Dr Ahmad Alfadhli MD,FRCPc Haya Alhabeeb Gastroebterology Center - PowerPoint PPT Presentation

Dr Ahmad Alfadhli MD,FRCPc Haya Alhabeeb Gastroebterology Center Mubarak Alkabeer Hospital

● What is a treat-to-target approach? Lessons from other therapy areas ● Rationale for a treat-to-target approach in IBD: Disease course modification as a realistic goal in IBD ● Implementation of a treat-to-target approach in IBD ● Evidence for a treat-to-target approach in IBD: REACT, POCER and now CALM ● Summary

● Aim: To avoid development of serious complications and disability in patients with chronic conditions ● Concept: Treating to a pre-defined treatment target that is associated with optimal long-term outcomes (goal-oriented approach) ● Strategy: Ongoing and regular monitoring of the target and/or surrogate marker, with optimisation of treatment when the target is not met ● Additional principles: ● All components ─ target, treatment and monitoring ─ are tailored to the needs of the individual patient ● De-escalation of therapy may be considered when treatment goals are achieved A T2T approach involves pre-defining a treatment target, in consultation with the patient, continuously monitoring disease activity, and modifying treatment until the target is reached Bouguen G et al. Clin Gastroenterol Hepatol 2015;13:1042-50; McKloskey et al. Int J Clin Rheumatol 2015;10:1-4.

T2T is well established in clinical practice Diabetes 1,2 Dyslipidaemia 5* HbA1c <7% (more or less LDL-C <3 mmol/L stringent goals (low/moderate CV may be risk patients), appropriate for <2.6 mmol/L (high individual CV risk patients), patients) <1.8 mmol/L (very high CV risk patients) Hypertension 3,4 *2013 AHA/ACC guideline on blood BP <140/90 mmHg cholesterol made no recommendations for specific (in most LDL-cholesterol or non-HDL targets. Stone NJ, et al. Circulation 2013. hypertensive patients) BP , blood pressure; HbA1c , glycated haemoglobin; LDL-C , Low-density lipoprotein cholesterol 1 . ADA . Diabetes Care 2017;40(Suppl1);S1-S132; 2 . ESC. Eur Heart J 2013;34:3035-87; 3. Mancia G et al. J Hypertens. 2013;31:1281 – 1357; 4. James PA et al. JAMA. 2014;311:507 – 520; 5. Catapano AL, et al. European Heart Journal 2016;37:2999 – 3058.

T2T concept is well established with increasing uptake in clinical practice Rheumatoid arthritis 1,2 Clinical remission (absence of signs and symptoms of significant inflammatory activity) or low disease activity 1. Smolen JS et al. Ann Rheum Dis 2010;69:631 – 7; 2. Smolen JS et al. Ann Rheum Dis 2015;0:1 – 13. doi:10.1136/annrheumdis-2015-207524

T2T recommendations exist, with emerging evidence Psoriasis Psoriatic arthritis 1,2 Body surface area Remission / inactive (BSA) ≤ 1% 3 disease of musculoskeletal Reduction in Psoriasis involvement, with Area Severity Index consideration of (PASI) ≥75% from extra-articular treatment initiation 4 manifestations, Physician global or low/minimal assessment (PGA) disease activity score 0 5 1. Smolen JS, et al. Ann Rheum Dis 2014;73:6-16; 2. Gossec L, et al. Ann Rheum Dis 2016;75:499-510; 3. Armstrong AW, et al . J Am Acad Dermatol 2017;76:291-98.; 4. Mrowietz U, et al. Arch Dermatol Res 2011;303:1-10; 5 . Gulliver W, et al . J Cutaneous Med Surg 2015;19:22-27

● Therapeutic advances have improved treatment outcomes and led to the proposal of stringent treatment targets ● Treatment algorithms are based on treatment targets ● Frequent monitoring allows treatment optimisation within specific timeframes ● Treatment targets should be tailored to the individual patient to optimise outcomes and minimise risk ● Target choice and therapeutic changes should be shared physician – patient decisions ● Information technology (electronic data capture, interactive algorithms and score calculation) can help integrate T2T into routine clinical practice

Disease course modification as a realistic goal in IBD

CD and UC are chronic progressive conditions, with a major clinical and patient burden Ongoing inflammatory activity results in the accumulation of bowel damage, which leads to complications and disability Theoretical patient with Crohn’s disease 1 Clinical evidence in Crohn’s disease Bowel damage (measured by the Lémann Index) Stricture increases over time Surgery Inflammatory activity in many CD patients Bowel damage ● Over median 23 months, bowel damage increased in >1/3 of Fistula / abscess patients 2 Stricture ● Over 5 years, bowel damage increased in 48% of patients 3 ● At 2 – 10 years post diagnosis, >50% had substantial damage 4 Onset Diagnosis Early disease Advanced disease 1. Pariente B, et al. Inflamm Bowel Dis 2011;17:1415 – 22; 2 . Duveau N, et al. J Crohns Colitis 2015; 9(Suppl1):S57; 3 . Bhagya Rau B, et al. J Clin Gastroenterol 2016;50:476 -82; 4 . Giletta C, et al. Clin GastroenterolHepatol 2015;13:633-40 10

