scholarly journals Efficacy and safety of levilimab, a monoclonal antibody to interleukin-6 receptors, in patients with rheumatoid arthritis

2021 ◽  
Vol 31 (4) ◽  
pp. 36-43
Author(s):  
P. Novikov ◽  
E. Shchegoleva ◽  
S. Moiseev
Keyword(s):  
Rheumatoid Arthritis ◽  
Monoclonal Antibody ◽  
Joint Disease ◽  
High Dose ◽  
Dosing Regimen ◽  
Double Blind ◽  
Low Disease Activity ◽  
Membrane Bound ◽  
Systemic Manifestations ◽  
Favorable Safety

Interleukin (IL)-6 is a proinlammatory cytokine contributing significantly to the pathogenesis of joint disease and systemic manifestations of rheumatoid arthritis (RA). Levilimab is a new original monoclonal antibody that blocks both soluble and membrane-bound IL-6 receptors. Efficacy and favorable safety profile of levilimab in combination with methotrexate were shown in two randomized double-blind placebo-controlled trials (AURORA and SOLAR) that included patients with active RA despite treatment with methotrexate alone. Both primary and multiple secondary efficacy endpoints including ACR response, low disease activity or remission rates, changes in RA activity scores, etc, confirmed a higher efficacy of levilimab compared to placebo. Profile of adverse events was typical for IL-inhibitors. Several observational studies suggested that unlike rituximab or medium or high dose glucocorticoids IL-6 receptors inhibitors do not worsen outcomes of COVID19 and do not impair immunogenicity of vaccines against COVID-19. Therefore, patients treated with levilimab should not delay vaccination or modify the dosing regimen prior to vaccination.

IRIDOCYCLITIS IN JUVENILE RHEUMATOID ARTHRITIS

PEDIATRICS ◽  
1969 ◽  
Vol 44 (1) ◽  
pp. 92-100 ◽  
Author(s):  
Jane Schaller ◽  
Carl Kupfer ◽  
Ralph J. Wedgwood
Keyword(s):  
Rheumatoid Arthritis ◽  
Juvenile Rheumatoid Arthritis ◽  
Signs And Symptoms ◽  
Joint Disease ◽  
Slit Lamp ◽  
Patients At Risk ◽  
Eye Involvement ◽  
Eye Examination ◽  
Systemic Manifestations ◽  
Polyarticular Disease

Eight of 70 children with juvenile rheumatoid arthritis have developed iridocyclitis. This complication occurred more frequently in patients with monoarticular and pauciarticular disease (29%) than in patients with polyarticular disease (2%). Seven of eight patients with iridocyclitis have monoarticular or pauciarticular disease; none has had prominent systemic manifestations or evidence of ankylosing spondylitis. Iridocyclitis preceded joint manifestations in two of the patients and followed arthritis by 1 to 10 years in six of the patients. Activity of iridocyclitis and arthritis seemed unrelated; four patients developed iridocyclitis while arthritis was inactive. In seven children iridocyclitis began insidiously without acute symptoms. Eye involvement has remained unilateral in six patients. Six children have had significant decrease in visual acuity, and six continue to have active ocular inflammation despite therapy. Iridocyclitis is potentially a major cause of disability in juvenile rheumatoid arthritis. Early signs and symptoms may be minimal. Patients at risk are those with limited forms of joint disease. Early detection and therapy are crucial for prevention of permanent ocular damage. Careful eye examination should be a routine part of physical examination of children with rheumatoid arthritis, and periodic slit lamp examinations should be performed even when arthritis is in remission.

scholarly journals 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

2016 ◽  
Vol 76 (5) ◽  
pp. 840-847 ◽  
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.

Immunogenicity and safety of high-dose versus standard-dose inactivated influenza vaccine in rheumatoid arthritis patients: a randomised, double-blind, active-comparator trial

2020 ◽  
Vol 2 (1) ◽  
pp. e14-e23 ◽  
Author(s):  
Inés Colmegna ◽  
Mariana L Useche ◽  
Katherine Rodriguez ◽  
Deirdre McCormack ◽  
Giuliana Alfonso ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Influenza Vaccine ◽  
Standard Dose ◽  
High Dose ◽  
Double Blind ◽  
Active Comparator ◽  
Comparator Trial

Toreforant, A Histamine H4 Receptor Antagonist, in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy: Results of 2 Phase II Studies

2016 ◽  
Vol 43 (9) ◽  
pp. 1637-1642 ◽  
Author(s):  
Robin L. Thurmond ◽  
Andrew Greenspan ◽  
Waldemar Radziszewski ◽  
Xie L. Xu ◽  
Ye Miao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Receptor Antagonist ◽  
Active Rheumatoid Arthritis ◽  
Dose Range ◽  
Joint Disease ◽  
Double Blind ◽  
Once Daily ◽  
Double Blind Placebo ◽  
Range Finding ◽  
Phase Ii Studies

