Clinical and gastroscopic evaluation of amtolmetin guacyl versus diclofenac in patients with rheumatoid arthritis.
OBJECTIVE
Amtolmetin guacyl (2-[2[1-methyl-5-(4-methylbenzoyl) pyrrol-2-yl] acetamido] acetic acid 2-methoxyphenyl ester) is a recently developed drug which, in preliminary studies, has shown effective anti-inflammatory properties with improved gastrointestinal safety. Our study was designed to investigate the efficacy and tolerability of amtolmetin guacyl 600 mg bid when compared to diclofenac 50 mg tid for 4 weeks.


METHODS
A total of 64 patients aged 18-80 years, suffering from rheumatoid arthritis for more than 6 months and American Rheumatism Association functional class I, II or III were randomized in a double blind manner to amtolmetin guacyl or diclofenac for 4 weeks. Clinical and endoscopic evaluation were performed at baseline and at the end of the treatment. The mucosa was graded by means of a rating system emphasizing mucosal erosions. Only patients with endoscopy grade 0-1 entered the trial.


RESULTS
The median post-treatment endoscopy injury scores were 0 (range 0-4) in the amtolmetin guacyl-treated patients and 2 (range 0-4) in the diclofenac-treated patients (p = 0.005). There were nine gastric ulcers: 1/32 (3%) in the amtolmetin guacyl group and 8/32 (25%) in the diclofenac group (p < 0.05; 95% confidence interval, -30-5%). 16/32 (50%) patients in amtolmetin guacyl group and 8/32 (25%) in diclofenac group had normal gastroduodenal findings (score = 0) (p < 0.05; 95% confidence interval, 5-50%). In patients with a history of peptic ulcer, a recurrence of gastric damage (score 3-4) was observed in 18% in the amtolmetin guacyl and in 53% in the diclofenac group (p < 0.05). The incidence of gastrointestinal symptoms did not differ in the two groups. Amtolmetin guacyl significantly reduced the number of swollen and painful joints, and the functional disability index; diclofenac significantly reduced the number of painful joints and the functional disability index score (p = ns).


CONCLUSIONS
Amtolmetin guacyl effectively controlled the symptoms of rheumatoid arthritis, with very limited gastric toxicity. If these findings are confirmed on a wider scale, the drug might become a valid alternative to current therapies, especially for patients at risk, such as those with rheumatoid arthritis simultaneously requiring steroids and second-line drugs, or those with a history of peptic ulcer.
Bianchi Porro
G
G
Chair of Gastroenterology, L Sacco University Hospital, Milan, Italy.
Montrone
F
F
Lazzaroni
M
M
Manzionna
G
G
Caruso
I
I
D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004008:Diclofenac / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D005773:Gastroscopy; D005998:Glycine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016481:Helicobacter Infections / Q000139:chemically induced / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D008875:Middle Aged; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011758:Pyrroles; C065762:ST 679; D004008:Diclofenac; D005998:Glycine