Conventional Oral Prednisone Versus High-Dose Dexamethasone for Management of Adult Immune Thrombocytopenia: A Prospective Randomized Multicenter Clinical Trial

Introduction Oral prednisone (PDN) is conventional standard initial management for adult immune thrombocytopenia (ITP). In recent years single arm studies propose that high-dose dexamethasone (HD-DXM) improves response rate and remission duration and reduces adverse effects, though a randomized trial demonstrated no superiority of HD-DXM. It still lacks evidence-based conclusion on which one is better in efficacy and safety. We conducted a prospective randomized multicenter clinical trial to compare the efficacy and safety of HD-DXM and PDN as first-line strategy for adult newly diagnosed ITP.

Methods We enrolled adult newly diagnosed ITP patients aging between 18 and 80 years, peripheral PLT count <30x10⁹/L or with bleeding symptoms. Diagnosis of ITP and definition of newly diagnosed ITP followed international working group report and ASH evidence-based guideline. A 1:1 randomization was assigned between HD-DXM and PDN arm. In HD-DXM arm, dexamethasone was administered orally at 40mg/d for 4 consecutive days. If PLT count remained or dropped below 30x10⁹/L by day 10, another four-day course of HD-DXM was given. Patients received prednisone orally at 1.0mg/kg/d for no more than 28 days in PDN arm, and then tapered rapidly to minimized maintenance dosage of <15mg/d in responders or stop in non-responders. Early response was evaluated according to criteria mentioned above. We defined sustained response as PLT count maintaining above 30x10⁹/L for 6 months or more. Responders underwent follow-up for at least 6 months or until relapse. Adverse effects were recorded for analysis of safety. Informed consent was obtained from all enrolled patients in accordance with the Declaration of Helsinki. This study was approved by Ethics Committee of each participating site and registered at http://clinicaltrials.gov/ as NCT01356511.

Results From Jan 2011 to May 2014, 182 newly diagnosed adult patients were enrolled from 9 sites over Shandong Province, China, with 92 randomized to HD-DXM arm (62 females and 30 males; age median 43, range 18~73 years) and 90 to PDN arm (68 females and 22 males; age median 44.5, range 18~76 years). Baseline PLT count were 8.93±8.19 (HD-DXM arm) and 10.60±8.67 (PDN arm) x10⁹/L, respectively. Overall response rate in HD-DXM arm was 84.8% (78/92) with 52.2% (48/92) CR, while in PDN arm 74.4% (67/90) and 28.9% (26/90). HD-DXM arm showed similar overall response (P=0.099) but higher CR rate (P=0.002). HD-DXM arm also demonstrated shorter time to response (3.21±1.35 vs. 5.97±4.28 days, P=0.001). 149 patients were available for evaluation of sustained response, 76 in HD-DXM arm and 73 in PDN arm, with follow-up of a median of 10(1-40) and 12(1-39) months, respectively. There was no statistically significant difference between the two arms in sustained response rate (39.5% vs. 49.3%, P=0.251). Generally both treatments were well tolerated. Adverse effects were recorded (HD-DXM/PDN), including hyperglycemia (3/5), hypertension (3/3), peptic ulcer (1/3), gaining weight (0/4), and infection trend (0/2).

Conclusion One or two courses of HD-DXM demonstrated higher CR rate and shorter time to response than PDN. HD-DXM could be a better first-line choice for adult ITP.