Abstract
Abstract
Introduction. Rituximab, humanized anti-CD20, was initially approved for the treatment of CD20-positive B cell lymphoma, but has recently been shown to be effective in the treatment of a wide range of autoimmune disorders. In a cohort of 25 patients, Stasi et al reported a 52% overall response rate in patients with chronic idiopathic thrombocytopenia (ITP) (Blood2001; 98:952–957). Overall response rates reported since then have been concordant, about 50%. Although rituximab has been increasingly employed for the treatment of ITP, the mechanism of immunological response is not clear. We investigated the effect of rituximab on titers of anti-platelet glycoprotein-specific antibodies in patients with refractory ITP.
Methods. We studied 12 patients with chronic ITP (9 females, 3 males) of ages ranging from 22–87 years, mean age 43 years. All had been treated with glucocorticoids and failed to sustain remission. Three patients failed splenectomy. Their previous medications were continued without major alteration of the dosages during the period of followup. Rituximab was given 375 mg/m2 weekly for 4 courses. Once remission was achieved, previous medications were gradually tapered and stopped completely if remission was sustained. Complete remission (CR) was defined as normalization of platelet counts that lasted longer than 4 months. Partial remission (PR) was defined as a doubling of platelet count if initial counts were ≥20,000 or an increase to ≥30,000 if counts were 20,000 or below. Non-responders (NR) showed neither. Lab studies included CBC, platelets, and blood chemistries. IgM and IgG antibodies against platelet glycoproteins (GP IIb/IIIa, GP Ib/IX, GP IV) were assayed by PAICA prior to and following rituximab therapy.
Results. Ten of 12 patients showed improvement of platelet counts following rituximab therapy. There were 6 CR, 4 PR and 2 NR. Among the 6 CR, remissions lasted for a range of 6–29 months with a mean of 17.0 months. Four of the 6 were able to stop previous therapy for ITP, and the other two were able to reduce their dosages by at least half. Among the 4 PR, remissions were maintained for 4–16 months (mean, 7.3 months). Anti-platelet antibodies became negative in 6 of 6 CR, in 3 of 4 PR and in 0 of 2 NR. Although on average, all anti-platelet antibodies tested were reduced after rituximab therapy, IgM anti-GP IIb/IIIa, IgM and IgG anti-GP Ib/IX and IgM anti-GP IV reached statistical significance (p<0.05). All patients tolerated rituximab well without adverse side effects.
Conclusions. Rituximab frequently induces long lasting clinical remissions that do not require further therapy for ITP and reduction or disappearance of autoantibodies in ITP, unusual features compared to other measures. This finding indicates that a putative mechanism of action of rituximab is inhibition or destruction of autoantibody-producing B cells in ITP. Rituximab is highly effective with minimal side effects and should be considered as primary therapy in patients with chronic ITP.