choline-magnesium-trisalicylate and Arthritis--Rheumatoid

Choline magnesium trisalicylate (3.0 g/day) and enteric-coated acetylsalicylic acid (3.0 g/day) have been compared in a double-blind, crossover study on 19 patients with rheumatoid arthritis using the double-dummy technique. Patients were allocated to receive 3-weeks' treatment with each trial drug in random sequence and were assessed at Weeks-1, 0, 3 and 6. Apart from an unexplained significant improvement in grip strength (p less than 0.01) that occurred in patients on choline magnesium trisalicylate when this followed aspirin but not when it preceded it, there was no significant clinical difference between treatments in any of the clinical parameters of improvement that were measured. There was also no clear difference in the side-effects profile produced by the two drugs, but the number of patients recruited to this study was small.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Choline; Disability Evaluation; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Pain Measurement; Randomized Controlled Trials as Topic; Salicylates

Previous studies of combinations of nonsteroidal drugs used in the treatment of rheumatoid arthritis (RA) have yielded conflicting results. We used standard methods to measure disease activity and high pressure liquid chromatography to measure plasma drug concentrations. We used doses of choline magnesium trisalicylate, adjusted to achieve therapeutic serum salicylate concentrations, and naproxen in a randomized, double-blind, placebo-controlled cross-over study of full dose trisalicylate (CMT), full dose naproxen (N), full dose of both (CMT-N), and half dose of both (cmt-n) to examine their relative efficacy and toxicity in treating RA. CMT-N was statistically superior to all other treatments in only 1 of 12 efficacy variables, but was equal to N and better than CMT or cmt-n for 7 variables. There were minimal differences among treatments for the other 4 efficacy variables. The mean percentage difference for the efficacy variables between CMT-N and N was 3%, between CMT-N and CMT was 10.6%, and between CMT-N and cmt-n was 10.5%. Thirteen percent of patients manifested toxic reactions during the initial open dose-adjustment salicylate run-in phase. During the double-blind phases of the study, CMT-N was more toxic than N, CMT, or cmt-n (7.5% versus 3.4%, 1.8%, and 3.7%, respectively). Tinnitus was more common when full-dose CMT was used; N (N or CMT-N) was associated with increased skin toxicity. Gastrointestinal complaints were equally common with all regimens. CMT-N, although sometimes statistically superior to CMT, N, or cmt-n, showed no clinically important additive or synergistic effect versus N or CMT alone.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Choline; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Naproxen; Random Allocation; Salicylates

Twenty-three patients with rheumatoid arthritis were given choline magnesium trisalicylate (CMT) (Trilisate; Adcock-Ingram) in a dose of 1.5 g (3 tablets) twice daily and were followed up for 6 weeks. Nineteen patients completed the study and the data obtianed were subjected to statistical analysis. There was a statistically significant improvement in the indices of inflammation. Seven patients developed tinnitus, which resolved on reduction of the dose to 1 g (2 tablets) twice daily. Four patients developed pruritus and minor gastro-intestinal side-effects were present in 3 patients, but all these side-effects were transient and no change in therapy was necessary.

Topics: Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Choline; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Salicylates

The results of three double-blind, multicentre trials are reviewed to compare the efficacy of acetysalicylic acid (ASA) and a non-acetylated salicylate, choline magnesium trisalicylate (CMT), in the treatment of rheumatoid arthritis. In each trial, patients were randomly assigned to receive comparable doses of salicylate as either ASA or CMT. Mean values for clinical indicators of rheumatoid arthritis (number of painful joints, articular index, number of swollen joints, swelling index, duration of morning stiffness) showed similar or greater improvement among groups of patients receiving CMT, compared to those receiving ASA. In addition, the incidence of gastro-intestinal side-effects was lower among patients receiving CMT.

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Choline; Clinical Trials as Topic; Double-Blind Method; Humans; Random Allocation; Salicylates

A double-blind study compared choline magnesium trisalicylate (Trilisate tablets, Purdue Frederick) (CMT) and ibuprofen (IPF) in the treatment of rheumatoid arthritis. The seven-week trial in 134 ambulatory patients, of whom 68 received CMT and 66 received IPF, was conducted as a multicentre study. Both CMT and IPF were highly effective in reducing significantly all symptoms that had worsened following the discontinuance of previous therapy. The anti-inflammatory effect of CMT produced a significantly (P less than 0.05) greater reduction in the number of swollen joints, compared to IPF, in patients completing all required visits. Further clinical study will be required before the full clinical significance of this observation emerges. Incidence of adverse effects for each drug did not differ significantly.

Topics: Adult; Aged; Arthritis, Rheumatoid; Choline; Female; Humans; Ibuprofen; Male; Middle Aged; Salicylates

We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Blood Proteins; Choline; Female; Humans; Ibuprofen; Kidney; Male; Metabolic Clearance Rate; Methotrexate; Middle Aged; Naproxen; Protein Binding; Salicylates

The kinetic interaction between salicylate and naproxen was investigated in 25 rheumatoid arthritis patients. Kinetic interactions were tested in serum after patients had been on each drug regimen for 1 month. Salicylate decreased serum naproxen concentration from 89.5 mg/liter to 65.9 mg/liter (P less than 0.001) and increased serum naproxen clearance by 56%. Naproxen had minimal effect on serum salicylate concentrations.

Topics: Arthritis, Rheumatoid; Choline; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Humans; Metabolic Clearance Rate; Naproxen; Random Allocation; Salicylates

A pilot study evaluated once-daily treatment of rheumatoid arthritis with choline magnesium trisalicylate (CMT) in patients diagnosed as having classical or definite rheumatoid arthritis, with morning stiffness as a major complaint. Twenty patients were selected who, in an earlier phase of the study, had found twice-daily treatment with CMT effective and tolerable. Efficacy was evaluated in 15 of these patients and safety was evaluated in all 20. Comparisons were made with the twice-daily regimen and with previous nonsteroidal anti-inflammatory drug (NSAID) therapy. Changes in clinical indicators (numbers of painful and swollen joints and the duration of morning stiffness) showed that once-daily treatment with CMT was as effective as twice-daily treatment with CMT or as treatment with other prior NSAIDs in controlling signs and symptoms of rheumatoid arthritis. Side effects in both the twice-daily and the once-daily treatment regimens were similar in incidence and nature.

Topics: Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Choline; Female; Hearing Loss; Humans; Male; Middle Aged; Pilot Projects; Salicylates; Tinnitus

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Choline; Female; Humans; Male; Middle Aged; Salicylates

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Choline; Humans; Salicylates