scholarly journals Efficacy and safety of an interleukin 6 monoclonal antibody for the treatment of systemic lupus erythematosus: a phase II dose-ranging randomised controlled trial

2016 ◽  
Vol 76 (3) ◽  
pp. 534-542 ◽  
Author(s):  
Daniel J Wallace ◽  
Vibeke Strand ◽  
Joan T Merrill ◽  
Serghei Popa ◽  
Alberto J Spindler ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Monoclonal Antibody ◽  
Phase Ii ◽  
Lupus Erythematosus ◽  
Response Rates ◽  
Primary Efficacy ◽  
Efficacy And Safety ◽  
Systemic Lupus ◽  
Post Hoc Analysis ◽  
Post Hoc

ObjectivesThis phase II trial evaluated the efficacy and safety of an interleukin (IL) 6 monoclonal antibody for systemic lupus erythematosus (SLE).MethodsPatients with active disease were randomised to placebo or PF-04236921 10 mg, 50 mg or 200 mg, subcutaneously, every 8 weeks with stable background therapy. SLE Responder Index (SRI-4; primary end point) and British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) were assessed at week 24. Post hoc analysis identified an enriched population based upon planned univariate analyses.Results183 patients received treatment (placebo, n=45; 10 mg, n=45; 50 mg, n=47; 200 mg, n=46). The 200 mg dose was discontinued due to safety findings and not included in the primary efficacy analysis. The SRI-4 response rates were not significant for any dose compared with placebo; however, the BICLA response rate was significant for 10 mg (p=0.026). The incidence of severe flares was significantly reduced with 10 mg (n=0) and 50 mg (n=2) combined versus placebo (n=8; p<0.01). In patients with greater baseline disease activity (enriched population), the SRI-4 (p=0.004) and BICLA (p=0.012) response rates were significantly different with 10 mg versus placebo. Four deaths (200 mg, n=3; 10 mg, n=1) occurred. The most frequently reported adverse events included headache, nausea and diarrhoea.ConclusionsPF-04236921 was not significantly different from placebo for the primary efficacy end point in patients with SLE. Evidence of an effect with 10 mg was seen in a post hoc analysis. Safety was acceptable for doses up to 50 mg as the 200 mg dose was discontinued due to safety findings.Trial registration numberNCT01405196; Pre-results.

scholarly journals Clinical response beyond the Systemic Lupus Erythematosus Responder Index: post-hoc analysis of the BLISS-SC study

2018 ◽  
Vol 5 (1) ◽  
pp. e000288 ◽  
Author(s):  
Ronald F van Vollenhoven ◽  
William Stohl ◽  
Richard A Furie ◽  
Norma Lynn Fox ◽  
James G Groark ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Clinical Trials ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Phase Iii ◽  
Controlled Study ◽  
Systemic Lupus ◽  
Post Hoc Analysis ◽  
Post Hoc

ObjectiveThe Systemic Lupus Erythematosus (SLE) Responder Index (SRI), developed as a primary outcome measure for use in clinical trials, captures improvement in SLE disease activity without concomitant worsening in disease manifestations. This study investigated the relationships between the SRI and clinical/laboratory correlates of SRI response in patients with SLE.MethodsThis was a post-hoc analysis of the phase III, double-blind, placebo-controlled study of subcutaneous BeLimumab in Subjects with Systemic lupus erythematosus - SubCutaneous (BLISS-SC). Patients were randomised to weekly belimumab 200 mg subcutaneously or placebo, plus standard SLE therapy. Changes from baseline to week 52 in clinical and laboratory parameters were compared among SRI responders and non-responders, irrespective of the treatment received.ResultsSRI responders (n=475) had significantly better (p<0.0001) outcomes compared with non-responders (n=358), including (by definition) higher proportions achieving ≥4-point improvement in Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (100.0% vs 2.0%), no worsening in British Isles Lupus Assessment Group (BILAG; 0 new BILAG A or ≤1 new BILAG B score; 100.0 % vs 50.3%) and no worsening (<0.3-point increase) in Physician’s Global Assessment score (100.0% vs 49.7%). Among patients receiving >7.5  mg/day corticosteroids at baseline, significantly more SRI responders had reductions in prednisone dose to ≤7.5 mg/day than non-responders. SRI responders reported lower flare rates and improvements in serological markers and Functional Assessment of Chronic Illness Therapy-Fatigue score than non-responders.ConclusionSRI response is associated with improvements in clinical and laboratory measures, strengthening its value as a clinically meaningful primary endpoint in clinical trials.

