Long-term efficacy, safety and immunogenicity in patients with rheumatoid arthritis continuing on an etanercept biosimilar (LBEC0101) or switching from reference etanercept to LBEC0101: an open-label extension of a phase III multicentre, randomised, double-blind, parallel-group study

Background To evaluate the long-term efficacy, safety and immunogenicity of continuing LBEC0101; the etanercept (ETN) biosimilar; or switching from the ETN reference product (RP) to LBEC0101 in patients with rheumatoid arthritis (RA). Methods This multicentre, single-arm, open-label extension study enrolled patients who had completed a 52-week randomised, double-blind, parallel phase III trial of LBEC0101 vs ETN-RP. Patients treated with ETN-RP during the randomised controlled trial switched to LBEC0101; those treated with LBEC0101 continued to receive LBEC0101 in this study. LBEC0101 (50 mg) was administered subcutaneously once per week for 48 weeks with a stable dose of methotrexate. Efficacy, safety and immunogenicity of LBEC0101 were assessed up to week 100. Results A total of 148 patients entered this extension study (70 in the maintenance group and 78 in the switch group). The 28-joint disease activity scores (DAS28)-erythrocyte sedimentation rate (ESR) were maintained in both groups from week 52 to week 100 (from 3.068 to 3.103 in the maintenance group vs. from 3.161 to 3.079 in the switch group). ACR response rates at week 100 for the maintenance vs. switch groups were 79.7% vs. 83.3% for ACR20, 65.2% vs. 66.7% for ACR50 and 44.9% vs. 42.3% for ACR70. The incidence of adverse events and the proportion of patients with newly developed antidrug antibodies were similar in the maintenance and switch groups (70.0% and 70.5%, 1.4% and 1.3%, respectively). Conclusions Administration of LBEC0101 showed sustained efficacy and acceptable safety in patients with RA after continued therapy or after switching from ETN-RP to LBEC0101. Trial registration ClinicalTrials.gov, NCT02715908. Registered 22 March 2016.This extension study was funded by LG Chem, Ltd. (formerly, LG Life Sciences, Ltd), Mochida Pharmaceutical Co., Ltd. and Korea Health Industry Development Institute

Cell wall N-glycan of Candida albicans ameliorates early hyper- and late hypo-immunoreactivity in sepsis

Severe infection often causes a septic cytokine storm followed by immune exhaustion/paralysis. Not surprisingly, many pathogens are equipped with various anti-inflammatory mechanisms. Such mechanisms might be leveraged clinically to control septic cytokine storms. Here we show that N-glycan from pathogenic C. albicans ameliorates mouse sepsis through immunosuppressive cytokine IL-10. In a sepsis model using lipopolysaccharide (LPS), injection of the N-glycan upregulated serum IL-10, and suppressed pro-inflammatory IL-1 beta, TNF-alpha and IFN-gamma. The N-glycan also improved the survival of mice challenged by LPS. Analyses of structurally defined N-glycans from several yeast strains revealed that the mannose core is key to the upregulation of IL-10. Knocking out the C-type lectin Dectin-2 abrogated the N-glycan-mediated IL-10 augmentation. Furthermore, C. albicans N-glycan ameliorated immune exhaustion/immune paralysis after acute inflammation. Our results suggest a strategy where the immunosuppressive mechanism of one pathogen can be applied to attenuate a severe inflammation/cytokine storm caused by another pathogen

Efficacy and safety of pegfilgrastim biosimilar MD‐110 in patients with breast cancer receiving chemotherapy: Single‐arm phase III

Abstract Introduction Pegfilgrastim is indicated to decrease the incidence of chemotherapy‐induced febrile neutropenia. It is the first granulocyte‐colony stimulating factor approved for prophylactic use regardless of carcinoma type and is marketed in Japan as G‐LASTA (Kyowa Kirin Co., Ltd., Tokyo, Japan). MD‐110 is a biosimilar of pegfilgrastim. This phase III, multicenter, open‐label, single‐arm study investigated the efficacy and safety of MD‐110 in early‐stage breast cancer patients receiving neoadjuvant or adjuvant myelosuppressive chemotherapy. Methods A total of 101 patients received the study drug. Each patient received docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 (TC) for four cycles on day 1 of each cycle. MD‐110 (3.6 mg) was administered subcutaneously on day 2 of each cycle. The primary efficacy endpoint was the duration of severe neutropenia during cycle 1 (days with absolute neutrophil count < 500/mm3). The safety endpoints were adverse events and the presence of antidrug antibodies. Results The mean (SD) duration of severe neutropenia for MD‐110 was 0.2 (0.4) days. The upper limit of the two‐sided 95% confidence interval for the mean duration of severe neutropenia was 0.2 days, below the predefined threshold of 3.0 days. The incidence of febrile neutropenia, the secondary efficacy endpoint, was 6.9% (7/101). Adverse events, occurring in more than 50% of patients, were alopecia, constipation, and malaise, which are common side effects of TC chemotherapy. Antidrug antibodies were negative in all patients. Conclusion MD‐110 was effective against chemotherapy‐induced neutropenia. No additional safety concern, compared with the originator, was observed in patients with breast cancer receiving TC chemotherapy.(JapicCTI‐205230)