Belimumab in SLE

Source : Medscape Medical News

October 26, 2009 (Philadelphia, Pennsylvania) — Positive 1-year results from the BLISS-52 study show that belimumab (Benlysta) achieved clinically meaningful improvements and was safe in patients with systemic lupus erythematosus (SLE).

Belimumab significantly reduced disease activity, disease flares, and use of steroids, and improved fatigue and quality of life, compared with placebo. BLISS-52 is the first of 2 pivotal phase 3 trials in SLE.

Belimumab (registered name Benlysta previously known as LymphoStat-B), is a fully human monoclonal antibody that specifically recognizes and inhibits the biological activity of B-Lymphocyte stimulator (BLyS), also known as B cell activation factor of the TNF family (BAFF).

If you analyse the inclusion and exclusion criterias, as below

Key Inclusion Criteria:
Clinical diagnosis of SLE by ACR criteria.
Active SLE disease.
On stable SLE treatment regimen.

Key Exclusion Criteria:
Pregnant or nursing
Have received treatment with any B cell targeted therapy.
Have received treatment with a biological investigational agent in the past year.
Have received IV cyclophosphamide within 180 days of Day 0.
Have severe lupus kidney disease.
Have active central nervous system (CNS) lupus.
Have required management of acute or chronic infections within the past 60 days.
Have current drug or alcohol abuse or dependence.
Have a historically positive test or test positive at screening for HIV, hepatitis B, or hepatitis C.

Many of the patients that may have been excluded where those that perhaps posed the most problems in the management of SLE ie those with severe lupus nephritis or cerebral lupus. Even those that have received cyclophosphamide and failed to respond within those 180 days were omited from the study. The sticky point to this is the fact that the cost of treatment to prevent ‘disease flares’ will negate the benefits as reported.

So what happens after week 52? Can these patients be taken off Belimumab? What is the duration of benefit after discontinuation of Belimumab? Which organ systems will have the greatest benefit when given Belimumab?

Only 42% of the study population were on immunosuppressants. Belimumab was said to be steroid sparing although it did not reach statistical significance. No mention whether immunosuppressants could be weaned off. Why only 42% were put on immunosuppressants is not very clear.

A similar study below did not show any benefits from Belimumab.

Arthritis Rheum. 2009 Sep 15;61(9):1168-78.
A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus.
Wallace DJ, Stohl W, Furie RA, Lisse JR, McKay JD, Merrill JT, Petri MA, Ginzler EM, Chatham WW, McCune WJ, Fernandez V, Chevrier MR, Zhong ZJ, Freimuth WW.

Cedars-Sinai Medical Center, University of California, Los Angeles, USA.
OBJECTIVE: To assess the safety, tolerability, biologic activity, and efficacy of belimumab in combination with standard of care therapy (SOC) in patients with active systemic lupus erythematosus (SLE). METHODS: Patients with a Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score >/=4 (n = 449) were randomly assigned to belimumab (1, 4, or 10 mg/kg) or placebo in a 52-week study. Coprimary end points were the percent change in the SELENA-SLEDAI score at week 24 and the time to first SLE flare. RESULTS: Significant differences between the treatment and placebo groups were not attained for either primary end point, and no dose response was observed. Reductions in SELENA-SLEDAI scores from baseline were 19.5% in the combined belimumab group versus 17.2% in the placebo group. The median time to first SLE flare was 67 days in the combined belimumab group versus 83 days in the placebo group. However, the median time to first SLE flare during weeks 24-52 was significantly longer with belimumab treatment (154 versus 108 days; P = 0.0361). In the subgroup (71.5%) of serologically active patients (antinuclear antibody titer >/=1:80 and/or anti-double-stranded DNA [anti-dsDNA] >/=30 IU/ml), belimumab treatment resulted in significantly better responses at week 52 than placebo for SELENA-SLEDAI score (-28.8% versus -14.2%; P = 0.0435), physician’s global assessment (-32.7% versus -10.7%; P = 0.0011), and Short Form 36 physical component score (+3.0 versus +1.2 points; P = 0.0410). Treatment with belimumab resulted in a 63-71% reduction of naive, activated, and plasmacytoid CD20+ B cells, and a 29.4% reduction in anti-dsDNA titers (P = 0.0017) by week 52. The rates of adverse events and serious adverse events were similar in the belimumab and placebo groups. CONCLUSION: Belimumab was biologically active and well tolerated. The effect of belimumab on the reduction of SLE disease activity or flares was not significant. However, serologically active SLE patients responded significantly better to belimumab therapy plus SOC than to SOC alone.

Certainly, unless you are flushed with cash, it is probably still not worthwhile to jump onto the bandwagon.

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