Safety and Efficacy of Open-label Subcutaneous Ixekizumab Treatment for 48 Weeks in a Phase II Study in Biologic-naive and TNF-IR Patients with Rheumatoid Arthritis

2015 ◽  
Vol 43 (2) ◽  
pp. 289-297 ◽  
Author(s):  
Mark C. Genovese ◽  
Daniel K. Braun ◽  
Janelle S. Erickson ◽  
Pierre-Yves Berclaz ◽  
Subhashis Banerjee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Fungal Infections ◽  
Joint Disease ◽  
Open Label ◽  
Double Blind ◽  
American College Of Rheumatology ◽  
Serious Infections ◽  
Open Label Extension

Objective.To evaluate ixekizumab, an anti-interleukin 17A monoclonal antibody, for safety and effectiveness through 64 weeks in biologic-naive and tumor necrosis factor–inadequate responder (TNF-IR) patients with rheumatoid arthritis.Methods.Patients completing the 16-week double-blind period of a phase II study were eligible to enter the open-label extension (OLE) for an additional 48 weeks of ixekizumab treatment. After a treatment hiatus between weeks 10 to 16, 232 biologic-naive and 158 TNF-IR patients entered the OLE with all patients receiving 160 mg ixekizumab at weeks 16, 18, and 20, and then every 4 weeks through Week 64.Results.A total of 201 (87%) biologic-naive and 99 (62%) TNF-IR patients completed the OLE. Treatment-emergent adverse events (AE) occurred in 168 (72%) biologic-naive and 115 (73%) TNF-IR patients during the OLE. Most AE were mild to moderate in severity and did not lead to study discontinuation. Serious AE (SAE) occurred in 17 (7%) biologic-naive patients, including 5 (2%) serious infections and 2 (1%) deaths. SAE occurred in 18 (11%) TNF-IR patients, including 4 (3%) serious infections and 1 (1%) death. No mycobacterial or invasive fungal infections were reported. Clinical responses [American College of Rheumatology (ACR) 20, ACR50, ACR70, and 28-joint Disease Activity Score with C-reactive protein] observed at Week 16 were maintained or improved through Week 64.Conclusion.Ixekizumab was well tolerated, and safety findings in the OLE were consistent overall with those in the double-blind period of this study. Clinical improvements observed with ixekizumab through Week 16 were maintained or improved in patients participating in the OLE through Week 64. Trial registration number: NCT00966875.

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 Longterm Safety and Efficacy of Subcutaneous Tocilizumab Monotherapy: Results from the 2-year Open-label Extension of the MUSASHI Study

2015 ◽  
Vol 42 (5) ◽  
pp. 799-809 ◽  
Author(s):  
Atsushi Ogata ◽  
Koichi Amano ◽  
Hiroaki Dobashi ◽  
Masayuki Inoo ◽  
Tomonori Ishii ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Activity ◽  
Additional Treatment ◽  
Joint Disease ◽  
Open Label ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Safety And Efficacy ◽  
American College Of Rheumatology ◽  
Open Label Extension

Objective.To evaluate the longterm safety and efficacy of subcutaneous tocilizumab (TCZ-SC) as monotherapy in patients with rheumatoid arthritis (RA).Methods.Of 346 patients who received 24 weeks of double-blind treatment with either TCZ-SC monotherapy, 162 mg every 2 weeks (q2w); or intravenous TCZ (TCZ-IV) monotherapy, 8 mg/kg every 4 weeks; 319 patients continued to receive TCZ-SC q2w in the 84-week open-label extension (OLE) of the MUSASHI study (JAPICCTI-101117). Efficacy, safety, and immunogenicity were evaluated for all patients treated with TCZ during 108 weeks.Results.The proportions of patients who achieved American College of Rheumatology 20/50/70 responses, low disease activity [28-joint Disease Activity Score (DAS28) ≤ 3.2], or remission (DAS28 < 2.6) at Week 24 were maintained until Week 108. The incidences of adverse events and serious adverse events were 498.3 and 16.9 per 100 patient-years (PY), respectively. The overall safety of TCZ-SC monotherapy was similar to that of TCZ-IV monotherapy. Rates of injection site reactions (ISR) through 108 weeks remained similar to rates through 24 weeks. ISR were mild and did not cause any patient withdrawals. No serious hypersensitivity events (including anaphylactic reactions) occurred. Anti-TCZ antibodies were present in 2.1% of patients treated with TCZ-SC monotherapy.Conclusion.TCZ-SC monotherapy maintained a favorable safety profile and consistent efficacy throughout the 108-week study. Like TCZ-IV, TCZ-SC could provide an additional treatment option for patients with RA.

