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


BACKGROUND
NCT01405196; Pre-results.
Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Daniel J
DJ
Wallace
Division of Immunology/Rheumatology, Stanford University, Palo Alto, California, USA.
Vibeke
V
Strand
Department of Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Joan T
JT
Merrill
Republican Clinical Hospital, Chisinau, Moldova.
Serghei
S
Popa
Centro Medico Privado de Reumatologia, Tucuman, Argentina.
Alberto J
AJ
Spindler
CEMIC, Buenos Aires, Argentina.
Alicia
A
Eimon
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Michelle
M
Petri
Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria.
Josef S
http://orcid.org/0000-0002-8899-9087
JS
Smolen
Pfizer Inc, Collegeville, Pennsylvania, USA.
Joseph
J
Wajdula
Pfizer Inc, Cambridge, Massachusetts, USA.
Jared
J
Christensen
Pfizer Inc, Cambridge, Massachusetts, USA.
Cheryl
C
Li
Pfizer Inc, Collegeville, Pennsylvania, USA.
Annette
A
Diehl
Pfizer Inc, Cambridge, Massachusetts, USA.
Michael S
MS
Vincent
Pfizer Inc, Cambridge, Massachusetts, USA.
Jean
J
Beebe
Pfizer Inc, Groton, Connecticut, USA.
Paul
P
Healey
PPD Inc, Rockville, Maryland, USA.
Sudhakar
S
Sridharan
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects*; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007279:Injections, Subcutaneous; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D011655:Pulmonary Embolism / Q000139:chemically induced; D018805:Sepsis / Q000139:chemically induced; D012720:Severity of Illness Index; D000067251:Symptom Flare Up; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000093242:Interleukin-6 Inhibitors; C000620303:PF-04236921
Autoimmune Diseases; Cytokines; Systemic Lupus Erythematosus; Treatment
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