Αναφορές εκβάσεων από τους ασθενείς (Patient Reported Outcomes): Μπορούν να αναβαθμίσουν τον τρόπο παρακολούθησης της νόσου; Γιώργος Μπάμιας

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1 Αναφορές εκβάσεων από τους ασθενείς (Patient Reported Outcomes): Μπορούν να αναβαθμίσουν τον τρόπο παρακολούθησης της νόσου; Γιώργος Μπάμιας

2 Σύγκρουση συμφερόντων Γιώργος Μπάμιας τιμητικές αμοιβές απο τις εταιρείες Abbvie Takeda Hellas MSD Shire Janssen Aenorasis S.A., Galenica Pfizer Genesys

3 Continuous response Selecting the right patient Selecting the right target Tight control of the disease Selecting the right biomarker Accomplishing the right outcome No disability Change in the natural course of the disease

4 Lack of a reliable indicator for disease control in UC RENAL DISEASE creatinine clearance/gfr DIABETES glycosylated haemoglobin ULCERATIVE COLITIS inflammation???

5 Clinical trials vs. real-world Difficulties with disease activity markers Doctors vs. patients conceptions Traditional model of medical visit Passive participation of the patient Lack of biomarkers

6 Only 31.1% of 206 patients with IBD (34% with CD, 26% with UC) would have been eligible to participate in any of the selected RCTs. This disconnect between clinical trials and clinical practice is one of the most likely reasons that everyday clinicians are slow to translate trials into practice CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2012;10:

7 Disease activity indices used in UC clinical trials have many limitations Composite score Complex, time consuming Uncertain correlation between individual components Uncertain weighing of each component High measurement variability Low statistical efficiency [low specificity and sensitivity of symptoms included] Lack objectivity [e.g. physician global assessment ] Mayo score

8 Disease activity assessment is physician and not patient oriented More than 50% of patients consider their disease moderate Only 1/3 of phycisians/nurses consider their patients disease moderate Schreiber S et al. BMC Gastroenterol. 2012;12:108.

9 The traditional follow-up model of periodical office visits provides a snapshot of the disease and may miss the long-term pattern Rubin DT et al. IBD. 2009

10 The treat to target concept 2 Resolution of symptoms alone is not a sufficient target. Objective evidence of inflammation of the bowel is necessary when making clinical decisions. Patient s experience of the disease Clinician s objective evidence of inflammation PROs ClinROs Combination Endpoint

11 What Are PRO(M)s [Patient Reported Outcomes (Measures)]? PROMs are standardized, validated questionnaires intended for completion by patients in order to measure their perceptions of their own functional status and well-being. A PRO is any report that comes directly from a patient about his or her health condition or its treatment without interpretation by healthcare professionals or anyone else

12 10...in addition to resolution of symptoms, the patient s individual goals should also be addressed. PROs can relate to symptoms, signs, functional status, perceptions, or aspects of functioning that are directly related to the disease status

13 PROMs, developed and validated according to rigorous criteria, are set to become a co-primary end point for clinical trials of therapy, together with objective measure[s]of inflammation.

14 Adaptation of FDA recommendation in recent, phase II/III clinical trials Ferrante et al. ECCO 2018

15 Data from a trial of rosiglitazone used to identify cut-points for detecting remission (patient rating of disease activity as perfect or very good ) for the full MCS, partial MCS, and PRO-2 that was based only on rectal bleeding and bowel frequency PRO-2 was comparable to the full MSC or the partial MSC Aliment Pharmacol Ther 2015; 42:

16 PURSUIT-M trial the importance of continuous response = Partial Mayo = Full Mayo Partial Mayo every 4 weeks Full Mayo at weeks 30 and 54 endoscopy to confirm the loss of response in every clinical flare Loss of response at any assessment = Treatment failure Continuous clinical reponse = response in all time points Sandborn WJ et al. Gastroenterology 2014;146:96 109

17 PURSUIT-M trial the importance of continuous response Clinical Gastroenterology and Hepatology Vol. 15, No. 8 Without CCR golimumab NO golimumab golimumab With CCR NO golimumab Corticosteroid use (%) Remission (%) Endoscopic healing (%) IBDQ score >170 (%)

18 PROs are sufficient to monitor continuous clinical response Reinisch W, et al UEGW, P1614. PRO1+2 Area under the curve= Endoscopy subscore Area under the curve= Partial Mayo score Area under the curve=0.9680

19 GO-COLITIS Response of PROs to treatment PROs of the partial Mayo score Stool frequency Baseline (n=205) Week 6 (n=198) Normal 3 (1.5%) 54 (27.3%) 1 2 stools more than normal 16 (7.8%) 61 (30.8%) 3 4 stools more than normal 64 (31.2%) 40 (20.2%) 5 or more stools more than normal 122 (59.5%) 43 (21.7%) Rectal bleeding No blood seen 6* (2.9%) 111 (56.1%) Sub-scores of the Mayo score Mean change (SD) from BL to Week 6 (all P<0.0001) Stool frequency -1.1 (1.0) Rectal bleeding -1.1 (0.9) PGA -1.1 (0.9) Streaks of blood with stool less than half the time 77 (37.6%) 57 (28.8%) Obvious blood with stool most of the time 94 (45.9%) 24 (12.1%) Blood alone passed 28 (13.7%) 6 (3.0%) *Protocol violations, but included in primary analysis Sebastian et al. UEGW 2016 #P0852.

20 Simpler biomarkers such as Fecal Calprotectin may substitute the need for endoscopy to provide objective absence of inflammation in patients with UC and may be combined with PROs for assessment of continuous response Cut-off : 174 μg/g with AUC = 0.956, sensitivity 91.9%, specificity 87.2%, P < CRP (> 5 mg/l): specificity 100 % Kostas A et al. WJG 2017;23:

21 PROs in real Figure world 1 medicine A combination of electronically reported PROs with a home-based test for a biomarker may facilitate the assessment of continuous response in UC The patient is directly involved, responsible for data collection and report and this may increase adherence to therapy Clinical Gastroenterology and Hepatology , e1DOI: ( /j.cgh )

22 E-health empowers patients with ulcerative colitis: a randomised controlled trial of the web-guided Constant-care approach Gut2010;59: (1) Better adherence to therapy (2) Better understanding of the disease (3) Shorter duration of flare (4) Fewer hospital visits (5) Better quality of life

23 Benefits of clinical use of PROs Better follow-up Patient motivation Lower cost