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

CD20 Blockade

B cells play an essential role in the development of SLE. Blocking B cells with rituximab, a chimeric mAb against antigen CD20, is well established in SLE. Because it is a chimeric antibody, can cause allergic responses in ~10% of SLE patients. Fully humanized mAbs anti-CD20 have been developed including ofatumumab and obinutuzumab.

Ofatumumab is a mAb IgG1 anti-CD20 approved for chronic lymphocytic leukaemia. Experience of its use in SLE is restricted to a small number of cases. For example, an SLE patient whose previous flares had responded to rituximab, but became allergic to it, received three infusions of ofatumumab and achieved an SLEDAI decrease from 15 to 2, a reduction of anti-dsDNA antibodies levels >90% and C3 normalization.[3] An SLE patient with autoimmune haemolytic anaemia refractory to rituximab, achieved B-cell depletion after ofatumumab, with remission of autoimmune haemolytic anaemia and a SLEDAI of 0.[4] Four patients with LN achieved proteinuria and anti-dsDNA reduction after ofatumumab.[5] Formal clinical trials in SLE are awaited.

Obinutuzumab, a glycol-engineered mAb anti-CD20, is being used in the treatment of non-Hodgkin's lymphoma. An in vitro study comparing rituximab to obinutuzumab in SLE demonstrated the latter to be a more efficient B-cell depletor.[6] A 52-week, phase II trial studying safety and efficacy in LN is currently recruiting (NCT02550652). Its primary outcome is complete renal response.

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