First Dose Of Rituximab Research Articles

The Efficacy of Bepotastine Besilate Compared With Hydroxyzine Pamoate for Preventing Infusion Reactions to the First Dose of Rituximab in Patients With Non-Hodgkin Lymphoma: Protocol for a Phase II, Double-Blind, Multicenter Randomized Trial.

Rituximab, an anti-CD20 monoclonal antibody, can cause infusion reactions (IRs), especially during the initial rituximab infusion therapy. Generally, patients are administered a histamine H1-receptor antagonist before the rituximab infusion, along with an antipyretic analgesic, to prevent or reduce IRs. Multiple retrospective case-control studies indicate that the second generation of histamine H1-receptor antagonists might be more effective than the first generation in suppressing IRs caused by the rituximab infusion. This study aimed to assess the efficacy of first- and second-generation histamine H1-receptor antagonists for preventing IRs resulting from the initial infusion of rituximab in patients diagnosed with non-Hodgkin lymphoma. This is a phase II, double-blind, active-controlled randomized trial. It will be a multicenter study conducted across 3 facilities that aims to enroll a total of 40 patients diagnosed with non-Hodgkin lymphoma who will receive their initial rituximab infusion. Participating patients will be administered hydroxyzine pamoate or bepotastine besilate, representing first- or second-generation histamine H1-receptor antagonists, respectively. This will be combined with 400-mg acetaminophen tablets taken approximately 30 minutes before the first infusion of rituximab. The primary end point of this trial is to assess severe IRs, equivalent to grade 2 or higher as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0, that occur within a 4-hour period after the initiation of rituximab infusion. The secondary end points include assessing the severity of the initial IR, the maximum severity of the IR, and the duration between rituximab infusion initiation and the onset of the first IR within a 4-hour period. Additionally, the trial will evaluate histamine H1-receptor antagonist-induced drowsiness using the visual analogue scale, with each patient providing their individual response. This study began with patient recruitment in April 2023, with 17 participants enrolled as of November 12, 2023. The anticipated study completion is set for February 2026. This study is the first randomized controlled trial comparing the effects of oral first- and second-generation histamine H1-receptor antagonists in preventing IRs induced by the initial administration of rituximab. The findings from this study hold the potential to establish the rationale for a phase III study aimed at determining the standard premedication protocol for rituximab infusion. Japan Registry of Clinical Trials jRCTs051220169; https://jrct.niph.go.jp/latest-detail/jRCTs051220169. DERR1-10.2196/54882.

Can quantitative monitoring of B cells evaluate the efficacy of Rituximab in primary CNS demyelinating disorders?

Abstract Introduction: Rituximab (RTX), initially approved for various blood cancers, is additionally used for the management of primary central nervous system (CNS) demyelinating disorders. This study aimed to quantify the % of B cells following RTX therapy in patients with primary CNS demyelinating disorders, so as to establish a correlation, if any, between the degree of B-cell depletion and clinical response(s). Materials and Methods: A prospective, observational study was conducted from February 2020 to August 2021 in 15 adults diagnosed with primary CNS demyelinating disorders. The % of B cells was quantified in terms of CD20 by flow cytometry, and clinical evaluation was by Expanded Disability Status Scale (EDSS) scores. Following the first dose of RTX, the %CD20 counts were measured 2 and 24 weeks later; subsequently, depending on the %CD20, RTX was administered. Accordingly, patients were divided into Group 1 (n = 7, %CD20 ≥ 1.5) and Group 2 (n = 8, %CD20 < 1.5) and followed up on the basis of CD counts till the completion of the study or until they were lost to follow-up. Safety was evaluated by recording of treatment-emergent adverse drug reactions (ADR). Results: In patients with CNS demyelinating disorders (n = 15), their median (interquartile range [IQR]) %CD20 and EDSS at baseline was 9.8 (5.6–18.8)% and 8.0 (7.5–8.0)%, respectively. In Group 1 (n = 7, %CD20 ≥ 1.5), there was a gradual decrease of %CD20 and EDSS, whereas in Group 2 (n = 8, %CD20 < 1.5), despite withholding RTX, patients remained asymptomatic, and their %CD20 remained <1.5 and EDSS showed a gradual decrease. 87% of patients experienced at least one ADR, the median (IQR) of ADRs per patient was 3 (0–3), and all 31 ADRs were infusion-related, with 100% recovery. Conclusion: RTX was relatively safe to use in these disorders, and monitoring its efficacy was adequately achieved using EDSS, with no additional benefits accrued by measuring %CD20 counts.

