Risk of opportunistic infections in patients treated with alemtuzumab for multiple sclerosis

Abstract

Alemtuzumab is a monoclonal anti CD-52 antibody recently approved for use in relapsing-remitting multiple sclerosis(MS). Given that the targeted antigen is primarily expressed on B and T lymphocytes, the administration of this biological drug is associated with rapid but protracted peripheral lymphopenia. Areas covered: The impact on infective risk of this immune impairment is still to be fully understood. In this review, we attempt to summarize all the available literature concerning opportunistic infections occurring in patients with MS receiving alemtuzumab. Infective adverse events were observed in more than 70% of patients in phase 2/3 RCTs, mainly of mild-to-moderate severity. Nevertheless, several post-marketing reports documented cases of serious, rare, and unexpected infections. Expert Opinion: Predictive risk factors and prognostic features of opportunistic infections in this setting still need to be exactly assessed. At present, the only recommended preventive measures consist in anti-herpetic prophylaxis, Listeria-free diet, Tuberculosis prophylaxis and annual Papillomavirus screening. Given the non-negligible risk of unpredicted infective events, we advise physicians to take into account patients' history of infectious diseases and vaccine status and to consider supplementary prophylactic strategies, including screening for Toxoplasma gondii and viral hepatitis serostatus as well as pre-emptive approaches to avert CMV reactivation and Pneumocystosis.

Immune Reconstitution Therapy or Continuous Immunosuppression for the Management of Active Relapsing–Remitting Multiple Sclerosis Patients? A Narrative Review

“…Treatment with alemtuzumab is associated with an increased risk of bacterial infections (including listeriosis and tuberculosis [TB]), viral infections (herpes simplex and zoster and human papillomavirus) and fungal infections [31,32]. The increased incidence of bacterial and fungal infections may be consistent with the drug's suppression of innate and adaptive immunity [33].…”

<p>Prevention Strategies to Minimize the Infection Risk Associated with Biologic and Targeted Immunomodulators</p>

“…26 PCP infection associated with alemtuzumab used in multiple sclerosis is extremely rare, and prophylaxis is not routinely recommended. 64 If alemtuzumab is administered for solid organ transplantation induction, the American Society of Transplant recommends PCP prophylaxis for at least 6-12 months after induction. Life long duration of PCP prophylaxis may be considered for lung and small bowel transplant or patients with chronic CMV infection or prior history of PCP infection.…”

“…10,14 HSV prophylaxis should be considered in multiple sclerosis patients with the initiation of each cycle of alemtuzumab therapy and continued for at least two months until CD4 + ≥200 cells/μL. 14,64 If alemtuzumab is administered for solid organ transplantation induction immunosuppressive therapy, HSV/VZV prophylaxis is recommended in CMV IgG Donor-/Recipient-(low-risk CMV) transplants. 15 Listeria-and toxoplasma-free diet should be recommended in patients under alemtuzumab therapy.…”

“…10 Therefore, ESCMID does not recommend CMV prophylaxis for multiple sclerosis patients on alemtuzumab. 10,64 Dasatinib has been associated with CMV reactivation, particularly in post-HSCT patients (adjusted hazard ratio, 7.65; 95% confidence interval, 1.84-31.7); 9,65 and ESCMID recommends monitoring of CMV infection in these individuals. Besides dasatinib, regular monitoring of CMV PCR and signs as well as symptoms of CMV disease is also recommended for patients receiving mogamulizumab.…”

Central Nervous System Opportunistic Infections

“…1 Listeria monocytogenes causes a brainstem meningoencephalitis in posttransplant patients or with use of medications causing T-lymphocyte dysfunction, including alemtuzumab. 2 CNS tuberculosis can mimic any neurologic syndrome and can cause meningitis, encephalitis, abscess formation, strokes, or myelopathy. This is very commonly associated with human immunodeficiency virus (HIV) infection, especially in the developing countries.…”