scholarly journals Ofatumumab for B cell depletion therapy in ANCA-associated vasculitis: a single-centre case series

Rheumatology ◽  
2016 ◽  
Vol 55 (8) ◽  
pp. 1437-1442 ◽  
Author(s):  
Stephen P. McAdoo ◽  
Rachna Bedi ◽  
Ruth Tarzi ◽  
Megan Griffith ◽  
Charles D. Pusey ◽  
...  
Keyword(s):  
B Cell ◽  
Case Series ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Single Centre ◽  
Anca Associated Vasculitis

scholarly journals P0374TREATMENT EFFICACY OF BIOSIMILAR RITUXIMAB (TRUXIMA) COMPARED TO THE ORIGINATOR (MABTHERA) IN PATIENTS WITH ANCA ASSOCIATED VASCULITIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
PEK GHE TAN ◽  
Jennifer O'Brien ◽  
Rachna Bedi ◽  
Megan Griffith ◽  
Marie Condon ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
B Cell ◽  
Induction Therapy ◽  
Subgroup Analysis ◽  
Treatment Efficacy ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Anca Associated Vasculitis ◽  
Infusion Reactions

Abstract Background and Aims Truxima is a biosimilar version of rituximab. It was licensed & launched in the United Kingdom in April 2017. A biosimilar medicine is made to be highly similar in quality, safety and efficacy to existing licensed “reference” biological medicine and the cost is often significantly lower. A recent systematic review showed comparable long-term efficacy and safety of biosimilar rituximab to the originator drug in treatment of rheumatoid arthritis and non-hodgkin’s lymphoma. Fewer data are available in regards to the efficacy of biosimilar rituximab in treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). A retrospective study was thus conducted in our centre to examine the efficacy of Truxima when compared to the reference rituximab (MabThera) in the treatment of patients with AAV. Method All patients with new or relapsing AAV who received first ever rituximab therapy between 1/1/2016 and 31/12/2018 were identified via hospital dispensing database. Patients were stratified into Truxima or MabThera treatment group depending on the version of rituximab administered. Primary outcomes that were assessed include: time to B cell depletion (defined as absolute B cell count (ABC) ≤10) and repletion (i.e ABC >10 and >20); time to antimyeloperoxidase(MPO)/antiproteinase 3(PR3)-ANCA negativity; Secondary outcomes assessed include: overall survival, time to major relapse (defined as relapse requiring further course of rituximab for remission induction); adverse events including episodes of neutropenia, hypogammaglobulinemia and major infusion reactions. Subgroup analysis in patients who received concomitant cyclophosphamide and rituximab or other induction therapy was performed to examine if it impacts on the treatment efficacy. Results 59 and 60 patients received Truxima and MabThera respectively for treatment of new or relapsing AAV. The baseline characteristic (age, gender, entry estimated Glomerular Filtration Rate, proportion of patients received concomitant cyclophosphamide, ANCA serology and organ involvement) of both group were comparable. All patients achieved clinical remission following induction treatment. Using Kaplan Meier analysis and log rank test, no difference was identified in time to B cell depletion or repletion (Figure 1&2), MPO/PR3-ANCA negativity (Figure 3), overall survival or major relapses requiring further rituximab as induction therapy. Treatment efficacy of Truxima and MabThera did not differ in subgroup analysis. However we observed that patients who received concurrent cyclophosphamide during induction therapy achieved MPO/PR3-ANCA negativity more rapidly compared to those who did not irrespective of the version of rituximab received. No difference in adverse events such as major infusion reactions was seen in either group upon first rituximab exposure. Two patients in each group developed reactions following repeated dosing of rituximab. Conclusion Biosimilar rituximab Truxima appears to have comparable treatment efficacy compared to the reference drug in our cohort of patients with AAV.

scholarly journals SAT0029 B cell depletion affects CD8 T cells in anca-associated vasculitis

2017 ◽  
Author(s):  
A Néel ◽  
M Bucchia ◽  
M Néel ◽  
M Rimbert ◽  
C Agard ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Cd8 T Cells ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Anca Associated Vasculitis

Rituximab Is Effective and Well Tolerated in Children with Hemophila and Factor VIII Inhibitors.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1031-1031 ◽  
Author(s):  
Nichola Cooper ◽  
Kate Khair ◽  
Mary Mathias ◽  
Ri Leisner
Keyword(s):  
B Cells ◽  
B Cell ◽  
Case Series ◽  
Cell Depletion ◽  
Response To Treatment ◽  
Extensive Literature ◽  
B Cell Depletion ◽  
Haemophilia B ◽  
Wide Range ◽  
Grade 3