#6071 RITUXIMAB FOR MAINTENANCE OF REMISSION IN ADULT MINIMAL CHANGE DISEASE

Abstract Background and Aims Maintaining remission in a minority of adult patients with minimal change disease remains challenging. Prolonged corticosteroid use is associated with severe adverse effects. A limited number of observational studies suggest that rituximab may be an alternative therapeutic option for remission maintenance, allowing steroid withdrawal. Method We retrospectively analysed the data of all adult patients with minimal change disease, who received rituximab in our centre between 2017 and 2022. Results A total of 14 adults with minimal change disease were treated with rituximab, six of whom had childhood-onset nephrotic syndrome. Six patients were steroid dependent. The median number of relapses was 6.5 (IQR 4.5-15.2) prior to rituximab. Thirteen patients had received at least ≥ 2 different immunosuppressive agents during their disease. Corticosteroid-related adverse events, including osteopenia, hypertension, cataract and diabetes mellitus were observed in 10 subjects. Rituximab was administered in a median time of 10.6 years (IQR 4.5-16.3) after diagnosis. All patients received 2 doses of 1g rituximab 2 weeks apart. The median age at rituximab administration was 31 years (IQR 18.7-49.0); all patients were in remission. Besides corticosteroids, concomitant immunosuppressive therapy included calcineurin inhibitors (n = 6) and mycophenolate acid analogues (n = 1). The median follow-up time after the first dose of rituximab was 44 months (IQR 9.5-67.2). Relapses occurred in 6/14 patients in a median time of 17.5 months (IQR 10.2-26.5). The number of relapses per year decreased to 0.27 from 0.87 (p < 0.001) after rituximab. Six patients received a repeat course of rituximab. One patient developed Pneumocystis Jirovecii pneumonia, that was successfully treated with cotrimoxazole. At the last follow-up visit, corticosteroids were discontinued in 8 out of 14 patients and calcineurin inhibitors in 3 out of 7 patients. Conclusion Rituximab is a reasonable therapeutic approach for maintaining remission and avoiding steroid toxicity in adult minimal change disease. Randomized controlled studies are needed to further evaluate the safety and efficacy of rituximab in these patients.

Monthly mini-dose rituximab for primary anti-PLA2R-positive membranous nephropathy: a personalized approach

BackgroundThe currently recommended dose of rituximab for primary membranous nephropathy is as high as that for lymphoma. However, the clinical manifestations of membranous nephropathy vary widely. Therefore, achieving individualized treatment is a topic that needs to be explored. This study assessed the efficacy of monthly mini-dose rituximab monotherapy in patients with primary membranous nephropathy.MethodsThis retrospective study included 32 patients with primary membranous nephropathy treated at Peking University Third Hospital between March 2019 and January 2023. All patients were anti-phospholipase A2 receptor (PLA2R) antibody-positive and received rituximab 100 mg intravenously monthly for at least 3 months without other immunosuppressive therapy. Rituximab infusions were sustained until either remission of the nephrotic syndrome or a minimum serum anti-PLA2R titer ˂ 2 RU/mL was achieved.ResultsThe baseline parameters included: proteinuria, 8.5 ± 3.6 g/day; serum albumin, 24.8 ± 3.4 g/L; and anti-PLA2R antibody, 160 (20–2659) RU/mL. B-cell depletion was achieved in 87.5% patients after the first dose of rituximab 100 mg and in 100% after the second equivalent dose. The median follow-up was 24 months (range 18–38). Twenty-seven (84%) patients achieved remission, with 11 (34%) patients achieving complete remission by last follow-up. The relapse-free survival from the last infusion was 13.5 months (range 3–27). Patients were stratified into the low-titer (< 150 RU/mL, n = 17) and high-titer groups (≥ 150 RU/mL, n = 15) based on the anti-PLA2R titer. Sex, age, urinary proteins, serum albumin, and estimated glomerular filtration rate at baseline did not differ significantly between the two groups. At 18 months, compared to the low-titer group, the rituximab dose (960 ± 387 vs 694 ± 270 mg, p = 0.030) was higher, while serum albumin (37.0 ± 5.4 vs 41.3 ± 5.4 g/L, p = 0.033) and the complete remission rate (13% vs 53%, p = 0.000) were both lower in the high-titer group.ConclusionsMonthly rituximab 100 mg appeared as a potential effective regimen for treating anti-PLA2R-associated primary membranous nephropathy with a low anti-PLA2R titer. The lower the anti-PLA2R titer, the lower the rituximab dose required to achieve remission.Trial registrationA retrospective study, registered at ChiCTR (ChiCTR2200057381) on March 10, 2022.

Therapeutic response to rituximab in seropositive neuromyelitis optica: Experience from a tertiary care center in South India.

