Jashin J. Wu, MD, was initially drawn to the study and treatment of psoriasis because he liked the idea of being able to look at a patient and make a diagnosis based mostly on a visual examination, rather than having to delve into labs and imaging. He said, “It seemed really interesting to be able to say ‘this is what it is,’ in most, though not all, cases after just a few seconds.”
Dr Wu found his niche and uncovered some significant psoriasis findings related to comorbidities and inflammation by delving deep into the vast Kaiser Permanente electronic medical records (EMRs).
Dr Wu, who is the founding director of dermatology research and director of the Psoriasis Clinic in the department of dermatology at Kaiser Permanente Los Angeles Medical Center, talks with The Dermatologist about his research and his interest in how the inflammatory effects of psoriasis can impact the entire body. “The fact that we are able to show that patients with psoriasis have different types of comorbidities that were not known before goes to show that systemic inflammation in general is bad,” he said.
Q. What inspired you to choose psoriasis as the subject of your research?
A. When I was a resident, I was already interested in psoriasis. That was just at the beginning of the biologic age, so I felt like there was a lot we could do for patients that could not be done in the past. I wanted to go to a place where I could look through EMRs to look at psoriasis comorbidities—in particular cardiovascular comorbidities and biologics. I decided to go to Kaiser Permanente because I knew they had a large database of patients with psoriasis, as well as patients using tumor necrosis factor (TNF) inhibitors. It would be hard to do what I’m doing anyplace else where they might have only a few hundred thousand patients in their EMR, whereas Kaiser Permanente has millions of patients.
Q. What inspired you to investigate the connection between psoriasis and cardiovascular disease and biologics?
A. Joel Gelfand, MD, had previously shown that patients with psoriasis were more likely to have heart attacks, and if they had severe disease they were even more likely to have heart attacks.1 He used a United Kingdom (UK) database, and at the time they did not have any biologics—all they really had was systemic agents, oral agents, and phototherapy, partly because it was an older database and partly because biologics are restricted much more in the UK. So, I thought: I wonder how the study would change if there were biologics in there and that is what led me to Kaiser Permanente’s EMR.
Q. Can you tell me about some highlights of your research?
A. In my most recent study, we found that treating psoriasis may improve cardiovascular risk. We used the MarketScan databases, and we had about 9000 patients on a TNF inhibitor and about 8500 patients on methotrexate. We wanted to see the number of major cardiovascular events that occurred in each of these cohorts of patients. In the first half of the study, we ran some Kaplan-Meier analyses to come up with a hazard ratio, and found that patients on TNF inhibitors have fewer cardiovascular events than those on methotrexate. The hazard ratio was 0.55, which was a significant finding.2
In the second part of the study, we looked at cumulative effects of these medications over time. The median follow-up period was about 24 months, and we showed that with every 6 months of cumulative exposure, TNF-inhibitor exposure was associated with about 11% risk reduction of cardiovascular events, and that at 3 years of cumulative exposure, there is about a 51% risk reduction for patients on a TNF inhibitor vs methotrexate.2
Several years earlier, I showed something similar using the Kaiser Permanente Southern California EMR.3
Story continues on page 2
Q. What have you found most challenging in this work?
A. In the beginning of my career, the challenges were that I did not know how to work in the system as well as I do now. I do not have any formal training in epidemiology. I had not done EMR research before coming to Kaiser Permanente. All I had was an idea. So, the challenging part was first getting the grant, which I got through Kaiser Permanente. Then the other challenging part was working with the statisticians and programmers to devise the study design to answer the questions that I had.
I have been in practice now for 9 years, so over time I have gotten a lot of experience doing this type of research so I do not need as much help from the statisticians and programmers, other than for them to run the stats. In terms of setting up the study design, I’m able to do that proficiently now.
Q. Why is the psoriasis/comorbidity connection the subject of so much research?
A. People with psoriasis, particularly those with more severe disease have an increased risk for a variety of other health problems, including obesity, diabetes, high blood pressure, high cholesterol, stroke, and heart attack. When you have all this systemic inflammation from psoriasis, there may be affects on many different parts of the body, which is probably driving many of the comorbidities. So now that we have found that treating psoriasis may improve cardiovascular risk, it will be interesting to see if advances in psoriasis treatment will eventually improve the risk of other noncardiovascular risks.
Q. This is an exciting time for psoriasis research. How is this affecting patients with psoriasis?
A. This definitely is an exciting time. There so many different levels of psoriasis research, there is comorbidities research such as those that I am doing; and there are clinical trials for new therapeutic biologics for psoriasis. There are already 7 FDA-approved biologics and probably another 4 coming in the next 2 to 3 years. There is a wealth of options, whereas just a few years ago there were not many at all.
