Use Of Rituximab Research Articles

The successful use of rituximab in IgA nephropathy patients with podocytopathy: a case series.

Immunoglobulin A nephropathy (IgAN) with podocytopathy is a rare pathological type of glomerular disease. The use of rituximab (RTX) in the treatment of glomerular diseases has increased in recent decades, but the efficacy of RTX in the treatment of patients with IgAN and podocytopathy has rarely been reported. This was a single-centre retrospective study of IgAN patients with podocytopathy who were treated with RTX as second-line therapy was conducted at our centre from 2019 to 2022. The aim of this study was to investigate the efficacy and safety of RTX in IgAN patients with podocytopathy. Seven out of eight patients met the criteria for complete remission following RTX therapy. Only one patient experienced adverse events (infectious diarrhoea and pulmonary infection) and experienced relapse 6 months after RTX therapy. The maximum relapse-free time after RTX therapy was 20 months, while the maximum relapse-free time before RTX therapy was only 6 months. The number of relapses before RTX therapy (per year) was one to four; moreover, seven patients did not relapse and maintained remission at the last follow-up despite steroid withdrawal after RTX therapy. Overall, RTX effectively reduced proteinuria, increased the maximum relapse-free time, reduced the number of relapses per year and helped patients stop steroid use as soon as possible. RTX also helped most patients achieve clinical remission. RTX appears to be an effective and safe alternative for treating IgAN patients with podocytopathy with steroid dependence or frequent relapse.

Factors influencing mortality in COVID-19-associated mucormycosis: The international ID-IRI study.

The emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), triggered a global pandemic. Concurrently, reports of mucormycosis cases surged, particularly during the second wave in India. This study aims to investigate mortality factors in COVID-19-associated mucormycosis (CAM) cases, exploring clinical, demographic, and therapeutic variables across mostly Asian and partly African countries. A retrospective, cross-sectional analysis of CAM patients from 22 medical centers across eight countries was conducted, focusing on the first 3 months post-COVID-19 diagnosis. Data collected through the ID-IRI included demographics, comorbidities, treatments, and outcomes. A total of 162 CAM patients were included. The mean age was 54.29±13.04 years, with 54% male. Diabetes mellitus (85%) was prevalent, and 91% had rhino-orbital-cerebral mucormycosis. Surgical debridement was performed in 84% of the cases. Mortality was 39%, with advanced age (hazard ratio [HR] = 1.06, [P<.001]), rituximab use (HR=21.2, P=.05), and diabetic ketoacidosis (HR=3.58, P=.009) identified as risk factors. The mortality risk increases by approximately 5.6% for each additional year of age. Surgical debridement based on organ involvement correlated with higher survival (HR=8.81, P<.001). The utilization of rituximab and diabetic ketoacidosis, along with advancing age, has been associated with an increased risk of mortality in CAM patients. A combination of antifungal treatment and surgical intervention has demonstrated a substantial improvement in survival outcomes.

COVID-19 Vaccination Before Initiating Rituximab Treatment Induces Strong Serological Response in Autoimmune Rheumatic Disease, Reducing Post-Pandemic Concerns About the Impact of Rituximab.

Rituximab (RTX)-treated patients exhibit suboptimal responses to COVID-19 vaccines. However, existing research primarily involves patients already receiving RTX when vaccines were introduced, failing to account for the current landscape where patients are vaccinated before initiating RTX. Our objective was to compare the serological response to COVID-19 vaccines in patients vaccinated before or after RTX initiation. We included 254 RTX-treated patients with autoimmune inflammatory rheumatic diseases (AIIRDs) and 113 blood donors (BDs) in a retrospective, observational cohort study. Patients were categorized based on the timing of RTX treatment relative to primary COVID-19 vaccination. Serological vaccine responses were assessed using three immunoassays, and logistic regression analysis was used to identify predictors of serological response. Patients vaccinated before initiating RTX treatment had significantly higher seroconversion rates of SARS-CoV-2 immunoglobulin G (87%) and neutralizing antibodies (91%) compared with those receiving RTX before and after vaccination (n = 132) (61% and 65%, respectively). In the logistic regression analysis, a positive serological response was associated with the number of vaccines administered >9 months after the last RTX treatment. Patients receiving the highest number of vaccines with >9 months after RTX showed a response comparable to that of the BDs. Vaccinating before RTX initiation yields a robust serological response in patients with AIIRDs. Furthermore, we highlight the reversibility of antibody impairment after RTX treatment cessation, provided that adequate vaccinations occur within a minimum of 9 months after RTX. Our findings offer essential insights for clinical decision-making regarding COVID-19 vaccination and RTX treatment, alleviating concerns about future RTX use.

