Cyclophosphamide vs rituximab for eradicating inhibitors in acquired hemophilia A: A randomized trial in 108 patients.

BACKGROUND: Acquired hemophilia A (AHA) is a rare autoimmune disorder due to autoantibodies against Factor VIII, with a high mortality risk. Treatments aim to control bleeding and eradicate antibodies by immunosuppression. International recommendations rely on registers and international expert panels. METHODS: CREHA, an open-label randomized trial, compared the efficacy and safety of cyclophosphamide and rituximab in association with steroids in patients with newly diagnosed AHA. Participants were treated with 1 mg/kg prednisone daily and randomly assigned to receive either 1.5-2 mg/kg/day cyclophosphamide orally for 6 weeks, or 375 mg/m2 rituximab once weekly for 4 weeks. The primary endpoint was complete remission over 18 months. Secondary endpoints included time to achieve complete remission, relapse occurrence, mortality, infections and bleeding, and severe adverse events. RESULTS: Recruitment was interrupted because of new treatment recommendations after 108 patients included (58 cyclophosphamide, 50 rituximab). After 18 months, 39 cyclophosphamide patients (67.2 %) and 31 rituximab patients (62.0 %) were in complete remission (OR 1.26; 95 % CI, 0.57 to 2.78). In the poor prognosis group (FVIII < 1 IU/dL, inhibitor titer > 20 BU mL-1), significantly more remissions were observed with cyclophosphamide (22 patients, 78.6 %) than with rituximab (12 patients, 48.0 %; p = 0.02). Relapse rates, deaths, severe infections, and bleeding were similar in the 2 groups. In patients with severe infection, cumulative doses of steroids were significantly higher than in patients without infection (p = 0.03). CONCLUSION: Cyclophosphamide and rituximab showed similar efficacy and safety. As first line, cyclophosphamide seems preferable, especially in poor prognosis patients, as administered orally and less expensive. FUNDING: French Ministry of Health. CLINICALTRIALS: gov number: NCT01808911.

[Diagnosis with defecography of puborectal muscle syndrome]. / Diagnosi mediante defecografia della sindrome del muscolo puborettale.

The puborectalis syndrome is a defecation disorder supported by the nonrelaxation of puborectalis sling with consequent dyschezia. We report on a series of 98 patients submitted to clinical examination, defecography, anorectal manometry, electromyography and intestinal transit time studies. Puborectalis anatomy and physiology are briefly reviewed. The main symptoms of puborectalis syndrome in our patients were incomplete defecation (89%) and intermittent evacuation (63%); 28% of patients turned to finger defecation. In all patients, defecography showed an abnormal increase in puborectalis impression on the posterior anorectal wall, reduced anorectal angle opening under straining (mean value: 113 degrees) and prolonged expulsion time with barium pooling in the ampulla (mean evacuation time: 38 seconds). Such anorectal abnormalities as rectal mucosal prolapse (47 cases) and anterior rectocele (36 cases) were also associated. In 33 of 98 patients (34% of cases), sling assessment by bidigital palpation at preliminary clinical examination revealed puborectalis hypertonia, which was later confirmed at defecography. Manometry was not specific for the diagnosis of puborectalis syndrome, detecting increased external anal sphincter pressure under straining in 24 of 35 patients (68.8%). Puborectalis activity was increased under straining in 16 subjects submitted to electromyography. Intestinal transit time studies showed a typical expulsion delay and radiopaque marker pooling in the ampulla in 18 of 23 patients (78.2%). In our experience, defecography is a useful, simple and noninvasive method for the accurate diagnosis of the puborectalis syndrome.