "NCT00096655 - A Randomized, Placebo-controlled, Double-blind Trial to Evaluate the Safety and Efficacy of Infliximab in Patients With Active Ulcerative Colitis"
      ["post_excerpt"]=>
      string(0) ""
      ["post_status"]=>
      string(7) "publish"
      ["comment_status"]=>
      string(4) "open"
      ["ping_status"]=>
      string(4) "open"
      ["post_password"]=>
      string(0) ""
      ["post_name"]=>
      string(155) "nct00096655-a-randomized-placebo-controlled-double-blind-trial-to-evaluate-the-safety-and-efficacy-of-infliximab-in-patients-with-active-ulcerative-colitis"
      ["to_ping"]=>
      string(0) ""
      ["pinged"]=>
      string(0) ""
      ["post_modified"]=>
      string(19) "2024-05-13 12:52:14"
      ["post_modified_gmt"]=>
      string(19) "2024-05-13 16:52:14"
      ["post_content_filtered"]=>
      string(0) ""
      ["post_parent"]=>
      int(0)
      ["guid"]=>
      string(204) "https://dev-yoda.pantheonsite.io/clinical-trial/nct00096655-a-randomized-placebo-controlled-double-blind-trial-to-evaluate-the-safety-and-efficacy-of-infliximab-in-patients-with-active-ulcerative-colitis/"
      ["menu_order"]=>
      int(0)
      ["post_type"]=>
      string(14) "clinical_trial"
      ["post_mime_type"]=>
      string(0) ""
      ["comment_count"]=>
      string(1) "0"
      ["filter"]=>
      string(3) "raw"
    }
  }
  ["project_date_type"]=>
  string(91) "Individual Participant-Level Data, which includes Full CSR and all supporting documentation"
  ["property_scientific_abstract"]=>
  string(2528) "Background:
The speed of which clinical and endoscopic remission is achieved in patients with sever UC is very important. Both IFX and TOF have been approved for induction of remission in UC but there is no information as to which agent can achieve this goal faster.
Objectives:
Comparing the speed of achievement of remission between IFX and TOF.
Study Design:
This will be a post-hoc analysis of the ACT (1 and 2) and OCTAVE (1 and 2) study. The IFX studies compared IFX with placebo and the other two TOF with placebo and their data is publicly available. Data will be requested from all these studies through the YODA and VIVLI platforms. The rates of remission in different time points in patients not receiving placebo will be calculated and the relative rapidity of response will be compared between IFX and TOF.
Participants
Patients were eligible for the IFX studies if they had a confirmed diagnosis of UC with a Mayo score of 6 to 12 or endoscopic subscore of 2 or more. The TOF studies enrolled similar patients with the additional requirement of previous treatment failure with other agents. We will use patients receiving 5mg/kg IFX from the IFX studies and 10mg TOF twice daily from the TOF studies. Subjects with previous biologic treatment failure in the TOF studies will be excluded.
Outcomes
- Clinical remission at week 8. Defined as adapted Mayo Score ?2 with stool frequency subscore ?1 and not greater than baseline, rectal bleeding subscore of 0, and Mayo endoscopic subscore ?1
- Clinical response at week 8. Defined as a decrease in adapted Mayo score ?2 points and ?30% from baseline and a decrease in rectal bleeding subscore ?1 or an absolute rectal bleeding score ?1.
- Clinical response at week 2. Defined as a decrease in partial adapted Mayo score ?1 point and ?30% from baseline and a decrease in rectal bleeding subscore ?1 or an absolute rectal bleeding score ?1.
Statistical Analysis
Descriptive statistics will be used to summarize the proportion of patients achieving clinical outcomes. Logistic regression will be used to model the likelihood of achieving outcomes. Propensity score matching will be used to compensate for differences in baseline characteristics and prior and concomitant treatments between treatment groups. The propensity scores will be obtained using a nonparsimonious logistic regression model based on age, sex, disease duration, and other pertinent variables available in studys' data." ["project_brief_bg"]=> string(1574) "Infliximab (IFX) is an anti-TNF chimeric antibody that was the first approved biologic treatment for ulcerative colitis. Unfortunately, not all patients respond or continue to respond favorably to IFX. Some patients might not tolerate the adverse events and some might simply not have access to it. Since IFX introduction, many other agents, including full-human anti-TNF antibodies, integrin receptor antagonists, and Janus kinase (JAK) inhibitors have been approved for initial treatment of UC or for patients not responding or ceasing to respond to other treatments.
Tofacitinib (TOF) is an oral small molecule JAK inhibitor and is technically not a biologic agent. It was initially approved for treating rheumatoid arthritis as a disease-modifying drug (DMARD) and there is considerable safety information from those studies. During the last decade, TOF has produced favorable results in ulcerative colitis and is now also approved for the initial treatment of this disease. The availability of TOF as an oral treatment has made it particularly attractive for many patients.
