The Scottish Medicines Consortium (SMC) has accepted iron isomaltoside 1000 5% (Diafer) for use within the NHS Scotland for the treatment of iron deficiency in adults with chronic kidney disease (CKD) on dialysis, when oral iron preparations are ineffective or cannot be used.
Iron isomaltoside is a low dose iron preparation, especially formulated for use in adults with chronic kidney disease on dialysis. Anaemia affects over two-thirds (68%) of people starting dialysis and having adequate iron stores is essential for achieving optimal haemoglobin (Hb) levels and maximum benefit from erythropoiesis-stimulating agents (ESAs). Decreased iron stores or decreased availability of iron are the most common reasons for resistance to the effect of these agents.
This SMC advice regarding iron isomaltoside takes into account the benefits of a Patient Access Scheme (PAS) that improves the cost-effectiveness of iron isomaltoside. This advice is contingent upon the continuing availability of the PAS in NHS Scotland or a list price that is equivalent or lower.
Professor Philip Kalra from Salford Royal Hospital and author of the PROPOSE study upon which the SMC review was based, commented: “The SMC’s advice is welcomed as this gives clinicians an effective alternative treatment for patients with CKD on dialysis."
The SMC advice is based on evidence from a phase III, randomised, open-label, 6-week non-inferiority study (PROPOSE) which compared 10% iron isomaltoside 1000, the higher strength of iron isomaltoside 1000 containing 100mg iron per mL, with iron sucrose in 351 patients with chronic kidney disease (CKD) receiving haemodialysis. The SMC accepted clinical equivalence between the 5% and 10% iron isomaltoside 1000 formulation.
The primary outcome of the PROPOSE study was the proportion of patients who maintained Hb ≥95g/L and ≤125g/L at week 6. The proportion of patients receiving iron isomaltoside 1000 10% versus iron sucrose, at equivalent doses, who achieved the primary outcome were 83% (187/226) versus 83% (95/115) p=0.01 in the final analysis set (and 84% (167/199) versus 82% (88/107), in the per protocol population. As the results were within the 10% margin, non-inferiority of iron isomaltoside 1000 10% to iron sucrose was demonstrated.
After six weeks of treatment, in the final analysis set, there were no significant differences between treatment groups in the secondary outcomes of change from baseline of Hb concentration, serum iron, TSAT, serum ferritin and reticulocyte count. There was also no significant difference between treatment groups in the patients’ energy levels, ability to do daily activities and overall quality of life assessed using the Linear Analogue Scale Assessment score.