A Phase II study of the efficacy and safety of rontalizumab (rhuMAb interferon-α) in patients with systemic lupus erythematosus (ROSE)

2015 ◽  
Vol 75 (1) ◽  
pp. 196-202 ◽  
Author(s):  
Kenneth C Kalunian ◽  
Joan T Merrill ◽  
Romeo Maciuca ◽  
Jacqueline M McBride ◽  
Michael J Townsend ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Phase Ii ◽  
Lupus Erythematosus ◽  
Phase Ii Study ◽  
Interferon Α ◽  
Efficacy And Safety ◽  
Systemic Lupus

scholarly journals POS0701 ANIFROLUMAB, AN ANTI-INTERFERON-Α RECEPTOR MONOCLONAL ANTIBODY IN SYSTEMIC LUPUS ERYTHEMATOSUS- A META ANALYSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 600.1-600
Author(s):  
A. Abdul Razzack ◽  
S. Abdul Razzack ◽  
P. Shenasan ◽  
N. Shenasan ◽  
S. Mishra ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Monoclonal Antibody ◽  
Adverse Effects ◽  
Lupus Erythematosus ◽  
Active Systemic Lupus Erythematosus ◽  
Interferon Α ◽  
Type I ◽  
Efficacy And Safety ◽  
Systemic Lupus ◽  
Receptor Monoclonal Antibody

Background:Type I interferons such as Anifrolumab have been implicated in Systemic lupus erythematosus (SLE) pathogenesis on the basis of increased interferon-stimulated gene expression and genetic susceptibility. Little is known regarding its efficacy and safety profile.Objectives:To assess the efficacy and safety of Anifrolumab in patients with SLE.Methods:Electronic databases (PubMed, Embase, Scopus, Cochrane) were searched from inception until December 15th, 2020. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p<0.05. The primary outcome of interest was British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA). Secondary outcomes included the proportion of patients who achieved an SLE responder index of 4 (SRI-4) reduction of 50% or more in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), reductions in the glucocorticoid dose and adverse effects.Results:A total of three studies1,2,3 with 839 participants (Anifrolumab=372, Placebo=467) were included in our analysis. Follow-up duration was at week 52. A statistically significant different was observed in the Anifrolumab arm in terms of BICLA response (OR 0.44 95%CI 0.34-0.59;p < 0.00001, I2=4), ≥50% reduction in CLASI activity score (OR 0.36 95%CI 0.21-0.60;p=0.0001, I2=0), glucocorticoid reduction (OR 0.41 95%CI 0.28-0.59;p<0.00001; I2=0) and SRI-4 response (OR 0.52 95% CI 0.30-0.90; p=0.02, I2=75). However, Adverse events were less likely in the placebo arm as compared to Anifrolumab (OR 1.54 95%CI 1.05-2.25; p=0.03; I2=0).Conclusion:Anifrolumab was found to be more effective than placebo for the management of SLE, but may also cause more severe adverse effects.References:[1]Morand EF, Furie R, Tanaka Y, Bruce IN, Askanase AD, Richez C, Bae SC, Brohawn PZ, Pineda L, Berglind A, Tummala R; TULIP-2 Trial Investigators. Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med. 2020 Jan 16;382(3):211-221. doi: 10.1056/NEJMoa1912196. Epub 2019 Dec 18. PMID: 31851795.[2]Furie R, Khamashta M, Merrill JT, Werth VP, Kalunian K, Brohawn P, Illei GG, Drappa J, Wang L, Yoo S; CD1013 Study Investigators. Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. Arthritis Rheumatol. 2017 Feb;69(2):376-386. doi: 10.1002/art.39962. PMID: 28130918; PMCID: PMC5299497.[3]Furie RA, Morand EF, Bruce IN, et al. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol 2019; 1(4):e208-e219.Disclosure of Interests:None declared

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