A review of the current use of rituximab in autoimmune diseases

Gürcan, Hakan M.; Keskin, Derin B.; Stern, Joel N. H.; Nitzberg, Matthew A.; Shekhani, Haris; Ahmed, A. Razzaque

doi:10.1016/j.intimp.2008.10.004

Cited by 281 publications

(208 citation statements)

References 179 publications

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“…However, minor treatable infections have been common in patients with B cell depletion, whereas severe infections occurred in a small minority 29 . In a recent review 31 In conclusion, rituximab induces a clinical effect not seen with other therapies in AIHA patients refractory to several treatments with little or tolerable associated toxicity. Therefore, this therapy should be considered as a potential early 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 18 treatment that may achieve a rapid and MR in this subset of patients.…”

Section: Discussionmentioning

confidence: 94%

Rituximab is an effective and safe therapeutic alternative in adults with refractory and severe autoimmune hemolytic anemia

et al. 2010

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Rituximab-induced B cell depletion has been proven to be a useful therapy for autoimmune hemolytic anemia (AIHA). The aim of this retrospective study was to evaluate the effectiveness of rituximab in the treatment of 36 patients with AIHA refractory to several treatments. These patients had received a median of four (1-8) previous treatments, and 13 patients had undergone splenectomy. Rituximab was administered by intravenous infusion at a dose of 375 mg/m2 once weekly for 4 doses in 29 patients, and 7 patients received 1-6 doses. Overall, 28 of 36 patients (77%) achieved response. Twenty-two patients (61%) reached a complete response (CR), and 6 patients (16%) obtained a partial response (PR). All patients that reached CR (61%) were able to maintain the response during more than 6 months with a median follow-up of 14 months (1-86 months). Sixteen patients maintained response (Maintained Response; MR) for more than 1 year. The predictors of MR were achievement of CR and negative Coombs test result. Splenectomized patients showed a better response rate than those non-splenectomized. Rituximab was well tolerated, and only one patient presented a transitory rash during infusion. Rituximab induced clinical responses in multi-treated severe refractory both warm and cold AIHA patients with little toxicity and consequently, this therapy should be considered as an early therapeutic option in this setting.Response to Reviewers: In order to read the response to reviewers see attachment. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 AbstractRituximab-induced B cell depletion has been proven to be a useful therapy for autoimmune hemolytic anemia (AIHA). The aim of this retrospective study was to evaluate the effectiveness of rituximab in the treatment of 36 patients with AIHA refractory to several treatments. These patients had received a median of four (1-8) previous treatments, and 13 patients had undergone splenectomy.Rituximab was administered by intravenous infusion at a dose of 375 mg/m 2 once weekly for 4 doses in 29 patients, and 7 patients received 1-6 doses.Overall, 28 of 36 patients (77%) achieved response. Twenty-two patients (61%) reached a complete response (CR), and 6 patients (16%) obtained a partial response (PR). All patients that reached CR (61%) were able to maintain the response during more than 6 months with a median follow-up of 14 months (1-86 months). Sixteen patients maintained response (Maintained Response; MR) for more than 1 year. The predictors of MR were achievement of CR and negative Coombs test result. Splenectomized patients showed a better response rate than those non-splenectomized. Rituximab was well tolerated, and only one patient presented a transitory rash during infusion. Rituximab induced clinical responses in multi-treated severe refractory both warm and cold AIHA pati...

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Section: Discussionmentioning

confidence: 94%

Rituximab is an effective and safe therapeutic alternative in adults with refractory and severe autoimmune hemolytic anemia

et al. 2010

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“…As these PCs do not express CD20, they are not depleted by rituximab, now commonly used in the treatment of a number of autoimmune conditions. 54 Despite this, immunosuppressive therapy does often reduce autoantibody titers, although it is interesting to note that after treatment with rituximab autoantibody levels often fall after clinical improvement has occurred (for example, see reference 55), and in many patients autoantibodies fall whereas those against previously experienced infection-related antigens do not. 56 The most likely explanation for these observations is that therapy, and in particular B cell depletion, is controlling inflammation, and that this in turn is reducing the inflammation-related PC survival niches in organs such as the kidney.…”

