Safety Of Rituximab Treatment Research Articles

Clinical case of steroid-dependent nephrotic syndrome in a child

Nephrotic syndrome (NS) is a common glomerular pathology encountered in pediatric practice. The main clinical signs are massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Among all cases of NS, 75 % of children have a histological variant of glomerular lesions in the form of minimal change di­sease that is sensitive to hormone therapy, but easily leads to relapse and steroid dependence. These children often need to extend the time of taking hormonal drugs or add other immunosuppressants, which can have significant toxicity. Available immunosuppressant treatment options include cyclophosphamide, cyclosporine A, tacrolimus, and mycophenolate mofetil. The use of rituximab is a possible alternative treatment for steroid-dependent nephrotic syndrome in children. However, the efficacy and safety of ritu­ximab in the treatment of childhood steroid-dependent nephrotic syndrome is still controversial. The purpose was to evaluate the efficacy and safety of rituximab treatment in a child with steroid-dependent nephrotic syndrome on the example of a clinical case from our own practice.

Efficacy and safety of rituximab for primary membranous nephropathy with different clinical presentations: a retrospective study.

Rituximab (RTX) is gaining increasing clinical acceptance in the treatment of primary membranous nephropathy (PMN), with demonstrated efficacy and safety. However, there are few clinical studies on RTX for PMN in Asian populations, especially in China. To observe and analyse the efficacy and safety of RTX treatment, 81 patients with PMN suffering from nephrotic syndrome (NS) were enrolled and divided into an initial therapy group, a conventional immunosuppressive therapy relapse group, and a conventional immunosuppressive therapy ineffective group according to their pre-RTX treatment background. Patients in each group were followed up for 12 months. The primary outcome was clinical remission at 12 months, and the secondary outcomes were safety and the occurrence of adverse events. At 12 months, 65 of 81 (80.2%) patients achieved complete (n=21, 25.9%) or partial (n=44, 54.3%) remission after rituximab treatment. Thirty-two of 36 (88.9%) patients in the initial therapy group, 11 of 12 (91.7%) patients in the relapse group and 22 of 33 (66.7%) patients in the ineffective group achieved clinical remission. All 59 patients with positive anti-PLA2R antibodies showed a decreasing trend in antibody levels after RTX treatment, and 55 (93.2%) of them achieved antibody clearance (<20 U/mL). Logistic regression analysis showed that a high anti-PLA2R antibody titer (OR=0.993, P=0.032) was an independent risk factor for nonremission. Adverse events occurred in 18 (22.2%) patients, of which 5 (6.2%) were serious adverse events, and none were malignant or otherwise fatal. RTX alone can effectively induce remission PMN and maintain stable renal function. It is recommended as the first choice of treatment and is also effective in patients who relapse and have poor responses to conventional immunosuppressive therapy. Anti-PLA2R antibodies can be used as a marker for RTX treatment monitoring, and antibody clearance is necessary to achieve and improve the rates of clinical remission.

Efficacy and safety of rituximab in treatment of systemic sclerosis: A retrospective study

Efficacy and safety of rituximab in treatment of systemic sclerosis: A retrospective study

Efficacy and safety of rituximab treatment in patients with idiopathic inflammatory myopathies: A systematic review and meta-analysis.

Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune diseases with various subtypes, myositis-specific antibodies, and affect multiple systems. The treatment of IIMs remains challenging, especially for refractory myositis. In addition to steroids and traditional immunosuppressants, rituximab (RTX), a B cell-depleting monoclonal antibody, is emerging as an alternative treatment for refractory myositis. However, the therapeutic response to RTX remains controversial. This meta-analysis aimed to systematically evaluate the efficacy and safety of RTX in patients with IIMs, excluding sporadic inclusion body myositis. PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and WanFang Data were searched for relevant studies. The overall effective rate, complete response rate, and partial response rate were calculated to assess the efficacy of RTX. The incidences of adverse events, infection, severe adverse events, severe infection, and infusion reactions were collected to evaluate the safety of RTX. Subgroup analyses were performed using IIM subtypes, affected organs, continents, and countries. We also performed a sensitivity analysis to identify the sources of heterogeneity. A total of 26 studies were included in the quantitative analysis, which showed that 65% (95% confidence interval [CI]: 54%, 75%) of patients with IIMs responded to RTX, 45% (95% CI: 22%, 70%) of patients achieved a complete response, and 39% (95% CI: 26%, 53%) achieved a partial response. Subgroup analyses indicated that the overall efficacy rates in patients with refractory IIMs, dermatomyositis and polymyositis, as well as anti-synthetase syndrome were 62%, 68%, and 62%, respectively. The overall efficacy rates for muscle, lungs, and skin involvement were 59%, 65%, and 81%, respectively. In addition, studies conducted in Germany and the United States showed that patients with IIMs had an excellent response to RTX, with an effective rate of 90% and 77%, respectively. The incidence of severe adverse events and infections was 8% and 2%, respectively. RTX may be an effective and relatively safe treatment choice in patients with IIMs, especially for refractory cases. However, further verification via randomized controlled trials is warranted.

Efficacy and Safety of Rituximab in Chinese Children With Refractory Anti-NMDAR Encephalitis.

Purpose: To assess the efficacy and safety of rituximab treatment as second-line immunotherapy in pediatric cases of anti-NMDA receptor (NMDAR) encephalitis.Methods: We retrospectively recruited 8 patients with anti-NMDAR encephalitis who were treated with rituximab as second-line immunotherapy. We evaluated the clinical features, laboratory examination results and treatment protocols of the Chinese children and defined good outcomes based on the modified Rankin scale (mRS) score (0–2) at the last follow-up.Results: A total of eight pediatric patients (median age 6.7 years; four female) with refractory anti-NMDAR encephalitis were recruited to the study. Rituximab was given after a median duration of disease of 57 days (range 50.5–113.75 days). The use of rituximab led to a significant reduction in the mRS and CD19+ B-cells compared to before rituximab infusion (P < 0.05). Five patients (62.5%) had a good outcome (mRS ≤ 2) including four patients (50%) who showed complete recovery (mRS = 0) at the last follow-up. Transient infusion adverse events were recorded in 2 patients (25%). Two patients (25%) had severe infectious adverse events (AEs) and two patients with grade 5 (death). None of the patients developed progressive multifocal leukoencephalopathy (PML).Conclusion: Our study provides evidence that rituximab can efficiently improve the clinical symptoms of anti-NMDAR encephalitis in children. However, due to the risk of adverse infections, rituximab should be restricted in pediatric patients with high rates of mortality and disability.

Treatment of fibrillary glomerulonephritis with rituximab: a 12-month pilot study.

Fibrillary glomerulonephritis (FGN) is a rare type of glomerulonephritis with poor prognosis, with no known effective therapies available for treatment. The objective of the study was to evaluate the efficacy and safety of rituximab in treatment of patients with FGN and to investigate the effect of rituximab on DNAJB9 levels. This was a pilot prospective clinical trial in which patients with idiopathic FGN were treated with two courses of rituximab (1 g each) 2 weeks apart at the beginning and then again at 6 months. Primary outcome was defined as preservation of kidney function at 12 months with stable or increased creatinine clearance. Secondary outcome was defined as achieving complete remission (CR) defined as proteinuria <300 mg/24 h or partial remission (PR) with proteinuria <3 g/24 h and at least 50% reduction in the proteinuria. DNAJB9 levels were also measured in the serum at baseline, 6 and 12 months. The creatinine clearance did not change significantly during this time, from 47.7 mL/min/1.73 m2 at baseline to 43.7 mL/min/1.73 m2 during follow-up (P = 0.15). Proteinuria declined from 4.43 (1.6-5.53) g/24 h at baseline to 1.9 (0.46-5.26) g/24 h at 12 months but did not reach significance (P = 0.06). None of the patients reached CR, and 3 of the 11 achieved PR. There was no change in the DNAJB9 levels following treatment with rituximab. The most common adverse event was nasal congestion, fatigue and muscle cramps. Treatment of patients with two courses of rituximab over a span of 6 months was associated with stabilization of renal function but did not result in a significant change in proteinuria and with no change in the DNAJB9 levels.

