Central nervous system lymphoma associated with natalizumab

Na, Angelika; Hall, Nick; Kavar, Bhadrakant; King, John

doi:10.1016/j.jocn.2013.10.018

Cited by 17 publications

(11 citation statements)

References 8 publications

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“…However, to date, no single study has assembled data from all RCTs to assess the risk of opportunistic infection or malignancy. Due to their rarity in clinical trials, until now estimates of the risk of these events occurring with anti‐integrin antibodies has relied on case reports and case series, mainly from the neurology literature . Our study has shown that the risk of such an event occurring in a treated patient is between 0.2% and 1.1%, and this should be balanced against the efficacy of these agents for patients with IBD, as well as the risk that patients are prepared to accept in exchange for remission of their symptoms, which may be quite different to that anticipated by clinicians .…”

Section: Discussionmentioning

confidence: 90%

Systematic review and meta‐analysis: opportunistic infections and malignancies during treatment with anti‐integrin antibodies in inflammatory bowel disease

Luthra

Peyrin–Biroulet

Ford

2015

Aliment Pharmacol Ther

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Summary Background Anti‐integrin antibodies are effective therapies for Crohn's disease (CD) and ulcerative colitis (UC). However, these drugs carry theoretical risks of opportunistic infection and malignancy. Aim To pool data from all placebo‐controlled studies, to estimate risk of opportunistic infection or malignancy with anti‐integrin antibodies. Methods MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched (up to December 2014). Randomised placebo‐controlled trials of anti‐integrin antibodies in adults with active or quiescent CD or UC were eligible. Dichotomous data were pooled to obtain a relative risk (RR) of opportunistic infection or malignancy, with 95% confidence intervals (CIs). Results The search strategy identified 1579 citations, 12 of which were eligible (four trials of natalizumab, six of vedolizumab and two of etrolizumab). The RR of developing an opportunistic infection was not significantly higher with non‐gut specific (2.34; 95% CI 0.05–108.72) or gut specific anti‐integrin antibodies (1.55; 95% CI 0.16–14.83). The RR was generally higher in trials of non‐gut specific anti‐integrin antibodies with duration of therapy ≥52 weeks (RR = 15.00; 95% CI 0.86–261), but remained non‐significant. The RR of malignancy was not elevated with non‐gut specific (1.57; 95% CI 0.19–12.74) or gut specific anti‐integrin antibodies (0.78; 95% CI 0.15–4.02). Conclusions Absolute numbers of opportunistic infections were higher with anti‐integrin antibodies, but this difference is not statistically significant. There was no increased risk of malignancy detected. Long‐term data in large prospective cohorts are needed to further assess this issue.

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Section: Discussionmentioning

confidence: 90%

Systematic review and meta‐analysis: opportunistic infections and malignancies during treatment with anti‐integrin antibodies in inflammatory bowel disease

Luthra

Peyrin–Biroulet

Ford

2015

Aliment Pharmacol Ther

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“…Several cases of melanoma have been reported in patients on natalizumab [ 10 – 12 ], but incidence appears similar between placebo and natalizumab and there is insufficient evidence to support a definitive link to natalizumab [ 11 , 13 , 14 ]. There have been 6 reported cases of CNS lymphoma in patients treated with natalizumab [ 15 – 19 ]. However, two of these patients may have had preexisting lymphoma and at least one was negative for EBV, suggesting that these lymphomas may not have been caused by natalizumab therapy, though potentiation of progression is not excluded [ 16 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Neuroimaging of Natalizumab Complications in Multiple Sclerosis: PML and Other Associated Entities

