Prednisone treatment of elderly-onset rheumatoid arthritis. Disease activity and bone mass in comparison with chloroquine treatment. Oral steroids as bridge therapy in rheumatoid arthritis patients starting with parenteral gold. A randomized double-blind placebo-controlled trial. Combination therapy with methotrexate and chloroquine in rheumatoid arthritis. A multicenter randomized placebo-controlled trial. Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Sulfasalazine in early rheumatoid arthritis. A 48-week double-blind, prospective, placebo-controlled study. Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group. Comparison of auranofin, gold sodium thiomalate, and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial. Group therapies for rheumatoid arthritis. A controlled study of two approaches. Diet therapy for rheumatoid arthritis. Levofloxacin treatment in patients with rheumatoid arthritis receiving methotrexate. A controlled study of concurrent therapy with a nonacetylated salicylate and naproxen in rheumatoid arthritis.
Prednisone is frequently used in the treatment of elderly-onset rheumatoid arthritis (RA), but the balance between efficacy and toxicity, including the effect on bone mass, has not been investigated in long-term studies. This prospective, randomized study was undertaken to compare disease activity and bone mass during long-term treatment with prednisone versus chloroquine in this patient population.
                Patients with active RA diagnosed at age > or = 60 were randomized to receive prednisone (15 mg/day for 1 month, with the dosage tapered as low as possible thereafter) (n = 28) or chloroquine (n = 28). Patients who did not show a response received other second-line drugs as an adjunct to prednisone or as a replacement for chloroquine. Bone mass was measured by dual-energy x-ray absorptiometry. The study duration was 2 years.
                During the 2 years, treatment with other second-line drugs was needed for 12 patients in the prednisone group (43%) and 8 in the chloroquine group (29%). Functional capacity and disease activity improved significantly in both groups and did not differ significantly between the groups, except for a greater improvement in the prednisone group at 1 month. Radiographic scores for joint destruction progressed similarly in both groups. There was a nonsignificant excess bone loss of 1.8% in the spine and 1.5% in the hip in the prednisone group, compared with the chloroquine group.
                Neither treatment was entirely satisfactory since a significant number of patients needed an additional second-line drug over the 2-year period. The efficacy of oral prednisone as bridge therapy in rheumatoid arthritis (RA) was studied. Forty patients starting aurothioglucose were randomized to receive either prednisone or placebo for 18 weeks. The dose was 10 mg/day in the first 12 weeks, 7.5 mg/day in weeks 13 and 14, 5 mg/day in weeks 15 and 16, and 2.5 mg/day in weeks 17 and 18. Patients were followed for 44 weeks. We found that disease activity was significantly lower in the prednisone group as early as week 1 and continued up to week 12. Response to prednisone was noticed in 60% of the patients. After tapering prednisone, a rebound deterioration was noticed at weeks 20 and 24 in 58% of the responders. No significant differences in X-ray progression were found between the two groups. We concluded that oral prednisone (10 mg/day) significantly reduces short-term disease activity in 60% of patients with active RA. The rebound deterioration after tapering the dose means that bridge therapy with prednisone using this dose-reduction scheme is not recommended. To compare the efficacy of the combination therapy Methotrexate (MTX) and Chloroquine (CHLO) with MTX and Placebo (PLA) in the treatment of Rheumatoid Arthritis. A total of 82 patients with Rheumatoid Arthritis (RA), diagnosed according to the American College of Rheumatology criteria, received orally either MTX 7.5 mg/week and CHLO 250 mg/day or MTX 7.5 mg/week and PLA 1 tablet/day. Adverse effects (AE) were monitored monthly and disease activity was assessed at 0, 2, 4 and 6 months. Sixty-eight patients completed the study. All outcome measures improved significantly in both treatment groups. Patients receiving MTX/CHLO ended the study with a significantly lower joint count, greater grip strength and better functional ability the patients in the MTX/PLA group, respectively; 4.5 vs 7.5 (P < 0.05), 113.3 vs 89.1 (P < 0.05) and 0.636 vs 0.811 (P < 0.05). Mild AE were more frequently observed in the MTX/CHLO, 17 events in 15 patients, compared to 9 events in 8 patients in the MTX/PLA group (NS). These data indicate that MTX/CHLO is slightly more efficacious and toxic than is MTX/PLA in the treatment of RA. Oral glucocorticoids combined with disease-modifying antirheumatic drugs are beneficial and retard radiologic joint damage in rheumatoid arthritis.