Given the now numerous choices for treating UC and their relatively comparable efficacy, the physician is left with the dilemma of which agent to use first. One of the factors which might affect a physician?s decision, among other concerns such as cost and availability, is the rapidity at which symptom resolution would be achieved. Unfortunately, few studies directly address this issue and there is considerable interest in the speed at which patients respond to different agents." ["project_specific_aims"]=> string(209) "In this study, we aim to use publicly available data from previous studies in the YODA and VIVLI platforms to determine and compare the time it takes for IFX or TOF to induce remission or clinical improvement." ["project_study_design"]=> string(0) "" ["project_study_design_exp"]=> string(0) "" ["project_purposes"]=> array(3) { [0]=> array(2) { ["value"]=> string(36) "Participant-level data meta-analysis" ["label"]=> string(36) "Participant-level data meta-analysis" } [1]=> array(2) { ["value"]=> string(69) "Meta-analysis using data from the YODA Project and other data sources" ["label"]=> string(69) "Meta-analysis using data from the YODA Project and other data sources" } [2]=> array(2) { ["value"]=> string(5) "Other" ["label"]=> string(5) "Other" } } ["project_purposes_exp"]=> string(0) "" ["project_software_used"]=> array(2) { ["value"]=> string(5) "STATA" ["label"]=> string(5) "STATA" } ["project_software_used_exp"]=> string(0) "" ["project_research_methods"]=> string(768) "We will request the data for the IFX studies (reference 1, NCT00036439, NCT00096655) from the YODA project and data from TOF studies (references 2 and 3, NCT01465763, NCT01458951, NCT00787202) from the VIVLI platform.
The IFX and TOF studies mentioned above include moderate to severe confirmed cases of UC defined as a Mayo score of 6-12 in addition to either a non-zero rectal bleeding subscore or an endoscopic subscore of 2 or more.
We will use patients receiving 5mg/kg IFX from the IFX studies in the primary analysis and sensitivity analysis will be done looking at the 10mg/kg group. We will use subjects randomized to10mg TOF twice daily from the TOF studies. Subjects with previous biologic treatment failure in the TOF studies will be excluded." ["project_main_outcome_measure"]=> string(601) "- Clinical remission at week 8. Defined as adapted Mayo Score ?2 with stool frequency subscore ?1 and not greater than baseline, rectal bleeding subscore of 0, and Mayo endoscopic subscore ?1
- Clinical response at week 8. Defined as a decrease in adapted Mayo score ?2 points and ?30% from baseline and a decrease in rectal bleeding subscore ?1 or an absolute rectal bleeding score ?1.
- Clinical response at week 2. Defined as a decrease in partial adapted Mayo score ?1 points and ?30% from baseline and a decrease in rectal bleeding subscore ?1 or an absolute rectal bleeding score ?1." ["project_main_predictor_indep"]=> string(25) "Tofacitinib vs infliximab" ["project_other_variables_interest"]=> string(0) "" ["project_stat_analysis_plan"]=> string(1159) "Descriptive statistics will be used to summarize the proportion of patients achieving clinical outcomes.
Logistic regression will be used to model the likelihood of achieving outcomes.
As this is not a head-to-head RCT, we will use different methods to limit the potential for confounding. We will use multiple logistic regression models adjusted for significant baseline co-variates on univariate analyses. We will also calculate propensity scores to create a cohort of matched participants with a similar distribution of baseline scores.
Univariate analyses will be conducted to identify any association between baseline covariates and the outcomes of interest. A p-value threshold of < 0.10 will be used for the selection of variables from univariate analyses to include in the multivariate models. Potential confounders as determined by univariate analyses will be adjusted for in the multivariate analysis. Depending on the results, we expect to include age, gender, treatment received, baseline PMS ?6, baseline Mayo endoscopic score of 3, concomitant immunomodulator use, concomitant steroid use, baseline CRP (mg/L), baseline albumin" ["project_timeline"]=> string(158) "Date to Start Project: 2022-3-1
Date to Complete Analysis: 2022-9-1
Date to Draft Manuscript: 2021-10-1
Date to Submit Manuscript: 2022-11-1" ["project_dissemination_plan"]=> string(379) "Results of this study may be shared by presentations and abstracts in scientific meetings and conferences. A manuscript will be submitted for publication. The VIVLI and YODA projects will be acknowledged in all study products. We will consider Digestive Disease Week (DDW) and United European Gastroenterology (UEGW) for the abstract and Clin Gastroenterol Hepatol for the paper." ["project_bibliography"]=> string(661) "

1. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005;353(23):2462-76. doi: 10.1056/NEJMoa050516 [published Online First: 2005/12/13]
2. Sandborn WJ, Su C, Sands BE, et al. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med 2017;376(18):1723-36. doi: 10.1056/NEJMoa1606910 [published Online First: 2017/05/04]
3. Sandborn WJ, Ghosh S, Panes J, et al. Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. N Engl J Med 2012;367(7):616-24. doi: 10.1056/NEJMoa1112168 [published Online First: 2012/08/17]

" ["project_suppl_material"]=> bool(false) ["project_coi"]=> array(2) { [0]=> array(1) { ["file_coi"]=> array(21) { ["ID"]=> int(9468) ["id"]=> int(9468) ["title"]=> string(6) "sm_coi" ["filename"]=> string(10) "sm_coi.pdf" ["filesize"]=> int(245177) ["url"]=> string(59) "https://yoda.yale.edu/wp-content/uploads/2019/08/sm_coi.pdf" ["link"]=> string(52) "https://yoda.yale.edu/data-request/2021-4757/sm_coi/" ["alt"]=> string(0) "" ["author"]=> string(4) "1363" ["description"]=> string(0) "" ["caption"]=> string(0) "" ["name"]=> string(6) "sm_coi" ["status"]=> string(7) "inherit" ["uploaded_to"]=> int(5635) ["date"]=> string(19) "2023-07-31 15:43:58" ["modified"]=> string(19) "2023-08-01 01:00:34" ["menu_order"]=> int(0) ["mime_type"]=> string(15) "application/pdf" ["type"]=> string(11) "application" ["subtype"]=> string(3) "pdf" ["icon"]=> string(62) "https://yoda.yale.edu/wp/wp-includes/images/media/document.png" } } [1]=> array(1) { ["file_coi"]=> array(21) { ["ID"]=> int(9359) ["id"]=> int(9359) ["title"]=> string(6) "nn_coi" ["filename"]=> string(10) "nn_coi.pdf" ["filesize"]=> int(848292) ["url"]=> string(59) "https://yoda.yale.edu/wp-content/uploads/2018/05/nn_coi.pdf" ["link"]=> string(52) "https://yoda.yale.edu/data-request/2021-4757/nn_coi/" ["alt"]=> string(0) "" ["author"]=> string(4) "1363" ["description"]=> string(0) "" ["caption"]=> string(0) "" ["name"]=> string(6) "nn_coi" ["status"]=> string(7) "inherit" ["uploaded_to"]=> int(5635) ["date"]=> string(19) "2023-07-31 15:38:32" ["modified"]=> string(19) "2023-08-01 01:00:34" ["menu_order"]=> int(0) ["mime_type"]=> string(15) "application/pdf" ["type"]=> string(11) "application" ["subtype"]=> string(3) "pdf" ["icon"]=> string(62) "https://yoda.yale.edu/wp/wp-includes/images/media/document.png" } } } ["data_use_agreement_training"]=> bool(true) ["certification"]=> bool(true) ["project_send_email_updates"]=> bool(true) ["project_status"]=> string(9) "published" ["project_publ_available"]=> bool(true) ["project_year_access"]=> string(4) "2022" ["project_rep_publ"]=> array(1) { [0]=> array(1) { ["publication_link"]=> array(3) { ["title"]=> string(31) "Digestive Diseases and