**4. Conclusion**

*Lupus - Need to Know*

*2.4.3 Obinutuzumab*

*2.4.4 Ofatumumab*

*2.4.5 Epratuzumab*

*2.4.6 Sifalimumab*

*2.4.7 Rigerimod*

results [138].

with Sjogren's syndrome [134].

phase IIb clinical trial in SLE [137].

**2.5 Supplementary therapeutic modalities**

to rituximab for B cell depletion treatment in SLE.

Obinutuzumab is a novel humanized type II glycoengineered anti-CD20 antibody

Ofatumumab is a fully human anti-CD20 monoclonal antibody [129]. It induces antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity in CD20-expressing B lymphocytes. Ofatumumab is highly potent in lysing B cells, as this appears to stem from its binding site on the short extracellular loop of the target CD20 protein and its slow release from the target molecule. Ofatumumab has been successfully applied in a patient with SLE and hypocomplementemia in combination with fresh frozen plasma [130]. Ofatumumab, has been used as B cell depleting therapy in SLE patients who developed severe infusion reactions to rituximab [131]. The agent was well tolerated and may be a safe and effective alternative

Epratuzumab is a humanized monoclonal antibody [132]. It targets CD22 on B cells and acts as B-cell modulating treatment through inhibition of B-cell receptor signaling. It has been applied in SLE [133] and found to be effective in SLE patients

Interferons (IFNs) are a family of potent immunostimulatory cytokines that are broadly divided into three subtypes, type I, type II and type III [135]. Of all the type I IFNs, IFNα is the most abundant and is well characterized. The role of interferons in autoimmunity, especially SLE is discussed [136]. Sifalimumab is a fully human monoclonal antibody against multiple IFN-α subtypes and has shown promise in a

Rigerimod is a peptide which reduces the stability of MHC molecules that present antigens to T cells, thus blocking antigen presentation to autoreactive T cells thereby blocking B cell maturation. It has been tested in SLE patients with encouraging

Recently efforts have been made to incorporate adjunct therapeutic agents in the treatment of SLE, so, as to reduce the toxicity of traditional drugs. Prasterone and vitamin D are two immunomodulatory agents, which have been applied in the treatment of SLE as supplements, in order to control disease activity and reduce the use of corticosteroids. Prasterone is a synthetic form of the hormone dehydroepiandrosterone [139]. Its use led SLE patients to better tolerate the tapering of corticosteroids [140]

[126]. In vitro studies have shown that obinutuzumab may induce superior B cell cytotoxicity as compared to rituximab in patients with SLE [126]. Obinutuzumab is considered an alternative B-cell depleting agent for the treatment of SLE [127]. It has been suggested that SLE patients with secondary non-response to rituximab should be preferentially switched to another B-cell depleting agent instead of belimumab [128].

**118**

Hydroxychloroquine and prednisone remain standard of care treatment for SLE. When flares occur the introduction of immunosuppressive agents and/or biologic drugs improves disease activity and disease outcome in SLE. Nowadays, the introduction of biologic agents, such as rituximab and belimumab have revolutionized the treatment of SLE and have opened new therapeutic horizons in all the spectrum of lupus disease.
