Rituximab, an effective first-line treatment for acute and relapsed TTP

The effect of rituximab on long-term evolution of TTP remains to be seen. An extended follow-up would determine if it decreases the frequency of relapses.

Issue: November 1, 2005

Rituximab (Rituxan; Genentech, Biogen Idec) demonstrates efficacy in patients with acute refractory thrombotic thrombocytopenic purpura (TTP) and anti-ADAMTS13 antibodies, according to a prospective, open-label study.

The trial results support previous preliminary data that reported rituximab as effective in this patient population, according to Fadi Fakhouri, MD, from the Necker Hospital for Sick Children in Paris. “[In addition], our results show … that rituximab is a promising prophylactic first-line treatment in selected patients with severe relapsing TTP and persistent anti-ADAMTS13 antibodies,” he said.

Fakhouri added that the tolerance of rituximab was excellent in both patients with acute TTP and those with severe relapsing disease.

“Despite these promising data, the effect of rituximab on long-term evolution of TTP remains to be ascertained,” said Fakhouri who noted that an extended follow-up would determine whether the drug decreases the frequency of relapses.

High-risk protease

ADAMTS13, a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13, is a protease that prevents platelet thrombi from forming within blood microcirculation. About 90% of patients with TTP lack ADAMTS13 in plasma due to genetic mutations, inherited TTP or circulating autoantibodies, according to the study.

Although plasma infusion is effective for most patients with TTP, patients with severe ADAMTS13 deficiencies require long-term plasma therapy to sustain remission. Researchers continue to search for effective complementary treatments for these high-risk patients.

Because rituximab has proven effective in some lymphoproliferative disorders and autoimmune diseases, Fakhouri and colleagues put the agent to the test in their high-risk population. Rituximab is typically used in the treatment of B-cell malignancies.

Acute and relapsed disease

Between February 2004 and January 2005, researchers enrolled six patients with acute refractory TTP and five patients in remission from severe relapsing TTP. All 11 patients were white.

The researchers used functional assays to test for ADAMTS13 plasma activity and circulating inhibitory anti-ADAMTS13 antibodies.

All patients received four weekly 375 mg/m² infusions of rituximab. Clinicians premedicated the patients with steroids, dexchlorpheniramine and paracetamol. Patients with acute TTP received infusions of 15 to 25 mL/kg of daily plasma infusions until clinical remission.

After achieving clinical remission, all patients underwent clinical evaluations, laboratory tests and testing for ADAMTS13 activity and anti-ADAMTS13 activity every three months.

Effective first-line treatment

The six patients who enrolled during an acute episode of TTP achieved clinical remission five to 14 days following the fourth cycle of rituximab. Eight weeks following rituximab and plasma therapy, researchers noticed that patients exhibited significant ADAMTS13 plasma activity

“In [the five] patients included during a remission phase of TTP, no clinical relapse occurred as expected,” noted Fakhouri. In fact, 24 weeks after their final dose of rituximab, all patients achieved biologic remission: detectable ADAMTS13 plasma activity and the absence of anti-ADAMTS13 antibodies.

All patients remained in clinical remission through follow-up, which was between six and 11 months.

One patient experienced mild hypotension during the first infusion of rituximab. Besides this case, researchers reported no adverse events during the follow-up period. – by Rebekah Cintolo

For more information:
Fakhouri F, Vernant JP, Veyradier A, et al. Efficiency of curative and prophylactic treatment with rituximab in ADAMTS13-deficient thrombotic thrombocytopenic purpura: a study of 11 cases. Blood. 2005;106:1932-1937.