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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-003262-25 | EudraCT Number | ||
| MK-8259-022 | Other Identifier | Merck Protocol Number |
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The purpose of this study is to evaluate serum soluble human ST2 protein, the receptor for Interleukin-33 (IL-33) and a member of the proinflammatory Interleukin-1 (IL-1) receptor superfamily, as a surrogate biological marker predictive of disease outcome and therapeutic response to golimumab treatment in participants with moderate to severe UC who have failed on prior conventional therapies. The primary endpoints of this study are to correlate serum soluble ST2 levels with endoscopic activity (endoscopic subscore of the Mayo score) and histological activity (Geboes index) of disease.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Golimumab treatment | Experimental | Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Golimumab | Biological | Golimumab 50mg/0.5 mL in a single-use, ready-to-use autoinjector. Golimumab is a fully human anti-TNF (tumor necrosis factor) alpha monoclonal antibody that will be administered SC. |
| Measure | Description | Time Frame |
|---|---|---|
| Serum ST2 Level at Week 6 | ST2, a serum biomarker, was collected at Week 6. ST2 levels were used to determine whether or not there is a correlation with endoscopic or histologic activity, or a clinical response to treatment in participants with moderate to severe Ulcerative Colitis. | Week 6 |
| Correlation of Serum Soluble ST2 Levels With Endoscopic Activity of Disease (Assessed by Endoscopy Subscore of Mayo Score) at Week 6 | ST2, a serum biomarker, was collected at Week 6. Endoscopic Mayo subscore is one of 4 components that comprise the total Mayo Score, a scale for assessing ulcerative colitis (UC) activity. Endoscopic Mayo subscore ranges from 0-3: 0 = normal or inactive disease, 1 = mild disease (erythema, decreased vascular pattern, mild friability); 2 = moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). A higher score indicates more severe disease. Moderate correlation was defined as a Spearman correlation (rs) coefficient between -0.5 to -0.3 or 0.3 to 0.5. | Week 6 |
| Correlation of Serum Soluble ST2 Levels With Histological Activity (Assessed by Geboes Index) at Week 6 | ST2, a serum biomarker, was collected at Week 6. Geboes index, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher score indicates more severe disease. Moderate correlation was defined as rs coefficient between -0.5 to -0.3 or 0.3 to 0.5. | Week 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Serum ST2 Level at Week 16 | ST2, a serum biomarker, was collected at Week 16. ST2 levels were used to determine whether or not there is a correlation with endoscopic or histologic activity, or a clinical response to treatment in participants with moderate to severe Ulcerative Colitis. | Week 16 |
| Correlation of Serum Soluble ST2 Levels With Endoscopic Activity (Assessed by Endoscopy Subscore of Mayo Score) at Week 16 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30989180 | Result | Magro F, Lopes S, Silva M, Coelho R, Portela F, Branquinho D, Correia L, Fernandes S, Cravo M, Caldeira P, Sousa HT, Patita M, Lago P, Ramos J, Afonso J, Redondo I, Machado P, Cornillie F, Lopes J, Carneiro F; Portuguese IBD Group [GEDII]. Low Golimumab Trough Levels at Week 6 Are Associated With Poor Clinical, Endoscopic and Histological Outcomes in Ulcerative Colitis Patients: Pharmacokinetic and Pharmacodynamic Sub-analysis of the Evolution Study. J Crohns Colitis. 2019 Oct 28;13(11):1387-1393. doi: 10.1093/ecco-jcc/jjz071. | |
| 31516554 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Golimumab Treatment | Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 13, 2017 |
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ST2, a serum biomarker, was collected at Week 16. Endoscopic Mayo subscore is one of 4 components that comprise the total Mayo Score, a scale for assessing ulcerative colitis (UC) activity. Endoscopic Mayo subscore ranges from 0-3: 0 = normal or inactive disease, 1 = mild disease (erythema, decreased vascular pattern, mild friability); 2 = moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). A higher score indicates more severe disease. Moderate correlation was defined as rs coefficient between -0.5 to -0.3 or 0.3 to 0.5. |
| Week 16 |
| Correlation of Serum Soluble ST2 Levels With Histological Activity (Assessed by Geboes Index) at Week 16 | ST2, a serum biomarker, was collected at Week 16. Geboes index, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher score indicates more severe disease. Moderate correlation was defined as rs coefficient between -0.5 to -0.3 or 0.3 to 0.5. | Week 16 |