Abstract B cell depletion with rituximab is routinely used for a wide range of autoimmune conditions, including a number of haematology conditions. While there is extensive literature on the use of rituximab in adults in both malignant and non-malignant conditions, there is less data on its use in children. We report the use of rituximab in 5 children with haemophilia and persistent FVIII (n=4) or FIX (n=1) inhibitors. Methods: 5 children, median age 5 (range 4 to 16) years with haemophilia A (n=4) or haemophilia B (n=1) and persistent inhibitors were treated with rituximab 375mg/m2 weekly × 4. Patients received pre-medication with paracetamol, hydrocortisone and piriton. All had failed immune tolerance (IT) as defined by the UKHCDO guidelines. 1 patient relapsed and received re-treatment. Results: 4 of 5 patients (80%) had a response to treatment with 3 complete responses (CR) with disappearance of inhibitor 4, 6, and 10 months from the start of rituximab; the 4th patient had a partial response (PR) with a fall from 31 to 1.4BU (still in PR at 6 months). Background details are shown in the table. One CR patient relapsed 25 months from treatment and had a second CR within 3 months of re-treatment. Inhibitor titres following rituximab are shown in the figure. 2 CR patients are still in CR at 5 and 15 months. All completed the 4 doses of rituximab with the expected infusion related side effects to the first dose. Patient 5 (haemophilia B) developed grade 3 symptoms with rigors, temperatures and abdominal pain following all 4 doses. B cells (detected by CD19 positivity on flow cytometry) were monitored in all patients. 4/5 had complete depletion of B cells within 1 month of treatment with return of B cells within 6 months (n=3) to 1 year (n=1). One patient (pt 5) did not deplete his B cells following rituximab therapy. This patient did not have a response to treatment (with an increase in the inhibitor levels after re-challenge with FIX) and suffered from the grade 3 reactions. In three patients IgM levels were slightly lower than normal (0.44 (NR >0.5)). There was no significant fall in IgG levels, no unusual infections and no fall in anti-Hep B antibodies titres. In summary, this case series shows that rituximab is useful in children with haemophilia with persistent inhibitors and failure of IT. It appears well tolerated with no immediate adverse effects. While there is a role for rituximab in patients refractory to IT, whether it should be used earlier in the disorder is not known. Further controlled trials are warranted. Finally, the lack of B cell depletion and subsequent lack of response in pt 5 is difficult to explain. We assume but have not confirmed that this patient has an inhibitor to rituximab. Patient details Patient/haemophilia type Age (years) Mutation Other diagnoses response to rituximab timing of response/duration of response (mos) depletion of B cells 1/A 4 stop codon excema Y, CR 9/23 Y 2/A 5 inversion int22h excema, ashma Y, CR 6/10+ Y 3/A 4 amino acid substitution Y, PR 1/6+ Y 4/A 11 deletion exon14 Y, CR 3/5+ Y 5/B 16 deletion N N Figure Figure

P0286B CELL REPOPULATION AFTER REMISSION INDUCTION WITH RITUXIMAB IN NEWLY DIAGNOSED PATIENTS WITH ANCA-ASSOCIATED VASCULITIS: DOES ONE SIZE FIT ALL?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Chiara Salviani ◽  
Alessandra Gina Gregorini ◽  
Guido Jeannin ◽  
Federico Alberici ◽  
Giovanni Cancarini ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
B Cell ◽  
Clinical Diagnosis ◽  
Cell Depletion ◽  
Remission Induction ◽  
B Cell Depletion ◽  
Cell Recovery ◽  
Anca Associated Vasculitis ◽  
Cell Repopulation

