Mucosal Healing Predicts Late Outcomes After the First Course of Corticosteroids for Newly Diagnosed Ulcerative Colitis SANDRO ARDIZZONE,* ANDREA CASSINOTTI,* PIERGIORGIO DUCA,‡ CRISTINA MAZZALI,‡ CHIARA PENATI,*GIANPIERO MANES,* RICCARDO MARMO,§ ALESSANDRO MASSARI,* PAOLA MOLTENI,* GIOVANNI MACONI,* andGABRIELE BIANCHI PORRO* *Department of Clinical Science, Gastroenterology Unit, ‡Section of Medical Statistics and Biometry, “L. Sacco” University Hospital, Milan; §Unità Operativa Gastroenterologia Polla, Azienda Sanitaria Locale Salerno, Italy CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2011;9:483–489 Department of Gastroenterology F1 Park hyunjin 1

Introduction Ulcerative colitis –Idiopathic inflammatory bowel disease –Moderate to severe active UC : Drug of choice - systemic corticosteroids –Treatment response : Clinical vs Endoscopic (Mucosal healing) Studies for Corticosteroid in newly dignosed UC –Small number and short-term clinical outcome (maximum, 1 y) –UC patients soon after diagnosis : fewer studies –Moreover, endoscopic response after CS : only a few studies –None for association between endoscopic observations and disease course 2

Aim Hospital-based inception cohort 5-year natural history Assessment –Early outcome : 3-month clinical and endoscopic response –Late outcome : subsequent clinical outcome The first CS therapy in patients with newly diagnosed UC Early and Late outcome Mucosal healing ? 3

Method – Study design and patients Study design –25-year hospital-based inception cohort –“L. Sacco” University Hospital –Clinical and endoscopic data : updated continuously by a database manager –Chart review : the end of the follow-up period by a single reviewer Patient’s characteristics –First diagnosis of moderate–severe active UC –Systemic steroid therapy within 12 months of diagnosis –Negative for Clostridium difficile and relative toxins 4

Method – Patient population Demographic and clinical data at baseline –Sex, family history of IBD, smoking habits, previous appendectomy, dates of birth/disease onset/disease diagnosis, disease extent, clinical and endoscopic activity, extraintestinal manifestations, date of the first CS therapy, CS regimen (drug, dosage, duration), previous and concomitant medications, and hospitalization at the time of the first steroid treatment Treatment –Systemic steroids (oral prednisone or parenteral methylprednisolone) –Starting dose : 40 to 60 mg/d –Tapered over a standard period of 3 months 5

Method – Assessment and F/U Clinical activity : Modified Powell–Tuck (PT) index –Remission (PT, 0–1), mild disease (PT, 2–5), moderate disease (PT, 6– 8), and severe disease (PT, 9) Endoscopic activity : Modified Baron index –Remission (Ba, 0: normal mucosa or mild erythema) –Mild activity (Ba, 1: granular or edematous, with loss of vascular pattern) –Moderate activity (Ba, 2: bleeding to light touch, erosion) –Severe activity (Ba, 3: spontaneous bleeding with ulceration) Follow up –After 3 and 6 months and then every 6 months for 60 months or until colectomy –After 3 and 6 months: PT index, Ba index, additional therapies, and clinical and endoscopic activity –Every 6 months : PT index, Ba index (if clinically necessary), and additional therapies 6

Method – Outcome Measures Early outcome –T3 : 3 mo from the start of CS therapy –(1) complete response (group A): Both clinical and endoscopic remission (PT, 0–1; Ba, 0) –(2) partial response (group B): clinical but no endoscopic remission (PT, 0–1; Ba, 1–3); –(3) no response (group C): persistence of intestinal symptoms and endoscopic lesions (PT, 2; Ba, 1–3). Late outcome –Five years after starting CS therapy –Relapse occurrence, type of relapse (general, systemic, or topical), time to relapse, number of relapses and UC-related hospitalization, immunosuppressive treatment, colectomy –Combined end point Hospitalizations, Immunosuppressive treatment, Colectomy. Definition –General relapse : onset of symptoms and signs of active disease (PT≥2 and Ba≥1) –Systemic relapse : requiring systemic CS –Topical relapse : requiring topical CS 7

Method – Statistical analysis Univariate analysis for patients baseline characteristics Chi-square test The Kaplan–Meier survival analysis and the log-rank test The Cox model Univariate and multivariate analyses Statistical significance : P value of 0.05 or less SAS 9.1 (SAS Institute,Cary, NC) 8

Results - patients 1032 patients refered for UC ( ) 225 patients : newly diagnosed UC 176 patients : Systemic CS within 12 months 157 patients 11 patients : no endoscopic f/u 8 patients : immunosuppressors at the time of diagnosis 9

Results - patients 10

Results – Early outcomes  Clinical remission : A + B  Persistent endoscopic activity : B + C  Clinical remission : A + B  Persistent endoscopic activity : B + C 11 Both clinical and endoscopic remission Clinical but no endoscopic remission

Results – Early outcomes(After 3 months) 12

Results – Early outcomes(After 3 months) 13

Results – Early outcomes(After 3 months) 14

Results – Late outcomes(After 5 years) 15

Results – Role of mucosal healing 16

Conclusion 17 Mucosal healing after corticosteroid therapy : asso/w a more aggressive disease course Endoscopic remission should be a key objective for pharmacologic therapy Mucosal healing after corticosteroid therapy : asso/w a more aggressive disease course Endoscopic remission should be a key objective for pharmacologic therapy

SUPPLEMENTARY 18

Powell-Tuck Index 19

Modified Baron index 20

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