Rituximab in the treatment of progressive interstitial lung disease associated with the antisynthetase syndrome

ObjectiveTo assess the real-world, long-term effectiveness of rituximab (RTX) as a rescue therapy in patients with antisynthetase syndrome and progressive interstitial lung disease (ASS-ILD).MethodsMulticentre observational retrospective longitudinal study of a cohort of patients with ASS-ILD that started treatment with RTX due to recurrent or ongoing progressive ILD despite therapy with glucocorticoids and immunosuppressants.ResultsTwenty-eight patients were analyzed. Examining the entire study population, before treatment with RTX the mean decline in %pFVC and %pDLCO from the ASS-ILD diagnosis to the initiation of RTX treatment (T0) was -6.44% and -14.85%, respectively. After six months of treatment, RTX reversed the decline in pulmonary function test (PFT) parameters: ∆%pFVC +6.29% (95% CI: -10.07 to 2.51; p=0.002 compared to T0) and ∆%pDLCO +6.15% (95% CI: -10.86 to -1.43; p=0.013).Twenty-four patients completed one year of therapy and 22 two years, maintaining the response in PFT: ∆%pFVC: +9.93% (95% CI: -15.61 to -4.25; p=0.002) and ∆%pDLCO: +7.66% (95% CI: -11.67 to -3.65; p<0.001). In addition, there was a significant reduction in the median dose of prednisone, and it could be suspended in 18% of cases. In 33% of patients who required oxygen therapy at the start of treatment, it could be discontinued.The frequency of adverse events reached 28.5% of cases.ConclusionBased on our results, RTX appears to be effective as rescue therapy in most patients with recurrent or progressive ASS-ILD unresponsive to conventional treatment. The use of RTX was well tolerated in the majority of patients.

Rituximab Therapy for Immune-Mediated Neurological Diseases: Our Experience at a Tertiary Care Centre.

Rituximab (RTX) is a monoclonal anti-CD20 chimeric antibody that inhibits B cell activity. However, it is an appealing substitute for traditional immunomodulatory drugs as a swiftly acting, targeted therapy with mounting evidence of efficacy and tolerance in numerous neuroinflammatory conditions. We discuss the scientific evidence for the use of RTX in neurological illnesses, as well as the dose, safety, and other practical elements of prescription. This study aims to assess and correlate the effects of RTX on immune-mediated neurological disorders. The primary objective of this study is to determine the outcomes in patients treated with RTX for the following conditions: myasthenia gravis (MG), autoimmune encephalitis, multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody disease (MOGAD), immune-mediated peripheral neuropathy, and inflammatory muscle disease. The secondary objective is to assess adverse drug reactions in patients treated with RTX. This is a prospective observational study conducted at a tertiary care centre. The data were analyzed for the period from May 2022 to May 2024. Approval was obtained from the institutional ethics committee before commencing the study, andwritten informed consent was obtained from all patients. A total of 56 patients were included in the study. The distribution of patients according to diseases is as follows: MG (17), MS (11), NMOSD (10), MOGAD (7), immune-mediated peripheral neuropathy (6), autoimmune encephalitis (3), and inflammatory muscle disease (2). However, one patient was lost to follow-up in the autoimmune encephalitis group. All patients experienced improvements in symptoms, and no relapse episodes have been reported except for one patient who had a relapse in the inflammatory muscle disease group. During the infusion process, some adverse drug reactions, such as chills and rigors, were observed, and two patients experienced major side effects, such as Pott's disease and cryptogenic organizing pneumonia. Nevertheless, overall, rituximab shows promise as an off-labelimmunosuppressive treatment for the aforementioned neurological immune-mediated diseases.

Clinical Features and Prognosis of Patients with CD5+ Diffuse Large B-Cell Lymphoma

To analyze the clinical characteristics and prognosis of patients with CD5+ diffuse large B-cell lymphoma (DLBCL). The clinical data of 161 newly treated DLBCL patients in Gansu Provincial Hospital from January 2013 to January 2020 were retrospectively analyzed. According to CD5 expression, the patients were divided into CD5+ group and CD5- group. The clinical characteristics and prognosis of the two groups were statistically analyzed. The median age of patients in CD5+ group was 62 years, which was higher than 56 years in CD5- group (P =0.048). The proportion of women in CD5+ group was 62.96%, which was significantly higher than 41.79% in CD5- group (P =0.043). The proportion of patients with IPI score > 2 in CD5+ group was 62.96%, which was higher than 40.30% in CD5- group (P =0.031). Survival analysis showed that the median overall survival and progression-free survival time of patients in CD5+ group were 27(3-77) and 31(3-76) months, respectively, which were both shorter than 30(5-84) and 32.5(4-83) months in CD5- group (P =0.047, P =0.026). Univariate analysis showed that advanced age, positive CD5 expression, triple or double hit at initial diagnosis, high IPI score and no use of rituximab during chemotherapy were risk factors for the prognosis of DLBCL patients. Further Cox multivariate regression analysis showed that these factors were also independent risk factors except for advanced age. CD5+ DLBCL patients have a worse prognosis than CD5- DLBCL patients. Such patients are more common in females, with advanced age and high IPI score, which is a special subtype of DLBCL.

Diagnosis, treatment, and long-term outcomes of pediatric pemphigus: a retrospective study at tertiary medical centers.

