Efficacy and safety of dapsone in adult primary immune thrombocytopenia

Abstract

To assess efficacy and safety of dapsone in adult immune thrombocytopenia (ITP), a multicenter randomized controlled trial (RCT) and a real-world cohort study were performed. Participants were adults with primary ITP, transient response to corticosteroids with/without intravenous immunoglobulin, and a platelet count of ≤30 × 109/L (or ≤50 × 109/L with bleeding). Patients in the RCT were randomized in arm A (prednisone × 3 weeks + dapsone for 12 months) or arm B (prednisone alone). The observational study involved dapsone initiation at 100 mg/d with standard follow-up. The primary end point was the response rate (platelet count of >30 × 109/L and ≥2× baseline level) at 52 weeks, with the response rate at 24 weeks and adverse events as secondary end points. The RCT enrolled 93 patients (54.8% female), with median age of 48.5 years (46 years in arm A; and 47 years in arm B). In the intention-to-treat analysis, 78.3% of patients in arm A discontinued dapsone after a median of 4.6 weeks because of adverse events (66.7%) or lack of efficacy (33.3%). The response rate at week 52 was 21.7% (95% confidence interval [CI], 10.9-36.4) in arm A vs 8.5% (95% CI, 2.7-18.6) in arm B (P = .17). The observational study, which was conducted after the end of the RCT, included 46 patients (52.2% female), median age of 50.7 years. Adverse events occurred in 30.4%, leading to discontinuation of dapsone in 23.9%, and 13.6% (95% CI 5.2-27.4) met the primary efficacy end point. Results from both studies showed an unfavorable risk-benefit ratio for the use of dapsone in adult primary ITP and suggest that, whenever available, second-line options should be used. This trial was registered at www.ClinicalTrials.gov as #NCT02627417 and #NCT02877706.

Graphical abstract

Figure 1.

Experimental plan of DAPS-ITP RCT. Eligible patients randomized to arm A received dapsone at 100 mg per day in combination with prednisone at a daily dose of 1 mg/kg for 2 weeks, then tapered, and stopped over 1 week for a total of 3 consecutive weeks. After prednisone withdrawal, patients in this arm continued to receive dapsone at the same dose for a total of 12 months unless they did not respond to treatment or in case of a dapsone-related AE graded ≥3. In that case, patients were classified as nonresponders and the subsequent treatment was chosen by the investigator at his/her discretion based on standard of care. Patients randomized to arm B received prednisone alone at a dose of 1 mg/kg per day for 2 weeks, then tapered, and stopped over a week for a total duration of 3 consecutive weeks. After this 3-week period, patients in arm B remained untreated and were monitored. In case of relapse, patients were classified as nonresponders and the subsequent treatment was chosen at the investigator’s discretion based on standard care. M12, Month 12; R, response; CR, complete response.

Figure 2.

Flow charts. (A) Flowchart of the DAPS-ITP trial. (B) Flowchart of the observational cohort study. IgIV, Intravenous Immunoglobulin; ITT, intention to treat; SAE, serious adverse event.

Figure 3.

Probability of dapsone discontinuation over time. (A) Probability of treatment discontinuation (experimental arm) or ITP relapse (control arm) over time in the DAPS-ITP trial (log-rank test). (B) Probability of dapsone discontinuation in the observational cohort study.