Radiologic evidence of disease modification in rheumatoid arthritis patients treated with cyclosporine. Results of a 48-week multicenter study comparing low-dose cyclosporine with placebo. Norwegian Arthritis Study Group. Adding low-dose cyclosporin A to parenteral gold therapy in rheumatoid arthritis: a double-blind placebo-controlled study. Cyclosporin in rheumatoid arthritis: a double blind, placebo controlled study in 52 patients. Controlled trial of cyclophosphamide in rheumatoid arthritis. Low-dose cyclosporin versus placebo in patients with rheumatoid arthritis. Combination of cyclosporine and leflunomide versus single therapy in severe rheumatoid arthritis. Remission of ordinary psoriasis following a short clearance course of cyclosporin. Combination treatment with methotrexate, cyclosporine, and intraarticular betamethasone compared with methotrexate and intraarticular betamethasone in early active rheumatoid arthritis: an investigator-initiated, multicenter, randomized, double-blind, parallel-group, placebo-controlled study. European trial of cyclosporine in chronic active Crohn's disease: a 12-month study. The European Study Group.
To evaluate the therapeutic efficacy of 46 weeks of treatment with cyclosporine (5 mg/kg/day) in patients with rheumatoid arthritis (RA).
                A 48-week randomized, double-blind, placebo-controlled, multicenter study of cyclosporine was conducted in 122 patients with active RA. Patients were evaluated by objective and subjective clinical and radiologic measurements at baseline and at the end of the study.
                Statistically significant improvement and clinically important changes were seen for the number of tender joints, number of swollen joints, pain score, duration of morning stiffness, and Lee's functional index in the cyclosporine-treated group at the end of the study. Radiographic examination showed that cyclosporine was capable of retarding joint destruction. In the cyclosporine-treated group, serum creatinine levels increased by 17.5 mumoles/liter (23%) at week 24 and by 21.8 mumoles/liter (26%) at week 48. There was no significant difference in mean serum creatinine levels in patients treated with cyclosporine alone and those treated with cyclosporine plus nonsteroidal antiinflammatory drugs. Five patients had to be treated with antihypertensive drugs, and 2 patients were withdrawn from the study because of increased serum creatinine.
                The study shows that cyclosporine seems to have disease-modifying effects in RA. A double-blind, randomized comparison between parenteral gold therapy (PGT) and cyclosporin A (CyA) vs PGT and placebo during 6 months was performed in 40 RA patients experiencing a decreasing effect of ongoing PGT. Patients' overall assessment of health was the only efficacy variable significantly better in the CyA- and PGT-treated vs the placebo- and PGT-treated group. Higher blood pressure and more signs of renal impairment were found during the 6 months treatment in the former compared with the latter group. Six months after the end of the combination therapy, a higher potassium value in the CyA-treated group was the only difference. In conclusion, no effects additional to those expected with single-drug therapy or additional risks of side-effects of either drug were found when combining low-dose CyA with ongoing PGT in RA patients with long disease duration. The efficacy and safety of cyclosporin A (CyA) for patients with rheumatoid arthritis were assessed in a four month double blind, placebo controlled study using an initial dosage of 5 mg/kg daily. Six patients withdrew from the study (two in the placebo group because of inefficacy of treatment and four in the CyA group because of side effects). These six patients were considered therapeutic failures. At the end of the trial the study treatment was considered as good or very good by 14 out of the 26 CyA group patients and by only two out of the 26 placebo group patients. Moreover, in the CyA group significant improvement was observed in five of the seven clinical assessment criteria. Clinical improvement was correlated with a decrease in C reactive protein, alpha 1 glycoprotein levels, and platelet count but not with erythrocyte sedimentation rate or rheumatoid factor titres. Renal toxicity (13 cases) remained the major problem in the management of these patients. This study shows that CyA is effective in active rheumatoid arthritis but requires close monitoring for toxicity. Twenty-four patients with severe progressive rheumatoid arthritis were randomly assigned to cyclophosphamide or placebo in a double-blind crossover trial. Eleven patients who completed 9 months on cyclophosphamide (average dose: 1.8 mg/kg/day) demonstrated significant decrease in painful joints, swollen joints, and morning stiffness and increase in grip strength when compared to 11 patients on placebo. After crossover, significant improvement was observed in patients switched to cyclophosphamide, and deterioration within 2 months was observed in most patients changed from drug to placebo. Serum immunoglobulins and rheumatoid factor titers decreased with cyclophosphamide but antibody response to Vi antigen was unaffected. Primary delayed immune response to 2,4-dinitrochlorobenzene was markedly depressed. Adverse effects were troublesome--hemorrhagic cystitis affected 4 patients and amenorrhea occurred in 3. Despite striking beneficial effect, cyclophosphamide should be prescribed cautiously and only in severe resistant cases of rheumatoid arthritis. 144 patients with severe rheumatoid arthritis from six centres were randomised to receive oral cyclosporin or placebo for 6 months. The initial daily dose of cyclosporin was 2.5 mg/kg, which was increased cautiously with monitoring of serum cyclosporin levels and creatinine; the mean stabilisation dose was 3.8 mg/kg. There were significant improvements in the cyclosporin-treated patients compared with the controls in the major outcomes of reduction of active joints (23% improvement), pain (24%), and functional status (16%); global improvement was 27%. In the cyclosporin group serum creatinine increased by a mean of 15.6 mumols/l and mean arterial blood pressure by 6.27 mmHg; these increases were controlled in all but 2 patients by dose adjustment without withdrawal from the study. This study assessed the efficacy and safety of combination (COMB) of cyclosporine (CSA) and leflunomide (LEF) versus each drug alone, in the treatment of severe rheumatoid arthritis (RA).