Pediatric pemphigus is a rare bullous disease that representsa diagnostic and therapeutic challenge; evidence on patients' response to various treatments and long-term surveillance data are lacking. We aimed to investigate pediatric pemphigus patients' characteristics, diagnosis, therapeutics, response, and long-term follow-up. This is a retrospective study of all pemphigus patients aged <18 years, diagnosed between 2000 and 2023, from three tertiary medical centers in Israel. The diagnosis was confirmed by positive immunofluorescence. Twelve pediatric pemphigus patients were included (mean age 10.7 ± 4.3 years, male:female ratio 1:1). Mean diagnostic delay was 11.1 ± 12.6 months (range 1.8-36 months). Most patients had pemphigus vulgaris with mucosal involvement (58.3%). First-line treatment for all patients included systemic corticosteroids (sCS), with a treatment duration (including tapering down) of 28 ± 18.4 months. Hospitalization did not yield better outcomes. Only three patients achieved sustained complete response with sCS treatment (25.0%), and the rest required additional therapeutics, most commonly rituximab. Rituximab showed a good safety profile and therapeutic response. Follow-up was recorded up to 18.1 years after diagnosis (mean: 5.6 years). Three of five patients with information available more than 5 years after the pemphigus diagnosis still exhibited disease symptoms. Pediatric pemphigus is associated with a significant diagnostic delay. While sCS can induce remission in most patients as a first-line treatment, long-term disease control requires additional immunomodulators. Long-term follow-up reveals a chronic yet mostly benign disease course in this population and advocates for the use of rituximab in pediatric pemphigus patients.

#340 Time dependent changes in the treatment of relapsing Minimal Change Disease – a multicenter cohort study

Abstract Background and Aims Prednisolone monotherapy is the most used initial immunosuppressive treatment for nephrotic syndrome in adults with Minimal Change Disease (MCD) but choice of treatment in relapsing MCD is not as well described. With the introduction of new drugs and increased concern relating to the adverse events of prednisolone, treatment might have changed over time. The aim of this study is to describe changes in daily clinical practice of relapsing MCD within the last 35 years. Method A multicenter, retrospective analysis of adult patients with biopsy proven MCD from 13 hospitals from 1987-2022 in Denmark and the Netherlands. Patients were identified from the pathology registers. Information on treatment and clinical outcomes was retrieved from health records. Relapse is defined when the nephrologist found indication to restart an immunosuppressive treatment or increase the ongoing immunosuppression in patients in partial or complete remission. Results We included 167 Dutch and 72 Danish patients (n = 239) with MCD. Most patients (n = 205, 86%) were initially treated with prednisolone monotherapy. Overall, 93% (n = 220) gained remission and 56% (n = 123) of those who went into remission had one or more relapse with 68% of these occurring in the first year after remission. At the time of relapse, 89% were in complete remission and 11% were in partial remission. At first relapse, prednisolone monotherapy was the most prescribed treatment both before and after 2010 (69% and 45%, respectively), while the use of CNI tripled after 2010 (p = 0.002) (10% to 32%). At second relapse, prescription of CNI after 2010 showed a five-fold increase compared with before 2010 (49% vs 10%, respectively) while the use of prednisolone monotherapy was halved (50% to 24%). The use of cyclophosphamide decreased by two-thirds (32% to 10%) after 2010. Before 2010, 54% of patients received prednisolone monotherapy for their third to 14th relapse, but after 2010 this decreased to 26%. The use of rituximab and CNI both increased and after 2010 these were both prescribed to about one third of patients at third to 14th relapse. The use of cyclophosphamide decreased from 30% to 2% comparing before and after 2010. Rituximab was only used after 2010, and more frequently with the number of relapses (6% at first relapse and 36% at third to 14th relapse). Regardless of the choice of treatment the rates of remission were high. Conclusion The treatment of relapses has changed over time with a reduced use of prednisolone monotherapy and cyclophosphamide and increased use of CNI and rituximab.

#581 Therapeutic management of patients with GPA and MPA: a nationwide observational study in France

Abstract Background and Aims Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are rare systemic necrotizing vasculitis. Treatment per rituximab was approved in 2013, and recent guidelines recommend corticosteroids sparing. A real-life pharmacoepidemiologic retrospective study was set up to describe the demographic characteristics of hospitalized GPA and MPA patients and compare the treatments of patients included before rituximab approval (over 2010–2012, Group 1) and after rituximab approval in France (over 2014–2017, Group 2). Method All adult patients hospitalized for GPA or MPA between January 1, 2010 and December 31, 2017 were included from the French National Health Insurance database (SNDS) which covers &amp;gt;97.5% of French population. Patients were separated in 2 groups according to their date of inclusion: (i) Over 2010-2012 for group 1 and (ii) over 2014-2017 for group 2. Descriptive analyses were performed. Kaplan-Meier method was used to model the duration of treatment induction and maintenance. Fine and Gray tests were used to compare treatment phases durations. Results The study involved 4445 prevalent GPA patients (including 1578 incident patients) and 1833 prevalent MPA patients (878 incident patients). Group 1 consisted of 694 and 283 GPA and MPA patients respectively; group 2 included 668 and 463 GPA and MPA patients respectively. Mean age and the sex ratio were stable over time. During the first year after inclusion, the proportion of patients with first-time hospitalized infections, diabetes or renal failure increased between 2010–2012 and 2014–2017. Between the two inclusion periods, the proportions of patients treated with rituximab increased both in the induction and maintenance phases whereas treatment with azathioprine declined (Table 1). As for methotrexate, cyclophosphamide and glucocorticoids, the proportions remained stable. Conclusion According to real-life, pharmacoepidemiologic data in GPA and MPA patients, the introduction of rituximab reduced the use of azathioprine without affecting the use of glucocorticoids, although corticosteroids sparing should become a standard of care with the emerging treatment regimens. No reductions in adverse events were observed with the increased use of rituximab.

