Complete recovery from refractory immune thrombocytopenic purpura in three patients treated with etanercept

Abstract

Management of patients with immune thrombocytopenic purpura (ITP) who have persistent, severe, and symptomatic thrombocytopenia following splenectomy is difficult and empirical. No single agent or regimen provides long-term success for most patients, and for most treatments it is difficult to assess whether benefits outweigh risks. We report three consecutive patients with critical chronic refractory ITP, who responded promptly and completely following treatment with etanercept, an inhibitor of tumor necrosis factoralpha. These patients had failed 6-11 previous treatments. In the first patient, etanercept was given for its approved indication: a flare of co-existing rheumatoid arthritis. The next two patients were treated with etanercept because of successful outcomes in the previous patients. Although etanercept appeared to be effective treatment for ITP in these 3 patients, the experimental nature of this treatment and the potential risks must be emphasized. On the basis of these case reports, a clinical trial has been initiated to systematically evaluate the efficacy and risks of etanercept in the management of children and adults with chronic ITP. Am. J. Hematol. 73:135-140, 2003.

Thrombocytopenia associated with the use of anti–tumor necrosis factor–α agents for psoriasis

“…Stinco, Piccirillo, and Patrone 9 described a patient receiving etanercept therapy who experienced mild thrombocytopenia that resolved spontaneously without the suspension of the drug, and later confirmed by re-exposure to the same agent with a similar platelet count evolution. Paradoxically, other reports describe the successful use of etanercept 23,24 and infliximab 25 for the treatment of refractory immune thrombocytopenic purpura.…”

The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia

“…Although studies evaluating TNF-α in the context of cITP are scarce, the use of a recombinant TNF-α receptor to neutralize TNF-α ameliorates the disease. 21 In agreement with previous results, 3,7 we observed that cITP patients have an upregulation of the Th1 lineage characterized by no detectable serum IL-4 (P<0.001, Figure 1) and increased serum median levels of IL-2 (17.3-fold increase), IL-12p70 (34.8-fold increase) and IFN-γ (1.6-fold increase) (P<0.001 for all, Figure 1), with a concomitant increased percentage of CD4+/IFN-γ+ cells (16.3±11.5 and 5.9±2.29 in patients and controls, respectively, P=0.04) (Figure 2A and B). We also observed that the serum level of IL-2 was correlated with IFN-γ (r=0.42, P<0.001).…”

Current treatment options for primary immune thrombocytopenia

“…Other agents that have been reported in the treatment of ITP are anti-CD154/CD40 [105,106], anti-Fcg RIII [107], soluble TNF-a receptor [108] and anti-IL-2 receptor [109]. These studies have failed to provide sufficient positive results to stimulate further studies.…”