4/16/2018. Updates in Crohn s Disease. Disclosures. Learning Objectives. Crohn s Disease is Progressive and Destructive

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1 4/16/218 Disclosures Updates in Crohn s Disease David T. Rubin, MD Joseph B. Kirsner Professor of Medicine Chief, Section of Gastroenterology, Hepatology and Nutrition University of Chicago Consultant and/or Grant Support Abbvie Abgenomics Allergan, Inc. Amgen Celgene Corporation Forward Pharma Genentech/Roche Janssen Pharmaceuticals Merck & Co., Inc. Miraca Life Sciences Napo Pharmaceuticals Pfizer Prometheus Laboratories Salix Pharmaceuticals, Inc. Samsung Bioepis Sandoz Pharmaceuticals Shire Takeda Target PharmaSolutions, Inc. UCB Pharma Board Membership/Other ACG Board of Trustees Co Founder, CFO, Cornerstones Health, Inc (non profit medical education organization) GoDuRn, LLC, Co Founder Learning Objectives At the conclusion of this presentation, participants will: Recognize the common risk factors and progression of Crohn s disease Understand the appropriate treatment options for Crohn s disease Emphasize more recent changes in the approach to management Understand the appropriate treatments to reduce post operative recurrence of Crohn s disease Gain insight into the use of therapeutic drug monitoring to reduce the risk of relapse, hospitalization and surgery Current CD Therapies Understand Your Patient Assess Risk Assessment of Disease Risk in Crohn s Disease Assess current and prior disease burden Crohn s Disease is Progressive and Destructive Progression of Digestive Damage and Inflammatory Activity in a Theoretical CD Patient Low Risk Age at initial diagnosis > 3 years Limited anatomic involvement No perianal and/or severe rectal disease Superficial ulcers No prior surgical resection No stricturing and/or penetrating behavior Moderate/High Risk Age at initial diagnosis < 3 years Extensive anatomic involvement Perianal and/or severe rectal disease Deep ulcers Prior surgical resection Stricturing and/or penetrating behavior Digestive Damage From controlling disease activity in terms of clinical symptoms and inflammatory markers Surgery To preventing progression of structural bowel damage Fistula/abscess Stricture Stricture Inflammatory Activity (CDAI, CDEIS, CRP) Disease Diagnosis onset Pre clinical Early disease Clinical Available at: Accessed March 25, Pariente B, et al. Inflamm Bowel Dis. 211;17(6):

2 4/16/218 Current CD Therapies Biologics Anti TNF Anti Integrins Anti IL 12/23 Loss of response Anti TNF agents Anti TNF for IBD CD CD UC UC CD UC Modified from van Schouwenburg PA, et al. Nat Rev Rhematol. 213;9(3): Comparative Effectiveness Study in CD (SONIC) Mucosal Healing as a Secondary End Point Status of U.S. Biosimilars for IBD Patients (%) % P=.6 P< % P= % 51/17 75/169 96/169 AZA + PBO Clinical Remission IFX + PBO IFX + AZA Patients (%) % P<.1 P=.2 P=.6 3.1% 43.9% 18/19 28/93 47/17 AZA + PBO Mucosal Healing IFX + PBO IFX + AZA Colombel JF, et al. N Engl J Med. 21;362:1383. Biosimilars for Remicade Inflectra (infliximab dyyb) 1,2 FDA approval: April 216 Renflexis (infliximab abda) 3 FDA approval: April 217 Ixifi (infliximab qbtx) 6 FDA approval: December US Food and Drug Administration. Accessed July Pfizer. Accessed October US Food and Drug