Safety and Effectiveness of SB2 (Infliximab Biosimilar) in Adult Patients with Immune-Mediated Inflammatory Diseases: A Post-Marketing Surveillance in Korea.

INTRODUCTION: SB2 is a biosimilar of infliximab (IFX), which is approved for rheumatoid arthritis (RA), ankylosing spondylitis (AS), adult and pediatric Crohn's disease (CD), adult and pediatric ulcerative colitis (UC), psoriatic arthritis (PsA), and plaque psoriasis (PsO). The drug approval process in Korea includes post-marketing surveillance (PMS) studies to re-examine the safety and effectiveness of approved new medications. METHODS: This was a prospective, multi-center, open-label, observational, phase 4 PMS study of IFX-naïve patients or patients switched from reference IFX or another IFX-biosimilar to SB2 in all approved indications. The primary endpoint was to evaluate the safety of SB2 reported as adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was to evaluate the effectiveness measured as investigators' overall effectiveness assessment, categorized as improved, stable, or worsened. Furthermore, disease-specific activity scores were collected for each indication [28-joint Modified Disease Activity Score (DAS28) for RA, Korean Bath Ankylosing Spondylitis Disease Activity Index (KBASDAI), Crohn's Disease Activity Index (CDAI), and Full Mayo Score for UC]. RESULTS: In the safety and effectiveness analysis, 180 and 128 patients were included, respectively. Most patients (83.9%) were IFX-naïve patients and 16.1% were switched patients. RA (48.9%) and AS (31.1%) were the most frequent indications. Overall, 23 (12.8%) patients reported AEs and 14 (7.8%) patients reported ADRs. Serious adverse events (SAEs) were reported by 3 (1.7%) patients. As per investigators' overall effectiveness assessments, SB2 was effective in 94.6% (105/111) of IFX-naïve patients and 82.4% (14/17) of switched patients. In IFX-naïve patients, disease activity scores decreased significantly from baseline to week 30 (week 24 for AS); mean (SD) changes of disease scores for each indication were DAS28 - 1.9 (0.79) for RA, KBASDAI - 3.8 (1.68) for AS, CDAI - 200.4 (112.47) for CD, and Full Mayo Score - 6.6 (2.92) for UC. The persistence rate of SB2 treatments was 88.3% with median treatment duration of 30.1 weeks. CONCLUSION: This PMS study of the IFX-biosimilar SB2 in Korea confirmed the safety and effectiveness of SB2 in major indications.

The influence of YMDD mutation patterns on clinical outcomes in patients with adefovir add-on lamivudine combination treatment.

BACKGROUND/AIM: The aim of this study was to assess the patterns of lamivudine (LAM)-resistant mutations and the influence on biochemical and virological responses to adefovir (ADV) add-on LAM combination therapy in patients with LAM-resistant chronic hepatitis B (CHB). METHODS: Seventy-eight CHB patients with confirmed genotypic resistance to LAM, who initiated ADV add-on LAM combination treatment, were enrolled at our institution between April 2007 and April 2009. RESULTS: The baseline tyrosine-methionine-aspartate-aspartate (YMDD) mutation patterns were as follows: rtM204I 45 (57.7%); and rtM204V + rtM204I/V 33 (42.3%). The decrease in the mean ± standard deviation (SD) serum log(10) HBV-DNA level did not differ between the patients carrying the rtM204I vs. rtM204IV +rtM204I/V mutations at 3, 6 and 12 months after the initiation of ADV add-on LAM combination treatment. The proportion of patients who achieved ALT normalization (<40 IU/L) 12 months after the initiation of ADV add-on LAM combination treatment were significantly higher in patients with a rtM204I mutation than rtM204V+ rtM204I/V mutations (39 [86.7%] vs. 22 [66.7%], P = 0.05). The proportion of patients in whom the log(10) HBV-DNA decreased <2 log(10) copies/ml, 6 months after the initiation of ADV add-on LAM combination treatment (non-responders), was significantly higher in patients with a rtM204V + rtM204I/V mutations than rtM204I mutation (7 [21.2%] vs. 2 [4.4%], P = 0.032). CONCLUSION: Biochemical response at 12 months from baseline was better in patients with a rtM204I mutation than rtM204V+ rtM204I/V mutations. In addition, early treatment failure was more common in patients with rtM204V+ rtM204I/V mutations than a rtM204I mutation.

Subjects with diarrhea-predominant IBS have increased rectal permeability responsive to tryptase.

BACKGROUND AND AIMS: Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) appear to have increased intestinal permeability; it has been suggested that activation of protease-activated receptor-2 (PAR-2) receptors is responsible for this alteration. The aims of this study are to evaluate (1) if rectal (large bowel) permeability is increased in IBS-D and (2) if tryptase plays a critical role in the altered permeability. METHODS: Rectal biopsies from 20 patients with IBS-D and 30 subjects without the condition (normal controls) were assessed for macromolecular permeability using horseradish peroxidase in Ussing chambers in the basal state and after addition of drugs to the basolateral side. Reverse-transcription polymerase chain reaction (RT-PCR) was performed using colonic biopsy tissues from patients with IBS-D and normal subjects. RESULTS: When tryptase was added to the basolateral (not mucosal) side of normal rectal biopsy tissues, permeability appeared to be proportional to the increase in tryptase concentration (P < 0.05) and was abolished by the addition of tryptase inhibitor (100 µM nafamostat; 1.568 ± 0.874 ng/2 h/mm(2) to 0.766 ± 0.661 ng/2 h/mm(2), n = 14, respectively, P < 0.01). Intestinal permeability in patients with IBS-D was significantly increased compared with controls (0.848 ± 0.0.600 ng/2 h/mm(2), n = 21, P < 0.01). Nafamostat significantly reduced the enhanced permeability in IBS-D (0.934 ± 0.589 ng/2 h/mm(2) to 0.247 ± 0.263 ng/2 h/mm(2), n = 14, respectively, P < 0.05). Transcription levels of PAR2 measured by RT-PCR did not differ between IBS-D and normal subjects. CONCLUSION: Tryptase seems to play an important role in the control of human colonic mucosal permeability, and enhanced tryptase activity was responsible for the increased permeability of rectal mucosa in IBS patients.

