Recent Developments in Biologic Therapies for the Treatment of Patients With Systemic Lupus Erythematosus

Pedro L. Carreira; David A. Isenberg

Disclosures

Rheumatology. 2019;58(3):382-387. 

In This Article

Blocking Immune Complexes

Fcγ receptors (FcγR) are transmembrane proteins that recognize the Fc region of IgG. The binding of immune complexes (ICs) and FcγR initiates intracellular signalling, which results in an autoimmune response. Most of the FcγR molecules act as activating receptors and only FcγRIIB is an inhibitory receptor. Both types of receptors are expressed on the same cells. Negative signalling by FcγRIIB is mainly important for the regulation of activated B cells. SLE patients have a lower expression of FcγRIIB.

SM101 is an extracellular version of the human FcγRIIB. It binds to IC in SLE and blocks the Fcγ-mediated signal. FcγRIIB was chosen as a therapeutic target because of its limited human polymorphism and lack of immunogenicity. In a 24-week phase IIa trial, 51 SLE patients were randomized to receive SM101 or placebo weekly for 4 weeks. The primary outcome was safety and the secondary outcomes included SLEDAI, BILAG, physician global assessment, global response and renal parameters. No serious AE were reported. The SRI-4 response was twice as high in the SM101 group and in LN results was even better.[23] The results seem promising but phase III trials are needed.

Rather than binding to IC, binding to the receptor itself can produce an inhibitory response. SM201 is an anti-FcγRIIB mAb, it binds to FcγRIIB but allows the binding between IC and the FcγRIIB. A pre-clinical study showed that SM201 had a synergic action with IC resulting in a better inhibition of B cells.[24] It also seems to be restricted to activated B cells, allowing a functional memory response. Clinical trials are needed to understand if it's a valid therapeutic.

A resume of ongoing trials relevant to the approaches discussed in this review are shown in Table 1.

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