Administration. Accessed April Biosimilar for Humira Amjevita (adalimumab atto) 4 FDA approval: September 216 Cyltezo (adalimumab adbm) 5 FDA approval: August US Food and Drug Administration. Accessed September Boehringer Ingelheim. ingelheim.us/press release Accessed September US Food and Drug Administration. Accessed February Early Anti TNF Effective in Reducing Internal Penetrating (B3), Not Stricturing (B2) in Early Pediatric CD Risk of Malignancy and Thiopurines Exposure in Pediatric IBD: The DEVELOP Registry Methods Multicenter prospective cohort trial (DEVELOP, n=5,42) Comparison with SEER database Results No increased malignancy risk with Biologics, including all anti TNF and non anti TNF agents, in the absence of thiopurines A 2.7 fold increased risk of malignancy in thiopurine exposed patients irrespective of biologic exposure Kugathasan S, et al. Lancet. 217;389(18): SEER, Surveillance, Epidemiology, and End Results; SIR, standardized incidence ratio Hyams JS, et al. Gastroenterology. 217;152(8):

3 4/16/218 Vedolizumab for Induction and Maintenance of Remission in CD (GEMINI II) GEMINI 2 and 3: Pooled Safety and Efficacy of Vedolizumab in Anti TNF Naïve CD Patients Week 6 Induction Results =6% Placebo (n=148) p=.23 Vedolizumab (n=22) Week 52 Maintenance Results =15% p<.1 =17% p<.1 39% 36% 4% Pooled Analysis of GEMINI 2 and 3 Clinical Remission* Summary of Adverse Events Percentage of Patients =8% p=.21 35% 3% 25% 2% 15% 1% 5% % 22% Clinical Remission VDZ / Placebo (n=153) VDZ / VDZ Q8w (n=154) VDZ / VDZ Q4w (n=154) *CDAI 15 with 1 point decrease from baseline Sandborn WJ, et al. N Engl J Med. 213;369(8): Sands B, et al. Gastroenterology. 214;147(3): Effect of Vedolizumab on Joint Symptoms in CD 553 Patients years of age; CD 3 months; CDAI score Treatment groups: - VDZ (n = 394) - VDZ/PLA (n=77) - PLA (n=82) Arthritis/arthralgia was observed in >9% of pts Resolution of baseline arthritis/arthralgia at week 52 - VDZ: 35% (128/367) - VDZ/PLA: 32% (23/71) - PLA: 23% (18/78) VDZ group were 32% more likely to achieve sustained resolution at baseline vs PLA group (HR 1.32; 95% CI ) GEMINI 2 Post Hoc Analysis Time to Sustained Resolution of Arthritis/Arthralgia in GEMINI 2 Ustekinumab Human interleukin 12 and 23 antagonist Indicated for adults with moderate to severe CD who: - Failed or were intolerant to treatment with immunosuppressive drugs or steroids, but never failed a TNF blocker - Failed or were intolerant to treatment with one or more TNF blockers Initial therapy: single IV infusion, weight based dosing Maintenance therapy: SC 9 mg dose 8 weeks after the initial IV dose, then every 8 weeks thereafter Stelara [package insert]. Horsham, PA: Janssen Biotech, Inc; September 216. Feagan B, et al. Gastroenterology. 217;152(5):S597. Ustekinumab Induction in CD: UNITI 1 and 2 Ustekinumab Maintenance in CD: IM UNITI Clinical remission at week 44 Anti TNF failure Feagan BG, al. N Engl J Med. 216;375(2): Feagan BG, al. N Engl J Med. 216;375(2):

