1. Optimising Treat to Target in Kingdom of Saudi Arabia
Briefing Slides for Round Table

2. Treat to Target Monitoring IBD patients
Subrata Ghosh, MD, FRCPC, FRCP, FRCPE, AGAF, FCAHS
Director, Institute of Translational Medicine
Professor of Translational Medicine University of Birmingham, UK

3. Disclosures Receipt of grants / research supports AbbVie, GSK, Vertex
Receipt of honoraria or consultation fees
Janssen, AbbVie, Pfizer, Receptos, Celgene, BMS, Takeda, Ferring, Falk, Gilead, Boehringer-Ingelheim
Participation in a company- sponsored speaker’s bureau
AbbVie, Janssen, Takeda, Ferring
Stock shareholder
None
Other support (please specify)

4. Walk a mile in our patients’ shoes…
Where and how can we OPTIMISE management to improve outcomes?
Target achieved? 1 2 3
Diagnosis and management plan
Life before illness
Onset of symptoms
Quality of life 4
Steroid use
Steroids are not intended for long-term use
Potential failure of conventional therapies
Biologic initiation 5 6
Adherence challenges
Change in quality of life in a theoretical IBD patient

5. Overall Lémann Index score = 23.25
Lémann Index measures bowel damage and the potential impact of treatment
MODULE 1
Why is treating to target important?
Proposed treat-to-target approach in IBD
Summary
What is treating to target?
Quantitative tool to assess cumulative structural bowel damage in CD1
Entire GI tract is evaluated for damage and an overall score calculated
WHERE in the GI tract?
WHAT severity of damage (surgery, stricturing lesions, penetrating lesions)?
EXTENT of surgery and lesions?
Used to assess damage progression,2–3 and to evaluate treatment strategy over time4, 5
Potential endpoint for disease-modification trials
Male with a small bowel resection (58 cm, 3 x 20 cm segments), stricturing and prestenotic dilatation (grade 3, 2 segments), small bowel fistula (grade 3), and anal stricturing (grade 3)
Upper tract = 0
Colon or rectum = 0
Small bowel = 2.2
Anus = 3.5
Overall Lémann Index score = 23.25
1. Pariente B, et al. Inflamm Bowel Dis 2011;17:1415–22; 2. Gilletta C, et al. . J Crohns Colitis 2015; 9(Suppl1):S57; 3. Bhagya Rau B, et al. J Clin Gastroenterol 2016;50:476–82; 4. Fiorino G, et al. J Crohns Colitis 2015;9:633–9; 5. Fiorino G et al. J Crohns Colitis 2016;10:

6. Lémann Index score significantly increased with disease duration in a prospective, cross-sectional, observational study in patients with CD
MODULE 1
Why is treating to target important?
Proposed treat-to-target approach in IBD
Summary
What is treating to target?
19.0
Median Lémann index score 20
138 patients with CD
Age (median): 34 years
CDAI (median): 187
CDAI <150 (n): 50
14.3 15
Median Lémann Index score increased with duration of disease
P<0.001 10
6.3
<2 years (n=45)
≥2 to <10 years (n=46)
≥10 years (n=47)
Disease duration in years
Pariente B, et al. Gastroenterology 2015;148:52–63

7. Treatment goals for inflammatory bowel disease continue to evolve
Future goals are moving toward changing the course of the disease1–4
MODULE 1
Why is treating to target important?
Proposed treat-to-target approach in IBD
Summary
What is treating to target?
Symptom improvement5
Clinical remission5
Steroid-free remission5,6
Mucosal healing6–9
Deep remission4,10
Reduction of
hospitalization,
surgeries11
Evolving endpoints
Goals of therapy in IBD have historically been based on symptomatic response with good control of symptoms and improved quality of life1
We now have objective measures of inflammation that may allow tighter control of the inflammatory process1
There is still a need for long-term observational studies to determine whether complete clinical and inflammatory remission is required in all patients1
1. Lichtenstein GR, et al. Am J Gastroenterol. 2018;113(4):481–517; 2. Regueiro MD, et al. Am J Gastroenterol. 2016;3(suppl):8–16; 3. Panaccione R, et al. Inflamm Bowel Dis 2013;19:1645–53; 4. Colombel JF, et al.
Dig Dis. 2012;30(suppl 3):107–111; 5. Colombel JF, et al. Gastroenterology 2007;132:52–65; 6. Colombel JF, et al. N Engl J Med 2010;362:1383–95; 7. Baert FJ, et al. Gastroenterology 2010;138:463–68; 8. Sandborn WJ, et al.
J Crohns Colitis 2010;4:S36; P060; 9. Louis E, et al. Gastroenterology. 2012;142(1):63–70.e5; 10. Colombel JF, et al. J Crohns Colitis 2010;4:S10; P16; 11. Feagan BG, et al. Gastroenterology. 2008;135(5):1493–1499.

