Rheumatology Advance Access originally published online on February 16, 2006
Rheumatology 2006 45(4):494-495; doi:10.1093/rheumatology/kei258
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LETTER TO THE EDITOR |
NICE risk factors for gastrointestinal adverse events in diclofenac users in general practice in Germany: comment on the article of Thompson et al.
Medizinische Hochschule, Hannover, 1 Pfizer Pharma GmbH, Karlsruhe and 2 IFNAP, Nuernberg, Germany
Correspondence to: H. Zeidler, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. E-mail: zeidler.henning{at}mh-hannover.de
SIR, Diclofenac is the most commonly prescribed non-steroidal anti-inflammatory drug (NSAID) in general practice in Germany and most other European countries. Following the introduction of cyclooxygenase (COX) II-selective inhibitors, the frequency of prescriptions of diclofenac has not changed between 1993 and 2003, as most recently reported by Thompson et al. for semirural practices in the UK [1]. Likewise, in Germany diclofenac holds its leading position among the most frequently used NSAIDs (23 849 509 prescriptions in 2002 and 19 951 061 in 2004; IMS Health Dataview Pharma). Therefore, the question of how many patients taking diclofenac in general practice are at risk of gastrointestinal (GI) adverse events according to the National Institute for Clinical Excellence (NICE) guidance on the use of COX II-selective drugs is important for practical and pharmacoepidemiological reasons [2]. After the withdrawal of rofecoxib from the market and the stopping of the marketing of valdecoxib, the German Drug Commission recommended the restricted prescription of COX II-selective inhibitors due to the increased cardiovascular risk [3].
In a pharmacoepidemiological study, we collected data from 9379 diclofenac users (65% of them with osteoarthritis and rheumatoid arthritis) under the care of practising physicians (n = 2121) around Germany to determine how many patients would fulfil the NICE criteria for being at high risk of GI adverse events. This study, conducted according to the German federal requirements for post-marketing surveillance studies, required no ethics approval or informed patient consent. In the total population, 75% of the diclofenac-treated patients had at least one NICE risk factor, a figure somewhat higher than the 64% reported by Thompson et al. [1]. The frequency of NICE criteria for each of the variables assessed is given in more detail in Table 1.
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Forty-five per cent of all patients were aged
65 yr and 13% had a clinical history of gastroduodenal ulcer, GI bleeding or gastroduodenal perforation. Furthermore, almost 30% of the patients received concomitant acetylsalicylic acid or glucocorticoids, and 29% (u = 2733) received a long-term diclofenac dosage greater than 100 mg/day. Regardless of age, 61% of the study population had comorbid medical conditions, such as hypertension, cardiovascular disorders, diabetes and renal and/or hepatic diseases, approximately one-third of patients exhibiting multimorbidity (u = 3279 patients). Twenty-eight per cent of all patients were treated with proton pump inhibitors (PPIs) or misoprostol, 11% with H2 receptor antagonists, and 8% with methotrexate. Of the patients fulfilling individual NICE criteria for high risk, 34% (u = 2383) were receiving a PPI or misoprostol concomitantly for gastroprotection. PPIs or misoprostol were also received by 62% of all patients with gastroduodenal perforations, 40% of the total population with concomitant use of medications known to increase the likelihood of upper GI events, and 39% of patients with a requirement for prolonged use of diclofenac at a dose above 100 mg/day. In conclusion, the results of both surveys, from the UK and Germany, show that most patients treated with diclofenac are at high risk of developing GI complications. Therefore, we agree with Thompson et al. that urgent advice is needed concerning the appropriate use of non-selective NSAIDs in primary care. The recent regulatory advice of the US Food and Drug Administration and the European Medicines Agency for the safer use of COX II-selective inhibitors and non-selective NSAIDs has to be included in such revised guidance [4–6]. In addition, more effective audits and monitoring of prescription practices should be a future priority for all officials, companies and physicians responsible for ensuring the optimal and safest therapy for rheumatic conditions in clinical practice.
M.M. is an employee of Pfizer. H.Z. has consultancies and honoraria from Pfizer, MSD and Boehringer Ingelheim, and research support from MSD. M.Ü. worked as a scientific adviser for Pharmacia from 2001 to 2003.
References
- Thompson PW, Tee L, McBride J, Quincey D, Strat Liddiard G. Long-term NSAID use in primary care: changes over a decade and NICE risk factors for gastrointestinal adverse events. Rheumatology 2005;44:1308–10.
[Abstract/Free Full Text] - National Institute for Clinical Excellence. Guidance on the use of cyclo-oxygenase (Cox) II selective inhibitors, celecoxib, rofecoxib, meloxicam and etodolac for osteoarthritis and rheumatoid arthritis. Technology Appraisal Guidance No. 27, July 2001. London: National Institute for Clinical Excellence: 1–14. Available at http:/www.nice.org.uk/docret.asp?d=180349
- Arzneimittelkommission der deutschen Ärzteschaft: Aus der UAW-Datenbank: Kardiovaskuläre Nebenwirkungen sind ein Klasseneffekt aller Coxibe: Konsequenzen für ihre zukünftige Verordnung. Dtsch Ärztebl 2005;101:3365–6.
- Food and Drugs Administration. FDA drug information on COX-2 selective (includes Bextra, Celebrex, and Vioxx) and non-selective non-steroidal anti-inflammatory drugs (NSAIDs). Available at http://www.fda.gov/cder/drug/infopage/cox2/
- European Medicines Agency. European Medicines Agency concludes action on COX-2 inhibitors. 27 June 2005. Available at http://www.emea.eu.int/Cox2inhibitors.htm
- European Medicines Agency. European Medicines Agency update on non-selective NSAIDs (press release). 17 October 2005. Available at http://www.emea.eu.int/htms/hotpress/h29896405.htm
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