Manoj Sharma et al. / Journal of Pharmacy Research 2012,5(9),4893-4896 Research Article Available online through ISSN: 0974-6943 http://jprsolutions.info

Use of NSAIDs in France: Analysis from French reimbursement (CNAM-TS) database

Manoj Sharma1*, Sinem E. Gulmez2, Régis Lassalle3, Nicholas Moore4 1Research Fellow. INSERM U657 Pharmaco-Epidémiologie, Service de Pharmacologie, Université de Bordeaux, Bordeaux, France. Manager, Global Pharmacovigilance Deptt. Panacea Biotec Ltd. New Delhi,India 2Associate Professor of Pharmacology, M.D., PhD. INSERM CIC-P 0005 Pharmaco-Epidémiologie, Service de Pharmacologie, Université de Bordeaux, Bordeaux, France. 3Statistician and Database Manager, INSERM CIC-P 0005 Pharmaco-Epidémiologie, Service de Pharmacologie, Université de Bordeaux, Bordeaux, France. 4Professor of Clinical Pharmacology, MD, PhD, FRCP(Edin), FISPE. INSERM CIC-P 0005 Pharmaco-Epidémiologie, Service de Pharmacologie, Université de Bordeaux, Bordeaux, France. Received on:07-06-2012; Revised on: 18-07-2012; Accepted on:25-08-2012

ABSTRACT Background: Reimbursement databases provide indirect data regarding drug use or its exposure. In France, approximately 85% of the general population is covered by the national health insurance system (Caisse Nationale d’ Assurance Maladie des Travaileurs Salariés (CNAM-TS), which reimburses prescribed drugs and other medical expenses to salaried persons and families. Since analysis of reimbursement databases ensures that the prescribed drugs have at least been dispensed, even if not used, the present study was conducted to assess the utilization pattern of and other NSAIDs in French population from reimbursement database (CNAM-TS). Method: Reimbursement data of NSAIDs (ATC code M01) were extracted from CNAM-TS database for the period 2002-2007. The defined daily doses (DDDs) were calculated from the number and size of packages of each NSAID and the different NSAIDs were ranked on the basis of total defined daily doses prescribed. Results: Paracetamol was the most used antipyretic and analgesic drug with the percentage consumption of 42.07%. The top ten NSAIDs were (10.23%), (8.70%), (6.92%), (6.88%), (6.46%), (4.97%), (3.70%), nimesulide (2.53%), (1.29%) and (1.12%). Conclusion: Analysis on the percentage of money reimbursed to patients and prescribers (special category and general category) reflects the prescription and consumption habits of prescribers and patients respectively. The ranking of the NSAIDs based on their consumption in French population were similar with previous studies where ketoprofen ibuprofen, piroxicam, diclofenac, and nimesulide were among the top 5 NSAIDs in Slovakia, Finland, Norway, Zagreb and Croatia.

