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

B-cell Intracellular Signalling Blockade—Bruton's Tyrosine Kinase

Bruton's tyrosine kinase (BTK) is a component of B-cell receptor signalling, involved in regulating cell proliferation and survival. Its blockade results in B-cell apoptosis. B-cells overexpressing BTK in mice led to anti-dsDNA antibody production and SLE-resembling organ involvement. Many inhibitors of BTK are in development, including ibrutinib and GDC-0853.

Ibrutinib is a tyrosine kinase selective and irreversible inhibitor. It binds to BTK causing B-cell apoptosis. Pre-clinical trials showed ibrutinib reduced levels of autoantibodies (anti-nucleosome, anti-histone and anti-ssDNA but not anti-dsDNA) and renal disease.[7] However, no current clinical trial is ongoing in SLE.

GDC-0853 is another BTK inhibitor.[8] A phase II trial in SLE is ongoing (NCT02908100), to evaluate the safety and efficacy in patients with moderate-to-severely active SLE.

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