8. TREAT-TO-TARGET STRATEGY
Treating to target in IBD: proposed stepwise algorithm for clinical practice
MODULE 1
Why is treating to target important?
Proposed treat-to-target approach in IBD
Summary
What is treating to target?
Active IBD
Target
Sustained target
1 Assess risk factors
2 Set appropriate target
3 Treat in a timely manner
4 Monitor regularly
5 Optimise therapy as necessary
TREAT-TO-TARGET STRATEGY
TARGET ACHIEVED
Continue monitoring to sustain the target
TARGET NOT ACHIEVED
Adapted from: Bouguen G, et al. Clin Gastroenterol Hepatol 2015;13:1042–50; Smolen JS, et al. Ann Rheum Dis 2015;0:1–13

9. Target recommendations for Crohn’s disease: treat beyond symptoms*
MODULE 1
Why is treating to target important?
Proposed treat-to-target approach in IBD
Summary
What is treating to target?
Clinical/PRO remission
&
Endoscopic remission
Resolution of abdominal pain and normalisation of bowel habit
Assess at least every 3 months during active disease
Resolution of ulceration
Assess 6–9 months during the active phase
Biomarkers: CRP and FCP are adjunctive measures of inflammation for monitoring CD (not targets)
Failure of CRP or FCP normalisation should prompt further endoscopic evaluation, irrespective of symptoms
*Resolution of symptoms alone is not a sufficient target; objective evidence of inflammation of the bowel is necessary when making clinical decisions
STRIDE, Selecting Therapeutic Targets in IBD; CRP, C-reactive protein; FCP: faecal calprotectin; PRO, patient-reported outcome
Peyrin-Biroulet L, et al. Am J Gastroenterol 2015;110:1324–38

10. Target recommendations for ulcerative colitis: treat beyond symptoms
MODULE 1
Why is treating to target important?
Proposed treat-to-target approach in IBD
Summary
What is treating to target?
Clinical/PRO remission
&
Endoscopic remission
Resolution of rectal bleeding and normalisation of bowel habit
Assess at least every 3 months during active disease
Resolution of friability and ulceration (Mayo 0–1)
Assess 3–6 months after initiating therapy
Biomarkers: CRP and FCP are adjunctive measures of inflammation for monitoring UC (not targets)
Failure of CRP or FCP normalisation should prompt further endoscopic evaluation, irrespective of symptoms
STRIDE, Selecting Therapeutic Targets in IBD; CRP, C-reactive protein; FCP: faecal calprotectin; PRO, patient-reported outcome
Peyrin-Biroulet L, et al. Am J Gastroenterol 2015;110:1324–38

11. Treat-to-target approach has been explored in IBD clinical studies
MODULE 1
Why is treating to target important?
Proposed treat-to-target approach in IBD
Summary
What is treating to target?
In algorithm-driven, prospective treatment studies, the treat-to-target approach was associated with a:
Lower rate of hospitalisation, surgery and complications in patients with established Crohn’s disease1
Combined immunosuppression algorithmic approach, treating to the target of clinical remission, compared with a conventional approach
Lower rate of endoscopic recurrence in postoperative Crohn’s disease2
Colonoscopy and treatment step-up for endoscopic recurrence, compared with risk-stratified drug therapy alone
Treating to target in IBD has been explored across a number of clinical studies in different patient populations.
Treat-to-target algorithm-driven approaches have led to positive outcomes in trials such as REACT,1
POCER,2 and most recently CALM.3
References:
Khanna R, et al. Lancet 2015;386;1825–34.
De Cruz P, et al. Lancet 2015:11;385:1406–17.
Colombel JF, et al. Lancet 2018;390:2779–89.
Higher rate of mucosal healing with absence of deep ulcers in early Crohn’s disease3
Treatment optimisation driven by biomarker levels (CRP and FCP) and clinical symptoms, compared with clinical symptoms alone
CRP, C-reactive protein; FCP: faecal calprotectin
1. Khanna R, et al. Lancet 2015;386;1825–34; 2. De Cruz P, et al. Lancet 2015:11;385:1406–17; 3. Colombel JF, et al. Lancet 2018;390:2779–89