4 4/16/218 Ustekinumab: Summary of Key Safety Events Through Week 52 Ustekinumab (s.c.) UST Induction Only (PBO s.c.) 9 mg q12w 9 mg q8w Combined Treated subjects who were randomized Duration of follow up (weeks) Subjects with, n (%) Death AE 111 (83.5) 16 (8.3) 17 (81.7) 213 (81.) SAE 2 (15.) 16 (12.1) 13 (9.9) 29 (11.) Infection 66 (49.6) 61 (46.2) 63 (48.1) 124 (47.1) Serious infection 3 (2.3) 7 (5.3) 3 (2.3) 1 (3.8) Discontinuation due to AE 8 (6.) 1 (7.6) 4 (3.1) 14 (5.3) Malignancy 1 (.8) 1 (.8) Major adverse CV event* Feagan BG, al. N Engl J Med. 216;375(2): Post Hoc Analysis Suggests Ustekinumab Effective for Perianal Disease in CD A combined post hoc analysis of UNITI 1, UNITI 2 and CERTIFI 12.3% had active perianal fistula (161 patients) Proportion of Patients (%) Fistula Resolution at Week 8 Among Randomized Patients with Open, Draining Fistulas at Baseline. Pooled Data from CERTIFI, UNITI 1 and UNITI 2 5 P=.134 P=.52 P= /71 16/66 18/65 37/15 Placebo 1 mg/kg and 13 mg 6 mg/kg and ~6 mg/kg Ustekinumab All UST Doses Combined Patients in Fistula Response ( 5% Reduction) in Primary Population Through Week 44 (52 Weeks Post Induction) in IM UNITI UST Induction Week 8 Clinical Responders with Open, Draining Fistulas at Baseline Randomized to SC Ustekinumab or Placebo in IM UNITI at Each Visit Through Week 44 Proportion of Patients (%) n=21 n=21 n=21 Placebo SC n=2 n=17 n= n=17 Weeks Post Maintenance Combined SC UST n=16* n=12 n=16* n=12 n=15* n=12 n=15* n=15 n=12 n=11 *P<.5 Sands BE, et al. Gastroenterology. 217;152(5):S185. University of Chicago Ustekinumab Experience ( ) 74 patients (57% Female) were prescribed UST CD, 5 IPAA, 1 IBD U - 73/74 patients failed anti TNFs Results: - Induction Response: 2/32 (62.5%) 1 - Induction Remission:12/32 (37%) 1-16 (59%) achieved and maintained HBI remission 1-2/6 (33%) achieved deep remission 2 - Steroid free at 6 month FU=17 (45%) 3 - Improvement of peri anal fistula at 6 month FU= 1/16 (62.5%) 3 Percentage of Patients 8% 7% 6% 5% 4% 3% 2% 1% % Response and Remission Based on Ustekinumab Dose Response at Induction mg/kg mg/kg Remission at induction Remission at 6 months 1 Krugliak Cleveland N, et al. Submitted to DDW. December Krugliak Cleveland N, et al. Presented at ACG. October 217. Abstract P Krugliak Cleveland N, et al. Presented at AIBD. November 217. Abstract P 31. Anti TNF Naïve Patients Do Better with Other Classes of Therapy Higher remission rates to vedolizumab in patients with CD and UC who are anti TNF naïve 1,2 Patients % 6% 5% 4% 3% 2% 1% % Clinical Remission to VDZ in CD 27% 52% 47% Anti-TNF Naïve 13% 28% 27% Prior Anti-TNF Failure Patients % 6% 4% 2% % Clinical Remission to VDZ in UC 19% 46% 48% Anti-TNF Naïve Higher remission rates to ustekinumab in patients with CD who are anti TNF naïve 3 Patients % 8% 6% 4% 2% % 49.% Clinical Remission to UST in CD 56.6% Anti TNF Naïve 65.4% 26.2% 38.6% 41.1% Prior anti TNF Failure Placebo 9 mg Q12w 9 mg Q8w 1 Sandborn WJ, et al. N Engl J Med. 213;369(8): Feagan BG, et al. N Engl J Med. 213;369(8): Sandborn W, et al. Gastroenterology. 216;15(4Suppl1):S Abstract % 37% 35% Prior Anti-TNF Failure Current CD Therapies 1. Initial 5. Target reached: treatment continue monitoring 2. Assessment of 4. Assessment of target target 3. Adjustment of treatment So What Should the Targets Be? Selecting Therapeutic TaRgets in Inflammatory Bowel Disease Endpoints UC TARGET: PRO: resolution of rectal bleeding and diarrhea/altered bowel habit and Endoscopic remission: Mayo endoscopic subscore of 1. Histological remission is an adjunctive goal. CD TARGET: PRO: resolution of abdominal pain and diarrhea/altered bowel habit; and Endoscopic remission: resolution of ulceration at ileocolonoscopy, or resolution of findings of inflammation on cross sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy. Biomarker remission (normal CRP and calprotectin) was considered an adjunctive target. Peyrin Biroulet, et al. Am J Gastroenterol. 215; 11:

5 4/16/218 Infliximab for Moderate to Severe Crohn s Disease in Children with Shorter Disease Duration p=.2 A Approach Leads to Superior Endoscopic and Deep Remission Outcomes CALM: A Prospective, Multicenter, Open label Randomized Study of Treatment Strategies 244 biologic and immunomodulator naïve patients with CD - All had clinical, endoscopic (CDEIS > 6) and biochemical (CRP >5 and or FC > 25) disease activity Primary endpoint: CDEIS < 4 and no deep ulceration at week 48 Patients (%) n=99 n=66 n=29 n=33 n=17 n=12 n=112, disease duration ~2 years P<.1 Lab Visits Clinical Management Week 1 CDAI decrease < 7 points compared CDAI 15 CRP 5 mg/l (Prior to randomization) to BL or CDAI > 2 FC 25 μg/g Prednisone use at week Weeks 11, 23, and 35 CDAI decrease < 1 points compared to BL or CDAI 2 CDAI 15 CRP 5 mg/l FC 25 μg/g Prednisone use a week prior to visit Prednisone use a week prior to visit Hyams J, et al. Gastroenterology. 27;132(3): Colombel JF, et al. Lancet. 218 Dec 23;39(1114): A Approach Leads to Superior Endoscopic and Deep Remission Outcomes CALM: A Prospective, Multicenter, Open label Randomized Study of Treatment Strategies Prednisone Burst & Taper Randomization 1:1 CM (n=122): Escalation Driven by CDAI, Prednisone Use Treatment Escalation: No Treatment ADA 16/ 8 mg, 4 mg EOW ADA 4 mg EOW ADA 4 mg EOW + AZA ADA 4 mg EW De Escalation: T2T (n=122): Escalation Driven by CDAI, FC, CRP, Prednisone Use ADA 4 mg EW + AZA 2.5 mg/kg/day Primary Endpoint at 48 Weeks After Randomization Percentage of Patients CDEIS <4 and No Deep Ulcerations 1 P= Weeks: Final Visit Clinical Management Treat to Target 37/122 56/122 Colombel JF, et al. Lancet. 218 Dec 23;39(1114): Colombel JF, et al. Lancet. 218 Dec 23;39(1114): Secondary Endpoints at 48 Weeks After Randomization CM Arm, n=122 T2T Arm, n=122 Percentage of Patients (%) Deep Biologic Mucosal Healing Mucosal Healing in Complete Endoscopic Remission Remission All Segments Endoscopic Response Remission P=.14 P=.6 P=.1 P=.229 P=.728 P= n=28 n=45 n=19 n=36 n=37 n=56 n=29 n=36 n=2 n=22 n=49 n=62 CDAI <15, CRP mg/l, CDEI <4 CDEIS <4, CDEIS = CDEIS <5 No Pred 8Wks, FC <25 μg/g, CDEIS <4 in Decrease >5 CDEIS <4, No CDEIS <4 All Segments Deep Ulceration Current CD Therapies Metronidazole/azathioprine combination therapy Low dose metronidazole Fecal calprotectin Anti TNF Anti IL 12/23 Colombel JF, et al. Lancet. 218 Dec 23;39(1114):

