A19: Rituximab Therapy has a Rapid and Durable Response for Refractory Cytopenia in Childhood‐Onset Systemic Lupus Erythematosus

Abstract

Background/Purpose: Cytopenias including thrombocytopenia and autoimmune hemolytic anemia(AIHA) are common in childhood‐onset SLE (cSLE) and may be refractory to conventional therapy with corticosteroids, IVIG and/or other immunosuppressives. Rituximab appears to be an effective therapy for cytopenias, although no long term studies have been completed, and few cSLE patients have been reported. Our objectives were to examine our experience, determine the rate and durability of response to rituximab, and evaluate its safety in our cSLE population with refractory cytopenias. Methods: A single center retrospective cohort study of patients diagnosed with cSLE between Jan 1, 2003 and Dec 31, 2012. Inclusion criteria were SLE diagnosed <18th birthday, refractory cytopenia (thrombocytopenia and/or AIHA) with inadequate response to conventional therapy, and treatment with rituximab during the study period. Demographic, clinical, laboratory, and treatment data were examined. Complete response for thrombocytopenia was defined as platelets >100 × 109/L, and for AIHA hemoglobin >120 g/L. B‐cell phenotyping was determined at regular intervals. Outcomes examined included the time to clinical response, time to B‐cell depletion, and the duration of response. Adverse events studied included the incidence of persistent (>12 months) hypogammaglobulinemia, infusion reactions and infections requiring hospitalization. Results: 398 patients were diagnosed with cSLE during the study period; 24 (6%) received rituximab for refractory cytopenia. Rituximab was given either as 4 weekly doses of 375 mg/m2 or 2 doses of 500 mg/m2 separated by 14 days, depending on the year. There was a female predominance (18/24, 75%), the median age was 13.2 y (range 4–18). Fifteen (63%) had thrombocytopenia, 5 (21%) had AIHA, and 4 (17%) had both. The median (IQR) time from cytopenia onset to rituximab therapy was 517 (237, 892) days. Complete response to 1st course of rituximab occurred by 30 days in 15 (63%), by 90 days in an additional 3 (13%) patients, by 180 days in 3 (13%) patients, and by 1 year in 2 (8%) patients; 1 patient failed to respond. For thrombocytopenia, the time to complete response was 17(13, 62) days and for AIHA 54 (24, 98) days. Five (21%) patients had one or more flare episodes at 21 (14.6, 27.3) months. No patient with thrombocytopenia in the absence of AIHA flared following 1st dose of rituximab. All patients who had B cell phenotyping had complete depletion of CD20 B cells at 16 (14, 30) days. The time to B cell reconstitution was 331 (175, 468) days. Transient infusion reactions included fever, erythematous pruritic rash, and hypotension in 2 patients. Four patients had transient hypogammaglobulinemia. Three patients had persistent undetectable IgG and received monthly IVIG replacement; 2 had recurrent infections. One patient (who was not hypogammaglobulinemic) had varicella zoster 10 weeks following rituximab. No other hospitalizations for infection were observed within 1 year of rituximab administration. Conclusion: Rituximab app...

A molecular perspective on rituximab: A monoclonal antibody for B cell non Hodgkin lymphoma and other affections

“…There are also recent confirmations on rituximab's effectiveness in non-oncological, and in particular autoimmune diseases, such as Rheumatoid arthritis (RA) (Wendler et al, 2014;Cambridge et al, 2014) [e.g. 8,9], multiple sclerosis (MS) (Castillo-Trivino et al, 2013;Palanichamy et al, 2014), systemic Lupus Erythematosus (SLE) (Olfat et al, 2014), and refractory pulmonary sarcoidosis (Sweiss et al, 2014). For instance, a study on Idiopathic thrombocytopenia purpura (ITP; as an autoimmune hematological disorder which considered by low platelet counts) showed rituximab had significant impact in elevating the platelet counts in 57% patients (Braendstrup et al, 2005).…”

Antibody replacement therapy in primary antibody deficiencies and iatrogenic hypogammaglobulinemia

“…These patients include adults and children with various autoimmune diseases, including SLE, autoimmune hemolytic anemia and autoimmune vasculitis. Most reports on symptomatic hypogammaglobulinemia do not elaborate on the effect of antibody replacement therapy on infection frequency or IgG levels [40,41,70,71].…”

Off-label use of rituximab in patients with systemic lupus erythematosus with extrarenal disease activity: a retrospective study and literature review

“…The results of the EXPLORER randomized controlled trial failed to show superiority of rituximab compared with placebo in patients with non-renal SLE (8). Some studies have shown efficacy in patients with severe autoimmune thrombocytopenia and haemolytic anemia (14)(15)(16). Also, some smaller open-labeled studies have reported a good response after rituximab (17)(18)(19)(20)(21)(22)(23).…”