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PRCA Update | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Has PRCA been reported in all Countries? No. As of 31 May 2002, confirmed PRCA cases have been received from 20 countries, including the USA. How many patients treated with EPREX/ERYPO have developed PRCA or antibodies? As of 31 May 2002, there are 141 case reports of suspected PRCA with epoetin treatment reported by health care professionals - all are patients with chronic kidney disease. 114 of the 141 are confirmed PRCA by bone marrow biopsy reports. 68 of the 114 cases are positive for anti-EPO antibodies. The worldwide reported incidence rate is 1.14 in 10,000 patient-years, which, is "rare". Some countries have higher reporting rates. 1 case report is clearly reported to be IV only administration. The remainder of cases where we have IV/SC information are associated with subcutaneous route of administration. Have PRCA and anti-EPO antibodies been seen with other epoetins? Yes. PRCA and anti-EPO antibodies also have been reported in patients taking other epoetin products. As of 31 May 2002, our data base contains 6 suspected PRCA cases with NeoRECORMON (epoetin beta, Roche), 5 of the 6 are confirmed PRCA cases. 3 of the 5 are positive for anti-EPO antibody. 2 of 5 cases do not have known results. Our data base contains 8 suspected cases of PRCA with EPOGEN-PROCRIT (epoetin alfa, Amgen), 7 of the 8 confirmed positive, 1 of the 7 positive for anti-EPO antibody. The vast majority of cases in our database are patients treated with EPREX/ERYPO. We do not have full access to knowledge of all PRCA reported cases with other epoetins. Have PRCA and anti-EPO antibodies been seen with EPOGEN-PROCRIT ? Yes. As of 31 May 2002, there are 8 PRCA suspected cases, with 7 of the 8 cases confirmed by bone marrow biopsy results. 1 of the 7 cases is positive for anti-EPO antibodies. PROCRIT and EPOGEN are identical products, both manufactured by Amgen (same bulk manufacturing source, same formulation). What other characteristics have been noted from the investigation? Other observations as of 31 May 2002:
Is EPREX being taken off the market or is its distribution restricted? No. We are providing a labeling update pertaining to the safety information for EPREX/ERYPO(epoetin alfa). The updated safety information is being communicated to provide the most recent information regarding worldwide reported cases of PRCA in patients treated with EPREX as of 31 May 2002. Is this information update happening only in Europe? No. This update is being provided to Health authorities globally. What about reported incidence by country? There is clearly a geographic clustering of reported cases. This clustering does not follow population statistics or product usage or EPREX/ERYPO sales volume.
What are the reasons for increased number of cases since 31 March data report? We continue to receive reports from years prior to 2001, and they are being included in the totals as they are received. Updates occur regularly that change the diagnosis by case, and some patients are added, while other patients are found not to have immune mediated PRCA. In the past month, we conducted a quality control survey of 1300 pre-existing case reports (1997-present) and discovered a number of "suspected" cases that had not been previously reviewed for a definite diagnosis. Over the past several months, the number of new immune mediated PRCA case reports seems to have reached a plateau. Will the label for EPREX change? YES. The changes made are reflected in the Dear Doctor Letter dated 17 July 2002. Is the safety of patients on EPREX at risk? The overall worldwide reporting rate of confirmed PRCA reports in chronic renal failure patients remain rare. EPREX has been used safely and effectively in the approved doses across multiple indications for more than 13 years in patients with anemia. Should I convert all my patients to an i.v. route of administration? While the company continues further investigation, scientific literature suggests that all exogenous proteins have the potential to elicit an immune response, particularly when administered via the subcutaneous route. Since the mid 1990's, administration of EPREX in CRF patients has changed from predominantly an intravenously administered to a predominantly subcutaneous administered product in most countries. Of the reported PRCA cases, the majority are patients treated by the subcutaneous route. At this time, we are changing EU labeling to reflect recommendation that IV route of administration should be used for hemodialysis patients, and that for other CRF patients, IV should be used if feasible. If not feasible, physicians should consider the risk/benefit of SC. (Please refer to the specific terminology in the SmPC (labeling). What should I do with my predialysis patients and my peritoneal patients? Should they be switched to the i.v. route of administration? EPREX should be administered by the intravenous route in chronic renal failure patients (predialysis, and peritoneal dialysis) where feasible. If the IV access is not feasible in a patient with CRF, the risk/benefit of SC administration should be considered for each patient. (Please refer to the specific terminology in the SmPC (labeling). Does this mean that predialysis and peritoneal dialysis patients are being put at risk if we do not switch them to iv administration? What is being suggested is that if IV access is not feasible in a patient with CRF, the physician should consider the risk/benefit of sc. administration for each patient. Does one have to use higher doses if administering EPREX via the intravenous route vs the subcutaneous route? The starting dose of EPREX should be 50 - 100 IU/kg 3x/wk. This applies for IV and for SC administration. What are the potential causes of PRCA in patients on EPREX? Despite the Company's extensive ongoing technical and clinical investigation examining the cases as well as the product characteristics, its manufacture and distribution, no definitive causative factors have been identified to date. We continue to investigate route of administration, product characteristics, patient characteristics, and how product handling and storage within the distribution system may impact the product. Like many biological products, EPREX must be maintained under specific conditions that are noted on the labeling. How is the company monitoring the development of immune mediated PRCA and anti-EPO antibody formation in patients treated with EPREX/ERYPO? Johnson and Johnson Pharmaceutical Research and Development (JJPRD) Drug Safety and Surveillance Department monitors and reports all post-marketing safety information for EPREX to global regulatory agencies. If there is a lack of efficacy, suspected PRCA or suspected antibodies in a patient, what should I do? We strongly urge physicians to report such cases to the Company immediately. What is considered "a sudden lack of efficacy"? Sudden lack of efficacy or resistance may be defined as a significant anemia that is unresponsive to escalating doses of erythropoietin. In patients developing sudden lack of efficacy, typical causes of non-response (e.g., iron, folate, or Vitamin B12 deficiency, aluminium intoxication, infection or inflammation, blood loss, and haemolysis) should be investigated first. If no cause can be identified, and PRCA is suspected, testing for erythropoietin antibodies and bone marrow examinations should be considered Patients should not be switched to another erythropoietin. Other causes of pure red cell aplasia should be excluded, and appropriate therapy instituted. If an antibody test has to be done for a patient, how should this request be handled? Provided that all other causes of lack of effect have been explored, you may contact our Medical Department at 8248944 (Dr. Lilia Reyes) or 8248945 (Dr. Alex Delgado). What are the PRCA incidence rates for SC vs IV? Utilizing available data (as of 31 May 2002), and available data from a limited number of countries (Canada, Finland, France, Germany, Italy, Norway, Spain, Switzerland, Sweden and United Kingdom) the estimated reporting rates (suspected PRCA cases 1998 to 2002) are:
How should patients with confirmed cases of PRCA be treated? The scientific literature indicates patients may respond to immunosuppressive therapy (This is based on a small number of patient experiences, however: there are no clinical trials that have determined the best course of therapy. Many patients become transfusion dependent).
For other questions not answered here, please contact our Medical Department at 8248944 (Dr. Lilia Reyes) or 8248945 (Dr. Alex Delgado). |
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