My rheumatologist said it is time to give up and seek a new drug for my lupus. After over six months of appeals trying to get infusions of Rituxan (Rituximab) approved that I had in a clinical trial 5 years ago, the insurance door is now shut. We hoped to get approval again because of my dramatic improvement and near-remission after two 1,000 mg infusions of the biologic drug Rituxan. Costs for those infusions were split between the drug company clinical trial for the medication and my insurance company for the infusion center and procedures. It made sense to use a drug again that worked so amazingly well. Lack of FDA approval of Rituxan for use in lupus was the insurmountable bar to getting it approved.
What did Rituxan Do?
What did Rituxan do that helped me so much? Let’s talk briefly about the science behind the medicines.
Rituxan is a murine monoclonal antibody. It worked by killing the B cells in my blood causing the auto-immune response in lupus. B cells make antibodies that turn the immune system against unwanted invaders, and unfortunately in lupus, also against the body’s own cells.
B cells are lymphocytes with a role in immune response that create immune antibodies. B cells are receptors for Blys proteins (B Lymphocyte Stimulator 285-amino acid long peptide glycoproteins) made by Myeloid stem cells in bone marrow. Blys stimulate the B cells to produce auto-immune antibodies. The first medication trial that successfully met its goals in treating lupus targeted Blys cells, destroying them earlier in the auto-immune process. Controlling Blys interrupts the auto-immune response one step earlier than Rituxan does by depleting B cells.
Rituxan does not kill B cells in certain tissues or “baby” B cells that are still developing in bone marrow. As a result, somewhere after about 4-6 months, the fledgling B cells matured and ventured out from my bone marrow back into my blood stream to do their job again. However, this time, the new generation of B cells was acting much more normally. The escalation of my lupus that had progressed over years to a multi-organ damaging severity was reset back to a moderate level near the beginning.
My improvement was simply amazing, and Lupus had suddenly changed its severity and course:
- Liver damage stopped
- Central nervous system involvement quieted
- Arthritis join pain and inflammation disappeared
- Colon inflammation stopped
- Mouth and nose ulcers vanished
- Dry mouth and eye symptoms resolved
- Discoid and malar rashes were gone
- Malaise went away
- Fatigue was almost absent
All of these improvements began to happen even before having a the second infusion 4 weeks after the first. The change was very dramatic and incredible. For the first time in over twenty-five years I awoke nearly every morning pain-free, clear-headed and feeling good. After almost ten years, I no longer took the cancer and transplant anti-rejection drugs Methotrexate and Imuran, nor did I need Ultram for pain. My steroids reduced to a maintenance dose of 5 mg of prednisone per day. For the first time in over twenty-five years I was able to stop taking the anti-inflammatory drug Sulindac, which I needed constantly to prevent my fingers joints from ballooning to double their normal size due to my lupus arthritis.
Why didn’t Rituxan get FDA approval?
Unfortunately, the clinical trials (including the one that helped me) failed to meet their specified goals and were inconclusive. However, researchers learned how to improve their clinical trial methods from those failures. The failures were not necessary due to Rituxan’s failure to help patients, but rather due to the inability to prove conclusively that the clinical trials provided specific answers. They realized that clinical trial design needed modification to get conclusive results.
The patients in the Rituxan clinical trials were using a number of other drug treatments at the same time. This weakened the researcher’s ability to decide if improvement was because of Rituxan or the other drugs the patients took for their lupus during the clinical trials. Many were taking chemotherapy drugs, and were using prednisone as needed to suppress lupus flares. Generally many patients improved over the trial, but it was impossible to prove which drug had helped them get better.
We already know that it works, and is now FDA approved for rheumatoid arthritis. Most lupus treatments are borrowed from treatments successfully used for rheumatoid arthritis. I hope that more testing of Rituxan for lupus happens in the future.
What is next?
My doctor is now submitting a request for approval of the new biologic lupus drug, Benlysta. The first clinical trials for lupus treatment that have ever worked were testing Benlysta, and now the FDA approved it specifically for treating Lupus in March of this year. Benylsta works similarly to Rituxan, and it is also a monoclonal antibody. It targets the immune system one step earlier in the auto-inflammatory response, causing reduction of Blys. This reduces the number of triggers that activate B cells in lupus. The studies show that Benlysta helps many lupus patients, although the results don’t sound as dramatic as those that I received after Rituxan. My doctor anticipates being able to convince the insurance company to pay the five-figure annual costs for Benlysta infusions.
If approved, there will likely be three 1-hour infusions, two weeks apart, and then monthly after that. I am encouraged and anticipating that I may soon be feeling better. You can find out more about Benlysta at the following sites: