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Imagine a patient suffering with horrible psoriasis for decades having failed “every available treatment.” Imagine him living all that time with “flaking, cracking, painful, itchy skin,” only to develop cirrhosis after exposure to toxic therapies.
Then imagine the experience for that patient when, 2 weeks after initiating treatment with a new interleukin-17 inhibitor, his skin clears completely.
“Two weeks later it’s all gone – it was a moment to behold,” said Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, who had cared for the man for many years before a psoriasis treatment revolution of sorts took the field of dermatology by storm.
“The progress has been breathtaking – there’s no other way to describe it – and it feels like a miracle every time I see a new patient who has tough disease and I have all these things to offer them,” he continued. “For most patients, I can really help them and make a major difference in their life.”
said Mark Lebwohl, MD, Waldman professor of dermatology and chair of the Kimberly and Eric J. Waldman department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Lebwohl recounted some of his own experiences with psoriasis patients before the advent of treatments – particularly biologics – that have transformed practice.
There was a time when psoriasis patients had little more to turn to than the effective – but “disgusting” – Goeckerman Regimen involving cycles of UVB light exposure and topical crude coal tar application. Initially, the regimen, which was introduced in the 1920s, was used around the clock on an inpatient basis until the skin cleared, Dr. Lebwohl said.
In the 1970s, the immunosuppressive chemotherapy drug methotrexate became the first oral systemic therapy approved for severe psoriasis. For those with disabling disease, it offered some hope for relief, but only about 40% of patients achieved at least a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75), he said, adding that they did so at the expense of the liver and bone marrow. “But it was the only thing we had for severe psoriasis other than light treatments.”
In the 1980s and 1990s, oral retinoids emerged as a treatment for psoriasis, and the immunosuppressive drug cyclosporine used to prevent organ rejection in some transplant patients was found to clear psoriasis in affected transplant recipients. Although they brought relief to some patients with severe, disabling disease, these also came with a high price. “It’s not that effective, and it has lots of side effects ... and causes kidney damage in essentially 100% of patients,” Dr. Lebwohl said of cyclosporine.
“So we had treatments that worked, but because the side effects were sufficiently severe, a lot of patients were not treated,” he said.
Enter the biologics era
The early 2000s brought the first two approvals for psoriasis: alefacept (Amevive), a “modestly effective, but quite safe” immunosuppressive dimeric fusion protein approved in early 2003 for moderate to severe plaque psoriasis, and efalizumab (Raptiva), a recombinant humanized monoclonal antibody approved in October 2003; both were T-cell–targeted therapies. The former was withdrawn from the market voluntarily as newer agents became available, and the latter was withdrawn in 2009 because of a link with development of progressive multifocal leukoencephalopathy.
Tumor necrosis factor (TNF) blockers, which had been used effectively for RA and Crohn’s disease, emerged next, and were highly effective, much safer than the systemic treatments, and gained “very widespread use,” Dr. Lebwohl said.
His colleague Alice B. Gottlieb, MD, PhD, was among the pioneers in the development of TNF blockers for the treatment of psoriasis. Her seminal, investigator-initiated paper on the efficacy and safety of infliximab (Remicade) monotherapy for plaque-type psoriasis published in the Lancet in 2001 helped launch the current era in which many psoriasis patients achieve 100% PASI responses with limited side effects, he said, explaining that subsequent research elucidated the role of IL-12 and -23 – leading to effective treatments like ustekinumab (Stelara), and later IL-17, which is, “in fact, the molecule closest to the pathogenesis of psoriasis.”
“If you block IL-17, you get rid of psoriasis,” he said, noting that there are now several companies with approved antibodies to IL-17. “Taltz [ixekizumab] and Cosentyx [secukinumab] are the leading ones, and Siliq [brodalumab] blocks the receptor for IL-17, so it is very effective.”