#1681 Efficacy and safety of combined treatment with rituximab and low doses of cyclophosphamide for ANCA associated renal vasculitis

Abstract Background and Aims Current guidelines recommend the use of rituximab (RTX) or cyclophosphamide (CP) as induction treatment for ANCA-associated vasculitis (AAV) with renal involvement. Some authors have described the combination of CP and RTX in the treatment of severe AAV, and recently a regimen of 6 cycles of low-dose CP combined with RTX has been used with good results. The aim our study was to compare the efficacy and safety of combined treatment with even lower doses of intravenous CP (2-3 cycles) and RTX, compared to standard treatment with RTX. Method We conducted a retrospective study that included 14 patients with histologically confirmed AAV, treated with an induction treatment scheme of corticosteroids, RTX and 2-3 cycles of intravenous CP. A case-control analysis was performed with 16 patients who received only corticosteroids and RTX in the same period, matched by propensity score for age, creatinine at presentation and histological parameters (sclerosed glomeruli, epithelial crescents and normal glomeruli). We compared renal and overall survival, and complications from immunosuppression in both groups. Results At presentation, patients treated with the combined regimen had a mean age of 67 ± 12.1 years, a mean glomerular filtration rate estimated by CKD-EPI of 19.8 ± 11.1 ml/min/1.73 m2, proteinuria of 1.6 (0.81- 1.84) g/24 hours and initial BVAS score of 18.5 ± 6.9. 78.6% of the patients were anti-MPO positive and 21.4% were anti-PR3 positive. According to Berden's classification, 85.7% had a mixed variant, 7.1% crescentic and 7.1% sclerotic, in the renal biopsy. The mean dose of CP was 1445 ± 384 mg, and of RTX was 2g. 28.6% required dialysis at presentation, of which 75% recovered kidney function. The duration of steroid treatment was 8 (4.6-16.9) months. Remission rate at 6 months was 71.4%, and after a median follow-up of 20 (15-35) months, 92.9% had remitted. During follow-up, 50% had serious infections; and at the end, 7.1% progressed to end-stage chronic kidney disease (ESKD). 21.4% of the patients included ended up dying. In comparison with the control group, patients who received the combined treatment had a higher remission rate (92.9% vs. 75%), a lower relapse rate (15.4% vs. 35.7%), lower progression to ESKD (7.1% vs. 20%) and lower mortality (21.4% vs 37.5%), with no differences for serious infections. Conclusion The association of low doses of cyclophosphamide to rituximab induction treatment could improve the prognosis in patients with severe ANCA-associated renal vasculitis.

#1577 Rituximab in patients with primary podocytopathies: case series

Abstract Background and Aims Rituximab (RTX) has been reported as an effective treatment alternative in primary forms of minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) associated with steroid dependence and frequent relapses. However, the optimal RTX regimen and the outcomes of further doses of RTX remain unclear. This study aimed to evaluate the use of induction and maintenance RTX therapy for adults with primary podocytopathies. Method We performed a retrospective case series on adult patients with steroid-dependent podocytopathies who received an induction RTX therapy. Maintenance therapy was performed at physician's discretion. Remission and relapse rates, concomitant corticosteroids and immunosuppressants use, B-cell depletion and adverse events were analyzed. Results Fourteen patients (mean age at start of RTX 29.1 ± 21.9 years) with MCD (n = 7) or FSGS (n = 7) were treated with 2 doses of 1000 mg 2 weeks apart (n = 13) or four doses of 375 mg/m2 (n = 1) of RTX. At last follow-up (mean 47.3 ± 101.7 months) ten patients were in complete remission and two remained in partial remission. A reduction in the number of relapses, number of patients under corticosteroids and immunosuppressants, and dose of prednisolone was observed when compared to baseline [14 (100%) vs 5 (35.7%); 8/14 (57.1%) vs 4/12 (33.3%); 13/14 (92.9%) vs 7/12 (58.3%); 20 mg/day vs 5.25 mg/day, respectively]. Maintenance RTX therapy was used in six patients, with sustained complete remission. Infusion reactions were observed in four patients (one required treatment withdrawal). Conclusion Our findings support the use of RTX for a steroid-free remission in podocytopathies and suggest that maintenance RTX is well-tolerated and associated with prolonged remission. Further studies are needed to confirm its efficacy and safety and establish the optimal induction and maintenance RTX regimen in steroid-dependent podocytopathies.

#2154 Rituximab in the treatment of PLA2R-associated membranous nephropathy: insights from a hospital centre experience