| Correlation of Serum Soluble ST2 Levels With Faecal Calprotectin Levels at Baseline and Week 6 and Week 16 | ST2 and faecal calprotectin, serum biomarkers, were collected at Week 6 and Week 16. Faecal calprotectin is a surrogate marker for the presence of intestinal inflammation and response to treatment in participants with Inflammatory Bowel Disease. Moderate correlation was defined as rs coefficient between -0.5 to -0.3 or 0.3 to 0.5. | Baseline, Weeks 6 and 16 |
| Correlation of Serum Soluble ST2 Levels With Clinical Activity (Assessed by Total Mayo Score) at Week 6 and Week 16 | ST2, a serum biomarker, was collected at Week 6 and Week 16. The total Mayo Score, is a scale for assessing UC activity and is the sum of 4 subscores (assessment of stool frequency [0-3], rectal bleeding [0-3], Physician's Global Assessment [0-3], and endoscopic Mayo subscore [0-3]) and has values that range from 0 to 12. Clinical remission: ≤2 points with no individual subscore > 1; Mildly active disease: 3-5 points; Moderately active disease: 6-10 points; Severely active disease: 11-12 points. A higher score indicates more severe disease. Moderate correlation was defined as rs coefficient between -0.5 to -0.3 or 0.3 to 0.5. | Weeks 6 and 16 |
| Change From Baseline to Week 6 in ST2 Levels in Participants With Active Versus Inactive UC | ST2, a serum biomarker, was collected at Baseline and Week 6. Active Ulcerative Colitis was defined as an endoscopic Mayo subscore ≥2 and inactive Ulcerative Colitis was defined as an endoscopic Mayo subscore of 0 or 1. | Baseline, Week 6 |
| Change From Baseline to Week 6 in ST2 Level According to Participant's Mayo Endoscopic Response at Week 16 (Maintained Response at Week 16 or Did Not Maintain Response at Week 16) | ST2, a serum biomarker, was collected at Baseline and Week 6. Comparison of participants who achieved endoscopic response [endoscopic Mayo subscore 0 or 1] at Week 6 and maintained response through Week 16 versus participants who did not maintain response throughout Week 16, regarding serum soluble ST2 at baseline, Week 6 and change between baseline and Week 6. | Baseline, Week 6 |
| Correlation of Endoscopic Mayo Subscore With Ulcerative Colitis Endoscopic Index Of Severity (UCEIS©) Overall Score at Week 6 and Week 16 | UCEIS© is a 3-item (vascular pattern, bleeding and erosion/ulceration) validated tool for assessing endoscopic severity of UC. Each item has 3 or 4 levels of severity and is given a score. The scores for each individual item are combined into a total score ranging from 1 to 11. A higher score indicates increased endoscopic severity of UC. Moderate correlation was defined as rs coefficient between -0.5 to -0.3 or 0.3 to 0.5. | Week 6 and Week 16 |
| Result |
| Magro F, Lopes S, Silva M, Coelho R, Portela F, Branquinho D, Correia L, Fernandes S, Cravo M, Caldeira P, Tavares de Sousa H, Patita M, Lago P, Ramos J, Afonso J, Redondo I, Machado P, Philip G, Lopes J, Carneiro F. Soluble human Suppression of Tumorigenicity 2 is associated with endoscopic activity in patients with moderate-to-severe ulcerative colitis treated with golimumab. Ther Adv Gastroenterol. 2019 Aug 30;12:1756284819869141. doi: 10.1177/1756284819869141. eCollection 2019. |
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| ID | Title | Description |
|---|---|---|
| BG000 | Golimumab Treatment | Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Serum human Suppression of Tumorigenicity 2 (ST2) level | ST2, a serum biomarker, was collected at Baseline. | Participants with available ST2 data | Mean | Standard Deviation | ng/mL |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Serum ST2 Level at Week 6 | ST2, a serum biomarker, was collected at Week 6. ST2 levels were used to determine whether or not there is a correlation with endoscopic or histologic activity, or a clinical response to treatment in participants with moderate to severe Ulcerative Colitis. | Participants with available Week 6 ST2 data. | Posted | Mean | Standard Deviation | ng/mL | Week 6 |
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| Primary | Correlation of Serum Soluble ST2 Levels With Endoscopic Activity of Disease (Assessed by Endoscopy Subscore of Mayo Score) at Week 6 | ST2, a serum biomarker, was collected at Week 6. Endoscopic Mayo subscore is one of 4 components that comprise the total Mayo Score, a scale for assessing ulcerative colitis (UC) activity. Endoscopic Mayo subscore ranges from 0-3: 0 = normal or inactive disease, 1 = mild disease (erythema, decreased vascular pattern, mild friability); 2 = moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). A higher score indicates more severe disease. Moderate correlation was defined as a Spearman correlation (rs) coefficient between -0.5 to -0.3 or 0.3 to 0.5. | Analysis population includes all participants who had received study medication, had at least one valid post-baseline assessment for the primary endpoint that correlates ST2 with endoscopic activity and/or histological activity, and had a Week 6 endoscopic Mayo subscore. | Posted | Number | 95% Confidence Interval | Spearman correlation (rs) coefficient | Week 6 |