KEY WORDS: Pharmacoepidemiology, drug utilization, French reimbursement database, nimesulide, NSAID. INTRODUCTION Background Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most com- trends in nimesulide and other NSAIDs consumption or utilization in France monly used classes of worldwide.[1] It has been estimated that from 2002 to 2007 and the secondary objective was to compare use of more than 30 million people take NSAID daily. [2] Patients with arthritis are different NSAIDs and other analgesic drugs before and after rofecoxib with- among the most frequent users of NSAID. The utilization of prescription of drawal in French population. NSAIDs needs to be evaluated as this facilitates in the reduction of the costs associated with the use of NSAIDs. MATERIAL AND METHODS: All NSAIDs reimbursed were extracted from CNAM-TS database for a 5- Reimbursement databases provide indirect data for drug utilization. In France, year period (2002-2007). Assessment of trends in nimesulide and other NSAID approximately 85% of the general population and 69% of those aged 65 consumption was studied as number of users of each drug and number of years and over are covered by the national health insurance system (Caisse DDD (defined daily dose) over the study period. Utilization was measured Nationale d’ Assurance Maladie des Travaileurs Salariés (CNAM-TS)), by total DDD.[6-7] NSAIDs prescribed at fixed dose combinations (i.e. which reimburses prescribed drugs and other medical expenses to salaried dextropropoxyphene in association with psycho-epileptics (ATC code persons and families. [3-5] All reimbursement claims are recorded in the com- N02AC54); acetylsaliclic acid in association with psycho-epileptics (ATC puterized databases of the CNAM-TS, which could provide data on drug code N02BA51) and formulations other than the solid oral dosage forms exposure. [4] Since analysis of reimbursement databases ensures that the pre- (tablets and capsules) were not included in the analysis. The numbers of scribed drugs have at least been dispensed, even if not used, we conducted boxes of each product were extracted with a separate identifier (CIP code) for the study to assess the utilization pattern of nimesulide and other NSAIDs each formulation package. Information pertaining to strength of the unit in French population from CNAM-TS. The primary objective was to study dose, number of packets reimbursed and the amount reimbursed was present in the database while information on daily dose or treatment duration was not *Corresponding author. recorded in the reimbursement database. Dr. Manoj Sharma Base of reimbursement refers to base of refund or repayment (a part or Global Pharmacovigilance Division fraction of price of the medicine) in Euros fixed by CNAM to decide the Panacea Biotec Ltd., percentage of the payment or the reimbursement to be made to patient. It MCIE, Mathura Road, New Delhi-110044, India Journal of Pharmacy Research Vol.5 Issue 9.September 2012 4893-4896 Manoj Sharma et al. / Journal of Pharmacy Research 2012,5(9),4893-4896 varies from one year to another and from type of product or medicine. The the 10 most consumed were piroxicam (6.92%), diclofenac (6.88%), celecoxib base of reimbursement was extracted for type of prescribers i.e special cat- (6.46%), naproxen (4.97%), rofecoxib (3.7%), nimesulide (2.53%) aceclofenac egory prescribers (prescribers from hospitals/surgeons/dentists/orthopedists) (1.29%) and nabumetone (1.12%). and private practitioners (other prescribers). A comparative analysis was made for the prescribing patterns of the prescribers. The prescribing pattern Analysis of the database showed that there was a significant increase in the was analyzed from the amount reimbursed to the special category and pri- consumption of paracetamol from the year 2002 (35.2%) to 2007 (48.8%), vate practitioners. which was followed by ketoprofen and ibuprofen (Table 1, Figure). In 2002, celecoxib consumption in French population was 10.3%, which further de- Data analysis creased to 3.5% in 2007 (Table 1). For rofecoxib there was a decrease in the The number of DDDs for each drug reimbursed was calculated in the follow- consumption from 2002 to 2004. From 2002-2007 the percentage of ing way: nimesulide consumption in French population increased from 2.1% to 2.9%. % NSAID Consumption = DDD sold of NSAID*100 / Total DDD sold of Analysis for the percentage of money reimbursed to patients in France all NSAIDs showed that from year 2002 to 2007 the maximum reimbursement of the amount was made for followed by indomethacine. The per- The percentage of reimbursement per year for individual NSAID was calcu- centage of reimbursement was same for paracetamol and celecoxib for the lated in the following way: period 2002 (73.4%). From 2002 to 2003 reimbursement percentage was nil Percentage of reimbursement = Amount reimbursed / Base of reimbursement for aceclofenac. There was no significant changes in the percentage of amount The prescribing patterns of two prescribers (special category prescribers vs reimbursed from year 2002-2007 for naproxen, mefanamic acid, piroxicam, other prescribers) was calculated in the following way. , nabumetone, (Table 2).

Percentage of amount of reimbursement by special category prescriber (pri- Analysis for percentage of amount reimbursed to general practitioners/pri- vate practitioners) = Base of reimbursement to private practitioner / Base of vate practitioners (GP) during the period 2002-2007 showed that more than reimbursement 95% of the base amount was reimbursed for ibuprofen, , acetyl- Percentage of amount of reimbursement by other prescribers = Base of (ASA), tenoxicam, and nabumetone. For other category pre- reimbursement to other prescriber / Base of reimbursement scribers more than 10% of the reimbursement base was reimbursed for drugs ketoprofen, phenylbutazone and indomethacine . RESULTS: A total of 26 NSAIDs were identified in CNAM-TS reimbursement database DISCUSSION: for the period 2002-2007. Among these, three NSAIDs, alminoprofene (ATC In France, publicly funded health system systematically covers the French code M01AE16), diacerine (ATC code M01AX21) and (ATC population.[8] In this system there are three main reimbursement databases code M01AX24), were not listed in the ATC / DDD index 2009. [7] There- covering the major public health insurance schemes. These three databases fore, the final analysis included 23 NSAIDs. The total DDD sold for all are: (1) Erasme (Extraction, Recherches, Analyses pour un Suivi Médico- NSAIDs for the period 2002-2007 was 5,793,972,577. Analysis for percent- Economique, CNAM-TS (Caisse Nationale d’Assurance Maladie des age of consumption showed that paracetamol is the highly consumed (42.07%) Travailleurs Salariés); (2) RSI (Régime Social des Indépendants); and (3) antipyretic and analgesic drug. The highly consumed NSAID was ketoprofen MSA (Mutuelle Sociale Agricole). The particularities [8] of French health (10.23%), followed by ibuprofen (8.7%) . Other NSAIDs that were among system make the possible use of the reimbursement databases for research as

Table 1. Consumption (%DDD) from 2002-2007.

