title: Efficacy and Safety of Subcutaneous and Intravenous Loading Dose Regimens of Secukinumab in Patients with Active Rheumatoid Arthritis: Results from a Randomized Phase II Study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of secukinumab, a fully human antiinterleukin-17A monoclonal antibody, administered with an intravenous (IV) or subcutaneous (SC) loading regimen versus placebo, in patients with active rheumatoid arthritis (RA).
  
  
  METHODS
  In this phase II, double-blind, double-dummy, 52-week study (ClinicalTrials.gov NCT01359943), 221 patients with inadequate response to methotrexate were randomized (2:2:1) to secukinumab, IV loading 10 mg/kg at baseline, Weeks 2 and 4, then SC 150 mg every 4 weeks (n = 88); secukinumab SC loading 150 mg once weekly for 5 weeks, then every 4 weeks (n = 89); or a matching placebo (followed by secukinumab 150 mg every 4 weeks starting Week 16; n = 44). The primary endpoint was superior efficacy of pooled secukinumab versus placebo using American College of Rheumatology 20% response (ACR20) at Week 12.
  
  
  RESULTS
  The primary efficacy endpoint was not met: ACR20 response at Week 12 was 49.2% for pooled secukinumab versus 40.9% for placebo (p = 0.3559). These variables improved significantly with pooled secukinumab versus placebo at Week 12 (all p < 0.05): the 28-joint Disease Activity Score (DAS28), patient's and physician's global assessment of disease activity, patient's assessment of RA pain, and high-sensitivity C-reactive protein levels. Results of continuous efficacy outcomes were similar between the IV and SC loading regimens. The most frequent adverse events were infections, with similar rates across secukinumab and placebo.
  
