Belimumab Treatment for IgG4-related Disease

IgG4-RD is associated with substantial morbidity and mortality, but there is no established therapy other than GCs for an acute flare. Up to date, no randomized prospective controlled studies have been performed for this disease, and no approved therapy is available. Although GCs are widely and effectively used for treatment of initial disease and flare, they are associated with substantial toxicity which limits their long-term use. Disease flares also occur in many patients either during the GC taper or after GC discontinuation. Patients need a treatment that will more effectively control their disease and avoid GC toxicity. This study will establish the safety and tolerability of Belimumab in IgG4-RD and its ability to reduce the risk of disease flares. There are currently no medicinal products approved for the treatment of IgG4-RD. The majority of cases follow a relapsing course that can lead to permanent tissue damage with attendant morbidity and potential mortality. Glucocorticoids are widely and effectively used for treatment of initial disease and of flare, but they do not prevent recurrence of active disease after their discontinuation and are associated with substantial toxicity. Patients also continue to relapse on the off-label steroid-sparing immunosuppressive medications used by some physicians to manage patients with IgG4-RD; thus, there is a high unmet medical need for more effective therapies in this patient population. The pathogenesis of IgG4-RD suggests that B-cell depletion may be an effective avenue for therapeutic intervention. Therapeutic depletion of B cells with rituximab reduces disease-relevant biomarkers and appears to have clinical benefit in uncontrolled, retrospective and prospective clinical studies. This study aims to define the efficacy and safety of Belimumab for the prevention of flares of this rare disease. In addition, the potential of Belimumab for minimizing GC exposure could limit the well-known adverse effects of GCs on bone, skin, muscle, adrenal gland, and eyes, and GC association with weight gain, diabetes, hypertension, and neuropsychiatric effects.