Neuromyelitis optica (NMO) is a severe central nervous system demyelinating disease caused by autoantibodies to anti-aquaporin-4 immunoglobulin-G (AQP4-IgG). Rituximab, a monoclonal antibody targeting CD20 cells, is effective in neuromyelitis optica spectrum disorder (NMOSD) in several observational studies and small randomized controlled trials. However, this includes both AQP4-IgG antibody positive and negative cases. Whether rituximab is more effective in seropositive NMO is unknown. The aim of the study was to determine the efficacy of rituximab in seropositive NMO. This single-center ambispective study with retrospective data collection and prospective follow-up included patients with NMOSD who were positive for AQP4-Ig-G and treated with rituximab. Efficacy outcomes assessed were annualized relapse rate (ARR), disability progression by expanded disability status scale (EDSS), very good outcome (defined as no relapse and an EDSS ≤3.5), and persistent antibody positivity. Safety was also monitored. Between June 2017 and December 2019, 15 AQP4-IgG-positive cases were identified. The mean (± SD) age was 36 ± 17.9 years and 73.3% were females. Transverse myelitis followed by optic neuritis was the most common presentations. Rituximab was initiated after a median period of 19-weeks from the disease onset. The mean number of rituximab doses received was 6.4 ± 2.3. After a mean follow-up duration of 107 ± 74.7 weeks from the first dose of rituximab, ARR significantly reduced from 0.5 ± 0.9 to 0.02 ± 0.08, difference 0.48 ± 0.86 (95% confidence intervals [CI], 0.0009-0.96; P = 0.05). The number of relapses also reduced significantly from 0.6 ± 0.8-0.07 ± 0.26 , a difference of 0.53 ± 0.91 (95% CI, 0.026-1.05; P = 0.041). EDSS also significantly reduced from 5.6 ± 2.5-3.3 ± 2.9 , a difference of 2.23 ± 2.36 (95% CI, 0.93-3.54; P = 0.003). Very good outcome was obtained in 73.3% (11 of 15); P = 0.002. AQP4-IgG remained positive in 66.7% (4 of 6) when repeated after a mean period of 149.5 ± 51.1 weeks after the first dose of rituximab. Neither pre-treatment ARR, EDSS, time to initiate rituximab, the total number of rituximab doses, or time to repeat AQP4-IgG were significantly associated with persistent antibody positivity. No serious adverse events were observed. Rituximab exhibited high efficacy and good safety in seropositive NMO. Larger trials in this subgroup are warranted to confirm these findings.

Rituximab as Initial Therapy in Adult Patients With Minimal Change Disease

Rituximab as Initial Therapy in Adult Patients With Minimal Change Disease

Rituximab treatment for systemic sclerosis-associated interstitial lung disease: a case series of 13 patients.

Systemic sclerosis (SSc) associated interstitial lung disease (ILD) is a common complication of SSc, with a high mortality, despite current available treatments. Rituximab has shown some promising, although varied, results for the treatment of SSc-ILD. To determine whether rituximab stabilised or improved pulmonary function at 12 months, in patients with SSc-ILD. A retrospective analysis of patients with SSc-ILD who progressed despite conventional therapy and received rituximab between 2008 and 2019 was performed at two tertiary centres. Baseline percentageforced vital capacity (FVC) and percentage diffusing capacity of carbon monoxide (DLCO) were compared with 1-year post the first dose of rituximab. Mean and median change in FVC (%) and DLCO (%) were calculated. For those with available data, the FVC (%) and DLCO (%) 2 years and 1year prior to rituximab were compared with the change 12-months post-rituximab. Thirteen patients were included in the analysis. All patients demonstrated stability in their pulmonary function testing at 1-year post-rituximab. The mean FVC (%) was 57.18 (±16.93 standard deviation (SD)) prior to rituximab and 59.75 (±18.83 SD) 12-month post-rituximab, demonstrating an increase of 2.57 (±4.70 SD; P-value 0.07). The mean DLCO (%) increased from 37.10 (±18.41 SD) prior to rituximab to 38.03 (±19.83) post-rituximab. The mean change in DLCO (%) was 0.93 (±5.05 SD; P-value 0.53). In the 2 years preceding rituximab, the mean FVC (%) and DLCO (%) declined by 9.25 and 9.66 respectively. This case series suggests that rituximab might stabilise pulmonary function tests, and delay deterioration in patients with progressive SSc-ILD. These findings add to the growing body of evidence suggesting a role for rituximab in the treatment of SSc-ILD.

IgG4-related prostatitis manifesting as urinary obstruction in a 28-year-old male

BackgroundImmunoglobulin G4-related disease (IgG4-RD) is a systemic lymphoproliferative disorder characterized by elevated serum IgG4 levels and tumefactive lesions that can involve nearly every organ system. Involvement of the prostate is rare but has been reported in limited cases.Case presentationA 28-year-old man of Asian descent with a history of sinusitis and priapism presented to hospital with rigors and voiding symptoms. He was diagnosed with IgG4-RD one month prior to presentation, following pathological analysis of a submandibular mass that demonstrated chronic sclerosing sialadenitis. On presentation, white blood cell count, C-reactive protein, and prostate serum antigen levels were all within normal limits. Examination was notable for a large, firm prostate, and a foley catheter was inserted. Contrast CT of the abdomen was unremarkable. Further workup revealed elevated serum IgG4 levels (9.22 g/L) and he was subsequently started on prednisone 35 mg daily. Imaging to screen for systemic IgG4-RD involvement demonstrated paravertebral soft tissue involvement and he was given rituximab 1000 mg IV × 2 doses. MRI revealed diffuse prostatitis. Five days after starting prednisone and one day after his first dose of rituximab, he successfully passed trial of void and was discharged home.ConclusionsIgG4-related prostatitis is a rare and underrecognized manifestation of IgG4-RD. Our case highlights the need to consider IgG4-related prostatitis as an etiology of urinary obstruction in young individuals. Resolution of symptoms following treatment with steroids may be diagnostic of IgG4-related prostatitis, and may potentially avoid the need for invasive diagnostic procedures such as prostate biopsy.

