title: Longterm Beneficial Effect of Canakinumab in Colchicine-resistant Familial Mediterranean Fever.
abstract: To assess the efficacy and safety of the interleukin-1β (IL-1β) inhibitor canakinumab in all adolescent and adult patients with familial Mediterranean fever (FMF) identified from the Greek National Registry for off-label drug use between 2010 and 2015.
  
  
  
  In this retrospective longitudinal outcome study, clinical and laboratory data were collected from 14 patients (7 men) aged median 38.5 years (range 13-70), with median disease duration of 14 years, and active FMF despite colchicine (n = 9) or both colchicine and anakinra (n = 5).
  
  
  
  All patients continued to receive canakinumab at last visit (median of 18 mos, range 13-53), which was initially given as monotherapy (n = 8) or in combination with colchicine and/or corticosteroids, every 4 (n = 7), 6 (n = 2), or 8 weeks (n = 5). Eleven patients (79%), including 6 receiving monotherapy, achieved complete clinical remission within 2 months (median), while normalization of all laboratory variables denoting inflammation occurred in 92% at 3 months (median). The remaining 3 patients achieved partial responses. Responses were sustained in all but 4 patients, who relapsed. Reducing the canakinumab administration interval from 8 or 6 weeks to 4 weeks led to suppression of disease activity in the relapsing patients. On the other hand, drug administration interval could be safely increased in 2 patients in remission. Corticosteroid doses were significantly reduced during followup. Canakinumab was well tolerated; 1 patient experienced a urinary tract infection and another one a viral gastroenteritis.
  
  
  
