Rituximab as maintenance therapy for ANCA-associated vasculitides: pooled analysis and long-term outcome of 277 patients included in the MAINRITSAN trials.

OBJECTIVE: To compare the long-term efficacy and safety of azathioprine (AZA), 18-month fixed-schedule rituximab (RTX), 18-month tailored RTX and 36-month RTX in preventing relapses in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who achieved a complete remission after induction therapy. Patients treated with 36-month RTX received either a fixed or a tailored regimen for the first 18 months and a fixed regimen for the last 18 months (36-month fixed/fixed RTX and 36-month tailored/fixed RTX, respectively). METHODS: The Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis (MAINRITSAN) trials sequentially compared: 18-month fixed-schedule RTX versus AZA (MAINRITSAN); 18-month fixed-schedule RTX versus 18-month tailored-RTX (MAINRITSAN2); and extended therapy to 36 months with four additional RTX infusions after MAINRITSAN2 versus placebo (MAINRITSAN3). Patients were then followed prospectively through month 84 and their data were pooled to analyse relapses and adverse events. The primary endpoint was relapse-free survival at month 84. RESULTS: 277 patients were enrolled and divided in 5 groups: AZA (n=58), 18-month fixed-schedule RTX (n=97), 18-month tailored-RTX (n=40), 36-month tailored/fixed RTX (n=42), 36-month fixed/fixed RTX (n=41). After adjustment for prognostic factors, 18-month fixed-schedule RTX was superior to AZA in preventing major relapses at month 84 (HR 0.38, 95% CI 0.20 to 0.71). The 18-month tailored-RTX regimen was associated with an increased risk of major relapse compared with fixed-schedule regimen (HR 2.92, 95% CI 1.43 to 5.96). The risk of major relapse was similar between 36-month fixed/fixed and 18-month fixed-RTX (HR 0.69, 95% CI 0.38 to 1.25). CONCLUSIONS: According to these results, it appears that the 84-month remission rate is higher with an 18-month fixed RTX regimen compared with AZA and 18-month tailored RTX. Also, extending RTX to 36 months does not appear to reduce the long-term relapse rate compared with the 18-month fixed RTX regimen. However, as this study was underpowered to make this comparison, further prospective studies are needed to determine the potential long-term benefits of extending treatment in these patients.

The Metamorphosis, struggling to adapt to a new condition. The lived experience of patients with Thrombotic microangiopathies diagnosed in the ICU. A qualitative study.

BACKGROUND: Using qualitative interviews, our objective was to better understand the experience of patients with Thrombotic microangiopathies (TMA), from discovering their disease in the ICU to the psychological, emotional, and social specifics of living with this rare disorder. MATERIAL AND METHODS: Patients were recruited at seven TMA centers belonging to the French national TMA referral network. A total of 15 patients, 15 relatives and 12 healthcare professionals participated. A majority of patients (n = 11/15) were women, median age was 41 (range 29-62) years, and median time elapsed since diagnosis was 6 (range 2-11) years. Interviews were analysed using thematic analysis. RESULTS: We derived 3 major themes from qualitative analysis: 1) Discovering TMA: experiencing a life-threatening emergency with open eyes; 2) TMA: a complex and diverse disease and care plan; 3) Living with TMA: taming fear and loneliness. CONCLUSIONS: Patients with TMA share common experiences with patients with other rare diseases, but also specific experiences related to their illness. Improved information at the onset and during the course of the illness, associated with enhanced care coordination plans would help TMA patients better cope with their illness and adhere to their care projects.

Adjusted value of thromboprophylaxis in hospitalized obese patients: A comparative study of two regimens of enoxaparin: The ITOHENOX study.

Thromboprophylaxis is a mainstay of hospital care in patients at high risk of thrombosis. Fixed doses of low-molecular-weight heparin (LMWH) are recommended for thromboprophylaxis in patients admitted to hospital for an acute medical condition. However, the distribution of LMWH is weight-based, and the efficacy of standard doses in obese patients may be decreased. Data for obese patients are mainly available in bariatric surgery with extremely obese patients who are at greater risk of venous thromboembolism than those hospitalized for a medical condition. We conducted a randomized control trial in medically obese inpatients (BMI≥30kg/m2) assessing two regimens of enoxaparin (40mg and 60mg SQ daily) in order to determine whether a stronger dosage would achieve higher anti-Xa level suitable for thromboprophylaxis. Between September 2013 and April 2015, 91 patients were included in the study (mean (±standard deviation) age was 70.4±10.7years, average BMI 37.8±6.4kg/m2). Main indications of thromboprophylaxis were mainly acute infection (50%), acute respiratory failure (10%), acute congestive heart failure (9%) and acute rheumatic disorders (18%). Average anti-Xa activity, measured 4h after the third administration of enoxaparin was 0.25±0.09IU/mL in group 1 (enoxaparin 40mg) and 0.35±0.13IU/mL in group 2 (enoxaparin 60mg) (P<10-3). The proportions of patients with normal anti-Xa activity (between 0.32 and 0.54IU/mL) were 31% (n=11) and 69% (n=24) in group 1 and 2 respectively (P=0.007). The proportions of anti-Xa activity measurement below the normal range were 64% and 36% in group 1 and 2 (P<10-3) respectively. Subgroup analysis focusing on high weight patients (above 100kg, n=45) showed a marked difference in the proportion of patients with normal anti-Xa activity between group 1 (9%) and 2 (44%) (P=0.009). No venous thromboembolism occurred during the study and one patient in group 1 died because of hemorrhagic shock due to a gastric ulcer. Incidence of adverse events was not different between the two groups (P=0.52). In conclusion, the ITOHENOX study shows in medically obese inpatients that thromboprophylaxis with enoxaparin 60mg provides higher control of anti-Xa activity, without more bleeding complications than the standard enoxaparin regimen. This trial is registered with ClinicalTrials.gov, number NCT01707732.