A randomised double‐blind trial of cyclosporin and azathioprine in refractory rheumatoid arthritis

Abstract

Fifty-two patients with severe rheumatoid arthritis (RA) from four Australian centres were randomised to receive cyclosporin A (CSA) (n = 25) or azathioprine (AZA) (n = 27) for six months. Initial mean doses of CSA and AZA were 4.2 mg/kg and 1.7 mg/kg respectively. The mean doses of CSA and AZA at six months were 3.4 mg/kg and 1.9 mg/kg. Assessments of side-effects and outcomes of benefit were made monthly by independent, blinded observers. Both treatment groups exhibited statistically significant improvement in standard outcome parameters when compared with baseline values. However, there were no statistically significant differences in these parameters between the two groups. There was a mean increase in serum creatinine concentration associated with CSA; no persons were withdrawn from the study for this reason. Seven CSA recipients (three gastrointestinal symptoms, two neurological symptoms, two other) and 12 AZA recipients (six gastrointestinal symptoms, four inefficacy, two other) withdrew from treatment prematurely. Seven CSA recipients became hypertensive and four required anti-hypertensive therapy. Adverse events not requiring cessation of therapy were more commonly seen among CSA patients. In this group of severely affected patients with RA both cyclosporin and azathioprine were effective therapies. CSA toxicities were predictable and manageable but required close monitoring.

The Use of Cyclosporine A in Rheumatology: a 2016 Comprehensive Review

“…Over the years, CyA has been proven to be more effective than placebo in disease control [5][6][7][8][9], even at long term [10], delaying radiological progression [11][12][13]. Controlled trials have shown CyA to be as effective as parenteral gold [14,15], D-penicillamine [16], hydroxychloroquine (HCQ) and azathioprine (AZA) [17][18][19], but less effective than methotrexate (MTX) [20][21][22].…”

The use of modelling to evaluate new drugs for patients with a chronic condition: the case of antibodies against tumour necrosis factor in rheumatoid arthritis

“…Sampling from conditional distributions Azathioprine G Azathioprine HAQ: none of the trials in the Cochrane library (azathioprine versus placebo, three trials including a grand total of 33 patients treated with effective doses of azathioprine) gives HAQ data. 62 G Only one of the studies, of azathioprine against other DMARDs, [63][64][65][66][67] appears to have HAQ data, but the azathioprine group in this study only had 27 patients. 67 The patients appeared to be a group with severe disease (baseline HAQ scores of 1.8).…”

“…62 G Only one of the studies, of azathioprine against other DMARDs, [63][64][65][66][67] appears to have HAQ data, but the azathioprine group in this study only had 27 patients. 67 The patients appeared to be a group with severe disease (baseline HAQ scores of 1.8). Change in HAQ at 6 months was recorded at 0.1 for azathioprine and for ciclosporin groups.…”

Immunosuppressive and cytotoxic pharmacotherapy for pulmonary disorders.

“…More recently, CsA has been increasingly used to treat diverse autoimmune disorders refractory to corticosteroids or other immunosuppressive agents (6). Randomized placebo-controlled trials have shown CsA to be effective in autoimmune uveitis (6,192), Behcet's syndrome (193), psoriasis (194), inflammatory dermatoses (6,195), inflammatory bowel disease (196)(197)(198)(199), primary biliary cirrhosis (200), rheumatoid arthritis (6,201,202), aplastic anemia (6), myasthenia gravis (6), chronic inflammatory demyelinating polyneuropathies (6), and nephrotic syndrome (6,137).Concomitant corticosteroid therapy may enhance response (6,199). Improvement may occur promptly (often within 1 to 3 wk of initiation of CsA), but relapse has been frequent upon its discontinuation (6,195,203).…”