Repeated decrease of CD4+ T-cell counts in patients with rheumatoid arthritis over multiple cycles of rituximab treatment

Lavielle, Matthieu; Mulleman, Denis; Goupille, Philippe; Bahuaud, Clément; Sung, Hsueh Cheng; Watier, Hervé; Thibault, Gilles

doi:10.1186/s13075-016-1152-5

Cited by 37 publications

(21 citation statements)

References 16 publications

(20 reference statements)

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“…A follow‐up study by the same group was published in 2016 where patients received up to seven cycles of treatment during the study period. Mean CD4 + T‐cell counts were above the upper limit of the reference range before each rituximab infusion and repeatedly reached the reference range at 6 months (and/or 3 months) post infusion . In patients with RA, repeated post‐treatment decrease in CD4 + T‐cell counts occurred over successive cycles of rituximab .…”

Section: Do Anti‐cd20 Antibodies Cause Cd4+ T Lymphopenia?mentioning

confidence: 95%

“…Mean CD4 + T‐cell counts were above the upper limit of the reference range before each rituximab infusion and repeatedly reached the reference range at 6 months (and/or 3 months) post infusion . In patients with RA, repeated post‐treatment decrease in CD4 + T‐cell counts occurred over successive cycles of rituximab . In minimal change nephrotic syndrome, remissions after rituximab therapy were associated with significant decrease in the frequency of CD4 + follicular helper T cells .…”

Section: Do Anti‐cd20 Antibodies Cause Cd4+ T Lymphopenia?mentioning

confidence: 96%

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Progressive multifocal leukoencephalopathy and anti‐CD20 monoclonal antibodies: What do we know after 20 years of rituximab

Focosi¹,

Tuccori

Maggi

2019

Reviews in Medical Virology

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In 1997, rituximab was the first monoclonal antibody clinically approved for the treatment of cancer. Ten years later, progressive multifocal leukoencephalopathy (PML), until that time a rare opportunistic infection mostly seen in AIDS patients, was added as a black box warning after retrospective case-control studies showed an increased incidence in both B-cell lymphoproliferative disorders and autoimmune diseases.Despite more than 5 million worldwide exposures to date (and about 500 000 new exposures per year), insufficient data collection has hampered identification of risk minimization strategies, and concerns have been raised about a class effect extending to the newer anti-CD20 monoclonal antibodies (ofatumumab, obinutuzumab, and ocrelizumab). Here, we report current PML case counts registered in the FAERS and EudraVigilance databases and comment on severe CD4 + T lymphopenia as a plausible common mechanism of action for anti-CD20 antibodies in causation of PML. K E Y W O R D SCD20, JC virus, obinutuzumab, ofatumumab, progressive multifocal leukoencephalopathy, rituximab

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Section: Do Anti‐cd20 Antibodies Cause Cd4+ T Lymphopenia?mentioning

confidence: 95%

Section: Do Anti‐cd20 Antibodies Cause Cd4+ T Lymphopenia?mentioning

confidence: 96%

Progressive multifocal leukoencephalopathy and anti‐CD20 monoclonal antibodies: What do we know after 20 years of rituximab

Focosi¹,

Tuccori

Maggi

2019

Reviews in Medical Virology

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“…The incidence rates of HZ were higher in rituximab (3.9 per 100 patient-years) and abatacept (8.5 per 100 patient-years) period compared to cDMARDs period. Several studies have been reported that rituximab induces T cell depletion, mainly of CD4+ T cells in patient with RA [21,22]. Based on these results, decreased of CD4+ T cell counts after rituximab therapy would be made and consequently might affect to RA patients to be more vulnerable to HZ.…”

