High-Dose Dexamethasone Preferable to Corticosteroids for Patients with Immune Thrombocytopenia

While ASH’s 2011 practice guidelines recommend first-line treatment with corticosteroids (typically prednisone) for adult patients with immune thrombocytopenia (ITP) only two-thirds of patients are likely to have an initial response, with a limited number of patients experiencing long-term remission. In addition, side effects associated with corticosteroids can outweigh the benefits of their long-term use.

Previous studies have found encouraging results in treating ITP with high-dose dexamethasone, but there have not been any head-to-head trials comparing high-dose dexamethasone with prednisone.

In an article published in Blood, Yu Wei, MD, from the Department of Hematology at Qilu Hospital of Shandong University in Jinan, China, and colleagues reported the results of a prospective, multicenter, open-label, randomized, controlled trial to compare the efficacy and safety of high-dose dexamethasone and conventional prednisone as a first-line therapy for newly diagnosed, treatment-naïve, primary ITP in adult patients.

Patients were screened for eligibility at nine centers in China from January 2011 to May 2014, with 195 patients included in the study. All patients had primary ITP and a baseline peripheral platelet count of <30×109/L or the presence of bleeding symptoms at enrollment. Patients with life-threatening bleeds were not included, nor were patients who had been previously treated with medication for ITP or had malignancy, active infection, hypertension, cardiovascular disease, or liver and kidney function impairment.

Patients were randomized 1:1 to receive:

  • Dexamethasone: 40 mg per day for four days (n=95; nonresponders received an additional four-day course of treatment)
  • Prednisone: 1 mg/kg per day for four weeks then tapered (n=97)

Each patient underwent a safety follow-up one month after therapy was stopped.

Across both arms, 155 patients (80.2%) presented with bleeding symptoms, generally mild to moderate. The majority of patients (116; 60.4%) had a baseline platelet count of ≤10 x 109/L; these patients also presented with significantly more severe bleeding manifestations than patients with a baseline platelet count of <10 x 109/L (p<0.001).

Dr. Wei and colleagues found that one or two courses of high-dose dexamethasone resulted in a higher incidence of overall initial response (IR) and sustained response (SR), compared with prednisone (TABLE). Response was defined as having a platelet count of ≥30 x 109/L and at least a two-fold increase of the baseline platelet count and absence of bleeding, with complete response (CR) defined as having a platelet count of ≥100 x 109/L and absence of bleeding.

Of the patients receiving high-dose dexamethasone, 67.4 percent responded to the initial treatment course, with 45.3 percent achieving CR.

Twenty-eight patients in the dexamethasone cohort did not respond to initial treatment and, of these, half responded to the additional treatment, with five patients achieving a CR.

Adding the second four-day course also increased the incidence of overall response (p=0.029), though the initial non-responders were less likely to achieve CR than those who did respond to the initial course of treatment (p=0.037), indicating that “initial CR was a definite positive predictor of better long-term outcomes,” the authors noted.

Patients treated with high-dose dexamethasone experienced fewer bleeding events than those treated with prednisone: 12 versus 25, respectively (p=0.028). Those patients also had lower bleeding scores (p=0.030).

Forty percent of patients in the high-dose dexamethasone cohort achieved a sustained response, compared with 41.2 percent of patients receiving prednisone (p=0.884) – indicating no significant difference in response between treatment groups.

The researchers noted that gender, age, and baseline platelet counts had no significant association with treatment response in either cohort. However, a baseline bleeding severity score (calculated by adding the points relevant to various clinical bleeding signs, including purpura, nosebleeds, and other factors) of ≥8 was associated with a lower initial response rate (odds ratio [OR] = 0.253; 95% CI 0.069-0.922 for high-dose dexamethasone; OR = 0.210; 95% CI 0.062-0.706 for prednisone).

At one year of follow-up, the number of patients in each cohort still responding were comparable (36.8% in the high-dose dexamethasone group vs. 33% in the prednisone group [p=0.650]), as was overall duration of response (p=0.522).

No deaths occurred in either treatment group. Most adverse events were mild to moderate and usually resolved spontaneously after treatment course was completed. Both treatments were deemed well-tolerated by the researchers, who also noted that “all adverse events had been previously described or reported.” The frequency of adverse events was higher in the prednisone arm, particularly with the incidence of Cushingoid appearance (13.4% and 0%) and weight gain (10.3% and 0%). “The better tolerance of high-dose dexamethasone might be attributed to its limited duration, as adverse events in this arm were usually transient and spontaneously resolved after the completion of medication,” Dr. Wei and colleagues explained.

“One or two courses of high-dose dexamethasone provides a more effective and more rapid response as initial treatment of ITP, with at least comparable long-term prognosis and better tolerance when compared with conventional prednisone,” Dr. Wei and colleagues concluded. “High-dose dexamethasone also enables patients to avoid the burden of long-term corticosteroids.”

“These findings resolve the long-term confusion about the superiority between the two corticosteroid regimens among ITP experts,” corresponding author Ming Hou, MD, also from Qilu Hospital of Shandong University, told ASH Clinical News. “Considering the shorter time to response and shorter administration course of high-dose dexamethasone, clinicians are now able to evaluate the initial response to corticosteroid therapy at an early time point and make immediate intervention to non-responders.”

High-dose dexamethasone could be a preferred corticosteroid strategy for first-line management of adult primary ITP; however, to better understand whether repeated courses of medication may yield better long-term outcomes, they added, “future randomized controlled trials should be designed to compare the effect of repeated courses versus a limited course of high-dose dexamethasone.”


Reference

Wei Y, Ji X, Wang Y, et al. High-dose dexamethasone versus prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial. Blood. 2015 October 19. [Epub ahead of print]

TABLE. Comparison of Outcomes Between the Two Arms
High-dose dexamethasone (n=95) Prednisone (n=97) p Value Odds ratio (95% CI)
Overall response, n (%) 78 (82.1) 67 (69.1) 0.044 2.054 (1.042-4.050)
Complete response, n (%) 48 (50.5) 26 (26.8) 0.001 2.789 (1.526-5.097)
Sustained response, n (%) 38 (40.0) 40 (41.2) 0.884 0.950 (0.534-1.690)
Sustained complete response, n (%) 26 (27.4) 17 (17.5) 0.120 1.773 (0.889-3.539)

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