Rituximab Infusion In Patients Research Articles

Impact of Split Dosing the First Rituximab Infusion in Patients with High Lymphocyte Count.

The most common adverse reactions to rituximab are infusion-related reactions (IRR). We evaluated the efficacy of split dosing the first rituximab infusion over two days to reduce IRR incidence in patients with hematological cancer and a high lymphocyte count. This is a retrospective observational study conducted in two healthcare centers in Quebec, Canada. The study enrolled patients with white blood cell counts ≥25.0 × 109/L who received their first rituximab dose for hematological cancer between December 2007 and May 2020. One healthcare center used asymmetrical split dosing, while the other used symmetrical split dosing. A total of 183 treatment episodes were collected from 143 patients. Among patients who received a fractionated dosing schedule, 42% developed an IRR from the first rituximab infusion compared with 50% for the standard protocol (adjusted relative risk, 0.89; p = 0.540). No significant difference was observed in IRR severity between either groups. However, 24% of patients who received the asymmetrical protocol developed an IRR compared to 68% for the symmetrical protocol (adjusted relative risk, 0.32; p = 0.003). These results suggest that an asymmetrical split dosing could be effective in reducing the incidence of IRR and is preferable to a symmetrical one.

Adverse infusion reactions to rituximab in systemic lupus erythematosus: a retrospective analysis

BackgroundTo undertake a retrospective review of patients with SLE who had received Rituximab in order to determine the rates and associated patient characteristics of clinically significant adverse infusion reactions.MethodsA descriptive analysis was undertaken of each infusion reaction, which was then assessed using the clinical information available to hypothesise on the possible underlying mechanism(s).ResultsRecords of 136 SLE patients previously treated with 481 individual infusions of Rituximab were reviewed. A total of 22 patients (17.6%) had 28 (5.8% of total infusions) documented clinically significant adverse infusion reactions. Average age at first Rituximab infusion in patients without a reaction was 37 years (range 16–73) compared with 30 years (range 18–56) in those with a reaction. A high proportion of men (18.2%) experienced an infusion reaction. Severity and type of reaction varied. 6.4% of those who had a reaction were not retreated.ConclusionsWhile Rituximab remains an important tool in the treatment of SLE it is important to be aware that rates of infusion reactions may be more significant in SLE than in other diseases. A prospective study is required to better characterise the reactions.

Idiopathic nephrotic syndrome and rituximab: may we predict circulating B lymphocytes recovery?

Rituximab (RTX) has been shown to be an efficient treatment for steroid-dependent nephrotic syndrome (SDNS). A long B cell depletion period seems to improve the duration of remission. This study reports the duration of B cell depletion after each RTX infusion in patients with nephrotic syndrome. We retrospectively report the data of 22 patients with a diagnosis of a SDNS or steroid-resistant nephrotic syndrome (SRNS) and a treatment with RTX in a single center. B cell depletion duration was compared to the first B cell depletion duration and to the previous B cell depletion duration in each patient. Twenty-two patients (5 girls) were included. Seventy-six periods of B cell depletions were compared to the first B cell depletion duration and to the preceding B cell depletion duration in the same patient. Total duration of B cell depletion was 26 (6-66) months. Individual post-RTX infusion B cell depletion duration was 5.1 (1.6-14) months. Median B cell depletion duration following the first RTX cure for children who had received 1 to 2 infusions at first cure was not statistically different of those who had received 3 to 4 infusions (p = 0.18). Comparing the B cell depletion induced by previous RTX courses and the following B cell depletion, 89.5% of patients had a similar duration within an open interval from 2months. Once the individual time interval until B cell recovery is determined, monitoring could be individualized by targeting the expected date of B cell recovery or by performing pre-emptive RTX injections.

Tolerance and safety of rapid 2-hour infusion of rituximab in patients with kidney-affecting autoimmune diseases and glomerulonephritides: a single-centre experience

ObjectiveAccording to the manufacturer’s documentation, rituximab (RTX) should be administered with slow infusion rates to prevent infusion-related adverse events (AEs). Nevertheless, slow infusions are time-consuming and uncomfortable for patients and...

