Patient and physician perspectives on IgG4-related disease: diagnosis, management, clinical trials, and advocacy
John Stone, MD, MPH, professor of medicine at Harvard Medical School and the Edward A. Fox chair in Medicine at the Massachusetts General Hospital in Boston, and Andrew Provencher discuss the impacts of IgG4-related disease. Andrew was diagnosed with IgG4-related disease a few years ago and shares his perspective on living with the condition, while Dr. Stone provides guidance on management and treatment. This video was developed in partnership with the IgG4ward! organization.
John Stone, MD, MPH:
I’m a rheumatologist and I have spent almost 2 decades now taking care of people living with a remarkably interesting disease called IgG4-related disease. I’m very pleased and grateful to Mr. Andrew Provencher, who has agreed to join us today and talk a bit about his case.
Andrew, would you introduce yourself?
Andrew Provencher:
Of course. Thanks for having me. My name is Andrew Provencher. I’m 44 years old living with IgG4-related disease.
John Stone, MD, MPH:
Thank you so much for joining us today. It’s very kind and generous of you to be here and tell us about your story, which in many ways is emblematic of IgG4-related disease and one of the ways that it is emblematic of this condition is that it took a while to be diagnosed. In fact, I think it’s fair to say we don’t know exactly when your disease began, but we do know how you came to be diagnosed and that was rather dramatic. I wonder if you could share a little bit about that story when you were diagnosed.
Andrew Provencher:
Sure. This all started for me, I didn’t really notice any prior symptoms leading up to this event, but in June of 2020 I had a mountain bike accident. I was out riding bicycles at a local mountain bike park at a ski resort. When I went over the handlebars, I broke my collar bone in a couple place, broke half my ribs, punctured and collapsed lung. An ambulance ride to the hospital showed they instantly did a CT scan that revealed a lot of lung nodules. When I was in the ER, pretty broken and they were just about to put a chest tube in the emergency room. Doctor told me this looks like a very aggressive form of cancer. I’ve seen this before and this is something you got to get right on and something you can’t drag your feet on.
John Stone, MD, MPH:
You were really feeling very much yourself up until you went over the handlebars and the aftermath of that. You didn’t have anything in terms of lung symptoms, cough, shortness of breath, decrease in energy? You obviously felt well enough to go for a mountain bike ride. You didn’t notice anything before?
Andrew Provencher:
Leading up to this I had probably written off some symptoms to maybe being out of shape and had some shortness of breath, maybe getting a little out of breath going upstairs and whatnot. But I just wrote it off to I need to get into better shape. No light bulbs were popping up saying something’s really wrong here.
John Stone, MD, MPH:
Well, that is one of the extraordinary things about IgG4-related disease. Patients can have a very big disease burden, and I’ve seen your imaging studies of your CT scans that they did in the emergency room there and you had a lot of big pulmonary nodules, yet you really had almost no symptoms. That’s true for patients with disease in other organ systems too. The pancreas, for example, can be involved; patients can have active pancreatitis and they have almost no symptoms. That’s one of the big dangers of this disease; it’s why it took us until 2003 to recognize that it is in fact a unique condition. It’s why the disease causes so much damage before it is diagnosed because it flies under the radar screen for a long time.
You were told that you had cancer. That must have come as quite a blow.
Andrew Provencher:
Correct. Like I said, I’m 44 years old. I thought I was in good health. I have 3 children and a wife at home. A lot was going through my mind when a doctor looked me in the eye and said, “I’ve seen this before. This is an aggressive form of cancer and you got to get on this.” We got out of the hospital, I got home, started healing up my bones and making appointments for all the -ologists, from hematologists to pulmonologists. I feel like we saw every doctor throughout the course of the next months.
John Stone, MD, MPH:
They must have been making plans to do a biopsy at that point to confirm the suspected diagnosis. They were planning on doing that?
Andrew Provencher:
Correct. It started off a little slow with scans and whatnot. I had all my PET scans I had, which would show the highlighted activity, and then I had bronchostomy where they pulled some lymph nodes that showed negative for all the bad things negative for carcinoma. They still weren’t convinced about what it was. After that, after some more doctor visits, some different opinions, I had a thoracic surgeon with a da Vinci robot do a lung biopsy and that showed the same thing, negative for all the negative things.