Efficacy and safety of rituximab in patients with refractory neuromyelitis optica spectrum disorders: A prospective observation in Iranian cases.

Background:Rituximab has been used successfully in the recent years for treatment of neuromyelitis optica spectrum disorders (NMOSD). However, a uniform treatment protocol for maintenance therapy and the best interval for evaluation and retreatment have not been postulated. We evaluated the efficacy and safety of rituximab treatment as second line therapy, in Iranian patients with refractory NMOSD, based on annualized relapse rate (ARR) and expanded disability status scale (EDSS).Methods:In this prospective before-after study, a total of 18 patients were treated with a loading dose of rituximab (375 mg/m2 weekly in 4 consecutive weeks). Flow cytometric determination of CD19+ B cell in peripheral blood sample was carried every 6 weeks and patients were re-treated based on B cell repopulation with a single dose of 375 mg/m2. Wilcoxon signed rank test was used to evaluate the ARR and EDSS before and after treatment. A p-value of <0.05 was considered statistically significant.Results:Of the 18 patients, 10 (55.5%) were relapse-free during the period of follow up. The EDSS scores were reduced in nine (50%) patients and stable in the remaining nine (50%). The mean EDSS score before and after treatment were 4.1±0.4 and 3.7±0.3, respectively, which was statistically significant. There was also a statistically significant reduction in median ARR after treatment (1.48 (range 0.47-5) vs. 0 (range 0-2)). Rituximab administration did not have significant adverse effect in 94% of patients.Conclusion:Repeated treatment with Rituximab is an effective and well-tolerated treatment in refractory NMOSD.

Efficacy of rituximab in resistant palindromic rheumatism: first report in literature.

Rituximab (RTX) provides significant clinical benefits in active rheumatoid arthritis (RA) patients with inadequate response to DMARDs and anti-TNF. There is no data regarding efficacy of RTX in seropositive Palindromic Rheumatism (PR), a forerunner of RA. To determine the efficacy and safety of RTX treatment in active PR patients exhibiting inadequate response to conventional synthetic DMARDs (csDMARDs). The retrospective study, over a period of 3years, included seropositive (RF ± antiCCP) PR patients with inadequate control of PR (> 4 attacks per months) despite combination csDMARDs and were treated with RTX. All the patientswere treated with an initial dose of 500mg RTX and later with a second infusion after 2 weeks' period in those who did not achieve adequate/ complete disease control. Patients were continued on csDMARDS and retreated with RTX on relapse of symptoms. Thirty-three seropositive PR patients with a mean age of 48.15 ± 14.2years, mean disease duration of 68.4 ± 68.2 months, mean follow up period of 24.3 ± 10.8months, were treated with RTX. 88% patients were on combination DMARDS and 79% patients were females.All patient achieved rapid and complete control of palindromic attacks with RTX. Fifteen patients had a relapse after a mean duration of 10.4 ± 5.5months and needed repeat RTX infusions following which remission was achieved. None of the patients progressed to RA till the end of the follow-up. No serious adverse effects were recorded. RTX treatment could be effective in achieving disease control in active palindromic rheumatism not responding to csDMARDs. • PR is thought to be a forerunner of RA and rituximab (RTX) has been found to be effective in RA. • Our study supports the hypothesis that B cells play an important role in the pathophysiology of PR and that the combination (RTX+ conventional drugs) can prevent the disease evolution into RA. • This 3-year retrospective study showed that rituximab was found to be effective in those who responded poorly to conventional drugs and remission was achieved in all patients. • Although it is a rare disease, we see palindromic rheumatism patients in India more often. As the symptoms are very debilitating in these patients, in those patients, not controlled on conventional drugs, rituximab offers newer promise in controlling the attacks and prevents further progression to RA.

