Rituximab In Patients Research Articles

Rituximab for anti-neutrophil cytoplasmic antibodies-associated vasculitis: experience of a single center and systematic review of non-randomized studies.

Rituximab (RTX) is becoming a standard treatment for patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) but heterogeneity exists regarding its use. We present our uncontrolled experience with RTX in patients with refractory AAV and also the results of a systematic review of non-randomized studies on RTX in AAV patients. We retrospectively reviewed the records of AAV patients treated with RTX following an inadequate response to immunosuppressives between 2011 and 2015. The systematic review covered all English articles listed in PubMed until June 2017. There were 25 AAV patients (21 GPA, four unclassified) treated with RTX (median 2, IQR 1-3 courses; median follow-up 24, IQR 17-50months). The kidney and the lung were the most commonly affected organs, observed in 14 and 16 patients, respectively. Complete remission rate was 72% at month 6 and 88% at month 12. Two patients had died and three serious adverse events occurred. The systematic review included 56 studies on 1422 patients with the majority being on refractory or relapsing disease. There was wide variability regarding disease characteristics, endpoints, concomitant immunosuppressives and RTX schedule. Most studies reported > 80% complete or partial remission rates with the lowest response (37.5%) for granulomatous lesions. The relapse rate was 30%. Infections and infusion reactions were the main adverse events. Our experience with RTX in refractory AAV is in line with the literature in terms of efficacy and safety. The systematic review underlines many uncertainties on its optimal use.

Low-dose Rituximab therapy in resistant idiopathic membranous nephropathy: single-center experience.

ABSTRACTBackgroundPersistent significant proteinuria has been associated with increased risk of progression to end-stage kidney disease in patients with idiopathic membranous nephropathy (IMN). Rituximab (RTX) therapy has given encouraging results in IMN, but most of the studies have used a higher dose, which is limited by the high cost as well as a potential increased risk of infections. Our study aimed to assess the efficacy and safety of low-dose RTX in patients with immunosuppression-resistant IMN.MethodsA total of 21 patients with treatment-resistant IMN treated with RTX from 2015 to 2016 at our center were included in the study. They received two doses of RTX (500 mg each) infusion 7 days apart. CD19 count was performed after 4 weeks. A single dose of RTX was repeated after 4–6 weeks if CD19 count was not depleted.ResultsThe mean standard deviation age of patients was 33.3 ± 12.3 years and 33.3% were females. Mean proteinuria before RTX therapy was 6.2 ± 2.2 g/day, serum creatinine was 0.9 ± 0.3 mg/dL and estimated glomerular filtration rate (eGFR) was 95.8 ± 26.9 mL/min/1.73 m2. All the patients were non-responders to prior immunosuppressive treatment. Twenty (95.2%) patients achieved targeted CD19 depletion with two doses of RTX. One patient required one additional RTX dose due to inadequate B-cell suppression. A total of 13 (61.9%) patients achieved remission with RTX therapy: 4 (19.0%) complete and 9 (42.9%) partial remission. Patients who did not respond to RTX had a significantly lower baseline eGFR compared with those who achieved remission (P = 0.022). One patient developed respiratory tract infection following RTX during the follow-up, which responded to a course of oral antibiotics. During median follow-up of 13.1 (10–23.9) months, four (19%) patients had deterioration in renal function and one patient relapsed after achieving partial remission. Renal survival was significantly better in patients who responded to RTX therapy as compared with those who did not achieve remission (P = 0.0037).ConclusionLow-dose RTX therapy is effective and safe in immunosuppression-resistant IMN.

