Tocilizumab Compared with Anakinra in Refractory Adult-Onset Still's Disease. Multicenter Study of 75 Patients

Leyre Riancho-Zarrabeitia¹, Vanesa Calvo-Río¹, Ricardo Blanco¹, Jose L. Hernández², Francisco Ortiz-Sanjuán¹, Alejandro Olivé³, Anne Riveros Frutos⁴, Santos Castañeda⁵, Javier Narváez⁶, Maria Luisa Velloso Feijoo⁷, M. Victoria Hernández⁸, Alberto Sifuentes Giraldo⁹, Olga Maiz-Alonso¹⁰, Esteban Rubio Romero¹¹, Cristina Mata-Arnaiz¹², Adela Gallego Flores¹³, Jordi del Blanco¹⁴, Catalina Gómez-Arango¹⁵, Sara Manrique-Arija¹⁶, Maria Carmen Ordoñez¹⁷, Inmaculada Ros Vilamajo¹⁸, Miguel Angel Caracuel-Ruiz¹⁹, Mercedes Freire²⁰, Jose Llobet²¹, Carlos Marras²², Concepción Moll Tuduri²³, Chamaida Plasencia²⁴, Rosa Roselló²⁵, Ana Urruticoechea²⁶, Inmaculada Jiménez-Moleón²⁷, José Antonio Bernal²⁸, Vera Ortiz-Santamaría²⁹, Juan Ramón De Dios³⁰, Mireia Moreno³¹, Jordi Fiter³², Marina de los Riscos³³, Patricia E. Carreira³³, María José Rodríguez Valls Sr.³⁴, Carmen Gonzalez-Vela³⁵, Javier Loricera¹, Natalia Palmou¹ and Miguel Angel Gonzalez-Gay¹, ¹Rheumatology, Hospital Universitario Marqués de Valdecilla. IDIVAL, Santander, Spain, ²Internal Medicine, Hospital Universitario Marqués de Valdecilla. IDIVAL, Santander, Spain, ³Rheumatology, Hospital U German Trias i Pujol, Badalona, Spain, ⁴Rheumatology, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain, ⁵Rheumatology, H.U. La Princesa, Madrid, Spain, ⁶Rheumatology, Hospital Universitario de Bellvitge, Barcelona, Spain, ⁷H Valme, Sevilla, Spain, ⁸Arthritis Unit, Rheumatology, Hospital Clinic, Barcelona, Spain, ⁹Department of Rheumatology, University Hospital Ramón y Cajal, Madrid, Spain, ¹⁰Rheumatology, HU Donostia, San Sebastián, Spain, ¹¹Rheumatology Department,, Hospital Universitario Virgen del Rocío, Sevilla, Spain, ¹²Rheumatology, Hospital Laredo, Santander, Spain, ¹³Rheumatology, Hospital de Mérida, Mérida, Spain, ¹⁴Rheumatology, H Sant Jaume, Calella, Spain, ¹⁵Rheumatology, Hospital Basurto,, Santander, Spain, ¹⁶Rheumatology, Hospital Universitario Carlos Haya, Malaga, Spain, ¹⁷HRU Carlos Haya, Malaga, Spain, ¹⁸Hospital Son Llàtzer, Palma de Mallorca, Spain, ¹⁹Plaza Cruz Roja, 1, Hospital Reina Sofia, Córdoba, Spain, ²⁰Hospital Universitario Juan Canalejo, La Coruña, Spain, ²¹Hospital San Pau, Barcelona, Spain, ²²Hospital Universitario Virgen de la Arrixaca, Murcia, Spain, ²³H Mateu Orfila, Mahón, Spain, ²⁴Rheumatology Unit, La Paz University Hospital-Rheumatology, Madrid, Spain, ²⁵H San Jorge, Huesca, Spain, ²⁶Hospital Can Misses, Ibiza, Spain, ²⁷Rheumatology, Hospital San Cecilio, Granada, Spain, ²⁸Sección de Reumatología, Hospital General Universitario de Alicante, Alicante, Spain, ²⁹Rheumatology, Hospital General. Granollers., Granollers, Spain, ³⁰Rheumatology, HU Álava, Vitoria, Spain, ³¹Hospital de Sabadell - Institut Universitari Parc Taulí, Sabadell, Spain, ³²Rheumatology, HU Son Espases. Palma de Mallorca., Palma de Mallorca, Spain, ³³Rheumatology, Hospital Universitario 12 de Octubre, Madrid, Spain, ³⁴Rheumatology, Rheumatolgy Unit. Hospital Jerez, Jerez, Spain, ³⁵Pathology, Hospital Universitario Marqués de Valdecilla. IDIVAL, Santander, Spain

