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The Global Rheumatology Alliance: Reviewing Accomplishments—Part 1
Drs Alfred Kim, Jeffrey Sparks, and Jean Liew review the creation and the accomplishments of the Global Rheumatology Alliance in tracking and studying the impact of COVID-19 among patients with inflammatory rheumatic diseases.
Alfred Kim, MD is is director of the Washington University Lupus Clinic and an assistant professor of medicine at Washington University School of Medicine in St. Louis, Missouri. Jeffrey Sparks, MD, is a rheumatologist and research scientist at Brigham and Women's Hospital and an associate professor of medicine at Harvard Medical School in Boston, Massachusetts. Jean Liew, MD, is an assistant professor of medicine in rheumatology at the Boston University School of Medicine.
Transcript:
Dr Alfred Kim: Hello, everyone. My name's Al Kim. I'm an adult rheumatologist at Barnes Jewish Hospital in St. Louis, Missouri, where I'm also the director of the Lupus Center at Washington University School of Medicine. And here today we are going to be talking everything COVID-19 Global Rheumatology Alliance with two of my dearest friends that were core members of this really important organization, Dr. Jeffrey Sparks and Dr. Jean Dr Liew. Jeff, go ahead and introduce yourself.
Dr Jeffrey Sparks: Sure. My name is Jeff Sparks. I'm a rheumatologist at Brigham Women's Hospital in Boston, Massachusetts.
Dr Kim: And Dr Liew
Dr Jean Liew: Hi. I'm an assistant professor in rheumatology at Boston University School of Medicine.
Dr Kim: So I think one of the most exciting things that I ever done in my career, and it may not be ever matched, was being a member of this really amazing organization. And I think I would like to break this up actually in 5 different parts. The very beginning, the genesis of it, is essentially this decentralized science medicine type of concept, was very grassroots. And so let's start off with that. But then I want to evolve into some of the accomplishments like the Hydroxychloroquine Brigade, the core major findings from the alliance, and then we'll wrap up with the discussion that you guys had internally about the decision to wind down the alliance around the time of EULAR 2022. And then we will reminisce at the end about our dear friend, Dr. Phillip Robinson. So, Jean, why don't you go ahead and start off with just the narrative of the genesis of the COVID-19 GRA?
Dr Liew: Okay. So the day or the day before the WHO declared the pandemic in March 2020, the story we've been telling is that Len Calabrese tweeted out whether there was going to be a registry looking at COVID-19 in people with rheumatic disease because the gastroenterology community had started one around IBD. And everyone just responded to that tweet, including the key players, the people who would eventually become the key players, Phillip Robinson in Australia and Jinoos Yazdany at UCSF. So they were immediately saying, "Well, Jinoos can use her infrastructure, and then Phil can use his collaborative spirit, getting lots of people on board and getting all the right people to take on these key roles to build this registry out of nothing and start collecting data on COVID-19 in people with rheumatic disease to answer the questions that were all on our minds." So that was really the beginning.
And in less than 2 weeks, the registry actually opened. So IRB, UCSF figuring out what data we wanted to collect, how to collect it rigorously, building that setup, less than 2 weeks. It was just the quickest anything's ever been done and it held up and collected so much useful data that we are still analyzing.
Dr Kim: Yeah. The genesis story is one that needs to be deeply analyzed because having the ability to put together a global organization with well-defined missions, goals, and of course, the passion of the members, and coordinating these efforts was really remarkable. I remember watching essentially from the sidelines initially on Twitter thinking, "My gosh, this is moving and maturing so fast." I think that though also helped us spark and motivate... no pun intended, Jeffrey... I think really one of the initial probably movements within the COVID-19 Global Rheumatology Alliance, which was our response to Didier Raoult's paper or whatever you call that, which drops in mid-March. And so Jeff, we were texting this. And just for a background, there were some people from Silicon Valley who... some of the Silicon Valley bros that were texting from March 13th to the 16th about hydroxychloroquine because there's in vitro data suggesting it may be antiviral. Then Elon Musk got on board on the 16th, and then the preprint from Raoult's group dropped on the 17th, and then Trump made a comment in a briefing on the 19th.
