Combination of Anti-Rh(D) and Danazol in Patients with Immune Thrombocytopenia
Authors: Varma Mala , Shapira Ilan , Nakhoul Ibrahim , Shulman Jonah , Lucido David , Kozuch Peter , Culliney Bruce , Mirzoyev Tahir , Machuca Maria , Grossbard Michael L. 
Published: October 2019

Abstract
Abstract 3343

Background
Anti-Rh(D) is an immune globulin against the Rh group and is used for the treatment of immune thrombocytopenia (ITP). A 75 μcg/kg dose induces an overnight response in 92% of patients and a median response duration of 46 days. More than 50% of patients treated intermittently with anti-Rh(D) continue to require therapy after one year. Danazol, an attenuated androgen, has a longer onset of action (median 3.1 months), but has steroid-sparing activity in ITP. We conducted a phase II study to determine whether danazol could lower the requirement for recurrent use of anti-Rh(D).

Methods
Twenty-six patients with ITP were enrolled. Treatment consisted of daily danazol 600 mg PO in combination with anti-Rh(D) 75 μg/kg IV on day 1, repeated whenever the platelet count (PLT) fell below 30,000/μL. After 1 year, danazol was reduced to 400 mg daily for 3 months then to 200 mg daily for 9 months. Chi-square analysis was used to compare requirement for just a single infusion of anti-Rh(D) with that in historical controls treated with anti-Rh(D) alone. The student t-test was used to compare rate of anti-Rh(D) usage over time in both groups. Results were analyzed by intent-to-treat.

Results
Patients' median age was 45 years (range 23–83 years). The male:female ratio was 1.9:1. Eleven (42%) were human immunodeficiency virus (HIV)-positive. Median time from diagnosis of ITP to enrollment was 10.5 months. Median PLT at enrollment was 15,000/μL. Nine (35%) of patients had received a median of one prior infusion of anti-Rh(D). Median duration of follow-up was 28.12 months. Nine (34.6%) of 26 study patients required just a single infusion of anti-Rh(D) in comparison with 1 (3.6%) of 28 control patients, p = 0.003. There was no correlation of age, sex, HIV status, and number of months from diagnosis of ITP with need for a single infusion of anti-Rh(D). At 1 year of follow-up, there was a 20% reduction in anti-Rh(D) use in comparison with historical controls: mean number of infusions per month 0.36 for study patients vs. 0.43 for controls, t = 0.9066, p > 0.05. Platelet responses in HIV-positive patients were not attributable to antiviral treatment. Study therapy was well-tolerated. Two patients stopped danazol due to intolerable adverse effects (grade III acne, grade II myalgias, grade I alopecia.)

Conclusion
Danazol demonstrates anti-Rh(D)-sparing activity. Greater than 1/3 of patients treated with the combination require just a single infusion of anti-Rh(D). The cost of an anti-Rh(D) infusion ($ 1500.00) is nearly one-half the cost of daily danazol for 1 year ($ 3600.00). Historical controls treated with anti-Rh(D) alone required a median of 5 infusions per year whereas patients treated with the combination in this study required a median of 2 infusions per year. This reduction in anti-Rh(D) use would have been associated with cost savings. This study was underpowered to detect a significant difference in rate reduction of anti-Rh(D) use over time. Future studies should evaluate the use of this combination in a larger population.

Disclosures:
No relevant conflicts of interest to declare.