12. CALM: Evidence for a treat-to-target approach in IBDvs
Quality-of-life data
Cost- effectiveness data
Evidence from other studies
Summary
Clinical evidence from CALM
MODULE 2
Tight control
Clinical management
Open-label, multicentre study in patients with early* moderate-to-severe CD
Patients (n=244) randomised to:
Tight control (treat-to-target approach) – Treatment optimisation based on biomarkers (CRP, FCP), steroid use and clinical symptoms (CDAI)
Clinical management – Treatment optimisation based on steroid use and clinical symptoms (CDAI)
Monitored every 12 weeks
Primary endpoint was mucosal healing (CDEIS <4) with absence of deep ulcers at week 48
CALM is the first study to show that timely optimisation of therapy based on clinical symptoms combined with biomarkers in patients with early* CD results in improved clinical and endoscopic outcomes than optimisation based on symptoms alone
*Early CD defined in CALM as CD diagnosis confirmed by endoscopy not >6 years before baseline
CDEIS, Crohn's Disease Endoscopic Index of Severity; CRP, C-reactive protein; FCP, faecal calprotectin
Colombel JF, et al. Lancet 2018;390:2779–89

13. CALM: Inclusion and exclusion criteria
Inclusion criteria1
Quality-of-life data
Cost- effectiveness data
Evidence from other studies
Summary
Clinical evidence from CALM
MODULE 2
CDAI ≥220 and ≤450 (no CS at baseline) CDAI ≥200 and ≤450 (≤20 mg CS for ≥7 days before baseline) CDAI >150 and ≤450 (>20 mg CS for ≥7 days before baseline)
Moderate to severe CD
CDEIS >6 and sum of CDEIS sub-scores >6 in ≥1 segment with ulcers
Active endoscopic disease
CDEIS2
Presence of deep/superficial ulceration
Surface involvement by disease or ulceration in ileum, right colon, transverse, left and sigmoid colon, and rectum
CRP ≥5 mg/L and/or FCP ≥250 µg/g at screening
Exclusion criteria1
Previous or current immunomodulator or biologic use
>2 previous courses CS or >3-month duration CS use at screening
CDAI, Crohn’s disease activity index; CDEIS, Crohn’s disease endoscopic index of severity; CRP, C-reactive protein; CS, corticosteroids; FCP, faecal calprotectin. 1. Colombel JF, et al. Lancet 2018;390:2779–89; 2. Mary JY, et al. Gut. 1989;30:983–9.

14. CALM study design: Steroid burst and randomisation
Quality-of-life data
Cost- effectiveness data
Evidence from other studies
Summary
Clinical evidence from CALM
MODULE 2
Tight control (n=122)
Prednisone 40 mg/day burst and taper
Clinical management (n=122)
Laboratory assessments
Week: -9 -4 -1 12 24 36 48
Early randomisation in patients with:
CDAI >220 AND
Steroid >4 weeks and needed tapering, including 2 weeks of prednisone ≥40 mg or an equivalent daily dosage
Steroid intolerance / contraindication
Investigator discretion
CDAI, Crohn’s disease activity index
Colombel JF, et al. Lancet 2018;390:2779–89

15. CALM study design: Treatment initiated at Week 0
Quality-of-life data
Cost- effectiveness data
Evidence from other studies
Summary
Clinical evidence from CALM
MODULE 2
Treatment with ADA if meeting ≥1 of below:
CDAI ≥150
CRP ≥5 mg/L
FCP ≥250 µg/g
Prednisone use
Tight control (n=122)
Prednisone 40 mg/day burst and taper
Clinical management (n=122)
Treatment with ADA if meeting ≥1 of below:
CDAI ↓ <70 vs baseline
CDAI >200
Laboratory assessments
Week: -9 -4 -1 12 24 36 48
ADA 40 mg EW + AZA
ADA 40 mg EW
ADA 160/80 mg, then 40 mg EOW†
No treatment
†Patients received ADA 160 mg at Week 0 and 80 mg at Week 2 if they were escalated from no treatment
ADA, adalimumab; AZA, azathioprine; CDAI, Crohn’s disease activity index; CRP, C-reactive protein; EOW, every other week; EW, every week; FCP, faecal calprotectin.
Colombel JF, et al. Lancet 2018;390:2779–89