Rituximab‐induced mild encephalopathy with a reversible splenial lesion syndrome (MERS): An adverse effect to add to the list

Mild encephalopathy with a reversible splenial lesion syndrome (MERS) is a rare clinico-radiological entity. Rituximab (RTX)-induced MERS has never been described before. Herein, we report the case of a 33-year-old patient diagnosed since 2017, with an IgG4-related disease (IgG4-RD). This diagnosis was retained in the face of a prolonged fever, sicca syndrome, hepatic damage and renal pseudotumour associated to a high level of IGg4 at 2.8g/L with suggestive renal histology. The patient was treated with corticosteroid therapy with persistence of renal impairment and nephrotic syndrome indicating RTX therapy. The patient received his first dose of RTX and presented neurological and respiratory impairments a few hours afterwards. An infectious investigation comprising a SARS CoV-2 PCR and viral PCRs (VZV, herpes and CMV) on cerebrospinal fluid (CSF) were negative. The HBV, HCV, HIV, Parvo B19, CMV, EBV, herpes, mycoplasma and syphilis serologies as well as Legionella antigenuria were also negative. The patient had received intravenous immunoglobulins (IVIG) and methylprednisone, associated with sodium valproate with favourable outcome. The diagnosis of MERS induced by RTX was retained in our patient according to clinical and radiological features. We herein report the first case of MERS following RTX in a patient treated for IgG4-RD.

Rituximab treatment in pediatric patients with steroid-dependent nephrotic syndrome: A tertiary hospital

BackgroundCorticosteroids have had a central role in the treatment of nephrotic syndrome. The management of these patients who become dependent to steroids is complex, involving different immunosuppressive drugs patterns. The monoclonal antibody anti CD20, Rituximab, is likely to have beneficial effects in cases of steroid-dependent nephrotic syndrome patients with no easy resolution, even when we cannot make a statement about the specific role in the impact. We bring our personal experience in pediatric patients treated with this medication during the last years, to provide a thorough overview and useful information about the role of Rituximab in this pathology. MethodsRetrospective study in patients with steroid-dependent idiopathic nephrotic syndrome controlled in the division of Pediatric Nephrology of a Spanish tertiary hospital in those patients who had received at least one treatment cycle of Rituximab, at any moment along the evolution of the disease. ResultsThe study involved 8 patients. All of them previously received immunosuppressive therapy. The Rituximab were administered as an intravenous infusion, in a dose of 375 mg/m2, and all doses were administered in a period during which the disease was in remission. The depletion of lymphocytes B (CD19, 0%) were confirmed after the first dose of Rituximab except for one, with a lymphocyte count of 1%. The period of depletion lasts 10,3 months (median; range 6,5–16 months), and only one of the patients registered a relapse of the disease in this period. A reduction of relapses suffered by patients has been shown after the treatment began (3,6 relapses/year in the previous year to the start of the treatment versus 0,1 relapses/year during the first year post-rituximab). The relapse-free survival in the first year reached 83,3% in patients who suffered more than one relapse (75% of patients), and without a relapse after the treatment began in 2 cases. One or more drugs could be removed in 87,5% of patients after the first cycle of rituximab. After the rituximab treatment, we reached a 96,5% decrease in the corticosteroids doses administered (28,5 mg/m2/day during the 3 months pre-treatment versus 1 mg/m2/day in the last 3 months of patient monitoring). Not a significant observed adverse effect attributed to the drug after the post-rituximab monitoring period (median 46,5 months, range 5–97 months). ConclusionThe favorable results reported after rituximab treatment in our patients seems to confirm the effectiveness of this drug in the steroid-dependent nephrotic syndrome, making that therapeutic option into consideration and legitimating the use of the drug in complex cases involving pediatric patients. Even so, it seems recommendable to design pertinent studies to clarify, among others, the optimum regimen of the treatment (dose, interval and cycles), clinical repercussion and potential adverse effects in long terms.

Remissions in Patients with Idiopathic Membranous Nephropathy Treated with Rituximab in Senegal

Objectives: This study aimed to evaluate the efficacy of Rituximab in the management of idiopathic membranous nephropathy (IMN) based on the following criteria: (I) Biological remission at three months (M3) and six months (M6); (II) change in mean proteinuria (24PU), mean serum albumin, and mean serum creatinine at M3 and M6; (III) and side effects. Methods: This retrospective descriptive and analytical study included patients with histologically confirmed IMN with positive plasma anti-PLA2R antibodies who received at least one dose of Rituximab after six months of follow-up without spontaneous remission. Patients with unexplainable records were not included. Results: A total of five patients (P1, P2, P3, P4, and P5), including four males and one female were analyzed. The mean age was 44.20 ± 23.14 years. All patients had IMN type 2. At inclusion, the mean albuminemia, mean creatinine, and mean 24hPU levels were 15.56 ± 5.27 g/L, 17.3 ± 7.6 mg/L, and 6.54 ± 1.13 g/24h, respectively. The median anti-PLA2R antibody titer was 100 IU with extremes of 10 and 800 IU. Partial remission was noted in three patients at M3 (P2, P4, and P5), and it was maintained until M6 in P2. No complete remission was observed. A significant decrease in mean 24hPU at M3 was noted (P &lt; 0.001). Generalized pruritus associated with seizures was noticed in P4 after the first dose of Rituximab. Conclusions: Partial remission was noted in three patients at M3, and one patient maintained this remission at M6. Rituximab significantly reduced 24hPU at M3 after administration. Rituximab administration was well tolerated by the patients.

