Auranofin improves outcome in early rheumatoid arthritis. Results from a 2-year, double blind placebo controlled study. Comparison of auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial. Auranofin is safe and superior to placebo in elderly-onset rheumatoid arthritis. Auranofin therapy and quality of life in patients with rheumatoid arthritis. Results of a multicenter trial. A multicentre double-blind comparison of auranofin, intramuscular gold thiomalate and placebo in patients with psoriatic arthritis. A double-blind placebo-controlled study of auranofin in patients with psoriatic arthritis. Radiographic evaluation of erosion in rheumatoid arthritis: double blind study of auranofin vs placebo. Adverse experience with methotrexate during 176 weeks of a longterm prospective trial in patients with rheumatoid arthritis. Preliminary evaluation in rheumatoid arthritis activity in patients treated with TNF-alpha blocker plus methotrexate versus methotrexate or leflunomide alone.
The effect of early initiation of auranofin (AF) therapy on outcome measures was studied in a controlled 24-month double blind trial in 138 patients with early rheumatoid arthritis (RA) using an intent to treat approach. Patients were randomized to AF or placebo but in case of insufficient effect or intolerable adverse events, they switched to open disease modifying antirheumatic drug therapy. Patients who started AF fared significantly better in improved joint swelling. Stanford Health Assessment Questionnaire index, Keitel functional test, and mental depression, and furthermore, radiologic progression was significantly retarded. Our results support a disease modifying beneficial effect of AF in early active RA.se A prospective controlled, double-blind multicenter trial compared placebo, auranofin (an orally administered gold complex), and parenteral gold sodium thiomalate (GST) in patients with active rheumatoid arthritis (RA). Of 193 patients who received any treatment, the only important improvement identified for either auranofin or GST was for pain/tenderness scores. When 161 patients who completed 20 weeks of treatment were examined, both auranofin and GST treatments were superior to placebo as measured by improvement in number of painful and/or tender joints, joint pain/tenderness scores, physician's assessment of disease activity, and decrease in erythrocyte sedimentation rate when elevated at entry. GST was superior to placebo in improvement of joint swelling scores, anemia, thrombocytosis, and rheumatoid factor. No drug-related remissions were observed. The only statistically significant advantages of GST over auranofin for efficacy were an increase in hemoglobin concentration and decrease of thrombocytosis with GST. Withdrawals for adverse effects were 5 times more frequent with GST treatment. Thrombocytopenia, proteinuria, elevated liver enzymes, "nitritoid" reactions, and "gold pneumonitis" were observed only in the GST treatment group. These results confirm that both parenteral and oral gold may be effective for the treatment of RA, that GST tends to show greater efficacy than auranofin, and that auranofin has fewer significant adverse effects than GST. However, long-term benefits, tolerability, and safety cannot be inferred from this study. The efficacy, toxicity and possible steroid-sparing properties of auranofin in the treatment of elderly-onset rheumatoid arthritis (EORA) were studied in a 2 yr prospective double-blind placebo-controlled clinical trial. Sixty-five patients with onset of arthritis after the age of 60 yr were randomized to either auranofin 3 mg b.i.d. [n = 31, age 70 (61-84) yr, median (range)] or placebo tablets [n = 34, age 72 (60-81) yr]. Oral prednisolone, starting dose 7.5 or 20 mg daily, was used as a rescue drug in patients with intolerable joint pain and stiffness and with C-reactive protein (CRP) > or = 20 mg/l, and was tapered down according to protocol guidelines. Patients receiving auranofin continued therapy for a longer period of time (55% completers) than those on placebo medication (18% completers). The auranofin group consumed significantly less prednisolone, 2.64 (0-11.85) mg/day [median (range)], compared to 5.0 (0-18.33) mg/day in the placebo group (P = 0.006). No group differences at 2 yr follow-up were found for changes in joint pain (P = 0.49), number of swollen joints (P = 0.61), Health Assessment Questionnaire score (P = 0.18) and radiographic damage score (Larsen-Dale index) of the hands (P = 0.84). Within-group changes in radiographic scores were also insignificant. The drop-out rate due to adverse events was surprisingly higher in the placebo group (41%) than in the auranofin group (10%) and, as expected, higher due to lack of effect (29 and 16%). The results indicate that auranofin is safe, superior to placebo and has steroid-sparing capacity in the treatment of EORA. The favourable radiographic outcome in both groups needs confirmation in future studies. In a six-month, randomized, double-blind study at 14 centers, auranofin (3 mg twice daily) was compared with placebo in the treatment of patients with classic or definite rheumatoid arthritis. All patients had unremitting disease for at least the previous six months and at least three months of therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs, oral steroids, and analgesics were allowed throughout the trial. Efficacy was analyzed in 154 patients who received auranofin and 149 who received placebo. To reflect an expanded view of outcome assessment, the measures used included some 20 nontraditional measures of functional performance, pain, global impression, and utility (worth or value) in addition to five standard clinical measures of rheumatoid synovitis (e.g., number of tender joints). The nontraditional measures were mainly in the form of structured questionnaires administered by trained interviewers. To minimize the statistical problem of multiple comparisons, most of