POS0928 NETAKIMAB EFFICACY IN ANTI-TNF-NAIVE AND ANTI-TNF-EXPERIENCED PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS: RESULTS OF SUBANALYSIS OF PHASE 3 ASTERA TRIAL

Background:According to previous studies, the effectiveness of interleukin-17 (IL-17) inhibitors was higher in anti-TNF-naïve patients with ankylosing spondylitis (AS) [1,2]. Netakimab (NTK) is a humanized anti-IL-17A antibody approved for the treatment of AS, psoriatic arthritis, moderate-to-severe plaque psoriasis in Russia and Belarus.Objectives:To compare the efficacy of NTK in anti-TNF-naïve patients with anti-TNF-experienced patients with active AS at week 16 of therapy.Methods:ASTERA (NCT03447704) is an ongoing phase 3 placebo (PBO)-controlled clinical study, aimed at evaluating NTK efficacy in AS [3]. 228 adult patients with active AS (BASDAI ≥ 4) were randomly assigned (1:1) to receive 120 mg NTK or PBO subcutaneously at week 0,1,2 and then q2w. This analysis includes 112 patients in NTK group. Efficacy endpoints included ASAS20/40, ASAS5/6 and ASAS partial remission (PR) at week 16 of therapy.Results:28 (25.0%) of 112 patients in NTK group had previous inadequate response/intolerance to anti-TNF (anti-TNF-IR): 24 (21.4%) – one anti-TNF, and 4 (3.6%) – two anti-TNF. 84 (75.0%) patients were TNF-naive. Achievement of ASAS criteria response at week 16 was similar in both groups (Table 1).Table 1.Efficacy of NTK at week 16ParameterTNF-naïve (n = 84)anti-TNF-IR (n = 28)p-value*ASAS20, n (%)52 (61.9%)17 (60.7%)0.91ASAS40, n (%)35 (41.7%)11 (39.3%)0.82ASAS5/6, n (%)39 (46.4%)11 (39.3%)0.51ASAS(PR), n (%)15 (17.9%) 4 (14.3%)0.78*- Fisher’s exact testConclusion:NTK 120 mg provided sustained improvements in signs and symptoms of AS in anti-TNF-naive and anti-TNF-IR patients at 16 weeks of therapy.References:[1]Blair HA, Dhillon S. Secukinumab: A Review in Ankylosing Spondylitis. Drugs. 2016;76(10):1023-30.[2]Dougados M, et al. Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W). Ann Rheum Dis. 2020;79(2):176-185.[3]Mazurov VI, et al. Efficacy and safety of Netakimab, anti-IL-17A monoclonal antibody, in patients with ankylosing spondylitis. Results of phase III international, multicenter, randomized double-blind clinical trial BCD-085-5/ASTERA. Nauchno-Practicheskaya Revmatologia=Rheumatology Science and Practice. 2020;58 (4):376–386 (In Russ).Acknowledgements:This study was sponsored by JSC BIOCAD.Disclosure of Interests:Shandor Erdes: None declared, V Mazurov: None declared, Tatiana Dubinina: None declared, Inna Gaydukova Speakers bureau: Abbvie, Biocad, Eli Lilly, MSD, Novartis, Pfizer, Sandoz, Alena Kundzer: None declared, Nikolaj Soroka: None declared, Anna Eremeeva Employee of: Biocad

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Long-term efficacy and safety of netakimab in the treatment of ankylosing spondylitis: results of Phase III international, multicenter, randomized double-blind clinical trial BCD-085-5/ASTERA

Modern Rheumatology Journal ◽

10.14412/1996-7012-2020-4-39-49 ◽

2020 ◽

Vol 14 (4) ◽

pp. 39-49

Author(s):

V. I. Mazurov ◽

Sh. F. Erdes ◽

I. Z. Gaydukova ◽

T. V. Dubinina ◽

A. M. Pristrom ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Phase Iii ◽

Upper Respiratory Tract ◽

Efficacy And Safety ◽

Double Blind ◽

Interleukin 17A ◽

Asas Criteria ◽

Magnetic Resonance Imaging Mri ◽

Tract Infections

Netakimab (NTK) is a humanized anti-interleukin-17A monoclonal antibody. To date, the drug has been approved to treat ankylosing spondylitis (AS), psoriatic arthritis, and plaque psoriasis. The paper gives the data obtained during 52-week follow-up of AS patients in the phase III ASTERA study.Objective: to study the efficacy and safety of NTK when used long in patients with active AS.Patients and methods. The investigation enrolled 228 patients with active AS, in whom nonsteroidal anti-inflammatory drugs or biological agents were ineffective. The patients were randomized in a 1:1 ratio to receive NTK 120 mg or placebo. The drug was administered subcutaneously at weeks 0, 1, 2, and then once every 2 weeks. Patients who received placebo and achieved a 20% improvement according to the ASAS criteria (ASAS20) were excluded from the study at week 16. At this week, patients who took placebo and did not achieve an ASAS20 response were switched to subcutaneous NTK at 120 mg dose once every two weeks. The follow-up period was 52 weeks.Results and discussion. Patients with active AS who received NTK were more likely to respond to treatment than those who took placebo. The proportion of people who achieved 40% improvement (ASAS40) during treatment with NTK increased throughout the follow-up period and amounted to 80.7% at week 52. Positive changes were achieved in all used clinical and laboratory parameters of AS activity. There was also a decrease in inflammatory changes, as shown by magnetic resonance imaging (MRI). The adverse events (AEs) were mainly laboratory abnormalities and upper respiratory tract infections. Treatment-related AEs were recorded in no more than one third of patients and they were mild to moderate. Severe AEs were singular.Conclusion. Response to NTK therapy generates in the first weeks of drug use and increases throughout a year. The safety profile of NTK when used long is generally favorable.