Tratamiento con rituximab en pacientes pediátricos con síndrome nefrótico córtico-dependiente. Experiencia en un hospital terciario

BackgroundCorticosteroids have had a central role in the treatment of nephrotic syndrome. The management of these patients who become dependent to steroids is complex, involving different immunosuppressive drugs patterns. The monoclonal antibody anti CD20, Rituximab, is likely to have beneficial effects in cases of steroid-dependent nephrotic syndrome patients with no easy resolution, even when we cannot make a statement about the specific role in the impact. We bring our personal experience in pediatric patients treated with this medication during the last years, to provide a thorough overview and useful information about the role of Rituximab in this pathology. MethodsRetrospective study in patients with steroid-dependent idiopathic nephrotic syndrome controlled in the division of Pediatric Nephrology of a spanish tertiary hospital in those patients who had received at least one treatment cycle of Rituximab, at any moment along the evolution of the disease. ResultsThe study involved 8 patients. All of them previously received immunosuppressive therapy. The Rituximab were administered as an intravenous infusion, in a dose of 375 mg/m2, and all doses were administered in a period during which the disease was in remission. The depletion of lymphocytes B (CD 19%) were confirmed after the first dose of Rituximab except for one, with a lymphocyte count of 1%. The period of depletion lasts 10.3 months (median; range 6.5-16 months), and only one of the patients registered a relapse of the disease in this period. A reduction of relapses suffered by patients has been shown after the treatment began (3.6 relapses/year in the previous year to the start of the treatment vs. 0.1 relapses/year during the first year post-rituximab). The relapse-free survival in the first year reached 83.3% in patients who suffered more than one relapse (75% of patients), and without a relapse after the treatment began in 2 cases. One or more drugs could be removed in 87.5% of patients after the first cycle of rituximab. After the rituximab treatment, we reached a 96.5% decrease in the corticosteroids doses administered (28.5 mg/m2/day during the 3 months pre-treatment vs. 1 mg/m2/day in the last 3 months of patient monitoring). Not a significant observed adverse effect attributed to the drug after the post-rituximab monitoring period (median 46.5 months, range 5-97 months). ConclusionThe favorable results reported after rituximab treatment in our patients seems to confirm the effectiveness of this drug in the steroid-dependent nephrotic syndrome, making that therapeutic option into consideration and legitimating the use of the drug in complex cases involving pediatric patients. Even so, it seems recommendable to design pertinent studies to clarify, among others, the optimum regimen of the treatment (dose, interval and cycles), clinical repercussion and potential adverse effects in long terms.

Retrospective observational study of temporal trends and outcomes of hepatitis B screening in patients receiving rituximab

ObjectiveHepatitis B reactivation (HBr) is strongly associated with rituximab therapy. Guidelines advise hepatitis B screening and use of preventive nucleoside analogue (NA) in patients at risk. In this study, we...

Moderate Risk of Hepatitis B Virus Reactivation in HBsAg\u2212/HBcAb+ Carriers Receiving Rituximab for Rheumatoid Arthritis

To investigate the incidence and risk factors of hepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg)−/ HBV core antibody (HBcAb)+ patients who underwent rituximab (RTX) therapy for rheumatoid arthritis (RA). From January 2000 through December 2017, a total of 134 RA patients with various HBV serostatuses who received RTX at Dalin Tzu Chi Hospital were screened. Finally, 50 HBsAg−/HBcAb+ patients were enrolled in this retrospective study. Baseline characteristics, comedications, and the occurrence of HBV reactivation were recorded. Four HBsAg−/HBcAb+ RA patients (8%; 4/50) experienced HBV reactivation after treatment with RTX. Hepatitis flare-up occurred in 2 of these 4 patients, with a fatal outcome in one. HBV reactivation occurred approximately 1–4 years after the first dose of RTX and 0.5–1.5 years after the last one. In HBsAg−/HBcAb+ patients, HBV reactivation was significantly more common in those who were HBV surface antibody (HBsAb)− at baseline than in those who were HBsAb+ (30% vs 4%; p = 0.02). A history of adalimumab use was associated with HBV reactivation (100% vs 39%; p = 0.02). A moderate risk of HBV reactivation was observed in HBsAg−/HBcAb+ RA patients receiving RTX therapy. The reactivation may induce acute hepatitis and even death. To reduce the risk of HBV reactivation, regular monitoring of liver function is insufficient; monitoring of viral load and HBsAg or prophylaxis with antiviral therapy should be considered.

