Fall down seven times, get up eight times. – Zen proverb
NOTE: This is not a typical treatment course for patients with EGPA/Churg-Strauss (not that there is such a thing as a “typical” EGPA patient!). It has taken several years and much trial and error to find a combination of medications to try and keep my immune system under control and it’s a work in progress. One of the most critical factors is to work with clinicians who are experts in treating patients with your form of vasculitis, especially for rare forms of vasculitis like EGPA/Churg-Strauss. If you are newly diagnosed or having setbacks in your treatment, please do not be discouraged by all of my ups and downs. Instead, I hope what you will see from my treatment course is that: 1) there are always more options for treatment; 2) progress is possible if you work with experienced clinicians and develop a treatment plan you can commit to; and 3) have some patience, it may take a while.
Disclosure: I was a patient in a GSK-sponsored clinical trial from March 2015 to May 2016 testing mepolizumab in EGPA/Churg-Strauss patients. For more details and a full list of disclosures, please see the Disclaimer page.
Flare #7. I am in my seventh flare since I started treatment for EGPA/Churg Strauss three and a half years ago, so I thought the Zen proverb above suits the occasion. Below is a summary of my prednisone tapers and vasculitis flares, and the steps taken to find a combination of immunosuppressive treatments to help control the disease activity. I’ve summarized all of this information in the graph to give a better sense of the literal ups and downs that I’ve been through during my treatment so far. Even though, as my rheumatologist says, “past performance is no indicator of future results”, I’m pretty sure that this is not going to be my last flare. And that’s okay.
Figure legend. Treatment course showing prednisone tapers, clinical symptoms, disease flares, and treatments received from October 2014 – April 2018. The graph shows my prednisone dose (mg/day) in red. I scored my clinical symptoms using the Birmingham Vasculitis Activity Score (BVAS) and BVAS scores are shown on the graph in black. The dotted line across the graph shows the level of 20 mg prednisone per day – my flares always occurred when I reached this point during my first two years of treatment. Flares are noted by red arrows at the top of the graph. The addition of methotrexate, mepolizumab, rituximab, and IVIG treatments are shown at the top of the graph. Note that the first three mepolizumab injections were received while I was enrolled in a double blind clinical trial in which I was randomized to the placebo control group so these injections were saline only, but subsequent monthly mepolizumab injections are the actual drug.
Diagnosis. I was diagnosed with EGPA/Churg-Strauss Syndrome, a rare and potentially life threatening form of vasculitis, in the fall of 2014. At the time, I thought that getting the diagnosis was going to be the hard part. Boy, was I wrong. I was diagnosed by a rheumatologist who is one of the world experts in EGPA/Churg-Strauss and just happens to be located in Philadelphia where I live. My symptoms included chronic rhinosinusitis, adult-onset asthma, pulmonary congestion, bronchiectasis, eosinophilia, mononeuritis (vocal cord paresis), peripheral neuropathy, purpura, hip joint pain, fatigue. Except for eosinophilia, my bloodwork was otherwise normal for inflammatory markers or antibodies, i.e., a normal ESR, normal CRP, and a negative ANCA titer.
Initial treatment approach – prednisone, azathioprine, methotrexate. I was extremely fortunate to get an early diagnosis so I had only suffered some mild nerve and lung damage, but the potential for further damage to my lungs, nerves, and possibly other organs, was high. For this reason, my rheumatologist felt it was important take an aggressive approach to control the inflammation. I would begin a treatment course familiar to many patients with vasculitis – starting with high doses of prednisone, a very powerful and very fast acting anti-inflammatory corticosteroid, followed by the addition of a second drug for maintenance immunosuppression, such as azathioprine or methotrexate. The prednisone would then be tapered gradually once the second drug was on board to control further inflammation. I began at 60 mg prednisone (a target of 1 mg/kg is the typical induction dose and I was 52 kg). I also started taking Bactrim to help prevent any possible respiratory infection due to having a suppressed immune system. Azathioprine was then added, but had to be discontinued within a few weeks due to severe GI intolerance. We switched to methotrexate and chose to use weekly subcutaneous injections to minimize possible GI side effects. After reaching maximum therapeutic doses of methotrexate for a month, we began tapering the prednisone. When I got down to 20 mg per day of prednisone, I had a flare, meaning that symptoms of active disease returned which included peripheral neuropathy, hip joint pain, fatigue, and purpura on my lower legs. Due to the flare, my prednisone was increased to 50 mg per day for one month.
