Author Topic: Increased risk of zoster infections with Gilenya  (Read 189 times)

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Offline agate

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From JAMA Neurology, January 14, 2015:

Varicella-Zoster Virus Infections in Patients Treated With Fingolimod:
Risk Assessment and Consensus Recommendations for Management

Ann M. Arvin, MD1; Jerry S. Wolinsky, MD2; Ludwig Kappos, MD, PhD3; Michele I. Morris, MD4; Anthony T. Reder, MD5; Carlo Tornatore, MD, PhD6; Anne Gershon, MD7; Michael Gershon, MD8; Myron J. Levin, MD9; Mauritz Bezuidenhoudt, MSc10; Norman Putzki, MD10

Author Affiliations

1Department of Pediatrics, Stanford University School of Medicine, Stanford, California
2Department of Neurology, The University of Texas Health Science Center at Houston
3Department of Neurology, University Hospital Basel, Basel, Switzerland
4Department of Infectious Diseases, University of Miami, Miami, Florida
5Department of Neurology, University of Chicago Medical Center, Chicago, Illinois
6Department of Neurology, MedStar Georgetown University Hospital, Washington, DC
7Department of Pediatrics, Columbia University, New York, New York
8Department of Pathology and Cell Biology, Columbia University, New York, New York
9Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora
10Novartis Pharma AG, Basel, Switzerland


Varicella-zoster virus (VZV) infections increasingly are reported in patients with multiple sclerosis (MS) and constitute an area of significant concern, especially with the advent of more disease-modifying treatments in MS that affect T-cell–mediated immunity.


To assess the incidence, risk factors, and clinical characteristics of VZV infections in fingolimod-treated patients and provide recommendations for prevention and management.

Design, Setting, and Participants

Rates of VZV infections in fingolimod clinical trials are based on pooled data from the completed controlled phases 2 and 3 studies (3916 participants) and ongoing uncontrolled extension phases (3553 participants). Male and female patients aged 18 through 55 years (18-60 years for the phase 2 studies) and diagnosed as having relapsing-remitting MS were eligible to participate in these studies. In the postmarketing setting, reporting rates since 2010 were evaluated.


In clinical trials, patients received fingolimod at a dosage of 0.5 or 1.25 mg/d, interferon beta-1a, or placebo. In the postmarketing setting, all patients received fingolimod, 0.5 mg/d (total exposure of 54 000 patient-years at the time of analysis).

Main Outcomes and Measures

 Calculation of the incidence rate of VZV infection per 1000 patient-years was based on the reporting of adverse events in the trials and the postmarketing setting.


Overall, in clinical trials, VZV rates of infection were low but higher with fingolimod compared with placebo (11 vs 6 per 1000 patient-years). A similar rate was confirmed in the ongoing extension studies. Rates reported in the postmarketing settings were comparable (7 per 1000 patient-years) and remained stable over time.

Disproportionality in reporting herpes zoster infection was higher for patients receiving fingolimod compared with those receiving other disease-modifying treatments (empirical Bayes geometric mean, 2.57 [90% CI, 2.26-2.91]); the proportion of serious herpes zoster infections was not higher than the proportion for other treatments (empirical Bayes geometric mean, 1.88 [90% CI, 0.87-3.70]). Corticosteroid treatment for relapses might be a risk factor for VZV reactivation.

Conclusions and Relevance 

Rates of VZV infections in clinical trials were low with fingolimod, 0.5 mg/d, but higher than in placebo recipients. Rates reported in the postmarketing setting are comparable. We found no sign of risk accumulation with longer exposure. Serious or complicated cases of herpes zoster were uncommon.

We recommend establishing the patient’s VZV immune status before initiating fingolimod therapy and immunization for patients susceptible to primary VZV infection. Routine antiviral prophylaxis is not needed, but using concomitant pulsed corticosteroid therapy beyond 3 to 5 days requires an individual risk-benefit assessment. Vigilance to identify early VZV symptoms is important to allow timely antiviral treatment.

The abstract can be seen here.
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SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.