Q. What triggered this cavalcade of options?
A. A few different factors were at play. From a basic science point of view, first, there have been numerous discoveries in the drivers of psoriasis. James Krueger’s, MD, PhD, lab has been instrumental in discovering the key pathways in psoriasis—so it all starts there. Biologics could not have been developed without his pioneering work in the field. Then the pharmaceutical companies went on to develop biologics that inhibit various aspects of the pathways. Hence, the numerous options that are in the pipeline today.
Q. What are some of the psoriasis advances that you are most excited about?
A. I’m very excited about the upcoming class of biologics for psoriasis: These are the 3 IL-23 inhibitors, which are all going through phase 3 FDA trials. They have a bit of an advantage over the current FDA-approved drugs in that they will have longer intervals between doses. Their efficacy is comparable to the IL-17 blockers, which are dosed every 2 to 4 weeks on maintenance, whereas the IL-23 blockers are dosed, either every 8 weeks or every 12 weeks on maintenance. This is significant for patients because longer intervals between doses means fewer reminders that they are sick.
Q. What does the psoriasis landscape of the future look like?
A. I think the IL-23 blockers potentially could be the dominant class in the next decade or two, but after that, honestly, I’m not sure if any biologics will be developed because there are only so many different pathways or cells to target.
References
1. Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296(14):1735-1741.
2. Wu JJ, Guérin A, Sundaram M, Dea K, Cloutier M, Mulani P. Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-α inhibitors versus methotrexate. J Am Acad Dermatol. 2017;76(1):81-90.
3. Wu JJ, Poon KY, Channual JC, Shen AY. Association between tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis. Arch Dermatol. 2012;148(11):1244-1250
Jashin J. Wu, MD, was initially drawn to the study and treatment of psoriasis because he liked the idea of being able to look at a patient and make a diagnosis based mostly on a visual examination, rather than having to delve into labs and imaging. He said, “It seemed really interesting to be able to say ‘this is what it is,’ in most, though not all, cases after just a few seconds.”
Dr Wu found his niche and uncovered some significant psoriasis findings related to comorbidities and inflammation by delving deep into the vast Kaiser Permanente electronic medical records (EMRs).
Dr Wu, who is the founding director of dermatology research and director of the Psoriasis Clinic in the department of dermatology at Kaiser Permanente Los Angeles Medical Center, talks with The Dermatologist about his research and his interest in how the inflammatory effects of psoriasis can impact the entire body. “The fact that we are able to show that patients with psoriasis have different types of comorbidities that were not known before goes to show that systemic inflammation in general is bad,” he said.
Q. What inspired you to choose psoriasis as the subject of your research?
A. When I was a resident, I was already interested in psoriasis. That was just at the beginning of the biologic age, so I felt like there was a lot we could do for patients that could not be done in the past. I wanted to go to a place where I could look through EMRs to look at psoriasis comorbidities—in particular cardiovascular comorbidities and biologics. I decided to go to Kaiser Permanente because I knew they had a large database of patients with psoriasis, as well as patients using tumor necrosis factor (TNF) inhibitors. It would be hard to do what I’m doing anyplace else where they might have only a few hundred thousand patients in their EMR, whereas Kaiser Permanente has millions of patients.
Q. What inspired you to investigate the connection between psoriasis and cardiovascular disease and biologics?
A. Joel Gelfand, MD, had previously shown that patients with psoriasis were more likely to have heart attacks, and if they had severe disease they were even more likely to have heart attacks.1 He used a United Kingdom (UK) database, and at the time they did not have any biologics—all they really had was systemic agents, oral agents, and phototherapy, partly because it was an older database and partly because biologics are restricted much more in the UK. So, I thought: I wonder how the study would change if there were biologics in there and that is what led me to Kaiser Permanente’s EMR.
Q. Can you tell me about some highlights of your research?
A. In my most recent study, we found that treating psoriasis may improve cardiovascular risk. We used the MarketScan databases, and we had about 9000 patients on a TNF inhibitor and about 8500 patients on methotrexate. We wanted to see the number of major cardiovascular events that occurred in each of these cohorts of patients. In the first half of the study, we ran some Kaplan-Meier analyses to come up with a hazard ratio, and found that patients on TNF inhibitors have fewer cardiovascular events than those on methotrexate. The hazard ratio was 0.55, which was a significant finding.2
In the second part of the study, we looked at cumulative effects of these medications over time. The median follow-up period was about 24 months, and we showed that with every 6 months of cumulative exposure, TNF-inhibitor exposure was associated with about 11% risk reduction of cardiovascular events, and that at 3 years of cumulative exposure, there is about a 51% risk reduction for patients on a TNF inhibitor vs methotrexate.2
Several years earlier, I showed something similar using the Kaiser Permanente Southern California EMR.3
Story continues on page 2
Q. What have you found most challenging in this work?
A. In the beginning of my career, the challenges were that I did not know how to work in the system as well as I do now. I do not have any formal training in epidemiology. I had not done EMR research before coming to Kaiser Permanente. All I had was an idea. So, the challenging part was first getting the grant, which I got through Kaiser Permanente. Then the other challenging part was working with the statisticians and programmers to devise the study design to answer the questions that I had.
