Biological Therapy in Refractory Neurobehçet’s Disease. Multicenter Study of 42 Patients

Alba Herrero-Morant¹, José Luis Martin-Varillas², Vanesa Calvo-Río³, Santos Castañeda⁴, Olga Maíz⁵, Ana Blanco⁶, Julio Sánchez⁷, Norberto Ortego⁸, Enrique Raya⁹, Anahy Maria Brandy-Garcia¹⁰, Alejandro Olive-Marques¹¹, Agueda Prior-Español¹², Clara Moriano¹³, Elvira Díez¹⁴, Rafael Melero¹⁵, Jenaro Enrique Grana Gil¹⁶, Álvaro Seijas-López¹⁷, Ana Urruticoechea-Arana¹⁸, Ángel Ramos-Calvo¹⁹, Concepcion Delgado-Beltran²⁰, Marta Loredo-Martinez²⁰, Eva Salgado²¹, Francisca Sivera²², Ignacio Torre²³, Javier Narvaez²⁴, Jose Luis Andreu²⁵, Olga Martinez²⁶, Ricardo Gómez de la Torre²⁷, Sabela Fernandez-Aguado²⁸, Susana Romero-Yuste²⁹, Gerard Espinosa³⁰, Miguel Ángel gonzalez-Gay³¹ and Ricardo Blanco³, ¹Hospital Universitario Marqués de Valdecilla, Santander, Spain, ²Hospital Sierrallana, Torrelavega, Spain, ³Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain, ⁴Hospital Universitario de la Princesa, Madrid, Spain, ⁵Hospital Universitario de Donostia, San Sebastián, Spain, ⁶Hospital Universitario de Donostia, San Sebastián, ⁷Hospital Universitario 12 de Octubre, Madrid, Spain, ⁸Medicine Department, Universidad de Granada, Granada, Spain, ⁹Hospital San Cecilio, Granada, Spain, ¹⁰Hospital Germans Trias i Pujol, Badalona, Spain, ¹¹Rheumatology Service. Hospital Germans Trias i Pujol, Barcelona, Spain, ¹²Department of Rheumatology, Germans Trias i Pujol. University Hospital, Badalona, Spain, ¹³Hospital Universitario de León, León, Spain, ¹⁴Hospital de León, León, Spain, ¹⁵Complexo Hospitalario Universitario de Vigo, Vigo, Galicia, Spain, ¹⁶Hospital Universitario de A Coruña, A Corua, Spain, ¹⁷Hospital Universitario de A Coruña, A Coruña, Spain, ¹⁸H. Can Misses, Elvissa, Spain, ¹⁹Complejo Hospitalario de Soria, Soria, Spain, ²⁰Hospital Clínico Lozano Blesa, Zaragoza, Spain, ²¹Complejo Hospitalario Universitario de Ourense, Ourense, Spain, ²²Hospital Universitario de Elda, Alicante, Spain, ²³Hospital Universitario de Basurto, Bilbao, Spain, ²⁴Division of Rheumatology, Hospital Universitario de Bellvitge, Barcelona, Spain, ²⁵Hospital Universitario Puerta de Hierro, Madrid, Spain, ²⁶H. Salamanca, Zamora, Spain, ²⁷H. Asturias, Oviedo, Spain, ²⁸Hospital Universitario de Cabueñes, Gijón, Spain, ²⁹Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain, ³⁰Hospital Clinic, Barcelona, Spain, ³¹Research group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Division of Rheumatology, Hospital Universitario Marqués de Valdecilla; School of Medicine, Universidad de Cantabria, Santander, Spain. Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Meeting: ACR Convergence 2021

Keywords: Behçet's Syndrome, Biologicals, neurology, Vasculitis

Session Information

Date: Tuesday, November 9, 2021

Session Title: Vasculitis – Non-ANCA-Associated & Related Disorders Poster II (1862–1888)

Session Type: Poster Session D

Session Time: 8:30AM-10:30AM

Background/Purpose: Neurobehçet’s disease (NBD) is a severe complication of Behcet’s disease (BD). Despite well-established therapies, with glucocorticoids and conventional immunosuppressants (cIS) a significant proportion of patients are refractory. The aim of this study is to assess efficacy and safety of biologic therapy (BT) in NBD refractory to glucocorticoids and at least one cIS.

Methods: Open-label multicenter study of refractory NBD from 22 different referral Spanish Hospitals. The main outcome variables were safety and clinical response measured at baseline, 6, 12 and 24 months. Other outcome variables were improvement in analytical parameters and corticosteroid-sparing effect of biological therapy.

