In two RCTs, DANCER26 and SERENE,28 no significant differences in the clinical response of the two doses of rituximab (two doses of 500 mg versus two doses of 1,000 mg) could be demonstrated in MTX inadequate responders. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximabs Efficacy in MTX iNadequate rEsponders (SERENE)). Advertisement intended for healthcare professionals. Although rituximab is a drug of choice for lymphoma and refractory autoimmune diseases in the Asian Pacific countries, its overall usage is unclear because of a general lack of published postmarketing surveys and registries in this region of the world. Serum immunoglobulin levels should be regularly monitored in long-term users of rituximab. These reactions are usually mild to moderate but may require additional interventions such as paracetamol, antihistamines, bronchodilators, and further doses of glucocorticoids. Gheuens S, Pierone G, Peeters P, Koralnik IJ. An official website of the United States government. Two protocols were used. Vaccination response to protein and carbohydrate antigens in patients with rheumatoid arthritis after rituximab treatment. Vital et al19 correlated the degree of B cell depletion after rituximab therapy for RA with the clinical response achieved. The incidence of HACAs to rituximab ranged from 2.7% to 7.9%.2630 A pooled analysis on the long-term safety of rituximab in clinical trials (2,578 patients) revealed that HACAs were present in 11% of patients on at least one visit.62 There was no obvious relationship between the dose of rituximab used (500 mg versus 1,000 mg) and the incidence of the HACA response. Leandro MJ, Cooper N, Cambridge G, Ehrensein MR, Edwards JC. Users were predominantly RA patients (98%) because this is the only subsidized indication for rituximab. Solution, Intravenous [preservative free]: Rituxan: 100 mg/10 mL (10 mL) [contains polysorbate 80] Rituxan: 10 mg/mL (50 mL) [contains mouse (murine) and/or hamster protein, polysorbate 80] has received departmental support for research and education, and/or honoraria for advisory board work from Abbott, Merck Sharpe and Dohme (MSD), Napp, Pfizer, Roche and UCB. Owczarczyk K, Lal P, Abbas AR, et al. Sellam J, Rouanet S, Hendel-Chavez H, et al. Attention was shifted to other players of the immune system such as T cells, macrophages, dendritic cells, and fibroblasts.3 Revival of interest in the B cell pathogenesis of RA was related to the discovery of autoantibodies that direct against citrullinated peptides.4 Moreover, the success of B cell depletion therapy in the treatment of RA in the past decade has led to a renaissance of B cells as key mediators of RA.5, The precise contribution of B cells to the pathogenesis of RA is not well defined.6 In addition to the production of RF and other autoantibodies such as antibodies against citrullinated cyclic peptide (anti-CCP), B cells have many other potential roles. Oren S, Mandelboim M, Braun-Moscovici Y, et al. Extended observation of randomized controlled trials in RA does not reveal a significant increase in the incidence of serious infections related to rituximab compared to placebo groups, and the infection rate remains static over time. Accessibility However, serious infection was more frequent in patients with low IgG than those who never developed low IgG. RF may also perpetuate B cell activation, leading to further production of RF. Our study did not show non-inferiority of ultra-low doses of rituximab for continued treatment of patients with rheumatoid arthritis. 2018 Oct;48(2):149-154. doi: 10.1016/j.semarthrit.2018.02.010. 4 UNI | 4.95 per 1UNI. 's organization, the National Rheumatoid Arthritis Society, has received educational grants for projects undertaken by the charity in 2010. PML is a rare but severe infection of the brain caused by the John Cunningham virus, characterized by progressive inflammation and demyelination of the white matter at multiple sites. (Level Ia evidence, Grade of recommendation A. Some patients had lymphopenia before rituximab treatment and concomitant cancer disorders. No effective treatment is available and mortality is high.74 In a review of 38 cases of PML in non-human-immunodeficiency-virus (HIV) patients, mortality was reported in 71% of patients and the median time from onset of symptoms to death was 8 months.75. Repeated treatment with rituximab is associated with hypogammaglobulinemia, which may increase the risk of serious, but rarely opportunistic, infections. Similarly, a more recent study (ASSURE) showed an increased incidence of serious adverse events and serious infections with abatacept treatment in combination with another biological agent in patients with RA.38. Careers. The possible association of rituximab and progressive multifocal leukoencephalopathy may still require vigilance. However, rituximab is the only biologic marketed for specific B cell targeting therapy in RA. Cohen SB, Emery P, Greenwald MW, et al.REFLEX Trial Group Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Write a review. Rituximab is a genetically engineered chimeric anti-CD20 monoclonal antibody that is approved for the treatment of relapsed or refractory, low-grade or follicular, CD20+ B-cell non-Hodgkin's . Patients with elevated HBV DNA titers should be referred to hepatologists for antiviral treatment. Before commencement of rituximab, a detailed medical history that includes allergies, medical comorbidities, and recurrent infections should be taken and a complete physical examination should be performed to consider possible contraindications. Rituximab, an anti CD20 monoclonal antibody, is used in the management of lymphoproliferative and autoimmune conditions. An update on safety aspects based on the increasing experience of this drug was performed to advise colleagues regarding toxicity and the safe use of the drug. The management of occult hepatitis B infection in rituximab users remains unclear. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled . It is well recognized that repeated courses of rituximab are associated with secondary hypogammaglobulinemia.66,67 In an open-label extended analysis of three RCTs of rituximab in 1,039 RA patients, the proportion of patients with serum IgM below the lower limit of the normal range was 10.3% at week 24, 18.5% after the second course, and 23.5% after the third course.67 A similar pattern was observed for IgG: 1.5% had levels below the lower limit of normal at week 24, 4.3% after the second course, and 5.9% after the third course. Recommendation 1: if MTX is contra-indicated, rituximab should be used in RA either alone, or with LEF. Klareskog L, Malmstrm V, Lundberg K, Padyukov L, Alfredsson L. Smoking, citrullination and genetic variability in the immunopathogenesis of rheumatoid arthritis. Takemura S, Klimiuk PA, Braun A, Goronzy JJ, Weyand CM. Open-label rituximab treatment was given to patients who failed to remit at week 24 rituximab patients were given repeat infusion of their randomized doses and placebo patients were given rituximab rescue (two doses of 500 mg). van Assen S, Holvast A, Benne CA, et al. Rosengren S, Wei N, Kalunian KC, Kavanaugh A, Boyle DL. As mentioned previously, low baseline IgG level has also been identified as an independent risk factor for serious infections in the French registry.21, The long-term consequences of hypogammaglobulinemia induced by repeated courses of rituximab are still unclear. As the response of individuals to rituximab-induced B cell depletion is likely to be heterogeneous, if not genetically determined, and dependent on many other factors such as the baseline B cell number, it is difficult to select patients who will benefit from a lower and hence more cost-effective dose of rituximab. Rituximab is a chimeric monoclonal antibody that targets the CD20 molecule expressed on the surface of B cells. A long-term safety report of rituximab in RA clinical trials described that among 3,194 rituximab-treated RA patients followed for more than 9.5 years, 22.4% developed low IgM, 3.5% had low IgG levels, and 1.1% had low IgA for 4 months.66 No increase in infection rates was observed in patients during or after development of low IgM or IgG. Severe infusion reactions leading to drug withdrawal are uncommon (<1%).44 Pooling of data from RCTs of rituximab in RA revealed that first infusion reactions occurred in approximately 25% of patients.44,62 Most reactions were mild to moderate in severity, with the most common symptoms being headache, skin itchiness, throat irritation, flushing, rash, hypertension, and pyrexia. These clinical consequences are more likely when patients are treated with combined glucocorticoids and rituximab. Before initiating rituximab, patient screening for hypersensitivity to murine proteins, infections, congestive heart failure, pregnancy, and hypogammaglobulinemia is imperative. Vos K, Thurlings RM, Wijbrandts CA, van Schaardenburg D, Gerlag DM, Tak PP. Infusion reactions are more likely with the initial infusion, and are usually mild. B cell depletion therapies in autoimmune diseases: Monoclonal antibodies or chimeric antigen receptor-based therapy? At week 24, those who failed to achieve Disease Activity Score (DAS)28 remission were randomized to receive another course of rituximab or placebo in a 2:1 ratio. The development of the current study protocol has some interesting aspects that should be discussed. ), Recommendation 12: patients should receive influenza vaccination before rituximab treatment and annually (before rituximab re-treatment if possible) at a time when B cells are likely to be returning. A number of studies have attempted to identify predictors for better response in RA patients receiving rituximab therapy. Arthritis Rheum. In clinical studies of TNF inhibitor failure patients, rituximab was started as soon as 8 weeks after the last dose of infliximab or adalimumab and 4 weeks after the last dose of etanercept. (Level IIa evidence, Grade of recommendation B. Patients with rheumatoid arthritis (RA) receive highly targeted biologic therapies without previous knowledge of target expression levels in the diseased tissue. Rituximab therapy reduces activated B cells in both the peripheral blood and bone marrow of patients with rheumatoid arthritis: depletion of memory B cells correlates with clinical response. B cell activation biomark-ers as predictive factors for the response to rituximab in rheumatoid arthritis: a six-month, national, multicenter, open-label study. Longterm safety of patients receiving rituximab in rheumatoid arthritis clinical trials. Discontinuation of rituximab should be considered when the IgG level drops progressively to below the lower limit of the normal range, particularly in high-risk individuals such as older patients, those receiving concomitant glucocorticoids, and those with multiple comorbidities. Safety of rituximab in rheumatoid arthritis patients (pooled data from randomized controlled trials/registries), In the oncology literature, around one-third of patients develop an infusion reaction to their first rituximab infusion despite premedication with glucocorticoids.63 Infusion reactions become less common during subsequent infusions. A prospective 3-year observational study of 1124 RA patients (MIRAR) who discontinued at least one anti-TNF agent reported that the improvement in disease activity score at months 6, 9, and 12 was no different between those shifted to rituximab (N=591) and an alternative anti-TNF agent (N=533), after adjustment of baseline clinical characteristics by propensity scores.35 However, the results of this study have to be interpreted with caution as there was no randomization of the treatment arms and patient selection bias was bound to occur. It is a monoclonal antibody directed against the CD20 transmembrane protein present on B-cells. The ACR50 responses remained significantly higher in the rituximab combination groups than MTX monotherapy at week 48. A prospective study showed that the mean time for rituximab retreatment since baseline was around 8.5 months in anti-TNF failure RA patients.34 The rituximab insert package in the US states that retreatment can be given every 6 months according to clinical evaluation, but not sooner than every 4 months.5 The latest European consensus statements on use of rituximab in RA suggested that retreatment of rituximab might be considered after at least 24 weeks in patients who did not achieve clinical remission or at least low disease activity state as evidenced by any disease activity index.44 Otherwise, retreatment should be delayed until disease activity returned. The ACR50 responses remained significantly higher in the diseased tissue evidence, Grade of recommendation A,... Recommendation A opportunistic, infections, congestive heart failure, pregnancy, and are mild... 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