Objective.To assess toreforant (selective histamine H4 receptor antagonist) in active rheumatoid arthritis (RA).Methods.In a phase IIa, double-blind, placebo-controlled test, 86 patients were randomized (2:1) to once-daily toreforant 100 mg or placebo for 12 weeks. In phase IIb, double-blind, placebo-controlled, dose-range–finding evaluations, 272 patients were randomized (1:1:1:1) to once-daily placebo or toreforant 3/10/30 mg. Primary efficacy endpoints for both studies were Week 12 changes in 28-joint Disease Activity Score–C-reactive protein (DAS28-CRP).Results.Phase IIa testing was terminated prematurely (patient fatality; secondary hemophagocytic lymphohistiocytosis). Posthoc analyses indicated toreforant 100 mg/day reduced RA signs/symptoms through Week 12. Phase IIb testing, however, showed no significant Week 12 improvement in DAS28-CRP with toreforant.Conclusion.Toreforant was not effective in phase IIb testing.

scholarly journals ASP5094, a humanized monoclonal antibody against integrin alpha-9, did not show efficacy in patients with rheumatoid arthritis refractory to methotrexate: results from a phase 2a, randomized, double-blind, placebo-controlled trial

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Tsutomu Takeuchi ◽  
Yoshiya Tanaka ◽  
Jay Erdman ◽  
Yuichiro Kaneko ◽  
Masako Saito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Monoclonal Antibody ◽  
Biological Activity ◽  
Disease Onset ◽  
Response Rates ◽  
Janus Kinase ◽  
P Value ◽  
Inadequate Response ◽  
Primary Efficacy ◽  
Double Blind

Abstract Background Rheumatoid arthritis (RA) is a chronic, debilitating autoimmune condition characterized by joint synovial inflammation. Current treatments include methotrexate (MTX), biologic agents, and Janus kinase (JAK) inhibitors. However, these agents are not efficacious in all patients and there are concerns regarding side effects and risk of infection as these treatments target immune-related pathways. Overexpression and activation of integrin alpha-9 (α9) on fibroblast-like synoviocytes are associated with RA disease onset and exacerbation. The humanized immunoglobulin G1 monoclonal antibody ASP5094 was designed to inhibit human α9 and is currently under investigation for the treatment of RA. Methods This phase 2a, multicenter, randomized, placebo-controlled, double-blind, parallel-group study (NCT03257852) evaluated the efficacy, safety, and biological activity of intravenous ASP5094 10 mg/kg in patients with moderate to severe RA that was refractory to MTX. Patients received ASP5094 or placebo every 4 weeks for a total of three administrations. Both treatment groups used concomitant MTX. The primary efficacy endpoint was the proportion of patients who responded per American College of Rheumatology 50% improvement using C-reactive protein (ACR50-CRP) after 12 weeks of treatment. Biological activity of ASP5094 was assessed via pharmacokinetics and pharmacodynamics of known downstream effectors of α9. Safety was also assessed. Results Sixty-six patients were enrolled and randomized to placebo (n = 33) or ASP5094 (n = 33). In the primary efficacy analysis, ACR50-CRP response rates were 6.3% and 18.2% at week 12 in the ASP5094 and placebo groups, respectively; a difference of − 11.9, which was not significant (2-sided P value = 0.258). No trends in ACR50 response rates were observed in subgroups based on demographics or baseline disease characteristics, and no significant differences between placebo and ASP5094 were identified in secondary efficacy or pharmacodynamic endpoints, despite achievement of target serum concentrations of ASP5094. Most treatment-emergent adverse events were mild to moderate in severity, and ASP5094 was considered safe and well tolerated overall. Conclusion Although no notable safety signals were observed in this study, ASP5094 was not efficacious in patients with moderate to severe RA with an inadequate response to MTX. Trial registration ClinicalTrials.gov, NCT03257852. Registered on 22 Aug. 2017

A randomized, double-blind, placebo-controlled study of cd4 monoclonal antibody therapy in early rheumatoid arthritis

1995 ◽  
Vol 38 (8) ◽  
pp. 1097-1106 ◽  
Author(s):  
Peter A. Van Der Lubbe ◽  
Ben A. C. Dijkmans ◽  
Hendrik M. Markusse ◽  
Ulla Nässander ◽  
Ferdinand C. Breedveld
Keyword(s):  
Rheumatoid Arthritis ◽  
Monoclonal Antibody ◽  
Early Rheumatoid Arthritis ◽  
Antibody Therapy ◽  
Controlled Study ◽  
Monoclonal Antibody Therapy ◽  
Double Blind ◽  
Double Blind Placebo
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