Serious infection risk after 1 year between patients with rheumatoid arthritis treated with rituximab or with a second TNFi after initial TNFi failure: results from The British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

ObjectivesBoth TNF inhibitors (TNFi) and rituximab (RTX), a B-cell depleting biologic, can disrupt the immune system in RA. RTX is licensed in Europe for use following TNFi failure. However, safety data on serious infections (SIs) are scarce for RTX in daily practice. This analysis aims to compare the risk of SIs in the first year after a switch to either TNFi or RTX in patients who have failed a first TNFi.MethodsThis study included patients with RA registered with the British Society for Rheumatology Biologics Register (BSRBR-RA) who switched to either a second TNFi or RTX after failing a first TNFi. Patients were followed until first SI, treatment discontinuation, last recorded follow-up or the end of the first year after the switch, whichever came first. SI was defined as requiring hospitalization, intravenous antibiotics or resulting in death. The risk of first SI was compared between TNFi and RTX using Cox proportional hazard models adjusted using propensity scores using inverse probability of treatment weighting.ResultsThis analysis included 3419 TNFi and 1396 RTX patients contributing 2765 and 1224 person-years (pyrs), respectively. SI occurred in 164 (4.8%) TNFi and 81 (5.8%) RTX patients giving a crude rate of 59 and 66 SI/1000 pyrs, respectively. The adjusted hazard ratio for SI was 1.0 (95% CI: 0.7, 1.4).ConclusionThe risk of SIs was comparable over the first year of treatment between TNFi and RTX treatment in patients who had failed a single prior TNFi.

Double-blind, randomized phase 3 study to compare efficacy and safety of the biosimilar CT-P10 to rituximab combined with CVP therapy in patients with previously untreated advanced-stage follicular lymphoma.

7532 Background: CT-P10 is a biosimilar candidate to the innovator rituximab (RTX). In patients with rheumatoid arthritis, CT-P10 has demonstrated equivalence in pharmacokinetics (PK) and efficacy (Yoo, ACR 2016). This study aimed to demonstrate non-inferiority of efficacy and PK equivalence between CT-P10 and RTX in patients with newly diagnosed advanced follicular lymphoma (AFL) (NCT02162771). PK equivalence was confirmed (Coiffier, ASH 2016). Methods: A total of 140 patients were randomized in a 1:1 ratio to receive CT-P10 or RTX (375 mg/m2 i.v) plus CVP (cyclophosphamide, vincristine, and prednisone) every 3 weeks over 8 cycles. Overall response rate (ORR) according to the 1999 IWG criteria over 24 weeks was assessed by the independent review committee. Results: Noninferiority of CT-P10 to RTX was shown for the primary efficacy endpoint of ORR. The ORR difference was 4.3% (Table) and the lower bound of the 95% confidence interval was -4.25%. B-cell depleted after the 1st infusion and remained as depleted over 8 cycles in both groups. Overall safety profile of CT-P10 was consistent with that of RTX and the proportion of patients with positive anti-drug antibody was similar in both groups (4.3% and 2.9%) for 24 weeks. Neither progressive multifocal leukoencephalopathy nor Hepatitis B virus reactivation was reported in each group. Conclusions: This study demonstrates noninferiority of efficacy of CT-P10 to RTX combined with CVP in previously untreated AFL. CT-P10 was well-tolerated and the safety profile including immunogenicity of CT-P10 was comparable to that of RTX over 8 cycles of induction period. Clinical trial information: NCT02162771. [Table: see text]

Anti-B cell therapy in patients with systemic lupus erythematosus

The paper presents an analytical literature review of the use of rituximab (RTM) in patients with systemic lupus erythematosus (SLE). It considers current views on the mechanisms of action of RTM, its efficacy in different organ damages in patients with SLE, particularly in those with lupus nephritis and central nervous system involvement. There is evidence suggesting that it is expedient to use RTM in patients with high activity of SLE, especially when the latter is refractory to standard therapy with glucocorticoids and cytostatics. Attention is paid to the steroidsparing effect of RTM and to the reduction of the risk of irreversible organ damages associated with high-dose prednisone. The paper discusses the possibility of using a RTM biosimilar (Acellbia) and prospects of RTM therapy for early SLE.

