A Randomized Trial of Daily Prednisone versus Pulsed Dexamethasone in Treatment-Naïve Adult Patients with Immune Thrombocytopenia: EIS 2002 Study

Abstract

Oral prednisone is considered the standard first-line therapy of adult immune thrombocytopenia, but its long-term efficacy is limited. We performed a prospective, randomized, multicenter trial comparing daily prednisone (1-2 mg/kg/day for 2-4 weeks with subsequent dose reduction) with six 3-week cycles of pulsed dexamethasone (0.6 mg/kg/day, days 1-4). The primary endpoint was remission duration. Of 26 patients enrolled, 22 were evaluable for response. Nine were treated with prednisone and 13 with dexamethasone. The median follow-up was 46 months. The initial response rate (PLT ≥50 × 10⁹/l) was 100% in both groups. Long-term remissions were significantly more frequent with pulsed dexamethasone than with daily prednisone (12 months posttreatment: 77 vs. 22%; p = 0.027). The side effects were similar, but patients on dexamethasone suffered significantly more often from insomnia, while patients on prednisone tended to have more infectious complications. Although the cumulative cortisol equivalent dose was comparable during the first 4 weeks of therapy, it was significantly higher in the dexamethasone arm than in the prednisone arm during the ensuing treatment period. We conclude that repeated cycles of pulsed dexamethasone are a good alternative to daily prednisone as a first-line treatment of immune thrombocytopenia. The duration and intensity of glucocorticoid therapy are important determinants of treatment outcome.

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“…The primary search yielded 157 citations, of which 7 RCTs met the inclusion criteria. [6][7][8]10,[12][13][14] A search of conference proceedings revealed one additional relevant study (abstract only). 9 In total, we included eight RCTs totaling 704 patients with acute primary ITP (κ ¼ 0.83).…”

“…All the RCTs included only adult patients; children younger than 16 years were not included. One study included relapsed ITP cases (5 out of 36 cases), 12 and in the other study 14 3 patients (out of total 22 patients) were secondary ITP due to lymphoid malignancy. Secondary thrombocytopenia patients due to hepatitis viral infection, systemic lupus erythematosus, and pregnancy were clearly excluded in these RCTs.…”

“…Secondary thrombocytopenia patients due to hepatitis viral infection, systemic lupus erythematosus, and pregnancy were clearly excluded in these RCTs. In one RCT from Matschke et al, 14 all patients were administrated prednisone (1 mg/kg/day) for 7 days before being randomized; we included this report in our analysis because we considered the differences in the outcomes between the groups to be derived from the effects of Dex versus PSL after randomization. Individual patient data were not available in any studies.…”

“…The median age of the participants ranged from 24 to 46 years. The intervention groups (Dex) consisted of high-dose Dex (40 mg/day for 4 days in most studies; 0.6 mg/kg/day for 4 days in one study 14 ). In three studies, patients were administered Dex monotherapy (one course of Dex; additional courses were added only in nonresponders) without any consolidation or tapering of the corticosteroid administration, [8][9][10] while in five studies, patients were administered Dex with posttherapy (two to six courses of Dex for all patients 6,13,14 or low-dose Dex 13 or PSL 7,12 accompanying the preceding courses of Dex, irrespective of the treatment effects in the first course of Dex).…”

“…Prednisone, instead of PSL, was used in four RCTs, 6,10,13,14 both of which were analyzed together as the PSL arm. Crossover from one arm to the other was allowed in two studies 12,14 (►Table 1), where we used intention-to-treat analysis. Intravenous immunoglobulin, 12 rituximab, 13 and/or thrombopoietin receptor agonist 13 were used in some studies for poor responders of these corticosteroid studies.…”