Abstract Background and Aims Rituximab (RTX) is recommended as the first-line therapy for PLA2R-associated Membranous Nephropathy in patients with a moderate to high risk of progressive loss of kidney function, according to the KDIGO 2021 guidelines. This recommendation is based on the superior long-term efficacy and improved safety profile of RTX. This study aims to assess the use of RTX for the treatment of for PLA2R-associated Membranous Nephropathy at a hospital centre. Method A retrospective study was conducted on patients diagnosed with PLA2R-associated Membranous Nephropathy who underwent their first RTX administration between 2017 and 2022 at a tertiary hospital centre. Exclusion criteria involved patients with less than 6 months of follow-up post-RTX. The study evaluated the occurrence of immune remission, clinical remission, as well as instances of immune and proteinuria relapse, and recorded any adverse events. Results A total of 11 patients were included, with 54.5% being male. The mean age was 60.4 ± 14.7 years, and the median disease duration 69.0 [8.0-87.0] months. The mean follow-up time post-RTX was 36.7 ± 23.3 months. Regarding the risk of progressive loss of kidney function, 8 patients were classified as high risk, 1 as moderate risk, and 2 as low risk. RTX served as the initial immunosuppressive therapy for only 3 patients. Additional immunosuppressive therapies post-RTX, including further RTX doses, were administrated in 63.6% (n = 7) of patients. No response was observed in 18.2% (n = 2). Immune remission was achieved in 81.8% (n = 9), mean time of 3.8 ± 1.4 months. Within this group 55.5% (n = 5) patients achieved complete remission, 22.2% (n = 2) experienced partial remission, and 22.2% (n = 2) maintained nephrotic proteinuria, with immune remission consistently preceding clinical remission. Relapses occurred in 45.5% (n = 5), at a mean time of 20.8 ± 13.5 months. Patients with lower serum albumin at time of RTX administration were more likely to experience non-response or relapse (T (9) = 2.51, p = 0.03), with a Youden Index cut-off of 3.2 g/dL, demonstrating a sensitivity of 100% and a specificity of 85.7%. Patients with anti-PLA2R exceeding 150 RU/mL exhibited no response or relapsed. Four patients (36.4%) remained free of relapses throughout the entire follow-up period, mean time of 22.8 ± 10.0 months, with 1 keeping RTX maintenance therapy. During the 6 months post-RTX, 36.4% (n = 4) of patients experienced adverse events. Conclusion Rituximab demonstrated both efficacy and safety in treating PLA2R-associated Membranous Nephropathy. However, lower serum albumin levels and anti-PLA2R &amp;gt; 150 RU/mL at time of RTX administration were associated with worse response. Given the substantial need for additional immunosuppression, and considering lower albumin values and higher anti-PLA2R titres as risk markers, it is recommended to closely monitor these patients. Anti-PLA2R titres showed a meaningful association with disease activity, preceding changes in proteinuria levels. Therefore, tracking disease progression through the measurement of anti-PLA2R titres not only guides clinical decisions but also enables a judicious approach to subsequent RTX administrations.

#1622 Minimal changes disease and myasthenia gravis: a logical association

Abstract Background and Aims Minimal changes disease (MCD) is responsible for 10-25% of nephrotic syndrome cases in adults. It can have a primary or secondary aetiology, being associated with diseases like infections, atopy or even haematological malignancies. There is a described association between MCD and myasthenia gravis (MG) in the literature, which we will explore in this case report. Clinical Case An autonomous 67 years old female, healthy except for overweight develops diplopia and dysphagia, being diagnosed with anti-musk MG (antibodies titters 2,2002 nmol/L). Thymoma presence was excluded by CT scan. She starts oral treatment with pyridostigmine without response. Two months later she develops generalized oedema. Analytically she had normal kidney function (Cr 0.7 mg/dL; BUN 28.5 mg/dL), hypoalbuminemia (2.09 g/dL), dyslipidaemia and nephrotic proteinuria of PCR 8g/g creat, without leucoeritrocyturia. Reno-vesical echography was normal. No alterations in immunological study except for a low IgG 396 mg/dL. Anti-PLA2R was negative. Kidney biopsy was performed, having 4 glomerulus that looked normal in optical microscopy. In our centre we do not have electronic microscopy available, so the biopsy was interpreted as MCD. She started prednisolone (PDN) 1 mg/kg/day with clinical improvement and resolution of the symptoms and proteinuria (0.062 g/g creat). In November 2022, while she was tapering the PDN, she had a myasthenic crisis, with MCD recurrency. She did 5 plasmapheresis sessions, the PDN dose was increased to 1 mg/kg/day and two rituximab administrations (1000 mg each) were done. There was an improvement in MG symptoms during 3 weeks and then she aggravated again. The proteinuria slowly decreased during 6 weeks until RPC 1.3 g/g creat and then started to aggravate when the corticosteroids were tapered. It was decided to initiate mycophenolate mofetil (MMF), there was improvement and both diseases are controlled until today, the patient is asymptomatic under 7.5 mg/day of prednisolone, with a PCR 0.2 g/g creat. Discussion The production of a circulating permeability factor by abnormal T cells, that causes the podocytes damage, is one of the possible explanations for MCD. There are reports of improvements with plasmapheresis (PF) by permeability factor remotion from circulation. MG is also caused by T cells antibodies attack, but the attack occurs against channels essential for the neuromuscular membrane function. The similarities of the mechanisms make the existence of a common branch in the t cells dysregulation seem plausible. Anti musk MG is very responsive to PF but it has a limited effect in time. Rituximab depletes B cells responsible for promoting the impaired T cells responses. It has been associated with longer remissions in cortico-sensitive MCD with relapsing disease. The exact same mechanism occurs when rituximab is used in MG. In this case the patient did not have a satisfactory response to rituximab as the patient kept dependent of high PDN doses, so we decided to initiate MMF with a complete remission of both pathologies and allowing the use of lower PDN doses. Take Home Message The association between MCD and myasthenia gravis is rare, especially in patients without thymoma. When we analyse the diseases physiopathology, we find common mechanisms that can justify the association. The identification of this relation can be advantageous making possible early rituximab use, that has been showing good results in both pathologies. In this particular clinical case, there was a recurrence with rituximab when we tapered the PDN, so the patient started MMF with good response and allowing lower PDN doses.

