Javier Carbone, Spain
Hospital general Universitario Gregorio Marañon Clinical ImmunologyPresenter of 2 Presentations
EVALUATION OF INTRAVENOUS TOCILIZUMAB FOR THE THERAPY OF MODERATE TO SEVERE GRAVES' OPHTHALMOPATHY
Abstract
Background and Aims
Thyroid-associated ophthalmopathy is an extrathyroidal manifestation of Graves disease, occasionally severe and refractory to treatment. The complications of this disease have a high negative impact in the quality of life of the patients. A infiltrating cytokine in the orbital tissue is interleukin-6. We here report efficacy and safety of the use of intravenous tocilizumab in moderate to severe Graves' ophthalmopathy in a single center.
Methods
Prospective case report. Clinical and Immunological data of 5 cases. Patients with moderate to severe Graves' ophthalmopathy were subsequently included to receive a protocol of monthly intravenous tocilizumab at a dose of 8 mg/kg/dose (total 4 doses). All reported a past or present history of dysthyroidism. Safety evaluation before tocilizumab infusions was performed.
Results
The administration of interleukin-6-receptor monoclonal antibody treatment was associated with a significant improvement in CAS scores (ocular symptoms, proptosis), and functional prognosis in all patients. Improvement of myxedema was also observed in a patient with this extrathyroidal manifestation of Graves disease. Improvement in the European Group on GO-proposed composite ophthalmic score was also observed. Patients communicated better quality of life after therapy. Infusions were tolerated well. In one patient a reduction to 4mg/kg/dose was introduced due to increase of liver transaminase levels. No infectious complications were observed. A significant decrease of anti-TSH-receptor antibody titers was documented (13.26 vs 3.6 IU/L, 2-sided T-test p=0.019).
Conclusions
These data further support the efficacy and tolerability profile of intravenous tocilizumab in moderate to severe or corticosteroid-resistant Graves' ophthalmopathy.
MANAGEMENT OF SECONDARY ANTIBODY DEFICIENCY WITH INTRAVENOUS IMMUNOGLOBULIN IN PATIENTS WITH PREVIOUS THERAPY WITH RITUXIMAB
Abstract
Background and Aims
Rituximab can be associated with symptomatic secondary antibody deficiency (SAD) in autoimmune diseases (AID). Severe or recurrent infections can develop. There are no established guidelines for evaluating and treating SAD after Rituximab. Intravenous immunoglobulin (IVIG) replacement therapy has been poorly evaluated as treatment for SAD in AID.
Methods
Retrospective analysis of prospectively collected data in a single center. 10 autoimmune disease patients [SLE (2), dermatomyositis (2), vasculitis (2), polymiositis (1), optic neuromyelitis (1), undifferentiated connective tissue disease (n=1), Wegener granulomatosis (1)] that developed severe infections and were found to have SAD after Rituximab. 7 (70%) were women, mean age 62 (39-79). SAD definition: IgG < 600 mg/dL + low anti-pneumococcal antibody titers (anti-PPS<5 mg/dL). Intervention: Non-specific 5% or 10% IVIG at a dose of 400mg/kg/month in addition to conventional antimicrobial therapy with the aims of contributing to control of infection, secondary prevention of re-infection and normalization of IgG (IgG>750 mg/dL). Time of IVIG therapy for analysis: 6 months. Clinical follow up: 6 months after the first dose of IVIG.
Results
A significant increase of IgG levels was demostrated: 865± 133 vs 542±68 mg/dL (p=0.02). A trend towards an increase of anti-PPS was observed: 3.86±1.44 vs 2.98±1.04 (p=0.12). The prevalence of infection was significantly lower during the IVIG period as compared with a similar period of time before IVIG: Infections 1±0.7 vs 3.8±0.8 (p<0.001).
Conclusions
Personalized immunoguided intervention of IVIG in autoimmune disease patients with SAD after Rituximab is associated with lower rates of reinfections. These results require evaluation in a randomized clinical trial.