Infusion reactions associated with rituximab treatment for childhood-onset complicated nephrotic syndrome.

Infusion reaction (IR) is defined as an adverse event within 24h after monoclonal antibody infusion. In non-Hodgkin lymphoma, IR incidence following rituximab treatment is high (77-80%), but there are no data in complicated nephrotic syndrome. Records of rituximab infusions in patients with complicated nephrotic syndrome between February 2006 and December 2014 at the National Center for Child Health and Development were reviewed. Rituximab was administered at doses of 375mg/m2. The severity of IR was evaluated using the Common Terminology Criteria for Adverse Events ver. 4.0. For 309 rituximab infusions in 159 patients (male, 110; median age, 12years), IR was observed in 165 infusions (53.4%). Respiratory symptoms were most common (66% of all events). Ninety-five percent of the IR was observed within 3h after rituximab infusion initiation. Sixty-eight percent of the events were classified as grade 1 and others classified as grade 2. Only 18% required medical intervention. CD20 cell count in patients with IR was significantly higher than in patients without IR. Incidence of IR was similar in subsequent rituximab treatment after B-cell recovery. Patients who experienced IR at first rituximab treatment were more likely to experience recurrent IR with subsequent treatments compared to those not having IR at initial treatment (odds ratio 3.64; p < 0.001). In patients with complicated nephrotic syndrome, respiratory symptoms were the major type of IR, mostly observed within 3h of infusion. Incidence of IR was lower and its severity milder in patients with complicated nephrotic syndrome than those with lymphoma.

Late-onset neutropenia after treatment with rituximab for rheumatoid arthritis and other autoimmune diseases: data from the AutoImmunity and Rituximab registry

ObjectivesTo evaluate the prevalence of late-onset neutropenia and its complications in patients treated with rituximab (RTX) for rheumatoid arthritis (RA) and other autoimmune diseases (AIDs) in a prospective registry.MethodsThe AutoImmunity...

Safety of infusing rituximab at a more rapid rate in patients with rheumatoid arthritis: results from the RATE-RA study.

BackgroundAs recommended in the current prescribing information, rituximab infusions in patients with rheumatoid arthritis (RA) take 4.25 hours for the first infusion and 3.25 hours for subsequent infusions, which is a burden on patients and the health care system. We therefore evaluated the safety of infusing rituximab at a faster rate for an infusion period of 2 hours in patients with RA.MethodsPatients with an inadequate response to anti-TNF who were rituximab-naive or -experienced received 2 courses of rituximab: Infusion 1 (Day 1) was administered over the standard 4.25 hours, and Infusions 2 (Day 15), 3 (Day 168) and 4 (Day 182) were administered over a faster 2-hour period. The primary endpoint was incidence of infusion-related reactions (IRRs) associated with Infusion 2.ResultsOf the 351 patients enrolled, 87% and 13% were rituximab-naive and -experienced, respectively. The incidence (95% CI) of IRRs associated with Infusion 1 was 16.2% (12.5%, 20.5%) and consistent with weighted historical incidence of 20.7% (19.4%, 22.1%). The incidence (95% CI) of IRRs associated with Infusions 2, 3, and 4 compared with respective weighted historical incidences at the standard infusion rate was 6.5% (4.1%, 9.7%) vs 8.1% (7.2%, 9.1%); 5.9% (3.5%, 9.3%) vs 11.5% (10.3%, 12.8%); and 0.7 (0.1%, 2.6%) vs 5.0% (4.2%, 6.0%), respectively. All IRRs were grade 1 or 2, except for 3 grade 3 IRRs associated with Infusion 1 and 2 grade 3 IRRs associated with Infusion 2. Four patients experienced a total of 5 grade 3 IRRs; 3 of these patients continued on to received subsequent infusions at the faster rate. There were no serious IRRs.ConclusionThis study demonstrated that rituximab can be administered at the faster infusion rate at the second and subsequent infusions without increasing the rate or severity of IRRs.

