Biology Reference
In-Depth Information
duration of treatment. In contrast, the excellent response observed in patients
with congestive heart failure reflects both the long duration of treatment and
the presence in many patients of concurrent renal insufficiency induced by low
cardiac output [84].
Of more immediate relevance is the difference in degree of response
between the two studies of patients with rheumatoid arthritis treated with
rHuEPO 300 U/kg weekly [80, 81]. This difference almost certainly reflects
the difference in iron supplementation. Only six of 36 patients studied by
Nordstrom and colleagues received iron supplementation [80], compared with
23 of 30 patients treated by Kaltwasser et al. [81]. The median serum ferritin
in the Nordstrom population (46.5 g/L) was below the definition chosen for
iron deficiency in the Kaltwasser study (50 g/L). Clearly iron supplementation
is a predictor of the hemoglobin response to rHuEPO.
Another predictor of the rHuEPO response in patient with ACD is the
degree of disease activity. Patients with rheumatoid arthritis with lower
C-reactive protein concentrations and erythrocyte sedimentation rates have
been reported to have better responses to rHuEPO [80]. Subcutaneous
rHuEPO administration has been reported to decrease disease activity in
patients with rheumatoid arthritis [79, 81, 85] and to improve functional clas-
sification of heart failure patients [84]; comparable results are not reported in
patients with rheumatoid arthritis treated with intravenous rHuEPO [74-76].
The adverse effects reported with rHuEPO in renal failure (exacerbation of
hypertension, seizures, pure red cell aplasia) are not described in patients with
ACD treated with rHuEPO.
Most of the studies evaluating the treatment ACD with rHuEPO use 300 to
450 U/kg subcutaneously in divided doses, generally three times weekly.
Failure to respond at eight to 10 weeks should prompt a 50% dose increase.
Although it has been studied primarily in cancer, there is no reason why the
commonly used single weekly dose of 40,000 U rHuEPO subcutaneously
should not be of equal efficacy in ACD. Failure to respond at six weeks should
lead to an increase in dose to 60,000 U/week. For reasons made clear in the
preceding paragraph, ferrous sulfate 325 mg three times a day should also be
administered to patients with ACD who do not show laboratory evidence of
iron overload. A trial of intravenous iron and rHuEPO should be considered in
patients with ACD with a poor response to rHuEPO and oral iron [86].
Treatment with iron by itself (not as an adjunct to rHuEPO), whether oral or
intravenous, is only useful in those patients with concurrent iron deficiency
[87-89].
The use of rHuEPO to allow autologous blood donations by patients with
ACD undergoing elective surgery (particularly orthopedic surgery) has been
reported [90, 91]. This setting represents a particular challenge, since the
ability to donate autologous blood is dependent on a normal hemoglobin or
hematocrit. The administration of rHuEPO to otherwise healthy individuals
allows collection of a larger quantity of autologous blood [92]. The quantity
of autologous blood collected from patients with rheumatoid arthritis after
