Lara C. Pullen, PhD

November 19, 2013

CHICAGO — Tacrolimus may be an option for patients with interstitial lung disease related to connective tissue difficulties, new research suggests.

Tacrolimus was effective in a series of 13 patients. "All patients had improved or stable lung capacity," Leah Witt, MD, from the University of Chicago, said here at CHEST 2013: American College of Chest Physicians Annual Meeting.

Lungs are frequently involved in connective tissue disease. Interstitial lung disease is frequently seen in patients with connective tissue problems and systemic sclerosis, polymyositis, dermatomyositis, and rheumatoid arthritis.

Tacrolimus is a calcineurin inhibitor with multiple immunomodulatory mechanisms. Its use in patients with connective tissue–related lung disease has not yet been investigated. However, controlled trials have shown that it is an effective treatment for patients with rheumatoid arthritis.

Anecdotal evidence suggests that tacrolimus is an effective treatment for other rheumatic diseases. One study found that tacrolimus could be useful for patients with refractory polymyositis with interstitial lung disease (Lancet. 1999;353:1762-1763). Tacrolimus reportedly helped patients with so-called mechanic's hands and severe muscle weakness.

To add to the body of work, Dr. Witt's team assessed patients from the University of Chicago database who had progressive interstitial lung disease related to connective tissue difficulties despite treatment with prednisone and an additional immunosuppressive agent.

The researchers evaluated the safety and efficacy of tacrolimus in combination with immunosuppressive therapy. "The goal, when starting tacrolimus, was to wean the prednisone," she explained.

Preliminary Work

Investigators conducted a retrospective analysis of prospectively collected data. They looked at demographics, clinical features, lung function, radiographic images, pathologic findings, and adverse events. They assessed response to therapy with percent change in forced vital capacity and difference in 6-minute walk test distance, and compared forced vital capacity measured before tacrolimus with best lung function during treatment.

Study participants received twice-daily tacrolimus 1 mg to 6 mg in addition to the medications the patients were already taking. Target tacrolimus serum trough level was 5 to 10 ng/mL.

The mean age of the patients was 56 years, and average length of treatment was 35.5 months, although this varied widely.

"In our population, the most common adverse event was pulmonary infection," Dr. Witt reported. Other common adverse effects were hypertension and hyperglycemia. None of the patients had a life-threatening adverse event, and none had a sustained elevation in creatinine.

Dr. Witt noted that the study was limited by the fact that it was small and was based in a single center.

"We were very excited to see these results," said session comoderator Rishi Raj, MD, from Northwestern University in Chicago. "We are starting to use this with our patients as well," he told Medical Medscape News.

The audience also responded positively, with comments ranging from "very interesting" to "very practical."

Dr. Witt explained that future work should include a prospective, randomized, controlled study to confirm the results of the case series.

Dr. Witt and Dr. Raj have disclosed no relevant financial relationships.

CHEST 2013: American College of Chest Physicians Annual Meeting. Presented October 30, 2013.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.