Results: We studied 42 patients (21 women/21 men; mean age 40.4±10.8 years). HLA B51 was positive in 15 (40.5%) out of 37 patients tested. Non-neurological manifestations were oral ulcers (n=41, 97.6%), genital ulcers (n=31, 73.8%), skin lesions (n=28, 66.7%), arthralgia (n=27, 64.3%), uveitis (n=21, 50.0%), arthritis (n=9, 21.4%), venous thrombosis (n=9, 21.4%) and arterial thrombosis (n=4, 9.5%). The underlying neurologic manifestation were parenchymal (n=34, 81 %) and non-parenchymal (n=17, 40.5%) involvement (TABLE). The first BT used was infliximab (n=20), adalimumab (n=13), golimumab (n=3), tocilizumab (n=3) and etanercept (n=2).

After 58.2±51.4 months since initiation of BT, neurological response was complete (n=27; 64.3%), or partial (11, 26.1%). Only 4 (9.5%) patients did not respond (FIGURE). After 6 months of BT, ESR improved from.31.5±25.6 to 15.3±11.9 mg/L (p=0.005) and CRP from 1.4 [0.2-12.8] to 0.3 [0.1-3] mg/L (p= 0.002). Likewise, a decrease in oral prednisone dose was also achieved from 45.6±17.3 mg/day at baseline to 5.17±2.85 mg/day after 24 months (p< 0.0001).

Primary failure was observed in 16 (38.1%) patients due to inefficacy (n=11, 68.8%) or adverse effects (n=5, 31.3%). Similarly, secondary failure was detected in 6 (14.3%) patients due to inefficacy (n=5, 83.3%) or adverse effects (n=1, 16.7%). No serious adverse effects were observed.

Conclusion: BT, especially monoclonal anti-TNF drugs, seems effective and safe in patients with refractory NBD.

TABLE: Underlying neurologic manifestation of 41 patients with refractory neurobehçet’s disease treated with biologic therapy

FIGURE: Neurological response after initiation of biological therapy

Disclosures: A. Herrero-Morant, None; J. Martin-Varillas, None; V. Calvo-Río, None; S. Castañeda, None; O. Maíz, None; A. Blanco, None; J. Sánchez, None; N. Ortego, None; E. Raya, None; A. Brandy-Garcia, None; A. Olive-Marques, None; A. Prior-Español, None; C. Moriano, None; E. Díez, None; R. Melero, None; J. Grana Gil, None; . Seijas-López, None; A. Urruticoechea-Arana, None; . Ramos-Calvo, None; C. Delgado-Beltran, None; M. Loredo-Martinez, None; E. Salgado, None; F. Sivera, None; I. Torre, None; J. Narvaez, None; J. Andreu, None; O. Martinez, None; R. Gómez de la Torre, None; S. Fernandez-Aguado, None; S. Romero-Yuste, Abbvie, 2, 6, MSD, 5, Pfizer, 5, Novartis, 5, Biogen, 2, 6, Amgen, 6, Grünenthal, 6, Kern Pharma, 6, Lilly, 2, 6, Roche, 6, Sandoz, 6, Sanofi, 6, UCB, 6, Janssen, 2, 6, Fresenius Kabi, 2, Gebro, 2, BMS, 2, 5, Galapagos, 2; G. Espinosa, None; M. gonzalez-Gay, None; R. Blanco, Brystol Myers Squibb, 6.

To cite this abstract in AMA style:

Herrero-Morant A, Martin-Varillas J, Calvo-Río V, Castañeda S, Maíz O, Blanco A, Sánchez J, Ortego N, Raya E, Brandy-Garcia A, Olive-Marques A, Prior-Español A, Moriano C, Díez E, Melero R, Grana Gil J, Seijas-López , Urruticoechea-Arana A, Ramos-Calvo , Delgado-Beltran C, Loredo-Martinez M, Salgado E, Sivera F, Torre I, Narvaez J, Andreu J, Martinez O, Gómez de la Torre R, Fernandez-Aguado S, Romero-Yuste S, Espinosa G, gonzalez-Gay M, Blanco R. Biological Therapy in Refractory Neurobehçet’s Disease. Multicenter Study of 42 Patients [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/biological-therapy-in-refractory-neurobehcets-disease-multicenter-study-of-42-patients/. Accessed September 25, 2022.

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