Basel, Switzerland (ots/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
"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
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'.
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
- 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
- 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 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
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.
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/prod
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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:
(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.
(4) For patients not currently treated with an erythropoiesis
stimulating agent (ESA), the recommended starting dose is 0.6
microgram/kg body weight, administered once every two weeks as a
single intravenous or subcutaneous injection in order to increase the
haemoglobin to greater than 11 g/dl (6.83 mmol/l). Patients currently
treated with an ESA can be converted to MIRCERA administered once a
month as a single intravenous or subcutaneous injection. The starting
dose of methoxy polyethylene glycol-epoetin beta is based on the
calculated previous weekly dose of darbepoetin alfa or epoetin at the
time of substitution. Summary of Product Characteristics for MIRCERA
in the EU, http://www.emeaeuropa.eu. Darbepoetin alfa in the
correction phase, the initial dose by subcutaneous or intravenous
administration is 0.45 microgram/kg body weight, as a single
injection once weekly. Alternatively, in patients not on dialysis,
an initial dose of 0.75 microgram/kg may be administered
subcutaneously as a single injection once every two weeks. In the
maintenance phase, Aranesp may continue to be administered as a
single injection once weekly or once every two weeks. In patients not
on dialysis, once the target haemoglobin has been achieved with once
every two week dosing, Aranesp may be administered subcutaneously
once monthly using an initial dose equal to twice the previous once
every two week dose.
(5) Machin D, Lewith GT, Wylson S. Pain measurement in randomized
clinical trials. A comparison of two pain scales. Clinical Journal of
(6) National Kidney Foundation web site. Available at:
http://www.kidney.org. Accessed August 9, 2007.
(7) Jurkovitz CT, Abramson JL, Vaccarino LV, Weintraub WS,
McClellan WM. Association of high serum creatinine and anemia
increases the risk of coronary events: results from the prospective
community-based atherosclerosis risk in communities (ARIC) study. J
Am Soc Nephrol. 2003;14:2919-2925.
(8) Pisoni RL, Bragg-Gresham JL, Young EW, et al. Anemia
management and outcomes from 12 countries in the Dialysis Outcomes
and Practice Patterns Study (DOPPS). Am J Kidney Dis. 2004;44:94-111.
(9) Perlman RL, Finkelstein FO, Liu L, et al. Quality of life in
chronic kidney disease (CKD): a cross-sectional analysis in the Renal
Research Institute-CKD study. Am J Kidney Dis. 2005;45:658-666.
(10) Evans RW, Rader B, Manninen DL. The quality of life of
hemodialysis recipients treated with recombinant human
erythropoietin. Cooperative Multicenter EPO Clinical Trial Group.
(11) Stevens JM, Auer J, Strong CA, et al. Stepwise correction of
anaemia by subcutaneous administration of human recombinant
erythropoietin in patients with chronic renal failure maintained by
continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant.
(12) Brazeau GA, Cooper B, Svetic KA, Smith CL, Gupta P. Current
perspectives on pain upon injection of drugs. J Pharm Sci.
(13) Frenken LA, van Lier HJ, Gerlag PG, den Hartog M, Koene RA.
Assessment of pain after subcutaneous injection of erythropoietin in
patients receiving haemodialysis. BMJj. 1991;303:288.
(14) Lui SF, Leung CB, Li PK, Lai KN. Pain after subcutaneous
injection of erythropoietin. BMJ. 1991;303:856.
(15) Granolleras C, Leskopf W, Shaldon S, Fourcade J. Experience
of pain after subcutaneous administration of different preparations
of recombinant human erythropoietin: a randomized, double-blind
crossover study. Clin Nephrol. 1991;36:294-298.
(16) Veys N, Vanholder R, Lameire N. Pain at the injection site of
subcutaneously administered erythropoietin in maintenance
hemodialysis patients: a comparison of two brands of erythropoietin.
Am J Nephrol. 1992;12:68-72.
(17) Bommer J, Weinreich T, Ritz E, Zeier M, Bommer G. Efficacy of
subcutaneous or intravenous recombinant human erythropoietin therapy
in dialysis patients (Abstract). Nephrol Dial Transplant. 1989;4:471.
(18) Veys N, Dhondt A, Lameire N. Pain at the injection site of
subcutaneously administered erythropoietin: phosphate-buffered
epoetin alpha compared to citrate-buffered epoetin alpha and epoetin
beta. Clin Nephrol. 1998;49:41-44.
(19) Yu AW, Leung CB, Li PK, Lui SF, Lai KN. Pain perception
following subcutaneous injections of citrate-buffered and
phosphate-buffered epoetin alpha. Int J Artif Organs.
(20) Frenken LA, van Lier HJ, Jordans JG, et al. Identification of
the component part in an epoetin alfa preparation that causes pain
after subcutaneous injection. Am J Kidney Dis. 1993;22:553-556.
(21) Frenken LA, van Lier HJ, Koene RA. Analysis of the efficacy
of measures to reduce pain after subcutaneous administration of
epoetin alfa. Nephrol Dial Transplant. 1994;9:1295-1298.
(22) Morris KP, Hughes C, Hardy SP, Matthews JN, Coulthard MG.
Pain after subcutaneous injection of recombinant human
erythropoietin: does Emla cream help? Nephrol Dial Transplant.
ots Originaltext: Roche Pharmaceuticals
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