Batch-to-Batch Consistency of SB4 and SB2, Etanercept and Infliximab Biosimilars.

BACKGROUND: Biosimilars must meet stringent regulatory requirements, both at the time of authorization and during their lifecycle. Yet it has been suggested that divergence in quality attributes over time may lead to clinically meaningful differences between two versions of a biologic. Therefore, this study investigated the batch-to-batch consistency across a range of parameters for released batches of the etanercept biosimilar (SB4) and infliximab biosimilar (SB2). METHODS: SB4 (Benepali®) and SB2 (Flixabi®) were both developed by Samsung Bioepis and are manufactured in Europe by Biogen at their facility in Hillerød, Denmark. A total of 120 batches of SB4 and 25 batches of SB2 were assessed for consistency and compliance with specified release parameters, including purity, post-translational glycosylation (SB4 only), protein concentration, and biological activity. RESULTS: The protein concentration, purity, tumor necrosis factor-α (TNF-α) binding, and TNF-α neutralization of all batches of SB4 and SB2 were within the strict specification limits set by regulatory agencies, as was the total sialic acid (TSA) content of all batches of SB4. CONCLUSIONS: Quality attributes of SB4 and SB2 batches showed little variation and were consistently within the rigorous specifications defined by regulatory agencies.

Patient Perceptions and Preferences of Two Etanercept Autoinjectors for Rheumatoid Arthritis: Findings from a Patient Survey in Europe.

INTRODUCTION: Benepali® was the first etanercept (Enbrel®) biosimilar to be approved in the European Union. Both Benepali and Enbrel are available as autoinjector devices. In a recent survey, nurses from France, Germany, Italy, Spain, and the United Kingdom (UK) reported that their patients with rheumatoid arthritis (RA) would prefer the Benepali autoinjector compared to the Enbrel MYCLIC autoinjector. To determine whether patients' perceptions were similar to those of the nurses, this survey evaluated patients' perceptions and preferences of the Benepali autoinjector versus the Enbrel MYCLIC autoinjector in the same five European countries. METHODS: Patients with RA using the Enbrel MYCLIC autoinjector participated in a 25-min, face-to-face questionnaire-interview. Patients were also shown an instructional video and device-handling leaflet, received a live demonstration on the Benepali autoinjector, and had access to both Benepali and Enbrel MYCLIC training autoinjectors. Patients rated the importance of ten autoinjector attributes on a seven-point scale (1 = not important at all; 7 = extremely important) and provided their autoinjector preferences based on specific attributes. Patients also gave their opinion on which autoinjector they would prefer to use for self-injection. RESULTS: Overall, 220 patients participated in the survey (France, n = 30; Germany, n = 65; Italy, n = 67; Spain, n = 12; UK, n = 46). 'Easy to operate the self-injection' was ranked as the most important attribute (mean score of 6.8), followed by 'easy to grip' (6.5), and 'intuitive/self-explaining usage' (6.3). Patients preferred the Benepali autoinjector, with the attribute of 'easier to operate' being a strong differentiator compared to the Enbrel MYCLIC autoinjector. Most patients (74%) reported that they would prefer to use the Benepali autoinjector over the Enbrel MYCLIC autoinjector. 'Easy to operate the self-injection' and 'button-free autoinjector' were key drivers when selecting an autoinjector. CONCLUSIONS: Patients in Europe reported a preference for the Benepali autoinjector compared to the Enbrel MYCLIC autoinjector. This finding is consistent with results from a recently reported nurse survey. FUNDING: Biogen.

Perceptions and Preferences of Two Etanercept Autoinjectors for Rheumatoid Arthritis: A New European Union-Approved Etanercept Biosimilar (Benepali®) Versus Etanercept (Enbrel®) - Findings from a Nurse Survey in Europe.

INTRODUCTION: Enbrel® (etanercept: manufactured by Immunex Corporation, Newbury Park, Thousand Oaks, CA 91320, USA) was the first biological disease-modifying anti-rheumatic drug approved for the treatment of rheumatoid arthritis (RA) in Europe. More recently, an etanercept biosimilar (Benepali®: manufactured by Biogen Inc, Cambridge, MA 02124, USA) was approved in the European Union. The perceptions and preferences of the Benepali autoinjector versus Enbrel MYCLIC autoinjector were evaluated by nurses from Europe. METHODS: The survey involved a 25-min face-to-face questionnaire-interview with nurses from France, Germany, Italy, Spain, and the UK, experienced in training patients on using the Enbrel MYCLIC autoinjector. Nurses viewed an instructional video and device-handling leaflet, received a live demonstration on the Benepali autoinjector and had access to both Benepali and Enbrel MYCLIC training autoinjectors. Nurses rated the importance of ten autoinjector attributes on a scale of 1-7 (1 = not important at all; 7 = extremely important) and provided their autoinjector preferences based on specific attributes. Nurses also gave their opinion on which autoinjector their patients with RA would prefer. RESULTS: A total of 149 nurses participated in this survey (France, n = 30; Germany, n = 40; Italy, n = 30; Spain, n = 19; UK, n = 30). 'Easy to operate the self-injection' was ranked as the most important attribute (mean score of 6.8), followed by 'easy to grip' (6.6) and 'intuitive/self-explaining usage' (6.6). Nurses preferred the Benepali autoinjector, with attributes of 'easier to operate' and 'more intuitive to use' being strong differentiators compared with the Enbrel MYCLIC autoinjector. Most nurses (86%) reported that their patients would prefer the Benepali autoinjector over the Enbrel MYCLIC autoinjector. 'Easy to operate the self-injection' and 'button-free autoinjector' were key drivers when selecting an autoinjector. CONCLUSION: Based on these survey results, nurses in Europe reported a preference for the Benepali autoinjector compared with the Enbrel MYCLIC autoinjector for the majority of attributes assessed. In particular, attributes of 'easy to operate' and 'more intuitive/self-explaining to use' were highly rated for the Benepali autoinjector, which may allow easy handling of the autoinjector. FUNDING: Biogen International GmBH.