John Stone, MD, MPH:
That was done through your chest wall with an incision in the skin?
Andrew Provencher:
Correct.
John Stone, MD, MPH:
Not a small procedure.
Andrew Provencher:
No. It was actually 5 robotic fingers that all made different incisions and went in and took what they needed and brought it out. It’s mind-blowing. At this point, I’m riding bicycles 1 minute and the next minute we’re going under all these important robots. Pretty overwhelming.
John Stone, MD, MPH:
You were thinking that you were not likely to live to see your boys grow up?
Andrew Provencher:
Sure. My kids are right now they’re 10, 9, and 7; at the time, they were a couple years younger. The things that go through a father’s head. Questioning…
John Stone, MD, MPH:
Yes. It is a very typical story for patients with IgG4-related disease. The IgG4ward! foundation held a caregivers conversation last week, and 3 out of the 4 patients who were there had stories that very much resembled yours. They had been told initially that they had cancer and it can be cancer in a lot of different kinds of organs because the disease is a multi-organ disease.
In our cohort of about 600 patients now at the Massachusetts General Hospital, we have about 30 patients who’ve undergone modified Whipple procedures, removal of most of the pancreas out of concern for possible pancreatic cancer because of the tendency of IgG4-related disease to cause mass lesions in organs all over the body; cancer is very often the initial diagnosis, which fortunately turns out to be wrong. But it leads to all kinds of anxiety before and even after the diagnosis of IgG4-related disease.
Fast-forward, you finally got to the right diagnosis and what were you told about treatment options? Do you remember?
Andrew Provencher:
At the time when I got my diagnosis, my doctor, he said, “I know what this is. I know how to treat it.” He discussed a couple of different forms of treatment and one of them was with a trial with a B-cell depletion therapy, which I got into. I immediately started a round of steroids with him and shortly after that I got into the trial and started with the double-blind placebo trial. Him or I did not know if I was getting the placebo in the first round. I started with that.
John Stone, MD, MPH:
That is the steroids, which were the treatment you were offered first or the treatment that is offered first for almost all patients across the world. The cornerstone of treatment remains steroids, glucocorticoids. There are many countries in the world where it’s really almost the only therapy that patients can receive. What we have learned about steroids is that they’re very good at high doses, moderate to high doses, meaning at least 40 mg a day of prednisone, equivalent. They’re very effective at controlling the disease and pushing the disease toward remission.
But over time, as the steroids are tapered because they have to be tapered because of the adverse effects, the great majority of patients are ultimately failed by prednisone. That is, they have a recurrence of their disease while they’re still on prednisone or shortly after coming off of prednisone, and then they have to go back on treatment, further treatment again. There are some peculiar characteristics of IgG4-related disease that make it exactly the worst disease to have to use steroids for treatment. This is because the disease very often targets the pancreas and the pancreas of course makes insulin, which is essential for normal blood glucose metabolism. The failure of the pancreas leads to diabetes, and steroids also increase the risk of diabetes by having an adverse effect on glucose metabolism.
Having to use steroids in this disease complicates what can already be a very difficult situation. We’ve therefore looked for other treatment options. There are a host of what we call non-biologic DMARDs; DMARDs is an acronym which stands for disease modifying anti-rheumatic drugs. These are drugs that have been around for 50 or 60 years in many cases. Drugs like methotrexate, mycophenolate mofetil, and they have not been tested thoroughly in randomized, doubled blind, placebo-controlled trials. There is some evidence that they help reduce the amount of steroids that patients need, but really these drugs have been largely quite understudied. My own experience with them is that they seem to work well as long as the prednisone is still on board; when the prednisone comes off, these drugs often don’t appear to be working as well as they were.
We have been looking for other treatment options and the B-cell depletion option, Andrew, is one of the ones that is being investigated thoroughly now. I should pause to thank you very much for your participation in the trial. It is only because of patients like you who agreed to participate in well-designed trials that we are ultimately able to make progress in this disease. I am very pleased to say that the results of that trial that you were in were a very positive result, and the results of that trial are going to be published very shortly in a major medical journal. It’s my hope that that approach using B-cell depletion will become the standard of care for patients with IgG4-related disease. It is only because of the 135 patients, one of whom was you, who agreed to participate in the trial. Thank you for that.
