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P176. Patient reported outcome measures derived from the Crohn's Disease Activity Index: Correlation between PRO2 and PRO3 scores and CDAI-defined clinical thresholds

R. Khanna1, G. D'Haens1,2, B.G. Feagan1,3, W.J. Sandborn1,4, M.K. Vandervoort1, G. Zou1, R.L. Rolleri5, E. Bortey5, B.G. Levesque1,4, 1Robarts Clinical Trials Inc., Robarts Research Institute, Western University, London, Ontario, Canada, 2University of Amsterdam, Academic Medical Center, Amsterdam, Netherlands, 3Western University, Department of Epidemiology and Biostatistics, Department of Medicine, London Ontario, Canada, 4University of California, San Diego, Division of Gastroenterology, La Jolla, United States, 5Salix Pharmaceuticals Inc., Clinical Development, Raleigh North Carolina, United States

Background

The Crohn's Disease Activity Index (CDAI) is a clinical measure of disease activity based on symptoms, signs, and laboratory tests. The US Food and Drug Administration has indicated that patient reported outcomes (PROs) should be used as a primary outcome measure in randomized controlled trials for Crohn's disease (CD). As no validated PROs exist for CD, we investigated whether the CDAI diary card items pain, stool frequency, and general well-being (recorded over 7 days), could be adapted to derive a PRO measure.

Methods

The methods for evaluating the accuracy of using patient-reported items on the CDAI diary card to discriminate patients with CDAI scores less than 150 (remission) from those having CDAI scores greater than 150, for generating optimal cut points for patient-reported items, and the operating properties of a 2- (stool frequency and pain) or 3- (stool frequency, pain, and general well-being) item outcome measure (PRO2 and PRO3) have been previously described [1]. PRO2 and PRO3 scores that correspond to clinically relevant CDAI-defined thresholds of mild, moderate, and severe disease (total score of 150, 220, and 450) and total score changes of 50, 70, and 100 points were determined by regressing CDAI scores on PRO2 and PRO3 values using data from a MTX induction trial [2].

Results

Optimal cut points were a mean daily stool frequency ≤1.5, a mean daily abdominal pain score ≤1, and mean daily general well-being score of ≤1. Effect estimates were similar using PRO2, PRO3, or the original CDAI-based outcomes in the MTX trial (Table 1).

PRO2 and PRO3 values corresponding to CDAI scores of 150, 220, and 450 points were 8, 14, and 34 and 13, 22, and 53 respectively, and the corresponding values for CDAI changes of 50, 70, and 100 points, were 2, 5, and 8 and 5, 9, and 14, respectively (Figure 1).

Figure 1. Relationship between PRO2, PRO3, and CDAI scores at follow up.

Table 1 (abstract P176). Outcome measure comparison at week 16 of a MTX induction trial
Definition of remissionTotal populationPopulation with orosomucoid >88 mg/dL
Met criteria, N (%)Effect-sizePMet criteria, N (%)Effect-sizeP
MTX (N = 94)Placebo (N = 47) (%) MTX (N = 42)Placebo (N = 23) (%)
CDAI
CDAI ≤15050 (53)19 (40)130.1723 (55)9 (39)160.11
CDAI ≤150, no prednisone37 (39)9 (19)200.02519 (45)4 (17)280.021
CDAI ≤150, normal orosomucoid44 (47)15 (32)150.1219 (45)7 (30)150.22
CDAI ≤150, no prednisone, normal orosomucoid35 (37)9 (19)180.0417 (40)4 (17)230.037
PRO2
PRO2 alone38 (40)12 (25)150.1220 (48)8 (35)130.13
PRO2, no prednisone27 (29)4 (9)200.01216 (38)3 (13)250.017
PRO2, normal orosomucoid32 (34)8 (17)170.05116 (38)5 (22)160.15
PRO2, no prednisone, normal orosomucoid25 (27)4 (9)180.01914 (33)3 (13)200.031
PRO3
PRO3 alone37 (39)12 (25)140.1520 (48)8 (35)130.13
PRO3, no prednisone26 (28)4 (9)190.01516 (38)3 (13)250.017
PRO3, normal orosomucoid31 (33)8 (17)160.06516 (38)5 (22)160.15
PRO3, no prednisone, normal orosomucoid24 (26)4 (9)170.02414 (33)3 (13)200.031

Conclusion

PROs derived from CDAI diary card items may be appropriate for use in clinical trials for CD.

1. Khanna R, D'Haens G, Feagan BG, et al. Evaluation of the operating properties of candidate patient reported outcomes for use in randomized controlled trials in Crohn's disease. Inflamm Bowel Dis 2013; abstract in press.

2. Feagan BG, Rochon J, Fedorak RN, et al. Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators. N Engl J Med 1995; 332: 292–7.