Retrospective analysis of rituximab therapy and splenectomy in childhood chronic and refractory immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) results from accelerated platelet destruction mediated by autoantibodies to platelet glycoproteins. Some patients with chronic ITP are refractory to all therapies [steroids, intravenous immunoglobulin (IVIG), anti-D and immunosuppresive drugs] and have chronic low platelet counts and episodic bleeding. We retrospectively evaluated the efficacy and safety of rituximab treatment and splenectomy in paediatric patients diagnosed with chronic and refractory ITP who were unresponsive to steroids, IVIG, cyclosporine and mycophenolate mofetil. Records of patients with chronic and refractory ITP in 459 patients with primary ITP who were followed up in our hospital from January 2005 to December 2014 were reviewed. Fifteen of patients received rituximab and/or applied splenectomy. Fifteen chronic ITP patients (10 boys, five girls) with a mean age of 10 years were enrolled in the study. Two of these patients were suffering from Evans syndrome. The median time since diagnosis of ITP was 10 years. The median follow-up duration after starting Rituximab and splenectomy were 13 and 9.5 months, respectively.None of the seven patients who were treated with rituximab achieved a response. A splenectomy was performed in six of the seven patients who had been treated with rituximab. Complete and partial responses were achieved in 67 and 33% of the patients, respectively. We evaluated the clinical characteristics and responses of chronic ITP patients who did not receive rituximab therapy and underwent a splenectomy. The success rate was 100% in the eight patients with chronic and refractory ITP. Rituximab therapy might not be beneficial for some children with severe chronic ITP who are refractory to standard agents. A splenectomy might be useful and preferable to rituximab.

Spotlight on the May 3 Issue

#### Notable in Neurology This issue features an article assessing whether migraine was associated with increased systemic right-to-left shunts or whether right-to-left shunts increased prevalence of brain infarcts and recurrence of migraine attacks and another article determining efficacy and safety of rituximab treatment as an immunotherapy treatment for autoimmune limbic encephalitis. A featured article focuses on investigating the association of seizures and fluoroquinolones and providing an estimation of the absolute risk. ### Brain stimulation and constraint for perinatal stroke hemiparesis: The PLASTIC CHAMPS Trial![Graphic][1]</img>![Graphic][2]</img> The authors demonstrated additive benefits of constraint-induced movement therapy (CIMT) and contralesional repetitive transcranial magnetic stimulation (rTMS) in enhancing long-term functional gains from … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif

Rituximab treatment for autoimmune limbic encephalitis in an institutional cohort.

To determine efficacy and safety of rituximab treatment as a second-line immunotherapy treatment for autoimmune limbic encephalitis (ALE) and to determine factors associated with functional improvement and favorable outcome following rituximab treatment. We recruited 80 patients with ALE who were treated with rituximab as a second-line immunotherapy from the Korea Autoimmune Synaptic and Paraneoplastic Encephalitis Registry and reviewed 81 patients without rituximab as a control. We grouped patients according to the detection or type of antibodies; in addition, we evaluated clinical, laboratory, first-line immunotherapy, and rituximab treatment profiles and defined main outcomes as improvements on the modified Rankin Scale (mRS) score and a favorable mRS score (0-2) at the last follow-up. Functional improvement occurred more frequently in the rituximab group compared to the control group. In the rituximab group, 30 (37.5%) patients had synaptic autoantibodies, 15 (18.8%) in the paraneoplastic autoantibodies, and 35 (43.8%) were antibody-negative. The effect of rituximab was the same regardless of autoantibody status. Additional monthly rituximab therapy and partial response to first-line immunotherapies were associated with mRS score improvements, as well as favorable mRS scores. mRS scores of 4-6 as the worst neurologic status predicted an unfavorable mRS score. There were no reported serious infusion-related or infectious adverse effects of rituximab. Rituximab is effective and safe as a second-line immunotherapy for ALE, regardless of autoantibody status. Additional monthly rituximab therapy might potentiate the efficacy of rituximab. This study provides Class IV evidence that rituximab improves mRS scores for patients with autoimmune limbic encephalitis who fail first-line therapy.

