Adalimumab Reference Product In Patients Research Articles

Pooled safety analysis from the VOLTAIRE clinical trials of adalimumab-adbm and adalimumab reference product in patients with rheumatoid arthritis, Crohn’s disease, and chronic plaque psoriasis

ABSTRACT Objectives This analysis reported the incidence of safety endpoints across five phase 3 randomized controlled clinical trials in patients with rheumatoid arthritis (RA), Crohn’s disease (CD), and chronic plaque psoriasis (PsO) who received ≥ 1 dose of adalimumab-adbm or adalimumab reference product (RP). Methods Exposure-adjusted incidence rates for safety endpoints were calculated per 100 patient-years and reported by disease indication and treatment arm. Subgroup analyses by patient age and sex were also conducted. Results The mean length of follow-up was 62 weeks, 48 weeks, and 32 weeks for patients with RA, CD, and PsO, respectively. Rates of serious adverse events (SAEs) and discontinuations due to adverse events (AEs) were similar among patients with RA and PsO, but slightly higher among those with CD. Incidence rates of all safety endpoints were consistent between the adalimumab-adbm and adalimumab RP treatment arms within each indication Subgroup analyses of patients with RA, CD, and PsO showed no between-group differences by age and sex. Conclusions In patients with RA, CD, and PsO, there were no differences between biosimilar adalimumab-adbm or the adalimumab RP regarding the rate of AEs, SAEs, discontinuations due to AEs, deaths, or any AEs of special interest.

50522 Interchangeability of SB5 and Adalimumab Reference Product in Patients with Moderate to Severe Chronic Plaque Psoriasis

50522 Interchangeability of SB5 and Adalimumab Reference Product in Patients with Moderate to Severe Chronic Plaque Psoriasis

Safety and efficacy of BI 695501 versus adalimumab reference product in patients with advanced Crohn’s disease (VOLTAIRE-CD): a multicenter, randomized, double-blind, phase 3 trial

Adalimumab is a type of drug known as a biologic used for chronic inflammatory diseases, such as Crohn’s. In these medical conditions, a protein called TNF is overproduced in the affected part of the body, which causes inflammation and damage. Adalimumab blocks the action of TNF to reduce this inflammation. The FDA defines a biosimilar as a biological product that is highly similar to and has no clinically meaningful differences in safety and effectiveness to an existing FDA-approved reference product. This means that there are more treatment options for chronically ill patients at a potentially lower cost. BI 695501 is an adalimumab biosimilar that has already demonstrated similar efficacy, safety and immunogenicity to adalimumab reference product in patients with chronic plaque psoriasis and rheumatoid arthritis. In this video, Professor Stephen Hanauer discusses the VOLTAIRE-CD study, which aimed to compare the safety and efficacy of the BI 695501 biosimilar in Crohn’s disease.

Safety and efficacy of BI 695501 versus adalimumab reference product in patients with advanced Crohn's disease (VOLTAIRE-CD): a multicentre, randomised, double-blind, phase 3 trial

