Fw: Treatment of severe autoimmune thrombocytopenic purpura

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----- Original Message -----

From: " Kathi " <pureheart@...>

Sent: Sunday, July 07, 2002 8:42 PM

Subject: Treatment of severe autoimmune thrombocytopenic purpura

> Correspondence

>

>

> Treatment of severe autoimmune thrombocytopenic purpura

>

>

> Sir--In their report, Bertrand Godeau and colleagues (Jan 5, p 23)1

> elegantly show that intravenous immunoglobulin is more effective for

> the acute treatment of severe autoimmune thrombocytopenic purpura than

> methylprednisolone. However their use of a platelet count less than

> 50x109/L as a surrogate marker for bleeding risk is slightly

> misleading. Bleeding risk is strongly correlated with age, the highest

> risk being patients older than 60 years,2 of whom their study only

> included small numbers.

>

> In fact a platelet count of more than 30x109/L, rather than more than

> 50x109/L is associated with an extremely low risk of haemorrhage.3 No

> mention is made of the difference in cost between these two treatments

> (around US$1228 vs $105 for a 70 kg patient), or the small but

> significant risks associated with intravenous immunoglobulin

> (anaphylaxis, haemolytic anaemia, aseptic meningitis).

>

> Thus, to recommend intravenous immunoglobulin and prednisone as

> first-line treatment for patients of all ages with severe

> thrombocytopenia (platelet count <20x109/L) will lead to substantial

> treatment-related expense and expose some patients to potential risks

> when their risk of fatal haemorrhage is very low.

>

> The treatment does work, but is it needed for everyone?

> Duncan Carradice

>

>

>

> --------------------------------------------------------------------------

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>

> Department of Haematology, Christchurch Hospital, Christchurch, New

> Zealand (e-mail:duncan.carradice@...)

>

>

> 1 Godeau B, Chevtet S, Varet B, et al. Intravenous immunoglobulin or

> high-dose methylprednisolone, with or without oral prednisone, for

> adults with untreated severe autoimmune thrombocytopenic purpura: a

> randomised, multicentre trial. Lancet 2002; 359: 23-29. [Text]

>

>

> 2 Cohen YC, Djulbegovic B, Shamai-Lubovitz O, Mozes B. The bleeding

> risk and natural history of idiopathic thrombocytopenic purpura in

> patients with persistent low platelet counts. Arch Intern Med 2000;

> 160: 1630-38. [PubMed]

>

>

> 3 Cortelazzo S, Finazzi G, Buelli M, Molteni A, Viero P, Barbui T.

> High risk of severe bleeding in aged patients with chronic idiopathic

> thrombocytopenic purpura. Blood 1991; 77: 31-33. [PubMed]

>

> Sir--We wonder why the primary outcome of Bertrand Godeau and

> colleagues' trial1 was the number of days with platelet count more

> than 50x109/L. It seems clear from the data that a platelet count at

> this concentration was of no real clinical use, especially in patients

> with no evidence of bleeding. Indeed the risk of fatal haemorrhage is

> extremely low even with a platelet count lower than 30x109/L.2

>

> The so-called wet autoimmue thromobcytopenic purpura group, which is

> at an increased risk of haemorrhage, was excluded. Physicians need

> definitive answers in patients with severe autoimmue thromobcytopenic

> purpura, especially in those who have bleeding episodes.

> Unfortunately, Godeau and colleagues do not answer that question for

> intravenous immunoglobulin or high-dose methylprednisolone. These two

> treatments seem equally effective in patients with severe autoimmue

> thromobcytopenic purpura and no sign of haemorrhage.

> Rama Balaraman

>

>

>

> --------------------------------------------------------------------------

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>

> Ellis Fischel Cancer Hospitals and Clinics, University of Missouri,

> 115 Business Loop 70 West, Columbia, MO 65203, USA

>

>

> 1 Godeau B, Chevret S, Varet B, et al. Intravenous immunoglobulin or

> high-dose methylprednisolone, with or without oral prednisone, for

> adults with untreated severe autoimmune thrombocytopenic purpura: a

> randomised, multicentre trial. Lancet 2002; 359: 23-29. [Text]

>

>

> 2 Cohen YC, Djulbegovic B, Shamai-Lubovitz O, Mozes B. The bleeding

> risk and natural history of ITP in patients with persistently low

> platelet counts. Arch Intern Med 2000; 160: 1630-38. [PubMed]

>

> Authors' reply

>

> Sir--We agree with the remarks of Duncan Carradice and Rama Balaraman

> that the use of a platelet count lower than 50x109/L as a surrogate

> marker for bleeding risk could be misleading. However, we show that

> the median number of days with platelet counts higher than 20x109/L

> (and two-fold the baseline value) between day 1 and day 21 after

> treatment was started is significantly higher in patients assigned

> intravenous immunoglobulin at randomisation than in those assigned

> high-dose methylprednisolone. The proportion of patients who have

> platelet counts greater than 20x109/L between day 2 and day 5 is also

> significantly higher in the intravenous immunoglobulin group.

>

> The number of days with platelet count greater than 20x109/L also

> differs significantly in patients receiving intravenous immunoglobulin

> plus prednisolone and those receiving high-dose methylprednisolone

> plus prednisolone. Thus, we clearly show that intravenous

> immunoglobulin acts more rapidly, more frequently, and for a longer

> time than high-dose methylprednisolone.

>

> As we note in the discussion, however, we are aware that clinical

> trials of autoimmune thrombocytopenic purpura should ideally focus on

> the effect of treatment on risk of severe bleeding or death, although

> these events are very rare. Thus, with these outcomes, we would need

> to enrol more than 1000 patients to show a clinical benefit, which is

> not feasible. We therefore chose platelet count as the primary outcome

> measure because it is a relevant and simple surrogate marker.

>

> We also agree that other considerations, such as the cost of the

> treatment, should be taken into account for the choice of treatment.

> As Carradice states, we show that intravenous immunoglobulin works

> and, contrary to the suggestion of Balaraman, that intravenous

> immunoglobulin is better than high-dose methylprednisolone. However,

> to the question of Carradice of whether it is needed for everyone, we

> answer in our report that, in our opinion, only patients with the most

> severe forms of autoimmune thrombocytopenic purpura should receive

> intravenous immunoglobulin and prednisone.

> *P Bierling, B Godeau

>

>

>

> --------------------------------------------------------------------------

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>

> *Laboratoire d'Immunologie Leucoplaquettaire (EFS Ile-de-France), and

> Service de Médecine Interne, Hôpital Henri Mondor, 94000 Créteil,

> France

>

>

http://www.thelancet.com/journal/vol359/iss9325/full/llan.359.9325.correspon

dence.21567.1

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