SAT0601 Anti-il6-receptor tocilizumab in graves’ orbitopathy. multicenter study of 29 patients

Abstract

ObjectivesTo assess the efficacy of Tocilizumab (TCZ) in refractory thyroid associated orbitopathy (TAO) due to Grave’s disease.MethodsMulticenter study of 29 patients with TAO refractory to conventional immunosuppressive therapy.ResultsWe studied 29 patients (58 eyes) (23 women/6 men); mean age at diagnosis 48.79±12.39 years. Besides oral corticosteroids and before the onset of TCZ, patients had been treated with pulses of intravenous methylprednisolone (n=24), methotrexate (n=2) and other drugs (methimazole in 4 cases, leflunomide in 1, selenium in 9). Urgent decompressive surgery had to be performed in 2 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=14 eyes) or moderate (n=22 eyes) disease. Moreover, patients presented exophthalmos (n=30 eyes), strabismus (n=17 eyes), muscle fibrosis (n=15 eyes) and dysthyroid optic neuropathy (n=1).TCZ was used in monotherapy (n=27) or combined with methotrexate (n=2) at 8 mg/kg/iv/4 weeks (n=24) or 162 mg/sc/week (n=5). TCZ yielded rapid and maintained improvement in all ocular parameters (TABLE).After a mean follow-up of 8.96±7.55 months using TCZ, all patients experienced ocular improvement, with TCZ withdrawal in 16 cases due to complete remission (n=5) or stability of ocular inflammation (n=11). Only 4 adverse effects were observed (neutropenia, external otitis, otitis media, costal osteitis).TABLE. Improvement of ocular parameters with TCZ therapy. Data are expressed as mean±SD or median[IQR].BASAL1 WEEK2 WEEKS1 MONTH3 MONTHS6 MONTHS1 YEAR VA0.7 [0.5–1]0.7 [0.6–1]0.8 [0.7–1]0.85 [0.7–1]1 [0.9–1]1 [0.7–1]1 [0.8–1]IOP19.22±4.2017.25±1.9016.75±2.3118.23±5.0017.39±3.5116.52±3.5616.00±3.41CAS4.97±1.724.85±2.95-3.40±2.282.34±1.711.29±1.121.11±0.85VA=visual acuity; IOP=intraocular pressure; CAS=clinical activity score (0/7 at baseline, 0/10 in the rest of time measures).ConclusionsTCZ appears to be useful in TAO treatment.Reference[1] Bartalena L, Baldeschi L, Dickinson AJ, et al. Consensus statement of the European group on Graves’ orbitopathy (EUGOGO) on management of Graves’ orbitopathy. Thyroid2008;18(3):333–346.Disclosure of InterestNone declared

Efectividad y seguridad de tocilizumab en 2 casos de orbitopatía tiroidea grave refractaria a corticosteroides. Hospital San José, Bogotá

“…Tocilizumab fue usado como monoterapia en 43 pacientes. Después de 7 meses de tratamiento en 10 casos se presentó remisión completa de la orbitopatía tiroidea, mejoría de la enfermedad en 12 pacientes y estabilidad del proceso in lamatorio en 3 pacientes; y en 2 casos la terapia fue ine icaz (19).…”

Progress in the pathogenesis of thyroid-associated ophthalmopathy and new drug development

“…A number of studies have shown that TCZ is safe and effective in treating TAO patients who were glucocorticoid insensitive. TCZ was also demonstrated to block the inflammatory cascade, improve clinical performance, and reduce CAS,[ 51 52 53 54 ] but it needs to be further verified in the clinical application. A variety of TNF-α monoclonal antibodies, such as etanercept, infliximab, and adalimumab, have shown good efficacy in TAO,[ 55 56 57 ] however most studies are case reports and large-scale population based studies have not been carried out.…”

Considerations for Use of Immune Checkpoint Inhibitors in Cancer Therapy for Patients with Co-Existing Thyroid Eye Disease

“…The blockade of IL-6 and the PD-1 axis has been shown to have synergistic antitumour effects through the induction of cytotoxic T cells and the inhibition of in vivo tumourigenesis in animal studies [ 55 , 56 ]. Anti-IL-6 receptor antibodies have also yielded rapid and sustained improvement in various ocular parameters in patients with refractory Graves’ orbitopathy [ 57 ]. A personalised strategy for patients highlights the importance of inter-disciplinary collaboration between clinical oncology and ophthalmology.…”