The Risk of Thromboembolism Associated with Treatment of ITP with Rituximab: Adverse Event Reported in Two Randomized Controlled Trials

Introduction Immune thrombocytopenia (ITP) is a disease characterized by low platelet count and increased risk of bleeding. However, there has been an increased focus on the risk of thromboembolism particularly venous thromboembolism (VTE) associated with ITP itself and with some of its therapies. Epidemiological studies have shown a doubling in the risk of VTE in ITP patients as compared to the general population. VTE has been reported with various ITP therapies including splenectomy, steroids, IVIG and thrombopoietin receptor agonists (TPO-RAs). In long-term studies on TPO-RAs, arterial and venous thrombosis occurred in 6% of treated patients. Rituximab, a monoclonal antibody directed against CD-20 on the B-cells is widely used as a treatment for ITP. It yields a response rate of 60% and is generally well-tolerated. However, to our knowledge VTE events following treatment with rituximab for ITP have not been reported. Aims We report thromboembolic adverse events encountered in 2 multicenter, randomized controlled trials (RCT) for adult ITP patients treated with rituximab: 1) Rituximab as second-line treatment for adult ITP (the RITP trial)(Ghanima et al, Lancet 2015; 385) and 2) The Rituximab Maintenance Therapy in ITP (The PROLONG Trial; NCT03010202) Methods RITP was a multicenter, randomized placebo-controlled trial in which adult patients with ITP unresponsive to corticosteroid and platelet count &lt;30x10⁹/L were enrolled. Of the 112 ITP patients, 55 patients were randomly assigned to 4 weekly infusions of 375 mg/m2 rituximab and the remaining received placebo. Concurrent treatment with corticosteroids only was allowed during the study. The steroid dose had to be tapered to the lowest dose that kept the platelet count &gt;20x10⁹/L. PROLONG is an ongoing multicenter, two-phase RCT. In the first phase, patients with ITP, who fail to achieve an adequate response to corticosteroids (prednisolone or dexamethasone) during the first year after diagnosis are randomized to receive rituximab 1000 mg twice with 15 days apart with or without dexamethasone 20 mg for 4 days starting with rituximab. In the secondphase, responding patients will be randomized at 24 weeks to maintenance therapy with 2 rituximab or placebo infusions separated by 24 weeks. Results Four venous thromboembolic events were reported in 4 patients: 2 of 55 patients who received rituximab in the RITP trial and 2 (one received dexamethasone+rituximab) of 52 patients included so far in the first phase of the PROLONG trial, which results in a VTE rate of 3.7% in the rituximab treated patients. No thromboembolic events were encountered in the placebo arm of the RITP study (n=54 patients, matched on age). Median time from treatment to event was 40.5 weeks, with 2 events occurring 7-14 weeks after the administration of the first dose of rituximab. Median platelet count at the time of VTE was 188x109/L. Characteristics of the 4 patients are shown in the table; none was splenectomized or received thrombopoietic agents before the VTE event. No arterial thromboembolic events were reported in the 2 trials. Conclusion The rate of VTE following treatment with rituximab in these 2 studies seems to be higher than what is expected in an adult ITP population and the general population (Norgaard et al. Br J Haematol. 2016;174). However, based on these results we cannot determine whether the venous thromboembolic events were just incidental events or triggered by the treatment and/or the normalization of platelet count or the presence of risk factors for VTE as old age and immobilization. Table Disclosures Tvedt: Ablynx, alexion and novartis: Consultancy. Michel:Novartis: Consultancy; Amgen: Consultancy; Rigel: Consultancy. Ghanima:Bayer: Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Pfizer/BMS: Research Funding.

P60 Rituximab use within the Scottish paediatric and adolescent rheumatology network: a review of five years’ experience