scholarly journals Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate)

2017 ◽  
Vol 77 (2) ◽  
pp. 212-220 ◽  
Author(s):  
Dinesh Khanna ◽  
Christopher P Denton ◽  
Celia J F Lin ◽  
Jacob M van Laar ◽  
Tracy M Frech ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Phase Ii ◽  
Controlled Trial ◽  
Safety Data ◽  
Open Label ◽  
Double Blind ◽  
Skin Score ◽  
Open Label Extension ◽  
Registration Number ◽  
Randomised Controlled

ObjectivesAssess the efficacy and safety of tocilizumab in patients with systemic sclerosis (SSc) in a phase II study.MethodsPatients with SSc were treated for 48 weeks in an open-label extension phase of the faSScinate study with weekly 162 mg subcutaneous tocilizumab. Exploratory end points included modified Rodnan Skin Score (mRSS) and per cent predicted forced vital capacity (%pFVC) through week 96.ResultsOverall, 24/44 (55%) placebo-tocilizumab and 27/43 (63%) continuous-tocilizumab patients completed week 96. Observed mean (SD (95% CI)) change from baseline in mRSS was –3.1 (6.3 (–5.4 to –0.9)) for placebo and –5.6 (9.1 (–8.9 to–2.4)) for tocilizumab at week 48 and –9.4 (5.6 (–8.9 to –2.4)) for placebo-tocilizumab and –9.1 (8.7 (–12.5 to –5.6)) for continuous-tocilizumab at week 96. Of patients who completed week 96, any decline in %pFVC was observed for 10/24 (42% (95% CI 22% to 63%)) placebo-tocilizumab and 12/26 (46% (95% CI 27% to 67%)) continuous-tocilizumab patients in the open-label period; no patients had >10% absolute decline in %pFVC. Serious infection rates/100 patient-years (95% CI) were 10.9 (3.0 to 27.9) with placebo and 34.8 (18.0 to 60.8) with tocilizumab during the double-blind period by week 48 and 19.6 (7.2 to 42.7) with placebo-tocilizumab and 0.0 (0.0 to 12.2) with continuous-tocilizumab during the open-label period.ConclusionsSkin score improvement and FVC stabilisation in the double-blind period were observed in placebo-treated patients who transitioned to tocilizumab and were maintained in the open-label period. Safety data indicated increased serious infections in patients with SSc but no new safety signals with tocilizumab.Trial registration numberNCT01532869; Results.

scholarly journals Long-term safety, efficacy and inhibition of radiographic progression with abatacept treatment in patients with rheumatoid arthritis and an inadequate response to methotrexate: 3-year results from the AIM trial

2011 ◽  
Vol 70 (10) ◽  
pp. 1826-1830 ◽  
Author(s):  
Joel M Kremer ◽  
Anthony S Russell ◽  
Paul Emery ◽  
Carlos Abud-Mendoza ◽  
Jacek Szechinski ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Radiographic Progression ◽  
Incidence Rates ◽  
Inadequate Response ◽  
Open Label ◽  
Serious Adverse Events ◽  
Double Blind ◽  
American College Of Rheumatology ◽  
Inadequate Responders

ObjectiveTo evaluate abatacept treatment over 3 years in patients with rheumatoid arthritis (RA) refractory to methotrexate (MTX).MethodsPatients randomised to abatacept or placebo (+MTX) during the 1-year double-blind period of the Abatacept in Inadequate responders to Methotrexate (AIM) trial received open-label abatacept (+MTX) in the long-term extension (LTE). Safety was assessed for patients who received ≥1 dose of abatacept, regardless of randomisation group. Efficacy was assessed for patients randomised to abatacept who entered the LTE.Results433 and 219 patients were randomised and treated with abatacept or placebo, respectively; 378 and 161 entered the LTE. At year 3, 440/539 patients were ongoing. No unexpected safety events were observed in the LTE. By year 3, incidence rates of adverse event and serious adverse events were 249.8/100 and 15.1/100 patient-years, respectively. Incidence rates were generally stable over time. At year 3, 84.8%, 63.4% and 37.5% of patients achieved American College of Rheumatology (ACR) criteria of 20, 50 and 70, respectively, compared with 82.3%, 54.3% and 32.4% of patients at year 1. Mean changes in Genant-modified Sharp scores were reduced progressively over 3 years, with significantly greater inhibition during year 3 compared with year 2 (p=0.022 for total score).ConclusionIn MTX-inadequate responders with RA, abatacept provided consistent safety and sustained efficacy over 3 years. The data suggest an increasing inhibitory disease-modifying effect on radiographic progression.

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