  
  CONCLUSIONS
  Although the primary endpoint (ACR20) was not met, secukinumab demonstrated improved efficacy in reducing disease activity over placebo as measured by DAS28 and other secondary endpoints.
authors.affiliation: From the Klinika Chorob Wewnetrznych i Reumatologii, Centralny Szpital Kliniczny MON Wojskowy Instytut Medyczny, Warsaw, Poland; Memorial University, St. John's, Newfoundland, Canada; Department of Internal Medicine, Research Laboratory and Academic Unit of Clinical Rheumatology, University of Genoa, Genoa, Italy; Novartis Pharma AG, Basel, Switzerland; and Novartis Pharmaceutical Corporation, East Hanover, New Jersey, USA.W. Tlustochowicz, MD, PhD, Klinika Chorob Wewnetrznych i Reumatologii, Centralny Szpital Kliniczny MON Wojskowy Instytut Medyczny; P. Rahman, MD, FRCPC, Memorial University; B. Seriolo, MD, Department of Internal Medicine, Research Laboratory and Academic Unit of Clinical Rheumatology, University of Genoa;G. Krammer, MS; A. Widmer, MSc; H.B. Richards, MD, Novartis Pharma AG; B. Porter, MD, PhD, MPH, Novartis Pharmaceutical Corporation. tlustochowicz@go2.pl.
authors.forename: Witold
authors.initials: W
authors.lastname: Tlustochowicz
authors.affiliation: From the Klinika Chorob Wewnetrznych i Reumatologii, Centralny Szpital Kliniczny MON Wojskowy Instytut Medyczny, Warsaw, Poland; Memorial University, St. John's, Newfoundland, Canada; Department of Internal Medicine, Research Laboratory and Academic Unit of Clinical Rheumatology, University of Genoa, Genoa, Italy; Novartis Pharma AG, Basel, Switzerland; and Novartis Pharmaceutical Corporation, East Hanover, New Jersey, USA.W. Tlustochowicz, MD, PhD, Klinika Chorob Wewnetrznych i Reumatologii, Centralny Szpital Kliniczny MON Wojskowy Instytut Medyczny; P. Rahman, MD, FRCPC, Memorial University; B. Seriolo, MD, Department of Internal Medicine, Research Laboratory and Academic Unit of Clinical Rheumatology, University of Genoa;G. Krammer, MS; A. Widmer, MSc; H.B. Richards, MD, Novartis Pharma AG; B. Porter, MD, PhD, MPH, Novartis Pharmaceutical Corporation.
authors.forename: Proton
authors.initials: P
authors.lastname: Rahman
authors.affiliation: From the Klinika Chorob Wewnetrznych i Reumatologii, Centralny Szpital Kliniczny MON Wojskowy Instytut Medyczny, Warsaw, Poland; Memorial University, St. John's, Newfoundland, Canada; Department of Internal Medicine, Research Laboratory and Academic Unit of Clinical Rheumatology, University of Genoa, Genoa, Italy; Novartis Pharma AG, Basel, Switzerland; and Novartis Pharmaceutical Corporation, East Hanover, New Jersey, USA.W. Tlustochowicz, MD, PhD, Klinika Chorob Wewnetrznych i Reumatologii, Centralny Szpital Kliniczny MON Wojskowy Instytut Medyczny; P. Rahman, MD, FRCPC, Memorial University; B. Seriolo, MD, Department of Internal Medicine, Research Laboratory and Academic Unit of Clinical Rheumatology, University of Genoa;G. Krammer, MS; A. Widmer, MSc; H.B. Richards, MD, Novartis Pharma AG; B. Porter, MD, PhD, MPH, Novartis Pharmaceutical Corporation.
authors.forename: Bruno
authors.initials: B
authors.lastname: Seriolo
authors.affiliation: From the Klinika Chorob Wewnetrznych i Reumatologii, Centralny Szpital Kliniczny MON Wojskowy Instytut Medyczny, Warsaw, Poland; Memorial University, St. John's, Newfoundland, Canada; Department of Internal Medicine, Research Laboratory and Academic Unit of Clinical Rheumatology, University of Genoa, Genoa, Italy; Novartis Pharma AG, Basel, Switzerland; and Novartis Pharmaceutical Corporation, East Hanover, New Jersey, USA.W. Tlustochowicz, MD, PhD, Klinika Chorob Wewnetrznych i Reumatologii, Centralny Szpital Kliniczny MON Wojskowy Instytut Medyczny; P. Rahman, MD, FRCPC, Memorial University; B. Seriolo, MD, Department of Internal Medicine, Research Laboratory and Academic Unit of Clinical Rheumatology, University of Genoa;G. Krammer, MS; A. Widmer, MSc; H.B. Richards, MD, Novartis Pharma AG; B. Porter, MD, PhD, MPH, Novartis Pharmaceutical Corporation.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Krammer
authors.affiliation: From the Klinika Chorob Wewnetrznych i Reumatologii, Centralny Szpital Kliniczny MON Wojskowy Instytut Medyczny, Warsaw, Poland; Memorial University, St. John's, Newfoundland, Canada; Department of Internal Medicine, Research Laboratory and Academic Unit of Clinical Rheumatology, University of Genoa, Genoa, Italy; Novartis Pharma AG, Basel, Switzerland; and Novartis Pharmaceutical Corporation, East Hanover, New Jersey, USA.W. Tlustochowicz, MD, PhD, Klinika Chorob Wewnetrznych i Reumatologii, Centralny Szpital Kliniczny MON Wojskowy Instytut Medyczny; P. Rahman, MD, FRCPC, Memorial University; B. Seriolo, MD, Department of Internal Medicine, Research Laboratory and Academic Unit of Clinical Rheumatology, University of Genoa;G. Krammer, MS; A. Widmer, MSc; H.B. Richards, MD, Novartis Pharma AG; B. Porter, MD, PhD, MPH, Novartis Pharmaceutical Corporation.
authors.forename: Brian
authors.initials: B
authors.lastname: Porter
authors.affiliation: From the Klinika Chorob Wewnetrznych i Reumatologii, Centralny Szpital Kliniczny MON Wojskowy Instytut Medyczny, Warsaw, Poland; Memorial University, St. John's, Newfoundland, Canada; Department of Internal Medicine, Research Laboratory and Academic Unit of Clinical Rheumatology, University of Genoa, Genoa, Italy; Novartis Pharma AG, Basel, Switzerland; and Novartis Pharmaceutical Corporation, East Hanover, New Jersey, USA.W. Tlustochowicz, MD, PhD, Klinika Chorob Wewnetrznych i Reumatologii, Centralny Szpital Kliniczny MON Wojskowy Instytut Medyczny; P. Rahman, MD, FRCPC, Memorial University; B. Seriolo, MD, Department of Internal Medicine, Research Laboratory and Academic Unit of Clinical Rheumatology, University of Genoa;G. Krammer, MS; A. Widmer, MSc; H.B. Richards, MD, Novartis Pharma AG; B. Porter, MD, PhD, MPH, Novartis Pharmaceutical Corporation.
authors.forename: Albert
authors.initials: A
authors.lastname: Widmer
authors.affiliation: From the Klinika Chorob Wewnetrznych i Reumatologii, Centralny Szpital Kliniczny MON Wojskowy Instytut Medyczny, Warsaw, Poland; Memorial University, St. John's, Newfoundland, Canada; Department of Internal Medicine, Research Laboratory and Academic Unit of Clinical Rheumatology, University of Genoa, Genoa, Italy; Novartis Pharma AG, Basel, Switzerland; and Novartis Pharmaceutical Corporation, East Hanover, New Jersey, USA.W. Tlustochowicz, MD, PhD, Klinika Chorob Wewnetrznych i Reumatologii, Centralny Szpital Kliniczny MON Wojskowy Instytut Medyczny; P. Rahman, MD, FRCPC, Memorial University; B. Seriolo, MD, Department of Internal Medicine, Research Laboratory and Academic Unit of Clinical Rheumatology, University of Genoa;G. Krammer, MS; A. Widmer, MSc; H.B. Richards, MD, Novartis Pharma AG; B. Porter, MD, PhD, MPH, Novartis Pharmaceutical Corporation.
authors.forename: Hanno B
authors.initials: HB
authors.lastname: Richards
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C555450:secukinumab
keywords: AUTOIMMUNE DISEASES; INTERLEUKINS; METHOTREXATE; MONOCLONAL ANTIBODY; RHEUMATOID ARTHRITIS; SECUKINUMAB