Comparative clinical study of enfenamic acid and aspirin in rheumatoid arthritis.
Enfenamic acid, N-phenylethyl anthranilic acid, has been recently introduced as a non-steroidal anti-inflammatory drug. In experimental animals, the drug is reported to possess anti-inflammatory, analgesic and anti-pyretic activity with negligible ulcerogenic activity. Acute and chronic toxicity studies conducted in rats and mice have shown it to be safe. The drug was also evaluated clinically on these parameters.,,,, Enfenamic acid was found to be an effective anti-inflammatory agent with good tolerance and minimal side effects. Therefore, a comparative evaluation of enfenamic acid and aspirin was undertaken in diagnosed cases of arthritis.
Twenty patients (8 males and 12 females) of different types of rheumatoid arthritis whose duration of disease was at least 6 months and who were admitted in the M.L.B. Medical College Hospital were selected for the study. Cut of these, 8 patients were of juvenile rheumatoid arthritis (4 polyarticular type, 3 pauci articular type and one systemic type) with mean age of 7 years and 12 were of adult type of rheumatoid arthritis with mean age of 32 years. Criteria, laid down by American Rheumatism Association (revised in 1963) were used for the diagnosis. According to these criteria, 9 cases were classical, 7 were definite and 4 were probable for rheumatoid arthritis. Patient were divided randomly into two groups of 10 patients each, having equal number (4 patients) of juvenile rheumatoid arthritis in each group and a non-crossover double blind clinical trial with aspirin (standard drug) and enfenamic acid was undertaken. A thorough clinical examination of the patients regarding classical features of the disease was carefully done. However, patients reporting symptoms like nausea, vomiting, epigastric pain, haematemesis and melaena were excluded from the study. All the previous medication was discontinued at least seven days before the trial. Aspirin and enfenamic acid were administered in daily doses of 2.4 g and 1.6 g respectively in identical looking capsules three times a day after food. Patients receiving either drug were examined daily for any adverse effects. No other drug was used concurrently during this period. Response of treatment was recorded after intervals of two and four weeks. Evaluation of digital joint circumference (P.I.P.), duration of morning stiffness, gripstrength, degree of pain, walking time, fever and E.S.R. was done before the treatment and at the end of 2 and 4, weeks of treatment. Adverse effects experienced by the patients during the treatment period were also recorded.
The assessment of grip-strength was done by the effort of the patient to raise the level of mercury column by squeezing the rubber ball.
(b) Digital-joint circumference (P.I.P.)
P.I.P. circumference was recorded with the help of a measuring tape.
(c) Walking time
It was evaluated by recording the time taken by the patient to walk down the distance of 50 feet.
(d) Assessment of pain
Subjective assessment of pain was done by the method of Punjabi et al. The degree of severity of pain was scored as 0,1,2,3.
The anti-pyretic activity was evaluated by using the clinical thermometer. The variations in average body temperature were recorded before treatment and after an interval of half, 3, 6 and 8 hours following drug administration.
It was measured by the method of Wintrobe.
(g) Side effects
Drug induced adverse effects were regularly recorded during the period of drug treatment.
The data obtained in the present study was analysed statistically by the Student's 't' test. Wilcoxon sign rank test was applied in non-parametric data.
Grip:-strength, walking time and digital joint circumference
[Table - 1] shows that both, aspirin and enfenamic acid, produced gradual and significant decrease in walking time and digital joint circumference. However, aspirin showed highly significant increase in grip-strength compared to enfenamic acid.
Both the drugs elicited a gradual and significant decrease in the duration of morning stiffness after one and two weeks of therapy. However, aspirin, as compared to enfenamic acid resulted in highly significant effect at the end of two weeks of therapy (p < 0.001).
After 4 weeks of treatment, aspirin treated patients showed a significant fall in E.S.R. from 53.40 ± 5.32 to 29.82 ± 3.77 (p < 0.01). However, enfenamic acid failed to show any significant change in this parameter.
Subjective assessment of pain
A significant improvement in the subjective assessment of pain sensation was recorded in both aspirin and enfenamic acid treated groups after two weeks of therapy. In aspirin treated group, the fall was from 2.8 ± 0.13 to 0.84 ± 0.16 while in enfenamic acid treated group, it was from 2.5 ± 0.16 to 1.2 ± 0.20. However, aspirin appeared to be more effective than enfenamic acid in this study (p < 0.001).
The peak effect of antipyretic activity in aspirin treated groups was attained after 3 hours and was highly significant (p < 0.001) than enfenamic acid and persisted for 8 hours of study. However, enfenamic acid also showed diminution in average body temperature which, though significant at the end of 3 hours, showed an upward trend beyond this period [Table - 2].
During the period of observation, aspirin showed greater potentiality for adverse effects than enfenamic acid. In the enfenamic acid treated group, three patients complained of nausea, one of vomiting and one of burning sensation in the epigastrium while in the aspirin treated group, five complained of nausea, and two each of vomiting, burning sensation and melaena.
In the previous studies by Sattur et al and Rao et al, enfenamic acid has been shown to produce improvement in all the parameters studied in patients of arthritis. In the present study also, enfenamic acid as well as aspirin produced significant improvement in patients having arthritis. On comparison, aspirin and enfenamic acid were found to be equi-effective on parameters like walking time and digital joint circumference. However, in the present study, aspirin was found to be superior in improving grip-strength and reducing morning stiffness and E.S.R. as compared to enfenamic acid. Aspirin also showed more marked analgesic action than enfenamic acid. In our study, both the drugs were found to possess anti-pyretic effect but reduction in temperature was not comparable as reported by Gupta et al, as aspirin was found to be more effective in this respect. However, we found enfenamic acid to be better tolerated in comparison to aspirin as adverse effects were observed more frequently with aspirin. Thus, both aspirin and enfenamic acid are effective in rheumatoid arthritis but on some of the parameters studied, aspirin had more effect.