Ten trials involving a total of 185 people were included. Study design and quality, corticosteroid dosages and outcomes varied widely. There was a reduction in oral corticosteroid dose favouring methotrexate in parallel trials ( weighted mean difference - mg per day, 95% confidence interval - to -) and also in cross-over trials ( weighted mean difference - mg per day, 95% confidence interval - to -). There was no difference between methotrexate and placebo for forced expiratory volume in one minute ( weighted mean difference litre, 95% confidence interval - to ). Hepatotoxicity was a common adverse effect with methotrexate compared to placebo ( odds ratio , 95% confidence interval to ).
Cyclosporine can cause some side effects. About 25% of people taking cyclosporine develop high blood pressure (hypertension). In addition, because cyclosporine can be tough on the kidneys, it can cause a substance called uric acid to build up in the blood (a state known as hyperuricemia). Sometimes this buildup of uric acid can cause gout, a condition that causes intense swelling in one of the joints, often the the big toe. If you already have gout, your condition may worsen while taking cyclosporine. Fortunately, many of these side effects go away as treatment with cyclosporine is reduced or stopped, so your doctor can work with you to adjust your dosage if you begin to experience these problems.
Instead of using a very high dose of one medication, Dr. Holland has found that moderate doses of a triple-drug regimen are preferable, such as the common three-agent protocol of prednisone, mycophenolate and tacrolimus. “By using multiple medications, you can lower the dose of each and thus reduce the risk of side effects,” he said. “And in selecting a T-cell inhibitor, we’ve found that tacrolimus is better tolerated and a little more efficacious than cyclosporine.” Although some published case series indicate that only short-term use of these immunosuppressive drugs is needed, “in our experience, it’s a minimum of two to three years,” explained Dr. Holland. “The duration depends on the patient. Those with ocular cicatricial pemphigoid or Stevens-Johnson syndrome tend to be particularly challenging, with conjunctival inflammation that can persist. They require long-term—and in some cases, lifetime—immunosuppression.”