Long-term safety of Benlysta

Lupus Foundation of America

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What is the topic?

Current standard therapy to manage lupus includes treatment with steroids, anti-malarial drugs, and immune-suppressing drugs (either alone or in combination). In 2011, the U.S. Food and Drug Administration recommended belimumab (Benlysta®) for approval as a treatment for lupus and the drug is now currently available for treatment of this disease. Belimumab has been tested for safety over a 72-week period. However, the safety of belimumab over a period of several years has not been thoroughly investigated.

What did the researchers hope to learn?

The researchers hoped to learn about the long-term safety of belimumab over a 4-year period.

Who was studied?

A total of 296 people with lupus participated in the study.

How was the study conducted?

The study included a 52-week double-blind trial in which patients received intravenous belimumab (1, 4, and 10 mg/kg; administered on days 0, 14, 28, and then every 28 days) plus standard therapy. Patients who completed the 52-week period then entered a 24-week open-label period during which time belimumab patients received the same dose or were switched to 10 mg/kg of belimumab; patients receiving placebo were switched to 10 mg/kg of belimumab at this time. Upon completion of the 24-week extension period, patients who achieved a satisfactory response to therapy were eligible to enter a long-term open-label period in order to received 10 mg/kg of belimumab every 28 days.

Standard (background) drug therapies could be altered at any time during the study period. However, the addition of cyclophosphamide or new biological agents was not allowed.

Adverse events and safety laboratory data were recorded every four and eight weeks, respectively. Adverse events were coded using the Medical Dictionary for Regulatory Affairs and were graded for severity using the Adverse Events Severity Grading Tables.

What did the researchers find?

Most of the patients included in the study were Caucasian women with an average age of 42 year who had lupus for an average of about eight years. Of the 364 patients who completed the 52-week study, 345 entered the 24-week extension and 321 of these completed it. Of these 321, 296 continued treatment with 10 mg/kg of belimumab in the long-term continuation study.

Upon entry to long-term continuation study period, 67% of patients were taking steroids, 70% of patients were taking anti-malarial drugs, and 50% were taking immune-suppressing drugs (including azathioprine, mycophenolate mofetil, methotrexate, or leflunomide).

Adverse events were similar for the placebo and belimumab groups in the initial portion of the study and either remained stable or declined over the 4-year belimumab exposure. The most common adverse events were arthraligia, upper respiratory tract infection, headache, fatigue, and nausea. The serious adverse events of highest incidence (5 patients in any year) were cellulitis and transient ischemic attack. There were five deaths during the 4-year belimumab exposure period, with two occurring during the initial double-blind part of the study and three occurring during the long-term continuation period. Only one of the deaths was felt to be related to the administration of belimumab.

Adverse events of special interest included infusion reactions, infections, opportunistic infections, and malignancies. Infusion reactions, infection rates, and malignancies were similar between placebo and belimumab groups during the initial, double-blind part of the study and/or during the long-term continuation period. Laboratory abnormalities were similar between placebo and belimumab groups in the initial study period (they were not required during the long-term continuation part of the study).

What were the limitations of the study?

There was no control group in the long-term continuation study.

What do the results mean for you?

Belimumab was well tolerated over a 4-year treatment period in combination with standard lupus drug therapy.

Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus
Merrill JT, Ginzler EM, Wallace DJ, McKay JD, Lisse JR, Aranow C, Wellborne FR, Burnette M, Condemi J, Zhong ZJ, Pineda L, Klein J, and Freimuth WW; on Behalf of the LBSL02/99 Study Group. (2012). 
Arthritis & Rheumatism. 2012 Jun 5. doi: 10.1002/art.34564.