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

Autor:	Wallace DJ; Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, California, USA., Strand V; Division of Immunology/Rheumatology, Stanford University, Palo Alto, California, USA., Merrill JT; Department of Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA., Popa S; Republican Clinical Hospital, Chisinau, Moldova., Spindler AJ; Centro Medico Privado de Reumatologia, Tucuman, Argentina., Eimon A; CEMIC, Buenos Aires, Argentina., Petri M; Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Smolen JS; Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria., Wajdula J; Pfizer Inc, Collegeville, Pennsylvania, USA., Christensen J; Pfizer Inc, Cambridge, Massachusetts, USA., Li C; Pfizer Inc, Cambridge, Massachusetts, USA., Diehl A; Pfizer Inc, Collegeville, Pennsylvania, USA., Vincent MS; Pfizer Inc, Cambridge, Massachusetts, USA., Beebe J; Pfizer Inc, Cambridge, Massachusetts, USA., Healey P; Pfizer Inc, Groton, Connecticut, USA., Sridharan S; PPD Inc, Rockville, Maryland, USA.
Jazyk:	angličtina
Zdroj:	Annals of the rheumatic diseases [Ann Rheum Dis] 2017 Mar; Vol. 76 (3), pp. 534-542. Date of Electronic Publication: 2016 Sep 26.
DOI:	10.1136/annrheumdis-2016-209668
Abstrakt:	Objectives: This phase II trial evaluated the efficacy and safety of an interleukin (IL) 6 monoclonal antibody for systemic lupus erythematosus (SLE). Methods: Patients 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. Results: 183 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. Conclusions: PF-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 Number: NCT01405196; Pre-results. (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)
Databáze:	MEDLINE
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