Alexa Kimball is a professor of dermatology at Harvard Medical School, with a research focus on psoriasis and hidradenitis suppurativa. She has published more than 375 papers, conducted more than 150 clinical trials and has extensive experience in drug development and innovation. Dr. Kimball’s team submitted a research proposal to access Vivli to conduct analysis relevant to their topic, “Effects of adalimumab on inflammation-associated abnormal hematologic patterns in patients with Hidradenitis Suppurativa”. The team’s completed research has recently been presented to the research community in publications including JAMA Dermatology. She sat down with Vivli to tell us more about accessing individual participant data to advance her research, and the potential for using biomarkers to improve clinical decision and treatment support.

Can you tell us a little bit more about your research and what led to your interest in researching this particular topic?

I started my early career studying psoriasis and other chronic inflammatory skin disease. And around probably 2011 or 2012, two things happened. I had a patient who was referred to me just coincidentally, with very severe hidradenitis suppurativa (HS) by a plastic surgeon who wanted help in her care, and at the same time I was asked by a colleague of mine at AbbVie to help design a clinical trial where we could see if we could get a drug approved because no drug had ever been approved. I remember the moment very vividly where I went: oh, my goodness, no one is studying this disease. All the questions I just learned to answer in psoriasis need to be asked. There’ll be different answers, but this is an extraordinary opportunity to find treatments for a really severe disease no one really knows about, but affects, as it turns out, 1% of the population. So, from that moment on, it was all in.

And how would you describe the current state of management of the condition—given that it remains relatively not well known or well studied. And what were you trying to address with the specific question for this research project?

We’ve made enormous progress in HS since I started. We now have three drugs approved—so, really important. But still, I would say, we have a ways to go to get all of our patients to where we would like to see them. The inspiration for these particular papers— actually, three that came through the Vivli research—was that we were looking at some of the more interesting questions that had not really been raised. First we had seen patients who had blood abnormalities like anemia during their disease course, and it improved when they got treated. Being able to look into a big study set that was placebo controlled to demonstrate that, in fact, the anemia and other blood level abnormalities were actually due to inflammation and the disease, not something else, was really important, and important that they improved. We had seen patients, for example, referred for bone marrow biopsies to work them up when, in fact, it was really their underlying disease. So—really helpful in explaining this co-association caused by the inflammation.

The second question we had is that a lot of the studies have very high placebo or high placebo response rates. And what we wanted to see was whether this was because the underlying disease was varying a lot? We were able to use as a surrogate the inflammatory marker CRP to show that some patients in the placebo groups also have improvement in the CRP. That finding suggests that their underlying disease was also improving. So that was just a nice way to biologically confirm that the placebo group was truly improving.

And then the third question was to try to see if CRP could predict who was going to respond and not respond. What we showed is that once you get into higher levels of inflammation, you do reduce your chances of responding. So, while there are good chances of responding in general, people who have the most severe inflammation do have less likelihood of responding. This is important because it helps design of clinical trials and also helps clinicians know what the likelihood of success is going to be, and also may help us eventually pick drugs. 

What do you expect the impact of these findings to be? In management and treatment for patients, and in guiding the course of future research?

Well, hopefully we can spread the word, so patients don’t get unneeded workups for other diseases they don’t have and reinforce that patients with more severe disease absolutely need more aggressive advanced therapy. That can change clinical care in some very important ways as we communicate it to dermatology and our colleagues. In terms of the other two studies—one helps really with clinical trial design, and reaffirms that we need to continue to raise the bar of efficacy with our drugs in order to manage that placebo rate. And then the third one, again, suggests that if you have patients with very high inflammation, you may have to think more aggressively about how you treat them.

Can you tell us a little bit about how you heard about Vivli, and what your experience was like of using the Vivli data repository for this research?

I’m always looking for ways to answer questions I have and getting access to a data set like this is remarkable. For people like me who have questions where we need individual patient level data, and ideally, placebo controlled large trials it’s an amazing resource. It allows us to look at questions that may not be high priorities for sponsors or to go back and answer questions we didn’t think of at the time. So being able to access that information helps us generate papers that will have substantial impact on patient care. It really shows the value of having that information available.

From a technical standpoint it was very easy to work with the group. They followed up with us a lot, so we felt highly cared for while getting through the process of outlining our project. It was all very straightforward and reasonable. And the platform was easy to use, and the teams were really responsive.

Would you say that the direction of your research has been changed or shaped in any way by the results of this research? Has it affected what you’re working on now, for example?

I do have more questions, and I think it has certainly raised awareness for me that there are questions that we will not be able to answer in a single HS clinical trial. Plus being able to aggregate across programs would be immensely valuable for things that are rarer. One of the things I’m trying to do is to encourage more people to open up their data sets like this for us. 

Setting the example really matters and I think these projects help to get the word out about why it is so useful to get this information out for these subsequent analyses. 

Is there anything you would tell other researchers about doing this kind of analysis?

I think it’s just raising awareness that these data sets are out there. Not only did I immediately go look and see what HS ones were there, but I wanted to know what was in psoriasis and what was in atopic dermatitis, and what were in other fields where I might have parallel types of questions. I think that awareness of those possibilities is really helpful as well.

Read more about Dr. Kimball’s research:

Effects of adalimumab on inflammation-associated abnormal hematologic patterns in patients with Hidradenitis Suppurativa (Vivli Research Request 7127)

C-Reactive Protein and Response to Adalimumab in Patients With Hidradenitis Suppurativa (JAMA Dermatology)

Interested in finding out more about how access to Vivli’s data repository can help advance your research? Find out more about how to search and request data.

Lower respiratory tract infections (LRTI) are a frequent complication for elderly patients with heart failure. Non-cardiovascular hospitalizations, including respiratory infections, cause around 50% of the hospitalizations in heart failure patients, making them comparable to cardiovascular hospitalizations in terms of health and resource use impact. However, little is known about the causes and associated prognosis of non-cardiovascular hospitalizations in patients with heart failure.

Empagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor, a class of medicines primarily used to lower blood sugar in adults with type 2 diabetes. In a recently completed study, Dr. João Pedro Ferreira and colleagues aimed to study the potential impact of empagliflozin on LRTI. The research team’s goal was to determine whether empagliflozin could reduce LRTI, due to its capacity to reduce oxidative stress and improve host defense mechanisms.

The research findings indicate that LRTI was frequent in the cohort of enrolled participants, and associated with a poor prognosis. The total number of LRTI events was reduced in the empagliflozin group, compared to placebo.

Using the Vivli platform enabled the research team to include previously unpublished data which were unavailable anywhere else. This research is another addition to the list of benefits of these SGLT2 inhibitor agents; Dr. Ferreira noted that, since heart failure exacerbations and respiratory infections often go “hand-in-hand”, showing that empagliflozin can reduce the incidence of these is good news for patients.

Next Steps

Read more
Non cardiovascular hospitalizations in heart failure and preserved ejection fraction (HFpEF) and the effect of empagliflozin (Vivli Data Request 8933)

Empagliflozin and risk of lower respiratory tract infection in heart failure with mildly reduced and preserved ejection fraction: An EMPEROR-Preserved analysis (European Journal of Heart Failure)

Find out more about requesting data from Vivli