Incidence of infusion-associated reactions with rituximab for treating multiple sclerosis: a retrospective analysis of patients treated at a US centre.

BACKGROUND: Rituximab is a monoclonal antibody approved for treating CD20-positive B-cell non-Hodgkin's lymphoma and rheumatoid arthritis but is used off-label for treating many autoimmune disorders, including multiple sclerosis (MS). Similarly to other monoclonal antibodies, the incidence of infusion-related reactions to rituximab is high. Reactions to monoclonal antibodies, including rituximab, vary widely in type and severity, but may include mild pruritis and rash to more severe complications such as Stevens-Johnson syndrome and anaphylactic reactions. OBJECTIVE: To assess the incidence of infusion-associated reactions in our MS patients receiving rituximab infusions and compare it to previous trials investigating rituximab for treating MS. METHODS: From 1 to 30 November 2009, we retrospectively reviewed medical charts from Partners Multiple Sclerosis Centre, Brookline, MA, USA, of patients being treated with rituximab for MS between 20 November 2007 and 24 November 2009 for evidence of infusion-associated reactions and further classified reactions on a grading scale. RESULTS: During the period studied, 70 patients were infused with rituximab. Infusion-associated events occurred in 25.7% of our patients. Reactions were mild to moderate and most commonly occurred during the first infusion. Most patients were able to complete the infusion after appropriate treatment of the reaction was administered, and most patients went on to receive subsequent doses without any further reactions. CONCLUSIONS: The occurrence of infusion-associated reactions to rituximab in patients with MS is fairly common. However, premedication that includes corticosteroids may reduce the incidence of reactions dramatically. Should they occur, proper treatment of reactions with histamine H(1) or H(2) receptor antagonists and infusion rate reduction is an effective management strategy in this situation.

Natalizumab in the treatment of multiple sclerosis.

Natalizumab is a monoclonal antibody, representing a new class of medication for treating relapsing multiple sclerosis (MS). Conventional treatments include interferons, glatiramer acetate and chemotherapies such as mitoxantrone and cyclophosphamide. These therapies offer only modest clinical benefits and are commonly not tolerated due to side effects. Natalizumab has been proven in large-scale, blinded, randomized, controlled trials to have an exceptional effect on preventing relapses, decreasing the risk of sustained progression of disability, and increasing the rate of disease-free patients over a 24-month period compared to placebo. These trials led to the speedy approval of natalizumab for treating relapsing MS, but its use was halted a few months after its induction after several cases of progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease affecting the central nervous system. After a long deliberation by an FDA advisory panel and strong support from the MS community, natalizumab was reapproved with stringent restrictions including patient, provider and site registration. Natalizumab is now considered second-line therapy for patients who have failed first-line agents such as interferon or glatiramer acetate. As little is known about additional risk factors for PML and other potential infections, patients and providers must work together to carefully decide if potential benefits outweigh these rare but potentially devastating complications.

Fingolimod: a novel immunosuppressant for multiple sclerosis.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of fingolimod, a novel immune modulator. DATA SOURCES: Information was obtained through a MEDLINE search (1966-February 2007) and from published abstracts. Search terms included fingolimod, FTY720, FTY-720, and sphingosine-1-phosphate receptor agonist. STUDY SELECTION AND DATA EXTRACTION: All English-language studies and abstracts pertaining to fingolimod were considered for inclusion. Preference was given to human data. DATA SYNTHESIS: Fingolimod is the first in a new class of immune modulators known as the sphingosine-1-phosphate receptor agonists. It is administered orally once daily and causes a dose-related reduction in the number of circulating lymphocytes by preventing their egress from secondary lymph organs, but it does not alter T-cell activation or proliferation. Bradycardia and lymphopenia are the most common adverse effects. Clinical trials have evaluated the efficacy of fingolimod in renal transplantation and multiple sclerosis (MS). Further research for renal transplantation will not take place, but Phase 3 studies in MS are underway, as Phase 2 study results are favorable. CONCLUSIONS: Due to its distinct mechanism of action and its oral administration, fingolimod may be a useful therapeutic option for patients with relapsing forms of MS. More data are needed to assess the safety and clinical utility of fingolimod.

Role of pharmacist counseling in preventing adverse drug events after hospitalization.

BACKGROUND: Hospitalization and subsequent discharge home often involve discontinuity of care, multiple changes in medication regimens, and inadequate patient education, which can lead to adverse drug events (ADEs) and avoidable health care utilization. Our objectives were to identify drug-related problems during and after hospitalization and to determine the effect of patient counseling and follow-up by pharmacists on preventable ADEs. METHODS: We conducted a randomized trial of 178 patients being discharged home from the general medicine service at a large teaching hospital. Patients in the intervention group received pharmacist counseling at discharge and a follow-up telephone call 3 to 5 days later. Interventions focused on clarifying medication regimens; reviewing indications, directions, and potential side effects of medications; screening for barriers to adherence and early side effects; and providing patient counseling and/or physician feedback when appropriate. The primary outcome was rate of preventable ADEs. RESULTS: Pharmacists observed the following drug-related problems in the intervention group: unexplained discrepancies between patients' preadmission medication regimens and discharge medication orders in 49% of patients, unexplained discrepancies between discharge medication lists and postdischarge regimens in 29% of patients, and medication nonadherence in 23%. Comparing trial outcomes 30 days after discharge, preventable ADEs were detected in 11% of patients in the control group and 1% of patients in the intervention group (P = .01). No differences were found between groups in total ADEs or total health care utilization. CONCLUSIONS: Pharmacist medication review, patient counseling, and telephone follow-up were associated with a lower rate of preventable ADEs 30 days after hospital discharge. Medication discrepancies before and after discharge were common targets of intervention.