Anti TNF-α Agents in Adult Onset Still Disease. A 4 Year Follow-up Study

PURPOSE. To evaluate the efficacy of Tumor Necrosis Factor alfa (TNF-α) blockade in patients with adult onset Still’s disease (AOSD), refractory to high doses of corticosteroid and disease modifying anti-rheumatic drugs (DMARDs). METHODS. In this prospective, non comparative case series, 9 patients (5 females, 4 males) with severe and highly active AOSD were treated with anti-TNF-α therapy (3 with infliximab, 5 with etanercept and 1 with adalimumab). The dose and mode of administration were those usually used in rheumatoid arthritis (RA). In five cases with chronic articular course, the treatment was added to methotrexate because of the persistence of high activity indexes of disease (DAS28 mean value: 3.8, HAQ mean value: 2.4). In the other four cases, anti-TNF agents were used as steroid sparing for systemic symptoms in patients with relapsing-remitting disease and persistent elevation of ESR and CRP in which both corticosteroid and cyclosporine A were not effective. All clinical and serological findings were collected by out-patient examination every three months. All the patients with chronic articular disease performed a gadolinium enhanced MR of affected joints once a year. The median follow-up period was 4 years (interquartile range -IQR- 3.5-5.5), while the median age at the beginning of biologic treatment was 35.5 years old (IQR 34-38.5). RESULTS. In patients with chronic articular course we observed a fairly good response with improvement of DAS28 and HAQ (respectively of 60% and 63%). Despite this, in three cases, a progression of MR findings consisting with erosive lesions was observed. One of these patients presented an infusional allergic reaction and so he switched to Adalimumab, achieving a satisfactory improvement. The subset of patients with systemic course showed a good response after the start of the therapy, resulting in the remission of the clinical picture and in a handy schedule of steroid tapering. In the cases in which the treatment was stopped, all the patients experienced a worsening in symptoms that leaded to reintegrate the anti-TNF drug beside a temporary increase in steroid dose. To date all the patients are still under treatment. CONCLUSION. Anti-TNFα agents may be helpful in controlling systemic and articular symptoms of refractory AOSD. When the therapy was stopped, the disease quickly flared up. Our data suggest that TNFα blockade should not be as effective in slowing down the articular damage as in improving systemic and osteo-articular symptoms. We also argue that anti-TNFα agents are not a conceivable first line therapy in AOSD. In our little case series the switching from one anti-TNF to another seems to be as efficacious as already been suggested for RA. Finally, anti-TNF molecules in AOSD seem to play above all a symptomatic role, expecially in the systemic forms of the disease.