#1283 Rituximab in addition to plasma exchange, cyclophosphamide and steroids for treatment of anti-GBM disease

Abstract Background and Aims Anti-GBM disease is a rare antibody-mediated vasculitis, usually treated with plasma exchange (PEX), cyclophosphamide (CYC) and steroids. There are limited data regarding the use of B-cell depleting therapies such as rituximab (RTX). We investigate the use of the addition of rituximab for the treatment of Anti-GBM disease. Method Ten-year (2012-2023) single-centre retrospective cohort study of patients with anti-GBM disease treated with or without rituximab, in addition to standard care, as first-line therapy. A Cox-proportional hazards regression model incorporating age, sex, ANCA status, dialysis need at presentation, lung haemorrhage, CYC (oral or IV) and RTX treatment was used to identify disease/treatment factors associated with outcome (death, end-stage kidney disease [ESKD], infection). Results Forty-five patients are included; baseline demographics, disease characteristics, treatments and outcomes are summarised in Table 1. In the Cox regression model, only increasing age was associated with risk of death (HR 1.08 [95% CI 1.02-1.17]). Age (HR 1.04 [1.01-1.08]), female sex (HR 4.93 [1.80-4.87]), and dialysis need at presentation (HR 5.28 [1.54-17.53]) were associated with ESKD-risk. Increasing age (HR 1.04 [1.00-1.09] and ANCA positivity (HR 3.08 [1.14-8.71]) were associated with risk of infection. The addition of rituximab was not significantly associated with risk of death (HR 0.82 (0.24-2.87), ESKD (HR 1.54 [0.64-3.96]) or infection 2.06 [0.67-5.71]. Conclusion Addition of rituximab to standard treatment for anti-GBM disease was not associated with improved renal outcome or survival benefit. However, rituximab use permitted lower cumulative doses of CYC and reduction in the number of PEX, without an increased risk of infection. Rituximab may have a role as a CYC- and PEX-sparing treatment in patients with anti-GBM disease.

#2256 Safety and effectiveness of avacopan beyond 52 weeks: experience to date in the Early Access Program (EAP)

Abstract Background and Aims ANCA-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), is characterized by a high burden of organ damage, as well as increased mortality [1]. Both the disease itself and the immunosuppression required for its management contribute significantly to poor prognosis [2]. Avacopan is a first-in-class C5aR1 antagonist that demonstrated efficacy and safety over 52 weeks in patients with GPA or MPA, and was associated with a significantly lower requirement of glucocorticoids for disease management [3]. Significant data on long-term avacopan use in the context of real-life settings are sparse. Here, we describe experience with avacopan in 59 patients with GPA or MPA treated beyond 52 weeks within an ongoing Early Access Program (EAP). Method Patients with newly diagnosed or relapsing severe, active GPA or MPA were treated in the EAP. Safety data, including lack of effect and other events (i.e., relapse or worsening of disease) in these patients were recorded in a CSL Vifor safety database from Feb 2019 – Dec 2023. We performed analysis of these data for patients treated beyond 52 weeks. Results 237 patients received ≥ 1 dose of avacopan with a median overall treatment duration of 7 months (range 1-45) at the time of this analysis. 43 of 237 patients had at least one adverse event (AE) reported (18.1%) with a median of 2 (range 1-11) AEs per patient; 19/237 (8.0%) patients experienced a serious AE (SAE). Most of the reported AEs belonged to the System Organ Classes (SOC) of infections and infestations, and gastrointestinal disorders, with COVID-19 being the most frequently-reported event. At the time of this analysis, 59 patients continued treatment beyond 52 weeks, with a median overall duration of treatment of 16 months (range 13-45). Within this group, 12 of 59 patients experienced at least one AE (20.3%) with a total of 46 AEs. 9/ 12 patients reported AEs during the first 52 weeks treatment, while in 3 patients the date of AE occurrence was not available (Table 1). The results in these 59 patients are summarized below. 6 patients experienced at least one SAE (7 SAEs in total). As in the overall EAP population, most of the reported AEs belonged to the SOC of gastrointestinal disorders, followed by infections and infestations, with COVID-19 being the most common AE occurring in 3 patients. 18 AEs were assessed as related to avacopan, with 3 events in 2 patients being classified as serious (deep vein thrombosis [DVT] in one patient, lower urinary tract symptoms and JC polyomavirus test positive in the second). The patient experiencing DVT temporary discontinued avacopan. In the patient who developed lower urinary tract symptoms with active replication of JC virus (1.728.405 copies/mL), avacopan was permanently withdrawn. According to the reporter, the concomitant use of prednisone, rituximab and denosumab could have contributed to these events. Three patients experienced events implying worsening of underlying disease. These events occurred within the first 52 weeks of treatment. The first patient experienced a vasculitis flare 6 months following avacopan initiation that coincided with an unintended dose reduction to 20 mg BID due to a product supply issue. The second patient experienced a worsening of known GPA related mononeuritis multiplex, possibly induced by concomitant treatment with isoniazid and a likely result of pharmacological interaction between rifampicin and avacopan. The third patient experienced an increase of creatinine, proteinuria and microhematuria in the context of avacopan withdrawal due to other events. Conclusion These results confirm that avacopan has a manageable safety profile with the potential to be effective beyond 52 weeks in sustaining disease control. Limitations of this analysis include potential underreporting, incomplete data and no control group.