Sciences" ["url"]=> string(60) "https://link.springer.com/article/10.1007/s10620-023-07956-8" ["target"]=> string(6) "_blank" } } } ["project_assoc_data"]=> array(1) { [0]=> string(8) "data_res" } ["project_due_dil_assessment"]=> array(21) { ["ID"]=> int(11227) ["id"]=> int(11227) ["title"]=> string(47) "yoda_project_due_diligence_assessment_2021-4575" ["filename"]=> string(51) "yoda_project_due_diligence_assessment_2021-4575.pdf" ["filesize"]=> int(142161) ["url"]=> string(100) "https://yoda.yale.edu/wp-content/uploads/2023/08/yoda_project_due_diligence_assessment_2021-4575.pdf" ["link"]=> string(93) "https://yoda.yale.edu/data-request/2021-4757/yoda_project_due_diligence_assessment_2021-4575/" ["alt"]=> string(0) "" ["author"]=> string(4) "1363" ["description"]=> string(0) "" ["caption"]=> string(0) "" ["name"]=> string(47) "yoda_project_due_diligence_assessment_2021-4575" ["status"]=> string(7) "inherit" ["uploaded_to"]=> int(5635) ["date"]=> string(19) "2023-08-09 17:31:33" ["modified"]=> string(19) "2023-08-09 19:14:34" ["menu_order"]=> int(0) ["mime_type"]=> string(15) "application/pdf" ["type"]=> string(11) "application" ["subtype"]=> string(3) "pdf" ["icon"]=> string(62) "https://yoda.yale.edu/wp/wp-includes/images/media/document.png" } ["project_title_link"]=> array(21) { ["ID"]=> int(11380) ["id"]=> int(11380) ["title"]=> string(31) "yoda_project_2021-4575-21-03-08" ["filename"]=> string(35) "yoda_project_2021-4575-21-03-08.pdf" ["filesize"]=> int(26755) ["url"]=> string(84) "https://yoda.yale.edu/wp-content/uploads/2023/08/yoda_project_2021-4575-21-03-08.pdf" ["link"]=> string(77) "https://yoda.yale.edu/data-request/2021-4757/yoda_project_2021-4575-21-03-08/" ["alt"]=> string(0) "" ["author"]=> string(4) "1363" ["description"]=> string(0) "" ["caption"]=> string(0) "" ["name"]=> string(31) "yoda_project_2021-4575-21-03-08" ["status"]=> string(7) "inherit" ["uploaded_to"]=> int(5635) ["date"]=> string(19) "2023-08-09 17:38:57" ["modified"]=> string(19) "2023-08-09 19:14:34" ["menu_order"]=> int(0) ["mime_type"]=> string(15) "application/pdf" ["type"]=> string(11) "application" ["subtype"]=> string(3) "pdf" ["icon"]=> string(62) "https://yoda.yale.edu/wp/wp-includes/images/media/document.png" } ["project_review_link"]=> array(21) { ["ID"]=> int(10638) ["id"]=> int(10638) ["title"]=> string(31) "yoda_project_review_-_2021-4575" ["filename"]=> string(35) "yoda_project_review_-_2021-4575.pdf" ["filesize"]=> int(3031527) ["url"]=> string(84) "https://yoda.yale.edu/wp-content/uploads/2023/08/yoda_project_review_-_2021-4575.pdf" ["link"]=> string(77) "https://yoda.yale.edu/data-request/2021-4757/yoda_project_review_-_2021-4575/" ["alt"]=> string(0) "" ["author"]=> string(4) "1363" ["description"]=> string(0) "" ["caption"]=> string(0) "" ["name"]=> string(31) "yoda_project_review_-_2021-4575" ["status"]=> string(7) "inherit" ["uploaded_to"]=> int(5635) ["date"]=> string(19) "2023-08-09 17:05:36" ["modified"]=> string(19) "2023-08-09 19:14:34" ["menu_order"]=> int(0) ["mime_type"]=> string(15) "application/pdf" ["type"]=> string(11) "application" ["subtype"]=> string(3) "pdf" ["icon"]=> string(62) "https://yoda.yale.edu/wp/wp-includes/images/media/document.png" } ["project_highlight_button"]=> array(3) { ["title"]=> string(22) "Publication Available!" ["url"]=> string(60) "https://link.springer.com/article/10.1007/s10620-023-07956-8" ["target"]=> string(6) "_blank" } ["search_order"]=> string(5) "-9940" } data partner
array(1) { [0]=> string(15) "johnson-johnson" }

