title: Efficacy of Anakinra in Refractory Adult-Onset Still's Disease: Multicenter Study of 41 Patients and Literature Review.
abstract: Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients. Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent. Forty-one patients (26 women/15 men) were recruited. They had a mean age of 34.4 ± 14 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2-6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3-47.5] mg/day at ANK onset to 5 [0-10] at 12 months. After a median [IQR] follow-up of 16 [5-50] months, the most important side effects were cutaneous manifestations (n = 8), mild leukopenia (n = 3), myopathy (n = 1), and infections (n = 5). ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations.
authors.affiliation: From the Hospital Universitario Marque[Combining Acute Accent]s de Valdecilla, IDIVAL, Santander (FO-S, RB, LRZ, MCG-V, VC-R, JL, NPF, TP, MAG-G); Hospital Universitario de La Princesa, IIS Princesa Madrid, Madrid (SC); Hospital Universitario Germans Trias i Pujol, Badalona (AO, AR); Hospital Valme, Sevilla (MLV-F); Hospital Universitario de Bellvitge Hospitalet, Barcelona (JN); Hospital San Cecilio, Granada (IJ-M); HU Donostia, San Sebastián (OMA); HRU Carlos Haya, Málaga (CO); HGU, Alicante, Alicante (JAB); Hospital Clinic of Barcelona, Barcelona (MVH); Hospital Ramón y Cajal, Madrid (WASG); Hospital Universitario Basurto, Bilbao (CGA, EGA, JBM); Hospital General Granollers, Granollers, Spain (VOS); H Sant Jaume, Calella (JDBB); HU Álava, Vitoria (JRDD); HU Parc Taulí, Sabadell (MM); HU Son Espases, Palma de Mallorca, Mallorca (JF); Hospital Universitario 12 de Octubre, Madrid (MdlR, PC); Hospital de Jerez, Jerez (MJRV); and Universidad de Cantabria, IDIVAL, Santander, and CIBER Epidemiology and Public Health (CIBERESP), Santander Spain. (JL).
authors.forename: Francisco
authors.initials: F
authors.lastname: Ortiz-Sanjuán
authors.forename: Ricardo
authors.initials: R
authors.lastname: Blanco
authors.forename: Leyre
authors.initials: L
authors.lastname: Riancho-Zarrabeitia
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
authors.forename: Alejandro
authors.initials: A
authors.lastname: Olivé
authors.forename: Anne
authors.initials: A
authors.lastname: Riveros
authors.forename: María L
authors.initials: ML
authors.lastname: Velloso-Feijoo
authors.forename: Javier
authors.initials: J
authors.lastname: Narváez
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Jiménez-Moleón
authors.forename: Olga
authors.initials: O
authors.lastname: Maiz-Alonso
authors.forename: Carmen
authors.initials: C
authors.lastname: Ordóñez
authors.forename: José A
authors.initials: JA
authors.lastname: Bernal
authors.forename: María V
authors.initials: MV
authors.lastname: Hernández
authors.forename: Walter A
authors.initials: WA
authors.lastname: Sifuentes-Giraldo
authors.forename: Catalina
authors.initials: C
authors.lastname: Gómez-Arango
authors.forename: Eva
authors.initials: E
authors.lastname: Galíndez-Agirregoikoa
authors.forename: Juan
authors.initials: J
authors.lastname: Blanco-Madrigal
authors.forename: Vera
authors.initials: V
authors.lastname: Ortiz-Santamaria
authors.forename: Jordi
authors.initials: J
authors.lastname: Del Blanco-Barnusell
authors.forename: Juan R
authors.initials: JR
authors.lastname: De Dios
authors.forename: Mireia
authors.initials: M
authors.lastname: Moreno
authors.forename: Jordi
authors.initials: J
authors.lastname: Fiter
authors.forename: Marina de Los
authors.initials: ML
authors.lastname: Riscos
authors.forename: Patricia
authors.initials: P
authors.lastname: Carreira
authors.forename: María J
authors.initials: MJ
authors.lastname: Rodriguez-Valls
authors.forename: M Carmen
authors.initials: MC
authors.lastname: González-Vela
authors.forename: Vanesa
authors.initials: V
authors.lastname: Calvo-Río
authors.forename: Javier
authors.initials: J
authors.lastname: Loricera
authors.forename: Natalia
authors.initials: N
authors.lastname: Palmou-Fontana
authors.forename: Trinitario
authors.initials: T
authors.lastname: Pina
authors.forename: Javier
authors.initials: J
authors.lastname: Llorca
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
mesh_terms: D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D012189:Retrospective Studies; D016706:Still's Disease, Adult-Onset / Q000188:drug therapy*
chemical_list: D007166:Immunosuppressive Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D011241:Prednisone