NEW YORK (Reuters Health) Jul 19 - Adding belimumab (Benlysta) to standard therapy for systemic lupus erythematosus (SLE) appears to be safe, based on results in patients who've been taking the drug for four years now.

BELIMUMAB WELL TOLERATED IN LUPUS PATIENTS

These individuals are participating in an ongoing open-label continuation study of belimumab's original phase II trial. The most recent data were reported online June 5th in Arthritis & Rheumatism.

"This is the first treatment approved for lupus in over 50 years," Dr. Joan T. Merrill from Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma told Reuters Health by email. "When a new treatment becomes available a major concern is how long the benefits might last and if it is safe to continue giving the treatment over long periods of time. This paper suggests that for a significant subset of patients who are (if you think about it) voting with their feet by staying in the study for so long, there are longer-term benefits and the safety profile is reassuring as well."

Belimumab is a human immunoglobulin G1lambda monoclonal antibody that binds to and inhibits soluble human B-lymphocyte stimulator, a cytokine critical for the maturation and survival of B cells, which is overexpressed in patients with SLE and other autoimmune diseases.

Three hundred forty-five patients entered a 24-week extension phase, and 296 continued treatment with belimumab 10 mg/kg monthly in the long-term continuation study.

Sixteen percent of patients discontinued treatment with belimumab during the first year, mostly as a result of patient request (6%) and adverse events (5%), and the rates of discontinuation declined over time.

Rates of serious and/or severe adverse events were similar for belimumab and placebo during the double-blind portion of the study and either remained stable or declined over the ensuing four years of belimumab exposure, the research team reports.

Common adverse events included arthralgia, upper respiratory tract infection, headache, fatigue, and nausea.

There were five deaths during the four years of belimumab exposure (0.4/100 patient-years), but only one was considered possibly related to the study drug (a case of cytomegalovirus pneumonia in year four).

Infection rates remained stable during the long-term continuation, resulting in discontinuation of belimumab in only four patients.

Rates of overall and serious and/or severe infections decreased after the first year of belimumab exposure regardless of the use of corticosteroids, although serious and/or severe infection rates were 2.5-fold higher in patients receiving corticosteroids at baseline.

Malignancies occurred at a rate of 0.34/100 patient-years during the four-year exposure period, which is similar to the background rate reported in patients with SLE (0.53/100 patient-years), the authors say.

Median IgG and IgA levels declined slightly during the first year of treatment but remained stable over the following three years, whereas median IgM and IgE levels declined further after year one of therapy. These changes were not associated with increases in infection rates.

"The treatment is currently approved for patients with blood tests positive for 'autoantibodies' who are not responding to usual treatments," Dr. Merrill said. "These were the major characteristics of patients participating in the pivotal studies of belimumab. But the more definitive question of which patients are likely to get the most benefit is still being studied."

"It needs to be underscored that we still have a lot to learn about it," Dr. Merrill said. "It also needs to be underscored that we have significantly more regulatory-standard safety and efficacy data on this treatment than any other of the (mostly unapproved) drugs that we commonly use as 'standard of care.'"

"It is also hoped that eventually we can get to a more sophisticated solution for how we think about and use all these new biologic treatments: to develop special blood tests that can not only predict more likely responders but also help optimize the dosing, but much work remains to be done on that," Dr. Merrill said.

The study was supported by Human Genome Sciences and GlaxoSmithKline, which employs four of the 13 authors and has financial relationships with five of the other authors.

SOURCE: http://bit.ly/MbjlWV

Arthr Rheum 2012.