Niflumic acid in the management of rheumatoid and osteoarthritisGH Tilve, JK Lengade, AV Bavadekar, KG Nair
Departments of Medicine and Orthopedics, Seth G. S. Medical College and K.E.M. Hospital, Bombay 400012., India
Correspondence Address: Source of Support: None, Conflict of Interest: None PMID: 1032826
Source of Support: None, Conflict of Interest: None
Nifumic acid in the dosage of 250 mg four times a day and Phenyl butazone 100 nag four times a day were given to 30 classical cases of rheumatoid arthritis and 10 cases of osteoarthritis in a designed double blind cross over trial to find out the efficacy and side effects o f niflumic acid.
Steroid therapy has taught us its long term dangers but so brilliant are its anti-inflammatory properties that the temptation to use it continues. It is interesting to note the efforts actually undertaken to substitute it by non-steroidal anti-inflammatory agents which no more expose patients to the risks of endocrine metabolic disorders, which more and more are limiting the indications of adrenal corticosteroids in rheumatological practice especially in the long term treatment of chronic inflammatory rheumatisms and degenerative diseases. ,,
The purpose of this report is to present the clinical observations on the efficacy and side effects of a new non-steroidal anti-inflammatory compound, "Niflumic acid" in the management of rheumatoid arthritis and osteoarthritis.
Niflumic acid is a derivative of nicotinic acid. Chemically it is 'trifluoromethyl-3-phenylamino)-2 Nicotinic acid See [Figure 1].
Extensive laboratory and animal studies have shown that niflumic acid is effective in inhibiting and suppressing experimentally produced inflammation.
Patients were selected from the Arthritis and Immunology Clinic of the K.E.M. Hospital, Bombay. Thirty classical cases of rheumatoid arthritis selected according to the revised criteria of American Rheumatism Association  were included in this study. All of them had acute exacerbations and none of them had received corticosteroids for at least 8 weeks prior to this study.
A detailed clinical, biochemical and radiological study of these 30 rheumatoid arthritis cases and 10 osteoarthritis cases was done and the different criteria and parameters were taken as base line. The trial was a double blind cross over. Niflumic acid 250 mg four times a day and phenylbutazone 100 mg four times a day were given daily and the patients were followed up weekly for five weeks in out-patients clinic. Both subjective and objective assessment were -made and recorded in the proforma.
The details of possible side effects were noted. Only spontaneous remarks or complaints were taken into consideration and investigated in detail. . Haematological investigations including total and differential leucocyte counts, ESR, levels of SGPT, SGOT, Blood Urea, Alkaline Phosphatase and the urine and stool examinations were done - prior to the administration of drugs, after two weeks and at the end of the trial.
The following indices were used for assessment: -
1.Morning Stiffness: The time taken for the morning stiffness to disappear was noted in minutes.
2. Grip strength: The cuff of standard sphygomanometer with mercury column type, was rolled up into a light cylindroid and the pressure was raised to 30 mm of mercury. The patient was asked to grip it in his fist, arms fully extended forwards and to squeeze the cuff without any support. The pressure to which the mercury column could be raised and sustained, was the grip strength. The mean of three readings was recorded.
3. Tenderness (hand articular index) Presence of tenderness in each proximal interphalangeal joint was noted. Depending upon the presence or absence of tenderness, each joint was given a score of 0 to 4.
4. Pool of finger swelling: Each interphalangeal joint was measured with a set of standard jeweller's rings. Each finger was assigned the score corresponding to the smallest ring that could pass over the joint without any difficulty. The pool of all this score was taken as the pool of finger swelling. This score has been assigned an arbitrary number corresponding to the jewel ring number.
6. Relief of pain: The patients were asked how much relief they have noted and accordingly the grade was recorded.
Marked .. 75% to 100% relief of pain.
Moderate ..50% to 75%-relief of pain.
Mild ..25% to 50%relief of pain.
Nil .. less than 25%.
7. Limitation of mobility: It was again assessed according to the patient and graded.
8. Global response: The subjective overall assessment of relief of pain, swelling, general feeling of well being, and improvement in the functional capacity of the patients were graded as excellent, good, satisfactory or no change at all.
9. Time taken to walk 10 meters distance was noted in cases of osteoarthritis.
There were 6 males and 24 females in rheumatoid arthritis with age distribution from 20 years to 55 years and duration of illness varying from 6 months to 144 months. In 10 cases of osteoarthritis studied, 9 were females and one was male with their age distribution from 30 years to 60 years and duration of illness from 6 months to 84 months.
At the conclusion of trial, analysis of the different indices of assessment were undertaken. For objective measurements, the mean of different indices of assessment at the onset of the study was calculated and was termed as base line from which the change in these indices and the mean readings were taken separately while patients were on niflumic acid and phenylbutazone.
The morning stiffness showed remarkable improvement with niflumic acid.