AB0751 Successfull maintenance treatment of granulomatous polyangiitis (wegener) with rituximab - a case series

BackgroundGranulomatous polyangiitis (GPA) is a chronic relapsing systemic vasculitis and repeated remission treatment with cyclophosphamide poses long term safety risks. Studies of rituximab (RTX) have reported successful remission in patients...

Rapid infusion with rituximab: short term safety in systemic autoimmune diseases

To describe the incidence, types and severity of adverse events, related to an accelerated regime of rituximab infusion in patients with various autoimmune diseases. Fifty-four patients with systemic autoimmune disease, to be treated with 1,000 mg of rituximab twice 2 weeks apart, participated. Pre-medication (oral prednisolone, anti-histamine and paracetamol) was administered 1-4 h before infusion start. The first infusion was administered over a period of 195 min. The second infusion over a period of 90 min. Any adverse events were classified using the Clinical Trials Classification of Adverse Events (CTCAE) v. 3.0. Ten patients (18.5%) experienced at least one infusion-related reaction (IRR) ever. The first infusion was associated with reactions in 4 CTCAE categories of which rhinitis were the most frequent. The CTCAE severity grading showed six patients (11.1%) had a grade 1 reaction. One patient (1.8%) had grade 2 events on both infusions and two patients (3.6%) had a grade 3 event on both infusions. RA patients more often had an infusion-related reaction (IRR) (9.2%) than the rest. The types of IRR were mostly of allergic or angio-oedematic nature. In practise, the rapid infusion was an easy to use regime and the second infusion is of time sparing significance to health professionals. No unexpected side effects were observed in relation to the accelerated regime.

Rituximab may form a complex with iGmκ mixed cryoglobulin and induce severe systemic reactions in patients with hepatitis C virus–induced vasculitis

To report on 6 cases of hepatitis C virus (HCV)-induced mixed cryoglobulinemia (MC) vasculitis in patients who developed severe systemic reactions after rituximab infusion, and to report the results of the in vitro analysis of the underlying immunologic mechanisms. Twenty-two HCV-infected patients with MC vasculitis received rituximab infusions (a low-dose protocol cycle with 375 mg/m2/week for 4 consecutive weeks in 18 patients and a high-dose protocol cycle with 1,000 mg on days 1 and 15 in 4 patients). Systemic drug reactions following rituximab infusion were recorded and analyzed clinically and immunochemically. Six of 22 patients (27.3%) experienced systemic drug reactions after rituximab infusion. Four patients developed a severe flare of MC vasculitis 1 or 2 days after rituximab infusion. Two patients developed serum sickness syndrome 7 and 9 days after the first 1,000 mg rituximab infusion. Compared with patients without drug reactions, those with drug reactions had higher mixed cryoglobulin levels (mean+/-SD 1.4+/-0.82 gm/liter versus 0.71+/-0.77 gm/liter; P=0.0475) and lower C4 levels (mean+/-SD 0.02+/-0.006 gm/liter versus 0.07+/-0.07 gm/liter; P=0.02), and more of them received 1,000 mg high-dose rituximab protocol (50% versus 6.25%; P=0.046). In vitro immunochemical assays showed that rituximab formed a complex with the cryoprecipitating IgMkappa that had rheumatoid factor (RF) activity. Moreover, the in vitro addition of rituximab to serum containing an RF-positive IgMkappa type II mixed cryoglobulin was associated with visibly accelerated cryoprecipitation. In HCV-associated MC vasculitis, rituximab may form a complex with RF-positive IgMkappa, leading to accelerated cryoprecipitation and to severe systemic reactions. Rituximab should be administered with caution in MC vasculitis, with use of the 375 mg protocol and plasma exchanges prior to rituximab infusion in patients with high baseline levels of mixed cryoglobulin.