[What's new in internal medicine: emerging treatments for systemic lupus erythematosus]

Abstract

Today corticosteroids plus hydroxychloroquine are the cornerstone in the treatment of Systemic Lupus Erythematosus (SLE). In severe cases, particularly in proliferative glomerulonephritis, cyclophosphamide or mycofenolate mofetil are used in induction and mycofenolate mofetil or azathioprine are used to maintain the remission. Corticosteroid sparing is an important goal. New and future treatments of SLE focus on B and T cells down regulation and co-stimulation, cytokine inhibition, and open the concept of immune vaccination. However, positive phase III randomized studies in SLE remain rare. Rituximab (a chimeric monoclonal anti-CD 20 antibody) was the first promising biologic agent showing interesting results in large case series but 2 phases III randomised studies didn't reach their primary objective. This probably emphasizes the limit of the current tools used for the evaluation of the disease and point out the design of the studies using high dose of corticosteroids, immunosuppressive drugs and the use of rituximab as add on treatment and are not face to face with conventional treatment. Abatacept (CTLA4-Ig) also failed to meet its primary end point in a randomised controlled trial in non-nephritis SLE. A post-hoc analysis suggests however that abatacept may be beneficial in lupus patients with arthritis however, it will probably never be approved for that indication. Belimumab (a human monoclonal antibody to BLyS) is the first biologic agent which reached its primary end point in 2 different randomised controlled trials using a new index for the evaluation of the activity of the diseases taking into account the physicians judgement (SLE responder index). Lots of phase I/II studies are currently ongoing particular targeting on interferon alpha, interleukin 6, B cell CD22 and C5 complement component.