Mepolizumab clinical trial. At this point, it seemed the methotrexate was not enough to control the vasculitis, so my next option would be to add a stronger immunosuppressant such as rituximab, which depletes B cells. Another alternative was an experimental drug, mepolizumab, which was being tested in a Phase III clinical trial to specifically target the eosinophils (the “E” in EGPA). My rheumatologist was participating in the trial and offered me a chance to enroll. This was the first trial of its kind for EGPA. It was a randomized double blind study, meaning that I would be randomly selected to receive mepolizumab or placebo control (saline) but neither my doctor nor I would know whether I was receiving the drug or the placebo control. After discussion with my rheumatologist, I decided to enroll in the trial for three reasons: 1) because the previous clinical trials testing mepolizumab in asthma patients showed a good safety profile and promising results in reducing eosinophil levels; 2) rituximab was a more potent immunosuppressant and therefore was a higher risk than mepolizumab; and 3) logistically, if I did not enroll in the trial at that point, I felt that I might miss the opportunity to access mepolizumab for several more years while it was still being tested and evaluated. The clinical trial would last for a year and had an intense schedule with monthly study visits, lots of blood work, pulmonary function tests, EKGs, and other tests. After evaluations, baseline study visits and labs, and lots of paperwork, I started receiving the monthly shots in March 2015, then started to taper my prednisone levels. After three months, I reached 20 mg prednisone and had flare #2, like clockwork. A biopsy of a fresh spot of purpura on my leg showed leukocytoclastic vasculitis which confirmed the flare. My rheumatologist said that since the treatment was not working, it was not in my best interest to continue in the trial, so he pulled me from the study. This meant that I would stop receiving monthly injections but I would continue with the monthly office visits and labs for follow up and collection of safety data for the remainder of the trial. My rheumatologist and I still did not know whether I had been receiving saline injections as part of the placebo control group or whether I had been receiving injections of mepolizumab. We would find out about a year later, after all of the enrolled patients had completed the trial, that I had been randomized to the placebo control group and had been receiving injections of saline, not mepolizumab.
Next up – rituximab. Now that mepolizumab had been crossed off the list, we proceeded with rituximab. Rituximab had been recently approved by the FDA for GPA/Wegener’s and MPA, two other forms of ANCA-associated vasculitis (AAV) with many similarities to EGPA/Churg-Strauss. Rituximab depletes B cells from the body, which are one of the major types of white blood cells and are important for producing antibodies as well as for regulating other immune cells. Treatment with rituximab would mean my immune system would be compromised and could put me at risk for infections so I continued taking Bactrim prophylactically. I received an induction course of rituximab which consisted of infusions of 375 mg/m2 rituximab once a week for four weeks in July 2015. Then I began my next prednisone taper. Flare #3 occurred when I hit 20 mg prednisone. As before, my symptoms were peripheral neuropathy, hip joint pain, and leg purpura. My labs showed no CD19+ B cells were present in my blood, which meant the rituximab was doing its job. We increased the prednisone up to 40 mg for one month and started another taper all over again, thinking that maybe we needed to give the rituximab some more time to kick in. Flare #4 occurred when I hit 20 mg prednisone. It had now been six months since my induction course of rituximab, so I received a maintenance course of rituximab, which consisted of two infusions of 1 g of rituximab two weeks apart in January 2016, then I started to taper the prednisone again. I continue to receive rituximab infusions every six months. I’ve had a total of five courses of rituximab so far.
IVIG for peripheral neuropathy. Flare #5 occurred when I hit 20 mg of prednisone in February 2016, with the usual symptoms of peripheral neuropathy, hip joint pain, and leg purpura. Since I had just completed a maintenance course of rituximab the month prior, my rheumatologist recommended we add another treatment to help control the peripheral neuropathy. I began receiving monthly IV infusions of immunoglobulin (IVIG), a treatment used for many types of peripheral neuropathy including the vasculitic peripheral neuropathy I was having as part of EGPA/Churg-Strauss vasculitis. Many patients with vasculitis may be receiving IVIG or subcutaneous immunoglobulins (SCIG) to help boost their immune system to fight infections if they are significantly immunosuppressed. But in my case, the IVIG has a different purpose – it is being used to treat the peripheral neuropathy where the IVIG acts like a sponge to block immune complexes that are causing the neuropathy. The IVIG treatments consist of 1 g per day for 2 days in a row every a month. The infusions are long and slow, taking about 6 hours each day.