Abstract Background Rituximab is an anti-CD20 chimeric monoclonal antibody that depletes pre-plasma B cells. It is used in paediatric rheumatology for conditions including juvenile systemic lupus erythematosus (jSLE), juvenile dermatomyositis (JDM), vasculitides and refractory juvenile idiopathic arthritis (JIA). We aim to describe the cohort of patients treated with rituximab in the Scottish Paediatric and Adolescent Rheumatology Network (SPARN) in a 5-year period, and assess the need for a network guideline. Methods A review of paper and electronic case records. Patients seen within the SPARN network who received Rituximab between 2014 and 2018 were included. Results Vasculitis Rituximab was given to 16 patients in 5 different SPARN centres between 2014 and 2018. Male: Female ratio was 1:4.3. Mean age at first dose of rituximab was 12.75 years. Mean disease duration pre rituximab was 1 year. 8 (50%) patients had jSLE, 7 multisystem and 1 isolated lupus nephritis. 3 had ANCA-positive vasculitis and 5 had other conditions. (1 had RF+ve JIA; 1 severe panuveitis; 1 had an unspecified autoinflammatory condition; 1 had COPA syndrome with severe interstitial lung disease and 1 had autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Documentation of pre-rituximab checks was poor. Baseline bloods were done in all 16 patients. 11 patients had lymphocyte subsets and 13 immunoglobulins documented. Disease-specific antibodies were measured in all patients in whom applicable (11). 11 had a chest x-ray prior to rituximab. In 9 cases a pre-rituximab pregnancy test was indicated: none were documented. In only 3 patients was a pre-rituximab history of recent infections documented. In 8 patients a discussion regarding treatment risks and benefits was documented. Post-infusion lymphocyte subset monitoring was variable but documented in 15. 1 patient was never B cell deplete. 9 never fully reconstituted. RTX dose information was available for 14. All received doses of 750mg/m2 with 6 having the dose capped at 1g. Dose frequency information was available for all. The majority (9) received 2 doses. Of the rest, 1 patient received a single dose. 3 received 3 doses, 2 had 4 and 1 had 5. All patients in whom information was available, received pre-medication with paracetamol, chlorphenamine and methylprednisolone (n = 14). 4 patients had side effects noted (rash/itch in 1, anaphylaxis in 1, facial flushing in 1 and post-infusion infection in 1). Clinical response was clearly documented in 8 patients, 7 of whom showed clinical improvement (2 had systemic jSLE, 2 had ANCA +ve vasculitis, 1 had isolated lupus nephritis, 1 had COPA syndrome and 1 had RF+ JIA). Conclusion Rituximab is used for a range of conditions and in a number of centres within SPARN. This review highlights variation in and poor documentation of pre-rituximab discussions and investigations, prescribing, monitoring and response. A SPARN rituximab protocol is being developed to address this. Conflicts of Interest The authors declare no conflicts of interest.

Disease course, progression and activity of neuromyelitis optica (NMOSD) in patients who were treated with Rituximab, 6 and 12 months after receiving the first dose of drug, in Isfahan city

IntroductionNeuromyelitis optica spectrum disease (NMOSD) is a chronic inflammatory and usually relapsing demyelinating disease which mainly involves optic nerve and spinal cord and also other parts of the central nervous system. Rituximab has been used for some neurological disorders with a probable autoimmune basis. Early and aggressive immunosuppression therapy is necessary to prevent clinical relapses and permanent disability in NMOSD. Rituximab, a monoclonal antibody against B cells, has been found effective in several recent studies. The objective of this study is to evaluate the clinical efficacy of Rituximab as a newly introduced treatment to NMOSD in Iran. Methods and MaterialsThis is an observational cohort study carried out,on 56 patients who have been diagnosed with NMOSD. The patients’ information registered in Kashani Hospital MS clinic. They received the first dose of Rituximab for approximately 6 months before the beginning of study. In the first session, every patient was interviewed and examined based on necessary information for the study. Follow up visits were done as needed in a period of 12 months after the first dose. Patient's age, sex, age of onset, presenting symptom, annual relapse rate, acute attacks, EDSS (primary, 6 and 12 months) were recorded. Comparative aims achieved by within group analysis before and after treatment. AntiAQP4 antibody had been checked before the start of study. patients divided into two groups based on the antibody test results for subgroup analysis. Data were analyzed using the IBM SPSS23 - United States software. Results56 known cases of NMOSD including 17.85% male and 82.15% female were under study. The Mean disease duration was 87.60±59.65 months and mean duration of treatment was 19.56±8.26.The mean EDSS score was primarily 4.83±1.87 and after treatment it decreased significantly (p-value<0.001) to 3.38±1.57 and 2.87±1.63 (6 months and 12 months later).There was a statistical difference between the annual mean relapse rate before and after treatment (p<0.001). The above mentioned index decreased from 1.43±1.107–0.147±0.27. Also, the mean number of attacks in one year before and after treatment were 1.97±0.57 and 0.28±0.45 with significant statistical difference (p<0.001).In the patients with positive anti AQP4 antibody,the mean EDSS decreased from 4.94±1.83–3.52±1.27 and 2.92±1.54. Annual mean relapse rate also decreased significantly from 1.35±0.85–0.10±0.19. Mean number of attacks in one year before and after treatment were 2.05±0.75–0.27±0.46 (p<0.001) respectively. ConclusionIn the current study, we found that Rituximab can significantly improve disability state and also can markedly reduce relapse rate in NMOSD patients.

Predictors of Relapse and Efficacy of Rituximab in Autoimmune Thrombotic Thrombocytopenic Purpura (TTP): A Multi-Institutional Registry-Based Analysis

