Study Shows Subcutaneous Injection With MIRCERA is Significantly Less Painful Than With SC Aranesp (1)

BASEL, Switzerland, October 29 /PRNewswire/ -- A new study on pain published today has found that subcutaneous (SC) injections of the new renal anaemia therapy MIRCERA is associated with significantly less pain immediately after injection than SC darbepoetin-alfa (Aranesp).(1) These findings are important because to date there has been minimal data regarding SC injection site pain in adults with different erythropoiesis-stimulating agents (ESAs), despite such pain being a common adverse event and a burden for patients with chronic kidney disease (CKD).

Complaints of pain with subcutaneous injections of traditional ESAs is known to cause physicians to treat their CKD patients via the intravenous route(2),(3) despite the fact that subcutaneous use can be more convenient and may ultimately improve compliance and persistence.

"These study findings provide important information for physicians when they are choosing ESA therapy for their patients. Repeated painful injections of what is often life-long treatment in these chronically ill kidney disease patients may affect compliance and could result in poor control of their anaemia. The statistically significant difference in pain experienced by the study participants given MIRCERA subcutaneously compared to darbepoetin alfa along with the less frequent dosing intervals MIRCERA has in its label(4) are important factors that physicians should consider when determining the treatment options for their patients," said Dr Frank Dougherty, Clinical Science Leader at Roche.

In the Roche-sponsored study, half of participants (53%) rated injection with darbepoetin alfa as more painful than MIRCERA injections.

The study

In a randomized, placebo-controlled, single centre, single blind study, healthy subjects (81 completed the study) received one of six potential treatment sequences (ABC/ ACB/ BAC/ BCA/ CBA/ CAB), involving SC injection on days 1, 29, and 57 of: (A) MIRCERA. 50 micrograms; (B) darbepoetin alfa 50 micrograms and (C) placebo (saline solution, 0.5mL).

The design of this trial ensured that any observed differences would not be a result of variation in subjects' pain perception. In addition, the trial methodology was standardized where possible to ensure that any observed differences in pain perception between SC treatments were unlikely to result from properties of the final preparation (e.g., drug concentration, injection volume) or injection procedure (e.g., needle size or sharpness, location of injection site, and staff's administration technique). Furthermore, all patients were blindfolded.

Subjects assessed their SC injection site pain immediately after dosing on two scales: the visual analogue scale (VAS) and the verbal rating scale (VRS).(5) The primary endpoint was pain VAS immediately after the SC administration and the secondary endpoints were pain VAS 1 hour after dosing; VRS immediately and at one hour after dosing, safety and tolerability. On the 100-mm VAS, subjects rated their pain from 0 mm ('no pain') to 100 mm ('pain as bad as it could be'). The 6-point VRS was a categorical scale where 0 = 'no pain', 1 = 'minimal pain', 2= 'slightly painful', 3='moderately painful', 4='very painful', and 5='extremely painful'.

Study Findings

Using both the VAS and VRS systems, MIRCERA was associated with significantly less pain.

-- The least square mean VAS was 21.5 following SC administration of MIRCERA compared to 33.4 following SC darbepoetin alfa, which was statistically significant. Placebo was associated with the lowest mean VAS value (16.0).

-- In most subjects, pain VAS 1 hour after administration was 0 mm ("no pain").

-- Using the VRS, just over half of subjects (53% - 43 out of 81) rated darbepoetin alfa as more painful than MIRCERA. Only 12% rated MIRCERA with a higher VRS score than darbepoetin alfa.

-- 34% of subjects gave MIRCERA and darbepoetin alfa equal VRS scores.

-- None of the MIRCERA treated subjects gave a rating of 'very painful' (VRS score 4) compared with 13% of subjects who were administered darbepoetin alfa.

-- One hour after administration, most subjects rated their pain VRS as 0 "no pain".

MIRCERA

MIRCERA was approved in the EU in July and in Switzerland and Norway in September. It has already been launched in Austria, Sweden, Germany and the UK. It is the first ESA in the EU that offers a convenient dosing schedule of once every two weeks to correct anaemia in all CKD patient types not previously treated. MIRCERA is also the first ESA in the EU approved to directly convert all CKD patients types previously treated with any ESA to once-monthly dosing. The capacity of MIRCERA to correct and sustain haemoglobin levels in patients with CKD-related anaemia, coupled with a reduced dosing frequency that is associated with less pain on injection offers physicians and patients a new treatment option. The safety and efficacy of MIRCERA in other indications has not been established.

CKD and Anaemia

Anaemia is a frequent complication of CKD and untreated patients suffer fatigue, reduced quality of life, and an increased risk of cardiovascular events.(6),(7),(8),(9),(10) The introduction of ESAs has substantially improved the management of renal anaemia and these treatments have become widely accepted as a replacement for red blood cell transfusions. However, a drawback with traditional ESAs is that they require frequent dosing in the majority of patients to maintain efficacy and injection site pain is a common adverse event.(11),(12),(13),(14),(15),(16),(17),(18),(19),(20),(21),(22) The unique activity of MIRCERA at the receptor involved in stimulating red blood cell production, coupled with its longer half-life compared to traditional ESAs, is believed to play an essential role in providing smooth and predicable control of anaemia with as few as 12 injections per year.

About Roche

For more information please visit http://www.roche.com

Notes to the Editor:

Additionally another study, regarding the mechanism of action of MIRCERA, has just been published in the journal Pharmacology. The article describes the different receptor binding properties of MIRCERA that may enable continuous stimulation of erythropoiesis and, combined with a long half-life and slow systemic clearance, permit administration at extended intervals. The abstract and manuscript for this study are available at http://content.karger.com/ProdukteDB/pro....

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References

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(1) Pannier A et al. Subcutaneous injection pain with C.E.R.A., a continuous erythropoietin receptor activator, compared with darbepoetin alfa. Current Medical Research and Opinion. 2007 23; 12: 3025-3032

(2) Weiss, L. Flexible dosing schemes for recombinant human erythropoietin - lessons from our daily practice. Nephrol Dial Transplant (2001) 16: (Suppl 7): 15 - 19.

(3) Veys N Ringoir S. The subcutaneous administration route of epoetin: advantages, pain at the injection site and patient acceptance. Int J Artifl Organs 1993 16; 1: 1-3.

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