Johns Hopkins Health Alert
Tackling B Cells to Fight Lupus
Systemic lupus erythematosus (SLE), or lupus, is an autoimmune disease, in which the immune system mistakenly attacks the body's own organs and tissues. The sites most commonly affected are the joints, skin, kidneys, heart, lungs, blood vessels and brain. Although lupus has no cure, several promising new therapies are under investigation.
Following the success of biologic drugs in treating rheumatoid arthritis (RA), researchers are now examining their potential for lupus. Unlike other immunosuppressants, which work by suppressing the entire immune system, biologics selectively target certain cells implicated in the development of the disease. A number of biologics, including Benlysta (a new drug for lupus approved by the FDA in March of 2011), target B cells -- immune system cells that make antibodies to viruses and other invading pathogens.
Scientists believe that in individuals who have lupus, the B-cell antibody production process goes awry, generating autoimmune antibodies (antibodies that attack and destroy the body's own healthy tissues) and secreting cytokines (proteins produced by certain immune system cells) that induce inflammation.
B-cell depletion therapy for lupus. One approach to tackling this aberrant antibody production is a process known as B-cell depletion therapy. Although early studies showed that the RA drug rituximab (Rituxan) effectively depleted B cells and reduced disease activity, two important phase III randomized, controlled trials failed to show any difference between Rituxan and placebo. Although the results were disappointing, scientists have not abandoned this strategy altogether. Preliminary evidence from additional studies suggests that Rituxan may help ameliorate some of the complications that can occur in people with lupus, such as antiphospholipid antibody syndrome.
B-cell receptor inhibition for lupus. Another approach, called B-cell receptor inhibition, is also under investigation. B-cell receptor inhibitors work by reducing the enhanced activation of B cells that occurs in people with lupus. Results from a small 12-week phase II randomized, controlled trial of the B-cell receptor inhibitor epratuzumab showed that it significantly reduced disease activity in patients with moderate to severe active lupus.
B-cell survivor-factor inhibition for lupus. A third strategy, and the one upon which Benlysta is based, is known as B-cell survivor-factor inhibition. Drugs in this class reduce the actions of a protein (B lymphocyte stimulator, or BLyS) that increases the life span and inflammatory potential of B cells.
In a study presented at the annual meeting of the American College of Rheumatology, researchers reported that in a 52-week phase III trial of 865 lupus patients, those who took 1 mg/kg or 10 mg/kg of the drug along with standard therapy (prednisone and immunosuppressants) had significant reductions in disease activity, flare rates, use of prednisone and time to first flare compared with placebo users. Data from an extension of that study to 76 weeks show that the results were sustained.
Posted in Arthritis on December 5, 2011
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I would like to comment on my use of Rituxan for Reumatoid Arthritis. I have had RA for over 20 years, though only dianosed and treated for ten years. I was on Remicade for nine years - it worked very well, but as it slowly stopped helping my Rheumatologist started me on Rituxan in May of 2009. I have found it has slowed down the progression of my RA a great deal. I have to add that I have always actively followed my doctor's instructions and have participated in water exercises and Qigong classes (more gentle than TiaChi and more involved in using ones mind). For my hands, I have containers of beans and also rice. I heat the beans in a microwave and then move my fingers, making fists - I can hear the cartlege breaking up . . . Also find it very helpful to move all my joints to try and keep as flexible as possible. I do have both knee replacements and one shoulder replacement - working hard to try and hold off the other shoulder replacement as long as possible. I am 80 years old and thankful to be doing as well as I am. I use a pair of walking sticks when I feel a need - though have to admit I do not do much walking.
Posted by: DAMLD2 | January 21, 2012 9:25 AM
Rituxan is an RA drug, not a lupus drug, but thanks for sharing.
Posted by: DeBartolo | January 21, 2012 10:04 AM
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IMHO, the most promising B-cell depletion therapy for lupus has nothing to do with biologic drugs - it's call UVA1 phototherapy. It has been clinically proven to be both highly effective, safe & it's very inexpensive for SLE patients to use at home.
I've been using it myself since 2004 with near miraculous results & I am not alone in that regard. Visit the Lupus Foundation of America's patient message board, and read through the "UVA1 Phototherapy" subject thread, listed in the "Lupus Treatments" subject forum.
You'll also find relevant research posted on my blog, lupusUVA1phototherapy.com ...Thank you....Anthony DeBartolo, Reporter/Editor/Publisher, Hyde Park Media.
Posted by: DeBartolo | December 6, 2011 6:44 PM