Lack of radiological and clinical benefit over two years of low dose prednisolone for rheumatoid arthritis: results of a randomised 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. Substitution of beclomethasone aerosol for oral prednisolone in the treatment of chronic asthma. A randomised trial of differentiated prednisolone treatment in active rheumatoid arthritis. Clinical benefits and skeletal side effects. Oral steroids as bridge therapy in rheumatoid arthritis patients starting with parenteral gold. A randomized double-blind placebo-controlled trial. A randomised placebo controlled 12 week trial of budesonide and prednisolone in rheumatoid arthritis. Prednisone treatment of elderly-onset rheumatoid arthritis. Disease activity and bone mass in comparison with chloroquine treatment. A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Myasthenia Gravis Study Group. [A double blind trial of alfacalcidol on patients with rheumatoid arthritis (RA)].
Evidence for disease modifying activity of low dose corticosteroid treatment in rheumatoid arthritis is contradictory. Studies showing radiological benefit suggest that continued treatment is required to sustain the effect.
                To evaluate the effect of low dose oral prednisolone in early rheumatoid arthritis on disease activity over two years.
                Double blind placebo controlled trial.
                Patients with rheumatoid arthritis, duration <3 years (n = 167), were started on a disease modifying antirheumatic drug (DMARD; sulphasalazine) and allocated by stratified randomisation to prednisolone 7 mg/day or placebo. Primary outcome measure was radiological damage, assessed by the modified Sharp method. Clinical benefit was a secondary outcome. A proactive approach to identifying and treating corticosteroid adverse events was adopted. Patients who discontinued sulphasalazine were offered an alternative DMARD.
                90 of 257 patients eligible for the study refused to participate (more women than men). Of those enrolled, 84% were seropositive for rheumatoid factor, median age 56 years, median disease duration 12 months, female to male ratio 1.8:1. Prednisolone was given to 84 patients; of these 73% continued prednisolone and 70% sulphasalazine at 2 years. Of the 83 patients on placebo, 80% continued placebo and 64% sulphasalazine at 2 years. There were no significant differences in radiological score or clinical and laboratory measures at 0 and 2 years.
                Low dose prednisolone conferred no radiological or clinical benefit on patients maintained on a DMARD over two years. Low dose corticosteroids have no role in the routine management of rheumatoid arthritis treated with conventional disease modifying drugs. 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. In a double-blind study 10 patients with chronic asthma received beclomethasone dipropionate 400 mug daily in a Freon propellant from a pressurized dispenser, and 10 patients received the Freon propellant alone. At the start of the trial each patient was receiving long-term maintenance treatment with oral prednisolone in a dose of 7.5 to 15 mg daily. The daily dose of prednisolone was reduced by 1 mg every four weeks and the patient's progress followed by regular clinical assessment and studies of pituitary-adrenal function. The trial was continued until the dose of prednisolone was reduced to zero or until asthmatic symptoms increased to an unacceptable level.In the 10 patients who received beclomethasone the mean maintenance dose of oral prednisolone was reduced by 5.6 mg/day but in only two cases could this drug be withdrawn completely. In the placebo group the mean reduction in dose was only 1.3 mg, thus there was a significant difference between the two groups (P <0.01). Studies of pituitary-adrenal function showed that a normal adrenal response to tetracosactrin stimulation returned only in the two patients from whom prednisolone was withdrawn.Hence the addition of beclomethasone dipropionate by inhalation to systemic corticosteroid therapy allows useful reductions to be made in the oral maintenance doses of corticosteroid. Reductions must be made with caution since there is wide individual variation in response to beclomethasone and in only a minority of patients can oral treatment by completely withdrawn. To study benefits and skeletal side effects of carefully monitored prednisolone treatment in patients with active rheumatoid arthritis.
                One hundred and two patients with active rheumatoid arthritis were randomly allocated to treatment with disease modifying anti-inflammatory drug (DMARD) alone or DMARD and prednisolone in a one year follow up study. Prednisolone was given in a dose regimen adapted to the disease activity of the individual patient. The mean dose was 6 mg and the mean cumulated dose was 2160 mg. Patients were followed up with disease activity parameters, radiograph of the hands (Larsen score), and bone mineral density (BMD) of the lumbar spine, distal forearm and hand. At one year 26 patients had withdrawn from the investigation leaving 76 patients for evaluation.
                The results showed that disease activity in the prednisolone treated group was reduced within two weeks. In the DMARD alone group disease activity was gradually reduced over months. At six months there was no difference between the groups as evaluated by an improvement score using a number of ACR criteria. Prednisolone in the present set up was not able to protect significantly against radiological disease progression, although there was a trend towards less progression in Larsen score in the prednisolone group, a matter that was further underlined in an intention to treat analysis. BMD data revealed a significant reduction in spinal BMD in the prednisolone group, whereas prednisolone seemed to have a protective effect against bone loss in the hand and distal forearm.