16. CALM study design: Treatment optimisation at Weeks 12, 24 and 36
Quality-of-life data
Cost- effectiveness data
Evidence from other studies
Summary
Clinical evidence from CALM
MODULE 2
Tight control (n=122)
Treatment escalation if meeting ≥1 of below:
CDAI ≥150
CRP ≥5 mg/L
FCP ≥250 µg/g
Prednisone use 1 week prior
Prednisone 40 mg/day burst and taper
Clinical management (n=122)
Treatment escalation if meeting ≥1 of below:
CDAI ↓ <100 vs baseline
CDAI ≥200
Prednisone use 1 week prior
Laboratory assessments †† ††
Week: -9 -4 -1 12 24 36 48
ADA 40 mg EW + AZA
ADA 40 mg EW
ADA 160/80 mg, then 40 mg EOW†
No treatment
†Patients received ADA 160 mg at Week 0 and 80 mg at Week 2 if they were escalated from no treatment; ††Patients who were de-escalated from ADA 40 mg EW + AZA, they continued receiving AZA after de-escalation.
ADA, adalimumab; AZA, azathioprine; CDAI, Crohn’s disease activity index; CRP, C-reactive protein; EOW, every other week; EW, every week; FCP, faecal calprotectin.
Colombel JF, et al. Lancet 2018;390:2779–89

17. CALM study design: Rescued patients followed tight control algorithm
Quality-of-life data
Cost- effectiveness data
Evidence from other studies
Summary
Clinical evidence from CALM
MODULE 2
Tight control (n=122)
Treatment escalation if meeting ≥1 of below:
CDAI ≥150
CRP ≥5 mg/L
FCP ≥250 µg/g
Prednisone use 1 week prior
Prednisone 40 mg/day burst and taper
Clinical management (n=122)
Treatment escalation if meeting ≥1 of below:
CDAI ↓ <100 vs baseline
CDAI ≥200
Prednisone use 1 week prior
Week: -9 -4 -1 12 24 36 48
Rescue
CDAI >300 for 2 consecutive visits 7 days apart or per investigator discretion
CDAI, Crohn’s disease activity index; CRP, C-reactive protein; FCP, faecal calprotectin
Colombel JF, et al. Lancet 2018;390:2779–89

18. CALM: Primary and key secondary endpoints
Quality-of-life data
Cost- effectiveness data
Evidence from other studies
Summary
Clinical evidence from CALM
MODULE 2
Primary endpoint (at 48 weeks)
CDEIS <4 (mucosal healing) and no deep ulcerations
Key secondary endpoints (all at 48 weeks)
Deep remission (CDAI <150, CDEIS <4, and no deep ulcers, absence of draining fistula, discontinuation of steroids ≥ 8 weeks)
Biologic remission (FCP <250 g/g, CRP <5mg/L, and CDEIS <4)
Mucosal healing (CDEIS <4)
Overall mucosal healing and mucosal healing in all segments (overall CDEIS <4 and CDEIS <4 in each segment)
Complete endoscopic remission (CDEIS = 0)
Endoscopic response (CDEIS decrease >5 points)
Steroid-free remission (CDAI <150 and discontinuation of steroid use ≥8 weeks) over time
CDAI, Crohn’s disease activity index; CDEIS, Crohn’s disease endoscopic index of severity; CRP, C-reactive protein; FCP, faecal calprotectin. Colombel JF, et al. Lancet 2018;390:2779–89

19. CALM: Primary endpoint at Week 48
Tight control resulted in significantly more patients achieving mucosal healing (CDEIS <4) with no deep ulcerations than clinical management
Quality-of-life data
Cost- effectiveness data
Evidence from other studies
Summary
Clinical evidence from CALM
MODULE 2
p=0.010
Patients (%)
37/122
56/122
Endoscopic scoring is based on site read. Cochran-Mantel-Haenszel test stratified by smoking status (yes/no) and weight (<70/≥70 kg) at screening. Non-responder imputation (NRI) analysis.
Colombel JF, et al. Lancet 2018;390(10114):2779–2789.

