Outcome of refractory to conventional and/or biologic treatment adult Still's disease following canakinumab treatment: Countrywide data in 50 patients.

OBJECTIVE: To assess the efficacy and safety of the IL-1b inhibitor canakinumab in all adults with refractory Still's disease identified from the National Organization For Medicines for off-label drug use. METHODS: In a retrospective longitudinal multicenter cohort of 50 patients (median age 39 years) with active Still's disease despite treatment with corticosteroids (n = 11), conventional and synthetic (n = 34) and/or biologic disease modifying anti-rheumatic drugs (n = 30), we assessed the efficacy of canakinumab 150-300 mg administered every 4 (n = 47) or 8 weeks (n = 3) as combination therapy or monotherapy (n = 7) during a median follow-up of 27 (3-84) months. RESULTS: Α complete response was initially observed in 78% of patients within 3 months (median), irrespective of age at disease onset. A partial response was evident in 20%. One patient had resistant disease. Treatment de-escalation was attempted in 15 of 39 complete responders and a complete drug discontinuation in 21 patients for 8 months (median). Eleven patients (22%) relapsed during treatment, one during de-escalation process, and 11 after treatment discontinuation. Overall, 9 of 11 relapses were successfully treated with canakinumab treatment intensification or re-introduction. At last visit, 18% of patients were off treatment due to remission and 26% due to disease activity. Canakinumab had a significant corticosteroid sparing effect allowing weaning in 21 of 41 cases. Infections (20%, severe 4%) and leucopenia (6%) led to treatment cessation in one patient. CONCLUSION: High rates of sustained remission were observed in this, largest so far, real-life cohort of adult patients with refractory Still's disease treated with canakinumab.

Ovarian function is preserved in women with severe systemic lupus erythematosus after a 6-month course of cyclophosphamide followed by mycophenolate mofetil.

OBJECTIVE: To evaluate whether a short duration treatment with cyclophosphamide (CYC) followed by mycophenolate mofetil (MMF) is associated with preservation of the ovarian function in female patients with systemic lupus erythematosus (SLE). METHODS: We retrospectively evaluated 61 premenopausal women with SLE treated for lupus nephritis (n=58), autoimmune hemolytic anemia (n=1) and central nervous system involvement (n=2). Thirty-nine patients received prolonged treatment with 1 g/m2 intravenous (IV) CYC pulses (group I). 22 patients received 5-7 monthly 1 g/m2 IV CYC pulses and afterwards 2 g/day MMF (group II). RESULTS: Disease activity was equally controlled using either regimen (p=0.76 and p=0.31 for disease remission and relapse respectively). Amenorrhea developed in 56% of women in group I (n=22) and 14% in group II (n=3) (p=0.01), whereas sustained amenorrhea developed in 51% (n=20) of women in group I versus 4% (n=1) in group II (p=0.05). Most women with amenorrhea in group I (86%) did not resume menses after the cessation of therapy versus one woman (33%) in group II. In logistic regression, group I had a 4-fold higher risk of amenorrhea and 5-fold higher risk of sustained amenorrhea compared to group II (p=0.001 and p=0.009 respectively). Age (p<0.001), cumulative CYC dose (p=0.001) and anti-Ro antibodies (p=0.002) were significant in terms of amenorrhea, while sustained amenorrhea was significantly associated with the patient age (p=0.026). CONCLUSION: We suggest that treatment with MMF following 5-7 IV pulses of CYC is an effective mean to control disease activity and preserve ovarian function in premenopausal women with SLE.