ANTI-CD19 MONOCLONAL ANTIBODY FOR SYSTEMIC LUPUS ERYTHEMATOSUS AND NEUROMYELITIS OPTICA SPECTRUM DISORDER

PV302 / #548 Case Report Poster Topic: AS24 - SLE-Treatment Introduction Systemic Lupus Erythematous (SLE) is a multisystem autoimmune disease involving different immune pathways including B cell dysregulation. B cell-directed agents have shown efficacy in SLE and lupus nephritis, prompting the development of therapies targeting CD19, a transmembrane protein on pro-B cells, immature and mature B cells, memory B cells, plasmablasts and plasma cells. Anti-CD19 monoclonal antibodies have shown efficacy for neuromyelitis optica spectrum disorder (NMOSD),[1] a demyelinating disorder that may coexist with SLE. It is unclear whether anti-CD19 monoclonal antibody may also be effective for treating SLE. Case Presentation With Investigation 1) A 35-year-old Caucasian man developed slurred speech, paresthesia, and gait disturbance, found to have demyelinating lesions, aquaporin-4 immunolgoblin G (IgG) >1:100,000 and was diagnosed with NMOSD in the setting of concomitant SLE with pleuro-pericardial effusions, positive antinuclear antibody (ANA), anti-double-stranded DNA (dsDNA), anti-ribonucleoprotein (RNP), antichromatin, anti-Smith, anti-SSA, anti-SSB, anticardiolipin, anti-β2-glycoprotein antibodies, low complement 3 (C3) and C4. He was treated with high-dose steroids, plasma exchange, hydroxychloroquine and azathioprine which was discontinued due to cytopenia. He was then given inebilizumab with improved neurologic deficits and MRI findings. His steroid doses were tapered off and he remains on inebilizumab and hydroxychloroquine with no signs of SLE or NMOSD activity 1 year later. 2) A 25-year-old African American woman diagnosed with SLE, class V lupus nephritis, polyarthritis, with positive ANA, antichromatin, anti-RNP, anti-Smith, and anti-SSA antibodies, low C3 and C4, treated with steroid taper, hydroxychloroquine and mycophenolate dose reduced due to cytopenia. She initially presented with unilateral vision loss and paresthesia although her diagnosis of NMOSD was not made until she completed neurologic workup a year after her SLE diagnosis, which showed demyelinating lesions on spine MRI and aquaporin-4 IgG >1:100,000. She was then started on rituximab but due to inadequate response in her neurologic symptoms she was switched to inebilizumab. Six months after initiation she has no signs of SLE activity and continues to have visual disturbances and paresthesia but not attributed to active demyelination. Literature Review There is limited data on the use of anti-CD19 monoclonal antibody for SLE. A trial with obexelimab for SLE did not meet the primary endpoint of proportion of patients reaching week 32 without loss of improvement.[2] However, there was a significant increase in time to loss of improvement in the obexelimab-treated patients. An ongoing trial is investigating the use of inebilizumab and blinatumomab, a bispecific CD19-directed CD3 T cell engager for SLE. One case series of 3 patients with SLE coexisting with NMOSD reported various therapies used for those patients including steroids, cyclophosphamide, rituximab, azathioprine, hydroxychloroquine.[3] There were no cases found in the literature of SLE and coexisting NMOSD treated with anti-CD19 antibodies. Discussion We present 2 cases of SLE with concurrent NMOSD controlled with anti-CD19 monoclonal antibody with remission of SLE activity. Compared to CD20, CD19 is expressed by more cells in the B cell lineage that may lead to greater inhibition of B cell signaling. Targeting CD19 may be effective for patients with coexisting SLE and NMOSD. References: [1.] Cree BAC. Lancet 2019;394(10206):1352-63. [2.] Merrill JT. Arthritis Rheumatol 2023;75(12):2185-94. [3.] Ochi MGS. Case Rep Rheumatol 2020;2020:8820071.