Dapsone salvage therapy for adult patients with immune thrombocytopenia relapsed or refractory to steroid and rituximab

Abstract

Dapsone is an antibacterial sulfonamide with anti-inflammatory property, which showed therapeutic activity in patients with immune thrombocytopenia (ITP) [1][2][3][4][5][6]; the activity in patients who showed refractoriness to rituximab is unknown. We evaluated the effect of dapsone in 20 consecutive adult patients, median age 51 years, with primary ITP previously treated at least with steroids and rituximab. Median baseline platelet count was 19 3 10 9 /L, and the median interval between diagnosis of ITP and dapsone therapy was 46 months. Response (platelet count 30 3 10 9 /L) and complete response (CR; platelet count 100 3 10 9 /L) were 55 and 20%, respectively; median time to response (TTR) was 1 month. All responders were able to interrupt any other specific anti-ITP treatment. The median duration of dapsone therapy in responders and the median response duration were 31 and 42 months, respectively. None of responders lost response during treatment. One patient in CR interrupted dapsone after 9 months and still maintained the response after 48 months. None of the patients interrupted the treatment for toxicity. All the patients were screened for normal glucose-6-phosphate-dehydrogenase (G6PD); two patients showed mild increase of methemoglobin (MHb). These results highlight the therapeutic activity and good safety profile of dapsone in patients with ITP who previously failed rituximab treatment. ITP is an acquired autoimmune disease characterized by increased platelet destruction, impaired megakaryocyte maturation with reduced platelet production, and possible hemorrhagic complications. Treatment is generally indicated for symptomatic patients, that is, those with active bleeding or very low platelet count (usually < 20-30 3 10 9 /L). Glucocorticoids, potentially associated with intravenous high-dose immunoglobulin in those cases with high risk of major bleeding, represent the standard first line of treatment [7]. However, despite the high initial therapeutic efficacy, in most cases, steroids tapering or withdrawal is followed by a drop in platelet count and the need for additional treatment. Treatment of patients with relapsed or refractory symptomatic ITP, particularly of those who are not eligible for, refused or failed splenectomy, still lacks a gold standard therapy. Dapsone is an antibacterial sulfonamide synthesized in 1908 with antimicrobial effect against leprosy, pneumocystic Jiroveci pneumonia in AIDS, toxoplamosis, and malaria. Since 1950s, dapsone also was recognized to have activity in a number of noninfectious inflammatory diseases of the skin as dermatitis herpetiformis and blistering disorders. The anti-inflammatory effect of dapsone is not fully understood, but it appears at least targeted against neutrophils, with interference of myeloperoxidase, inhibition of lysosomal enzymes, chemotaxis, and integrin-mediated adherence function. This agent is contraindicated in patients with G6PD deficiency and has a good safety profile. Hemolytic anemia and an increase of methemoglobin (MHb) are the ma...

Dapsone in dermatology and beyond

“…For eosinophilic fasciitis , there are impressive case reports about the efficacy of dapsone [142]. Dapsone has been used in several clinical studies in patients with immune thrombocytopenia ( ITP ) in which the disease was refractory against standard therapy [40, 51, 52, 176]. Surprisingly, dapsone showed compelling efficacy both in adults and in children [40].…”

Dapsone therapy for refractory immune thrombocytopenia patients: a case series

“…Several retrospective studies demonstrated that dapsone provides an effective, inexpensive, and well-tolerated alternative for patients with refractory ITP (Table 2) [12131415181920]. …”

Is there still a place for “old therapies” in the management of immune thrombocytopenia?

“…The first use of dapsone during ITP was reported in the 1990's by Durand et al [18], and its efficacy was further confirmed in larger series ( Table 2) [19][20][21][22][23][24][25][26][27].…”

“…Once the response is obtained, the drug can be tapered progressively. In rare cases, the response persists after dapsone discontinuation [21,23,25,26]. In cases of relapse, a new response could be achieved by resuming the drug, but sometimes after a long interval [29].…”