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Nabumetone & meloxicam gastrointestinal safety

Nabumetone search
Outcome
Results
Meloxicam search
Results
Comment

The increasing focus on serious gastrointestinal adverse effects of NSAIDs is resulting in more information becoming available. Two new meta-analyses concentrate on nabumetone [1] and meloxicam [2].

Nabumetone search


Data on randomised controlled comparisons with NSAIDs in patients with osteo- or rheumatoid arthritis was sought, together with postmarketing, open, or extended studies. They had to be on adults and only the English language literature was searched.

Outcome


The major outcome sought was perforation, ulcer, or bleed (PUB). Only patients with haematemesis or haematochezia were included, and not those with positive stool tests with no other confirmation.

Results


The relevant results were from eight comparative studies in which nabumetone was compared with NSAID over periods from 1.5 to six months. The overall incidence of PUBs with nabumetone was 3 in 4,847 patients (0.06%) compared with 24 of 2,621 patients (0.9%). The analysis by patient years (Table) shows a slightly more flattering picture because two of the three bleeds with nabumetone occurred in studies in which the exposure could not be estimated.

Table: PUB events with nabumetone and NSAIDs

Treatment Patient years exposure Number of patients Number with PUB Percent per 100 patient years over 3-6 months
Nabumetone 1147 4098 1 0.09
NSAID 590 1874 17 2.9

Meloxicam search


A MEDLINE search for English language studies was augmented by hand searching US gastroenterology proceedings. No unpublished information was sought. The outcome of PUB was defined as gastric perforation, endoscopic ulcer in a patient with dyspepsia or abdominal pain, and/or gastrointestinal bleeding.

Results


Data from six studies with 19,331 patients in total were analysed, with meloxicam doses of 7.5 mg or 15 mg a day, over periods of 4-24 weeks (for most patients it was four weeks). The comparison was with NSAIDs at standard doses. Actual data are not given, but the summary odds ratio was 0.52 (95%CI 0.28 to 0.96).

Comment


It is interesting to compare these meta-analyses with those done for trials with rofecoxib [3], with similar numbers of patients on NSAIDs and with similar mean duration of exposure (0.3-0.4 years). In the both the crude rate of PUBs with NSAIDs was about 1% (0.9% in nabumetone studies, 1% in rofecoxib studies). It was unfortunate that the meloxicam review did not give event rates, because the definition of PUB (including endoscopically diagnosed ulcer in a patient with dyspepsia or abdominal pain) may have been different, and the event rates would show this.

The crude estimates of PUB rates for both placebo and rofecoxib were about 0.6%. For nabumetone it was only a tenth of this, at 0.06%. This difference is not easily explained by obvious differences in patient populations, as both studies involved patients with osteoarthritis and/or rheumatoid arthritis with apparently similar ages. Inclusion criteria, or definition of PUB, which was not specific for nabumetone, might provide an answer. The most likely reason for any differences, though, is probably in the very small numbers of events.

On limited data, nabumetone seems safer than classical NSAIDs. On meloxicam there is insufficient evidence to make a judgement from the meta-analysis.

Reference:

  1. J-Q Huang, S Sridhar, RH Hunt. Gastrointestinal safety profile of nabumetone: a meta-analysis. American Journal of Medicine 1999 107 (6A): 55S-64S.
  2. P Schoenfeld. Gastrointestinal safety profile of meloxicam: a meta-analysis and systematic review of randomized controlled trials. American Journal of Medicine 1999 107: 48S-54S.
  3. MJ Langman et al. Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs. JAMA 1999 282: 1929-1938.
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