Section: Discussionmentioning

confidence: 99%

Local Renal Autoantibody Production in Lupus Nephritis

Espéli¹,

Bökers²,

Giannico³

et al. 2011

Journal of the American Society of Nephrology

130

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Autoantibodies are central to the pathogenesis of several autoimmune diseases including systemic lupus erythematosus. Plasma cells secrete these autoantibodies, but the anatomical sites of these cells are not well defined. Here, we found that although dsDNA-specific plasma cells in NZB/W mice were present in spleen and bone marrow, a large number were in the kidneys and their number correlated with the serum dsDNA-IgG titer. We observed renal plasma cells only in mice with nephritis, where they located mainly to the tubulointerstitium of the cortex and outer medulla. These cells had the phenotypic characteristics of fully differentiated plasma cells and, similar to long-lived bone marrow plasma cells, they were not in cell cycle. In patients with lupus nephritis, plasma cells were often present in the medulla in those with the most severe disease, especially combined proliferative and membranous lupus nephritis. The identification of the kidney as a major site of autoreactive plasma cells has implications for our understanding of the pathogenesis of lupus nephritis and for strategies to deplete autoreactive plasma cells, a long-standing therapeutic aim.

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“…One cycle of each immunotherapy was defined as 500 to 1000 mg methylprednisolone for 5 days, 0.4 g/kg IVIG for 5 days, and ≥ 4 consecutive plasmapheresis treatments. Rituximab (375 mg/m 2 weekly for 4 weeks) was administrated after the determination of an inadequate clinical response to first-line immunotherapy [29]. In every patient, antihistamine and acetaminophen was administered 1 h before the rituximab infusion, to prevent or ameliorate infusion-related adverse effects.…”

Section: Treatmentsmentioning

confidence: 99%

Tocilizumab in Autoimmune Encephalitis Refractory to Rituximab: An Institutional Cohort Study

et al. 2016

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A considerable portion of autoimmune encephalitis (AE) does not respond to conventional immunotherapies and subsequently has poor outcomes. We aimed to determine the efficacy of tocilizumab, an anti-interleukin-6 antibody, in rituximab-refractory AE compared with other treatment options. From an institutional cohort of AE, 91 patients with inadequate clinical response to first-line immunotherapy and following rituximab were retrospectively reviewed. Patients were grouped according to their further immunotherapy strategies. Thirty (33.0 %) patients were included in the tocilizumab group, 31 (34.0 %) in the additional rituximab group, and 30 (33.0 %) in the observation group. Outcomes were defined as the favorable modified Rankin Scale scores (≤2) at 1 and 2 months from the initiation of each treatment strategy and at the last follow-up. Favorable clinical response (improvement of the modified Rankin Scale scores by ≥ 2 points or achievement of the mRS scores ≤ 2) at the last follow-up was also analyzed. The tocilizumab group showed more frequent favorable mRS scores at 2 months from treatment initiation and at the last follow-up compared with those at the relevant time points of the remaining groups. The majority (89.5 %) of the patients with clinical improvement at 1 month from tocilizumab treatment maintained a long-term favorable clinical response. No serious adverse effects of rituximab or tocilizumab were reported. Therefore, we suggest that tocilizumab might be a good treatment strategy for treating AE refractory to conventional immunotherapies and rituximab. The tocilizumab-mediated clinical improvement manifests as early at 1 month after treatment initiation.

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A review of the current use of rituximab in autoimmune diseases

Cited by 281 publications

References 179 publications

Rituximab is an effective and safe therapeutic alternative in adults with refractory and severe autoimmune hemolytic anemia

Rituximab is an effective and safe therapeutic alternative in adults with refractory and severe autoimmune hemolytic anemia

Local Renal Autoantibody Production in Lupus Nephritis

Tocilizumab in Autoimmune Encephalitis Refractory to Rituximab: An Institutional Cohort Study

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