Randomized trial of prolonged chloroquine therapy in advanced pulmonary sarcoidosis. Methotrexate is steroid sparing in acute sarcoidosis: results of a double blind, randomized trial.
Sarcoidosis may cause severe ventilatory impairment requiring corticosteroid treatment. Chloroquine (CQ) can be an effective treatment for lung sarcoidosis with few side effects, but has not been accepted as standard therapy. We investigated the benefits of prolonged CQ therapy in 23 symptomatic patients with biopsy-proven pulmonary sarcoidosis (duration, >/= 2 yr). Patients were initially treated for 6 mo with CQ, 750 mg/d, tapering every 2 mo to 250 mg/d. Eighteen patients were then randomized to either a Maintenance group (CQ, 250 mg/d) or to an Observation group (no CQ). After the initial treatment, significant improvement was observed in symptoms, pulmonary function, angiotensin-converting enzyme, and lung gallium scan. Patients randomized to the Maintenance group showed a slower decline in pulmonary function (FEV1, 51.4 +/- 28.2 ml/yr [Maintenance] versus 196.3 +/- 33.4 ml/yr [Observation], p < 0.02) and had fewer relapses: 2 of 10 patients in the Maintenance group at 29.5 +/- 4.9 mo versus 6 of 8 patients in the Observation group at 15.5 +/- 2.9 mo. Adverse effects were seen mainly during high-CQ dosage. We conclude that CQ should be an important consideration for the treatment and maintenance of chronic pulmonary sarcoidosis. Methotrexate has been steroid sparing for some patients with chronic sarcoidosis. We wished to determine whether methotrexate can be steroid sparing in the first year of corticosteroid therapy in sarcoidosis.
                Patients with new onset, symptomatic disease within four weeks of starting on prednisone were randomized to receive either methotrexate or placebo for the next year. They were seen monthly and prednisone dosage was tapered following a pre-determined schedule.
                Of 24 patients enrolled, only 15 received at least six months of therapy. Since methotrexate appears to take six months to be effective, only patients who completed six or more months of therapy were evaluated. The amount of prednisone per day decreased for both groups: methotrexate (First 6 months: Median 26 (Range 15-37) mg/day); Second 6 months 8 (1-22) mg/day, p < 0.01) and placebo (First 6 Months 28 (24-33) mg/day; Second 6 months 16 (11-22) mg/day, p < 0.02), with less prednisone used for the methotrexate patients versus placebo in the last six months (p < 0.01). There was also less weight gain for those patients receiving methotrexate. There was no difference in toxicity between methotrexate and placebo. The difference between methotrexate versus placebo was not seen when all patients (including the dropouts) were analyzed.
                Methotrexate can be a steroid sparing agent in acute sarcoidosis.
The current body of evidence supporting the use of immunosuppressive agents and cytotoxic therapies is limited. Side-effects associated with some of the therapies were severe.