20. CALM: Secondary endpoints at Week 48
Tight control resulted in significantly higher rates of deep remission, biologic remission and mucosal healing than clinical management
Quality-of-life data
Cost- effectiveness data
Evidence from other studies
Summary
Clinical evidence from CALM
MODULE 2
p=0.014
p=0.006
p=0.010
p=0.229
p=0.728
p=0.067
Patients (%)
Deep remission
CDAI <150, CDEIS <4 and no deep ulcers, no draining fistula, discontinuation of corticosteroids for ≥8 weeks
Biologic remission
CRP <5 mg/L, FCP <250 µg/g, CDEIS <4
Mucosal healing
CDEIS <4
Overall mucosal healing plus mucosal healing in all segments
Overall CDEIS <4, CDEIS <4 in all segments
Complete endoscopic remission
CDEIS=0
Endoscopic response
CDEIS decrease >5 points
Colombel JF, et al. Lancet 2018;390(10114):2779–2789.

21. CALM: Steroid-free remission over Weeks 11–48
Tight control resulted in significantly more patients achieving steroid-free remission at each study visit versus clinical management
Quality-of-life data
Cost- effectiveness data
Evidence from other studies
Summary
Clinical evidence from CALM
MODULE 2
p=0.009
p=0.003
p=0.007
p<0.001
Patients (%)
Steroid-free remission, CDAI <150 and discontinuation of steroid use for at least 8 weeks.
Cochran-Mantel-Haenszel test stratified by smoking status (yes / no) and weight (<70 / ≥70 kg) at screening. NRI analysis.
Colombel JF, et al. Lancet 2018;390(10114):2779–2789.

22. CALM: Safety findings
Clinical management (n=122) n (%)
Tight control (n=122) n (%) AE
100 (82)
105 (86)
SAE
25 (21)
22 (18)
AE leading to adalimumab discontinuation
16 (13)
17 (14)
Infection
57 (47)
61 (50)
Serious infection
12 (10)
6 (5)
Opportunistic infection
excluding oral candidiasis and tuberculosis
Active tuberculosis
1 (1)
Latent tuberculosis
2 (2)
Malignancy
Deaths
Quality-of-life data
Cost- effectiveness data
Evidence from other studies
Summary
Clinical evidence from CALM
MODULE 2
Safety profile was similar between treatment groups and consistent with the known safety profile of adalimumab in CD
Colombel JF, et al. Gastroenterology 2017;152(Supplement 1):S155.

23. Proportion of patients without CD flare* Weeks after randomisation
CALM: time to CD flare
1.0
Proportion of patients without CD flare*
0.8
Log-rank p=0.010
0.6
HR=0.4 (95% CI: 0.2, 0.8) p=0.012
0.4
Clinical management
0.2
Tight control 10 20 30 40 50
Weeks after randomisation
Patients at risk:
CM:
TC:
122 97
107 94
105 85
101 78 94 75 86
Early significant separation in the time to CD flare* between the CM and TC groups
*Increase in CDAI ≥70 points from one week prior to randomisation OR early randomisation and CDAI > CD: Crohn’s disease; CM: clinical management; TC: tight control. Colombel JF, et al. Gastroenterology 2017;152(Suppl 1):S155; Colombel JF, et al. United European Gastroenterol J 2017:Abstract 1057

24. CALM: rates of CD-related hospitalisations after randomisation
29 events
14 events
n=122 PY=103.6
n=122 PY=106.3
Significantly fewer events of CD-related hospitalisations were observed in the TC group than in the CM group
E: events; PY: patient-years. Colombel JF, et al. Gastroenterology 2017;152(Suppl 1):S155; Colombel JF, et al. United European Gastroenterol J 2017:Abstract 1057.

25. CALM study design: Quality of life assessed at Weeks 12, 24, 36 and 48
Cost- effectiveness data
Evidence from other studies
Summary
Clinical evidence from CALM
MODULE 2
Quality of life data
Tight control (n=122)
Prednisone 40 mg/day burst and taper
Clinical management (n=122)
Quality-of-life assessments
Week: -9 -4 -1 12 24 36 48
Quality-of-life measures:
Inflammatory Bowel Disease Questionnaire (IBDQ; range 32–224)
SF-36 Physical Component Summary score (SF-36 PCS; range 0–100)
SF-36 Mental Component Summary score (SF-36 MCS; range 0–100)
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F; range 0–52)
Patient Health Questionnaire-9 (PHQ-9; range 0–27)
Work Productivity and Activity Impairment (WPAI) questionnaire (range 0–100)
Pannacione R. ECCO 2018; Oral DOP071

