ACTHAR GEL for Sarcoidosis-Associated Calcium Dysregulation: An Open-label Pilot Study

Sarcoidosis is a multisystem granulomatous disease of unknown cause. Although sarcoidosis most commonly affects the lung, it may affect any organ. Although corticosteroids are recognized as the drug of choice for sarcoidosis. ACTH(adrenocorticotropic hormone) is the only drug that is FDA-approved for this disorder. However, there is limited data on the efficacy of ACTH for this condition.

Calcium metabolism is disregulated in active sarcoidosis. The primary abnormality in calcium metabolism stems from an increased 1-α hydroxylase activity in sarcoid alveolar macrophages that converts 25-hydroxyvitamin D to 1, 25-dihydroxyvitamin D, the active form of the vitamin. This can result in hypercalcemia, hypercalciuria, nephrocalcinosis, nephrolithiasis, interstitial nephritis, glomerulonephritis, acute and chronic kidney disease. Importantly, almost of the renal manifestations stem from disordered calcium metabolism. Unlike other organ manifestations of sarcoidosis, the disorder of calcium metabolism is more common in whites compared to african americans.Compared to hypercalcemia, hypercalciuria is three times more common in sarcoidosis, nevertheless, it has largely been ignored.

In general, the patient with hypercalcemia should be advised to avoid sunlight, curtail intake of major sources of dietary calcium and vitamin D, and drink ample fluids.If the patient is symptomatic, serum calcium is greater than 11 mg/dl, the serum creatinine is elevated, or the patient has nephrolithiasis, drug therapy is usually required. The drug of choice is prednisone at an initial daily dose of 20 - 40 mg/day.Unfortunately, prolonged corticosteroid therapy may result in unacceptable side effects including osteoporosis. This is particularly important as elevated calcitriol observed in patients with sarcoidosis can further jeopardize bone structure by resorption. Alternative medications that have shown benefit for sarcoidosis associated calcium dysregulation have included chloroquine,hydroxychloroquine, ketoconazole.

Not only may ACTHER GEL have obvious anti-inflammatory effects by resulting in corticosteroid production, but it may also activate melanocortin receptors. The melanocortin system has powerful anti-inflammatory properties that may be beneficial in the treatment of sarcoidosis.

We believe that there are several specific advantages of assessing the effectiveness of anti-sarcoidosis therapy by examining sarcoidosis-associated disorders of calcium metabolism.