USE OF RITUXIMAB IN PATIENTS WITH SYSTEMIC MANIFESTATIONS OF PRIMARY SJOGREN'S SYNDROME

The data on the efficacy of rituximab (RTM) in systemic manifestations of primary Sjogren's syndrome (PSS) are limited by single trials. Objective: to evaluate the efficacy of RTM in patients with the systemic manifestations of PSS. Subjects and methods. RTM therapy was performed in 24 patients with the systemic manifestations of PSS. The mean dose of a RTM for induction therapy cycle was 2±0.3 g. Nine patients received RTM monotherapy and 12 were treated with RTM in combination with cyclophosphan. A complete clinical response was defined as complete disappearance of pre-treatment clinical manifestations; a partial one was interpreted as more than 50% improvements in some signs or cessation of half of the existing signs. A complete immunological response implied normalization of a low baseline C4 level, disappearance of cryoglobulinemia and monoclonal immunoglobulins in serum and/or their light chains in urine; a partial one meant normalization or cessation of more than half of the initial signs. The remaining cases were regarded as no treatment response. A recurrence was considered to be the reoccurrence of at least one pretreatment sign during a 3-month or more follow-up. Results. At 3 months after RTM therapy, a complete or partial clinical response was observed in 71.4% (15/21) and 19% (4/21) of cases, respectively. A complete or partial immunological response was obtained in 50% (10/20) and 25 (5/20) of the patients, respectively. At 6 months, a clinical and immunological recurrence was noted in 25% (5/20) and 33% (6/18) of the patients, respectively. There was a reduction in median ESSDAI from 8 (7–10) (median, 25th and 75th percentiles) to 3 (2–4) at 3–6 months (p<0.001). After RTM therapy, medium serum BAFF concentrations in 9 patients decreased from 1.71 (0.66–2.73) to 0.68 (0.62–2.58) ng/ml (normal value <0.8 ng/ml). Conclusion. RTM shows good efficacy in treating systemic forms of PSS.

Absence of response to rituximab in patients with refractory primary immune thrombocytopenia

To explore the possible causes for an absence of response to rituximab (RTX) in patients with refractory immune thrombocytopenia (ITP). A total of 20 refractory ITP patients on RTX therapy and 10 health volunteers were recruited from 2008 to 2013. Memory T lymphocytes (Tm) (CD4(+)CD45RO(+)) and B lymphocytes (CD19(+)CD20(+)) in peripheral blood (PB) were examined by flow cytometry (FCM). And enzyme-linked immunosorbent assay (ELISA) was employed for detecting the platelet-associated antibodies IgG/IgM (PAIgG/IgM). (1) 12 patients with refractory ITP achieved a good response after therapy with RTX (effective RTX group) and 8 cases failed to respond (ineffective RTX group). The PB levels of CD4(+)CD45RO(+)Tm were 41.33% ± 9.62% and 45.36% ± 8.57% respectively at pre-therapy and post-therapy in ineffective RTX group. And significant differences existed between ineffective and effective RTX groups (22.36% ± 11.57%, 26.65% ± 6.32%) versus health volunteers (19.72% ± 7.35%, 20.64% ± 7.35%) (all P < 0.05) . No statistical differences existed in the PB level of CD4(+)CD45RO(+)Tm between pre-therapy and post-therapy in ineffective or effective RTX group (both P > 0.05); (2) The PB level of CD19(+)CD20(+)B lymphocytes in RTX ineffective group was lower than that at pre-therapy in RTX effective group (16.36% (6.17%-27.53%) vs 45.72% (35.80%-57.19%), P < 0.05) . No significant difference existed in the level of CD19(+)CD20(+)B at post-therapy between ineffective and effective RTX groups (6.67% (4.09%-19.17%) vs 5.19% (3.78%-17.39%), P > 0.05). And significant differences existed in the PB level of CD19(+)CD20(+)B between pre-therapy and post-therapy in ineffective or effective RTX group (both P > 0.05); (3) PAIgG/IgM was not detected in RTX ineffective group. And PAIgG/IgM was found in 11 cases at pre-therapy versus 1 case at post-therapy in RTX effective group. CD4(+)CD45RO(+)Tm is probably associated with an absence of response to RTX in patients with refractory ITP.

