Single Center Experience with Rituximab as First Line Immunosuppression Regimen for Acquired Hemophilia
Authors: Boles Jeremiah , Key Nigel S. , Kasthuri Raj S. , Ma Alice D. 
Published: October 2019

Abstract
Abstract 1419
The use of Rituximab (R), a chimeric monoclonal antibody against CD20, has been reported in the treatment of various non-neoplastic immune disorders including Acquired Hemophilia (AH). Approximately 1/3 of patients with AH are refractory to traditional immunosuppressive regimens (e.g. prednisone/cyclophosphamide) and therefore R has been advocated as an initial therapeutic option. When R is utilized in the treatment of AH it has typically been paired with corticosteroids. However, there is considerable morbidity associated with prolonged courses of corticosteroids in what is typically an elderly patient population. Published case series investigating single agent R have been limited to very small numbers of cases. Therefore, we investigated the use of single agent R as the first line immunosuppressive regimen in patients with AH.

Methods:
We identified all patients evaluated at the University of North Carolina for AH from 8/2005 until 8/2010. Demographic data and clinical characteristics were available for all patients. Complete remission (CR) was defined as FVIII:c >70 IU/dL or Bethesda Inhibitor Unit (BIU) titer of 0.

Results:
Our single center experience includes data on 22 patients with an average age of 76 years (range 52–92). 55% were male and 59% self identified as Caucasian and 18% African American. 86% were diagnosed during the course of an inpatient admission to our medical center. The remaining patients were clinic referrals that completed their evaluation and treatment as outpatients.
At diagnosis the average BIU titer was 193 BU/mL (range 1–1148, median 49.5, IQR 17.8–177.8) and the average FVIII:c was 3.5 IU/dL (range 0–25, median 1.0, IQR 0–5.3). The average time from onset of symptoms (hemorrhage, elevated aPTT, etc) to diagnosis was 27 days (range 1–240, median 14, IQR 7–26.3). The following associated conditions were noted: a) infection (4.2%), b) past malignancy (12.5%), c) active or suspected malignancy (25%), d) autoimmune disorder (25%), and e) idiopathic (33.3%). Notably our series includes no cases of postpartum AH.
Of these 22 patients, 2 were lost to follow-up after their initial hospitalization. Six additional patients died during their initial hospitalization or were discharged to hospice (unrelated to their response to immunosuppressive treatment). Notably, there were no statistically significant differences between these groups in regards to baseline FVIII levels or BIU titers. Fourteen patients were therefore evaluable for response to an initial immunosuppressive regimen. Of these, 12 received R as a single agent, 1 received a combination of R and prednisone (initiated prior to referral), and 1 received prednisone and cyclophosphamide. Of the 12 individuals who received R alone, 7/12 achieved a CR with 1 additional patient (who is under active follow-up) achieving a PR. The remaining 4 patients required additional immunosuppressive agents to achieve a CR (most commonly cyclophosphamide, although one patient required both cyclophosphamide and another course of R). Additional immunosuppressive agents were employed when BIU titer was not felt to be responding adequately. One of these 4 relapsed after an initial CR had been achieved.
Those patients who achieved a CR or PR on R alone had an average baseline BIU titer of 51 (range 1–163, median 22, IQR 5.3–112.8) vs. those who achieved CR with multiple lines of therapy who had an average initial BIU titer of 712 (range 34–1148, median 833.5, IQR 192.8–1111). This difference was statistically significant (p=0.0283). There was no significant difference in baseline FVIII levels between these two groups. Approximated time to CR was also not statistically significant between the two groups (median 127 vs. 258 days, p=0.1274). No significant adverse reactions were encountered in patients treated with R.

Conclusion:
R appears to be an effective single agent immunosuppressive agent in AH with little morbidity, especially in patients with baseline BIU titers <150. Additional agents may be indicated for patients with higher baseline titers. This appears to be the largest single center experience with first line immunosuppression in AH with single agent R described to date.

Disclosures:
No relevant conflicts of interest to declare.