Endocrine Abstracts

Background

Serum B cell stimulating factor (BAFF) has been shown to be elevated in Graves’ disease (Vannucchi 2012). In addition, BAFF and its receptor have been shown to be expressed on lymphocytes infiltrating the thyroid in Graves’ disease and also on thyrocytes (Campi 2015).

Aims

We tested in a single-blind randomized controlled trial (EudraCT 2015–002127–26) whether the administration of the anti-BAFF monoclonal antibody belimumab (BMB), approved for therapy of SLE, is effective in active moderate-severe Graves’ Orbitopathy (GO) as compared to first line treatment iv methylprednisolone (MP).

Methods

We randomized 27 patients with active, moderate severe GO and detectable serum TSH receptor antibodies (TRAb), euthyroid for at least 3 months, whether untreated or previously treated with iv steroids (relapsing GO). 14 received iv belimumab at 0, 14, 28 days and then every four weeks for five cycles of infusion and 13 iv MP, 833 mg/ weekly for 6 cycles, followed by one cycle of 425 mg/week. The first dose of belimumab was associated to a full dose (833 mg) of MP (inception dose). Patient were studied at 12, 24 weeks (primary end point) and followed-up for 48 weeks. In addition to assessment of the CAS (primary end point), proptosis and the titers of TRAb (secondary end points) were also measured.

Results

In both groups of patients the CAS decreased significantly at 24 weeks (P < 0.0001). At 12 weeks patients on MP had a significantly lower CAS than those on BMB (4.75 ± 0.3 1.5 ± 0.5 vs 4.15 ± 0.2 2.54 ± 0.5, P < 0.009). At 24 weeks 12/13 patients on MP (CAS 1.00 ± 0.4) and 13/14 on BMB (CAS 1.38 ± 0.3) had inactive disease. Proptosis improved in all patients (P < 0.05) and in MP patients more significantly than BMB (P < 0.04). Serum TRAb levels decreased significantly (P < 0.01) in both groups of patients. Two patients in each arm developed optic neuropathy. BMB treatment was very well tolerated, with 1 major and 4 minor side effects vs 2 and 3, when compared to MP.

Conclusions

BMB is as effective as iv MP in the treatment of active GO, inducing inactivation in more than 92% of subjects. While its effect is somewhat slower than that of MP, its tolerability is very good. BMB is suggested to be an excellent alternative to MP when this is contraindicated or not effective.

Funding

GLAXOSmithKline, Verona and Fondazione IRCCS Ca’ Granda, Milan, Italy.