scholarly journals Filgotinib in combination with methotrexate or as monotherapy versus methotrexate monotherapy in patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: the phase 3, randomised controlled FINCH 3 trial

2021 ◽  
pp. annrheumdis-2020-219213
Author(s):  
René Westhovens ◽  
William F C Rigby ◽  
Désirée van der Heijde ◽  
Daniel W T Ching ◽  
William Stohl ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Primary Endpoint ◽  
Active Rheumatoid Arthritis ◽  
Health Assessment ◽  
Signs And Symptoms ◽  
Janus Kinase ◽  
Phase 3 ◽  
Double Blind ◽  
Acr20 Response ◽  
American College Of Rheumatology

ObjectivesTo investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure.MethodsThis 52-week, phase 3, multicentre, double-blind clinical trial (NCT02886728) evaluated once-daily oral filgotinib in 1252 patients with RA randomised 2:1:1:2 to filgotinib 200 mg with MTX (FIL200 +MTX), filgotinib 100 mg with MTX (FIL100 +MTX), filgotinib 200 mg monotherapy (FIL200), or MTX. The primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 24.ResultsThe primary endpoint was achieved by 81% of patients receiving FIL200+ MTX versus 71% receiving MTX (p<0.001). A significantly greater proportion treated with FIL100+ MTX compared with MTX achieved an ACR20 response (80%, p=0.017) at week 24. Significant improvement in Health Assessment Questionnaire-Disability Index was seen at week 24; least-squares mean change from baseline was −1.0 and −0.94 with FIL200+MTX and FIL100+MTX, respectively, versus −0.81 with MTX (p<0.001, p=0.008, respectively). Significantly higher proportions receiving FIL200+MTX (54%) and FIL100+MTX (43%) achieved DAS28(CRP) <2.6 versus MTX (29%) (p<0.001 for both) at week 24. Hierarchical testing stopped for comparison of ACR20 for FIL200 monotherapy (78%) versus MTX (71%) at week 24 (p=0.058). Adverse event rates through week 52 were comparable between all treatments.ConclusionsFIL200+MTX and FIL100+MTX both significantly improved signs and symptoms and physical function in patients with active RA and limited or no prior MTX exposure; FIL200 monotherapy did not have a superior ACR20 response rate versus MTX. Filgotinib was well tolerated, with acceptable safety compared with MTX.

scholarly journals 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

2017 ◽  
Vol 77 (4) ◽  
pp. 488-494 ◽  
Author(s):  
Hiroaki Matsuno ◽  
Masato Tomomitsu ◽  
Atsushi Hagino ◽  
Seonghye Shin ◽  
Jiyoon Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Active Rheumatoid Arthritis ◽  
Reference Product ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Acr20 Response ◽  
American College Of Rheumatology ◽  
Parallel Group ◽  
Registration Number

ObjectiveTo 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.MethodsThis 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.ResultsIn 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.ConclusionThe 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 numberNCT02357069.

scholarly journals Efficacy and safety of filgotinib alone and in combination with methotrexate in Japanese patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: Subpopulation analyses of 24-week data of a global phase 3 study (FINCH 3)

2021 ◽  
Author(s):  
Tatsuya Atsumi ◽  
Yoshiya Tanaka ◽  
Tsukasa Matsubara ◽  
Koichi Amano ◽  
Naoki Ishiguro ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Event ◽  
Primary Endpoint ◽  
Active Rheumatoid Arthritis ◽  
Japanese Patients ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
American College Of Rheumatology ◽  
Remission Rates ◽  
Event Rates