BI 695501 is a biosimilar that has demonstrated similar efficacy, safety, and immunogenicity to adalimumab reference product in patients with rheumatoid arthritis and chronic plaque psoriasis. The VOLTAIRE-CD study aimed to compare the efficacy and safety of BI 695501 with adalimumab reference product in patients with Crohn's disease. This phase 3, randomised, double-blind study was done at 92 centres in 12 countries across Europe and the USA in patients aged 18-80 years with moderately to severely active Crohn's disease (Crohn's Disease Activity Index [CDAI] score 220-450). Patients were randomly assigned 1:1 using an interactive response technology system to the BI 695501 group or adalimumab reference product group, stratified by previous exposure to infliximab (yes vs no) and simple endoscopic score for Crohn's disease at screening (<16 vs ≥16). All investigators involved in trial assessments or procedures and all patients were masked to treatment allocation until week 24. Patients received BI 695501 (40 mg/0·8 mL formulation) or adalimumab reference product (either 40 mg/0·4 mL citrate-free or 40 mg/0·8 mL) 160 mg on day 1 and 80 mg on day 15, followed by 40 mg every 2 weeks, via subcutaneous injection. The primary endpoint was the proportion of patients with clinical response (CDAI decrease ≥70 points) at week 4, with an exploratory non-inferiority margin of 0·76 for the lower limit of the two-sided 90% CI of the risk ratio (RR). The primary analysis was done in a modified full analysis set of all patients who received at least one dose of study medication and had a baseline and at least one post-baseline CDAI assessment. Safety was assessed in all patients who received at least one dose of study medication. After week 4, responders were treated until week 46; those randomly assigned to adalimumab reference product switched to BI 695501 at week 24. This study is registered at ClinicalTrials.gov (NCT02871635) and EudraCT (2016-000612-14). Between Jan 4, 2017, and April 5, 2018, 147 patients were enrolled and randomly assigned to BI 695501 (n=72) or adalimumab reference product (n=75). At week 4, 61 (90%) of 68 patients in the BI 695501 group and 68 (94%) of 72 in the adalimumab reference product group had a clinical response (adjusted RR 0·945 [90% CI 0·870-1·028]). In the safety analysis set, 45 (63%) of 72 patients in the BI 695501 group and 42 (56%) of 75 in the adalimumab reference product group had an adverse event during weeks 0-24; 31 (43%) and 34 (45%) had adverse events during weeks 24-56. The most common drug-related treatment-emergent adverse events during weeks 0-24 were weight increase (three [4%] patients in the BI 695501 group) and injection-site erythema and upper respiratory tract infection (three [4%] patients for each event) in the adalimumab reference product group. The only drug-related TEAEs reported in two or more patients during weeks 24-56 were weight increase and increased γ-glutamyltransferase, which occured in two (3%) patients each in the BI 695501 group. No drug-related TEAEs were reported in two or more patients during weeks 24-56 in the adalimumab reference product followed by BI 699501 group. Serious adverse events occurred in six (8%) patients in the BI 695501 group and eight (11%) in the adalimumab reference group between weeks 0-24, and two (3%) and nine (12%) patients between weeks 24-56. Adverse events of special interest occurred in two (3%) patients in each treatment group during weeks 0-24 (acute sinusitis and pulmonary tuberculosis in the BI 695501 group and anal abscess and postoperative wound infection in the adalimumab reference product group) and two (3%) patients in each group during weeks 24-56 (psoas abscess and hypersensitivity in the BI 695501 group and pulmonary tuberculosis and erythematous rash in the adalimumab reference product followed by BI 699501 group). Safety and efficacy were similar in patients with Crohn's disease treated with BI 695501 or adalimumab reference product. Treatment benefits were maintained in patients receiving adalimumab reference product who switched to BI 695501. These results further support the existing licensure of BI 695501 as an alternative to adalimumab reference product for patients with Crohn's disease, as well as the other indications for which BI 695501 is approved. Boehringer Ingelheim.

Similar efficacy, safety, and immunogenicity of the biosimilar BI 695501 and adalimumab reference product in patients with moderate-to-severe chronic plaque psoriasis: results from the randomized Phase III VOLTAIRE-PSO study