Impact of reconstruction methods and pathological factors on survival after pancreaticoduodenectomy.

BACKGROUND: Surgery remains the mainstay of therapy for pancreatic head (PH) and periampullary carcinoma (PC) and provides the only chance of cure. Improvements of surgical technique, increased surgical experience and advances in anesthesia, intensive care and parenteral nutrition have substantially decreased surgical complications and increased survival. We evaluate the effects of reconstruction type, complications and pathological factors on survival and quality of life. MATERIALS AND METHODS: This is a prospective study to evaluate the impact of various reconstruction methods of the pancreatic remnant after pancreaticoduodenectomy and the pathological characteristics of PC patients over 3.5 years. Patient characteristics and descriptive analysis in the three variable methods either with or without stent were compared with Chi-square test. Multivariate analysis was performed with the logistic regression analysis test and multinomial logistic regression analysis test. Survival rate was analyzed by use Kaplan-Meier test. RESULTS: Forty-one consecutive patients with PC were enrolled. There were 23 men (56.1%) and 18 women (43.9%), with a median age of 56 years (16 to 70 years). There were 24 cases of PH cancer, eight cases of PC, four cases of distal CBD cancer and five cases of duodenal carcinoma. Nine patients underwent duct-to-mucosa pancreatico jejunostomy (PJ), 17 patients underwent telescoping pancreatico jejunostomy (PJ) and 15 patients pancreaticogastrostomy (PG). The pancreatic duct was stented in 30 patients while in 11 patients, the duct was not stented. The PJ duct-to-mucosa caused significantly less leakage, but longer operative and reconstructive times. Telescoping PJ was associated with the shortest hospital stay. There were 5 postoperative mortalities, while postoperative morbidities included pancreatic fistula-6 patients, delayed gastric emptying in-11, GI fistula-3, wound infection-12, burst abdomen-6 and pulmonary infection-2. Factors that predisposed to development of pancreatic leakage included male gender, preoperative albumin < 30g/dl, pre-operative hemoglobin < 10g/dl and non PJ-duct to mucosa type of reconstruction. The ampullary cancers presented at an earlier stage and had a better prognosis than pancreatic cancer and cholangiocarcinoma. Early stage (I and II), negative surgical margin, well and moderate differentiation and absence of lymph node involvement significantly predicted for longer survival. CONCLUSIONS: PJ duct-to-mucosa anastomosis was safe, caused least pancreatic leakage and least blood loss compared with the other methods of reconstruction and was associated with early return back to home and prolonged disease free and overall survival.

Laparoscopic versus open cholecystectomy in patients with liver cirrhosis: a prospective, randomized study.

BACKGROUND: Gallstones are more common in patients with liver cirrhosis than in healthy individuals. Higher morbidity and mortality were reported in cirrhotic patients with either laparoscopic or open cholecystectomy. The aim of this study was to compare laparoscopic and open cholecystectomy in cirrhotic patients with symptomatic cholelithiasis in a prospective, randomized manner. MATERIALS AND METHODS: Thirty patients with symptomatic cholelithiasis associated with Child-Pugh class A or B liver cirrhosis were prospectively and randomly grouped equally to either laparoscopic or open cholecystectomy. The two groups were compared regarding operative time, morbidity, mortality, postoperative liver function, and hospital stay. RESULTS: The two groups were comparable regarding demographic data, preoperative and postoperative Child-Pugh scoring, mean operative time (57.3 minutes for laparoscopic and 48.5 for open), and complications (33.3% for each). Hospital stay was shorter for the laparoscopic group. One conversion (6.7%) to open surgery was reported. No periopertive mortality occurred in either group. CONCLUSIONS: For Child-Pugh class A and B cirrhotics, laparoscopic cholecystectomy is comparable to the open approach regarding operative time, morbidity, mortality, and effect on liver function, but with shorter hospital stay. Considering the other well-documented advantages of the laparoscopic approach, namely, less pain, earlier mobilization and feeding, and better cosmoses, laparoscopic cholecystectomy would be the first choice in cirrhotic patients.