6 4/16/218 Medical Prevention of Clinical and Endoscopic Recurrence of Crohn s Disease Clinical Recurrence Endoscopic Recurrence Placebo 25% 77% 53% 79% 5 ASA 24% 58% 63% 66% Budesonide 19% 32% 52% 57% Nitroimidazole 7% 8% 52% 54% AZA/6MP 34% 5% 42 44% Anti TNF variable 9 25% Metronidazole/Azathioprine Combination Therapy for Post Operative Recurrence High risk pts (n=81) = (age <3, smokers, steroids <3 months, second resection, perforated/abscess) N=4 metronidazole 25 mg TID 3 months + AZA 2 3 tabs N=41 metronidazole 25 mg TID 3 months + placebo % patients with endoscopic recurrence (>i2) post surgery Regueiro M. Inflamm Bowel Dis. 29;15(1): D'Haens GR, et al. Gastroenterology. 28;135(4): Low Dose Metronidazole for Prevention of Postop CD Recurrence Early Diagnosis and Treatment of Postoperative Endoscopic Recurrence of CD: Partial Benefit of Infliximab. A Pilot Study Retrospective chart review Patients with ileal resection receiving lowdose metronidazole vs. control Primary endpoint: endoscopic recurrence (Rutgeerts i2) of CD Low dose metronidazole reduces recurrence of CD and is well tolerated Percent of patients Endoscopic recurrence by 12 months 1.% Low dose metronidazole Control 8.% 8.% p=.58 6.% 54.3% 45.7% 4.% 2.% 2.%.% No recurrence Recurrence Surgery (curative resection) n=43 Colonoscopy after 6 months IFX Positive (Rutgeerts 2) n=24 Randomized 5 mg/k at,2,6 then q8 wks No Treatment 5 ASA n= g/d Outcomes at 54 Weeks Endoscopic Endoscopic Clinical Remission Improvement Recurrence 5 ASA % % 18% IFX 54% 69% % Outcomes: Rutgeerts < 2 Calprotectin: Elevated at 2 months in the majority of those who recurred Elevated in a minority of those who did not Colonoscopy at 54 weeks 5 ASA, 5 aminosalicylic acid; IFX, infliximab Glick L, et al. Poster presentation at ECCO 217; Barcelona, Spain. Sorrentino D, et al. Dig Dis Sci. 212;57(5):1341. Patterns of Fecal Calprotectin in CD Patients After Surgery FC (mg/kg) FC (mg/kg) FC (mg/kg) Surgery Endoscopy/beginning of treatment No Recurrence Recurrence No response to treatment Recurrence Response to infliximab Months Methods Results Laparoscopic Ileocolic is a Reasonable Alternative to Infliximab in Isolated Terminal Ileal Crohn s The LIR!C Trial Multicentre RCT of LIR vs. IFX in thiopurine/steroid refractory terminal ileal CD Primary outcome QOL (IBDQ) 143 patients randomised: 7 IFX (2/3 combo Rx) vs. 73 LIR Crossover at median 4 years follow up: LIR IFX 16.4% IFX LIR 37.1% At 1 year there was no statistical difference in disease specific QOL (IBDQ) However LIR was associated with higher general health QOL on SF36 in the physical scale (MD 3.2, P<.5) and mental subscale (MD 4.1, P<.5) IBDQ Total Scores (Mean, 95% CI) P<.1 P=.257 P=.6 IBDQ Total Scores Mean at 12 months: 5.1, 95% Cl , P=.245 Visit P=.196 P=.67 P=.245 Infliximab Laparoscopic XXXXXXX XXXXXX Surgery Endoscopy/beginning of treatment Sorrentino D, et al. Dig Dis Sci. 212;57(5): LIR, Laparoscopic Ileal Resection; IFX, Infliximab; QOL, Quality of Life; MD, Mean Difference; IBDQ, Inflammatory Bowel Disease. Ponsioen CY, et al. Lancet Gastroenterol Hepatol. 217;2(11):

7 4/16/218 Infliximab Prevents Endoscopic Recurrence in Post operative CD (PREVENT) Post Operative Crohn s Endoscopic Recurrence Prevention Based on Risk and Endoscopy (POCER) Rutgeerts i2 at 18 months Active Care (n=122) 62/122 (51%) P=.28 Standard Care (n= 52) 17/ 52 (33%) ADA immediately postop (n=28) 16/28 (57%) P =.2 ADA initiated if i 2 at 6 months (n=32) 13/32 (41%) Treatment according to risk of recurrence at 6 month colonoscopy, is superior to drug therapy alone. Patients randomized 45 days from surgery. *Primary endpoint was clinical recurrence at week 76 defined as a composite endpoint of CDAI changes, endoscopic recurrence and/or fistulizing disease. Regueiro M, et al. Gastroenterology. 