I have been in practice now for 9 years, so over time I have gotten a lot of experience doing this type of research so I do not need as much help from the statisticians and programmers, other than for them to run the stats. In terms of setting up the study design, I’m able to do that proficiently now.
Q. Why is the psoriasis/comorbidity connection the subject of so much research?
A. People with psoriasis, particularly those with more severe disease have an increased risk for a variety of other health problems, including obesity, diabetes, high blood pressure, high cholesterol, stroke, and heart attack. When you have all this systemic inflammation from psoriasis, there may be affects on many different parts of the body, which is probably driving many of the comorbidities. So now that we have found that treating psoriasis may improve cardiovascular risk, it will be interesting to see if advances in psoriasis treatment will eventually improve the risk of other noncardiovascular risks.
Q. This is an exciting time for psoriasis research. How is this affecting patients with psoriasis?
A. This definitely is an exciting time. There so many different levels of psoriasis research, there is comorbidities research such as those that I am doing; and there are clinical trials for new therapeutic biologics for psoriasis. There are already 7 FDA-approved biologics and probably another 4 coming in the next 2 to 3 years. There is a wealth of options, whereas just a few years ago there were not many at all.
Q. What triggered this cavalcade of options?
A. A few different factors were at play. From a basic science point of view, first, there have been numerous discoveries in the drivers of psoriasis. James Krueger’s, MD, PhD, lab has been instrumental in discovering the key pathways in psoriasis—so it all starts there. Biologics could not have been developed without his pioneering work in the field. Then the pharmaceutical companies went on to develop biologics that inhibit various aspects of the pathways. Hence, the numerous options that are in the pipeline today.
Q. What are some of the psoriasis advances that you are most excited about?
A. I’m very excited about the upcoming class of biologics for psoriasis: These are the 3 IL-23 inhibitors, which are all going through phase 3 FDA trials. They have a bit of an advantage over the current FDA-approved drugs in that they will have longer intervals between doses. Their efficacy is comparable to the IL-17 blockers, which are dosed every 2 to 4 weeks on maintenance, whereas the IL-23 blockers are dosed, either every 8 weeks or every 12 weeks on maintenance. This is significant for patients because longer intervals between doses means fewer reminders that they are sick.
Q. What does the psoriasis landscape of the future look like?
A. I think the IL-23 blockers potentially could be the dominant class in the next decade or two, but after that, honestly, I’m not sure if any biologics will be developed because there are only so many different pathways or cells to target.
References
1. Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296(14):1735-1741.
2. Wu JJ, Guérin A, Sundaram M, Dea K, Cloutier M, Mulani P. Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-α inhibitors versus methotrexate. J Am Acad Dermatol. 2017;76(1):81-90.
3. Wu JJ, Poon KY, Channual JC, Shen AY. Association between tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis. Arch Dermatol. 2012;148(11):1244-1250
Jashin J. Wu, MD, was initially drawn to the study and treatment of psoriasis because he liked the idea of being able to look at a patient and make a diagnosis based mostly on a visual examination, rather than having to delve into labs and imaging. He said, “It seemed really interesting to be able to say ‘this is what it is,’ in most, though not all, cases after just a few seconds.”
Dr Wu found his niche and uncovered some significant psoriasis findings related to comorbidities and inflammation by delving deep into the vast Kaiser Permanente electronic medical records (EMRs).
Dr Wu, who is the founding director of dermatology research and director of the Psoriasis Clinic in the department of dermatology at Kaiser Permanente Los Angeles Medical Center, talks with The Dermatologist about his research and his interest in how the inflammatory effects of psoriasis can impact the entire body. “The fact that we are able to show that patients with psoriasis have different types of comorbidities that were not known before goes to show that systemic inflammation in general is bad,” he said.
Q. What inspired you to choose psoriasis as the subject of your research?
A. When I was a resident, I was already interested in psoriasis. That was just at the beginning of the biologic age, so I felt like there was a lot we could do for patients that could not be done in the past. I wanted to go to a place where I could look through EMRs to look at psoriasis comorbidities—in particular cardiovascular comorbidities and biologics. I decided to go to Kaiser Permanente because I knew they had a large database of patients with psoriasis, as well as patients using tumor necrosis factor (TNF) inhibitors. It would be hard to do what I’m doing anyplace else where they might have only a few hundred thousand patients in their EMR, whereas Kaiser Permanente has millions of patients.