EFFICACY AND SAFETY OF RITUXIMAB IN CHILDREN WITH SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS OF A RETROSPECTIVE STUDY OF THE CASE SERIES

Background. Blocking of B lymphocytes producing autoantibodies in systemic lupus erythematosus (SLE) may be an effective strategy for pathogenetic treatment, including in children. Objective: Our aim was to assess the efficacy and safety of rituximab treatment (chimeric monoclonal antibodies to CD20) in children with severe SLE refractory to glucocorticosteroids and immunosuppressants. Methods. We studied the case histories of children with SLE admitted to the rheumatology department of the SCCH between 2004 and 2013. The treatment results were assessed by the SELENA SLEDAI Disease Activity Index, Damage Index scale, and dynamics of the values of laboratory disease activity indices. Results. We analyzed the results of rituximab treatment in 12 patients for 24 weeks, 11 of them — for 48 weeks. The preparation was administered intravenously at a dose of 375 mg/m 2 of the body surface area to administer 4 times weekly (n = 10) or 2 times with an interval of 2 weeks ( n = 2). After 48 weeks of rituximab treatment, SELENA SLEDAI index values decreased from 16 (11, 21) to 1 (0, 2) (p < 0.001), Damage Index — from 3.5 (1.0, 5.0) to 1.0 (0.0, 3.0) (p = 0.024), complement component C4 concentration increased from 0.13 (0.04, 0.19) to 0.43 (0.18, 0.50) g/l (p = 0.017), the number of antibodies to double-stranded DNA decreased from 73.5 (11.5, 245.0) to 1.9 (0.0, 40.0) IU/ml (p = 0.004). Depletion of B lymphocytes was recorded in all patients after 24 and 48 weeks of rituximab treatment. Prednisolone dose was reduced from the initial 0.80 (0.43, 1.00) mg/kg per day to 0.20 (0.17, 0.30) after 48 weeks (p = 0.025). Disease exacerbations during 48 weeks have not been reported. Such serious adverse events as pneumonia ( n = 2), neutropenia ( n = 5), Herpes zoster infection ( n = 2), hypogammaglobulinemia ( n = 8) were noted. Conclusion. High efficacy and satisfactory risk-benefit profile of rituximab treatment in children with severe SLE refractory to glucocorticosteroids and immunosuppressants have been shown.

Treatment Outcomes With Rituximab in 100 Patients With Neuromyelitis Optica: Influence of FCGR3A Polymorphisms on the Therapeutic Response to Rituximab.

Despite the increased use of rituximab therapy in neuromyelitis optica spectrum disorder (NMOSD), the overall efficacy and safety of long-term rituximab treatment in a large group of patients is uncertain. Furthermore, the identification of a predictor of rituximab response is an important issue for assessing the individual risk-benefit of therapy and making treatment decisions. To assess the long-term clinical efficacy and safety of rituximab treatment in patients with NMOSD and the influence of fragment c gamma receptor 3A (FCGR3A) polymorphisms on rituximab response. A retrospective review of 100 patients with relapsing NMOSD treated with rituximab for at least 6 months, from February 1, 2006, to January 31, 2015, at the institutional referral center. After induction therapy, a single infusion of rituximab (375 mg/m2) as maintenance therapy was administered whenever a reemergence of CD27+ memory B cells among peripheral blood mononuclear cells occurred. Using an allele-specific polymerase chain reaction-based method, the gene polymorphisms FCGR3A-V158F were assessed. The primary end point was annualized relapse rate; disability (Expanded Disability Status Scale score), safety of rituximab treatment, event of insufficient memory B-cell depletion following rituximab, and time to retreatment of rituximab were secondary end points. By January 31, 2015, a total of 100 patients received repeated rituximab treatment during a median of 67 months. Of these patients, 41 had more than 5 years' follow-up and 24 had more than 7 years' follow-up. The annualized relapse rate was reduced significantly by 96% (mean [SD] annualized relapse rate of prerituximab vs postrituximab, 2.4 [2.0] vs 0.1 [0.6]) and disability improved or stabilized in 96% of patients. Rates of adverse events were generally stable. The FCGR3A-F allele was associated with a risk of relapse while receiving rituximab treatment (additive model, P < .05; recessive model, P = .04; maximum, P = .03) and insufficient memory B-cell depletion (additive model, P = .03; recessive model, P = .03; maximum, P = .03). Repeated rituximab treatment for NMOSD was observed in an increasing number of patients and increasing duration of exposure and maintained good efficacy and a safety profile consistent with previous reports. The finding of a relationship between FCGR3A genetic polymorphisms and rituximab response suggests the importance of individualized rituximab treatment strategies in NMOSD.

