Inhibition of the TNF-pathway: use of infliximab and etanercept as remission-inducing agents in cases of therapy-resistant chronic inflammatory disorders.

OBJECTIVE: To examine the potential of the two tumour necrosis factor (TNF) inhibitors infliximab and etanercept as remission-inducing agents in chronic therapy-resistant inflammatory disorders of immune or non-immune pathogenesis.

METHODS: 14 patients with adult Still's disease/macrophage activation syndrome (4), Wegener's disease (3), Behçet's disease (3), keratoscleritis (1), lymphomatous tracheo-bronchitis (1) Cogan's syndrome (1), and rapidly destructive crystal arthropathy (1) were treated with infliximab (n = 10) and etanercept (n = 4). All patients showed organ-threatening progression of their diseases with resistance to conventional immunosuppressive medication. Therapeutic benefit was assessed clinically and by documenting organ-specific functional and morphological alterations. Side effects were compared with the data of our clinic's rheumatoid arthritis (RA) patients treated by TNF inhibitors.

RESULTS: A rapid and dramatic beneficial effect was documented in 9 patients and a moderate one in 5. Best responses (clinical and laboratory parameters) were seen in patients with macrophage activation syndrome/adult Still's disease and Behçet's disease, while the results were less impressive in those with Wegener's disease, Cogan's syndrome, idiopathic cerato-scleritis and lymphomatous tracheobronchitis. In all cases immunosuppressive agents and systemic glucocorticoids could be reduced or discontinued.

CONCLUSIONS: TNF inhibition may be highly effective in patients with severe, therapy-resistant chronic inflammatory disorders.