Pilot Study Sheds Light on a Potential New Approach for Treating Lupus Nephritis
Lupus nephritis, which can damage and scar the kidneys, is one of the most common and serious complications of lupus. Between 50 and 60 percent of people with lupus will develop lupus nephritis within 10 years of their lupus diagnosis, and the rate is even higher among children with the disease. Lupus nephritis is more prevalent in African Americans and Hispanics than in Caucasians.
If left untreated, lupus nephritis can lead to renal failure. Unfortunately, there is not an FDA-approved drug that was developed specifically to treat lupus nephritis. Treatment of lupus nephritis often includes oral steroids in combination with either cyclophosphamide or mycophenolate mofetil. Oral steroids, especially when taken chronically, can have serious side effects (including hair loss, weight gain, skin changes) and may lead to non-adherence (treatment failure). In children, the side effects of steroids can be even more severe, often causing slow growth, short stature and potentially impaired reproductive function.
Now, a new study conducted by Dr. Liz Lightstone and colleagues at the Imperial College London NHS Healthcare Trust Lupus Center suggests that with the right induction regimen, it may be possible to avoid maintenance (long-term) treatment with oral steroids. The study, published in a recent issue of Annals of the Rheumatic Diseases, is the first time in 60 years that any study has challenged the accepted wisdom that lupus nephritis has to be treated with oral steroids.
While this pilot study was effective at inducing high rates of remission in adults with lupus nephritis, and even in reducing systemic flares without using steroids, it is important to note that the research evaluated a small population and further research is needed before this treatment protocol can be adopted to treat lupus nephritis on a large scale.
Many of the patients in the study were presenting with their lupus or lupus nephritis for the first time as that is the group who are less likely to already be on steroids. It is not possible to simply stop steroids if patients have been on them for significant periods of time. That said, patients on maintenance steroids or with life-threatening lupus or requiring dialysis were excluded from the study.
Dr. Lightstone and her colleagues plan to next further assess their findings in a prospective, multi-center, international, randomized controlled trial (The Rituxilup Trial NCT01773616). Findings from this trial may, for the first time, offer a realistic possibility of discarding oral steroids, the most toxic element in standard long-term treatment of lupus.
The Lupus Foundation of America is dedicated to finding new ways to better understand and treat lupus nephritis, and we applaud Dr. Lightstone and her colleagues for their continuous work in this field. More information about lupus nephritis can be found here.
More about the Study
The study reports on findings from the first 50 consecutive patients, treated with 2 doses of rituximab (1 g) and methyl prednisolone (500 mg) on days 1 and 15, and maintenance treatment of mycophenolate mofetil. In the study, all patients had at least one year of follow-up and some significantly more. Researchers saw better than expected outcomes with excellent rates of complete remission as early as 6 months and very high by 1 year. When looking at the combination of complete and partial remission at one year, the rates were outstanding. Relapses that did occur where mostly later than one year and were typically easy to treat. Researchers saw few problems from extra renal lupus. Of the 45 patients who “stuck” to the regimen, only 2 needed oral steroids for longer than 2 weeks for extra renal problems.
Condon MB, Ashby D, Pepper RJ, Cook HT, Levy JB, Griffith M, Cairns TD, and Lightstone L. (2013). Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids.Annals of the Rheumatic Diseases 72: 1280-1286. [Epub ahead of print]