Rituximab in multiple sclerosis: Frequency and clinical relevance of anti-drug antibodies

Dunn, Nicky; Juto, Alexander; Ryner, Malin; Manouchehrinia, Ali; Piccoli, Luca; Fink, Katharina; Piehl, Fredrik; Fogdell‐Hahn, Anna

doi:10.1177/1352458517720044

Cited by 83 publications

(80 citation statements)

References 19 publications

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“…However, although the presence of ADAs was associated with incomplete B cell depletion, no relationship could be established with adverse events or patient outcomes. 211 Accordingly, it remains unclear how important an issue ADAs are for anti-CD20 mAbs, and further study is required to clarifiy the significance of this phenomenon.…”

Section: Anti-drug Antibodiesmentioning

confidence: 99%

Anti-CD20 monoclonal antibodies: reviewing a revolution

Casan

Wong

Northcott

et al. 2018

Human Vaccines & Immunotherapeutics

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Since the inception of rituximab in the 1990s, anti-CD20 monoclonal antibodies have revolutionised the treatment of B cell hematological malignancies and have become a cornerstone of modern gold-standard practice. Additionally, the potent efficacy of these agents in depleting the B cell compartment has been used in the management of a broad array of autoimmune diseases. Multiple iterations of these agents have been investigated and are routinely used in clinical practice. In this review, we will discuss the physiology of CD20 and its attractiveness as a therapeutic target, as well as the pharmacology, pre-clinical and clinical data for the major anti-CD20 monoclonal antibodies: rituximab, obinutuzumab and ofatumumab.

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Section: Anti-drug Antibodiesmentioning

confidence: 99%

Anti-CD20 monoclonal antibodies: reviewing a revolution

Casan

Wong

Northcott

et al. 2018

Human Vaccines & Immunotherapeutics

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“…The therapeutic use of monoclonal antibodies and other biopharmaceutical products can result in an immune response to the drug that, in some cases, affects its efficacy due to the production of neutralizing ADAs 5 . Several clinical studies have measured ADA levels in sera of selected cohorts of patients and concluded that not all antibody responses lead to drug neutralization [6][7][8][9][10][11] . However, an explanation for these heterogeneous responses and an integrated characterization of the B and T cell responses to the drug are still missing.…”

mentioning

confidence: 99%

A single T cell epitope drives the neutralizing anti-drug antibody response to natalizumab in multiple sclerosis patients

Cassotta

Mikol

Bertrand

et al. 2019

Nat Med

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“…In our case, it may be a coincidence that this very patient did not experience any CWD or relapses while on RTX. However, in a cross‐sectional study by Dunn et al, samples were collected from 339 RTX‐treated subjects with MS to determine the clinical relevance of ADA. The authors showed that RTX was associated with a high degree of ADA, which in turn correlated significantly with incomplete B‐cell depletion.…”

Section: Discussionmentioning

confidence: 99%

Rituximab in multiple sclerosis at general hospital level

2020

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| 491 wileyonlinelibrary.com/journal/ane | INTRODUC TI ONSeveral new disease-modifying therapies (DMTs) have emerged during the last decades for people with multiple sclerosis (MS), which brings both opportunities and challenges to daily praxis. There are multiple issues other than drug efficacy that must be addressed before deciding on treatment modality. Besides disease-related inflammatory aggressiveness and subjects' susceptibility to drug-specific adverse events, subjects' preferences, and cost-benefit aspects also have to be taken into consideration. As a consequence, a gap is developing between the national guidelines authorized by the Swedish Medical Products Agency 1 and real-life treatment selection.Sweden stands out with its high use of off-label rituximab (RTX), representing approximately 40% of all ongoing DMTs in MS care. 2 Furthermore, a Swedish study that included subjects with MS from three tertiary academic hospitals showed that as many as 53.3% of all subjects were given RTX as the primary DMT for MS. 3 The published data extracted from the Swedish MS registry show increased Objectives: The use of rituximab (RTX) in multiple sclerosis (MS) is a rapidly increasing choice of disease-modifying therapy. Efficacy outside specialized university hospital-based care is not yet systematically investigated. Our aim was to evaluate off-label RTX treatment for MS at a general hospital in Sweden. Materials and Methods: Subjects with definite MS with at least one rituximab infusion were eligible for inclusion in this retrospective, observational study. Effect was evaluated by monitoring clinical disability, annual relapse rate, new lesions on MRI, and safety by the incidence and severity of adverse events. Results: Among the 83 included subjects, 15 had clinical worsening of disease during the median 23.5 (1-76) months of follow-up after RTX initiation: 7/66 with relapsing-remitting multiple sclerosis (RRMS) and 8/17 with progressive subtypes (PMS).Cumulative survival without worsening was 86% in RRMS and 30% in PMS. The annual relapse rate before RTX vs follow-up dropped from 0.38 to 0.05 (P < .00001).Subjects with new enhancing lesions on MRI during the first year before RTX initiation vs the year after dropped from 0.94 to 0.024 (P < .00001) and was only seen in RRMS (1.05-0.31, P = .00003). Adverse events were mainly mild. Thirty-six out of 53 non-infusion-related adverse events were infections, of which four were serious, including a case of pneumonia with concomitant late-onset neutropenia. Conclusions:Rituximab was as effective and safe when given at a general hospital outpatient clinic compared with results from previous university hospital-based studies. Vigilance is required concerning severe adverse events. K E Y W O R D Smultiple sclerosis, rituximab, safety management

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Rituximab in multiple sclerosis: Frequency and clinical relevance of anti-drug antibodies

Abstract: Rituximab treatment is associated with a high degree of ADAs, which correlates with efficacy of B-cell depletion; however, the clinical relevance of ADAs remains uncertain.

Cited by 83 publications

References 19 publications

Anti-CD20 monoclonal antibodies: reviewing a revolution

Anti-CD20 monoclonal antibodies: reviewing a revolution

A single T cell epitope drives the neutralizing anti-drug antibody response to natalizumab in multiple sclerosis patients

Rituximab in multiple sclerosis at general hospital level

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