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a distinct and lethal subtype of thrombotic microangiopathy (TMA) requiring treatment with therapeutic plasma exchange (TPE). However, a significant proportion of patients suffer relapses of TTP, and predictors of relapse remain unclear. Whether rituximab (RTX) affects relapse rates in TTP is uncertain. We employed a multi-institutional, registry-based approach to study the effect of RTX on relapse in autoimmune TTP and identify predictors of relapse.Methods: Consecutive adult patients presenting with acute autoimmune TTP (thrombocytopenia (<150 x 109 platelets/L) and schistocytes associated with an ADAMTS13 activity level of ≤10%) at 5 academic medical centers between 2004 and 2017 were studied. We recorded demographic information, laboratory parameters, treatment, and outcomes, including complications of TPE, death, and relapse. Extended Cox proportional hazards regression was used to identify variables associated with hazard of relapse. Kaplan-Meier survival analysis was used to study the impact of RTX on risk of relapse.Results: Within our combined dataset, we identified 124 patients with autoimmune TTP. Patients were treated with a median (IQR) of 14 (8-22) TPE treatments until clinical remission was achieved. Seventy-five percent of patients experienced at least one complication from TPE; most common were mild urticarial reactions, but more serious allergic reactions including anaphylaxis occurred in 19% of TPE courses, and one patient died as the result of line-associated bacteremia during TPE. Of the 109 patients with 90-day or more follow up data, 8 (7.3%) died following presentation with TTP; five of these 8 deaths occurred in patients who presented in a moribund state or did not received TPE within the first 24 hours of hospitalization. Thirty-four patients (27%) subsequently relapsed, with a median time to relapse of 1.75 years. RTX was given to 48% of patients. The median time to the first dose of RTX was 12 (7-23) days following presentation. We observed a 3.6% increase per year in the proportion of patients presenting for the first time with acute TTP who were treated with RTX. Kaplan Meier analysis performed on the entire cohort did not show an overall difference in relapse free survival between patients who received RTX and those who did not (Figure 1) but did suggest the presence of a short-term benefit from RTX. A sensitivity analysis using only patients who presented with a first episode of TTP yielded similar results. Extended Cox multivariate analysis showed that the following parameters were independently associated with increased risk of relapse: younger age (HR=2.94, 95% CI: 1.2-7.2, P=0.018), non-O blood group (HR=2.11, 95% CI: 1.03-4.3, P=0.041), and history of a prior episode of TTP (HR=3.05, 95% CI: 1.4-6.6, P=0.005). By contrast, RTX reduced the risk of relapse (HR=0.15, 95% CI 0.03-0.68) but this protective effect appeared to diminish over time. ADAMTS13 inhibitor titer at initial presentation did not predict relapse.Conclusions: Although a significant number of patients experienced complications from treatment with TPE, death from TTP was infrequent and generally associated with delay in seeking medical care or initiating treatment. Use of RTX was associated with short-term protection from relapse but not long-term relapse free survival. Age, non-O blood group, and prior TTP were significantly associated with an increased risk of relapse. Further studies in independent datasets are required to validate the role of these risk factors in identifying patients who would benefit most from therapies directed at prevention of relapse in TTP. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

1601. Effect of Preemptive Rituximab Therapy on Epstein–Barr Reactivation in Allogenic Hematopoietic Stem Cell Pediatric Transplants

BackgroundChildren with Epstein–Barr virus (EBV) viremia after hematopoietic stem cell transplantation (HSCT) are at increased risk of post-transplant lymphoproliferative disease (PTLD). Our aim was to assess whether pre-emptive rituximab reduced EBV-viral load (EBV-VL) and the risk of developing PTLD.MethodsWe retrospectively included all children who had a positive EBV-VL within 12 months after an allogenic HSCT (2007–2015) in a single tertiary pediatric hospital. Whole blood EBV-VL was monitored weekly using a real-time PCR, during the first 100 days after HSCT and then monthly until 6 months post-HSCT or until EBV-VL became undetectable. EBV-VL clearance was defined as two negative EBV-VL at least 1 week apart. Pre-emptive rituximab was defined as a treatment administered before the occurrence of PTLD. We determined the impact of pre-emptive rituximab on EBV-VL clearance, using a marginal structural cox model, adjusting for age at transplant, time between transplant and first positive EBV-VL, in-vivo T-cell depletion at induction, value of EBV-VL at the first dose of rituximab, and the EBV-VL value at the current and previous time point.ResultsOf 214 children who underwent allogenic HSCT, EBV DNA was detected in 87 (41%) children. Children who received rituximab after diagnosis of PTLD were excluded, leading to a cohort of 78 children. Twenty-two (28%) children received pre-emptive rituximab. Mean (SD) age was similar in both groups (10 [5] year). First post-transplant positive EBV-VL was earlier in the pre-emptive rituximab group (mean of 55 [54] vs. 113 [96] days; P < 0.05) and first positive EBV-VL was higher in the pre-emptive rituximab group (mean of 3.4 [0.6] vs. 3.0 [0.6] log10/mL; P < 0.05). In adjusted analyses, pre-emptive rituximab was associated with a higher likelihood of EBV-VL clearance (hazard ratio 1.86; 95% confidence interval 1.10–3.14; Figure 1). Of the 10 children who developed PTLD, none had received pre-emptive rituximab.ConclusionEBV viremia is frequent in children with allogenic HSCT. Our results suggest that pre-emptive rituximab is associated with more rapid EBV-VL clearance. The effect of rituximab on the risk of PTLD needs to be better defined.Figure 1.Inverse probability of EBV viremia clearance in children.Disclosures All authors: No reported disclosures.

Rituximab‐associated posterior reversible encephalopathy syndrome

Rituximab‐associated posterior reversible encephalopathy syndrome