Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty patients with definite or classical active rheumatoid arthritis were stratified by the minimization procedure to auranofin (6 mg/day) or penicillamine (go slow and low regime). This investigation is a prospective planned 3 year patient and 'doctor-open' as well as 'doctor-blind' clinical trial. This article describes the results after 12 months. Both drugs decreased disease activity and improved the functional capacity in a similar way. Two patients in the auranofin group and 5 in the penicillamine group stopped treatment due to major side effects. Four other patients in the auranofin group left treatment: 2 due to death from unrelated cause and 2 according to the Helsinki II Declaration. After one year a further patient in the auranofin group and 2 in the penicillamine group stopped treatment due to lack of clinical effect. Side effects due to auranofin were statistically more frequent distal in the gastrointestinal tract (loose stools/diarrhoea) than with penicillamine. In contrast, penicillamine produced significantly more side effects in the oral cavity (mainly taste disturbances) than auranofin. Other side effects were about equal in the two groups, but 2 cases of severe proteinuria and one with obstructive lung disease were observed in the penicillamine group. Only 3 patients did not complain of any untoward effect during the 12-month period. We conclude that on the basis of this one year investigation it is an open question whether one should select auranofin or penicillamine for the treatment of clinical active rheumatoid arthritis.
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PMID:Auranofin versus penicillamine in rheumatoid arthritis. One-year results from a prospective clinical investigation. 308 5

Damaging effects on the gastrointestinal tract of proglumetacin maleate (PGM), a new indomethacin (IND) derivative, were examined in comparison with those of IND. Gastric and small intestinal lesions were maximum 4 and 24 hr after a single oral administration of PGM, respectively. Ulcerogenic effects of PGM on the gastric mucosa were approximately 1/7 and 1/10 times as potent as those of IND on a molar ratio 4 hr after single oral dosing to fasting and feeding rats, respectively. PGM was also less active on the small intestinal mucosa 24 hr after single oral dosing. After repeated dosing for 7 days, ulcerogenic effects of PGM were about 1/3 and 1/2 times more potent than those of IND on the gastric and the small intestinal mucosa, respectively. The weak ulcerogenicity of PGM appears to be due to the fact that it has little direct action on the gastrointestinal mucosa. On the other hand, protective effects of PGM on diarrhea induced by arachidonic acid in mice were about 1/2 times as potent as those of IND in both 1 and 4 hr pretreatments. So PGM must have less inhibitory effects on prostaglandin biosynthesis in the intestine than IND. PGM is a safer drug than IND because it has less damaging effect on the gastrointestinal mucosa. Therefore, it may be much more useful for the treatment of chronic inflammatory disorders like rheumatoid arthritis.
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PMID:[Pharmacological studies on proglumetacin maleate, a new non-steroidal anti-inflammatory drug. (3) Damaging effects on the gastrointestinal tract]. 309 53

Auranofin (SKF-D 39162) is an oral gold preparation for the treatment of rheumatoid arthritis. One of its major side effects is diarrhoea. To determine one possible mechanism for this we compared the effects of auranofin and myochrysine on intestinal water and solute transport in the rat. Jejunal perfusion with 2 mM auranofin (n = 5) induced fluid and electrolyte secretion and inhibited glucose absorption (p less than 0.01). Auranofin (0.2 mM) induced fluid secretion in the jejunum (n = 5; p less than 0.01) and colon (n = 6; p less than 0.01). In contrast, 2 mM myochrysine enhanced jejunal water and electrolyte absorption (n = 6; p less than 0.02). Both compounds enhanced absorption of mannitol (p less than 0.01). Perfusion of 0.2 mM auranofin for two hours had no significant effect on mucosal c-AMP levels (n = 4). After perfusion for two hours with 2 mM auranofin the jejunal mucosa showed severe injury by light and scanning electronmicroscopy while myochrysine had no apparent effect. The damage after perfusion with 0.2 mM auranofin for two hours was less severe. Auranofin was more rapidly absorbed than myochrysine (p less than 0.05). These effects provide an explanation for the diarrhoea associated with auranofin therapy.
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PMID:Effects of auranofin and myochrysine on intestinal transport and morphology in the rat. 311 69

