Neoral®

A randomised double-masked trial compared cyclosporine with prednisolone in 56 patients with bilateral sight-threatening non-infectious intermediate or posterior uveitis. Visual acuity or vitreous haze improved in only 13 of 28 patients (46%) in each arm, and macular oedema resolved in 7 of 15 on cyclosporine against 10 of 16 on prednisolone (p=0.376). Twenty-eight patients per arm cannot exclude a real difference, so this is a failure to detect one rather than a demonstration that the two are equal, and the authors' own word is that only 46% improved: two mediocre options, not two good ones. Patients who failed both drugs alone improved on the combination. The notable adverse effects were rises in serum creatinine and hypertension. Formulation caveat, which comes from the dates rather than from the paper: this trial published in 1991 and the Neoral microemulsion reached the market in 1995, so it necessarily used the original oil-based formulation. The two are not interchangeable without blood-level monitoring, and Neoral gives higher exposure per milligram, so neither the response rate nor the creatinine and blood-pressure signal transfers dose for dose.

The Systemic Immunosuppressive Therapy for Eye Diseases cohort followed 373 patients starting cyclosporine as their single non-corticosteroid agent. Sustained complete control of inflammation was reached by 33.4% at 6 months and 51.9% at 1 year, and corticosteroid-sparing success, meaning controlled inflammation on prednisone of 10 mg a day or less, by 22.1% and 36.1%. Toxicity ended treatment within a year in 10.7%, and patients over 55 were more than three times as likely to stop for toxicity as those aged 18 to 39, so an alternative agent may suit older patients better. The authors describe the drug as modestly effective. The cohort spans 1979 to 2007 and so straddles both the oil-based and microemulsion formulations.