26. CALM: Quality of life improvements over Weeks 12–48
Cost- effectiveness data
Evidence from other studies
Summary
Clinical evidence from CALM
MODULE 2
Quality of life data
Tight control improved quality of life measures beyond the improvements seen with clinical management1
Quality of life measure
Average change from baseline difference between TC and CM over 48 weeks
IBDQ
9.90*
SF-36 PCS
2.25*
SF-36 MCS
3.61*
FACIT-F
4.37*
PHQ-9a
–1.57*
WPAI–work time missedab
–4.31%
WPAI–impairment while workingab
–6.24%
WPAI–overall work impairmentab
–7.23%
WPAI–daily activity impairmenta
–6.40%*
Numerically higher improvement across all measures
Improvement in most measures from Week 12
Impact on cost-effectiveness (e.g. in the UK2)
QoL measures give an indication of a patient’s physical and mental health, and motivation and ability to take part in life’s activities
e.g. IBDQ includes questions about fatigue, feeling frustrated, energy levels, feeling worried or depressed, feeling embarrassed, and satisfaction with life3
a. A higher value of PHQ-9 represents a higher level of symptoms of depression; a higher value of WPAI represents a higher percentage of work productivity affected
b. Answered by patients who were employed (approximately 50% of the population)
* p<0.05 tight control vs clinical management, using mixed models accounting for longitudinal measures, baseline smoking status, baseline weight, and corresponding baseline outcome values
1. Pannacione R. ECCO 2018; Oral DOP071; 2. Panaccione R, et al. United European Gastroenterol J 2017;5(5S):OP017; 3. Guyatt G, et al. Gastroenterology 1989;96:804–10

27. How is cost-effectiveness calculated?
Evidence from other studies
Summary
Clinical evidence from CALM
MODULE 2
Quality-of-life data
Cost- effectiveness data
Cost-effectiveness analysis compares the costs and health effect of an intervention to assess the extent to which it provides value for money
Cost-effectiveness ratio (CER) = Cost of treatment A
Success of treatment A
Quality-adjusted life-year (QALY) is a measure of quantity and quality of life (1 QALY = 1 year of perfect life)
Direct costs (medical and patient expenses) and indirect costs (impact on productivity and intangibles)
If comparing two interventions, A and B:
Incremental CER (ICER) = Difference in cost of treatment A and B
Difference in success of treatment A and B
…A is dominant over B if it has both a lower cost and a greater health effect
Cohen DJ, Reynolds MR. J Am Coll Cardiol 2008;52(25):2119–26; Zilberberg MD, Shorr AF. Clin Microbiol Infect 2010;16:1707–12

28. CALM cost-effectiveness calculation in the UK
Direct medical costs1
Evidence from other studies
Summary
Clinical evidence from CALM
MODULE 2
Quality-of-life data
Cost- effectiveness data
Hospitalisation costs
Average number of CD-related hospitalisations from CALM
Hospital cost data from UK-based research, from NHS perspective
Model designed to evaluate cost-effectiveness of tight control versus clinical management using data from CALM and costs in the UK1–3
Adalimumab
dose costs
Number of adalimumab doses estimated from CALM
UK list prices used for ADA costs
Other direct medical
costs
Including outpatient visits, laboratory tests and endoscopic procedures
Quality-adjusted life-years (QALYs)
Incremental cost-effectiveness ratio (ICER): Δ Costs / Δ QALYs between tight control and clinical management
CDAI: Crohn’s disease activity index; EQ-5D, EuroQol- 5 Dimension (an instrument to measure quality of life)
1. Panaccione R, et al. United European Gastroenterol J 2017;5(5S):OP017; 2. (accessed March 2018); 3. Buxton, et al. Value in Health 2007;10(3):214–20.

29. CALM cost-effectiveness outcomes in the UK
Evidence from other studies
Summary
Clinical evidence from CALM
MODULE 2
Quality-of-life data
Cost- effectiveness data
Outcomes (over 48 weeks)
Tight control minus clinical management
Remission rate*
14.8%
CD-related hospitalisations (event/person year)
–0.15
Adalimumab doses (40 mg)
6.15
Other direct medical costs
–£226
CD-related hospitalisation costs
–£1,270
Adalimumab dose costs
£2,165
Compared with clinical management, tight control had:
Higher remission rate
Fewer CD-related hospitalisations
More adalimumab doses
* Predicted time in remission is the model’s estimate of the proportion of time spent with CDAI under 150 over 48 weeks, estimated using CALM data
Panaccione R, et al. United European Gastroenterol J 2017;5(5S):OP017.

