Efficacy and safety of adalimumab biosimilar (HS016) in inflammatory bowel disease from the real-world study

Abstract

Objective: Adalimumab (ADA) is an effective treatment for inflammatory bowel disease (IBD), both ulcerative colitis (UC) and Crohn's disease (CD). The equal effect between the original ADA and biosimilars from Europe and the United States has been shown. However, the biosimilar of ADA is different in China. The effectiveness and safety data of ADA biosimilar (HS016) in China have yet to be discovered. Patients and methods: 91 patients (75 CD, 16 UC) received HS016 treatment and were enrolled in this study. Therapeutic response and safety profiles were analyzed. Therapeutic drug monitoring (TDM) was also carried out among nonresponse patients. After being considered as "nonresponse" (after three or 6 months of treatment), 20 patients' serum TNFα concentrations were measured and correlated to their disease severity. Results: Among active CD patients (n = 61), 75.4% (46/61) at 12 w, 73.8% (45/61) at 26 w, 50.8% (31/61) at 52 w achieved the clinical response, respectively; 55.7% (34/61) at 12 w, 65.6% (40/61) at 26 w, and 45.9% (28/61) at 52 w achieved clinical remission. The maintained remission rates of CD (n = 14) in clinical remission were 100% (14/14) at 12 w, 78.6% (11/14) at 26 w, and 63.6% (7/11) at 52 w, respectively. Among active UC patients, 37.5% (6/16) at 12 w and 50% (8/16) at 26 w achieved clinical response. Total adverse event rates were 5.5% (5/91) during 52-week visits. Due to the inadequate serum drug concentration, 30.4% (7/23) of patients had poor clinical responses. Elevations of serum anti-drug antibodies occurred in one additional patient (4.3%). Conclusion: ADA biosimilar HS016 had good efficacy and safety in Chinese IBD patients.

Keywords: Crohn’s disease; adalimumab biosimilar; therapeutic drug monitoring; therapeutic effect evaluation; ulcerative colitis.

FIGURE 1

Flow diagram of patient selection. A total of 103 patients received treatment with HS016 during this period, 91 patients, met the inclusion and exclusion criteria, entered the study. 83 patients completed the 12-week and 26-week follow-ups, and 61 patients completed the 52-week follow-up. All data in this study were obtained from the patients mentioned above. IBD, inflammatory bowel disease; HS016, adalimumab biosimilar, CD, Crohn’s disease; UC, ulcerative colitis.

FIGURE 2

Distribution of disease severity in CD patients based on HBI scores at baseline. Crohn’s disease patients were divided into different groups based on disease severity, as HBI score, 0–4 points as clinical remission (n = 14, 18.7%), 5–7 points as mid active (n = 30, 40%), 8–16 points as moderate activity (n = 30, 40%), and >16 points as severe activity (n = 1, 1.3%) (Reinisch et al., 2011). 98% of active patients were mild to moderate (n = 60). CD, Crohn’s disease; HBI, Harvey-Bradshaw Index.

FIGURE 3

The treatment outcomes of CD patients. (A) The clinical response and clinical remission rates among active CD patients. After 12-week, 26-week, and 52-week treatment, patients’ HBI scores were assessed and documented as clinical response (HBI score decrease ≥3 points) and clinical remission (HBI score ≤4 points); (B) The endoscopic response and endoscopic remission rates among active CD patients. After 12 w and 26 w of treatment, patients’ SES-CD scores were assessed and documented as endoscopic response (SES-CD score decrease ≥50%) and endoscopic remission (SES-CD score ≤3 points or “no visible ulcer” at endoscopy); (C) The clinical maintenance remission rates of CD patients. After 12-week, 26-week, and 52-week treatment, patients’ HBI scores were assessed. The patients, whose HBI score ≤4 points during every assessment, were documented as clinical maintenance remission. CD, Crohn’s disease; HBI, Harvey-Bradshaw Index; SES-CD, Simplified Endoscopic Score for Crohn’s Disease.

FIGURE 4

CD patients’ change of every index was observed at baseline, week 12, week 26, and week 52. (A) Change of leukocytes among CD patients at baseline, week 12, week 26, and week 52; (B) Change of hemoglobin among CD patients at baseline, week 12, week 26, and week 52; (C) Change of ESR among CD patients at baseline, week 12, week 26, and week 52; (D) Change of CRP among CD patients at baseline, week 12, week 26, and week 52. The data represent the mean ± SD *p < 0.05, **p < 0.01, ****p < 0.001, ns, p > 0.05 by one-way ANOVA. CRP, C-reactive protein; ESR, erythrocyte sedimentation rate.

FIGURE 5

TDM and serum TNF-α concentration were analyzed among portal CD patients. Patients who did not respond after a minimum of 12-week treatment underwent TDM and serum TNF-α concentration (A) Therapeutic drug concentration in 23 patients. 23 patients included 9 patients with primary non-response, 9 patients who did not show response under endoscopy at the 26-week follow-up, and 5 patients who did not achieve clinical remission at the 26-week follow-up. (B) Correlation analysis between serum TNF-α concentration and SES-CD score in 20 patients. The results indicate that there is no correlation between serum TNF-α concentration and SES-CD score. (r = 0.3605, p = 0.1184) (C) Correlation analysis between serum TNF-α concentration and CRP in 20 patients. (r = 0.4196, p = 0.0655). CD, Crohn’s disease; TDM, Therapeutic drug monitoring; SES-CD, Simplified Endoscopic Score for Crohn’s Disease; CRP, C-reactive protein.