pi country
array(1) { [0]=> string(6) "Canada" }

pi affil
array(1) { [0]=> string(5) "Other" }

products
array(1) { [0]=> string(8) "remicade" }

num of trials
array(1) { [0]=> string(1) "2" }

res
array(1) { [0]=> string(1) "1" }

2021-4757

General Information

How did you learn about the YODA Project?: Colleague

Conflict of Interest

Request Clinical Trials

Associated Trial(s):
  1. NCT00036439 - A Randomized, Placebo-controlled, Double-blind Trial to Evaluate the Safety and Efficacy of Infliximab in Patients With Active Ulcerative Colitis
  2. NCT00096655 - A Randomized, Placebo-controlled, Double-blind Trial to Evaluate the Safety and Efficacy of Infliximab in Patients With Active Ulcerative Colitis
What type of data are you looking for?:

Request Clinical Trials

Data Request Status

Status: Published

Research Proposal

Project Title: A Comparison of the Rapidity of Clinical Response between Infliximab and Tofacitinib for Ulcerative Colitis.

Scientific Abstract: Background:
The speed of which clinical and endoscopic remission is achieved in patients with sever UC is very important. Both IFX and TOF have been approved for induction of remission in UC but there is no information as to which agent can achieve this goal faster.
Objectives:
Comparing the speed of achievement of remission between IFX and TOF.
Study Design:
This will be a post-hoc analysis of the ACT (1 and 2) and OCTAVE (1 and 2) study. The IFX studies compared IFX with placebo and the other two TOF with placebo and their data is publicly available. Data will be requested from all these studies through the YODA and VIVLI platforms. The rates of remission in different time points in patients not receiving placebo will be calculated and the relative rapidity of response will be compared between IFX and TOF.
Participants
Patients were eligible for the IFX studies if they had a confirmed diagnosis of UC with a Mayo score of 6 to 12 or endoscopic subscore of 2 or more. The TOF studies enrolled similar patients with the additional requirement of previous treatment failure with other agents. We will use patients receiving 5mg/kg IFX from the IFX studies and 10mg TOF twice daily from the TOF studies. Subjects with previous biologic treatment failure in the TOF studies will be excluded.
Outcomes
- Clinical remission at week 8. Defined as adapted Mayo Score ?2 with stool frequency subscore ?1 and not greater than baseline, rectal bleeding subscore of 0, and Mayo endoscopic subscore ?1
- Clinical response at week 8. Defined as a decrease in adapted Mayo score ?2 points and ?30% from baseline and a decrease in rectal bleeding subscore ?1 or an absolute rectal bleeding score ?1.
- Clinical response at week 2. Defined as a decrease in partial adapted Mayo score ?1 point and ?30% from baseline and a decrease in rectal bleeding subscore ?1 or an absolute rectal bleeding score ?1.
Statistical Analysis
Descriptive statistics will be used to summarize the proportion of patients achieving clinical outcomes. Logistic regression will be used to model the likelihood of achieving outcomes. Propensity score matching will be used to compensate for differences in baseline characteristics and prior and concomitant treatments between treatment groups. The propensity scores will be obtained using a nonparsimonious logistic regression model based on age, sex, disease duration, and other pertinent variables available in studys' data.

Brief Project Background and Statement of Project Significance: Infliximab (IFX) is an anti-TNF chimeric antibody that was the first approved biologic treatment for ulcerative colitis. Unfortunately, not all patients respond or continue to respond favorably to IFX. Some patients might not tolerate the adverse events and some might simply not have access to it. Since IFX introduction, many other agents, including full-human anti-TNF antibodies, integrin receptor antagonists, and Janus kinase (JAK) inhibitors have been approved for initial treatment of UC or for patients not responding or ceasing to respond to other treatments.
Tofacitinib (TOF) is an oral small molecule JAK inhibitor and is technically not a biologic agent. It was initially approved for treating rheumatoid arthritis as a disease-modifying drug (DMARD) and there is considerable safety information from those studies. During the last decade, TOF has produced favorable results in ulcerative colitis and is now also approved for the initial treatment of this disease. The availability of TOF as an oral treatment has made it particularly attractive for many patients.
Given the now numerous choices for treating UC and their relatively comparable efficacy, the physician is left with the dilemma of which agent to use first. One of the factors which might affect a physician?s decision, among other concerns such as cost and availability, is the rapidity at which symptom resolution would be achieved. Unfortunately, few studies directly address this issue and there is considerable interest in the speed at which patients respond to different agents.

Specific Aims of the Project: In this study, we aim to use publicly available data from previous studies in the YODA and VIVLI platforms to determine and compare the time it takes for IFX or TOF to induce remission or clinical improvement.

