Management of refractory systemic rheumatic diseases

The management of refractory systemic rheumatic diseases remains a challenging issue. New immunosuppressive drugs have been developed which might improve long-term outcome, with a reasonably toxicity profile. Moreover, better understanding of the mechanisms underlying some of the systemic rheumatic disease has raised hopes for more targeted immunointerventions. In Europe, current therapy of severe systemic rheumatic diseases (SRD) usually consists in a sequential treatment with a short course of an incisive remission-inducing immunosuppressive (IS) regimen [such as high dose glucocorticoids (GC) combined to cyclophosphamide (CYC)] followed by a long term but less toxic remission-maintaining IS regimen aimed at preventing relapses [such as low dose GC combined with azathioprine (AZA)]. This approach was recently supported by prospective studies performed in ANCA-associated vasculitis (1) and lupus nephritis (2). However, significant number of patients with SRD fail to respond to this standard regimen and treatment of these refractory cases has become one of the many rheumatologist's nightmares. Interestingly, some recent advances in basic immunology, in our understanding of the pathogenic mechanisms operating in SRD and in biotechnology have opened new prospects, some of them already applied in clinical practice. In this paper, these features will be reviewed with systemic lupus erythematosus (SLE) as an example.