Rituximab plus standard of care for treatment of primary immune thrombocytopenia: a systematic review and meta-analysis

Rituximab is commonly used as a treatment for primary immune thrombocytopenia to induce and maintain remission. The benefit of adding rituximab to standard-of-care treatment is uncertain. We did a systematic review and meta-analysis of randomised controlled trials assessing the efficacy and safety of rituximab for treatment of adults with primary immune thrombocytopenia. We searched Medline, Embase, and the Cochrane database in duplicate and independently from inception up to July 31, 2014, for relevant studies. Primary outcomes were the proportion of patients achieving a complete platelet count response and a partial platelet count response (as defined in primary studies) that was maintained until the end of follow-up. We also assessed bleeding, infection, and infusion reactions. Our database search returned 468 abstracts, of which five trials (with total of 463 patients) were eligible for analysis. No patients had splenectomy at the time of enrolment. Median follow-up was 6 months (IQR 6-12). Complete response (>100 × 10(9) platelets per L without rescue therapy) was more common with rituximab than with standard of care (weighted proportions: 46·8% vs 32·5%; relative risk [RR] 1·42, 95% CI 1·13-1·77; p=0·0020). Partial response was not significantly different between groups (57·6% vs 46·7%; RR 1·26, 95% CI 0·95-1·67; p=0·11). Rituximab was not associated with a reduction in bleeding (9·2% vs 5·2%; RR 1·34, 95% CI 0·63-2·87; p=0·44) or an increase in infections (20·1% vs 12·1%; RR 1·40, 95% CI 0·87-2·26; p=0·17). Rituximab can improve complete platelet count responses by 6 months in patients with immune thrombocytopenia. Evidence for sustained responses beyond 6-12 months is limited. Clinicians must consider the goals of treatment before prescribing rituximab. None.

Safety of rituximab in the routine treatment of rheumatoid arthritis in Italy in patients refractory to anti-TNFa drugs: results from the observational retrospective-prospective RUBINO study.

The paper reports the results from the observational retrospective-prospective RUBINO study conducted in Italy to assess the safety of rituximab in the treatment of rheumatoid arthritis (RA) in routine clinical practice. The percentage of patients who manifested at least one grade 3 or 4 adverse event (AE) assessed by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v.3) during the observation period (primary objective) was evaluated. The percentage of patients manifesting a severe AE (SAE), clinical response to rituximab treatment, clinical remission according to disease activity score for 28 joints (DAS28) criteria, markers of disease and quality of life were also assessed. Fifty-three Italian rheumatology centers took part in the study. Patients with a diagnosis of RA and inadequate response to anti-tumor necrosis factor b (anti-TNFa) drugs were enrolled. Participating patients had previously received at least one cycle of rituximab, and treatment was still ongoing at the time of recruitment. Out of 205 patients enrolled, 60% manifested no form of AE, 14.2% had at least one grade 3 or 4 AE, and 11.2% patients reported an SAE. The overall percentage of patients manifesting AEs (40%) was lower compared to the DANCER (81% and 85%), REFLEX (85%) and RESET (85% and 69%) studies, but higher than that observed in the CERERRA registry (from 10.2% to 13.9%). This difference may be due to the shorter observation period applied in the CERERRA registry (only 12 months) compared to the RUBINO study (up to 3 years). All parameters of RA activity (erythrocyte sedimentation rate, C-reactive protein, health assessment questionnaire score, DAS28) improved significantly during the study.