40 CD endoscopic index of severity (CDEIS) Clinically 35 ENDOSCOPIC DISEASE ACTIVITY quiescent 30 disease, All patients, N=121 n=21 Weak correlation of CDAI and CDEIS 25 (r=0.31) (r=0.32 * ; p<0.001) 20 15 10 5 0 0 50 100 150 200 250 300 350 400 450 500 550 600 650 700 CD activity index (CDAI) CLINICAL DISEASE ACTIVITY *Correlation coefficient after square root transformation Cellier C, et al . Gut 1994; 35: 231-5

Disease outcomes Patient-reported outcomes Impact on work / school Abdominal Bowel pain damage and Impact on social and complications professional life Nutrition Clinical Diarrhoea Surgery visits Medication Hospitalisations Fatigue side effects Anaemia Colonoscopy / Mortality imaging Impaired Blood / Cancer Poor growth / QoL / faecal test risk weight loss disability monitoring 12

A traditional step-up approach can result in: ● Treatment step-up that is based on symptoms only SURGERY ● Continued inflammation that leads to bowel damage and disease BIOLOGICS complications ● Undertreatment of a proportion THIOPURINES of patients ● Patients at high risk of developing poor outcomes receiving effective STEROIDS intervention too late 5-ASA (in UC) Bouguen G, et al. Clin Gastroenterol Hepatol 2015;13:1042-50.

Need to determine as early as possible who is at a high risk of developing disease complications Simple demographic and clinical features can help identify high-risk patients at diagnosis and throughout the disease course 1 Indolent Aggressive disease disease Traditional step-up Early intensive therapy Avoid intensive therapy, Assure early intensive immunosuppression and therapy to avoid adverse events complications 1. Torres J, et al. J Crohns Colitis 2016;10:1385-1394

Week 12 mucosal healing by disease duration 100 100 Placebo EOW (n=61) Adalimumab 40 mg EOW (n=62) Patients with mucosal 80 80 healing (%) 60 60 40 40 20 20 0/8 4/9 4/10 7/39 9/43 1/14 0 <2 Y Yea ears rs <5 Y Yea ears rs ≥5 Years Crohn’s disease duration NRI; N=123 patients with ulceration at baseline screening All patients (CDAI 220 – 450) received open-label adalimumab 160-/80-mg induction therapy at weeks 0/2 and were randomised at week 4 to receive maintenance therapy with adalimumab 40 mg every other week or placebo Mucosal healing defined as absence of mucosal ulceration Sandborn WJ, et al . J Crohn’s Colitis ( Suppl) 2010;4:S36 – 7.

More effective treatments Treatment optimisation Earlier intervention Symptom Clinical Steroid-free Mucosal Deep improvement 1 remission 1 remission 1,2 healing 3-6 remission 7-8 Induce and Clinical maintain remission with mucosal healing 1. Colombel JF , et al. Gastroenterology 2007;132:52 – 65. 5. Sandborn WJ, et al. J Crohn’s Colitis 2010;4:S36. 2. Colombel JF, et al. Dig Dis 2012(Suppl. 3):107 – 11. 6. Louis E, et al. Gastroenterology 2012;142:63 – 70. 3. Colombel JF, et al. N Engl J Med 2010;362:1383 – 95. 7. Colombel JF, et al. J Crohn’s Colitis 2010;4:S11. 4. Baert FJ, et al. Gastroenterology 2010;138:463 – 68. 8. PanaccioneR, et al. Inflamm Bowel Dis 2013;19:1645 – 53. 16

Mucosal healing status at 1 year and risk of surgery Ulcerative colitis (n=338) Crohn’s disease (n=106) Mucosal healing at 1 year 1.0 1.0 with no surgery after 1-year visit with no surgery after 1-year visit Proportion of UC patients Proportion of CD patients Mucosal healing at 1 year 0.9 0.9 No mucosal healing at 1 year 0.8 0.8 0.7 0.7 No mucosal healing at 1 year 0.6 0.6 0 1 2 3 4 5 6 7 8 0 1 2 3 4 5 6 7 Time in years after 1-year visit Time in years after 1-year visit Froslie KS, et al . Gastroenterology 2007;133:412 – 22