Endoscopic Comparison of the Gastroduodenal Safety and the Effects on Arachidonic Acid Products between Meloxicam and Piroxicam in the Treatment of Osteoarthritis

Abstract

Our objective was to evaluate the efficacy, the gastroduodenal safety, and the effects on arachidonic acid products of meloxicam, a new acidic enolic non-steroidal anti-inflammatory drug which preferentially inhibits cyclo-oxygenase-2 over cyclo-oxygenase-1, versus piroxicam in patients with osteoarthritis of the knee. Meloxicam 7.5 mg or piroxicam 20 mg daily was administered for 4 weeks in this double-blind parallel-groups randomised study. The efficacy for pain relief of the two tested medications was assessed by means of visual analogue scale and other clinical parameters. Pre- and post-treatment endoscopies were performed, and the findings were scored and recorded. The gastric fluid was aspirated at each time and prostaglandin E2, thromboxane B2 and leukotriene B4 were determined by ELISA. There was no significant difference between the groups regarding the primary efficacy. Changes in endoscopic findings by means of Lanza score showed statistically significant differences between the two treatment groups in favour of meloxicam at all sites--gastric, duodenal and total. Within-group comparisons showed a statistically significant difference (worsening) in gastric and total score with piroxicam, but no significant difference with meloxicam. The frequency of clinically relevant cases (total score >2) also showed a statistically significant worsening in the piroxicam group. The better GI tolerability of meloxicam was also suggested by fewer adverse GI events and no withdrawals due to adverse events compared with piroxicam. The pre-/post-study gastric juice concentration of PGE2, TXB2, and LTB4 in the meloxicam group was 135.2 +/- 85.8/71.2 +/- 32.2, 116.3 +/- 81.7/99.4 +/- 107.5 and 388 +/- 321/223 +/- 98 pg/ml respectively. The pre-/post-study gastric juice concentration of PGE2, TXB2 and LTB4 in the piroxicam group was 105.7 +/- 43.1/68.2 +/- 34.9, 94.0 +/- 50.9/105.9 +/- 121.1 and 625 +/- 1574/828 +/- 1464 pg/ml, respectively. Both meloxicam and piroxicam significantly inhibited gastric PGE2 levels after 4 weeks' treatment; however, there was no difference between these two groups. Neither of these medications had an effect on TXB2. Only meloxicam inhibited LTB4 concentration significantly, and the between-groups difference was significant. Meloxicam 7.5 mg once daily had better gastrointestinal tolerability and an efficacy comparable to that of piroxicam 20 mg over 4 weeks in patients with osteoarthritis of the knee.

Clinical trial: comparison of ibuprofen‐phosphatidylcholine and ibuprofen on the gastrointestinal safety and analgesic efficacy in osteoarthritic patients

“…Numerous pilot studies have used erosions as surrogate markers of ulcers that have been linked to life‐threatening GI perforation and haemorrhage. The rate of erosions of ibuprofen‐PC appears to be consistent with the rate of erosions found in trials using meloxicam, rofecoxib, celecoxib and the combination of naproxen/cimetidine 18, 21–24 . As the latter agents have been shown to have lower ulcer rates than traditional NSAIDs, erosions may be an important surrogate marker of ulcers.…”

A comparison of the cost-effectiveness of five strategies for the prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: a systematic review with economic modelling

“…One study reported that "the code for each medication package was supplied in a sealed envelope and opened at the end of the trial" 121 and one that computer allocation was centralised and used centralised personnel. 37 Baseline characteristics appeared comparable in 10 studies, unclear in 23 and not comparable in 18. Studies were assessed as 'unclear' because insufficient information was provided regarding age, sex and type and duration of arthritis.…”

“…Extra outcome data were provided for only eight of these studies. [37][38][39][40][41][42][43][44] Five offered data on outcomes not previously recorded for that study, five offered information that no events had occurred in some outcomes and four offered data differing from those already collected from the study publication(s). Replies about the same eight studies and one further study 45 provided extra information on study quality (method of randomisation, allocation concealment, etc.…”

“…107,116,122 Authors of five studies provided additional information on outcomes when contacted. 37,38,40,42,44 Participants Thirty-eight studies included only adults with OA and nine studies included only adults with RA. Two studies included participants with 'degenerative joint disease', one study included participants with both OA and RA and one study only recruited participants with AS.…”