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| Primary | Correlation of Serum Soluble ST2 Levels With Histological Activity (Assessed by Geboes Index) at Week 6 | ST2, a serum biomarker, was collected at Week 6. Geboes index, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher score indicates more severe disease. Moderate correlation was defined as rs coefficient between -0.5 to -0.3 or 0.3 to 0.5. | Analysis population includes all participants who had received study medication, had at least one valid post-baseline assessment for the primary endpoint that correlates ST2 with endoscopic activity and/or histological activity, and had a Week 6 Geboes index score. | Posted | Number | 95% Confidence Interval | rs coefficient | Week 6 |
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| Secondary | Serum ST2 Level at Week 16 | ST2, a serum biomarker, was collected at Week 16. ST2 levels were used to determine whether or not there is a correlation with endoscopic or histologic activity, or a clinical response to treatment in participants with moderate to severe Ulcerative Colitis. | Participants with available Week 16 ST2 data. | Posted | Mean | Standard Deviation | ng/mL | Week 16 |
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| Secondary | Correlation of Serum Soluble ST2 Levels With Endoscopic Activity (Assessed by Endoscopy Subscore of Mayo Score) at Week 16 | ST2, a serum biomarker, was collected at Week 16. Endoscopic Mayo subscore is one of 4 components that comprise the total Mayo Score, a scale for assessing ulcerative colitis (UC) activity. Endoscopic Mayo subscore ranges from 0-3: 0 = normal or inactive disease, 1 = mild disease (erythema, decreased vascular pattern, mild friability); 2 = moderate disease (marked erythema, absent vascular pattern, friability, erosions); 3 = Severe disease (spontaneous bleeding, ulceration). A higher score indicates more severe disease. Moderate correlation was defined as rs coefficient between -0.5 to -0.3 or 0.3 to 0.5. | Analysis population includes all participants who had received study medication and had at least one valid post-baseline assessment for the primary endpoint that correlates ST2 with endoscopic activity and/or histological activity, and had a Week 16 endoscopic Mayo subscore. | Posted | Number | 95% Confidence Interval | rs coefficient | Week 16 |
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| Secondary | Correlation of Serum Soluble ST2 Levels With Histological Activity (Assessed by Geboes Index) at Week 16 | ST2, a serum biomarker, was collected at Week 16. Geboes index, is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher score indicates more severe disease. Moderate correlation was defined as rs coefficient between -0.5 to -0.3 or 0.3 to 0.5. | Analysis population includes all participants who had received study medication and had at least one valid post-baseline assessment for the primary endpoint that correlates ST2 with endoscopic activity and/or histological activity, and had a Week 16 Geboes index score. | Posted | Number | 95% Confidence Interval | rs coefficient | Week 16 |
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| Secondary | Correlation of Serum Soluble ST2 Levels With Faecal Calprotectin Levels at Baseline and Week 6 and Week 16 | ST2 and faecal calprotectin, serum biomarkers, were collected at Week 6 and Week 16. Faecal calprotectin is a surrogate marker for the presence of intestinal inflammation and response to treatment in participants with Inflammatory Bowel Disease. Moderate correlation was defined as rs coefficient between -0.5 to -0.3 or 0.3 to 0.5. | Analysis population includes all participants who had received study medication and had a valid faecal calprotectin assessment at time point (Baseline, Week 6, and Week 16). | Posted | Number | 95% Confidence Interval | rs coefficient | Baseline, Weeks 6 and 16 |
