Corticosteroids have been used for more than 30 years as a first-line treatment for adult immune thrombocytopenia (ITP).1 The most common regimen is oral prednisone 1 mg/kg/d, slowly tapering to the lowest possible dose (based on platelet count) during a period of weeks. Although several clinical trials have suggested that a four-day course of high-dose dexamethasone (HD-DXM) may be an effective alternative,2,3 expert guidelines have continued to recommend “longer courses of corticosteroids… over shorter courses of corticosteroids”.4 The preference for longer steroid courses has been based, at least in part, on the lack of a comparator group in the previously published studies of HD-DXM.
Dr. Yu Wei and colleagues have now compared the efficacy and safety of high-dose dexamethasone (HD-DXM) versus prednisone in nearly 200 adult patients with ITP. In this prospective, randomized, open-label trial, participants received either DXM 40 mg/d for four days (n = 95) or prednisone 1 mg/kg/d for four weeks, followed by a four to six week taper (n = 97). For patients on the HD-DXM arm, if the platelet count had not reached 30 × 109/L by day 10, a second four-day course of DXM (40 mg/d) was administered. Patients on the prednisone arm were permitted to continue a maintenance dose, provided it was less than 15 mg/d. The authors defined an initial response as platelet count greater than 30 × 109/L and at least two-fold increase of the baseline count without bleeding; they defined an initial complete response as platelet count greater than 100 × 109/L without bleeding. Patients were considered to have achieved an initial response if they met the corresponding milestones on or before day 10 in the HD-DXM arm and day 28 in the prednisone arm. Among those patients who achieved an initial response, a sustained response was reached if 1) no bleeding occurred, 2) no additional ITP-modifying treatment was used, and 3) the platelet count remained greater than 30 × 109/L for six consecutive months.
The proportion of patients who achieved an overall initial response was higher in the group that received HD-DXM (82.1% vs. 67.4% in the prednisone group, P = .044) and the rate of complete response also favored HD-DXM (50.5% vs. 26.8%; p=0.001). Additionally, patients on the HD-DXM arm responded more quickly. The likelihood of achieving a sustained response was similar: 40 percent in the HD-DXM arm and 41.2 percent in the prednisone arm (P = 0.884). While the frequency of some adverse effects (e.g., mood disorder or insomnia) was similar in both groups, weight gain and/or Cushingoid appearance affected more than 10 percent of the prednisone-treated patients (vs. none of the patients treated with HD-DXM).
The results of this randomized, controlled trial suggest that HD-DXM may have some important advantages over a more traditional, longer course of prednisone for the initial treatment of ITP. First, this option would likely be preferred by many patients simply on the basis of convenience. For most patients, a four-day course of treatment (with one possible iteration 10 days later) will be much less burdensome than a two- to three-month course of therapy. This trial indicates that both interventions will cause a small number of patients to experience insomnia or mood disorder, but there is no evidence from this study that the frequency of these psychotropic effects would be significantly more common with HD-DXM. Alternatively, adverse effects typically associated with longer steroid exposures (weight gain, Cushingoid facies, and hyperglycemia) can be expected more frequently with a prednisone taper. Finally, since more than half of adult patients will ultimately require some treatment other than corticosteroids, the HD-DXM strategy may offer the advantage of permitting the clinician to identify which patients will require additional therapy (e.g., splenectomy, rituximab or a thrombopoietin mimetic agent) sooner. If the physician and the patient value these potential advantages, they can now proceed with HD-DXM knowing that it is at least as effective as a prednisone taper for both short- and long-term responses.
McMillan R. Chronic idiopathic thrombocytopenia purpura. N Engl J Med. 1981;304:1135-1147.
Cheng Y, Wong RS, Soo YO, et al. Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med. 2003;349:831-836.
Mazzucconi MG, Fazi P, Bernasconi S, et al. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood. 2007;109:1401-1407.
Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190-4207.
Conflict of Interests
Dr. Garcia indicated no relevant conflicts of interest.
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