216;15(7): Step up with anti TNF therapy, based on colonoscopy findings at 6 months, is a viable strategy in high risk patients DeCruz P, et al. Lancet. 215;385(9976): Fecal Calprotectin Can Predict Postoperative CD Endoscopic Recurrence Prospective study of 136 post operative CD patients using 318 stool samples (POCER STUDY) Using a cut off of > 1ug/g, fecal calprotectin identifies which patients require colonoscopy and allows 41% of patients to avoid colonoscopy Fecal Calprotectin Concentration at 6 Months Compared to Rutgeert s Score Impact of Preoperative Vedolizumab on Surgical Outcomes Retrospective case control analysis of patients receiving presurgical therapy: vedolizumab (n=64) anti TNF (n=129) non biological therapy (n=25) Vedo demonstrated no effect on risk of 3 day postoperative complications in UC (p=.4) or CD (p=.35) Rate of 3 day postop complication Rate of Postop Complication by Therapy Vedolizumab.29 P =.4.5 Anti TNF α agents Non biological therapy P = UC (N = 72) CD (N = 12) Wright EK, et al. Gastroenterology : Yamada A, et al. Am J Gastroenterol. 217;112: Perioperative UST is Not Associated With Increased Post operative Complications Compared with Anti TNF A Canadian Multicenter Retrospective Cohort Study CD patients treated with ustekinumab undergoing abdominal surgery (29 216) Postoperative outcomes compared vs. random sampling of control patients treated with anti TNF therapy An Updated Algorithm for Prevention of Post Op Recurrence in Crohn s Postoperative Outcomes Ustekinumab Cohort (n=2) Anti TNF Cohort (n=4) P value Wound infection 3 days 1 (5%) 2 (5%) 1. Wound infection > 3 days Anastomotic leakage 3 days 3 (7.5%).54 Anastomotic leakage > 3 days Abscess 3 days 4 (1%).29 Abscess > 3 days 2 (5%).54 Nonsurgical site infection 3 days 3 (7.5%).54 Non surgical site infection >3days Ileus /bowel obstruction 3 (15%) 4 (1%).67 Mortality at 6 months CD patients receiving pre operative UST did not experience an increase in post operative complications, despite a higher rates of concurrent immunosuppression (methotrexate or corticosteroids>2mg/day and immunomodulator) Shim HH, et al. Gastroenterology. 217;152(5):S577. Christensen B, Rubin DT. Recurrent Crohn s disease: Medical prophylaxis. In: Fichera A, Krane MK, eds. Crohn s Disease: Basic Principles. 215:

8 4/16/218 Therapeutic Drug Concentration Monitoring (TDM) Treatment Optimization Based on Class of Therapy Helps prevent risk of relapse Reduces risk of hospitalizations and surgery Reactive testing of drug concentration and antibodies - Better directs care and more cost effective Proactive TDM improves outcomes and cost effective - During maintenance - During induction - When stopping immunomodulator (in combination with anti TNF) - Optimized (biologic) monotherapy When restarting after a drug holiday Optimized Infliximab Levels (3 7 mcg/ml) Associated with Stable Maintenance (TAXIT) TAILORIX: Dose Intensification Based on Trough levels Not Superior to That Based on Symptoms Alone Clinically based (CB) and trough level based (LB) groups 1 p= Patients (%) (N=122) (N=126) CB group LB group Clinical Remission Relapse free survival.8.6 LogRank p=.38 Breslow p= CB Group LB Group Maintenance phase (weeks) 36% 43% 48% 49% 51% 45% Proportion of patients without ulceration at week 54 Proportion of patients in endoscopic remission TAXIT: Prospective controlled Trough level Adapted infliximab Treatment Vande Casteele N, et al. Gut. 215;64(1): Vande Casteele N, et al. Gastroenterology. 