Anti-IL6-Receptor Tocilizumab in Graves’ Orbitopathy. Multicenter Study of 46 Patients

Belén Atienza-Mateo¹, José Luis Martín-Varillas¹, Vanesa Calvo-Río², Rosalía Demetrio-Pablo³, Diana Prieto Peña², Monica Calderón Goercke², Elia Valls-Pascual⁴, Beatriz Valls-Espinosa⁵, Olga Maiz-Alonso⁶, Ana Blanco⁷, Ignacio Torre-Salaberri⁸, Verónica Rodriguez-Mendez⁹, Angel Garcia-Aparicio¹⁰, Raúl Veroz González¹¹, Vega Jovaní¹², Diana Peiteado¹³, Margarita Sanchez Orgaz¹⁴, Santos Castañeda¹⁵, Eva Tomero¹⁶, Francisco J. Toyos Sáenz de Miera¹⁷, Valvanera Pinillos¹⁸, Elena Aurrecoechea¹⁹, Ángel Mora²⁰, Arantxa Conesa²¹, Manuel Fernández²², Nuria Avilés²³, J. Antonio Troyano²⁴, Miguel Angel González-Gay¹ and Ricardo Blanco¹, ¹Rheumatology, Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain, ²Rheumatology, Rheumatology. Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain, ³Hospital Universitario Marqués de Valdecilla. IDIVAL. Santander. Universidad de Cantabria. Spain, Santander, Spain, ⁴Hospital Universitario Doctor Peset. Valencia. Spain, Valencia, Spain, ⁵Rheumatology, Hospital Universitario Doctor Peset. Valencia. Spain, Valencia, Spain, ⁶Hospital Universitario Donostia. San Sebastian. Spain, Donostia, Spain, ⁷Ophtamology, Hospital Universitario Donostia. San Sebastian. Spain, San Sebastian, Spain, ⁸Rheumatology, Hospital Universitario de Basurto. Bilbao. Spain, Bilbao, Spain, ⁹Ophthalmology, Hospital Universitario de Basurto. Bilbao. Spain, Bilbao, Spain, ¹⁰Rheumatology, Hospital de Toledo. Toledo. Spain, Toledo, Spain, ¹¹Rheumatology, Hospital de Mérida. Badajoz. Spain, Mérida, Spain, ¹²Rheumatology, Hospital General Universitario de Alicante. Spain, Alicante, Spain, ¹³Rheumatology, Rheumatology, La Paz University Hospital, Madrid, Spain, ¹⁴Ophthalmology, Hospital Universitario La Paz. Madrid. Spain, Madrid, Spain, ¹⁵Rheumatology, Hospital La Princesa. Madrid. Spain, Madrid, Spain, ¹⁶Rheumatology, Hospital de La Princesa. Madrid. Spain, Madrid, Spain, ¹⁷Hospital Virgen de La Macarena. Sevilla. Spain, Sevilla, Spain, ¹⁸Rheumatology, Hospital San Pedro. Logroño. La Rioja. Spain, Logroño, Spain, ¹⁹Rheumatology, Hospital de Sierrallana. Torrelavega. Spain, Torrelavega, Spain, ²⁰Ophthalmology, Hospital de Sierrallana. Torrelavega. Cantabria. Spain, Torrelavega, Spain, ²¹Rheumatology, Hospital Clínico Universitario de Valencia. Spain, Valencia, Spain, ²²Hospital Universitario de Guadalajara. Spain, Guadalajara, Spain, ²³Rheumatology, Hospital Puerta del Mar. Cádiz. Spain, Cádiz, Spain, ²⁴Ophthalmology, Hospital Universitario Clínico San Carlos. Madrid. Spain, Madrid, Spain

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Graves' disease and tocilizumab

Session Information

Date: Tuesday, October 23, 2018

Title: Miscellaneous Rheumatic and Inflammatory Diseases Poster III: Sarcoid, Inflammatory Eye Disease, and Autoinflammatory Disease

Session Type: ACR Poster Session C

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

Background/Purpose: To assess the efficacy of Tocilizumab (TCZ) in refractory thyroid associated orbitopathy (TAO) due to Grave’s disease.

Methods: Multicenter study of 46 patients with TAO refractory to conventional immunosuppressive therapy.

