INTRODUCTION:

Chronic kidney disease (CKD) is a progressive loss of function over several months to years, characterized by gradual replacement of normal kidney.¹Anaemia is a common risk factor for end-stage renal failure and cardiovascular events.²Anaemia is one of the most common complications in patients with CKD and correction of anaemia may improve the quality of life of a patient.³Anaemia is more common in patients with diabetes than without diabetes, and the problem is further exaggerated in patients with renal impairment.⁴The most common reason for a decreased haemoglobin levels in CKD patients is due to low production of erythropoietin hormone from kidney.⁵

The standard therapy for correction of anaemia in CKD patients is erythropoiesis-stimulating agents (ESAs).⁶Continuous erythropoietin receptor activator (CERA) is a long-acting ESA being developed for once-monthly dosing was found to be highly effective.⁷It was also seen that administering CERA at extended intervals may shorten anaemia management, reduce the burden on patients, and also decrease time consumption process for health care staff.⁸Methoxy polyethylene glycol-epoetin beta (Mircera) is a continuous erythropoietin receptor activator, with a long half-life approximately 130 hours, used in treating anaemia associated with chronic kidney disease (CKD), both on and not on dialysis, who had not previously received an ESA, Mircera is administered intravenously or subcutaneously once every 2 weeks which is resulted in increasing haemoglobin levels.⁹Present treatment for patients with chronic renal anaemia require close monitoring and dose adjustments. Mircera allows Hb to be maintained within the target level.¹⁰

MATERIALS AND METHODS:

The Study was carried out for a period of 6 months in tertiary care hospital

Study Instrument: Haemoglobin levels

Inclusion Criteria:

· Patients with anaemia in CKD

· CKD Patients who have not undergone Dialysis.

Exclusion Criteria:

· Patients having uncontrolled hypertension associated with CKD.

· Patients who are not willing to participate in this study.

METHOD:

Mircera was given either IV/SC at the dose of 0.6 μg/kg every 2week for six months in ESA Naive Patients who were not on dialysis. This study involves prospective analysis of haemoglobin levels for every month until six months of the completion of the Mircera therapy in CKD patients. The study is carried out by the collection and documentation of general information of the patient including personal history, family background, clinical findings, investigations and medical illness associated with CKD. All enrolled patients will be assessed with haemoglobin levels for every 4 weeks.

Finally the documented haemoglobin levels are evaluated for the final outcome. The study was conducted after obtaining informed consent from the patient. This study was approved by the Ethics committee.

RESULTS:

After applying inclusion and exclusion criteria and extensive analysis of the collected data yielded the following results, Out of the 70 patients selected for the study, 50 patients agreed to participate in this study. Among the study group, males are found to be high (56%) compared to the Female population. The age group 45-49 were found to be highly affected with CKD compared to any other age group. In the study group, 28% (n=14) of patients were having comorbid conditions like Diabetes mellitus, 22% (n=11) with Hyperlipidemia, 12% (n=6) with Asthma and 18% (n=9) with Osteoarthritis.

In this study used to assess the efficacy of the drug MIRCERA in anaemia in chronic kidney disease .The baseline haemoglobin frequency was 7.41(±0.78).

Treatment Pattern:

In ESA-naive patients, the recommended starting dose is 0.6 μg/kg administered once every 2 weeks as a subcutaneous or intravenous injection, in order to reach a haemoglobin level of 11 g/dL. The dose may be increased by approximately 25% if haemoglobin levels increase by 1.0 g/dL over a month. Further increases of approximately 25% may be made once per month until the individual target haemoglobin level is reached. If a haemoglobin level of 11 g/dL is reached for an individual patient, Mircera may be continued once per month using a dose equal to twice the previous dose once every 2 weeks.

Table 1: comparison between baseline haemoglobin levels and 12 weeks haemoglobin levels

Baseline haemoglobin	12 weeks	P value
7.41(±0.78)	9.45(±0.64)	<0.0001

Table 1 shows the comparison between mean and standard deviation of baseline haemoglobin levels and haemoglobin levels after 12 weeks and result were found to be statistically significant (0.0001)

Table 2 comparison between12 weeks haemoglobin levels and 24 weeks haemoglobin levels

12 weeks	24 weeks	P value
9.45(±0.64)	12.23(±0.74)	<0.0001

Table 2 shows the comparison between mean and standard deviation of haemoglobin levels at 12 weeks and haemoglobin levels after 24 weeks and result were found to be statistically significant (0.0001)

Table 3: comparison between baseline haemoglobin levels and 24 weeks haemoglobin levels

Baseline haemoglobin	24 weeks	P value
7.41(±0.78)	12.23(±0.74)	<0.0001

Table 3 shows the comparison between mean and standard deviation of baseline haemoglobin levels and haemoglobin levels after 24 weeks and result were found to be statistically significant (0.0001).