And I believe it was around that time, Jeff, you actually texted me that evening saying, "We’ve got to do something about this." So I guess take it from there because that weekend from March 20th, which is a Friday, through the 22nd, when we finished it, was an intense period of discussion and a lot of writing for actually a brief commentary.
Dr Sparks: Yeah. I'll say that we're recording this almost exactly 3 years after this all went down. So it's kind of reminiscing. It's an odd feeling. And I remember when things really hit and when the genesis of GRA happened, I happened to be on vacation in Chile, and I remember seeing tweets from Phil and Jinoos, and I was obviously scrambling to get back home because the trip was cut short. And I remember thinking, "Wow. This was bad luck on my part because I really would've liked to have been part of the core group." And it was just circumstances that I was seeing emails... You wait 10 minutes then and things already moved past you. So I was a little bummed that I missed out on the GRA, but I guess there was still opportunity. So back when I actually landed is when the hydroxychloroquine stuff really was coming through and I had learned about things like Zoom and Slack, which were foreign terms to me before then.
Yeah. So I was telling Al about my trials and tribulations on my trip and this Trump conference happened. And I think we both had that lightning moment where this is going to impact our patients and we're a bit skeptical that this is going to actually be useful. And we could just see the momentum going and imagine all of the people hoarding medications. And we really galvanized very quickly and wrote a paper on Google Docs, which was very novel at the time, to write something collaboratively. And incredibly, I think it was within 6, 7 hours, there was a good draft. And within 36 hours, there was a basically final draft. And I don't know if you remember, Al, we submitted that to New England Journal of Medicine. We actually thought it had a good shot, and they quickly rejected it.
Dr Liew: And it got leaked.
Dr Sparks: ... "Oh, right. Maybe we are rheumatologists," put in our place. And then we submitted to Annals of Internal Medicine, and we also got a very quick response. And to our surprise it was, "This is really important." They already had line edits and they said, "Can you get us the final draft in 24 hours?" And it was by far the quickest turnaround I've ever had for a paper. And we knew that we were onto something there.
Dr Kim: Yeah. So actually I do want to come back to the leak because that was actually a little bit crazy. But I'm actually looking back at the Hydroxychloroquine Brigade black channel that Jean had created as the paper was being submitted. And actually from resubmission to acceptance, it was 8 minutes. It was submitted at 7:16 in the morning in Central Time, and it was accepted at 7:24, which is remarkable. But Jean, yeah, you mentioned that while it was under review at the New England Journal, people already had copies of the draft, which was really fascinating.
Dr Liew: And then the other comment is this was novel that we were collaborating and it's maybe a dozen coauthors. We were all writing, and we were writing over each other's stuff. And the only reason it took so long, 3 days... We could have written this in 1 and submitted something, but it took 3 days because everyone wanted it to just be exactly what is something that we could all agree on. So we wrote and rewrote in just cycles 24-7 because people were writing in different time zones across the world. We only took 3 days because we wanted to be send a clear message that we could all agree on, and having a dozen rheumatologists across the world agree on something is difficult.
Dr Kim: Yeah. So for the audience, this piece that we're talking about starts off with the question, “A Rush to Judgment,” and it came out in the Annals of Internal Medicine. The final copy came out in June 16th, that particular issue. So if you guys in the audience want to take a look at that, I was rereading and it's just really interesting to see the initial draft, which I saved, and then the final version, just how amazing it was to be able to work with all these people that were coauthors on it.
And I think that's the other aspect here too that I want to eventually evolve into and then discuss the core accomplishments, is the number of people that I met through the Hydroxychloroquine Brigade, including you, Jean, we've never met before then, really gave me comfort about the future of rheumatology because I didn't know most of the people that we were working with, but we are linked together by this need to make sure that there's civil discourse of the discussion of hydroxychloroquine. Meeting you, Mike Putman, Sebastian Sattui, whole bunch of people that I had never met before and finally met in-person this past year at ACR, was really reassuring.
And actually, again, I mentioned earlier, for me, this was probably going to be the highlight of my career, largely because of the people that I was able to work with. So it was a real honor.