ABSTRACT Background: BI 695501 is an approved biosimilar to Humira® reference product (RP). Research design and methods: In this randomized Phase III trial (VOLTAIRE-PSO), patients with moderate-to-severe chronic plaque psoriasis received BI 695501 or adalimumab RP (24-week treatment). Primary efficacy endpoint: the proportion of patients with ≥75% reduction in Psoriasis Area and Severity Index (PASI 75) response at week 16 (±18% equivalence limits for two-sided 95% confidence interval between treatment groups). Safety, pharmacokinetics, and immunogenicity were also assessed. Results: Baseline characteristics were balanced between treated groups (BI 695501, n = 159; adalimumab RP, n = 158). PASI 75 response rates (full analysis set, n = 158; n = 157) were 68.2% (BI 695501) and 70.4% (adalimumab RP) at week 16 (95% CI: −14.4%, 8.7%), and 75.3% and 72.4%, at week 24, respectively. At week 24, 41.5% (BI 695501) and 44.9% (adalimumab RP) of treated patients had treatment-emergent adverse events (AEs), 3.1% and 4.4% had serious AEs, and 0.0% and 1.9% had AEs of special interest. Of treated patients, 75.3% (BI 695501) and 77.9% (adalimumab RP) were anti-drug antibody-positive. Conclusion: These data demonstrate equivalent efficacy and highly similar safety and immunogenicity between BI 695501 and adalimumab RP in patients with chronic plaque psoriasis. Study identifier: NCT02850965

13097 Biosimilar BI 695501 demonstrates clinical equivalence to adalimumab reference product in patients with moderate to severe chronic plaque psoriasis through 24 weeks

Introduction: BI 695501 is bioequivalent to US-licensed and EU-approved adalimumab reference product (RP) [1]. Here we present week 24 efficacy, safety, and immunogenicity data from a study comparing BI 695501 with adalimumab-RP (US-licensed) in patients with moderate to severe chronic plaque psoriasis.

Long-term safety, immunogenicity and efficacy comparing FKB327 with the adalimumab reference product in patients with active rheumatoid arthritis: data from randomised double-blind and open-label extension studies

Background/ObjectiveFKB327 is a biosimilar of the antitumour necrosis factor adalimumab reference product (RP). A randomised, double-blind (DB) phase 3 study compared the efficacy of FKB327 with the RP in patients...

P052 Biosimilar BI 695501 Demonstrates Non-Inferior Efficacy and Comparable Safety to Adalimumab Reference Product in Patients With Active Crohn's Disease

BACKGROUND:BI 695501 has demonstrated bioequivalence to both the US-licensed and EU-approved adalimumab reference product (RP) in rheumatoid arthritis. The aim of this head-to-head trial was to evaluate the similarity of BI 695501 and EU-approved adalimumab RP, by comparing efficacy, endoscopic impr

Long-term safety, efficacy, and immunogenicity of adalimumab biosimilar BI 695501 and adalimumab reference product in patients with moderately-to-severely active rheumatoid arthritis: results from a phase 3b extension study (VOLTAIRE-RAext)

ABSTRACT Objective: To evaluate long-term safety, efficacy, and immunogenicity of BI 695501 in patients with moderately-to-severely active rheumatoid arthritis (RA) who have completed VOLTAIRE-RA. Methods: Eligible patients for this phase 3b open-label extension study (VOLTAIRE-RAext), who had completed 48 weeks’ treatment with BI 695501 (Group A), 24 weeks each of adalimumab RP then BI 695501 (Group B), or 48 weeks of adalimumab RP (Group C) in VOLTAIRE-RA, were enrolled. Results: Altogether, 430 patients received BI 695501 fortnightly for 48 weeks: Group A, n = 225; Group B, n = 103; Group C, n = 102. The proportion of patients with drug-related adverse events (AEs; overall 20.2%) was similar across Groups A, B, and C: 21.3%, 20.4%, and 17.6%, respectively. The majority of treatment-emergent AEs were non-serious and of mild/moderate intensity. Consistent with adalimumab RP’s safety profile, most drug-related AEs were in the system organ class infections and infestations. BI 695501 and adalimumab RP responses at the end of VOLTAIRE-RA were sustained during VOLTAIRE-RAext and all efficacy and immunogenicity endpoints were similar across groups. Conclusion: Over 2 years, BI 695501 showed similar safety, efficacy, and immunogenicity to adalimumab RP, independent of initial treatment in VOLTAIRE-RA. No previously unknown adalimumab side effects were identified. Clinical trial registration: NCT02640612.