Abstract Background and Aims Rituximab (RTX) is one of the mainstays of ANCA-associated vasculitis (AAV) treatment. Nevertheless, studies specifically addressing the B cell repopulation in AAV patients after remission induction with RTX are still scanty and with conflicting results. Moreover, the role of B cell monitoring in the management of RTX-based maintenance therapy still remains to be fully elucidated. In this study, we evaluated B cell repopulation after a single course of RTX in treatment-naïve patients with AAV. Method We included all consecutive patients with new diagnosis of AAV from December 2009 to December 2017, treated with a single course of RTX for remission induction, with a follow-up ≥12 months. B cell recovery, re-treatment for relapse or rise in ANCA titer and scheduled re-treatment were considered as the termination of observation period. B cell count was performed by flow cytometry (Beckman Coulter Navios©) every 2 weeks during the 1st month, every 4 weeks until the 6th month, then every 12 weeks. B cell recovery was defined as CD19 count ≥10 cells/μl. Results Seventy-four patients (38% M, 62% F) met the inclusion criteria. Mean age was 63±21 years. MPA, GPA and EGPA were diagnosed in 49 (66%), 24 (33%) and 1 (1%) patients, respectively. ANCA were positive in 65 (88%) patients, with 50 (68%) anti-MPO and 15 (20%) anti-PR3. Overall median follow-up was 40 months (IQR 25-60). All patients achieved remission and complete B cell depletion after RTX. Twenty-two (31%) patients received plasma-exchange and 20 (29%) steroid pulses. Maintenance therapy with azathioprine or methotrexate was started in 10 (14%) patients. Seventeen (23%) patients received re-treatment with RTX (10 patients for relapses, the remaining cases for B cell recovery and/or a rise in ANCA titre or scheduled re-treatment). B cell recovery was observed in 39 (53%) patients, after a median time of 27 months (IQR 20-38). Particularly, only 7% of patients recovered B cells at 12 months (Figure 1). Univariate analysis showed significant correlation of persistent B-cell depletion with diagnosis of MPA vs GPA (p<0.001), ANCA anti-MPO vs anti-PR3 (p=0.009), higher serum creatinine (p<0.0001) and older age (p=0.004) (Figure 2). Sex, plasma-exchange at induction, steroid pulses, cumulative dose of RTX and maintenance therapy did not affect B cell recovery. Multivariate analysis confirmed significant association between B cell recovery and better renal function (RR 2.655, IC 1.254-5.615, p= 0.011) and clinical diagnosis of GPA (RR 2.466, IC 1.211-5.021, p=0.013). Conclusion After a single course of RTX for remission induction, we observed a very long-lasting B cell depletion in the large majority of our patients. Clinical diagnosis of MPA and a worse renal function were significantly correlated to persistent B cell depletion. These data question the need for scheduled RTX re-treatments in all AAV patients regardless of clinical diagnosis and features.

scholarly journals Pregnancy outcomes following maternal treatment with rituximab prior to or during pregnancy: a case series

2021 ◽  
Author(s):  
Kirstie Perrotta ◽  
Elizabeth Kiernan ◽  
Gretchen Bandoli ◽  
Rachel Manaster ◽  
Christina Chambers
Keyword(s):  
B Cell ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Pregnancy Outcomes ◽  
Case Series ◽  
Outcome Data ◽  
Adverse Outcomes ◽  
Cell Depletion ◽  
Premature Delivery ◽  
B Cell Depletion

Abstract Objective Rituximab is a CD20-directed cytolytic antibody used for non-Hodgkin lymphoma, chronic lymphocytic leukaemia, and rheumatoid arthritis, and off-label for juvenile idiopathic arthritis, multiple sclerosis and lupus. Due to concerns about infant B cell depletion, the manufacturer recommends avoiding rituximab throughout pregnancy and for 12 months prior to conception. This study aims to add to the limited data on pregnancy outcomes in women with exposure to rituximab. Methods Data were obtained from MotherToBaby Pregnancy Studies. Participants were prospectively enrolled into this observational study between 2007 and 2019. Pregnancy exposure and outcome data were collected from medical records, telephone interviews, and dysmorphology examinations. Outcomes examined include spontaneous abortion, stillbirth, premature delivery, pregnancy complications, major and minor anomalies, small for gestational age, neonatal complications, and serious infections. Results We classified 19 women with exposure to rituximab into three groups. Group A included three women who received rituximab during pregnancy. Group B included three women who received their last infusion before conception, but had assumed pregnancy exposure due to the drug’s long half-life. Group C included 13 women who used rituximab in the two years prior to pregnancy, with the last infusion given no sooner than five half-lives prior to conception. Three children had a major structural defect. Preterm delivery occurred in two pregnancies, and two infants were small for gestational age on birth weight. No cases of B cell depletion were reported. Conclusion No pattern of major structural anomalies or other adverse outcomes were reported in this case series.

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