But moving on then to the core accomplishments of the GRA… I don't know how many papers came out of this effort so far. But certainly, I would say 90% of the papers, if not higher, were really first to report various associations of medications, et cetera, risk factors, with a COVID-19 outcome. So I guess I'll just open the floor up to the both of you, some of the core major accomplishments, and then some of the ones that you felt like really hit home for you guys.
Dr Liew: Yeah. I'll start because I want to save the RA paper for Jeff because he loved that. But we had our first paper within a month of the registry opening. So everything happened really quickly, and most of our really big findings from the registry came out within just a few months of that initial period. And then things moved slower after that. So we were the first to note that a higher dose of prednisone use at the time of COVID diagnosis was associated with worse outcomes, bearing in mind that our registry only captured people with rheumatic disease who all had a diagnosis of COVID. So we have no comparators that didn't have COVID. We have no comparators that didn't have a rheumatic disease. But when you compare people who are on a high dose of prednisone versus those who are, say not on prednisone at all, you saw that there was a higher odds of having a bad COVID outcome like hospitalization or death. So we could see that.
Then we saw that disease activity was also associated worse outcomes. We saw that there was an interaction between steroid dose and disease activity, and we saw that there was a signal for rituximab, as you would expect, with B-cell depletion, and worse outcomes with COVID. So these were things that held up over time. They held up across other registries. They held up in population-level studies, including from Scandinavian countries where they are able to collect basically all your confounders that you want. So these are all things that we were the first to show them, and they were replicated across other studies. So Jeff, onto you.
Dr Sparks: Well, I think obviously the physician registry has been the crown jewel of the GRA, and it's really incredible how productive it has been. I think this is the vision that Phil and others had at the very beginning, is let's have a case report form that will be comprehensive but not so imposing so that people will actually enter the data. I've entered a lot of cases in there. It takes as little as 2 minutes, probably as long as 10, and we're able to really find the hard outcomes that patients and clinicians care about. And if you think about... There was obviously a lot of fear at the beginning related to immune suppression and specific medications. And a lot of the findings were actually fairly reassuring, in particular related to TNF inhibitors.
And so at the very beginning, of course, we were clamoring for cases. There weren't that many cases overall. And to cobble together cases at your own institution was really tough. But to do it globally and obviously to share the data quickly, I think was a really great vision. And at the beginning, it was kind of lumping, and as cases became more plentiful, we were able to split, and were able to do papers related to specific medications, specific diseases, specific disease states. And so I was lucky to lead the first disease-specific investigation with Zach Wallace, and we were really interested in medications in a single disease related to rheumatoid arthritis, and really to the best of our ability trying to grapple with the confounding by indication.
So we did really reiterate the finding that rituximab had really high risk for poor outcomes. Not only was it the signal there was just remarkable, but also it was a bit reassuring that the TNF inhibitor patients did pretty well. Abatacept did pretty well. Interleukin-6 inhibitor patients did pretty well, JAK inhibitors probably somewhere in the middle. So I think there's both findings that could reassure them. And there's also findings that really home in on a specific population where you need to think about risk mitigation strategies. And I think it dovetailed nicely into the vaccine era as far as trying to prioritize people and obviously trying to get our patients vaccinated as quickly as possible.
Dr Kim: When I think back about that era, that time, that was one of the most difficult times as a provider, where you had no answers and there was so much fear when these data came out so quickly. I mean, that was a huge accomplishment. I think for me, other core accomplishments really was the shared leadership structure. I felt like every paper had a different set of senior authors, different lead authors doing the effort. Of course, there were so many questions that could have been asked. And again, the speed and the necessity to be able to get the information out really necessitated splitting the responsibilities amongst all the GRA members. But I think that's something that the GRA should be really, really proud about, is just that everyone is going to have a role here. And if you want to take it, just go ahead. We'll help you, and everyone is sure that the rigor of the analyses will hold through in the end will be durable.
Don't miss part two of this podcast with Drs. Al Kim, Jean Liew, and Jeffrey Sparks, as they review the accomplishments of the Global Rheumatology Alliance and remember the late Phil Robinson, who was so instrumental in its creation.