In an open multicenter trial, 90 patients with rheumatoid arthritis were treated with a daily dose of 6 mg auranofin. The duration of the treatment was 12 months. A significant improvement in the following parameters was observed: grip strength, number of swollen and painful joints after the 4th month, blood erythrocyte sedimentation rate decreased significantly after the 2nd month. Of the 90 patients, 56 (62.3%) completed the therapy, in 14 (15.5%) it was discontinued because of side effects and in 8 (8.9%) because of inefficacy. 12 patients (13.3%) stated other reasons for discontinuing the therapy (non compliance). The reported side-effects were mostly gastrointestinal, especially diarrhoea and loose stools. The evaluation of results referring to the duration of the disease shows that patients with a duration of less than 2 years reacted better to the improvement with auranofin therapy than patients with a longer sickness history.
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PMID:[Clinical effectiveness and tolerance of auranofin in patients with chronic polyarthritis. Results of a multicenter long-term study]. 314 87

The association between HLA antigens and adverse drug reactions (ADR), (e.g. proteinuria, haematological abnormalities, stomatitis, diarrhoea and dermatitis) in rheumatoid arthritis (RA) to sodium aurothiomalate (gold) and to D-penicillamine (PA) were studied in 32 patients. Thirty-eight RA patients treated with gold and PA, and with no ADR to these drugs, were used as controls. The frequency of HLA B8 was significantly (p less than 0.05) increased among RA patients with ADR compared to plasma donors. DR3 was also significantly increased (p less than 0.05) in RA patients with haematological ADR compared to plasma donors. Haematological ADR occurred significantly (p less than 0.05) more often in DR3 positive patients (55%) than among DR3 negative RA patients (27%).
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PMID:HLA antigens and adverse drug reactions to sodium aurothiomalate and D-penicillamine in patients with rheumatoid arthritis. 315 29

The incidence, severity, and management of diarrhea during longterm administration of auranofin (AF)--up to 33 months--were evaluated prospectively in 137 patients with active rheumatoid arthritis. At least 1 episode of diarrhea was reported in 101 patients (74%), but the rate of occurrence/patient-months of therapy was 24% (569 events/2,370 patient-months of treatment). The monthly prevalence declined from a range of 30-40% during the initial 6 months to about 10% for patients treated for 18-24 months. Most diarrhea was intermittent and mild; only 11 patients (8%) discontinued treatment because of diarrheal symptoms. No intervention was required in 46 of the 101 patients affected. In 44 others, loose stools were successfully managed with antidiarrheal medications, a reduction in dosage, or both. Although diarrhea is a common event during AF administration, particularly early in therapy, for most patients it usually does not significantly interfere with treatment.
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PMID:Incidence and management of diarrhea during longterm auranofin therapy. 326 56

Twenty-six patients with severe rheumatoid arthritis who had completed a randomized crossover trial of methotrexate elected to continue to receive the drug in a long-term prospective study. At 36 months, 16 patients remained in the study. Over this period of time, significant improvement was noted in the number of painful and swollen joints, physician and patient global assessments, erythrocyte sedimentation rate, and prednisone dose. Adverse reactions occurred in 16 patients (62%), including nausea, alopecia, headache, stomatitis, herpes zoster, and diarrhea. Mild leukopenia (3 patients), thrombocytopenia (3 patients), and elevated transaminase levels (8 patients) resolved with temporary drug discontinuation. No patient withdrew due to drug toxicity. Liver biopsy specimens in 17 patients after 24 months of treatment showed no evidence of fibrosis or cirrhosis. A significant increase in the percentage of T3 and T4 blood cells and increases in lymphocyte proliferation to concanavalin A and purified protein derivative of tuberculin were found after 2 years of therapy. Our findings indicate that methotrexate has remained effective over 36 months of therapy, with acceptable toxicity levels and no evidence of systemic immunosuppression.
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PMID:Long-term prospective trial of low-dose methotrexate in rheumatoid arthritis. 291 60