215;148(7): CDAI, Crohn s Disease Activity Index D Haens G, et al. Gastroenterology. 216; 15(4):S143. Improved Long term Outcomes in Patients Receiving Proactive Compared With Reactive Monitoring of IFX Serum Concentrations Less Treatment Failure with Proactive TDM Multicenter (BIDMC and UPenn), retrospective, observational study. 264 consecutive patients with IBD - Responded to infliximab and received maintenance therapy - Proactive or reactive TDM, based on the first infliximab concentration / antibodies to infliximab (ATI) measurement (Prometheus Labs) Outcomes: Treatment failure, IBD related surgery, hospitalization, antibodies to infliximab (ATI), and serious infusion reaction (SIR) Papamichael K, et al. Clin Gastroenterol Hepatology. 217;15(1): Papamichael K, et al. Clin Gastroenterol Hepatology. 217;15(1):

9 4/16/218 Proactive Infliximab (IFX) Drug Monitoring is Associated With Less Surgery and Hospitalization It was the level, not the combination! SONIC Post Hoc Analysis IBD Related Surgery (%) Proactive TDM, 7 Reactive TDM, IBD Related Hospitalization (%) Proactive TDM, 7 Reactive TDM, Twice as many patients achieved steroid free remission at week 26 from higher quartiles of IFX monotherapy compared to those on combination therapy with low IFX concentrations Corticosteroid Free Remission at Week 26 Follow Up After Start of IFX TDM (Years) Follow Up After Start of IFX TDM (Years) Papamichael K, et al. Clin Gastroenterol Hepatology. 217;15(1): Q1: <.84 µg/ml; Q2: µg/ml; Q3: µg/ml; Q4 5.2 µg/ml. Colombel JF, et al. Gastroenterology. 217;152(5):S Higher Infliximab Trough Levels Are NOT Associated With an Increase in Adverse Events Single center, retrospective analysis of patients treated with IFX with at least one IFX trough level (Prometheus); AEs documented during a 6 month period IFX <15 IFX >15 (N=9) (N=9) P Value AEs, Total N(%) 3 (33) 17 (18.8).4 Serious, N(%) 3 (3.3) 3 (3.3) 1. Infections, Total N(%) 17 (18.8) 11 (12.2).3 Serious, N(%) 3 (3.3) 3 (3.3) 1. Opportunistic, N(%) 6 (6.6) 4 (4.4).74 Skin AEs, N(%) 5 (5.5) 6 (6.6) 1. Summary: Updates in Crohn s Disease Include prognosis in treatment decisions Treat early with effective therapy Employ strategies Vedolizumab and Ustekinumab are safe, effective new(er) options in CD and for perioperative management Monotherapy may be effective if there are sufficient drug levels present Infusion reactions, N(%) 1 (11.1) <.1 Other, N(%) 4 (4.4).12 Greener T, et al. Gastroenterology. 217;152(5):S18. Question 1 According to the results of the CALM study A. Treating to target was associated with increased mucosal healing, deep remission, and biologic remission B. Treating to target was only associated in increased biologic remission C. The clinical management group was treated to a CDAI of <15 D. The treat to target group had more adverse events E. A higher proportion of patients in the clinical management group achieved the primary endpoint at week 48 compared to the treat to target group 9