Two Randomized Controlled Trials of Hyaluronic Acid Fillers for the Correction of Nasolabial Folds.

YVOIRE Classic s (YC) and Restylane (RES) have similar rheological properties, which suit mid-dermis injection, while the rheological properties of YVOIRE Volume s (YV) are comparable to those of Perlane (PER), which suit deep dermis injection to treat deep wrinkles. Two similarly designed studies aimed to evaluate the performance and safety of YC and YV injected into the nasolabial folds (NLFs). METHODS: These were split-face designed, evaluator-blind, noninferiority studies. Fifty-eight subjects with moderate-to-severe NLFs were enrolled in the first study and treated with YC and RES, and 57 subjects were enrolled in the second study and treated with YV and PER. The Wrinkle Severity Rating Scale ranged from 1 (no visible fold) to 5 (extremely deep and long folds), and subject satisfaction was evaluated. RESULTS: The least squares mean Wrinkle Severity Rating Scale scores (standard error) at week 26 were 2.56 (0.09) for both YC- and RES-treated NLFs and 2.89 (0.08) and 2.91 (0.08) for YV- and PER-treated NLFs, respectively. The difference between the groups was 0 and 0.02, and the lower limit of its 95% confidence interval was -0.0725 and -0.0125, which was greater than the predefined margin (-0.29), proving the noninferiority of YC and YV to RES and PER, respectively. The safety profiles and subject satisfaction of YC and YV were similar to those of RES and PER, respectively. CONCLUSION: YC is comparable to RES and YV is comparable to PER in terms of performance and safety profiles, with NLF-correcting effects lasting for up to 26 weeks.

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.

Phase III, multicentre, double-blind, randomised, parallel-group study to evaluate the similarities between LBEC0101 and etanercept reference product in terms of efficacy and safety in patients with active rheumatoid arthritis inadequately responding to methotrexate.

OBJECTIVE: To evaluate the similarities between LBEC0101 (etanercept biosimilar) and the etanercept reference product (ETN-RP) in terms of efficacy and safety, including immunogenicity, in patients with active rheumatoid arthritis despite methotrexate treatment. METHODS: This phase III, multicentre, randomised, double-blind, parallel-group, 54-week study was conducted in Japan and Korea. The primary efficacy endpoint was the change from baseline in the disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) at week 24. American College of Rheumatology 20% (ACR20) response rate, adverse events (AEs), pharmacokinetics and development of antidrug antibodies (ADAs) were also evaluated. RESULTS: In total, 374 patients were randomised to LBEC0101 (n=187) or ETN-RP (n=187). The least squares mean changes from baseline in DAS28-ESR at week 24 in the per-protocol set were -3.01 (95% CI -3.198 to -2.820) in the LBEC0101 group and -2.86 (95% CI -3.051 to -2.667) in the ETN-RP group. The estimated between-group difference was -0.15 and its 95% CI was -0.377 to 0.078, which was within the prespecified equivalence margin of -0.6 to 0.6. ACR20 response rates at week 24 were similar between the groups (LBEC0101 93.3% vs ETN-RP 86.7%). The incidence of AEs up to week 54 was comparable between the groups (LBEC0101 92.0% vs ETN-RP 92.5%), although fewer patients in the LBEC0101 group (1.6%) than the ETN-RP group (9.6%) developed ADAs. CONCLUSION: The clinical efficacy of LBEC0101 was equivalent to that of ETN-RP. LBEC0101 was well tolerated and had a comparable safety profile to ETN-RP. TRIAL REGISTRATION NUMBER: NCT02357069.