scholarly journals 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

RMD Open ◽  
2020 ◽  
Vol 6 (1) ◽  
pp. e000987
Author(s):  
Mark C Genovese ◽  
Herbert Kellner ◽  
Yasumasa Arai ◽  
Rafael Muniz ◽  
Rieke Alten
Keyword(s):  
Rheumatoid Arthritis ◽  
Active Rheumatoid Arthritis ◽  
Reference Product ◽  
Open Label ◽  
Double Blind ◽  
Open Label Extension ◽  
To Receive ◽  
Switching Treatment ◽  
All Treatment

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 with active rheumatoid arthritis (RA) inadequately controlled with methotrexate (MTX). A subsequent randomised open-label extension (OLE) study with treatment switching assessed long-term safety, efficacy, pharmacokinetics and immunogenicity of FKB327 compared with the RP.MethodsPatients with moderate-to-severe, active RA on a stable dose of MTX were randomised 1:1 to receive FKB327 or the RP (40 mg subcutaneously every other week) for 24 weeks. Patients who completed the DB study were enrolled in the OLE and rerandomised 2:1 to receive FKB327 or the RP; two-thirds continued on the same treatment and one-third switched for 30 weeks. All patients received FKB327 through Week 76. Long-term efficacy, safety and immunogenicity were assessed.ResultsOf 728 patients in the DB study, 645 were enrolled in the FKB327-OLE study. The American College of Rheumatology (ACR)20 response rates for all treatment groups at Week 30 in the OLE ranged from 83.2% to 85.9%. ACR20 response rates remained stable for all patients regardless of single- or double-switching treatment and were similar for all treatment sequences through Week 76. The safety profile and incidence of antidrug antibodies were comparable across sequences.ConclusionEfficacy, safety and immunogenicity were similar among patients with RA treated with FKB327 or the RP for up to 2 years, and were not affected by single- or double-switching treatment.

scholarly journals Long-term efficacy and safety in patients with rheumatoid arthritis continuing on SB4 or switching from reference etanercept to SB4

2017 ◽  
Vol 76 (12) ◽  
pp. 1986-1991 ◽  
Author(s):  
Paul Emery ◽  
Jiří Vencovský ◽  
Anna Sylwestrzak ◽  
Piotr Leszczyński ◽  
Wieslawa Porawska ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Response Rates ◽  
Comparable Efficacy ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Term Efficacy ◽  
Open Label Extension ◽  
Extension Period

ObjectivesSB4 (Benepali, Brenzys) is a biosimilar of reference etanercept (ETN). In a randomised, double-blind, 52-week study, SB4 demonstrated comparable efficacy and safety to ETN in patients with rheumatoid arthritis (RA). The open-label extension period evaluated long-term efficacy, safety and immunogenicity when continuing SB4 versus switching from ETN to SB4.MethodsIn the randomised, double-blind phase, patients received weekly subcutaneous administration of 50 mg SB4 or ETN with background methotrexate for up to 52 weeks. Patients in the Czech Republic and Poland who completed the 52-week visit were enrolled in the open-label extension period and received SB4 for 48 additional weeks. Efficacy, safety and immunogenicity were assessed up to week 100.ResultsOf 245 patients entering the extension period, 126 continued to receive SB4 (SB4/SB4) and 119 switched to SB4 (ETN/SB4). American College of Rheumatology (ACR) response rates were sustained and comparable between SB4/SB4 and ETN/SB4 with ACR20 response rates at week 100 of 77.9% and 79.1%, respectively. Other efficacy results, including radiographic progression, were also comparable between the groups. After week 52, rates of treatment-emergent adverse events were 47.6% (SB4/SB4) and 48.7% (ETN/SB4); one patient/group developed non-neutralising antidrug antibodies. No cases of active tuberculosis or injection-site reactions were reported during the extension period. One patient (SB4/SB4) died of hepatic cancer.ConclusionsSB4 was effective and well tolerated over 2 years in patients with RA. Efficacy, safety and immunogenicity were comparable between the SB4/SB4 and ETN/SB4 groups, showing no risk associated with switching patients from ETN to SB4.Trial registration numberNCT01895309; 2012-005026-30

scholarly journals FKB327, an adalimumab biosimilar, versus the reference product: results of a randomized, Phase III, double-blind study, and its open-label extension

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Mark C. Genovese ◽  
Josephine Glover ◽  
Maria Greenwald ◽  
Wieslawa Porawska ◽  
Elias Chalouhi El Khouri ◽  
...  
Keyword(s):  
Response Rate ◽  
Reference Product ◽  
Double Blind Study ◽  
Open Label ◽  
Double Blind ◽  
Acr20 Response ◽  
Drug Concentrations ◽  
Open Label Extension ◽  
Acr20 Response Rate ◽  
All Treatment

