University of Glasgow and
1 Gartnavel General Hospital, Glasgow, UK
SIR, The National Institute for Clinical Excellence (NICE) has recently provided guidance on the prescription of celecoxib, rofecoxib, etodolac and meloxicam [1]. They are selective inhibitors of cyclooxygenase 2 (COX-2), which are thought to be specifically implicated in the production of the prostaglandins involved in mediating pain and inflammation. This is opposed to standard non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit both COX-1 and COX-2. The major gain obtained from use of COX-2-selective inhibitors is a reduction in gastroduodenal injury, in particular ulceration and its complications, which may be attributed to long-term use of non-selective NSAIDs, especially at high doses [23]. The guidelines state that COX-2-selective inhibitors should be considered in those deemed to be at high risk of serious gastrointestinal (GI) complications. These include those aged over 65 yr, those with a clinical history of gastroduodenal ulcer, GI bleeding or gastroduodenal perforation, patients also prescribed medications known to increase the likelihood of upper GI adverse events, such as steroids and anticoagulants, the presence of serious comorbidity, such as cardiovascular disease, renal or hepatic impairment, diabetes and hypertension, and patients requiring the prolonged use of maximum recommended doses of standard NSAIDs.
In patients taking low-dose aspirin, the benefit of using COX-2-selective inhibitors is reduced, and the prescription of COX-2-selective inhibitors in these patients is not justified. It is also recommended that those taking COX-2 inhibitors in preference to standard NSAIDs should not simultaneously be prescribed GI-protective medication, as there is no evidence to suggest that this further reduces potential GI adverse events. Patients attend rheumatology clinics with a variety of diagnoses and a large proportion will require analgesia and the prescription of an anti-inflammatory agent. In view of the recent guidelines issued by NICE, we sought to examine whether our current prescribing practice is in accordance with the guidelines, and if not, what impact implementation of the guidelines would have.
One hundred and forty-two consecutive patients attending the out-patient clinics at a teaching hospital were interviewed using a standardized questionnaire. Most patients had an inflammatory arthritis [rheumatoid arthritis (RA), psoriatic arthritis (PsA), other inflammatory arthropathy (ankylosing spondylitis and Crohn's-related arthritis) or osteoarthritis (OA)]. Patient characteristics were recorded, including age, disease type and duration, current NSAID use, comorbidity, concomitant drug use and history of previous gastroduodenal disease. Case notes were used to verify the information obtained.
Three patients declined to participate in the audit. One hundred and thirty-nine patients agreed to be interviewed. The median patient age was 60 yr (range 1887). RA was the main diagnosis in 79 (57%) patients, PsA in 17 (12%), OA in 19 (14%) and other types of inflammatory arthritis in the remaining 24 (17%). There was a median disease duration of 6 yr (range 160) for the entire cohort. Overall, 61% of patients had comorbidity known to be associated with a high risk of GI adverse events, as shown in Table 1. Forty-eight (35%) patients had previously had upper GI investigations with endoscopy and/or barium meal, and 33 (23%) had a confirmed diagnosis of peptic ulceration or GI haemorrhage. Ten (7%) patients were receiving oral corticosteroids and two patients were receiving warfarin for anticoagulation. Overall, 26 (19%) patients were receiving low-dose aspirin, of whom six were prescribed a COX-2-selective drug.
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Of the 76 patients receiving standard NSAIDs, 14 (18%) were not eligible for COX-2 inhibitors because of concomitant use of aspirin. However, 42 (55%) patients met the criteria for the use of COX-2 inhibitors: 51% were over 65 yr old, 49% had relevant comorbidity, 4% were receiving corticosteroids or warfarin and 18% had a history of peptic ulcer disease. Proton pump inhibitors, H2 blockers or misoprostol were prescribed in 22 (52%) of those patients who fulfilled the criteria for COX-2-selective inhibition.
Of the 38 patients not receiving NSAIDs, many had relative contraindications to their use: 42% had a history of peptic ulceration and 18% were receiving treatment with warfarin or corticosteroids. No information was available about whether these patients were not on NSAID therapy because of these contraindications or because an NSAID was not clinically indicated, but it is likely that some would be candidates for COX-2-selective inhibitor therapy.
In our cohort, the majority of patients currently receiving COX-2-selective inhibitors at present meet the criteria suggested by NICE for the selection of patients. However, a significant number of these patients were also receiving aspirin, and most (68%) were still receiving GI protection. In addition, 55% of patients receiving standard NSAIDs were eligible for the use of COX-2-selective inhibitors, and would be expected to benefit from a decreased risk of adverse GI events were they to be prescribed them. Amongst the whole population of patients receiving NSAID therapy, this audit suggests that at least 56% meet the criteria for the use of COX-2-selective inhibitor therapy. Twenty per cent of patients were receiving NSAID therapy and low-dose aspirin therapy, and it is possible that the number of patients who would benefit from COX-2 therapy would rise if some of these patients had their aspirin therapy changed to alternative antiplatelet therapy (for instance with clopidogrel). Some of the patients not receiving any NSAID therapy might also be eligible for COX-2-selective inhibitor therapy. The overall economic impact of the switch to COX-2-selective inhibitors would depend on the magnitude of cost savings through a reduction in adverse GI side-effects, and on whether the widespread use of GI protection could be reduced. This has wider implications for prescribing practices.
Notes
Correspondence to: D. Porter, Department of Rheumatology, Floor 7, Gartnavel General Hospital, Great Western Road, Glasgow G12 0YN, UK.
References