Year % DDD Selective COX-2 inhibitor Non selective Celecoxib Rofecoxib Nimesulide Nabumetone Paracetamol Ketoprofen Ibuprofen Piroxicam Diclofenac Naproxen Aceclofenac

2002 10.3 8.3 2.1 1.28 35.2 8.44 7.91 7.53 6.68 5.6 0.00 2003 9.1 8.4 2.2 1.05 37.2 8.94 8.86 7.22 6.40 5.5 0.00 2004 9.5 6.1 2.5 1.20 38.6 9.78 8.26 6.44 6.44 5.2 0.88 2005 3.5 2.8 1.45 44.9 11.08 8.99 7.46 7.49 5.1 2.05 2006 3.3 2.7 1.08 46.8 11.41 9.00 6.92 7.29 4.5 2.42 2007 3.5 2.9 0.71 48.8 11.48 9.09 6.09 6.96 4.1 2.22

Table 2: Consumption (%DDD) of NSAIDs per year.

Year Paracetamol Ketoprofen Ibuprofen Celecoxib Rofecoxib Nimesulide

2002 35.2 8.44 7.91 10.3 8.3 2.1 2003 37.2 8.94 8.86 9.1 8.4 2.2 2004 38.6 9.78 8.26 9.5 6.1 2.5 2005 44.9 11.08 8.99 3.5 - 2.8 2006 46.8 11.41 9.00 3.3 - 2.7 2007 48.8 11.48 9.09 3.5 - 2.9

Journal of Pharmacy Research Vol.5 Issue 9.September 2012 4893-4896 Manoj Sharma et al. / Journal of Pharmacy Research 2012,5(9),4893-4896 the large size of these databases covers the entire French population. The CONCLUSION database also covers that population whose income is insufficient to pay for The present study provides a baseline data for monitoring future consump- their own . tion or prescribing trends of NSAIDs in French population. The study demonstrates a reduction of celecoxib use in patients due to withdrawal of In France, drug dispensing is made for a maximum of 30 days irrespective of rofecoxib in 2004 with a consequent increase in the use of paracetamol and whatever the actual prescription may be (i.e. a drug which is prescribed for classic NSAIDs such as ibuprofen and ketoprofen. 90 days will be dispensed in three times). [3] As in most European countries, in France also drugs are dispensed in packages which are indivisible by the ACKNOWLEDGEMENT: pharmacist. At each dispensation, the pharmacist automatically submits Manoj Sharma conducted the study as “Sandwich-Ph.D” research fellow reimbursement claims electronically. Analyses of reimbursement databases during the period 2009-2010 in the Department of Pharmacology,Unit ensure that the prescribed drugs have at least been dispensed. [5] In the Pharmacovigilance and Pharmacoepidemiology (INSERMU657) of the uni- present study, analysis was based on the information related to number of versity of Bordeaux ,FRANCE. packets reimbursed and the cost / amount reimbursed to patient, prescriber (general practitioner / hospital practitioner) available in the CNAM-TS reim- PREVIOUS PRESENTATION: bursement database. Paracetamol was the most frequently used antipyretic The abstract of the study was submitted to International Conference on and analgesic drug. The top 10 NSAIDs included ketoprofen, ibuprofen, Pharmacoepidemiology (ICPE)-2010 held at Brighton, UK. The abstract piroxicam, diclofenac, celecoxib, naproxen, rofecoxib, nimesulide, aceclofenac was published as abstract no: 403 in the Pharmacoepidemiology and Drug and nabumetone. Our results on the ranking of the NSAIDs based on their Safety 2010; 19: S1–S347 official journal of International Society of consumption in French population were similar with the findings made on Pharmacoepidemiology. the ranking of the NSAIDs in other studies [9-10] where ketoprofen, ibuprofen, piroxicam, diclofenac and nimesulide were ranked amongst the top 5 NSAIDs REFERENCES: in Slovakia, Finland, Norway Zagreb, and Croatia. In comparison to the 1. Chan FK, Hung LC, Suen BY, Wu JC, Lee KC, Leung VK, Hui AJ, NSAIDs analyzed in this study the percentage consumption of paracetamol To KF, Leung WK, Wong VW, Chung SC, Sung JJ. 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Source of support: Nil, Conflict of interest: None Declared

Journal of Pharmacy Research Vol.5 Issue 9.September 2012 4893-4896