ABSTRACT Objectives To evaluate the efficacy and safety of filgotinib for Japanese patients with rheumatoid arthritis (RA) and limited or no prior methotrexate (MTX) exposure. Methods Data up to 24 weeks were analysed for 71 Japanese patients from a 52-week global Phase 3 study. Patients with RA and limited or no prior MTX exposure were randomised in a 2:1:1:2 ratio to filgotinib 200 mg plus MTX, filgotinib 100 mg plus MTX, filgotinib 200 mg, or MTX. Maximum MTX dose was 15 mg/week. Primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at Week 24. Results Week 24 ACR20 rates in Japanese patients were 82.6%, 90.9%, 83.3%, and 80.0% for filgotinib 200 mg plus MTX, filgotinib 100 mg plus MTX, filgotinib 200 mg, and MTX, respectively. Greater ACR20 rates with filgotinib vs MTX occurred at Week 2. Greater proportions receiving filgotinib vs MTX achieved DAS28-CRP &lt;2.6 at Weeks 12 and 24. Adverse event rates were comparable across treatments and between the Japanese and overall populations. Conclusions While Week 24 ACR20 rates were similar, filgotinib provided faster responses and higher remission rates vs MTX. In Japanese patients with RA and limited or no prior MTX exposure, filgotinib was generally well tolerated.

Efficacy and safety of pamapimod in patients with active rheumatoid arthritis receiving stable methotrexate therapy

2009 ◽  
Vol 69 (2) ◽  
pp. 364-367 ◽  
Author(s):  
R E Alten ◽  
C Zerbini ◽  
S Jeka ◽  
F Irazoque ◽  
F Khatib ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Active Rheumatoid Arthritis ◽  
Study Drug ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Acr20 Response ◽  
American College Of Rheumatology ◽  
European League Against Rheumatism ◽  
Efficacy Measure ◽  
The Individual

Objective:To determine the efficacy and safety of pamapimod in adult patients with active rheumatoid arthritis (RA) who had an inadequate clinical response to methotrexate (MTX).Methods:Patients receiving stable doses of MTX were randomised to one of six dose groups and received 12 weeks of double-blind pamapimod (up to 300 mg once daily) or matching placebo. The primary efficacy measure was the proportion of patients with ⩾20% improvement in RA based on the American College of Rheumatology criteria (ACR20) at 12 weeks. Secondary measures were ACR50, Disease Activity Score (DAS)/European League Against Rheumatism (EULAR) responses and the individual ACR core set of parameters. Safety measures included adverse events (AEs), laboratory testing and immunology assessments.Results:On a background of MTX, the percentage of patients with an ACR20 response at week 12 in the pamapimod groups (31% to 43%) was not significantly different from placebo (34%). Secondary efficacy end points showed a similar pattern. AEs were typically mild and included infections, gastrointestinal disturbances, dizziness and rashes; AEs resulting in discontinuation of study drug were primarily attributed to infections.Conclusion:In patients with active RA receiving stable doses of MTX, pamapimod showed non-significant improvement in efficacy outcomes compared to placebo.

scholarly journals A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy

2015 ◽  
Vol 76 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Paul Emery ◽  
Jiří Vencovský ◽  
Anna Sylwestrzak ◽  
Piotr Leszczyński ◽  
Wieslawa Porawska ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Primary Endpoint ◽  
Reference Product ◽  
Phase Iii ◽  
Pharmacokinetic Parameters ◽  
Weekly Dose ◽  
Double Blind ◽  
Acr20 Response ◽  
American College Of Rheumatology ◽  
Parallel Group

ObjectivesTo compare the efficacy and safety of SB4 (an etanercept biosimilar) with reference product etanercept (ETN) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) therapy.MethodsThis is a phase III, randomised, double-blind, parallel-group, multicentre study with a 24-week primary endpoint. Patients with moderate to severe RA despite MTX treatment were randomised to receive weekly dose of 50 mg of subcutaneous SB4 or ETN. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 24. Other efficacy endpoints as well as safety, immunogenicity and pharmacokinetic parameters were also measured.Results596 patients were randomised to either SB4 (N=299) or ETN (N=297). The ACR20 response rate at week 24 in the per-protocol set was 78.1% for SB4 and 80.3% for ETN. The 95% CI of the adjusted treatment difference was −9.41% to 4.98%, which is completely contained within the predefined equivalence margin of −15% to 15%, indicating therapeutic equivalence between SB4 and ETN. Other efficacy endpoints and pharmacokinetic endpoints were comparable. The incidence of treatment-emergent adverse events was comparable (55.2% vs 58.2%), and the incidence of antidrug antibody development up to week 24 was lower in SB4 compared with ETN (0.7% vs 13.1%).ConclusionsSB4 was shown to be equivalent with ETN in terms of efficacy at week 24. SB4 was well tolerated with a lower immunogenicity profile. The safety profile of SB4 was comparable with that of ETN.Trial registration numbersNCT01895309, EudraCT 2012-005026-30.