Study Design:

What is the purpose of the analysis being proposed? Please select all that apply.: Participant-level data meta-analysis Meta-analysis using data from the YODA Project and other data sources Other

Software Used: STATA

Data Source and Inclusion/Exclusion Criteria to be used to define the patient sample for your study: We will request the data for the IFX studies (reference 1, NCT00036439, NCT00096655) from the YODA project and data from TOF studies (references 2 and 3, NCT01465763, NCT01458951, NCT00787202) from the VIVLI platform.
The IFX and TOF studies mentioned above include moderate to severe confirmed cases of UC defined as a Mayo score of 6-12 in addition to either a non-zero rectal bleeding subscore or an endoscopic subscore of 2 or more.
We will use patients receiving 5mg/kg IFX from the IFX studies in the primary analysis and sensitivity analysis will be done looking at the 10mg/kg group. We will use subjects randomized to10mg TOF twice daily from the TOF studies. Subjects with previous biologic treatment failure in the TOF studies will be excluded.

Primary and Secondary Outcome Measure(s) and how they will be categorized/defined for your study: - Clinical remission at week 8. Defined as adapted Mayo Score ?2 with stool frequency subscore ?1 and not greater than baseline, rectal bleeding subscore of 0, and Mayo endoscopic subscore ?1
- Clinical response at week 8. Defined as a decrease in adapted Mayo score ?2 points and ?30% from baseline and a decrease in rectal bleeding subscore ?1 or an absolute rectal bleeding score ?1.
- Clinical response at week 2. Defined as a decrease in partial adapted Mayo score ?1 points and ?30% from baseline and a decrease in rectal bleeding subscore ?1 or an absolute rectal bleeding score ?1.

Main Predictor/Independent Variable and how it will be categorized/defined for your study: Tofacitinib vs infliximab

Other Variables of Interest that will be used in your analysis and how they will be categorized/defined for your study:

Statistical Analysis Plan: Descriptive statistics will be used to summarize the proportion of patients achieving clinical outcomes.
Logistic regression will be used to model the likelihood of achieving outcomes.
As this is not a head-to-head RCT, we will use different methods to limit the potential for confounding. We will use multiple logistic regression models adjusted for significant baseline co-variates on univariate analyses. We will also calculate propensity scores to create a cohort of matched participants with a similar distribution of baseline scores.
Univariate analyses will be conducted to identify any association between baseline covariates and the outcomes of interest. A p-value threshold of < 0.10 will be used for the selection of variables from univariate analyses to include in the multivariate models. Potential confounders as determined by univariate analyses will be adjusted for in the multivariate analysis. Depending on the results, we expect to include age, gender, treatment received, baseline PMS ?6, baseline Mayo endoscopic score of 3, concomitant immunomodulator use, concomitant steroid use, baseline CRP (mg/L), baseline albumin

Narrative Summary: Active ulcerative colitis (UC) is a disabling condition and rapid resolution of symptoms is a main concern of both patients and their physicians. There are many choices for initial treatment but very few studies have compared the speed at which remission is achieved between different agents. In this study, we are planning to compare the rapidity of response to infliximab (IFX), a chimeric monoclonal anti-TNF antibody, and tofacitinib (TOF), an oral small molecule JAK inhibitor. We will be using data from the ACT and OCTAVE induction studies.

Project Timeline: Date to Start Project: 2022-3-1
Date to Complete Analysis: 2022-9-1
Date to Draft Manuscript: 2021-10-1
Date to Submit Manuscript: 2022-11-1

Dissemination Plan: Results of this study may be shared by presentations and abstracts in scientific meetings and conferences. A manuscript will be submitted for publication. The VIVLI and YODA projects will be acknowledged in all study products. We will consider Digestive Disease Week (DDW) and United European Gastroenterology (UEGW) for the abstract and Clin Gastroenterol Hepatol for the paper.

Bibliography:

1. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005;353(23):2462-76. doi: 10.1056/NEJMoa050516 [published Online First: 2005/12/13]
2. Sandborn WJ, Su C, Sands BE, et al. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med 2017;376(18):1723-36. doi: 10.1056/NEJMoa1606910 [published Online First: 2017/05/04]
3. Sandborn WJ, Ghosh S, Panes J, et al. Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. N Engl J Med 2012;367(7):616-24. doi: 10.1056/NEJMoa1112168 [published Online First: 2012/08/17]