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OP0202 Efficacy and safety of tofacitinib, an oral janus kinase inhibitor, in patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: opal beyond, a randomised, double-blind, placebo-controlled, phase 3 trial

10.1136/annrheumdis-2017-eular.2443 ◽

2017 ◽

Cited By ~ 3

Author(s):

DD Gladman ◽

WFC Rigby ◽

VF Azevedo ◽

F Behrens ◽

R Blanco ◽

...

Keyword(s):

Tumour Necrosis ◽

Kinase Inhibitor ◽

Janus Kinase ◽

Inadequate Response ◽

Efficacy And Safety ◽

Phase 3 ◽

Double Blind ◽

Janus Kinase Inhibitor ◽

Double Blind Placebo ◽

Necrosis Factor

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Faculty Opinions recommendation of Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis: Sixteen-Week Results From a Phase III Randomized, Double-Blind, Placebo-Controlled Trial in Patients With Prior Inadequate Response to or Intolerance of Tumor Necrosis Factor Inhibitors.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734268130.793576219 ◽

2020 ◽

Author(s):

Pedro Machado

Keyword(s):

Tumor Necrosis ◽

Axial Spondyloarthritis ◽

Controlled Trial ◽

Phase Iii ◽

Inadequate Response ◽

Tumor Necrosis Factor Inhibitors ◽

Efficacy And Safety ◽

Double Blind ◽

Double Blind Placebo ◽

Necrosis Factor

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Efficacy and Safety of Epratuzumab in Moderately to Severely Active Systemic Lupus Erythematosus: Results From Two Phase III Randomized, Double-Blind, Placebo-Controlled Trials

Arthritis & Rheumatology ◽

10.1002/art.39856 ◽

2017 ◽

Vol 69 (2) ◽

pp. 362-375 ◽

Cited By ~ 78

Author(s):

Megan E. B. Clowse ◽

Daniel J. Wallace ◽

Richard A. Furie ◽

Michelle A. Petri ◽

Marilyn C. Pike ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Active Systemic Lupus Erythematosus ◽

Phase Iii ◽

Controlled Trials ◽

Efficacy And Safety ◽

Systemic Lupus ◽

Two Phase ◽

Double Blind ◽

Double Blind Placebo

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Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2016-210310 ◽

2016 ◽

Vol 76 (5) ◽

pp. 840-847 ◽

Cited By ~ 112

Author(s):

Gerd R Burmester ◽

Yong Lin ◽

Rahul Patel ◽

Janet van Adelsberg ◽

Erin K Mangan ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Active Rheumatoid Arthritis ◽

Activity Index ◽

Joint Disease ◽

Phase Iii ◽

Inadequate Response ◽

Efficacy And Safety ◽

Double Blind ◽

End Point

ObjectivesTo compare efficacy and safety of sarilumab monotherapy with adalimumab monotherapy in patients with active rheumatoid arthritis (RA) who should not continue treatment with methotrexate (MTX) due to intolerance or inadequate response.MethodsMONARCH was a randomised, active-controlled, double-blind, double-dummy, phase III superiority trial. Patients received sarilumab (200 mg every 2 weeks (q2w)) or adalimumab (40 mg q2w) monotherapy for 24 weeks. The primary end point was change from baseline in 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) at week 24.ResultsSarilumab was superior to adalimumab in the primary end point of change from baseline in DAS28-ESR (−3.28 vs −2.20; p<0.0001). Sarilumab-treated patients achieved significantly higher American College of Rheumatology 20/50/70 response rates (sarilumab: 71.7%/45.7%/23.4%; adalimumab: 58.4%/29.7%/11.9%; all p≤0.0074) and had significantly greater improvement in Health Assessment Questionnaire-Disability Index (p=0.0037). Importantly, at week 24, more patients receiving sarilumab compared with adalimumab achieved Clinical Disease Activity Index remission (7.1% vs 2.7%; nominal p=0.0468) and low disease activity (41.8% vs 24.9%; nominal p=0.0005, supplemental analysis). Adverse events occurred in 63.6% (adalimumab) and 64.1% (sarilumab) of patients, the most common being neutropenia and injection site reactions (sarilumab) and headache and worsening RA (adalimumab). Incidences of infections (sarilumab: 28.8%; adalimumab: 27.7%) and serious infections (1.1%, both groups) were similar, despite neutropenia differences.ConclusionsSarilumab monotherapy demonstrated superiority to adalimumab monotherapy by improving the signs and symptoms and physical functions in patients with RA who were unable to continue MTX treatment. The safety profiles of both therapies were consistent with anticipated class effects.Trial registration numberNCT02332590.

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