P494 The efficacy and safety of adalimumab for patients with moderately to severely active ulcerative colitis and predictors of response in Korea

S. Shin Shin1, S.J. Park2, Y. Kim1, J.P. Im3, H.J. Kim4, K.M. Lee5, J.W. Kim6, S.A. Jung7, J. Lee8, S.B. Kang9, S.J. Shin10, E.S. Kim11, Y.S. Kim12, T.O. Kim13, H.S. Kim14, D.I. Park15, H.K. Kim16, E.S. Kim17, Y.H. Kim18, D.H. Kim19, D. Teng20, J.H. Kim1, W.Y. Kim1, C.H. Choi1

1Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea, 2Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea, 3Department of Internal medicine, Seoul National University College of Medicine, Seoul, Republic of Korea, 4Department of Gastroenterology, Kyung Hee University Hospital, Seoul, Republic of Korea, 5Department of Gastroenterology, The Catholic University of Korea St. Vincent’s Hospital, Suwon, Republic of Korea, 6Department of Gastroenterology, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea, 7Department of Gastroenterology, Ewha Womans University Hospital, Seoul, Republic of Korea, 8Department of Internal Medicine, Chosun University College of Medicine, Gwagju, Republic of Korea, 9Department of Gastroenterology, The Catholic University of Korea Daejeon ST. Mary’s Hospital, Daejeon, Republic of Korea, 10Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea, 11Department of Gastroenterology, Korea University Anam Hospital, Seoul, Republic of Korea, 12Department of Gastroenterology, Inje University Seoul Paik Hospital, Seoul, Republic of Korea, 13Department of Gastroenterology, Inje University Haeundae Paik Hospital, Busan, Republic of Korea, 14Department of Gastroenterology, Chonnam National University Hospital, Gwagju, Republic of Korea, 15Department of Internal Medicine, Sungkyunkwan University School of Medicine- Kangbuk Samsung Hospital, Seoul, Republic of Korea, 16Department of Gastroenterology, Inha University Hospital, Incheon, Republic of Korea, 17Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea, 18Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, 19Abbvie Ltd., Abbvie Ltd., Seoul, Republic of Korea, 20AbbVie Pte. Ltd., AbbVie Pte. Ltd., Singapore, Singapore

Background

The aim of this study to assess the efficacy and safety of adalimumab (ADA), a monoclonal antibody against tumour necrosis factor α (TNF-α), and to explore predictors of response in Korean patients with ulcerative colitis (UC).

Methods

We conducted a prospective observational multicenter study over 56 weeks in adult patients with moderately to severely active UC. Clinical response and remission were assessed by Mayo score. Mucosal healing was defined as Mayo subscore 0 or 1. Faecal calprotectin (FC) were assessed at baseline, week 8 and 56. Adalimumab drug levels were checked at week 8 and at loss of response. Missing or incomplete data were handled using the nonresponder imputation method.

Results

A total of 146 patients were enrolled and included in the analysis. Clinical response rates were 52.1% (76/146) and 37.7% (55/146) at week 8 and 56, respectively. Clinical remission was achieved in 24.0% (35/146) and 21.9% (32/146) of patients at week 8 and 56. Steroid-free remission rates were 21.2% (31/146) at week 56. Mucosal healing rates were 39.0% (57/146) and 30.1% (44/146) at week 8 and 56. Prior use of anti-TNF-α did not affect the clinical and endoscopic responses. Treatment persistence was achieved in 57.5% (84/146) of patients at week 56. Adalimumab drug level was significantly higher in patients with clinical response (10.8 vs. 8.0, p = 0.004), clinical remission (11.7 vs. 8.8, p = 0.007) and mucosal healing (11.0 vs. 8.5, p = 0.010) at week 8. Adalimumab dose was escalated to 40 mg weekly in 25 (17.1%) patients, and clinical response and remission were achieved in 40% and 20% of patients at week 56, respectively. Mean faecal calprotectin levels were significantly more decreased in clinical responders compared with non-responders at week 8 (336.3 mg/kg vs. 628.8 mg/kg, p < 0.001). The Fecal calprotectin levels are well correlated with endoscopic severity, and the best cut-off value to predict mucosal healing was 274 mg/kg. The lower endoscopic severity, higher body mass index and higher serum albumin level at baseline were associated with a clinical response at week 8. The lower Mayo score, lower C-reactive protein level, clinical response (74.5% vs. 38.5%, p < 0.001) and mucosal healing (52.7% vs. 30.8%, p = 0.008) at week 8 were associated with clinical response at week 56. Serious adverse drug reactions were identified in 2.7% (4/146) of patients including 1 case of pulmonary tuberculosis.

Conclusion

Adalimumab is safe and effective for induction and maintenance in Korean patients with UC, regardless of prior anti-TNF therapy. Adalimumab drug level is associated with the efficacy of induction therapy. A better response to induction therapy can predict a better long-term response.