  Treatment with canakinumab in an individualized dosing scheme results in rapid and sustained remission in colchicine-resistant FMF.
authors.affiliation: From the Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, and Department of Pathophysiology, Medical School, and Bone Metabolic Unit, First Department of Orthopedics, Medical School, and First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens; Clinical Immunology Unit, Second Department of Internal Medicine, and Fourth Department of Internal Medicine, and First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School, Thessaloniki; Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, Larissa; Private Rheumatologist, Patras, Greece.|K. Laskari, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens; P. Boura, MD, PhD, Clinical Immunology Unit, Second Department of Internal Medicine, Aristotle University Medical School; G.N. Dalekos, MD, PhD, Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly; A. Garyfallos, MD, PhD, Fourth Department of Internal Medicine, Aristotle University Medical School; D. Karokis, MD, PhD, Private Rheumatologist; D. Pikazis, MD, PhD, Pathophysiology, Medical School, National and Kapodistrian University of Athens; L. Settas, MD, PhD, First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School; G. Skarantavos, MD, PhD, Bone Metabolic Unit, First Department of Orthopedics, Medical School, National and Kapodistrian University of Athens; E. Tsitsami, MD, PhD, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens; P.P. Sfikakis, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens.
authors.forename: Katerina
authors.initials: K
authors.lastname: Laskari
authors.affiliation: From the Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, and Department of Pathophysiology, Medical School, and Bone Metabolic Unit, First Department of Orthopedics, Medical School, and First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens; Clinical Immunology Unit, Second Department of Internal Medicine, and Fourth Department of Internal Medicine, and First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School, Thessaloniki; Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, Larissa; Private Rheumatologist, Patras, Greece.|K. Laskari, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens; P. Boura, MD, PhD, Clinical Immunology Unit, Second Department of Internal Medicine, Aristotle University Medical School; G.N. Dalekos, MD, PhD, Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly; A. Garyfallos, MD, PhD, Fourth Department of Internal Medicine, Aristotle University Medical School; D. Karokis, MD, PhD, Private Rheumatologist; D. Pikazis, MD, PhD, Pathophysiology, Medical School, National and Kapodistrian University of Athens; L. Settas, MD, PhD, First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School; G. Skarantavos, MD, PhD, Bone Metabolic Unit, First Department of Orthopedics, Medical School, National and Kapodistrian University of Athens; E. Tsitsami, MD, PhD, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens; P.P. Sfikakis, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens.
authors.forename: Panagiota
authors.initials: P
authors.lastname: Boura
authors.affiliation: From the Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, and Department of Pathophysiology, Medical School, and Bone Metabolic Unit, First Department of Orthopedics, Medical School, and First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens; Clinical Immunology Unit, Second Department of Internal Medicine, and Fourth Department of Internal Medicine, and First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School, Thessaloniki; Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, Larissa; Private Rheumatologist, Patras, Greece.|K. Laskari, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens; P. Boura, MD, PhD, Clinical Immunology Unit, Second Department of Internal Medicine, Aristotle University Medical School; G.N. Dalekos, MD, PhD, Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly; A. Garyfallos, MD, PhD, Fourth Department of Internal Medicine, Aristotle University Medical School; D. Karokis, MD, PhD, Private Rheumatologist; D. Pikazis, MD, PhD, Pathophysiology, Medical School, National and Kapodistrian University of Athens; L. Settas, MD, PhD, First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School; G. Skarantavos, MD, PhD, Bone Metabolic Unit, First Department of Orthopedics, Medical School, National and Kapodistrian University of Athens; E. Tsitsami, MD, PhD, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens; P.P. Sfikakis, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens.
authors.forename: George N
authors.initials: GN
authors.lastname: Dalekos
authors.affiliation: From the Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, and Department of Pathophysiology, Medical School, and Bone Metabolic Unit, First Department of Orthopedics, Medical School, and First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens; Clinical Immunology Unit, Second Department of Internal Medicine, and Fourth Department of Internal Medicine, and First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School, Thessaloniki; Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, Larissa; Private Rheumatologist, Patras, Greece.|K. Laskari, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens; P. Boura, MD, PhD, Clinical Immunology Unit, Second Department of Internal Medicine, Aristotle University Medical School; G.N. Dalekos, MD, PhD, Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly; A. Garyfallos, MD, PhD, Fourth Department of Internal Medicine, Aristotle University Medical School; D. Karokis, MD, PhD, Private Rheumatologist; D. Pikazis, MD, PhD, Pathophysiology, Medical School, National and Kapodistrian University of Athens; L. Settas, MD, PhD, First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School; G. Skarantavos, MD, PhD, Bone Metabolic Unit, First Department of Orthopedics, Medical School, National and Kapodistrian University of Athens; E. Tsitsami, MD, PhD, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens; P.P. Sfikakis, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Garyfallos
authors.affiliation: From the Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, and Department of Pathophysiology, Medical School, and Bone Metabolic Unit, First Department of Orthopedics, Medical School, and First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens; Clinical Immunology Unit, Second Department of Internal Medicine, and Fourth Department of Internal Medicine, and First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School, Thessaloniki; Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, Larissa; Private Rheumatologist, Patras, Greece.|K. Laskari, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens; P. Boura, MD, PhD, Clinical Immunology Unit, Second Department of Internal Medicine, Aristotle University Medical School; G.N. Dalekos, MD, PhD, Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly; A. Garyfallos, MD, PhD, Fourth Department of Internal Medicine, Aristotle University Medical School; D. Karokis, MD, PhD, Private Rheumatologist; D. Pikazis, MD, PhD, Pathophysiology, Medical School, National and Kapodistrian University of Athens; L. Settas, MD, PhD, First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School; G. Skarantavos, MD, PhD, Bone Metabolic Unit, First Department of Orthopedics, Medical School, National and Kapodistrian University of Athens; E. Tsitsami, MD, PhD, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens; P.P. Sfikakis, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Karokis