FRI0296 Is There A Difference in the Effectiveness in the Treatment of Rheumatoid Arthritis with Rituximab in Patients with Rheumatoid Factor Positive and Negative? A Systematic Review

BackgroundSince the description of the efficacy of rituximab (RTX) in treating patients with rheumatoid arthritis (RA), the use of this drug has been extended. However it is not clearly established...

FRI0392 Efficacy of Rituximab in Systemic Manifestations of Primary Sjogren's Syndrome

BackgroundThere is lack sufficient data on efficacy of Rituximab (RTX) in primary Sjogren's syndrome (pSS) with systemic manifestations.ObjectivesTo evaluate the efficacy of RTX in patients with systemic manifestations of primary...

FRI0386 Efficacy and Safety of Off-Label Use of Rituximab in Refractory Lupus: Data from the Italian Multicenter Registry

BackgroundDespite the failure of two randomized controlled trials a number of open-label studies and registries suggested the efficacy of rituximab (RTX) in systemic lupus erythematosus (SLE).ObjectivesThe aim of this observational...

AB0434 Relation of Subclinical Ultrasound Detected Synovitis and Peripheral B-Cell Counts in Rheumatoid Arthritis Patients Treated with Rituximab

BackgroundThe clinical response in patients with Rheumatoid Arthritis (RA) to rituximab (RTX) has been shown to be related with the presence of B-cells in the synovi. To date this has...

A Single Center Experience in Biological Therapy for the Treatment of Rheumatoid Arthritis in Saudi Arabia

Background: Biological therapy is indicated in the treatment of RA (Rheumatoid Arthritis) after failure of disease-modifying anti-rheumatic drugs (DMARDS) by the ACR/EULAR recommendations. The objective of the study is to describe the characteristics of Saudi patients at the initiation of biological therapy and to evaluate clinical effectiveness of this therapy measured by the disease activity score DAS 28. Methods: This was a retrospective cohort study of RA (rheumatoid arthritis) patients in King Fahad Hospital in Jeddah, Saudi Arabia from January 2005-July 2011. Data were collected from the medical records of all RA patients on biological therapy including: demographics, disease characteristics, comorbid illnesses and DAS 28 score over a period of 1 year. Results: 139 patients were studied (mean age 46 ± 13 years), of which 118 (84%) were females; mean duration of affliction with RA was 7.2 years ranging 1-45 years. Rheumatoid factor (RF) was positive in 88 patients (63.3%) and one or more comorbidities were present in 102 patients (73.3%). First choice of biological drug was ADA (Adalimumab) 44 patients (31.7%) and RTX (Rituximab) was the 2nd frequently prescribed biological drug. Mean DAS 28 activity at baseline was in ADA 41 patients (6.10 ± 1.62), ETA (Etarnercept) 29 patients (6.64 ± 1.42) and RTX 50 patients (6.7 ± 1.32). Moderate to good EULAR response was obtained in 74%, 85.7% and 53.3% at 6 months in ADA, ETA and RTX patients respectively. Moderate to good EULAR response was obtained in 61.8%, 86.6% and 72% in ADA, ETA AND RTX patients respectively at 1 year of treatment. Therapeutic effectiveness was comparable with the response rates in published observational trials. Conclusion: Our data demonstrate daily clinical practice in management of RA. The pattern of prescription is in agreement with the ACR/EULAR recommendations for initiation of biologicals in the treatment of RA.

Effects of Rituximab on the Development of Viral and Fungal Infections in Renal Transplant Recipients

