In a potential breakthrough for lupus care, Oklahoma Medical Research Foundation scientists have discovered that many patients experiencing disease remission can safely taper off a commonly prescribed maintenance drug without sparking a relapse.
Their finding is crucial because prolonged use of the drug, mycophenolate mofetil, can have serious side effects.
During a clinical trial spanning six years, OMRF physician-scientists Eliza Chakravarty, M.D., and Judith James, M.D., Ph.D., found that people with lupus who stopped taking the drug remained in remission almost as often as those who continued taking it.
“Most clinical trials test whether new medications can improve symptoms, but this was the first one in the U.S. focused on understanding when and how we can stop a major lupus medication,” said James, who is OMRF’s executive vice president & chief medical officer. “This study also laid the foundation for ongoing work to help us predict which patients in remission should stay on medication.”
The trial involved 102 people with lupus in 19 clinics and hospitals nationwide, including OMRF’s Rheumatology Center of Excellence. It was funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, through the Autoimmunity Centers of Excellence. The journal The Lancet Rheumatology published the study’s findings Jan. 29.
Lupus is an autoimmune disease that can cause damage to the joints, skin, kidneys, heart and lungs. Marked by flares followed by periods of remission, lupus primarily strikes women. The most common form, systemic lupus erythematosus (SLE), causes or contributes to more than 3,000 annual deaths in the U.S., according to the Centers for Disease Control and Prevention.
Mycophenolate mofetil, an immunosuppressant sold under the trade name CellCept, originally received Food and Drug Administration approval in 1995 to treat or prevent organ rejection following kidney transplants. Scientists soon discovered the drug also controls severe lupus symptoms.
“The problem is that patients would stay on it forever, because we just didn’t know what would happen if they went off it,” Chakravarty said
Long-term use of mycophenolate mofetil can cause increased risk of infection, malignancies, gastritis, miscarriages and severe birth defects. Physicians warn people with lupus not to take the drug while pregnant or when breastfeeding.
Chakravarty, a rheumatologist who chairs OMRF’s Institutional Review Board, said the idea for the clinical trial first came to her in 2008 after several patients confided that they had stopped taking the drug due to its high cost, the nausea and malaise it induces, or their desire to have children.
“Anecdotally, I noticed that the next time I saw them, some of those people had not experienced any relapse,” Chakravarty said. “That’s when I knew this needed much closer examination.”
The study closely monitored patients in remission from SLE. Roughly half remained on mycophenolate mofetil for the 14-month study period, while the other half weaned off over the first three months and then remained off.
The results: Those who stopped taking the drug were 7% more likely to experience significant symptom relapse but also were less susceptible to infections than those who continued taking the drug, researchers found.
“Although further study is needed, these results may help guide rheumatologists’ conversations with their patients on the risks and benefits of stopping medication,” said James, a National Academy of Medicine member who holds the Lou C. Kerr Endowed Chair in Biomedical Research at OMRF.
She cautioned that people with lupus who take mycophenolate motefil should not stop without consulting their physician.
“The holy grail of further studies would be data to predict with more certainty who will experience problems by going off medication, and who won’t,” Chakravarty said.
The study received additional support from NIAID grant Nos. U19AI1082714 and UM1AI144292, and No. P30AR073750 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, also part of the National Institutes of Health.