                One hundred six patients with active RA refractory to at least one disease modifying antirheumatic drug (methotrexate obligatorily) were entered into a 12-month open, prospective trial and were randomly allocated to receive either CSA 2.5 to 5 mg/kg/day, or LEF 20 mg/day, or the combination of both at the same initiating dose.
                The American College of Rheumatology 50% (ACR50) response rates for the 3 groups were COMB 80%, CSA 40%, and LEF 42% (p = 0.001). Combination therapy was also significantly better than CSA and LEF at the more stringent 70% response rate (69% vs 34% vs 30%, respectively; p = 0.001). Comparable Disease Activity Score 28 reduction rates were noted at trial termination for all 3 treatment arms: COMB -2.74 vs CSA -2.53 vs LEF -2.28 (p nonsignificant). Discontinuation rates were more common in LEF vs CSA arm (p = 0.046). No unexpected or serious adverse drug effects were identified in the combination group during the 12-month period.
                The combination of CSA and LEF in patients with refractory RA provided statistically significant benefit in ACR50 and ACR70. Adverse events were not substantially increased. We set out to show that the assumption is incorrect that continuous treatment with cyclosporin is necessary in psoriasis, as this tenet forms a basis for current recommended treatment regimens. Sixty patients with mild to moderate plaque psoriasis were allocated at random to treatment with oral cyclosporin 5 mg/kg/day (30 patients) or topical dithranol and ultraviolet B therapy (30 patients) for up to 16 weeks until clear (median time 6 weeks cyclosporin and 8 dithranol), and the times to relapse compared. The patients were seen monthly for up to 8 months, and the severity and the extent of psoriasis were assessed. Relapse, defined as return of psoriasis to 50% of the area at the start of the trial or patient demand for further treatment, was not significantly different between the groups (hazard ratio 1.11, 95% CI 0.55-2.32). No patients suffered a rebound of severe disease and none relapsed in the first 8 weeks after stopping treatment. The relapse rate was higher following cyclosporin from 8 to 28 weeks after treatment and following dithranol from 28 to 34 weeks. The patients with arthritis had a higher median joint severity score at relapse than prior to treatment with cyclosporin. At the end of 8 months, 5 patients treated with dithranol and 8 patients with cyclosporin remained clear, 75% and 67% having relapsed. We conclude that rapid relapse does not occur after clearance of mild to moderate plaque psoriasis with cyclosporin and the relapse rate was no different from dithranol treatment. To investigate whether disease control can be achieved in early active rheumatoid arthritis (RA) by treatment with methotrexate and intraarticular betamethasone, and whether the addition of cyclosporine to the regimen has any additional effect.
                Patients (n = 160) were randomized to receive methotrexate 7.5 mg/week plus cyclosporine 2.5 mg/kg of body weight/day (combination therapy) or methotrexate plus placebo-cyclosporine (monotherapy). At weeks 0, 2, 4, 6, and 8 and every 4 weeks thereafter, betamethasone was injected into swollen joints (maximum 4 joints or 4 ml per visit). Beginning at week 8, if synovitis was present, the methotrexate dosage was increased stepwise up to 20 mg/week, with a subsequent stepwise increase in the cyclosporine or placebo-cyclosporine dosage up to 4 mg/kg.
                At 52 weeks, 20% improvement according to the American College of Rheumatology criteria (ACR20) was achieved in 85% of the combination therapy group versus 68% of the monotherapy group (P = 0.02). The median individual overall ACR response (ACR-N) in the 2 groups was 80.0% (interquartile range 40.1-91.8%) and 54.5% (interquartile range 2.4-87.8%), respectively (P = 0.025). At 48 and 52 weeks, ACR remission criteria were met in 35% of the combination therapy group and 28% of the monotherapy group. Progression in the Larsen score at 52 weeks was -0.2 +/- 6.5 and 0.4 +/- 6.9 (mean +/- SD) in the combination therapy and monotherapy groups, respectively. Serum creatinine levels increased by 7%, and hypertrichosis was more prevalent, in the combination therapy group.
                Combined treatment with methotrexate and intraarticular glucocorticoid showed excellent disease control and stopped the progression of erosions in patients with early active RA, who had a poor prognosis. Addition of cyclosporine improved the ACR20 and ACR-N responses, whereas the ACR50 and ACR70 responses, remission rates, and radiographic changes did not differ between the 2 study groups. The role of cyclosporine in Crohn's disease is controversial. This study aimed to delineate the long-term effect of cyclosporine in chronic active Crohn's disease.
                One hundred eighty-two patients from 33 European centers were included. The patient cohort was stratified at entry into a stratum with low Crohn's Disease Activity Index (CDAI) ( < 200) and high CDAI ( > 200). The low-activity group continued to receive the pretrial steroid dose for 2 months, and the high-activity group received 1 mg.kg-1.day-1 prednisone initially. During months 3 and 4, the dose of steroids was reduced stepwise to 5 mg/day in all patients. Placebo and cyclosporine (5 mg.kg-1.day-1) were administered throughout the 12-month study period. The main parameter of efficacy was the CDAI, and the main end point was the number of patients in remission at month 12.
                During cyclosporine therapy, 35% (95% confidence interval [95% Cl], 25%-46%) of the patients achieved a full remission (CDAI, < 150) after 4 months compared with 27% (95% Cl, 18%-38%) in the placebo group (P > 0.05). At month 12, only 20% (95% Cl, 12%-31%) vs. 20% (95% Cl, 12%-31%) of the patients had maintained a continuous remission. No major differences between treatment groups were found within each of the two strata.
                The long-term treatment of chronic active Crohn's disease with cyclosporine plus low-dose steroids does not offer an advantage compared with low-dose steroids alone.
Cyclosporine has an important clinical benefit in the short-term (up to one year) treatment of patients with progressive rheumatoid arthritis.