Background. Rituximab is becoming increasingly utilized in renal transplant recipients; however, its association with infections remains unclear. Methods. We reviewed the incidence of viral and fungal infections in kidney transplant recipients treated with () or without () rituximab (RTX) in addition to standard immunosuppression. Results. Infections occurred in 134 (30%) patients, with a greater proportion in RTX versus no RTX patients (47% versus 28%; ). Viral infections occurred in 44% and 27% of RTX and no RTX patients, respectively (). This was largely driven by the frequency of BK viremia and noncytomegalovirus/non-BK viruses in RTX patients (27% versus 13% () and 15% versus 2% (), resp.). Fungal infections also occurred more often in RTX patients (11% versus 3 %; ). Multivariate analysis revealed deceased donor recipient (odds ratio = 2.5; ) and rituximab exposure (odds ratio = 2.2; ) as independent risk factors for infection. Older patients, deceased donor recipients, those on dialysis longer, and those with delayed graft function tended to be at a greater risk for infections following rituximab. Conclusions. Rituximab is associated with an increased incidence of viral and fungal infections in kidney transplantation. Additional preventative measures and/or monitoring infectious complications may be warranted in those receiving rituximab.

Impact of rituximab trials on the treatment of ANCA-associated vasculitis

ANCA-associated vasculitis (AAV) is a subgrouping of autoimmune disorders characterized by a chronic relapsing course. Induction therapy is usually effective, but 70% of patients will relapse and 20% develop refractory disease. In the relapsing and refractory subgroups, treatment is complicated by the cumulative exposure to toxic drugs that contribute to poor long-term outcomes. The anti-CD20 monoclonal antibody rituximab (RTX) depletes B cells, and the success of this targeted therapy has contributed to the evidence supporting a central role for B cells in AAV pathogenesis. Initial proof of RTX effectiveness originated from small, prospective trials and retrospective surveys conducted in AAV patients with relapsing and refractory disease; high remission rates permitted the reduction of glucocorticoids (GCS) doses and withdrawal of immunosuppressives. There has been controversy over the effectiveness of RTX in patients with predominantly granulomatous manifestations, where response rates have varied between studies, in part due to different RTX dosing regimens. These studies were followed by comparison of RTX against cyclophosphamide (CYC) for remission induction of new or relapsing AAV in two randomized trials, which led to the licensing of RTX for this indication. Subsequent attention has been turned to the use of RTX as a relapse prevention agent, to the potential for GCS sparing and to RTX-associated toxicity. We will discuss the impact that the results of RTX clinical trials have had on the management of AAV patients.

FRI0264 Treatment with rituximab in patients with systemic sclerosis

BackgroundLung involvement in the form of interstitial lung disease (ILD) is one of the most serious manifestations of systemic sclerosis (SSc). ILD develops in up to 80% of patients with...

FRI0226 Rituximab versus abatacept in rheumatoid arthritis patients with an inadequate response to prior biologic therapy: a retrospective single-center study

BackgroundPatients with RA who experience an inadequate response to TNF inhibitor (TNFi) therapy (TNF-IR) may be successfully treated using an alternative TNFi or a biologic with a different mode of...

THU0043 The Alternative CD20 Transcript Variant is not Expressed in B Cells and Synovial Tissue from Patients with Rheumatoid Arthritis

Backgrounddetermining predictive factors for response to biologics may help to select appropriate treatment in patients with RA. Rituximab (RTX) is a chimeric monoclonal antibody directed against the membrane CD20 protein...

THU0104 No expression of an alternative CD20 transcript variant in B cells from patients with rheumatoid arthritis

BackgroundTargeting B cells is an effective therapy in rheumatoid arthritis (RA). Rituximab (RTX) is a chimeric monoclonal antibody directed against the membrane CD20 protein present on B cells. Predictive factors...

OP0213 Rituximab Versus Azathioprine for Maintenance in Antineutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis (MAINRITSAN): Follow Up at 34 Months

BackgroundThe prospective, randomized, controlled MAINRITSAN trial compared rituximab (RTX) to azathioprine (AZA) to maintain ANCA-associated vasculitis (AAV) remission. Once remission was obtained with a conventional regimen, patients were randomly assigned...

THU0120 Long-term safety of rituximab: 10-year follow-up in the rheumatoid arthritis global clinical trial programme

ObjectivesTo evaluate the long-term safety of rituximab (RTX) in rheumatoid arthritis (RA) patients in a global clinical trial programme.MethodsA pooled observed case analysis of safety data from patients with moderate...