Abstract Objective To compare the efficacy, serum drug concentrations, immunogenicity, and safety of FKB327 with the adalimumab reference product (RP) in combination with methotrexate in patients with moderate-to-severe, active rheumatoid arthritis (RA). Methods Patients were randomized 1:1 in a double-blind study (NCT02260791), received 40 mg of FKB327 or RP by subcutaneous injection every other week for 24 weeks (Period I), then re-randomized 2:1, remaining on the same study drug or switching to the other up to week 54 in an open-label extension (Period II, NCT02405780). Efficacy was evaluated using American College of Rheumatology (ACR20) response rate difference at week 24 with equivalence margins of ± 13% and − 12% to + 15% using 95% and 90% confidence intervals (CIs), respectively. Efficacy, serum drug concentrations, immunogenicity, and safety were compared at week 54. Results A total of 730 patients were randomized in Period I (n = 367 FKB327, n = 363 RP), and 645 transitioned to Period II (n = 216 FKB327–FKB327, n = 108 FKB327–RP, n = 108 RP–FKB327, n = 213 RP–RP). At week 24, ACR20 response rates were 74.1% with FKB327 versus 75.7% with RP. 95% and 90% CI of the response rate difference were − 7.9 to 4.7% and − 7.3 to 3.6%, respectively, meeting predefined equivalence margins. The ACR20 response rate remained over 70% of patients to week 54 with all treatment sequences. In Period I, mean trough serum drug concentrations were slightly higher for patients receiving FKB327 than those receiving RP. Mean concentrations were stable over time and reflected steady state in Period II. The proportions of patients with samples positive for neutralizing antidrug antibodies (ADAs) were comparable (57.7% with FKB327 vs. 55.5% with RP) at week 24, and no consistent difference in ADA were seen between continuous and switched treatments in Period II. Efficacy was slightly reduced in the small proportion of patients with high ADA titers in all treatment groups. No clinically significant differences were observed in the incidence of commonly reported treatment-emergent adverse events between the treatments across Periods I and II. Conclusion FKB327 was equivalent to RP in clinical efficacy and demonstrated comparable safety and immunogenicity in patients with moderate-to-severe RA. No effect of switching between FKB327 and RP was observed. Trial registration ClinicalTrials.gov, NCT02260791, Registered 29 July 2014. ClinicalTrials.gov, NCT02405780, Registered 17 July 2015.

Short- and Long-Term Cardiovascular Effects of Mixed Amphetamine Salts Extended-Release in Adolescents With ADHD

CNS Spectrums ◽  
2005 ◽  
Vol 10 (S15) ◽  
pp. 22-30 ◽  
Author(s):  
Timothy E. Wilens ◽  
Thomas J. Spencer ◽  
Joseph Biederman
Keyword(s):  
Extended Release ◽  
Cardiovascular Effects ◽  
Dose Titration ◽  
Open Label ◽  
Double Blind ◽  
Once Daily ◽  
Open Label Extension ◽  
Short And Long Term ◽  
Clinically Significant

AbstractObjectiveAssess cardiovascular effects of once-daily mixed amphetamine salts extended release (MAS XR) in adolescents (13–17 years of age) with attention-deficit/hyperactivity disorder (ADHD).MethodsBlood pressure (BP), pulse, and electrocardiograms were assessed in 327 healthy subjects during a 4-week, randomized, double-blind, placebo-controlled, forced dose-titration study. Placebo (n=69) or once-daily MAS XR(10, 20, 30, or 40 mg) was administered to subjects ≤75 kg (n=233); 50- and 60-mg MAS XR was administered to subjects >75 kg (n=25). One hundred thirty-eight subjects participated in a 6-month, open-label extension study.FindingsChanges in BP and QTcB (Bazett's formula) intervals at 4 weeks with MAS XR were not significantly different from the placebo group. Pulse increased by 5.0 and 8.5 bpm after 3 weeks with MAS XR 20 and 50 mg/day, respectively (P≤.002). After 6 months of open-label MAS XR treatment, mean increases in systolic BP (1.7 mm Hg; P=.0252) and pulse (4.4 bpm; P<.0001) were statistically, but not clinically, significant diastolic BP was not significantly changed (0.6 mm Hg) A decrease in QTcB interval (-4.6±19.9 msec) was statistically (P=.009), but not clinically, significant. There were no serious cardiovascular adverse events.ConclusionCardiovascular effects of short- and long-term MAS XR treatment (≤60 mg/day) were minimal in otherwise healthy adolescents with ADHD.

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