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evident
Original paper
2011LancetRheumatology/Immunology

BLISS-52

Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial

RCTSystemic lupus erythematosus

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Overview

In seropositive active SLE, IV belimumab 1 or 10 mg/kg plus standard care raised the week-52 SRI response versus placebo.

Clinical takeaway

Belimumab improved the composite SRI at week 52 in seropositive active SLE on standard care. Use the modified ITT rates, and do not treat every SRI component as independently positive: the 1 mg/kg BILAG component was not significant.

Key result

Week-52 SRI response (modified ITT) was 58% with belimumab 10 mg/kg (OR 1.83, 95% CI 1.30-2.59; p=0.0006) and 51% with 1 mg/kg (OR 1.55, 95% CI 1.10-2.19; p=0.0129) versus 44% with placebo.

Practice impact

Add IV belimumab to standard care for seropositive active SLE when a week-52 SRI response is the goal.

Evidence

Study design

Multicentre, randomised, placebo-controlled, phase 3 trial with masked treatment assignment and modified intention-to-treat analysis.

Enrollment

867

Follow-up

Primary efficacy at week 52; infusions continued until week 48.

Geography

Latin America, Asia-Pacific, eastern Europe

Clinical question

Does intravenous belimumab improve the SLE Responder Index at week 52 compared with placebo when added to standard care?

Population

  • Adults 18 years or older with seropositive active SLE and a SELENA-SLEDAI score of at least 6.
  • 867 were randomly assigned (289 to belimumab 1 mg/kg, 290 to 10 mg/kg, 288 to placebo); 865 were treated and analysed (288, 290, and 287).

Intervention

Belimumab 1 mg/kg or 10 mg/kg by intravenous infusion over 1 hour on days 0, 14, and 28, then every 28 days until 48 weeks, plus standard of care.

Comparator

Placebo infusions on the same schedule plus standard of care.

Primary outcome

Improvement in the Systemic Lupus Erythematosus Responder Index (SRI) at week 52 versus baseline: SELENA-SLEDAI reduction of at least 4 points; no new BILAG A organ domain score and no more than 1 new B score; and no worsening (less than a 0.3 increase) in Physician's Global Assessment.

In the modified ITT analysis, both belimumab doses improved week-52 SRI versus placebo: OR 1.83 (95% CI 1.30-2.59; p=0.0006) for 10 mg/kg and OR 1.55 (95% CI 1.10-2.19; p=0.0129) for 1 mg/kg.

Odds ratio (10 mg/kg vs placebo) / 1.83 / 95% CI 1.30-2.59 / p=0.0006

Key results

  • In the modified ITT population, SRI response at week 52 was 148 of 288 (51%) with belimumab 1 mg/kg (OR 1.55, 95% CI 1.10-2.19; p=0.0129) and 167 of 290 (58%) with 10 mg/kg (OR 1.83, 95% CI 1.30-2.59; p=0.0006) versus 125 of 287 (44%) with placebo.
  • A SELENA-SLEDAI reduction of at least 4 points occurred in 53% with 1 mg/kg (OR 1.51, 95% CI 1.07-2.14; p=0.0189) and 58% with 10 mg/kg (OR 1.71, 95% CI 1.21-2.41; p=0.0024) versus 46% with placebo.
  • No new BILAG A or no more than 1 new B flare: 78% with 1 mg/kg (OR 1.38, 95% CI 0.93-2.04; p=0.1064, not significant) and 81% with 10 mg/kg (OR 1.62, 95% CI 1.09-2.42; p=0.0181) versus 73% with placebo.
  • No PGA worsening: 79% with 1 mg/kg (OR 1.68, 95% CI 1.15-2.47; p=0.0078) and 80% with 10 mg/kg (OR 1.74, 95% CI 1.18-2.55; p=0.0048) versus 69% with placebo.

Harms

  • Rates of adverse events were similar across belimumab 1 mg/kg, 10 mg/kg, and placebo.
  • Serious infection was reported in 22 (8%), 13 (4%), and 17 (6%) patients, respectively.
  • Severe or serious hypersensitivity reactions on an infusion day were reported in two (<1%), two (<1%), and no patients, respectively.
  • No malignant diseases were reported.

Clinical Use

Practice impact

  • Consider adding intravenous belimumab to standard care in seropositive active SLE when the goal is a week-52 SRI response.

Applicability

  • Most applicable to adults with seropositive SLE and SELENA-SLEDAI of at least 6, treated in Latin America, Asia-Pacific, and eastern Europe, and analysed by modified ITT.

Limitations

  • 867 were randomized and 865 were treated and analysed; percentages use the modified ITT denominators.
  • The 1 mg/kg BILAG component had a confidence interval that included no effect (OR 1.38, 95% CI 0.93-2.04; p=0.1064).
  • The interpretation statement about being the first approved targeted biologic is not a trial efficacy result.

Common misinterpretations

  • A positive composite SRI does not mean every component was significant at both doses.
  • This is add-on therapy to standard of care, not belimumab monotherapy.
  • Results are for seropositive active SLE, not all lupus phenotypes.

Citation

Navarra SV, Guzmán RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721-731. doi:10.1016/S0140-6736(10)61354-2

Significantly higher SRI rates were noted with belimumab 1 mg/kg (148 [51%], odds ratio 1·55 [95% CI 1·10-2·19]; p=0·0129) and 10 mg/kg (167 [58%], 1·83 [1·30-2·59]; p=0·0006) than with placebo (125 [44%]) at week 52.