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Drug Updates

Michele B. Kaufman, PharmD, BCGP  |  Issue: July 2009  |  July 1, 2009

Have there been reports of PML in patients treated with tumor necrosis–a antagonists? According to Furst, there have been unconfirmed reports documenting PML associated with both etanercept and infliximab therapy.11 In addition, there was a case reported in a patient with refractory RA who was treated with etanercept.12 In this case, an elderly woman had failed many therapies for RA, including prednisolone, auranofin, penicillamine, methotrexate (MTX), leflunomide, cyclophosphamide, and others. She also received daily isoniazid (INH) due to a possible history of tuberculosis. She ultimately received etanercept 25 mg twice weekly with rapid symptom resolution. During the subsequent month, the INH was changed to rifampin, and the etanercept was continued. Five months later, she was admitted to the hospital for severe malaise and appetite loss with subsequent incontinence, a gradual decline in her ability to communicate, and dementia. Eventually she developed seizures and loss of consciousness.

Upon work-up, the patient had neck rigidity, and the cerebrospinal fluid (CSF) showed an elevated protein concentration of 84 mg/dL (normal, 10–40 mg/dL) and a cell count of 30/3 mL (normal, 0/3–10/3 mL). An MRI showed high-intensity lesions disseminated bilaterally throughout the white matter. The patient was initially inaccurately diagnosed and treated for encephalomeningitis. After consulting with a neurologist, she was clinically diagnosed with PML. Attempts to detect JC virus via polymerase chain reaction (PCR) were unsuccessful, leading to two negative results. The patient generally stayed in bed, but with supportive treatment she improved enough to sit up to have meals. She was subsequently transferred to another facility to undergo rehabilitation. The authors noted that PML can be diagnosed by examining the CSF and by evaluating clinical symptoms. Examining MRI scans is also useful. The sensitivity of JC virus-DNA PCR in CSF is reported to be approximately 74% to 92%. The authors also noted that this patient had most of the PML features minus the JC virus in the CSF.

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Calabrese and Molloy reported that vigilance is warranted in the rheumatology community when it comes to recognizing and pursuing a diagnosis of PML, especially when it is suspected via identifying clinical signs and symptoms and MRI findings.13 Rheumatologists need to know about PML, be aware of its symptoms, be able to assist patients in making informed treatment decisions, and educate them about the risks and benefits of immunosuppressive therapies.

Michele Kaufman is a freelance medical writer based in New York City.

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References

  1. AGS Panel on Pharmacological Management of Persistent Pain in Older Persons. AGS Clinical Practice Guideline: Pharmacological Management of Persistent Pain in Older Persons Executive Summary. American Geriatrics Society. www.americangeriatrics.org/education/executive_summary.shtml. Published April 21, 2009. Accessed June 3, 2009.
  2. American Geriatrics Society announces new guidelines to improve pain management, quality of life, and quality of care for older patients. American Geriatrics Society. www.americangeriatrics.org/news/pain043009.shtml. Published May 1, 2009. Accessed June 3, 2009.
  3. AGS Panel on Persistent Pain in Older Patients. The management of persistent pain in older patients. JAGS. 2002;50:S205-S224.
  4. AGS Panel on Pharmacological Management of Persistent Pain in Older Persons. Pharmacological Management of Persistent Pain in Older Persons. American Geriatrics Society. www.americangeriatrics.org/education/final_recommendations.pdf. Published April 2009. Accessed June 3, 2009.
  5. Fick DM, Cooper JW, Wade WE, Waller JL, Maclean R, Beers MH. Updating the Beers criteria for potentially inappropriate medication use in older adults—results of a US consensus panel of experts. Arch Intern Med. 2003;163:2716-2724.
  6. New CellCept (mycophenolate mofetil) medication guide to be distributed by pharmacists. Food and Drug Administration. www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm093666.pdf. Published January 2009. Accessed June 3, 2009.
  7. Suicidal behavior and ideation and antiepileptic drugs. Food and Drug Administration. www.fda.gov/cder/drug/infopage/antiepileptics. Published May 5, 2009. Accessed June 3, 2009.
  8. Highlights of prescribing information: Rituxan. Genentech. www.gene.com/gene/products/information/pdf/rituxan-prescribing.pdf. Published September 2008. Accessed June 3, 2009.
  9. Waknine Y. Tysabri suspended from US market. Medscape. www.medscape.com/viewarticle/500466. Published February 28, 2006. Accessed June 3, 2009.
  10. Richwine L. Tysabri approved for treatment of Crohn’s disease, with restrictions. Medscape. www.medscape.com/viewarticle/568830. Published January 15, 2008. Accessed June 3, 2009.
  11. Furst DE. The risk of infections with biologic therapies for rheumatoid arthritis. Semin Arthritis Rheum. 2008 Dec 29 (Epub ahead of print).
  12. Yamamoto M, Takahashi H, Wakasugi H, et al. Leukoencephalopathy during administration of etanercept for refractory rheumatoid arthritis. Mod Rheumatol. 2007;17:72-74.
  13. Calabrese LH, Molloy ES. Progressive multifocal leukoencephalopathy in the rheumatic diseases: Assessing the risks of biologic immunosuppressive therapies. Ann Rheum Dis. 2008;67(Suppl III):iii64-iii65.
  14. UCB’s CIMZIA (certolizumab pegol) approved by the U.S. FDA for adult patients suffering from moderate to severe rheumatoid arthritis. UCB. www.ucb.com/news/newsdetail?det=1314787 Published May 14, 2009. Accessed June 3, 2009.
  15. Hitti M. Heartburn drug Prevacid goes over the counter. Web MD. www.webmd.com/heartburn-gerd/news/20090514/heartburn-drug-prevacid-goes-over-the-counter. Published May 14, 2009. Accessed June 3, 2009.
  16. Chugai shares fall after deaths among Actemra users. Reuters. www.reuters.com/article/rbssHealthcareNews/idUST37022720090318. Published March 18, 2009. Accessed June 3, 2009.
  17. Takahashi Y, Maxwell K. Roche partner discloses drug dangers. Wall Street Journal. http://online.wsj.com/article/SB123735013931766981.html. Published March 19, 2009. Accessed June 3, 2009.

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Filed under:Drug Updates Tagged with:ApprovalsLabeling Changesmycophenolate mofetilNonsteroidal anti-inflammatory drugs (NSAIDs)NSAIDsPipeline

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