title: Meta-analysis of efficacy and tolerability data on iron proteinsuccinylate in patients with iron deficiency anemia of different severity.
abstract: Iron proteinsuccinylate (ITF 282, CAS 93615-44-2) is an iron derivative for the oral treatment of iron deficiency anemia. Its efficacy and tolerability have been proved in about 1800 patients, enrolled in 3 multicenter clinical trials. The first aim of this meta-analysis is to verify the increase of hemoglobin (Hb) in these patients (891 treated with ITF282, 644 treated with iron sulphate and 236 treated with iron-polysterene sulphonate). The 3 studies show homogeneous Hb increases. ITF 282 appeared to provide, from time 0 to the 30th day of treatment, a similar or lesser increase in Hb in comparison to the reference drugs, while from the 30th day of treatment to the 60th day its efficacy was always greater than that of the reference medications. The data have been further analyzed by subdividing the patients in three classes, according to the severity of the anemia: basal Hb < or = 9 g/dl, > 9 < or = 11 g/dl, > g/dl. During the 60-day treatment, both ITF 282 and the reference drugs induced the most significant increase in Hb in the patients affected by the most severe anemia. The meta-analytic evaluation of the 3 trials results has been extended to tolerability data. Most side effects were related to the gastrointestinal tract. Their incidence resulted signficantly lower for ITF 282 than that for the reference drugs (9.4% vs. 20.4%, p < 0.01). The comparative sub-analysis of the side effect distribution into the patients populations shows that ITF 282 is definitely better tolerated in pregnant women (relative risk 0.321, p < 0.01). The time course of Hb increases and the tolerability data suggest a different mechanism by which ITF 282 and the reference drugs are effective. Since the main difference between ITF 282 and the reference drugs is the form in which the iron is presented to the gastrointestinal mucosa, it may be supposed that the reference drugs, providing free divalent iron ions for absorption, could induce some kind of irritative condition of the gastrointestinal mucosa, which results in a reduced long-term absorption capacity, as well as in a higher incidence of gastroenteric adverse events. ITF 282, providing protein-bound iron, would not permit the process supposed with divalent iron, thus resulting in prolonged absorption capacity (that is higher hemoglobin recovery) and higher gastrointestinal tolerability.
authors.affiliation: Institut für Medizinische Informatik und Biomathematik, Westfälische Wilhelms-Universität Münster, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Köpcke
authors.forename: M C
authors.initials: MC
authors.lastname: Sauerland
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018798:Anemia, Iron-Deficiency / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D008667:Metalloproteins / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D013386:Succinates / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D006454:Hemoglobins; D008667:Metalloproteins; D013386:Succinates; C055066:iron protein succinylate