Rituximab in Previously Treated Primary Immune Thrombocytopenia Patients: Evaluation of Short- and Long-Term Efficacy and Safety

The anti-CD20 chimeric monoclonal antibody rituximab has been effectively used in the treatment of patients with primary immune thrombocytopenia (pITP). We retrospectively evaluated 19 patients affected by pITP resistant to 2 or more lines of therapy who were treated with rituximab. Nine of the 19 patients showed an initial response (47.4%). The sustained response rate was 31.6% (6/19). The median follow-up of the patients was 53.2 months (range 9.2-92.9). Disease-free survival at 48 months was 62.2%. Following rituximab treatment, a proportion of patients (42%) recovered a normal B lymphocyte number. During the follow-up, no opportunistic or severe infectious complications were observed. These data confirm, over a long period of observation, the efficacy and safety of rituximab treatment in the management of patients with resistant pITP.

Rituximab Is Highly Effective In The Treatment Of Patients With Autoimmune Blood Cytopenias, Particularly When It Is Followed By a Post-Induction Consolidation / Maintenance Phase

Rituximab is a chimeric anti-CD20 monoclonal antibody, which targets both, autoreactive and neoplastic B-lymphocytes, thus representing a rational therapeutic approach for patients with various autoimmune disorders. However, although rituximab has been used asa treatment option for patients with autoimmune blood cytopenias, its optimal use has not yet been established.In an effort to analyze the effectiveness and safety of rituximab treatment in this patient population, we have retrospectively analyzed treatment outcome of 147 patients with various autoimmune blood cytopenias or related disorders (AutoImmuneHemolytic Anemia-AIHA N=31, Immune Thrombocytopenic Purpura-ITP N=67, Thrombotic Thrombocytopenic Purpura-TTP N=32, Evans'Syndrome-ES N=10, Acquired Hemophilia-AH N=4, Anti-Phospholipid Syndrome-APS N=2 and Immune Neutropenia-IN N=1). Eligible patients should have received at least 3 courses of rituximab treatment, unless would have been died earlier due to treatment-related causes.Patients were 68 male and 79 female, with a median age of 52 years (range 15-87 years) and were treated following 1-7 (median 2) lines of previous treatment, for an early (<12 months, N=42) or a late relapse (>12 months, N=39) or for refractory disease (N=48), at a median of 3.4 months following initial diagnosis (range 0.1-430 months). Eighteen patients received rituximab as first-line treatment due to contra-indication (N=10) or intolerance (N=8) of corticosteroids. Rituximab was administered at the classical dose of 375 mg/m2 (N=113) or at a reduced dose of 200 mg/m2 (N=26), whereas 8 patients initially received 375 mg/m2 for 1-6 cycles and continued with the reduced dose.Each patient received a median of 6 courses of rituximab (range 1-60 courses). Four out of 143 patients were HBsAg positive, and 62/133 were anti-HBc positive. These patients received lamivudineprophylaxis,throughout rituximab treatment and up to 6 months following rituximab withdrawal. Seven patients (4.8%) received <3 courses of treatment and were not considered evaluable for response. Overall, complete response was achieved by 102 patients (72.9%), partial response by 15(10.7%) whereas 23 patients (16.3%) did not respond. Complete response was 64.5%, 75.4%, 74.2% and 76.5% for patients with AIHA, ITP, TTP and other diseases, respectively. Response rate was similar for patients treated with 375 mg/m2 and for those received 200 mg/m2 (76/113∼67.3% versus 18/26∼69.2%, respectively, p:n.s) and did not also differ significantly,in relation to patient's age, previous splenectomy and lines of previous treatment. Four patients received only one treatment course, due to a major allergic reaction or death, unrelated to treatment and were excluded from the analysis. Manageable reactions were observed in at least 13 patients. After a median follow-uptime of 28 months (range 2-143 months), 32 responded patients relapsed (9/26 with AIHA, 14/53 with ITP, 4/25 with TTP, and 5/25 with other diseases). However, only 10/88(11.4%)of the patients, who received post-remission consolidation/maintenance treatment, did relapse, as compared to 21/55 (38.2%)of the patients, who did not receive such a treatment (p<0.01).After a median follow-up time of 45 months, 128 patients are alive, 102 of them in complete response, 14 in partial, and 12 in active/refractory disease. Thirteen patients have died, 8 of them due to causes related to refractory disease and 5 from unrelated causes, and finally 6 patients have been lost from follow-up.Rituximab represents an effective second-line treatment approach for patients with autoimmune blood cytopenias. The dose of 200 mg/m2 is equally effective to the dose of 375 mg/m2. Patients receiving post-remission maintenance appear to exhibit more durable and sustained responses. Disclosures:Off Label Use: This abstract analyzes retrospectively the experience of the clinical use of Rituximab as second-line treatment of patients with refractory/relapsed autoimmune blood cytopenias. Although not yet approved as treatment in this group of patients, rituximab is extensively used in these disorders, but no specific guidelines, prospective studies or large retrospective studies have been published by now.

