Background/Purpose:   Etanercept is a subcutaneous antiTNF inhibitor approved to treatment of Rheumatoid Arthritis (RA). In literature there are few data about the achievement of a biological free remission in patients treated initially with a combined therapy (i.e. MTX plus antiTNF agent) and there are no data about influence of gender on clinical response to biological or DMARD therapy.  Aims of our study were to evaluate the Òbiologic-freeÓ sustained remission rate in patient with RA that achieved a persistent DAS28< 2.6 with a combined  therapy MTX plus etanercept and to evaluate the possible influence of gender or menopausal status on clinical response to etanercept.

Methods: A cohort of 169 Italian patients with active (DAS28 >5.1) rheumatoid arthritis (RA) attending the outpatient clinics of the Division of Rheumatology of Fornaroli Magenta Hospital (Milan, Italy)  from January  2000 to January 2005 were enrolled in this study and treated with Etanercept as first line biological therapy (50mg/weekly) combines with methotrexate (MTX) (7.5-15 mg/weekly). All patients were prospectively followed every 3 months until now. When a clinical remission (DAS28-ESR <2.6) was obtained and sustained for at least 12 months, the patient interrupted biological treatment. Clinical, laboratory and disease activity measures were obtained at 3, 6 and 12 months after biological discontinuation. If after 12 months a DAS28-ESR worsening > 1.2 was observed, then etanercept was reintroduced and the patient was categorized as relapsed, otherwise the patient was considered as in persistent remission. Statistical Analysis was performed with a Cox regression model based on clinical variables collected was used to predict the odds of develop a biologic free remission status and the cumulative probability of persistent remission

Results: 169 patients were enrolled (37 males, 132 females). Mean etanercept treatment duration was 3.01± 2,7 (0,08-11,35) years. Mean disease duration from diagnosis to last follow up was 15 years ± 8.4. Mean disease duration from diagnosis to enrolment  was 8±7.7 years. During the study 34 patients (20.12%) obtained a biologic free persistent remission (25% observed in 3.9 years of treatment, 50% observed in 6.59 years of treatment, 75% observed in 7.8 years of treatment) (Figure 1). Our model showed a increased risk of disease relapsing in women (odd ratio of 1.306, p=0.01) and in long standing disease (odd ratio of  1.11, p=0.03) (Figure 2) (Figure 3).  The 50% of remission in males were observed  in 2.8 years of treatment with etanercept, in females in 4.1 years.

Conclusion: In our study we observed a significant rate of biologic free persistent remission with etanercept. Gender seems to influence the clinical response with a lower probability of persistent remission in females. Others study are necessary to confirm these data in the future.