                To investigate the clinical efficacy, disease-modifying properties, and side effects of low-dose glucocorticoids as monotherapy for previously untreated patients with early active rheumatoid arthritis.
                2-year randomized, double-blind, placebo-controlled clinical trial.
                2 outpatient rheumatology clinics.
                81 patients with early active rheumatoid arthritis who had not been treated with disease-modifying antirheumatic drugs.
                41 patients were assigned to 10 mg of oral prednisone per day, and 40 were assigned to placebo. Nonsteroidal anti-inflammatory drugs were allowed in both groups. After 6 months, sulfasalazine (2 g/d) could be prescribed as rescue medication.
                Clinical variables were assessed at baseline and every 3 months; radiologic studies were performed every 6 months. Adverse effects were documented every 3 months.
                In the first 6 months, the prednisone group showed more clinical improvement than the placebo group. This effect was not seen after 6 months except in grip strength and the 28-joint score for tenderness. Use of additional therapies was significantly less common in the prednisone group, particularly in the first 6 months. More than 65% of those who completed the study were not taking sulfasalazine. After month 6, radiologic scores showed significantly less progression in the prednisone group than in the placebo group. No clinically relevant adverse effects were observed, except for a higher incidence of osteoporotic fractures in the prednisone group.
                Prednisone, 10 mg/d, provides clinical benefit, particularly in the first 6 months, and substantially inhibits progression of radiologic joint damage in patients with early active rheumatoid arthritis and no previous treatment with disease-modifying antirheumatic drugs. Because of their limited disease-modifying effects, glucocorticoids should be combined with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis. To investigate the efficacy and tolerability of sulfasalazine (SSZ) in the treatment of early rheumatoid arthritis (RA).
                Eighty patients (symptomatic disease < 12 months) were randomly assigned to treatment with SSZ or placebo for 48 weeks. Clinical, laboratory, and scintigraphic data were used to determine the effects of treatment.
                SSZ was superior to placebo in reducing the laboratory features of inflammation, the clinical parameters of disease activity, as well as the scintigraphic activity in the joints. Furthermore, fewer erosive changes developed in the joints of patients receiving active treatment, but the difference between treatment groups did not reach statistical significance.
                SSZ is effective in the treatment of RA, and its onset of action is rapid. The results support the view that SSZ retards the development of joint erosions. However, like other conventional disease-modifying antirheumatic drugs, its remission-inducing ability is insufficient. Leflunomide is a reversible inhibitor of de novo pyrimidine synthesis shown to be effective in a phase 2 trial in 402 patients with active rheumatoid arthritis (RA).
                To compare the efficacy and safety of leflunomide treatment with placebo and methotrexate treatment in patients with active RA.
                Randomized, double-blind, placebo, and active-controlled 12-month study.
                Forty-seven university and private rheumatology practices in the United States and Canada.
                Diagnosis of RA by the American College of Rheumatology (ACR) criteria for duration of 6 months or longer and no previous methotrexate treatment.
                Leflunomide treatment (20 mg/d), placebo, or methotrexate treatment (7.5-15 mg/wk).
                American College of Rheumatology success rate (completed 52 weeks of treatment and met the ACR > or = 20% response criteria), disease progression as assessed by x-ray films, and improvement in function and health-related quality of life using the intent-to-treat population.
                The 482 patients studied were predominantly women (mean age, 54 years; mean disease duration, 6.7 years) for whom a mean of 0.8 disease-modifying antirheumatic drugs had failed. The ACR response and success rates for patients receiving leflunomide treatment (52% and 41%, respectively) and methotrexate treatment (46% and 35%, respectively) were significantly higher than those for patients receiving placebo (26% and 19%, respectively) (P<.001), and they were statistically equivalent, with mean time to initial response at 8.4 weeks for patients receiving leflunomide vs 9.5 weeks for patients receiving methotrexate therapy. X-ray analyses demonstrated less disease progression with leflunomide (P=.001) and methotrexate (P = .02) therapy than with placebo. Leflunomide and methotrexate treatment improved measures of physical function and health-related quality of life significantly more than placebo (P<.001 and P<.05, respectively). Common adverse events for patients receiving leflunomide treatment included gastrointestinal complaints, skin rash, and reversible alopecia. Asymptomatic transaminase elevations resulted in treatment discontinuations for 7.1% of patients receiving leflunomide therapy, 1.7% of patients receiving placebo, and 3.3% of patients receiving methotrexate therapy.