Results: We studied 46 patients (85 eyes) (37 women/9 men); mean age at diagnosis 49.2±11.8 years. Besides oral corticosteroids and before the onset of TCZ, patients had been treated with pulses of intravenous methylprednisolone (n=42), radioactive iodine (n=4), methotrexate (n=2) and other drugs (methimazole in 8 cases, leflunomide in 1, azathioprine in 1, selenium in 11). Urgent decompressive surgery had to be performed in 7 patients. According to the classification of severity of the EUGOGO group (European Group on Graves’ Orbitopathy) using the clinical activity score (CAS), before TCZ onset patients whose data were available had severe (n=27 eyes) or moderate (n=34 eyes) disease. Moreover, patients presented exophthalmos (n=53 eyes), strabismus (n=37 eyes), muscle fibrosis (n=38 eyes) and dysthyroid optic neuropathy (n=10 eyes). TCZ was used in monotherapy (n=43) or combined with methotrexate (n=2) or azathioprine (n=1) at 8 mg/kg/iv/4 weeks (n=41) or 162 mg/sc/week (n=5). TCZ yielded rapid and maintained improvement in all ocular parameters as shown in Table 1. After a mean of 7.42±6.41 months using TCZ and a mean follow-up of 16.47±11.99 months, all patients experienced ocular improvement, with TCZ withdrawal in 28 cases due to complete remission (n=10), improvement (n=12) or stability of ocular inflammation (n=3), inefficacy (n=2) and total thyroidectomy (n=1). Only 5 relevant adverse effects were observed (neutropenia, external otitis, otitis media, costal osteitis and gingival hyperplasia, 1 each).

Conclusion: TCZ appears to be useful in TAO treatment.

TABLE. Improvement of ocular parameters with TCZ therapy. Data are expressed as mean±SD or median[IQR].

	BASAL	1 WEEK	2 WEEKS	1 MONTH	3 MONTHS	6 MONTHS	1 YEAR
VA	0.9 [0.7-1]	0.8 [0.7-1]	1 [0.8-1]*	1 [0.7-1]*	1 [0.8-1]*	1 [0.7-1]*	1 [0.85-1]*
IOP	19.18±3.94	17.25±1.90	17.60±2.72	18.35±4.49*	17.89±3.85*	17.08±3.62*	16.84±3.56*
CAS	4.63±1.61	4.66±2.61	–	2.97±1.91*	1.91±1.52*	0.97±0.99*	0.77±0.80*

*p<0.05

Abbreviations: VA= visual acuity; IOP= intraocular pressure; CAS= clinical activity score (0/7 at baseline, 0/10 in the rest of time measures).

Disclosure: B. Atienza-Mateo, None; J. L. Martín-Varillas, None; V. Calvo-Río, None; R. Demetrio-Pablo, None; D. Prieto Peña, None; M. Calderón Goercke, None; E. Valls-Pascual, None; B. Valls-Espinosa, None; O. Maiz-Alonso, None; A. Blanco, None; I. Torre-Salaberri, None; V. Rodriguez-Mendez, None; A. Garcia-Aparicio, None; R. Veroz González, None; V. Jovaní, None; D. Peiteado, None; M. Sanchez Orgaz, None; S. Castañeda, None; E. Tomero, None; F. J. Toyos Sáenz de Miera, None; V. Pinillos, None; E. Aurrecoechea, None; Á. Mora, None; A. Conesa, None; M. Fernández, None; N. Avilés, None; J. A. Troyano, None; M. A. González-Gay, None; R. Blanco, None.

To cite this abstract in AMA style:

Atienza-Mateo B, Martín-Varillas JL, Calvo-Río V, Demetrio-Pablo R, Prieto Peña D, Calderón Goercke M, Valls-Pascual E, Valls-Espinosa B, Maiz-Alonso O, Blanco A, Torre-Salaberri I, Rodriguez-Mendez V, Garcia-Aparicio A, Veroz González R, Jovaní V, Peiteado D, Sanchez Orgaz M, Castañeda S, Tomero E, Toyos Sáenz de Miera FJ, Pinillos V, Aurrecoechea E, Mora Á, Conesa A, Fernández M, Avilés N, Troyano JA, González-Gay MA, Blanco R. Anti-IL6-Receptor Tocilizumab in Graves’ Orbitopathy. Multicenter Study of 46 Patients [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/anti-il6-receptor-tocilizumab-in-graves-orbitopathy-multicenter-study-of-46-patients/. Accessed .

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