Honce

Nagae

Nyberg

2015

Multiple Sclerosis International

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Natalizumab (Tysabri) is a monoclonal antibody (α4 integrin antagonist) approved for treatment of multiple sclerosis, both for patients who fail therapy with other disease modifying agents and for patients with aggressive disease. Natalizumab is highly effective, resulting in significant decreases in rates of both relapse and disability accumulation, as well as marked decrease in MRI evidence of disease activity. As such, utilization of natalizumab is increasing, and the presentation of its associated complications is increasing accordingly. This review focuses on the clinical and neuroimaging features of the major complications associated with natalizumab therapy, focusing on the rare but devastating progressive multifocal leukoencephalopathy (PML). Associated entities including PML associated immune reconstitution inflammatory syndrome (PML-IRIS) and the emerging phenomenon of rebound of MS disease activity after natalizumab discontinuation are also discussed. Early recognition of neuroimaging features associated with these processes is critical in order to facilitate prompt diagnosis, treatment, and/or modification of therapies to improve patient outcomes.

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“…Several studies show that after natalizumab discontinuation a disease activity worse than prenatalizumab status, may occur [95]- [97], indicating a rebound effect, similar to an immune reconstitution inflammatory syndrome [98]. A recent study [99] who had reached clinical and radiological stability after 24 natalizumab courses demonstrated a 4 fold higher ARR after one year of withdrawal in 73 natalizumab quitters compared with 35 continuers; however no rebound activity was observed in this cohort [89]. Lo Re et al [100] observed 132 MS patients treated with A c c e p t e d M a n u s c r i p t natalizumab, whose 37 patients remained therapy-free; a significant higher risk of both clinical and radiological relapses were observed in natalizumab quitters when compared with natalizumab continuers after a 1 year.…”

Section: ) Withdrawal Issuesmentioning

confidence: 68%

“…However, there are a few authors reporting the onset of lymhpoma in MS natalizumab treated patients during the post-marketing phase. In particular, there are 6 case reports in literature describing the onset of primary central nervous system lymphoma (PCNSL) during natalizumab treatment (5 MS patients and 1 patient affected by Crohn disease) [89]. All authors reported an Epstein-Barr virus (EBV)-negative B-cell lymphoma, raising doubts on the immunosuppressant effect of natalizumab as a causative agent for the PCNSLs development, given the pivotal role of EBV in the PCNSL onset in immunocompromised patients.…”

Section: ) Malignanciesmentioning

confidence: 99%

Long-term safety evaluation of natalizumab for the treatment of multiple sclerosis

Clerico

Artusi

Liberto

et al. 2017

Expert Opinion on Drug Safety

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Natalizumab is a humanized monoclonal antibody highly effective in relapsing-remitting multiple sclerosis (MS). Important concerns about its safety have been pointed out mainly because of the risk of progressive multifocal leukoencephalopathy (PML), caused by the opportunistic John-Cunningham virus (JCV). Areas covered: This review analyzes all the safety aspects related to the use and safety of natalizumab in MS patients. Other than PML, post-marketing, safety red-flags have been reported, as liver or haematological serious adverse events. Pregnancy evidences will be pointed out. The risk of PML depends on: concomitant or previous immunosuppression, exposure duration, anti-JCV antibody level. In natalizumab-related PML the average survival is 77%; prognostic features and information for the earliest identification of PML have been identified to maximally reduce its incidence, mortality and morbidity. Expert opinion: Natalizumab is a highly effective drug for MS patients but its safety issues represent a relevant limitation and impose strict clinical surveillance of treated patients. Some post-marketing safety red-flags have been pointed out, with higher attention to severe liver failures and limphoma cases. If PML and its consequences are considered the most relevant issues, a continuous surveillance must be maintained also regarding other possible SAEs like liver diseases and malignancies.

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Central nervous system lymphoma associated with natalizumab

Cited by 17 publications

References 8 publications

Systematic review and meta‐analysis: opportunistic infections and malignancies during treatment with anti‐integrin antibodies in inflammatory bowel disease

Systematic review and meta‐analysis: opportunistic infections and malignancies during treatment with anti‐integrin antibodies in inflammatory bowel disease

Neuroimaging of Natalizumab Complications in Multiple Sclerosis: PML and Other Associated Entities

Long-term safety evaluation of natalizumab for the treatment of multiple sclerosis

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