30. Total direct medical costs Quality-adjusted life-years
CALM: Cost-effectiveness of tight control versus clinical management in the UK
Evidence from other studies
Summary
Clinical evidence from CALM
MODULE 2
Quality-of-life data
Cost- effectiveness data
Total direct medical costs
Quality-adjusted life-years
0.684
£13,296
£12,627
0.652
Costs (£000)
QALYs
Δ costs = £669
(95% CI: £2,529, –£1,994)
ICER: Δ costs / Δ QALYs =
Δ QALY = 0.032
(95% CI: 0.042, 0.021)
£20,913 / QALY (95% CI: £94,116 to –£61,457 [TC dominant])
Panaccione R, et al. United European Gastroenterol J 2017;5(5S):OP017.

31. Regular monitoring involves baseline and ongoing assessments
EXAMPLE MONITORING SCHEDULE:
Monitor disease regularly
Assess risk of disease progression
Treat in a
timely manner
Summary
MODULE 3
Refer and diagnose patients quickly
Tailor your treat-to-target approach
Engage patients
Baseline (e.g. diagnosis, flare)
Ongoing monitoring
4–6 weeks
3 months
6 months
12 months
FCP CRP
TAUS
TAUS
FCP
and/or
CRP
TAUS
FCP
and/or
CRP
TAUS
FCP
and/or
CRP
TAUS
Endoscopy
Endoscopy (UC)
Endoscopy (CD)
Resolution of friability and ulceration
(Mayo 0–1) 3–6 months after
initiating therapy and at
3-month intervals
during the active phase
Resolution of ulceration
6–9 month intervals
during
the active phase
Timeframe for assessing endoscopic targets1
CRP, C-reactive protein; FCP, faecal calprotectin; TAUS, Transabdominal ultrasound
1. Peyrin-Biroulet L, et al. Am J Gastroenterol 2015;110:1324–38

32. CDEIS <4 and no deep ulcers (CDEIS decrease >5 from baseline)
Interpreting faecal calprotectin test results: FCP 250 μg/g as a guide to next steps
Monitor disease regularly
Assess risk of disease progression
Treat in a
timely manner
Summary
MODULE 3
Refer and diagnose patients quickly
Tailor your treat-to-target approach
Engage patients
Guide to interpreting FCP test results
Patients (%) 20
100 40 60 80
74.2
13.6
p<0.001
72/97
8/59
77.3
35.6
75/97
21/59
CDEIS <4 and no deep ulcers
(Primary endpoint)
Endoscopic response
(CDEIS decrease >5 from baseline)
CALM assessment of FCP levels in patients achieving endoscopic outcomes at Week 481
<250 μg/g
≥250 μg/g
FCP 100–250 µg/g
Inflammation possible
Further tests* may be required to confirm presence / absence of inflammation2
*Further tests may include another FCP test, TAUS or other imaging modalities
FCP ≥250 µg/g
Active inflammation likely
Optimise therapy to address ongoing inflammation2
CDEIS, Crohn's disease endoscopic index of severity; FCP, faecal calprotectin
1. Reinisch W, et al. Presented at ECCO 2018:OP015; 2. Adapted from Bressler B, et al. Can J Gastroenterol Hepatol 2015;29:369–72

33. Suggested monitoring to support a treat-to-target approach
Monitor disease regularly
Assess risk of disease progression
Treat in a
timely manner
Summary
MODULE 3
Refer and diagnose patients quickly
Tailor your treat-to-target approach
Engage patients Do
Don’t
Measure and record all baseline levels to track disease activity over time (endoscopy, FCP, CRP, )
Regularly monitor disease activity using non-invasive objective markers (CRP, FCP, )
Measure and record precise, standardised descriptions of endoscopic lesions (type, location, depth, extent)
Adopt appropriate monitoring for different patient situations
Rely on symptoms to monitor disease activity alone
Assume symptoms alone relate to active disease
Take short-cuts: be thorough in understanding disease activity in each patient
CRP, C-reactive protein; FCP, faecal calprotectin; TAUS, Transabdominal ultrasound