SAT0136 RELATIVE EFFICACY AND SAFETY OF TOFACITINIB, BARICITINIB, UPADACITINIB, AND FILGOTINIB, IN COMPARISON WITH ADALIMUMAB IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS: A BAYESIAN NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1005.1-1005
Author(s):  
Y. H. Lee ◽  
G. G. Song
Keyword(s):  
Rheumatoid Arthritis ◽  
Active Rheumatoid Arthritis ◽  
Response Rate ◽  
Meta Analysis ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Acr20 Response ◽  
Randomized Controlled ◽  
Acr20 Response Rate

Background:Methotrexate (MTX), an effective disease-modifying antirheumatic drug (DMARD) [2], is the most widely used DMARD for the treatment of rheumatoid arthritis (RA). However, not all patients are responsive to the drug; 30% of the patients discontinue therapy within 1 year of commencing the treatment, usually because of the lack of efficacy or undesirable adverse effects Small-molecule Janus kinase inhibitors are clinically developed for the treatment of RA.Objectives:The aim of this study is to investigate the relative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in comparison with adalimumab in patients with active RA and having inadequate responses to MTX.Methods:We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib, and adalimumab in RA patients having inadequate responses to MTX.Results:Four RCTs, comprising 5,451 patients, met the inclusion criteria. The baricitinib 4mg+MTX and upadacitinib 15mg+MTX group showed a significantly higher American College of Rheumatology 20% (ACR20) response rate than the adalimumab 40mg+MTX group. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that baricitinib 4mg+MTX had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by upadacitinib 15mg+MTX, tofacitinib 5mg+MTX, filgotinib 200mg+MTX, filgotinib 100mg+MTX, adalimumab 40mg+MTX, and placebo+MTX. The upadacitinib 15mg+MTX and baricitinib 4mg+MTX groups showed significantly higher ACR50 and ACR70 response rates than adalimumab 40mg+MTX. In terms of Herpes zoster infection, the ranking probability based on the SUCRA indicated that placebo+MTX were likely to be the safest treatments, followed by filgotinib 200mg+MTX, filgotinib 100mg+MTX, adalimumab 40mg+MTX, tofacitinib 5mg+MTX, upadacitinib 15mg+MTX, and baricitinib 4mg+MTX. Regarding safety analysis, no statistically significant differences were found between the respective intervention groups.Conclusion:In RA patients with an inadequate response to MTX, baricitinib 4mg+MTX and upadacitinib 15mg+MTX showed the highest ACR response rates, suggesting a difference in efficacy among the different JAK inhibitors.References:[1]Fleischmann R, Mysler E, Hall S, Kivitz AJ, Moots RJ, Luo Z, DeMasi R, Soma K, Zhang R, Takiya LJTL (2017) Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial. 390:457-468[2]Taylor PC, Keystone EC, van der Heijde D et al (2017) Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med 376:652-662[3]Fleischmann R, Pangan AL, Mysler E, Bessette L, Peterfy C, Durez P, Ostor A, Li Y, Zhou Y, Othman AA (2018) A phase 3, randomized, double-blind study comparing upadacitinib to placebo and to adalimumab, in patients with active rheumatoid arthritis with inadequate response to methotrexate. ARTHRITIS & RHEUMATOLOGY. WILEY 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, pp[4]Combe B, Kivitz A, Tanaka Y, van der Heijde D, Matzkies F, Bartok B, Ye L, Guo Y, Tasset C, Sundy J (2019) LB0001 EFFICACY AND SAFETY OF FILGOTINIB FOR PATIENTS WITH RHEUMATOID ARTHRITIS WITH INADEQUATE RESPONSE TO METHOTREXATE: FINCH1 PRIMARY OUTCOME RESULTS. BMJ Publishing Group Ltd, ppDisclosure of Interests:None declared

scholarly journals Randomised Double-Blind Trial of Combination Antibiotic Therapy in Rheumatoid Arthritis