Q. What inspired you to investigate the connection between psoriasis and cardiovascular disease and biologics?
A. Joel Gelfand, MD, had previously shown that patients with psoriasis were more likely to have heart attacks, and if they had severe disease they were even more likely to have heart attacks.1 He used a United Kingdom (UK) database, and at the time they did not have any biologics—all they really had was systemic agents, oral agents, and phototherapy, partly because it was an older database and partly because biologics are restricted much more in the UK. So, I thought: I wonder how the study would change if there were biologics in there and that is what led me to Kaiser Permanente’s EMR.
Q. Can you tell me about some highlights of your research?
A. In my most recent study, we found that treating psoriasis may improve cardiovascular risk. We used the MarketScan databases, and we had about 9000 patients on a TNF inhibitor and about 8500 patients on methotrexate. We wanted to see the number of major cardiovascular events that occurred in each of these cohorts of patients. In the first half of the study, we ran some Kaplan-Meier analyses to come up with a hazard ratio, and found that patients on TNF inhibitors have fewer cardiovascular events than those on methotrexate. The hazard ratio was 0.55, which was a significant finding.2
In the second part of the study, we looked at cumulative effects of these medications over time. The median follow-up period was about 24 months, and we showed that with every 6 months of cumulative exposure, TNF-inhibitor exposure was associated with about 11% risk reduction of cardiovascular events, and that at 3 years of cumulative exposure, there is about a 51% risk reduction for patients on a TNF inhibitor vs methotrexate.2
Several years earlier, I showed something similar using the Kaiser Permanente Southern California EMR.3
Story continues on page 2
Q. What have you found most challenging in this work?
A. In the beginning of my career, the challenges were that I did not know how to work in the system as well as I do now. I do not have any formal training in epidemiology. I had not done EMR research before coming to Kaiser Permanente. All I had was an idea. So, the challenging part was first getting the grant, which I got through Kaiser Permanente. Then the other challenging part was working with the statisticians and programmers to devise the study design to answer the questions that I had.
I have been in practice now for 9 years, so over time I have gotten a lot of experience doing this type of research so I do not need as much help from the statisticians and programmers, other than for them to run the stats. In terms of setting up the study design, I’m able to do that proficiently now.
Q. Why is the psoriasis/comorbidity connection the subject of so much research?
A. People with psoriasis, particularly those with more severe disease have an increased risk for a variety of other health problems, including obesity, diabetes, high blood pressure, high cholesterol, stroke, and heart attack. When you have all this systemic inflammation from psoriasis, there may be affects on many different parts of the body, which is probably driving many of the comorbidities. So now that we have found that treating psoriasis may improve cardiovascular risk, it will be interesting to see if advances in psoriasis treatment will eventually improve the risk of other noncardiovascular risks.
Q. This is an exciting time for psoriasis research. How is this affecting patients with psoriasis?
A. This definitely is an exciting time. There so many different levels of psoriasis research, there is comorbidities research such as those that I am doing; and there are clinical trials for new therapeutic biologics for psoriasis. There are already 7 FDA-approved biologics and probably another 4 coming in the next 2 to 3 years. There is a wealth of options, whereas just a few years ago there were not many at all.
Q. What triggered this cavalcade of options?
A. A few different factors were at play. From a basic science point of view, first, there have been numerous discoveries in the drivers of psoriasis. James Krueger’s, MD, PhD, lab has been instrumental in discovering the key pathways in psoriasis—so it all starts there. Biologics could not have been developed without his pioneering work in the field. Then the pharmaceutical companies went on to develop biologics that inhibit various aspects of the pathways. Hence, the numerous options that are in the pipeline today.
Q. What are some of the psoriasis advances that you are most excited about?
A. I’m very excited about the upcoming class of biologics for psoriasis: These are the 3 IL-23 inhibitors, which are all going through phase 3 FDA trials. They have a bit of an advantage over the current FDA-approved drugs in that they will have longer intervals between doses. Their efficacy is comparable to the IL-17 blockers, which are dosed every 2 to 4 weeks on maintenance, whereas the IL-23 blockers are dosed, either every 8 weeks or every 12 weeks on maintenance. This is significant for patients because longer intervals between doses means fewer reminders that they are sick.
Q. What does the psoriasis landscape of the future look like?
A. I think the IL-23 blockers potentially could be the dominant class in the next decade or two, but after that, honestly, I’m not sure if any biologics will be developed because there are only so many different pathways or cells to target.
References
1. Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296(14):1735-1741.
2. Wu JJ, Guérin A, Sundaram M, Dea K, Cloutier M, Mulani P. Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-α inhibitors versus methotrexate. J Am Acad Dermatol. 2017;76(1):81-90.
3. Wu JJ, Poon KY, Channual JC, Shen AY. Association between tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis. Arch Dermatol. 2012;148(11):1244-1250