Analysis of rectal dynamic and static compliances in patients with irritable bowel syndrome.

AIMS: Our aim was to investigate whether the dynamic and static compliances differ between patients with irritable bowel syndrome (IBS) and normal subjects. MATERIALS AND METHODS: Fifty-five IBS patients (age range 20-65 years, mean age 39.0 years, 28 women and 27 men; 36 diarrhea-predominant IBS (IBS-D) patients and 19 constipation-predominant IBS (IBS-C) patients) with symptoms that fulfilled the Rome-II criteria and 21 healthy controls (age range 25-58 years, mean age 37.8 years; 11 women and ten men) were recruited. The anorectal functions, including dynamic compliance, were evaluated via barostat tests. A power exponential model was used for the evaluation of static compliance. RESULTS: There was no significant difference in dynamic compliance between the normal subjects and the IBS patients (10.3+/-3.1 and 8.9+/-2.9 mmHg, respectively, P>0.05). However, even though no significant difference was detected in the overall shape of the curve (beta; P>0.05), there were significant differences in the kappa and P (half) between the normal subjects and the IBS patients (P<0.05), respectively. When we compared the dynamic and static compliances between the IBS-C and IBS-D patients, there were no significant differences found (P>0.05). CONCLUSIONS: An exponential model provided good fit to the actual data, and there were significant differences in static compliance between the normal subjects and the IBS patients. This result can reveal the altered biomechanical properties of the gut wall in IBS patients.

Factors affecting abdominal pain during colonoscopy.

OBJECTIVE: The actual degree of pain or discomfort experienced during colonoscopy varies between patients. This prospective study was conducted to determine what variables, apart from the endoscopist's skill, are associated with a patient's discomfort during this procedure. DESIGN/METHODS: From December 2003 to September 2004, 646 colonoscopy examinations performed by three experienced endoscopists were analysed. Midazolam and meperidine were administered intravenously 10 min before the procedure. The degree of patient discomfort was assessed by asking more than five times during the procedure and by using a visual analogue pain scale (0-10) examined up to 7 days after the procedure. Patients were divided into sub-groups as follows: (1) comfortable group (n=304), no complaint during the procedure; and (2) uncomfortable group (n=342), more than one complaint during the procedure. RESULTS: The correlation between the degree of patient discomfort and the results of the visual analogue pain scale was statistically significant (r2=0.118, P<0.01). Chi-squared analyses demonstrated that female gender, younger age (480 s), technically difficult insertion, and lower body mass index (BMI) are factors associated with uncomfortable procedure. Multivariate analysis demonstrated that younger age, female gender, lower BMI, difficulty of examination, and previous gynaeco-pelvic surgery in female gender are independent factors associated with discomfort during colonoscopy. CONCLUSIONS: An uncomfortable colonoscopic procedure will be expected in younger, female patients with a history of gynaeco-pelvic surgery.

Prevalence and risk factors of non-alcoholic fatty liver disease among Korean adults.

BACKGROUND AND AIM: Differences in the prevalence of non-alcoholic fatty liver disease (NAFLD) between Eastern and Western populations are primarily attributable to differences in definitions and biased population selection. Thus, the aim of the present study was to accurately determine the actual prevalence of NAFLD by sonography and to characterize the risk factors for NAFLD. METHODS: The present cross-sectional study was performed with data obtained from 6,648 subjects, all of whom were older than 20 years of age (3,530 men and 3,118 women). The term 'non-drinker' was applied to men who consumed less than 30 g alcohol/day and to women who consumed less than 20 g alcohol/day. Non-alcoholic fatty liver disease was defined as a sonographically detected fatty liver in the absence of viral hepatitis in a non-drinker. RESULTS: Of the 1,613 subjects who were diagnosed with sonographic fatty liver, 1,240 were non-drinkers and had no viral hepatitis. Overall, the unadjusted and age-adjusted prevalences of NAFLD were 18.7% (23% in men, 13.7% in women) and 16.1% (21.6% in men, 11.2% in women), respectively. Multivariate analysis revealed that several risk factors were profoundly associated with the prevalence of NAFLD, including obesity, insulin resistance, hyperlipidemia and hyperglycemia in both genders, as well as age, menopausal status and estrogen medication in women only. CONCLUSIONS: These results demonstrate that the prevalence of NAFLD in Korean adults, according to sonographic surveys, is comparable to that seen in more developed countries. From the perspective of increasing obesity, the high prevalence rates noted in the study may herald an increased burden of chronic liver disease in the Korean population.