Background: BAFF is a Serum B cell stimulating factor shown elevated in Graves’ disease, compared to controls (Vannucchi 2012). BAFF and its receptor are expressed on lymphocytes infiltrating the thyroid in Graves’ disease as well as on thyrocytes themselves (Campi 2015).
Aims: A single-blind randomized controlled trial (EudraCT 2015-002127-26) has been conducted to test the efficacy of the anti-BAFF monoclonal antibody belimumab (BMB) in active moderate-severe Graves’ Orbitopathy (GO) compared to iv methylprednisolone (MP).
Methods: We studied the first 20 of the planned 40 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). They received iv belimumab at 0,14, 28 days and then every four weeks for five cycles of infusion or 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. Patient were studied at 12, 24 weeks (primary end point) and followed-up for 48 weeks. In addition to the CAS (primary end point), Gorman diplopia score and proptosis (secondary end points) were also measured.
Results: In both groups CAS decreased significantly at 24 weeks (P < 0.0001). At 12 weeks patients on MP had a significantly lower CAS than those on BMB (4.8–1.4 vs 4.18–2.45, P < 0.02). At 24 weeks 9/10 patients had inactive disease (mean CAS with MP 1.33 and with BMB 1.5). No differences were observed in the proptosis and the Gorman score for diplopia with either treatment (P = NS). Only one patient (BMB) developed optic neuropathy after the first infusion. In addition, among patients treated with BMB, we observed one with increased blood pressure, one with headache and dizziness, one with nausea and bile vomiting. Among patients treated with MP, two developed fasting hyperglicemia, one headache, one insomnia, one increased nervousness. Two patients trated with BMB developed epigastralgy, but they were not on pump inhibitor, unlike all patients treated with MP.
Conclusions: The interim analysis suggests that BMB is as effective as iv MP in the treatment of active GO, inducing inactivation in approximately 90% of subjects. Its effect is slower than MP, but its tolerability is very good. If the data is confirmed, BMB is suggested to be a good alternative to MP. Finally, the side-effects profile of BMB is better than MP.
05 Sep 2020 - 09 Sep 2020