Fifty-eight patients with rheumatoid arthritis (RA) entered a double blind trial of auranofin (AF) designed to assess dose response relationships and longterm outcome. Multivariate analysis of repeated measures with trend analysis and discriminant function analysis of standard measures of RA activity were applied to a randomized double blind trial of AF at daily doses of 4, 6 and 8 mg over 6 months. Improvement occurred in each group. There was a highly significant (p less than 0.001) linear trend in the 6 mg group, 73% of whom showed linear improvement. A significant correlation (p less than 0.05) was found between response of individual patients and AF dose (mg/kg/day), but there was no significant correlation between dosage and mean steady state serum gold concentration. No significant correlation was seen between outcome and pretreatment demographic and disease variables. In a subsequent 6 month phase of dosage adjustment, aiming for optimal dosage, no advantage resulted from increasing the dose above 6 mg/day. Patients apparently benefiting from treatment continued an open long-term trial of AF. By 45 months, 33.5% had stopped treatment due to lack of efficacy and 14.5% due to toxicity, mainly rash and diarrhea.
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PMID:Dose response studies and longterm evaluation of auranofin in rheumatoid arthritis. 328 Jul 95

Proquazone is a non-steroidal anti-inflammatory agent (NSAID) which, unlike most other NSAIDs, does not have a free acid group in its structure. It is advocated for use in rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, musculoskeletal disorders, acute inflammatory conditions and acute pain states such as dysmenorrhoea, postoperative pain and headache. Published data in small groups of patients indicate that proquazone 300 to 900 mg/day in 3 divided doses is a possible alternative to aspirin, ibuprofen, indomethacin, and naproxen in rheumatoid arthritis, and to indomethacin and ibuprofen in ankylosing spondylitis. Similarly, proquazone 300 to 900 mg/day is as effective as aspirin, diclofenac, ibuprofen, indomethacin and naproxen in patients with osteoarthritis. Preliminary studies have confirmed the efficacy of proquazone in acute inflammatory disorders, and shown that it provides useful analgesic relief in acute pain states such as dysmenorrhoea, headache and after minor surgery. Evidence from small groups of patients with rheumatoid arthritis treated for a year or more suggests that proquazone may inhibit or arrest progression of bone erosions. However, these encouraging findings clearly need confirmation in a larger number of patients studied under well-controlled conditions. The overall impression from clinical trials to date is that proquazone at dosages of greater than or equal to 900 mg/day produces a high incidence of gastrointestinal symptoms such as diarrhoea (in approximately 30% of patients). However, these effects were usually of mild to moderate severity and transient in nature and in most comparative studies the overall tolerability of proquazone was assessed as being comparable to that of other NSAIDs tested. Similarly, withdrawal from therapy due to side effects was no greater with proquazone than with other NSAIDs evaluated. Initial experience with lower dosages of proquazone (300 to 450 mg/day) suggest that efficacy is maintained and tolerability markedly improved. Thus, at present, proquazone would seem to be as effective as other NSAIDs used in the management of rheumatoid arthritis and osteoarthritis. However, further studies are needed to fully evaluate the efficacy and tolerability of this agent, especially at the lower daily dosages currently recommended, and to clarify whether it does have significant 'disease modifying' potential.
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PMID:Proquazone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in rheumatic diseases and pain states. 329 21

Auranofin (triethylphosphine gold), an oral gold preparation, has recently been made available, and along with injectable gold preparations, is of therapeutic value for rheumatoid arthritis. Serious gold toxicity is uncommon, and drug-related deaths rare. Many potential adverse reactions are similar, including dermatitis, stomatitis, thrombocytopenia, leucopenia, and proteinuria, generally with increased incidence in the injectable gold-treated patients. Oral gold is associated with benign lower gastrointestinal side effects, including diarrhoea, loose stools and abdominal cramps that are often dose-related and resolve spontaneously. The incidence of severe reactions such as thrombocytopenia, aplastic anaemia and exfoliative dermatitis is lower with oral gold than injectable preparations, and contributes to a superior risk-benefit ratio. The treatment of gold toxicity depends on the type and extent of organ involvement.
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PMID:Adverse reactions with oral and parenteral gold preparations. 329 22


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