                This study does not allow any firm conclusions for or against the treatment of rheumatoid arthritis with prednisolone. The data suggest that the beneficial effects of prednisolone are not as clear cut in established rheumatoid arthritis as in early disease. Furthermore the data indicate that treatment in the chosen relatively low dose does not provide sufficient control of disease. On the other hand the spinal bone loss observed in the prednisolone group does invite considerations about using higher doses. 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 budesonide, a locally acting glucocorticoid with minimal systemic exposure, with conventional glucocorticoid treatment and placebo in rheumatoid arthritis.
                A double blind, randomised, controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis, comparing budesonide 3 mg daily, budesonide 9 mg daily, prednisolone 7.5 mg daily, and placebo. Particular attention was paid to the pattern of clinical response and to changes in the four week period following discontinuation of treatment.
                There were improvements in tender joint count and swollen joint count on budesonide 9 mg compared with placebo (28% for tender and 34% for swollen joint counts, p<0.05). Prednisolone 7.5 mg gave similar results, while budesonide 3 mg was less effective. ACR20 response criteria were met by 25% of patients on placebo, 22% on budesonide 3 mg, 42% on budesonide 9 mg, and 56% on prednisolone 7.5 mg. A rapid and significant reduction in symptoms and signs in response to budesonide 9 mg and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks. There was no evidence that budesonide provided a different pattern of symptom control from prednisolone, or that symptoms became worse than placebo treatment levels after discontinuation of glucocorticoid treatment. Adverse effects attributable to glucocorticoids were equally common in all groups.
                The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved within a short time of initiating treatment, are maintained for three months, and are not associated with any rebound in symptoms after stopping treatment. 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. We compared prednisolone (PRED) and azathioprine (AZA) versus prednisolone alone in the treatment of MG. Prednisolone alone or combined with azathioprine is widely used in the treatment of MG, but no randomized placebo-controlled comparative trial data are available. The prednisolone dose and clinical outcome were compared in a multicenter randomized double-blind study of 34 MG patients who were followed up for 3 years. One group (PRED + AZA) received prednisolone (on alternate days) plus azathioprine (2.5 mg/kg); the other group received prednisolone on alternate days plus placebo (PRED + PLAC). Initial high-dose prednisolone (1.5 mg/kg on alternate days) was tapered at remission to the minimal dose required to maintain remission. The prednisolone dose did not differ significantly between the two groups at 1 year (median values: PRED + AZA, 37.5 mg on alternate days; PRED + PLAC, 45 mg on alternate days) but was reduced at 2 and 3 years in the PRED + AZA group (median value at 3 years: PRED + AZA, 0 mg on alternate days; PRED + PLAC, 40 mg on alternate days; p=0.02). Relapses and failures to remit over the 3 years were more frequent in the PRED + PLAC group. There was a sharp rise in the anti-acetylcholine receptor (AChR) titers in the PRED + PLAC group at 2 years. Incidence of side effects was slightly less in the PRED + AZA group. Azathioprine as an adjunct to alternate day prednisolone in the treatment of antibody-positive generalized MG reduces the maintenance dose of prednisolone and is associated with fewer treatment failures, longer remissions, and fewer side effects. A double blind comparative trial was performed in order to study the efficacy and safety of alfacalcidol (1 alpha-OH-D3) in a total of 140 patients with RA admitted to 31 institutes, using a placebo as the control. The treatment period was 16 weeks. The doses of 1 alpha-OH-D3 were 1.0 microgram/day and 2.0 micrograms/day. It was permissible to use non-steroid anti-inflammatory drugs for basic treatment and oral steroidal preparations for maintenance treatment without changing the doses of these drugs during the study period in patients who had been treated with them before participating in the study (for oral steroidal preparations, the dose was limited to 5 mg/day or less as prednisolone). The percentage of patients with slight improvement was about 10% higher in 1 alpha-OH-D3 groups than in placebo group, but the difference between them was not significant. The results tended to be better in the treated groups than in the placebo group, but there was no significant difference between them with regard to duration of morning stiffness, number of joints with pain, number of joints with swelling and Lansbury's index. The effects of 1 alpha-OH-D3 on various immunological parameters including lymphocyte subsets were not clearly demonstrated. However, interestingly, the ratio of OKT-4/OKT-8 was found not to change in patients whose initial value was normal, while it tended to decrease after 1 alpha-OH-D3 treatment in patients whose initial value was abnormally high. The improvement of bone atrophy was judged by microdensitometry (MD) method using X-ray picture of hands. The indexes of bone density (GS max, GS min and sigma GS/D) demonstrated that 1 alpha-OH-D3 prevents reduction in bone density. 1 alpha-OH-D3 did not trigger hypercalcemia in any case. However there was a slight but significant increase of serum Ca value in the group with higher dose (2.0 micrograms/day). Taking the efficacy into consideration, the dose of 1.0 microgram/day was judged to be suitable for long-term treatment.
Prednisolone in low doses (not exceeding 15 mg daily) may be used intermittently in patients with rheumatoid arthritis, particularly if the disease cannot be controlled by other means. The risk of harms needs to be considered, however, especially the risk of fractures and infections. Since prednisolone is highly effective, short-term placebo controlled trials studying the clinical effect of low-dose prednisolone or other oral corticosteroids are no longer necessary.