#1960 Incidence of cancer in ANCA associated vasculitis (AAV)

Abstract Background and Aims We investigated the incidence rate and type of cancer in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in our Institute. Method We retrospectively included 210 patients with AAV [106 patients with microscopic polyangiitis (MPA), 93 with granulomatosis with polyangiitis (GPA) and 11 patients with eosinophilic GPA (EGPA)], and reviewed their medical records. We collected demographic, clinical and laboratory data. We selected patients with history of cancer, patients diagnosed with paraneoplastic AAV and patients who developed malignant disease after AAV. We reviewed the use of glucocorticoid and immunosuppressive drugs. Results Between 1993-2024 there were 16 patients with AAV who had cancer during their life in our Department. There were eight patients with malignancy-associated AAV. Two patients were simultaneously diagnosed with kidney carcinoma and vasculitis. One patient's serum was positive for cytoplasmatic ANCA, the other patient's for pANCA. Complete resection of cancer and renal biopsy was performed, they got steroid monotherapy. Five patients were diagnosed with pANCA vasculitis a few months (1-5) after the diagnosis of malignancies (two pts with breast carcinoma, two pts with ovarium carcinoma, one patient with ventricular carcinoma). In one case the pAAV was established after 5 months of oropharyngeal tumor's resection. Two patients had history of malignancy (one pts had colon carcinoma 4 ys before the appearance of AAV, the other patient had breast carcinoma 10 ys before the AAV). In both cases there were examinations for malignancy with negative results. In these cases the vasculitis was not associated with carcinoma. The therapeutic approach included the use of corticosteroids, plasmapheresis, and cyclophosphamide or rituximab. Six patients were observed malignancy 0.5-10 years after the diagnosis of AAV. There was one pancreas, one ventricular, two lung and two bladder carcinoma. Conclusion In our study we focused on the relationship of malignancy and AAV. Between the 210 patients with AAV eight cases (3.8%) were malignancy-associated, in one case cANCA associated, the other cases pANCA was presented. Treating paraneoplastic vasculitis can be challenging. Individualized treatment strategy tailored to patients' needs is crucial. Six patients were diagnosed with solid tumor during the follow-up. The cumulative overall cancer incidence rates were 1.4% and 2.8% at 5 and 10 years, respectively. Only in one patient with bladder cancer was treated with the cumulative CYC doses ≥ 36 g. No leukemia or non melanotic skin cancer (NMSC) was represented contrary to other studies.

#1739 Combination rituximab &amp; low-dose IV cyclophosphamide induction therapy for severe multi-system eosinophilic granulomatosis with polyangiitis

Abstract Background and Aims Current guidelines advise rituximab (RTX) or cyclophosphamide treatment for organ-threatening disease in eosinophilic granulomatosis with polyangiitis (EGPA). However, conventional treatment is often limited by partial efficacy, toxicity, high relapse rate and steroid dependency. We investigate the use of a combined RTX, low-dose cyclophosphamide, and steroid regimen for treatment of severe EGPA. Method Single-centre retrospective cohort study of patients treated with a combination induction regimen for severe EGPA (with kidney, cardiac or neurological involvement) between 2012-23. Data reported as median (±IQR) Results Eighteen patients (10 male; age 56 years [52-62]) are included. At treatment, BVAS was 16.3 [14-20], peak eosinophil count 9.3 × 109/L [5-13], C-reactive protein (CRP) 122 mg/L [80-193]. Eleven cases were ANCA positive (10 MPO-, 1 PR3-ANCA.) The proportions of patients affected by active/new respiratory, ENT, neurological, and gastrointestinal disease were 18/18 (100%), 14/18 (78%), 11/18 (61%), and 1/18 (6%), respectively. 11/18 (61%) had cardiac involvement (troponin 10345 ng/L [1240-7621]) and 6/18 (33%) had necrotising glomerulonephritis confirmed by renal biopsy (creatinine 123 µmol/L [83-167]). Cumulative cyclophosphamide dose was 3.5g [3.0-3.5] and total RTX dose was 2g. Initial prednisolone dose was 0.5-1.0 mg/kg/day, and this was rapidly weaned to 5 mg daily at a median time of 6.1 months [3.9-7.2], and 9/18 (50%) had steroids withdrawn completely by 11.7 months [4.6-20.6]. First-line maintenance treatment was azathioprine or MMF. By 6 months, all achieved disease remission as assessed by BVAS (all 0) and improved laboratory parameters: CRP 1 mg/L, eosinophil count 0.1 × 109/L, and ANCA testing negative. In those with renal disease, kidney function improved or stabilised in all (creatinine 95 µmol/L). In those with cardiac disease (11/18), magnetic resonance imaging was performed at baseline and at follow up (median time of 3.7 months) in all patients. Of these, 9/11 (82%) had oedema on initial scan and this improved in all cases; 10/11 (91%) had late gadolinium enhancement at baseline, which persisted in every case, though with significantly lower burden. The median follow-up period was 38 months [14-55]. At 1, 3 and 5 years, 100%, 92% and 76% of patients were in sustained remission (Fig. 1A). Three patients experienced relapse; one patient had major relapse with skin involvement requiring reinduction treatment; two patients had minor ENT relapse requiring retreatment with glucocorticoids. Infection-free survival at 1, 3 and 5 years was 94%, 78%, 62%, respectively (Fig. 1B). There were no deaths. Conclusion This regimen provided rapid disease control in patients with severe multi-system EGPA, including those with life-threatening cardiac manifestations, and enabled rapid glucocorticoid tapering and withdrawal. Disease-free remission was sustained during long-term follow up. Combination induction regimens may have a role in the treatment of organ-threatening disease in EGPA.