Marked decrease (more than 20% of basal) was observed in 18 cases of rheumatoid arthritis (59.4%) with niflumic acid and in 10 cases (2%) with phenylbutazone. There was no change in 5 cases (16.5%) of morning stiffness time with phenylbutazone and 1 case with niflumic acid. The mean basal morning stiffness time decreased from 145.16 minutes to 86.26 minutes in case of niflumic acid. In case of phenylbutazone it decreased from 114.0 minutes to 91.66 minutes.
In osteoarthritis morning stiffness decreased from 32.5 minutes to 20.5 minutes with niflumic acid, but with phenylbutazone it increased from 30.5 to 32.5 minutes.
The grip strength showed marked improvement with niflumic acid. Mean values of grip strength were 95.13, 96.70 (mm of Hg) and were increased to 108.16, 105.4, with niflumic acid and phenyibutazone respectively.
Peal of Finger swelling:
The mean values of pool of finger swelling were reduced from 112.73 and 117.16 to 100.4 and 114.43 with niflumic acid and phenylbutazone, respectively.
The mean index subsided from 12.4, and 10.4 to 7.53 and 6.3 with niflumic acid and phenylbutazone respectively.
The mean basal level decreased from 64.81 and 61.5 (mm 1st hr) to 60.91 and. 57.12 (mm 1st hr) with niflumic acid and phenylbutazone respectively. In cases of osteoarthritis the E.S.R. levels dropped from mean values 25.6 and 58.44 (mm 1st hr) to 20.6 and 51.82 (mm 1st hr) with niflumic acid and phenylbutazone respectively.
Time taken to walk 10 meters of distance (in seconds)
In cases of osteoarthritis the mean values decreased from 27.0 and 26.2 (seconds) to 14.85 and 2525 seconds with niflumic acid and phenylbutazone respectively.
Relief of pain:
Marked to satisfactory response for relief of pain was noted in 96.67% and 8;1.35% with niflumic acid and phenyibutazone respectively.
Limitation of mobility:
Improvement in mobility was observed in 96.67% of the patients treated with niflumic acid as compared to 60.20% of the patients treated with phenylbutazone.
It was observed that 96.67% of the patients treated with niflumic acid had satisfactory response as compared with 80.2% of the patients treated with phenylbutazone.
Time taken to walk 10 meters in seconds was reduced from 27.0 seconds to 14.85 seconds and 26.2 seconds to 25.25 seconds with niflumic acid and phenylbutazone respectively in cases of osteoarthritis.
Out of 40 cases (30 of rheumatoid arthritis and 10 of osteoarthritis) . who had received niflumic acid and phenyibutazone in this study, 7.5% and 10% had side effects with niflumic acid and phenylbutazone respectively.
The loose motions and pain in abdomen as a side effect with niflumic acid could be controlled easily with antispasmodics.
This, study was undertaken to evaluate the efficacy and side effects of, niflumic acid in the management of rheumatoid arthritis and osteoarthritis and to compare it with the established anti-inflammatory drug phenylbutazone.
The overall subjective improvement was noted in 96.6% with niflumic acid as compared to 80.2% with phenylbutazone. Sood et al  noted 71% and 95.3% overall improvement in their open and double blind trial with niflumic acid respectively.
The statistically significant improvement in objective parameters of morning stiffness time, grip strength, pool of finger swelling, tenderness (hand articular index), functional status and levels of E.S.R, proved that niflumic acid has potent analgesic, anti-inflammatory and anti-rheumatic effects.
Morning stiffness which is one of the crippling symptoms of the disease was reduced remarkably in 59.4% cases with niflumic acid in this study.
Relief of pain was markedly seen with niflumic acid than phenylbutazone (96.67% and 83.33%) respectively.
Marked relief in limitation of mobility was seen with 59.4% and 33% of cases with niflumic acid and phenylbutazone respectively in our study. Similar findings are noted by Sood et al  with marked relief in limitation of mobility in 47.6% and 23% of cases with niflumic acid and phenylbutazone respectively.
In this study, 96.67% and 80.2% of case, had satisfactory global response with niflumic acid and phenylbutazone respectively. Fournie et al  had satisfactory global response with niflumic acid in 56.8% of cases in their study.
In our study, 7.5% and 10% of cases had side effects with niflumic acid and phenylbutazone respectively. The side effects such as loose motions and diffuse pain in the abdomen could be easily con , trolled with anti-spasmodics.. Gastric side effects and peptic ulcerations are well known side effects of the anti-inflammatory drugs. ,, Probably niflumic acid produces lower gastro-intestinal upsets. Further studies are needed to find out the non-ulcerogenic effects wish niflumic acid. In an- open trial with niflumic acid conducted by Sood et al  for a period of 3 months, none of the patients demonstrated occult blood in their stools.
Niflumic acid could be used in patients with peptic ulcerations associated with rheumatic diseases which is the greatest advantage over the other anti-inflammatory drugs.
We are grateful to the Dean, Seth G.S. Medical College and K.E.M. Hospital, Bombay, for allowing us to use the hospital material and to publish the data.[Table 1],[Table 2],[Table 3],[Table 4],[Table 5],[Table 6]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]