Intest Res.  2022 Jul;20(3):350-360. 10.5217/ir.2021.00049.

Clinical outcomes and predictors of response for adalimumab in patients with moderately to severely active ulcerative colitis: a KASID prospective multicenter cohort study

• Shin SY
• Park SJ
• Kim Y
• Im JP
• Kim HJ
• Lee KM
• Kim JW
• Jung SA
• Lee J
• Kang SB
• Shin SJ
• Kim ES
• Kim YS
• Kim TO
• Kim HS
• Park DI
• Kim HK
• Kim ES
• Kim YH
• Kim DH
• Teng D
• Kim JH
• Kim W
• Choi CH
• on behalf of the IBD Research Group of the Korean Association for the Study of Intestinal Diseases

• KMID: 2531989
• DOI: http://doi.org/10.5217/ir.2021.00049

Abstract

Background/Aims
This study assessed the efficacy and safety of adalimumab (ADA) and explored predictors of response in Korean patients with ulcerative colitis (UC).
Methods
A prospective, observational, multicenter study was conducted over 56 weeks in adult patients with moderately to severely active UC who received ADA. Clinical response, remission, and mucosal healing were assessed using the Mayo score.
Results
A total of 146 patients were enrolled from 17 academic hospitals. Clinical response rates were 52.1% and 37.7% and clinical remission rates were 24.0% and 22.0% at weeks 8 and 56, respectively. Mucosal healing rates were 39.0% and 30.1% at weeks 8 and 56, respectively. Prior use of anti-tumor necrosis factor-α (anti-TNF-α) did not affect clinical and endoscopic responses. The ADA drug level was significantly higher in patients with better outcomes at week 8 (P<0.05). In patients with lower endoscopic activity, higher body mass index, and higher serum albumin levels at baseline, the clinical response rate was higher at week 8. In patients with lower Mayo scores and C-reactive protein levels, clinical responses, and mucosal healing at week 8, the clinical response rate was higher at week 56. Serious adverse drug reactions were identified in 2.8% of patients.
Conclusions
ADA is effective and safe for induction and maintenance in Korean patients with UC, regardless of prior anti-TNF-α therapy. The ADA drug level is associated with the efficacy of induction therapy. Patients with better short-term outcomes were predictive of those with an improved long-term response.

Keyword

Inflammatory bowel disease; Tumor necrosis factor inhibitors; Treatment outcome

Figure

• 

  Fig. 1. Clinical response, remission, steroid-free remission, and mucosal healing rates according to the Mayo score at week 8 and 56 (A). Clinical outcomes according to prior anti-TNF-α therapy at week 8 (B) and at week 56 (C). Clinical response rates according to the use of immunomodulator at baseline (D). Clinical outcomes did not differ whether the patients had experienced anti-TNF therapy or not, and concomitant use of immunomodulator did not affect clinical response rate. TNF, tumor necrosis factor; AZA, azathioprine; 6-MP, 6-mercaptopurine.

• 

  Fig. 2. Serum adalimumab concentration (μg/mL) according to clinical outcomes at week 8. Mean serum adalimumab levels were significantly higher in patients who achieved clinical response, remission, and mucosal healing than in those without clinical response, remission, and mucosal healing, respectively, at week 8.

• 

  Fig. 3. Changes in mean fecal calprotectin and C-reactive protein levels from baseline in clinical responders and nonresponders at week 8 (A, B) and in patients with and without mucosal healing at week 8 (C, D). Fecal calprotectin and C-reactive protein levels significantly improved in patients achieving clinical response and mucosal healing compared with patients without clinical response and mucosal healing, respectively, at week 8. aP<0.05.

• 

  Fig. 4. Fecal calprotectin (FC) levels according to endoscopic subscore (A), FC level to predict mucosal healing (B) and endoscopic remission (C) on receiver operating characteristic (ROC) curve. FC levels were well correlated with patients’ endoscopic activities. The predictive level was 274.8 mg/kg for mucosal healing and 98 mg/kg for endoscopic remission, respectively. AUC, area under the ROC curve.

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