A retrospective analysis of the clinicopathological features and prognostic value of MAPK12 protein expression in diffuse large B-cell lymphoma.

Mitogen-activated protein kinase 12 (MAPK12), also known as p38γ, is a member of the p38 MAPK family and plays a crucial role in tumor occurrence and invasion. However, there is still uncertainty regarding MAPK12 involvement in diffuse large B-cell lymphoma (DLBCL). Our study investigated the expression of MAPK12 mRNA in various types of cancer using bioinformatic analysis. Furthermore, we performed immunohistochemistry (IHC) to detect the expression of MAPK12 in patients with DLBCL and compared clinical indicators and survival rates. We found that the high expression rate of MAPK12 was 43.1% in DLBCL patients. Several clinical indicators, including IPI scores, Hans classifications, LDH levels, and Ki-67 expression were closely associated with MAPK12 expression. Survival analysis revealed that higher expression of MAPK12 was significantly correlated with shorter progression-free survival (PFS) and overall survival (OS) in DLBCL patients. In addition, both univariate and multivariate analyses revealed IPI score, MAPK12 expression, and rituximab use as the independent OS risk factors (P < 0.05). To explore the functional role of MAPK12 in DLBCL, weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) were used to confirm the involvement of MAPK12 in the regulation of type II interferon production, positive regulation of lymphocyte proliferation, and other related biological processes. DLBCL patients have poor prognoses when MAPK12 levels are high, which is expected to be a therapeutic target and prognostic factor.

Epstein-Barr Virus Monitoring after an Allogeneic Hematopoietic Stem Cell Transplant: Review of the Recent Data and Current Practices in Canada.

Epstein-Barr virus-related post-transplantation lymphoproliferative disorder (EBV-PTLD) is a serious complication following hematopoietic stem cell transplantation (HSCT). A pre-emptive strategy using rituximab, which aims to manage patients early at the time of EBV reactivation to avoid PTLD, has been recommended by the most recent ECIL-6 guidelines in 2016. However, there is still a great heterogeneity of viral-load monitoring protocols, targeted patient populations, and pre-emptive treatment characteristics between centers, making precise EBV monitoring recommendations difficult. We conducted a literature review from the most recent publications between 1 January 2015 and 1 August 2023, to summarize the emerging data on EBV-PTLD prevention strategies in HSCT recipients, including the EBV-DNA threshold and use of rituximab. We also present the results of a survey of current practices carried out in 12 of the main HSCT centers across Canada. We confirm that pre-emptive rituximab remains an efficient strategy for EBV-PTLD prevention. However, there is an urgent need to perform prospective, randomized, multicentric trials with larger numbers of patients reflecting current practices to determine the best clinical conduct with regards to rituximab dosing, timing of treatment, and criteria to initiate treatments. Longer follow-ups will also be necessary to assess patients' long-term outcomes.

The landscape of real-world evidence of rituximab utilization and clinical outcomes in patients with cancer, rheumatoid arthritis, and multiple sclerosis: A scoping review.

Rituximab (RTX) is an anti-CD20 monoclonal antibody that is used to treat various conditions in cancer, rheumatoid arthritis (RA), and multiple sclerosis (MS). Although RTX has been used in the United States for almost 3 decades, questions remain regarding its real-world utilization and effectiveness. To describe the state of observational research and real-world evidence evaluating RTX in oncology, RA, and off-label use in MS. A broad search was conducted in MEDLINE, Embase, and CINAHL covering the period of January 2010 to June 2022. Two reviewers independently screened all identified records for each disease category (cancer, RA, MS) beginning with title review, followed by abstract, and full-text review to identify relevant publications to include in the final analysis. Data were extracted and summarized for each disease based on overall trends, similarities, and differences across included studies and stratified by disease state. A total of 260 studies met eligibility criteria, with 79 studies for the RA cohort, 144 for cancer, and 37 for MS. Across all disease cohorts, most studies (n = 189; 72.7%) were retrospective. 171 (65.8%) studies used hospital or electronic health record data as their data source and 65 (23.2%) used registry databases. Most studies (n = 153; 58.8%) assessed the effectiveness of RTX measured by disease-specific endpoints, followed by safety (n = 60; 23.1%), treatment patterns (n = 32; 12.3%), and descriptive analyses assessing treatment adherence and economic burden of disease (n = 16; 6.2%). Although safety was not the primary outcome for most studies, the majority of studies across all disease states still reported some form of safety measure. Conclusive statements on RTX's benefit varied across disease states, with MS having the most (n = 30; 81.1%) studies suggesting the drug's positive benefit. There were limited studies assessing RTX use, associated economic burden, and biosimilar switching. The findings underscore the need for health care providers to better understand the treatment landscape and utilization of RTX, particularly in terms of patient selection, timing of initiation, and long-term outcomes. Real-world evidence can help support health care decisions and treatment using rituximab.