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 No unpublished information was sought.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:
- J-Q Huang, S Sridhar, RH Hunt. Gastrointestinal safety profile of
nabumetone: a meta-analysis. American Journal of Medicine 1999 107 (6A):
55S-64S.
- 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.
- MJ Langman et al. Adverse upper gastrointestinal effects of rofecoxib
compared with NSAIDs. JAMA 1999 282: 1929-1938.
|
previous
story in this issue
