Remission in lupus occurs when symptoms previously observed have not surfaced in some time. Such patients are generally advised to continue taking medication in low doses to prevent a relapse, but according to a new study presented Wednesday at the European League Against Rheumatism Annual Congress (EULAR 2014), gradually stopping immunosuppressant therapy may reduce incidence of lupus flare-ups. Seventy percent of patients who were clinically stable showed no flare-ups within the first two years of stopping medications. Half were successful within three years, and this proportion remained stable for up to five years.
Lupus is a chronic, auto-immune disease where the immune system of the body starts attacking normally healthy tissues. It is thought to be a genetic disorder caused by gene polymorphisms. Though lupus affects different people differently, common symptoms include: joint pain, swelling, kidney complications, and skin rashes. It is also characterized by flares where the symptoms of fatigue and/or fever, and remissions where the symptoms subside.
Lupus treatments also vary according to the severity, age, and other considerations. But the general drugs approved by the FDA include corticosteroids, antimalarials, monoclonal antibody belimumab, and also aspirin. High-dose corticosteroids such as prednisone, and immunosuppressants such as azathioprine (AZA), methotrexate (MTX), and mycophenolate mofetil (MMF) are used when lupus becomes life-threatening and causes kidney inflammation, lung or heart problems, and central nervous system symptoms.
But the goal of most physicians is to try to stop or reduce the use of long-term immunosuppressant usage without a potential relapse as long-term drug use comes with its associated complications. "Until now, information on whether and how immunosuppressant therapy might be stopped in lupus patients after achieving low disease activity or remission has been limited," said lead author Dr. Zahi Touma, assistant professor of medicine, clinician-scientist, Division Of Rheumatology, University of Toronto, Canada, according to a press release.
"The results from our study provide useful guidance on how best to stop the immunosuppressant without triggering a flare. For example, patients who discontinued their immunosuppressant more slowly were less likely to flare within two years. Those lupus patients who were serologically active at the time the immunosuppressant was stopped were much more likely to flare on follow-up visits," he added.
The study tracked 1,678 patients who were registered at the Toronto Lupus Clinic, all of whom were in clinical remission. Out of these, 973 had been prescribed an immunosuppressant; and 99 had stopped taking it, of which 56 had been on AZA, 25 on MTX, and 18 on MMF. Of the 99 patients who stopped their immunosuppressant, 25 flared within two years (16 on AZA; 7 on MTX and 2 on MMF; p=0.31); 17 patients experienced a flare after year two.
Comparing patients who flared within two years to those who did not, the percentage of patients with positive serology at the time their immunosuppressant was stopped was greater in those who flared, 68 percent vs. 42 percent. In the no-flare group, the length of time from the start of tapering to stopping the immunosuppressant was a little less than two years, significantly slower than the 0.9 years in the group who did experience a flare.
At the start of tapering, the average age of the patients was around 40 years and the disease duration was 11.4±9.4 years. Forty-six of the patients had follow-up available beyond two years; 32 were followed beyond three years; 26 beyond four years; and 24 beyond five years. Using a Kaplan-Meier curve for the time to flare, at one, two, three, four, and five years, the percentage of patients who flared was 17 percent, 30 percent, 46 percent, 49 percent, and 51 percent respectively.
Flare was evaluated within two years of immunosuppressants being stopped and also at any time after it was stopped. Three time points were identified for each patient, the start of decreasing the immunosuppressant, which was at least 25 percent of the dose, the stop time of the immunosuppressant, and the end of the study — defined as the date of flare, or last clinic visit after the immunosuppressant was stopped.
An estimated 1.5 million Americans have some form of lupus and five million cases of lupus have been reported around the world. Lupus is more prevalent in African-Americans, Hispanics/Latinos, Asians, Native Americans, Alaska Natives, Native Hawaiians, and other Pacific Islanders. Women are also more susceptible to it than men, and 90 percent of patients diagnosed are women.