Rheumatoid arthritis secondary non-responders to TNF can attain an efficacious and safe response by switching to certolizumab pegol: a phase IV, randomised, multicentre, double-blind, 12-week study, followed by a 12-week open-label phase

2014 ◽  
Vol 73 (12) ◽  
pp. 2174-2177 ◽  
Author(s):  
Michael H Schiff ◽  
Johannes von Kempis ◽  
Ronald Goldblum ◽  
John R Tesser ◽  
Ruediger B Mueller
Keyword(s):  
Rheumatoid Arthritis ◽  
Certolizumab Pegol ◽  
Open Label ◽  
Double Blind ◽  
Open Label Phase ◽  
Phase Iv

scholarly journals Efficacy and safety of bimekizumab as add-on therapy for rheumatoid arthritis in patients with inadequate response to certolizumab pegol: a proof-of-concept study

2019 ◽  
Vol 78 (8) ◽  
pp. 1033-1040 ◽  
Author(s):  
Sophie Glatt ◽  
Peter C Taylor ◽  
Iain B McInnes ◽  
Georg Schett ◽  
Robert Landewé ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Certolizumab Pegol ◽  
Inadequate Response ◽  
Proof Of Concept ◽  
Efficacy And Safety ◽  
Open Label ◽  
Double Blind ◽  
Reactive Protein ◽  
Dual Inhibition

ObjectiveEvaluate the efficacy and safety of dual neutralisation of interleukin (IL)-17A and IL-17F with bimekizumab, a monoclonal IgG1 antibody, in addition to certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA) and inadequate response (IR) to certolizumab pegol.MethodsDuring this phase 2a, double-blind, proof-of-concept (PoC) study (NCT02430909), patients with moderate-to-severe RA received open-label CZP 400 mg at Weeks 0, 2 and 4, and 200 mg at Week 6. Patients with IR at Week 8 (Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP))>3.2) were randomised 2:1 to CZP (200 mg every 2 weeks (Q2W)) plus bimekizumab (240 mg loading dose then 120 mg Q2W) or CZP plus placebo. The primary efficacy and safety variables were change in DAS28(CRP) between Weeks 8 and 20 and incidence of treatment-emergent adverse events (TEAEs).ResultsOf 159 patients enrolled, 79 had IR at Week 8 and were randomised to CZP plus bimekizumab (n=52) or CZP plus placebo (n=27). At Week 20, there was a greater reduction in DAS28(CRP) in the CZP-IR plus bimekizumab group compared with the CZP-IR plus placebo group (99.4% posterior probability). The most frequent TEAEs were infections and infestations (CZP plus bimekizumab, 50.0% (26/52); CZP plus placebo, 22.2% (6/27)).ConclusionsPoC was confirmed based on the rapid decrease in disease activity achieved with 12 weeks of CZP plus bimekizumab. No unexpected or new safety signals were identified when neutralising IL-17A and IL-17F in patients with RA concomitantly treated with CZP, but the rate of TEAEs was higher with dual inhibition.

scholarly journals Design of a phase IV randomised, double-blind, placebo-controlled trial assessing the ImPact ofResidual Inflammation Detected via Imaging TEchniques,Drug Levels and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab inClinical Remission Rheumatoid ArThritis (RA) patients (PREDICTRA)

BMJ Open ◽  
2018 ◽  
Vol 8 (2) ◽  
pp. e019007 ◽  
Author(s):  
Paul Emery ◽  
Gerd R Burmester ◽  
Esperanza Naredo ◽  
Yijie Zhou ◽  
Maja Hojnik ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Remission ◽  
Imaging Techniques ◽  
Controlled Trial ◽  
Patient Characteristics ◽  
Fixed Dose ◽  
Open Label ◽  
Double Blind ◽  
The Impact ◽  
Phase Iv