Andrew Provencher:
I appreciate that, Dr. Stone. It truly is an honor. I recently spoke with a doctor in Italy, Emanuele Della-Torre, and since I got into the IgG4-related disease and started learning about it, I have been so grateful for all that’s come my way, but I would stop there. What he told me in Italy, he said, be grateful because all I was doing was just telling this doctor how grateful I was to be part of this and to be part of this moving forward. He told me, “Well be grateful and with that move forward.” It really set me on a course to advocate and to just push this thing forward. Any chance I get, I just want to spread information about it and let others know that there’s a plan in place.
John Stone, MD, MPH:
That is a wonderful way to make lemonade out of lemons because you were given a pretty hefty dose of lemons 4 or 5 years ago when you were diagnosed with this condition that almost no one had heard of. You have come through the other side of it now; you have contributed to knowledge that the human race has about the treatment of this disease and help lead to a new era of therapy. I’m very grateful to you for that.
You mentioned an important word in what you said a minute ago, and that is advocacy. We’ve both become very involved in advocacy for patients with this disease. A little bit over a year ago, it was my honor to found a patient advocacy group for patients with IgG4-related diseases called the IgG4ward! foundation. Over the past year, we’ve been able to get off to a wonderful start, including helping to complete the clinical trial that we mentioned and to play a big role in the 5th International Symposium on IgG4-Related Disease for doctors and investigators, which was held in Milan, organized by Dr. Della-Torre, the physician whom you mentioned.
We’ve also held almost monthly fireside chats for patients or caregivers, conversations. Coming up in just a couple of weeks, we are holding the foundation’s first international patient jamboree called the IgG4ward! Jam. It has been really a wonderful ride over the past year for us in advocacy, and I look forward to what we’re going to accomplish together in the future years.
Andrew Provencher:
I’m looking forward to it as well. It’s amazing. It’s astonishing how the progress that you and the foundation have made. I mean, when I was diagnosed, we looked around on the internet and found maybe 1 or 2 videos and now the information is out there. It’s factual information. It’s really nice, with Dr. Google and the internet, it’s really easy to jump on there and find some things and get concerned, but it’s a nice place with the foundation to have factual information that you can go and trust it. Amazing for a patient.
John Stone, MD, MPH:
Well, thank you. The first goal of the foundation is to be a trusted source of truth for people living with IgG4-related disease.
I wonder if I could ask you, Andrew, now that you have come through treatment and you continue to be on treatment and you continue to be monitored, and that is appropriate because it is possible for the disease to come back. Patients certainly need to be monitored and many need to be treated on an ongoing basis. Are there things that you fear most about the future for yourself with IgG4-related disease? Are there things that still keep you up about this diagnosis at night?
Andrew Provencher:
What the picture looks like for me, 10, 20 years down the road, maybe my own mortality, I kind of question and see what that’s going to look like. I try not to stay there and get lost there, but it is a concern in the back of my mind. For now, maybe I just park that a little to the side and just keep moving forward.
John Stone, MD, MPH:
I think that is exactly the right way to park it; park it on the side. I am confident that if we follow your disease closely and monitor it for recurrence and use treatments effectively and have better treatments as the treatments go by, then this disease is not going to affect your longevity. You will live to see your grandchildren, maybe your great-grandchildren as well. Look forward one day to the ability to understand completely what has caused this disease and then being able to cure it. I do feel like that is something that we can achieve over the course of my career and your career as a patient. It would be wonderful to be able to declare yourself cured one day.
Andrew Provencher:
Yeah, I’m very much so looking forward to that, Dr. Stone. Like I said, I’m grateful to be a part of this grateful. Grateful. Now I’ll take that grateful and move forward with it. Like I said, any way that I can advocate, any way that I can spread information and awareness about the disease, I take an opportunity to do so. I usually am maybe a shy, anxious type who doesn’t really share, and I’m nervous about talking in front of people and whatnot. With this, it just kind of fades away because I’m so passionate about it; I’m living it.
John Stone, MD, MPH:
This is a great way to close. Your case has been a paradigm of IgG4-related disease, and you are really a model about how patients with any disease should respond to it to help not only themselves, but others with the disease as well. Thank you again for taking the time to talk with me today.
Andrew Provencher:
Thank you, Dr. Stone. It truly is an honor.