Success! Then another flare. With the rituximab on board and the monthly IVIG infusions, I was now able to taper my prednisone dose below 20 mg per day for the first time in June 2016. Very exciting indeed! We then did a long and slow taper down to 10 mg prednisone. When I reached 10 mg of prednisone in September, I began to slowly develop symptoms of a flare – the peripheral neuropathy and hip joint pain began to return, and a few leg purpura popped up here and there. Plus, I had developed some sinonasal symptoms, some sputum from my lungs, and was beginning to get shortness of breath when climbing stairs. Since all of the organ systems involved at the time of my diagnosis were now showing symptoms of disease activity, it seemed that I had reached my limit and I did not think I would be able to maintain my prednisone dose at 10 mg per day.
Mepolizumab – this time for real. It was now September 2016. The mepolizumab study had recently concluded, and I was eligible to receive mepolizumab injections through a long term access program available to patients who had been enrolled in the clinical trial. My rheumatologist and I discussed adding mepolizumab to see whether it could help stabilize the flares. Since mepolizumab had shown good results with controlling lung symptoms due to eosinophil activity, I was eager to put mepolizumab to the test and see what it could do for the respiratory symptoms I was having. We decided to keep my prednisone dose at 10 mg per day and add the mepolizumab,
A year at 10 mg prednisone. The mepolizumab did the trick. I was able to hold on at 10 mg of prednisone while I started receiving monthly mepolizumab shots (300 mg subQ/month). The respiratory symptoms began to subside after the second shot, then the peripheral neuropathy gradually subsided as well. In addition to the daily prednisone, I was now receiving the following combination of medications: rituximab every six months, monthly IVIG infusions, monthly mepolizumab shots. These drugs taken together allowed me to minimize the prednisone dose, which I was able to continue at 10 mg prednisone per day for twelve months.
As good as it gets? After being on a stable regimen for a whole year, my rheumatologist and I had an in depth discussion in September 2017 about my treatment goals. Given all of the ups and downs I had before, being on a stable regimen was great, but I was still relying on several powerful immunosuppressants, each of which has risks of side effects and long term toxicities. So it is important to minimize exposure and always be cautious of overmedication. After a year of stable chemically induced remission, it was time to try and reduce one of the medications. We ruled out any changes in rituximab or mepolizumab and focused on IVIG or prednisone. We chose prednisone, the drug with the biggest impact on long term toxicity and my quality of life. I started a slow and incremental taper to 5 mg and held at 5 mg prednisone until March 2018. During this time, symptoms of a flare began to develop including peripheral neuropathy, hip joint pain, mild sputum production, and sinonasal symptoms. In April, I could no longer ignore the increasing symptoms any longer and flare #7 became “official”.
What’s next? It’s now May of 2018. Due to the flare last month, I had to increase my prednisone to 40 mg per day for a month. I am now tapering my way back down to 10 mg prednisone and will hold there for a while. I’ll continue with the monthly IVIG infusions and the monthly mepolizumab shots. I’ll be due for another maintenance course of rituximab in July. My rheumatologist and I will revisit the treatment plan every three months and reevaluate when we should try and make any adjustments. Maybe we will try to reduce the prednisone below 10 mg again and maybe next time it will work out. If not, no problem, we’ll try it again or we’ll try something else. If at first you don’t succeed, try try again.
What is my advice for patients trying to find a treatment plan that works for them? As you can see from the graph, my treatment course looks like quite an ordeal. What I see in the graph is the power of the patient working in close collaboration with the clinical care team. I believe that I could only accomplish this because of my partnership with my rheumatologist, his expertise in treating patients with EGPA/Churg-Strauss, and the trust and communication we have built during this time. If you feel that your clinician is not giving you what you need, or that you may have run out of treatment options, please consider another opinion with an experienced clinician who may have more options for you. Think about your own goals for your treatment plan and don’t stop until you are satisfied that you are doing everything possible to try to meet those goals.
For more about my disease course. For a summary of my diagnosis with EGPA/Churg-Strauss Syndrome, see here.