IntroductionThe current American College of Rheumatology and European League Against Rheumatism treatment recommendations advise tapering biological disease-modifying antirheumatic drug (bDMARD) therapy in patients with rheumatoid arthritis (RA) who achieve stable clinical remission while receiving bDMARDs. However, not all patients maintain remission or low disease activity after tapering or discontinuation of bDMARDs. The aim of the ImPact ofResidual Inflammation Detected via Imaging TEchniques,Drug Levels and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab inClinical Remission Rheumatoid ArThritis (RA) study, or PREDICTRA, is to generate data on patient and disease characteristics that may predict the clinical course of a fixed dose-tapering regimen with the bDMARD adalimumab.Methods and analysisPREDICTRA is an ongoing, multicentre, phase IV, randomised, double-blind, parallel-group study of adalimumab dose tapering controlled by withdrawal in participants with RA who achieved stable clinical remission while receiving adalimumab. The study includes a screening period, a 4-week lead-in period with open-label adalimumab 40 mg every other week and a subsequent 36-week double-blind period during which participants are randomised 5:1 to adalimumab 40 mg every 3 weeks (taper arm) or placebo (withdrawal arm). The primary explanatory efficacy variables are lead-in baseline hand and wrist MRI-detected synovitis and bone marrow oedema scores, as well as a composite of both scores; the dependent variable is the occurrence of flare up to week 40. Additional efficacy variables, safety, pharmacokinetics, biomarkers and immunogenicity will also be assessed, and an ultrasound substudy will be conducted.Ethics and disseminationThe study is conducted in accordance with the International Conference on Harmonisation guidelines, local laws and the ethical principles of the Declaration of Helsinki. All participants are required to sign a written informed consent statement before the start of any study procedures.Trial registration numberEudraCT 2014-001114-26 andNCT02198651; Pre-results.

scholarly journals Predictors of Remission Maintenance after Etanercept Tapering or Withdrawal in Early Rheumatoid Arthritis: Results from the PRIZE Study

2018 ◽  
Vol 12 (1) ◽  
pp. 179-188
Author(s):  
Paul Emery ◽  
Ronald Pedersen ◽  
Jack Bukowski ◽  
Lisa Marshall
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Rheumatoid Arthritis ◽  
Methotrexate Therapy ◽  
Sustained Remission ◽  
Open Label ◽  
Double Blind ◽  
Reduced Dose ◽  
Open Label Phase ◽  
Das28 Remission ◽  
Dose Combination

Objective: To explore the influence of early treatment response to etanercept-methotrexate therapy on sustained remission after tapering/withdrawal of etanercept in methotrexate/biologic-naïve patients with early rheumatoid arthritis in the PRIZE study (ClinicalTrials.gov: NCT00913458). Method: In the initial 52-week open-label phase, enrolled patients received once-weekly etanercept 50 mg plus methotrexate. Patients who achieved DAS28 ≤3.2 at week 39 and <2.6 at week 52 were randomized to etanercept 25 mg plus methotrexate, methotrexate monotherapy, or placebo once weekly for 39 weeks in the double-blind phase. The relationships between responses in the open-label phase and sustained remission (DAS28 <2.6 at weeks 76 and 91, without glucocorticoid rescue therapy from weeks 52 to 64) in the double-blind phase were analyzed. Results: In the open-label phase, 70% of patients achieved DAS28 remission at week 52. In the double-blind phase, 63%, 40%, and 23% of patients had sustained DAS28 remission in the reduced-dose combination-therapy, methotrexate-monotherapy, and placebo groups, respectively. In patients receiving reduced-dose combination therapy, sustained remission was more likely in those who achieved DAS28 remission (p = 0.005) or low disease activity (p=0.044) in a shorter time, and who had a lower DAS28 (p = 0.016) or achieved ACR/EULAR Boolean remission (p < 0.05) at the end of the open-label phase. In patients receiving methotrexate monotherapy, sustained remission was associated with a lower acute-phase response (C-reactive protein, p = 0.007; erythrocyte sedimentation rate, p = 0.016) at the end of the open-label phase. Conclusion: Fast response and suppression of inflammation with etanercept-methotrexate therapy may predict successful etanercept tapering/withdrawal in patients with early rheumatoid arthritis.

scholarly journals Managing pasireotide-associated hyperglycemia: a randomized, open-label, Phase IV study

Pituitary ◽  
2021 ◽  
Author(s):  
Susan L. Samson ◽  
Feng Gu ◽  
Ulla Feldt-Rasmussen ◽  
Shaoling Zhang ◽  
Yerong Yu ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Rescue Therapy ◽  
Antidiabetic Drugs ◽  
Cushing's Disease ◽  
Oral Antidiabetic Drugs ◽  
Open Label ◽  
Oral Antidiabetic ◽  
Open Label Phase ◽  
Core Phase ◽  
Phase Iv

Abstract Purpose Pasireotide is an effective treatment for acromegaly and Cushing’s disease, although treatment-emergent hyperglycemia can occur. The objective of this study was to assess incretin-based therapy versus insulin for managing pasireotide-associated hyperglycemia uncontrolled by metformin/other permitted oral antidiabetic drugs. Methods Multicenter, randomized, open-label, Phase IV study comprising a core phase (≤ 16-week pre-randomization period followed by 16-week randomized treatment period) and optional extension (ClinicalTrials.gov ID: NCT02060383). Adults with acromegaly (n = 190) or Cushing’s disease (n = 59) received long-acting (starting 40 mg IM/28 days) or subcutaneous pasireotide (starting 600 µg bid), respectively. Patients with increased fasting plasma glucose (≥ 126 mg/dL on three consecutive days) during the 16-week pre-randomization period despite metformin/other oral antidiabetic drugs were randomized 1:1 to open-label incretin-based therapy (sitagliptin followed by liraglutide) or insulin for another 16 weeks. The primary objective was to evaluate the difference in mean change in HbA1c from randomization to end of core phase between incretin-based therapy and insulin treatment arms. Results Eighty-one (32.5%) patients were randomized to incretin-based therapy (n = 38 received sitagliptin, n = 28 subsequently switched to liraglutide; n = 12 received insulin as rescue therapy) or insulin (n = 43). Adjusted mean change in HbA1c between treatment arms was – 0.28% (95% CI – 0.63, 0.08) in favor of incretin-based therapy. The most common AE other than hyperglycemia was diarrhea (incretin-based therapy, 28.9%; insulin, 30.2%). Forty-six (18.5%) patients were managed on metformin (n = 43)/other OAD (n = 3), 103 (41.4%) patients did not require any oral antidiabetic drugs and 19 patients (7.6%) were receiving insulin at baseline and were not randomized. Conclusion Many patients receiving pasireotide do not develop hyperglycemia requiring oral antidiabetic drugs. Metformin is an effective initial treatment, followed by incretin-based therapy if needed. ClinicalTrials.gov ID: NCT02060383.

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]

scholarly journals Subcutaneous Abatacept for the Treatment of Rheumatoid Arthritis: Longterm Data from the ACQUIRE Trial

2014 ◽  
Vol 41 (4) ◽  
pp. 629-639 ◽  
Author(s):  
Mark C. Genovese ◽  
César Pacheco Tena ◽  
Arturo Covarrubias ◽  
Gustavo Leon ◽  
Eduardo Mysler ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Severe Disease ◽  
Incidence Rates ◽  
Phase Iii ◽  
Inadequate Response ◽  
Open Label ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Link Type

Objective.Assess longterm tolerability, safety, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate-refractory patients with rheumatoid arthritis (RA).Methods.The phase III, multinational Abatacept Comparison of Sub[QU]cutaneous Versus Intravenous in Inadequate Responders to MethotrexatE (ACQUIRE) trial comprised a 6-month, randomized, double-blind (DB) period, in which patients received intravenous (IV) or SC ABA, plus MTX, followed by an open-label, longterm extension (LTE), in which patients received SC ABA, 125 mg/week. Safety and efficacy from the LTE (∼3.5 yrs of exposure) are reported.Results.Patients who completed the DB period (1372/1385, 99.1%) entered the LTE; 1134 patients (82.7%) kept taking the treatment at time of reporting. Mean (SD) was 31.9 months (6.8); median (range) exposure was 33.0 (8–44) months. Patients entering the LTE had longstanding, moderate-to-severe disease [mean 7.6 (7.9) yrs and DAS28 (C-reactive protein) 6.2 (0.9)]. Incidence rates (events/100 patient-yrs) were reported for serious adverse events (8.76, 95% CI 7.71, 9.95), infections (44.80, 95% CI 41.76, 48.01), serious infections (1.72, 95% CI 1.30, 2.27), malignancies (1.19, 95% CI 0.86, 1.66), and autoimmune events (1.31, 95% CI 0.95, 1.79). Twenty-seven patients (2%) experienced injection-site reactions; all except 1 were mild. American College of Rheumatology 20, 50, and 70 responses achieved during the DB period were maintained through the LTE, and on Day 981 were 80.2% (95% CI 77.2, 83.2), 63.5% (95% CI 58.2, 68.9), and 39.5% (95% CI 34.0, 44.9) for patients who kept taking SC ABA, and 80.0% (95% CI 77.0, 83.0), 63.2% (95% CI 57.8, 68.7), and 39.2% (95% CI 33.7, 44.7) for those who switched from IV to SC ABA.Conclusion.These findings support SC ABA as a well-tolerated and efficacious longterm treatment for patients with RA and inadequate response to MTX (ClinicalTrials.gov identifier NCT00559585).

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