                Clinical responses following administration of leflunomide, a new therapeutic agent for the treatment of RA, were statistically superior to those with placebo and equivalent to those with methotrexate treatment. Both active treatments improved signs and symptoms of active RA, delayed disease progression as demonstrated by x-ray films, and improved function and health-related quality of life. 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. An important unanswered question about rheumatoid arthritis (RA) is how the patient's psychological or emotional state relates to disease activity and functional status. No controlled studies of psychotherapeutic interventions in RA have been reported. To test the hypothesis that a psychosocial intervention would lead to improvement in functional status or disease activity, 57 RA patients were randomly assigned to 1 of 3 groups, which received: 1) conventional group psychotherapy; 2) group assertion/relaxation training; or 3) no treatment (control group). Patient and physician questionnaires collected at baseline, immediately after the interventions, and 12 months after baseline provided outcome data on functional status, social and psychological adaptation, psychological symptoms, and disease activity. There were few outcome measures for which either treatment resulted in significantly higher scores than were seen in controls, though more improvement did occur among patients who received conventional group psychotherapy. Although diet therapy for arthritis has received considerable publicity, there is little objective information about its efficacy. We undertook a 10-week, controlled, double-blind, randomized trial of patients with active rheumatoid arthritis (RA). Twenty-six patients completed the study; 11 were on an experimental diet (a specific popular diet free of additives, preservatives, fruit, red meat, herbs, and dairy products) and 15 were on a "placebo" diet. Of 183 variables analyzed, there were no clinically important differences among rheumatologic, laboratory, immunologic, radiologic, or nutritional findings between patients on experimental and placebo diets. Six RA patients on the placebo and 5 on the experimental diet improved by objective criteria. Improvement averaged 29% for patients on placebo and 32% for patients on experimental diets. Two patients on the experimental diet improved notably, elected to remain on the experimental diet following the study period, have continued to improve, and noted exacerbations of disease upon consuming nonexperimental diet foods. Our study failed to provide evidence of objective overall clinical benefit of this diet as followed by a group of patients with longstanding, progressive, active RA. However, our data are not inconsistent with the possibility that individualized dietary manipulations might be beneficial for selected patients with rheumatic disease. Sulfasalazine and tetracyclines are effective against rheumatoid arthritis (RA). Levofloxacin, the bacteriologically active isomer of ofloxacin, is used in the treatment of infections caused by periodontopathic bacteria and facultative anaerobic bacteria. The aim of this study is to evaluate the clinical efficacy, safety, and tolerability of levofloxacin in patients with rheumatoid arthritis.
                In a 6-month, double-blind trial, we randomly assigned 76 patients with persistently active rheumatoid arthritis despite at least 6 months of methotrexate therapy at a stable dose of 15 to 25 mg per week to receive either levofloxacin (500 mg) or placebo orally once daily while continuing to receive methotrexate. The change from baseline to six months in the swollen-joint count and tender-joint count was the primary measure of efficacy. Secondary endpoints included pain, quality of life, duration of morning stiffness, erythrocyte sedimentation rate, C-reactive protein level, and physician's and patient's global assessments. The data were also analyzed to determine the number of patients meeting American College of Rheumatology criteria for 20, 50, and 70% improvement.
                The levofloxacin plus methotrexate was associated with the greatest reduction in the number of swollen or tender joints (P < 0.001). The levofloxacin plus methotrexate group also had significant improvement in many of the secondary outcome measures (P < 0.001). Levofloxacin was well tolerated. There were no dose-limiting toxic effects.
                In patients with active rheumatoid arthritis who received methotrexate, treatment with levofloxacin significantly improved the signs and symptoms of rheumatoid arthritis. 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.
Based on the limited data available, moderate-term prednisone treatment of RA appears to be superior to placebo and comparable to treatment with aspirin or chloroquine in improving several common rheumatoid arthritis disease activity measures.