A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia

Abstract

SummaryThe impact of first-line treatment with the anti-CD 20 chimeric monoclonal antibody rituximab in patients with warm-antibody reactive autoimmune haemolytic anaemia (WAIHA) is unknown. We report the first randomized study of 64 patients with newly diagnosed WAIHA who received prednisolone and rituximab combined (N = 32) or prednisolone monotherapy (N = 32). After 12 months, a satisfactory response was observed in 75% of the patients treated with rituximab and prednisolone but in a significantly smaller proportion (36%) of those given prednisolone alone (P = 0Á003). Furthermore, relapse-free survival was significantly better after the combined therapy than after prednisolone monotherapy (P = 0Á02). After 36 months, about 70% of the patients were still in remission in the rituximab-prednisolone group, whereas only about 45% were still in complete or partial remission in the prednisolone group. There was no significant difference between the two groups regarding adverse reactions to the studied medications. Likewise, serious adverse events were equally distributed, and no allergic reactions to rituximab were recorded. In conclusion, our data show that using rituximab and prednisolone combined rather than prednisolone alone as first-line treatment in WAIHA increases both the rate and the duration of the response.

Characteristics and outcome of warm autoimmune hemolytic anemia in adults: New insights based on a single‐center experience with 60 patients

“…The efficacy and safety of rituximab given in newly diagnosed primary wAIHA is being evaluated in a double-blind placebo controlled randomized trial (Clinical Trials.gov identifier: NCT01181154). The recent report of a doubleblind randomized prospective Danish study of 64 cases of wAIHA, mixing both primary and secondary wAIHA, provides strong evidence in favor of the early use of rituximab for wAIHA [11]. Results of another prospective but uncontrolled study were reported by an Italian group [10] and showed a high rate of efficacy of low-dose rituximab especially for wAIHA as compared with cold AIHA.…”

“…However, since 2000, rituximab has been increasingly used as second-or third-line treatment first in children and then in adults [8][9][10][11]. We previously reported the characteristics of 83 cases of AIHA, including 72 of wAIHA seen at our institution between 1980 and 2000, before the era of rituximab [5], and found an overall mortality rate of 18%.…”

Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients

“…In these atypical cases, the diagnosis, made after extensive laboratory workup and exclusion of other causes of hemolysis, is frequently deferred, with consequent delay in therapy. 1,2,[5][6][7] Treatment of AIHA is still not evidence based and is mainly accomplished according to expert opinions and individual experience, [8][9][10][11] with few prospective therapeutic trials [12][13][14][15] and large but dated comprehensive clinical studies. 16 Moreover, the temporal sequence of second-line options is still controversial, and no predictors of outcome are available.…”

Autoimmune Hemolytic Anemia:Focusing on Therapy According to Classification

“…In this study, 64 newly diagnosed wAIHA patients were treated eıther with steroid monotherapy or with combination of rituximab and steroid. The response rate and relapse free survival rates were statistically better in the combination group [46].…”