SOM230 Graves Orbitopathy pilot trial

Graves* ophthalmopathy (GO), or Graves Orbitopathy, is clinically present in
~25% of patients with Graves* disease (hyperthyroidism). There is consensus
that patients with active, moderate-to-severe GO qualify for immunosuppression:
weekly pulses of intravenous methylprednisolone for 12 weeks are recommended.
However, because of disappointing response rates to prednisolone, alternative
treatments with similar efficacy but less side effects would be welcome, not
only in patients in whom steroids are contraindicated.
A number of studies, have demonstrated that octreotide and lanreotide do not
improve or marginally improve eye changes as compared to placebo despite the
fact the orbital fibroblast expresses the somatostatin receptor. The cause of
these disappointing results could well be the low affinity of octreotide and
lanreotide for all somatostatin receptors except subtype sst2, whereas in GO a
clear up regulation of sst1 and sst5 on OF has been observed.
Pasireotide (SOM230) indeed has a greater inhibitory effect on in vitro
proliferation of orbital fibroblasts than octreotide, and both pasireotide and
octreotide inhibit human lymphocyte proliferation albeit acting at different
concentrations.
Result of a recent trial that we have performed showed disappointing results
when moderate to severe GO patients were treated with intravenous prednisolone
with improvement of a predefined response criterium in only ~50% of cases.
Previous studies showed higher response rates, which may have been due to the
fact that in these early studies patients with more severe GO were included.
However, the response to intravenous prednisolone underscores the need of
additional therapies.

Therefore, we aim to investigate in a pilot trial the effect of SOM230 on
predefined endpoints in patients with moderate to severe GO whom have
contraindications for prednisolone therapy or decline from prednisolone therapy
for other reasons.

Prospective observational

Admnistration of SOM230 (Pasireotide)

Patients will receive three times injection with long acting pasireotide 60mg
(intramuscularly) and normal evaluation on the outpatient clinic will ensue.
Mild hyperglycemia can be expected and will be monitored.