authors.affiliation: From the Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, and Department of Pathophysiology, Medical School, and Bone Metabolic Unit, First Department of Orthopedics, Medical School, and First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens; Clinical Immunology Unit, Second Department of Internal Medicine, and Fourth Department of Internal Medicine, and First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School, Thessaloniki; Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, Larissa; Private Rheumatologist, Patras, Greece.|K. Laskari, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens; P. Boura, MD, PhD, Clinical Immunology Unit, Second Department of Internal Medicine, Aristotle University Medical School; G.N. Dalekos, MD, PhD, Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly; A. Garyfallos, MD, PhD, Fourth Department of Internal Medicine, Aristotle University Medical School; D. Karokis, MD, PhD, Private Rheumatologist; D. Pikazis, MD, PhD, Pathophysiology, Medical School, National and Kapodistrian University of Athens; L. Settas, MD, PhD, First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School; G. Skarantavos, MD, PhD, Bone Metabolic Unit, First Department of Orthopedics, Medical School, National and Kapodistrian University of Athens; E. Tsitsami, MD, PhD, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens; P.P. Sfikakis, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pikazis
authors.affiliation: From the Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, and Department of Pathophysiology, Medical School, and Bone Metabolic Unit, First Department of Orthopedics, Medical School, and First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens; Clinical Immunology Unit, Second Department of Internal Medicine, and Fourth Department of Internal Medicine, and First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School, Thessaloniki; Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, Larissa; Private Rheumatologist, Patras, Greece.|K. Laskari, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens; P. Boura, MD, PhD, Clinical Immunology Unit, Second Department of Internal Medicine, Aristotle University Medical School; G.N. Dalekos, MD, PhD, Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly; A. Garyfallos, MD, PhD, Fourth Department of Internal Medicine, Aristotle University Medical School; D. Karokis, MD, PhD, Private Rheumatologist; D. Pikazis, MD, PhD, Pathophysiology, Medical School, National and Kapodistrian University of Athens; L. Settas, MD, PhD, First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School; G. Skarantavos, MD, PhD, Bone Metabolic Unit, First Department of Orthopedics, Medical School, National and Kapodistrian University of Athens; E. Tsitsami, MD, PhD, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens; P.P. Sfikakis, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens.
authors.forename: Loukas
authors.initials: L
authors.lastname: Settas
authors.affiliation: From the Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, and Department of Pathophysiology, Medical School, and Bone Metabolic Unit, First Department of Orthopedics, Medical School, and First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens; Clinical Immunology Unit, Second Department of Internal Medicine, and Fourth Department of Internal Medicine, and First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School, Thessaloniki; Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, Larissa; Private Rheumatologist, Patras, Greece.|K. Laskari, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens; P. Boura, MD, PhD, Clinical Immunology Unit, Second Department of Internal Medicine, Aristotle University Medical School; G.N. Dalekos, MD, PhD, Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly; A. Garyfallos, MD, PhD, Fourth Department of Internal Medicine, Aristotle University Medical School; D. Karokis, MD, PhD, Private Rheumatologist; D. Pikazis, MD, PhD, Pathophysiology, Medical School, National and Kapodistrian University of Athens; L. Settas, MD, PhD, First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School; G. Skarantavos, MD, PhD, Bone Metabolic Unit, First Department of Orthopedics, Medical School, National and Kapodistrian University of Athens; E. Tsitsami, MD, PhD, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens; P.P. Sfikakis, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens.
authors.forename: Grigoris
authors.initials: G
authors.lastname: Skarantavos
authors.affiliation: From the Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, and Department of Pathophysiology, Medical School, and Bone Metabolic Unit, First Department of Orthopedics, Medical School, and First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens; Clinical Immunology Unit, Second Department of Internal Medicine, and Fourth Department of Internal Medicine, and First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School, Thessaloniki; Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, Larissa; Private Rheumatologist, Patras, Greece.|K. Laskari, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens; P. Boura, MD, PhD, Clinical Immunology Unit, Second Department of Internal Medicine, Aristotle University Medical School; G.N. Dalekos, MD, PhD, Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly; A. Garyfallos, MD, PhD, Fourth Department of Internal Medicine, Aristotle University Medical School; D. Karokis, MD, PhD, Private Rheumatologist; D. Pikazis, MD, PhD, Pathophysiology, Medical School, National and Kapodistrian University of Athens; L. Settas, MD, PhD, First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School; G. Skarantavos, MD, PhD, Bone Metabolic Unit, First Department of Orthopedics, Medical School, National and Kapodistrian University of Athens; E. Tsitsami, MD, PhD, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens; P.P. Sfikakis, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens.
authors.forename: Elena
authors.initials: E
authors.lastname: Tsitsami
authors.affiliation: From the Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, and Department of Pathophysiology, Medical School, and Bone Metabolic Unit, First Department of Orthopedics, Medical School, and First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens; Clinical Immunology Unit, Second Department of Internal Medicine, and Fourth Department of Internal Medicine, and First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School, Thessaloniki; Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly, Larissa; Private Rheumatologist, Patras, Greece. psfikakis@med.uoa.gr katerina_laskari@yahoo.gr.|K. Laskari, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens; P. Boura, MD, PhD, Clinical Immunology Unit, Second Department of Internal Medicine, Aristotle University Medical School; G.N. Dalekos, MD, PhD, Department of Medicine and Research Laboratory of Internal Medicine, School of Medicine, University of Thessaly; A. Garyfallos, MD, PhD, Fourth Department of Internal Medicine, Aristotle University Medical School; D. Karokis, MD, PhD, Private Rheumatologist; D. Pikazis, MD, PhD, Pathophysiology, Medical School, National and Kapodistrian University of Athens; L. Settas, MD, PhD, First Department of Internal Medicine, Rheumatology Section, Aristotle University Medical School; G. Skarantavos, MD, PhD, Bone Metabolic Unit, First Department of Orthopedics, Medical School, National and Kapodistrian University of Athens; E. Tsitsami, MD, PhD, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens; P.P. Sfikakis, MD, PhD, Rheumatology Unit, First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens. psfikakis@med.uoa.gr katerina_laskari@yahoo.gr.
authors.forename: Petros P
authors.initials: PP
authors.lastname: Sfikakis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003078:Colchicine / Q000627:therapeutic use; D010505:Familial Mediterranean Fever / Q000188:drug therapy*; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D056687:Off-Label Use; D012074:Remission Induction; D019233:Retreatment; D012189:Retrospective Studies; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053590:Interleukin 1 Receptor Antagonist Protein; C541220:canakinumab; D003078:Colchicine
keywords: CANAKINUMAB; FAMILIAL MEDITERRANEAN FEVER; INTERLEUKIN 1