Section: Discussionmentioning

confidence: 84%

Risk of Herpes Zoster in Patients with Rheumatoid Arthritis Undergoing Biologic Disease-Modifying Therapy

et al. 2017

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Objective. Rheumatoid arthritis (RA) patients suffer from an increased risk of herpes zoster (HZ) partially due to immunosuppressant medications. This study investigated HZ in RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs), as compared with conventional DMARDs (cDMARDs). Methods. This retrospective case series study assembled record information of 277 RA patients who received bDMARDs after failure of at least one cDMARDs at Seoul National University Hospital between August 2003 and February 2015. Following capture of baseline information and identification of HZ episodes, crude HZ incidence rates per 100 patient-years (95% confidence intervals) were calculated. Results. For 718 treatment courses, 277 (38.6%) comprised cDMARDs, 66 (9.2%) infliximab, 175 (24.4%) etanercept, 95 (13.2%) adalimumab, 9 (1.3%) golimumab, 41 (5.7%) rituximab, 31 (4.3%) abatacept, and 24 (3.3%) tocilizumab. There were 37 HZ episodes, 16 during cDMARD treatment courses, and 21 accompanying bDMARDs, two with infliximab, eight with etanercept, five with adalimumab, and three each with rituximab and abatacept. The crude HZ incidence rate per 100 patient-years was 2.4 (1.4∼3.9) for cDMARDs, 2.2 (0.3∼7.9) for infliximab, 1.8 (0.8∼3.6) for etanercept, 3.7 (1.2∼8.4) for adalimumab, 3.9 (0.8∼11.0) for rituximab, and 8.5 (1.8∼23.1) for abatacept. Conclusion. We conclude that bDMARDs do not always increase the risk of HZs in RA patients, although HZ rates vary for different bDMARDs. (J Rheum Dis 2017;24:220-226)

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“…In addition, all patients showed a relevant CD4-lymphopenia (all patients < 200/µL) with low levels of naïve CD4 cells (< 10% in all patients). Of note, while hypogammaglobulinemia is an expected and known adverse event following RTX treatment, it has been reported that RTX treatment can induce CD4-lymphopenia [26][27][28].…”

Section: Discussionmentioning

confidence: 99%

Rituximab-Containing Treatment Regimens May Imply a Long-Term Risk for Difficult-To-Treat Chronic Hepatitis E

Schulz

Biedermann

Bock

et al. 2020

IJERPH

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Hepatitis E virus (HEV) infection is an emerging disease in industrialized countries which is usually characterized by a self-limited course. However, there is an increased risk of HEV persistence in immunocompromised risk populations, comprising patients following solid organ transplantation or hematological malignancies. Recently, chronic HEV infection following rituximab-containing treatment regimens has been described. Here we report five patients with chronic hepatitis E after prior rituximab therapy for various indications. We determined the immunological characteristics of these patients and analyzed the development of ribavirin (RBV) treatment failure-associated mutations in the HEV genome. One patient became chronically HEV-infected 110 months after administration of rituximab (RTX). Immunological characterization revealed that all patients exhibited significant hypogammaglobulinemia and CD4+ T cell lymphopenia. One patient permanently cleared HEV following weight-based ribavirin treatment while three patients failed to reach a sustained virological response. In depth mutational analysis confirmed the presence of specific mutations associated with RBV treatment failure in these patients. Our cases indicate that rituximab-containing treatment regimens might imply a relevant risk for persistent HEV infection even years after the last rituximab application. Moreover, we provide further evidence to prior observations suggesting that chronically HEV infected patients following RTX-containing treatment regimens might be difficult to treat.

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Repeated decrease of CD4+ T-cell counts in patients with rheumatoid arthritis over multiple cycles of rituximab treatment

Cited by 37 publications

References 16 publications

Progressive multifocal leukoencephalopathy and anti‐CD20 monoclonal antibodies: What do we know after 20 years of rituximab

Progressive multifocal leukoencephalopathy and anti‐CD20 monoclonal antibodies: What do we know after 20 years of rituximab

Risk of Herpes Zoster in Patients with Rheumatoid Arthritis Undergoing Biologic Disease-Modifying Therapy

Rituximab-Containing Treatment Regimens May Imply a Long-Term Risk for Difficult-To-Treat Chronic Hepatitis E

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