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Angela Smith ◽  
Caroline Doré ◽  
Peter Charles ◽  
Alena Vallance ◽  
Tara Potier ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Placebo Group ◽  
Active Treatment ◽  
Active Rheumatoid Arthritis ◽  
Controlled Trial ◽  
Primary Outcome Measure ◽  
Good Evidence ◽  
Double Blind ◽  
Acr20 Response ◽  
Significant Difference

Objective. A combination of intravenous clindamycin and oral tetracycline has been used for many years as a treatment for active rheumatoid arthritis (RA), despite the absence of good evidence for its efficacy. A single-blind pilot study of this therapy suggested that a double-blind placebo-controlled trial was warranted.Methods. Patients with active RA were randomised in a 2 : 1 ratio to receive active treatment or placebo for 25 weeks. The active treatment consisted of intravenous clindamycin in a reducing regime, and oral tetracycline twice daily three times a week. 50 patients were to be recruited. The primary outcome measure was the proportion of patients achieving an ACR20 response.Results. An interim statistical analysis was performed after 20 patients had completed the study. Two patients in the active group achieved an ACR20 response, with none in the placebo group (NS). There was a better ESR20 response in the placebo group (P=.02). There were no other significant differences between the groups. The results indicated that it was unlikely that a significant difference in ACR20 response would emerge if the remaining 30 patients were recruited. The trial was therefore halted.Conclusion. This antibiotic regime is unlikely to be a valuable therapy for active rheumatoid arthritis.

Efficacy and Safety of Belimumab in Patients with Rheumatoid Arthritis: A Phase II, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study

2013 ◽  
Vol 40 (5) ◽  
pp. 579-589 ◽  
Author(s):  
William Stohl ◽  
Joan T. Merrill ◽  
James D. McKay ◽  
Jeffrey R. Lisse ◽  
Z. John Zhong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Phase Ii ◽  
B Lymphocyte ◽  
Tumor Necrosis Factor Inhibitor ◽  
Open Label ◽  
Double Blind ◽  
Acr20 Response ◽  
Link Type ◽  
American College Of Rheumatology

Objective.To evaluate the efficacy/safety of belimumab in patients with rheumatoid arthritis (RA).Methods.Patients fulfilling American College of Rheumatology (ACR) criteria for RA for ≥ 1 year who had at least moderate disease activity while receiving stable disease-modifying antirheumatic drug (DMARD) therapy and failed ≥ 1 DMARD were randomly assigned to placebo or belimumab 1, 4, or 10 mg/kg, administered intravenously on Days 1, 14, and 28, and then every 4 weeks for 24 weeks (n = 283). This was followed by an optional 24-week extension (n = 237) in which all patients received belimumab. Primary efficacy endpoint was the Week 24 ACR20 response.Results.Week 24 ACR20 responses with placebo and belimumab 1, 4, and 10 mg/kg were 15.9%, 34.7% (p = 0.010), 25.4% (p = 0.168), and 28.2% (p = 0.080), respectively. Patients taking any belimumab dose who continued with belimumab in the open-label extension had an ACR20 response of 41% at 48 weeks. A similar ACR20 response (42%) at 48 weeks was seen in patients taking placebo who switched in the extension to belimumab 10 mg/kg. Greater response rates were observed in patients who at baseline were rheumatoid factor-positive, anticitrullinated protein antibody-positive, or tumor necrosis factor inhibitor-naive, or had elevated C-reactive protein levels, Disease Activity Score 28 > 5.1, or low B lymphocyte stimulator levels (< 0.858 ng/ml). Adverse event rates were similar across treatment groups.Conclusion.In this phase II trial, belimumab demonstrated efficacy and was generally well tolerated in patients with RA who had failed previous therapies. [ClinicalTrials.gov identifier NCT00071812]

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