DISCUSSION:

Mircera was effective in treating patients with anaemia in chronic kidney disease who were not on dialysis. Patient baseline haemoglobin levels were seen and noted and were treated with Mircera and haemoglobin levels were seen for every month and according to the study baseline, 12 weeks and 24 weeks of haemoglobin levels were compared. The present study showed that Mircera was effective to treat renal anaemia in CKD naive patients, not on dialysis when administered once every 2 weeks and maintains stable haemoglobin levels. Our results are in accordance with the Yukitoshi Sakao et al as they analyzed the effect of Mircera when given twice weekly and every month and compared the outcome. They concluded that Mircera when given twice weekly found to be more effective compared to every month dose.²

The present study showed that Mircera was effective to treat renal anaemia in diabetic CKD patients, not on dialysis. Our results are in accordance with the Sameer G et al as they concluded that administration of CERA once every two weeks was effective in increasing and maintaining the target Hb levels.¹¹

LIMITATIONS:

Limitation of the study was for a short period and the sample size was small, with no comparison with other ESAs.

CONCLUSION:

Mircera was found to be effective in maintaining haemoglobin levels in CKD patients not on dialysis when given twice weekly for 6 months. Further investigation is required to identify the efficacy of Mircera in other health conditions.

ABBREVIATION:

MIRCERA-Methoxy polyethylene glycol-epoetin beta

CERA- Continuous Erythropoietin Receptor Activator

CKD- Chronic Kidney Disease

Hb- Haemoglobin

ESAs- Erythropoiesis-Stimulating Agents

REFERENCE:

1. Barbara G. et al and Wells, joseph T. Dipiro pharmacotherapy handbook 7^th edition “chornic kidney disease “chapter no 76 page no 858.

2. Naro Ohashi et al.,2012 Yukitoshi Sakao, Hideo Yasuda “Methoxy polyethylene glycol-epoetin beta for anemia with chronic kidney disease” International Journal of Nephrology and Renovascular Disease 2012:5 53–60.

3. K Iseki et al.,2007 and K Kohagura “Anemia as a risk factor for chronic kidney disease” 7International Society of Nephrology/ Kidney International (2007) 72,S4–S9; doi:10.1038/sj.ki.5002481.

4. Astor BC et al, and Muntner P ,Levin A, Eustace JA, Coresh J. “Association of kidney function with anemia” the Third National Health and Nutrition Examination Survey (1988-1994) Arch Intern Med. 2002;162:1401–8. [PubMed].

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6. Francesco Locatelli el al, and Salvatore Mandolfo ,Massimo Menegato Adorati “Efficacy and safety of once-monthly continuous erythropoietin receptor activator in patients with chronic renal anemia” Jnephrol2013 società italiana di nefrologia - issn 1121-84280.

7. Amir Hayat, et al.,2008 Dhiren Haria, and Moro O Salifu“ Erythropoietin stimulating agents in the management of anemia of chronic kidney disease” Patient Prefer Adherence. 2008; 2: 195–200.

8. McGahan L, et al “Continuous erythropoietin receptor activator (Mircera) for renal anemia.” Issues Emerg Health Technol. 2008 Feb;(113):1-6.[PubMed].

9. Curran MP, et al and McCormack PL. “Methoxy polyethylene glycol-epoetin beta: a review of its use in the management of anaemia associated with chronic kidney disease”. Drugs. 2008;68:1139–56.[PubMed].

10. Fliser D, et al and Kleophas W, Dellanna F,. “Evaluation of maintenance of stable haemoglobin levels in haemodialysis patients converting from epoetin or darbepoetin to monthly intravenous C.E.R.A. the MIRACEL study”. Curr Med Res Opin. 2010;26(5):1083-1089.

11. Sameer G et al.,2014 and Vankar, Pinaki Dutta, “Efficacy and safety of continuous erythropoietin receptor activator (CERA) in treating renal anaemia in diabetic patients with chronic kidney disease not on dialysis” Indian J Med Res. 2014 Jan; 139(1): 112–116.

Received on 13.05.2017 Modified on 17.07.2017

Research J. Pharm. and Tech 2017; 10(11): 3807-3809.

DOI: 10.5958/0974-360X.2017.00691.6