This appraisal reviews the additional evidence collected as part of the managed access agreement for belimumab for systemic lupus erythematosus (NICE technology appraisal guidance 397). The company submission included the BLISS 52 and BLISS 76 randomised controlled trials comparing intravenous belimumab plus standard therapy (from now, referred to as belimumab) with placebo plus standard therapy (from now, referred to as standard therapy). The company presented results for the new high disease activity population (HDA-2) population based on the pooled trials and new evidence from the BLISS SC randomised controlled trial comparing a new subcutaneous formulation of belimumab with standard therapy. The primary outcome of all studies was the response rate at week 52 compared with baseline. This was assessed with the Systemic Lupus Erythematosus Responder Index 4 (SRI 4), which is a composite measure of disease activity. Belimumab showed a statistically significant improvement in SRI 4 response rate at 52 weeks compared with standard therapy in the HDA 2 population across the BLISS SC, and pooled BLISS 52 and BLISS 76 trials. The committee concluded that belimumab improved SRI 4 response rate at 52 weeks compared with standard therapy. However, the results are uncertain because the trials were short, so the long-term benefit is unknown. The committee also noted that the long-term extension studies did not have comparator arms. It concluded that they did not provide long-term effectiveness evidence for belimumab compared with standard therapy. The cost-effectiveness estimates are also uncertain. But there is an unmet need for effective treatments in people with systemic lupus erythematosus, and some benefits of belimumab may not be taken into account in the cost-effectiveness results. After consultation, the company updated its confidential patient access scheme for belimumab. The company's deterministic base-case incremental cost-effectiveness ratio (ICER), using the updated patient access scheme for belimumab, compared with standard therapy was £12,335 per quality-adjusted life year (QALY) gained for the intravenous formulation of belimumab and £8,480 per QALY gained for the subcutaneous formulation. Using the updated patient access scheme for belimumab, the evidence review group’s (ERG) deterministic base-case ICERs were £30,278 per QALY gained for the intravenous formulation of belimumab and £29,313 per QALY gained for the subcutaneous formulation. The committee considered that the most plausible ICERs for belimumab compared with standard therapy would likely fall in between the company's and ERG's base-case deterministic ICERs. Therefore, it considered that both formulations of belimumab would be a cost-effective use of NHS resources.