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Anakinra, Still's disease, tocilizumab and treatment

Session Information

Date: Sunday, November 8, 2015

Title: Miscellaneous Rheumatic and Inflammatory Diseases Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Interleukin (IL)-1 and IL-6 are pivotal cytokines in the pathogenesis of adult-onset Still’s disease (AOSD). Our aim was to compare the efficacy and safety of tocilizumab (TCZ) versus anakinra (ANK) given for at least 1 year to AODS patients refractory to conventional treatment.

Methods: Multicenter study (31 hospitals) of 75 patients (TCZ; n=34 and ANK; n 41) with AODS refractory to conventional immunosuppressive drugs and in many cases also to other biological agents.

Results: Comparisons of the group of patients with TCZ and ANK were: a) Average age: 39±16 vs. 34±14 years (p=0.2) b) Percentage of women: 76.5% vs. 63.4% (p=0.2) c) Median disease duration 4.2 [1-9] vs. 2.2 [0.3 to 4.9] years (p=0.14) d) Average dose of prednisone 15±9.9 mg/day vs. 28.3±22 mg/day (p=0.013) e) Median of conventional

immunosuppressants (2 [1-3] vs 1 [1-2] (p=0.05) f) Median of other biological therapies: 1 [0-2] vs. 0 [0-1] (p=0.04). The initial dose of i.v. TCZ were: 8 mg/kg/4 weeks (n=22), 8 mg/kg/2 weeks (n=10) and 4 mg/kg/4 weeks (n=2). ANK dose was 100 mg/day s.c. Both biologic agents were often combined with a conventional immunosuppressive drug (55.9% vs 70.7%; p=0.2). Both biologi agents yielded a quick and sustained improvement of all clinical and laboratory parameters (Table). The improvement in the clinical parameters was similar in both groups. However an earlier improvement of CRP and ESR was observed following TCZ therapy. After a median follow-up of 19 months [12-31] with TCZ and 15.5 months [4.5 to 50] with ANK (p=0.1), the major adverse effects in the TCZ group were: elevation liver enzymes (n=4), mild to

moderate leucopenia (4), upper respiratory tract infection (3), pneumonia (1), pyelonephritis and severe enterocolitis (1) and spondylodiscitis (1). In the group of ANK: skin lesions (n=8), mild leucopenia (3), myopathy (1), respiratory infection by P. aeruginosa and gluteal abscess (1), herpes zoster (1), osteomyelitis (1) and infection of urinary tract (2). While none of the TCZ-treated required discontinuation of the drug due to inefficacy, ANK had to be discontinued for this reason in 11 patients (p=0.001). Adverse effects leading to discontinuation of the drug were observed in 2 patients with TCZ and 4 patients with ANK (p=0.54).

Conclusion: TCZ and ANK are associated with a rapid and sustained clinical improvement in most patients with refractory AODS. However, TCZ appears to be more effective than ANK.

TABLE. Clinical manifestations and laboratory parameters (patients with TCZ vs. ANK)

