Availability of iron and degree of inflammation modifies the response to recombinant human erythropoietin when treating anemia of chronic disease in patients with rheumatoid arthritis.
Forty-six patients with rheumatoid arthritis (RA) and documented anemia of chronic disease (Hb < 100/110 g/l) were randomized to receive either human recombinant erythropoietin (r-HuEPO, n = 36, 300 U/kg body weight) or placebo (n = 10) for 12 weeks in a multicenter study. An adequate response was defined as elevation of Hb > or = 120 g/l. Relevant clinical and laboratory assessments were made to evaluate efficacy and secure safety. A significant elevation in Hb from week 10 onwards was noted in twenty-six patients (five drop-outs) out of nine patients receiving placebo (one drop-out) (12 +/- 1.2 g/l vs 4 +/- 0.5 g/l; Hb elevation from 95 g/l to 107 g/l vs 93 g/l to 97 g/l, P < 0.05). Only 14.6%, however, were considered responders according to preset criteria. In the responders a lower initial CRP, a significant reduction in ESR but not in CRP was seen compared to the remaining r-HuEPO group. A significant elevation of energy level was noted in the r-HuEPO group; otherwise, no differences in clinical variables were seen. No serious adverse effects were noted. When analyzing patients receiving oral iron in combination with r-HuEPO and adding five additional, openly selected patients receiving both adequate iron supplementation and r-HuEPO, there was a significant weekly elevation of Hb from week 8 onwards in favor of combination therapy over the ones only receiving r-HuEPO (18 +/- 1.1 g/l vs 7 +/- 1.1 g/l, P < 0.05). The initial six responders had now reached ten of whom seven belonged to the combination therapy group. Response to r-HuEPO in RA patients appears to be dependent on availability of iron and on the degree of inflammation. If r-HuEPO treatment is considered, iron deficiency should always be corrected and strenuous efforts should have been made to control the disease itself.
Nordström
D
D
Department of Rheumatology, Helsinki University Central Hospital, Finland. dan.nordstrom@huch.fi
Lindroth
Y
Y
Marsal
L
L
Hafström
I
I
Henrich
C
C
Rantapää-Dahlqvist
S
S
Engström-Laurent
A
A
Fyhrquist
F
F
Friman
C
C
D000328:Adult; D000368:Aged; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D002908:Chronic Disease; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007501:Iron / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D004921:Erythropoietin; D007501:Iron