the measures were grouped into four composites--clinical (standard measures), functional, global, and pain--and the treatment effect for each composite was tested at the 0.0125 level of significance. Auranofin was superior to placebo in the clinical (p = 0.003), functional (p = 0.001), and global (p = 0.007) composites and trended similarly in the pain composite (p = 0.021). Individual measures within the composites consistently favored auranofin. Other measures, not part of the composites, also favored auranofin, including a patient utility measure designed for this study, the PUMS (p = 0.002). Results confirm the hypothesis that the favorable effect of auranofin on clinical synovitis is accompanied by improvements across a range of outcomes relevant to the patient's quality of life. The efficacy and safety of the oral gold compound auranofin and intramuscular gold thiomalate have been compared in a placebo-controlled, double-blind, four-centre trial in 82 patients with psoriatic arthritis requiring remittive drug therapy. There were statistically significant falls in Ritchie articular index, visual analogue pain score and ESR at 12 and 24 weeks following i.m. gold but no significant changes in the auranofin group. Intramuscular gold was safe and more effective than auranofin as a second-line, suppressive antirheumatic agent for patients with psoriatic arthritis when followed for 6 months. Two hundred thirty-eight patients with psoriatic arthritis were entered into a 6-month, multicenter, double-blind trial comparing auranofin and placebo. Polyarthritis (greater than 5 tender joints) was present in 90% of the patients, and 94% were seronegative. Auranofin treatment was statistically superior to placebo treatment, according to physician's global assessment and functional scores. A trend in favor of auranofin treatment was seen for each of the other disease parameters studied. Psoriasis worsened in 6 auranofin-treated patients and in 3 placebo-treated patients. The incidence and nature of other side effects were similar to those observed in similar trials of patients with rheumatoid arthritis. Our observations suggest that the use of auranofin in the treatment of psoriatic arthritis is safe, although its therapeutic advantage over treatment with nonsteroidal antiinflammatory drugs alone is modest. PA radiographs of hands and wrists from a randomized 6 month study of auranofin (AF) vs placebo followed by 6 months of open AF were scored for progression of erosive disease by 2 independent readers. The readers were blinded both to treatment and sequence (month 0 vs month 12) of the films. The results of our study demonstrate a reduction in the advancement of erosive disease during AF therapy compared to placebo. Adverse experience occurred with a high frequency in a longterm (greater than 3 years), prospective, double blind, followed by an open trial of methotrexate (MTX) therapy in 45 patients with rheumatoid arthritis (RA). Adverse experiences occurred in 96% of patients, and the discontinuation rate was 44% over 176 weeks. No hepatic or pulmonary fibrosis occurred. Unusual toxicities included weight loss (2 patients), systemic fungal infections (2 patients), and transient noncirrhotic ascites (1 patient). Baseline white blood cell counts and creatinine may help predict adverse experiences. The full dose-toxicity spectrum of MTX RA is not yet fully defined. Methotrexate (MTX) is a first-line disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA). Leflunomide (LEF) and the biologic agents entered the arsenal of DMARDs in 1998. Therapeutic properties of new drugs are still under survey. The purpose of this study was to evaluate and compare the efficacy of MTX, LEF and a biologic agent (TNF-alpha blocker) combined with MTX in reducing disease activity in RA. Seventy-eight patients with active RA underwent a 24-week treatment with MTX 15 mg/week (30 pts), LEF 20 mg/day (30 pts) or a TNF-alpha blocker (etanercept 25 mg 2x weekly or infliximab 3 mg/kg in the week 0, 2, 6 and every 8 weeks thereafter) plus MTX 15 mg/week (18 pts). Only patients with RA resistant to MTX were included in groups receiving LEF or a biologic agent. During follow-up, patients' characteristics, disease characteristics, and clinical and laboratory data were registered. RA activity was evaluated using the ESR, tender and swollen joint counts, the duration of morning stiffness, disease activity score-28 (DAS 28), visual analogue scale (VAS) and health assessment questionnaire (HAQ). Treatment efficacy was demonstrated with ACR 20, 50 and 70 criteria. All groups revealed statistically significant improvement in all disease activity parameters measured. The percentage improvements were similar in groups treated with MTX and LEF and--except for VAS--significantly greater in the group treated with a biologic agent. Disease activity assessed by DAS 28 decreased significantly in all groups: the results were comparable in groups treated with MTX and LEF and significantly more prominent in the group treated with a TNF-alpha blocker. The ACR 20, 50 and 70 improvements amounted, respectively: 100, 50 and 7% in MTX group 87, 60 and 13% in LEF group and 100, 83 and 50% in a biologic agent group. The study revealed equal effectiveness of MTX and LEF in reducing disease activity in rheumatoid arthritis. The efficacy of a TNF-alpha blocker combined with MTX was higher than that of each conventional DMARDs, especially with regard to ACR 70 criteria (considerable improvement after treatment). LEF was equally effective as MTX in patients unable to continue MTX treatment due to the drug's ineffectiveness.
Auranofin appears to have a small clinically and statistically significant benefit on the disease activity of patients with RA. The beneficial effects appear to be modest compared to drugs such as methotrexate or parenteral gold. Its effects on long term health status and radiological progression are not clear at this time.