Abstract
Background Due to the variable course of thyroid eye disease (TED), treatment should be tailored
to disease severity, individual risk factors, and clinical course. This study is based
on a retrospective analysis at the orbital centre of the University Eye Clinic Essen
and evaluates the efficacy of the IL-6 receptor blocker tocilizumab as a second-line
therapy in patients with therapy-refractory TED.
Patients/Methods After approval of cost coverage, 20 patients were treated with tocilizumab over a
mean period of 4.8 ± 2.7 months. The following parameters were assessed: sex, age,
underlying thyroid disease, disease activity and severity, prior therapies, visual
acuity, intraocular pressure, eyelid position, exophthalmos, monocular excursions,
strabismus/diplopia, levels of TSH receptor antibodies (TRAb), and adverse events.
Results The female-to-male ratio was 3 : 1. Mean patient age was 58.2 ± 8.5 years. The majority
(90%, n = 18) had Gravesʼ disease; one patient had primary hypothyroidism and one
was euthyroid. All patients had previously failed various treatment regimens (median
cumulative steroid dose 4.6 g [1.5 – 7.5 g], 55% mycophenolate, 65% orbital apex radiation,
20% balanced orbital decompression). Among 17 patients with detectable TRAb at baseline,
mean antibody levels decreased by 48.4%. A reduction of at least 30% was achieved
in 70.6% of these patients (n = 17). A decrease in the Clinical Activity Score (CAS)
by ≥ 2 points was observed in 70% of cases. The mean inflammation score (maximum 20
points per patient) decreased from 8.8 ± 3.9 to 3.4 ± 2.4. The effect on exophthalmos
was moderate: mean reduction was 0.9 ± 1.8 mm (range − 6 mm to + 3 mm). A decrease
of ≥ 2 mm was documented in 25% of patients, whereas an increase was noted in 12.5%
(0.5 to 3 mm). Improvement in
ocular motility was documented in 22.5% of patients, while 10% showed deterioration.
Discussion This cohort exclusively included therapy-refractory patients, some with protracted
disease. The significant reduction in inflammation and particularly in TRAb levels,
as a biomarker of disease activity, demonstrate the efficacy of tocilizumab in this
highly selected population. Tocilizumab may therefore be an important treatment option
for patients with high antibody levels and predominantly inflammatory disease manifestations.
Further studies are warranted to evaluate whether it reduces the risk of relapse after
successful treatment with an IGF-1 receptor blocker.
Keywords
Orbit - thyroid eye disease - teprotumomab - proptosis