	Basal TCZ (34) / ANK (41)	1 Month TCZ (34) / ANK (41)	3 Months TCZ (34) / ANK (37)	6 Months TCZ (34) / ANK (32)	12 Months TCZ (32) / ANK (27)
Fever, %	58.8 / 78 #	5.9 / 17.1	5.9 / 10.8	5.9 / 0	5.9 / 7.4
Articular, %	97.1 / 87.8	67.6 / 48.7	44.1 / 34.1	26.5 / 28.1	32.4 / 29.6
Rash,%	58.8 / 58.5	5.9 / 9.8	5.9 /10.8	5.9 / 0	5.9 / 3.7
Lymphadenopathy and/or visceromegalies, %	25 / 39	19 / 23	0 / 14	0 / 6	0 / 4
CRP (mg/dl) median [IQR]	8.9 [3.9-23.2] / 8.9 [4.4-14.9]	0.2 [0.1-1.6] / 1.1 [0.13-3.8] *	0.1 [0.01-0,7] / 0.62 [0.1-1.5] *	0.2 [0.01-0.9] / 0.5 [0.2-1.3] *	0.2 [0.03-1.1] / 0.3 [0.06-1.3] *
ESR 1st hr, median [IQR]	52 [45-69] / 60.5 [39-87]	4 [2-12] / 16.5 [10-37] *	4 [2-9] / 16 [6-30] *	4 [2-8] / 8 [4-20] *	2 [2-12] / 6 [2-18]
Leukocytes/mm3, mea± SD	13534±6023 / 15121±7752	8983±4550 / 8101±3655	8044±4360 / 7808±3002	7579±3588 / 7844±2297	8683±3658 / 7843±2703
Anemia, Hb (g/dl), mean±SD	11.9±1.36 / 10.9±2.07	12.9±1.2 / 12.2±2.03	13.3±1.1 / 12.86±2.13	13.3±1.3 / 13.37±1.6	14±1.3 / 13.7±1.5
Ferritin (ng/ml), median [IQR]	480 [200-808] / 998 [196-4212]	239 [39-358] / 456 [55-1182]	100 [73-132] / 121 [24-353]	107 [53-187] / 179 [52-339]	90 [63-115] / 125 [58-253]

Disclosure: L. Riancho-Zarrabeitia, None; V. Calvo-Río, None; R. Blanco, None; J. L. Hernández, None; F. Ortiz-Sanjuán, None; A. Olivé, None; A. Riveros Frutos, None; S. Castañeda, None; J. Narváez, None; M. L. Velloso Feijoo, None; M. V. Hernández, None; A. Sifuentes Giraldo, None; O. Maiz-Alonso, None; E. Rubio Romero, None; C. Mata-Arnaiz, None; A. Gallego Flores, None; J. del Blanco, None; C. Gómez-Arango, None; S. Manrique-Arija, None; M. C. Ordoñez, None; I. Ros Vilamajo, None; M. A. Caracuel-Ruiz, None; M. Freire, None; J. Llobet, None; C. Marras, None; C. Moll Tuduri, None; C. Plasencia, None; R. Roselló, None; A. Urruticoechea, None; I. Jiménez-Moleón, None; J. A. Bernal, None; V. Ortiz-Santamaría, None; J. R. De Dios, None; M. Moreno, None; J. Fiter, None; M. de los Riscos, None; P. E. Carreira, None; M. J. Rodríguez Valls Sr., None; C. Gonzalez-Vela, None; J. Loricera, None; N. Palmou, None; M. A. Gonzalez-Gay, None.

To cite this abstract in AMA style:

Riancho-Zarrabeitia L, Calvo-Río V, Blanco R, Hernández JL, Ortiz-Sanjuán F, Olivé A, Riveros Frutos A, Castañeda S, Narváez J, Velloso Feijoo ML, Hernández MV, Sifuentes Giraldo A, Maiz-Alonso O, Rubio Romero E, Mata-Arnaiz C, Gallego Flores A, del Blanco J, Gómez-Arango C, Manrique-Arija S, Ordoñez MC, Ros Vilamajo I, Caracuel-Ruiz MA, Freire M, Llobet J, Marras C, Moll Tuduri C, Plasencia C, Roselló R, Urruticoechea A, Jiménez-Moleón I, Bernal JA, Ortiz-Santamaría V, De Dios JR, Moreno M, Fiter J, de los Riscos M, Carreira PE, Rodríguez Valls MJ Sr., Gonzalez-Vela C, Loricera J, Palmou N, Gonzalez-Gay MA. Tocilizumab Compared with Anakinra in Refractory Adult-Onset Still’s Disease. Multicenter Study of 75 Patients [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/tocilizumab-compared-with-anakinra-in-refractory-adult-onset-stills-disease-multicenter-study-of-75-patients/. Accessed .

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/tocilizumab-compared-with-anakinra-in-refractory-adult-onset-stills-disease-multicenter-study-of-75-patients/