THU0324 Rituximab for severe disease flares in childhood ANCA vasculitides

BackgroundChildren with ANCA vasculitides frequently present with life-threatening organ manifestations including alveolar hemorrhage, critical subglottic stenosis and renal failure due to rapidly progressive glomerulonephritis (GN). The current initial management for...

AB0848 Rituximab treatment for spondyloarthritis. A nationwide series: Data from the air registry

BackgroundOnly few data are available about rituximab (RTX) in spondyloarthritis.ObjectivesThe aim of this study was to evaluate efficacy and safety of rituximab treatment in several subsets of spondyloarthritis (SpA) using...

Efficacy and Safety of Prolonged Rituximab Treatment in Patients with Systemic Juvenile Idiopathic Arthritis

Aim : to assess efficacy and safety of rituximab treatment in children with systemic juvenile idiopathic arthritis under prolonged follow-up. Patients and methods: results of treatment of 60 children (33 girls and 27 boys) with systemic variant of juvenile idiopathic arthritis being followed-up in rheumatology department of the Federal State Institution «Scientific Centre of Children Health» of RAMS (FSI «SCCH» RAMS) were analyzed. The mean age of children was 8,7 years. The mean duration of disease course at the moment of first rituximab administration was 5,3 years. At the beginning of rituximab therapy all children had active articular syndrome, severe systemic manifestations and significantly increased laboratory markers of activity. As the signs of improvement the authors used pediatric criteria of the American College of Rheumatology. The treatment was approved by the local ethic committee of the FSI «SCCH» RAMS; the patients’ representatives and patients older than 14 years old had signed informed agreement. Results: remission was induced in 26 of 60 (43%) patients: in 9 of them after the 1 st course of treatment, in 8 — after the 2 nd , in 6 — after the 3d and in 3 — after the 4 th . The maximal duration of remission was 5 years 4 months, minimal — 6 months. Other genetically engineered drugs were administered to 34 (57%) of the patients: due to the primary inefficiency in 15, secondary inefficiency — in 10; due to partial inefficiency — in 9 children. The drug was well-tolerated in most of the patients. Undesirable effects were represented by transfusional reactions to the rituximab infusion, infections with different severity and granulocytopenia. Conclusions: rituximab has high efficiency in patients with severe systemic variant of juvenile idiopathic arthritis. The drug induced remission in patients who had been considered almost incurable, with low status of physical and social adaptation.