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| Secondary | Correlation of Serum Soluble ST2 Levels With Clinical Activity (Assessed by Total Mayo Score) at Week 6 and Week 16 | ST2, a serum biomarker, was collected at Week 6 and Week 16. The total Mayo Score, is a scale for assessing UC activity and is the sum of 4 subscores (assessment of stool frequency [0-3], rectal bleeding [0-3], Physician's Global Assessment [0-3], and endoscopic Mayo subscore [0-3]) and has values that range from 0 to 12. Clinical remission: ≤2 points with no individual subscore > 1; Mildly active disease: 3-5 points; Moderately active disease: 6-10 points; Severely active disease: 11-12 points. A higher score indicates more severe disease. Moderate correlation was defined as rs coefficient between -0.5 to -0.3 or 0.3 to 0.5. | Analysis population includes all participants who had received study medication and had at least one valid post-baseline assessment for the primary endpoint that correlates ST2 with endoscopic activity and/or histological activity, and total Mayo score at Weeks 6 and 16. | Posted | Number | 95% Confidence Interval | rs coefficient | Weeks 6 and 16 |
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| Secondary | Change From Baseline to Week 6 in ST2 Levels in Participants With Active Versus Inactive UC | ST2, a serum biomarker, was collected at Baseline and Week 6. Active Ulcerative Colitis was defined as an endoscopic Mayo subscore ≥2 and inactive Ulcerative Colitis was defined as an endoscopic Mayo subscore of 0 or 1. | Analysis population includes all participants who had received study medication and had at least one valid post-baseline assessment for the primary endpoint that correlates ST2 with endoscopic activity and/or histological activity at Week 6. | Posted | Mean | Standard Deviation | ng/mL | Baseline, Week 6 |
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| Secondary | Change From Baseline to Week 6 in ST2 Level According to Participant's Mayo Endoscopic Response at Week 16 (Maintained Response at Week 16 or Did Not Maintain Response at Week 16) | ST2, a serum biomarker, was collected at Baseline and Week 6. Comparison of participants who achieved endoscopic response [endoscopic Mayo subscore 0 or 1] at Week 6 and maintained response through Week 16 versus participants who did not maintain response throughout Week 16, regarding serum soluble ST2 at baseline, Week 6 and change between baseline and Week 6. | Analysis population includes all participants who had received study medication and achieved endoscopic response at Week 6. | Posted | Mean | Standard Deviation | ng/mL | Baseline, Week 6 |
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| Secondary | Correlation of Endoscopic Mayo Subscore With Ulcerative Colitis Endoscopic Index Of Severity (UCEIS©) Overall Score at Week 6 and Week 16 | UCEIS© is a 3-item (vascular pattern, bleeding and erosion/ulceration) validated tool for assessing endoscopic severity of UC. Each item has 3 or 4 levels of severity and is given a score. The scores for each individual item are combined into a total score ranging from 1 to 11. A higher score indicates increased endoscopic severity of UC. Moderate correlation was defined as rs coefficient between -0.5 to -0.3 or 0.3 to 0.5. | Analysis population includes all participants who had received study medication and had at least one valid post-baseline assessment for the primary endpoint that correlates ST2 with endoscopic activity and/or histological activity, and UCEIS overall score at Week 6 and Week 16. | Posted | Number | 95% Confidence Interval | rs coefficient | Week 6 and Week 16 |
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Up to 16 weeks
Analysis population includes all participants who received at least one dose of study medication.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Golimumab Treatment | Golimumab 200 mg initially administered by subcutaneous (SC) injection at Week 0, followed by 100 mg at Week 2 and then 50 mg or 100 mg every 4 weeks (per prescribing information) up to 16 weeks. | 0 | 38 | 4 | 38 | 4 | 38 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Colitis ulcerative | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Colitis ulcerative | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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The investigator agrees not to publish or publicly present any interim results of the trial without the prior written consent of the sponsor. The investigator further agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| May 31, 2018 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D003093 | Colitis, Ulcerative |
| ID | Term |
|---|---|
| D003092 | Colitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D015212 | Inflammatory Bowel Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
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| ID | Term |
|---|---|
| C529000 | golimumab |
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