Another novel biologic – bimekizumab – is on the horizon. It blocks both IL-17a and IL-17f, and appears highly effective in psoriasis and psoriatic arthritis (PsA). “Biologics were the real start of the [psoriasis treatment] revolution,” he said. “When I started out I would speak at patient meetings and the patients were angry at their physicians; they thought they weren’t aggressive enough, they were very frustrated.”
Dr. Lebwohl described patients he would see at annual National Psoriasis Foundation meetings: “There were patients in wheel chairs, because they couldn’t walk. They would be red and scaly all over ... you could have literally swept up scale like it was snow after one of those meetings.
“You go forward to around 2010 – nobody’s in wheelchairs anymore, everybody has clear skin, and it’s become a party; patients are no longer angry – they are thrilled with the results they are getting from much safer and much more effective drugs,” he said. “So it’s been a pleasure taking care of those patients and going from a very difficult time of treating them, to a time where we’ve done a great job treating them.”
Dr. Lebwohl noted that a “large number of dermatologists have been involved with the development of these drugs and making sure they succeed, and that has also been a pleasure to see.”
Dr. Gottlieb, who Dr. Lebwohl has described as “a superstar” in the fields of dermatology and rheumatology, is one such researcher. In an interview, she looked back on her work and the ways that her work “opened the field,” led to many of her trainees also doing “great work,” and changed the lives of patients.
“It’s nice to feel that I really did change, fundamentally, how psoriasis patients are treated,” said Dr. Gottlieb, who is a clinical professor in the department of dermatology at the Icahn School of Medicine at Mount Sinai. “That obviously feels great.”
She recalled a patient – “a 6-foot-5 biker with bad psoriasis” – who “literally, the minute the door closed, he was crying about how horrible his disease was.”
“And I cleared him ... and then you get big hugs – it just feels extremely good ... giving somebody their life back,” she said.
Dr. Gottlieb has been involved in much of the work in developing biologics for psoriasis, including the ongoing work with bimekizumab for PsA as mentioned by Dr. Lebwohl.
If the phase 2 data with bimekizumab are replicated in the ongoing phase 3 trials now underway at her center, “that can really raise the bar ... so if it’s reproducible, it’s very exciting.”
“It’s exciting to have an IL-23 blocker that, at least in clinical trials, showed inhibition of radiographic progression [in PsA],” she said. “That’s guselkumab those data are already out, and I was involved with that.”
The early work of Dr. Gottlieb and others has also “spread to other diseases,” like hidradenitis suppurativa and atopic dermatitis, she said, noting that numerous studies are underway.
Aside from curing all patients, her ultimate goal is getting to a point where psoriasis has no effect on patients’ quality of life.
“And I see it already,” she said. “It’s happening, and it’s nice to see that it’s happening in children now, too; several of the drugs are approved in kids.”
Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, also a prolific researcher – and chair of the guidelines committee that published two new sets of guidelines for psoriasis treatment in 2019 – said that the field of dermatology was “late to the biologic evolution,” as many of the early biologics were first approved for PsA.
“But over the last 10 years, things have changed dramatically,” he said. “After that we suddenly leapt ahead of everybody. ... We now have 11 biologic drugs approved for psoriasis, which is more than any other disease has available.”
It’s been “highly exciting” to see this “evolution and revolution,” he commented, adding that one of the next challenges is to address the comorbidities, such as cardiovascular disease, associated with psoriasis.
“The big question now ... is if you improve skin and you improve joints, can you potentially reduce the risk of coronary artery disease,” he said. “Everybody is looking at that, and to me it’s one of the most exciting things that we’re doing.”
Work is ongoing to look at whether the IL-17s and IL-23s have “other indications outside of the skin and joints,” both within and outside of dermatology.
Like Dr. Gottlieb, Dr. Menter also mentioned the potential for hidradenitis suppurativa, and also for a condition that is rarely discussed or studied: genital psoriasis. Ixekizumab has recently been shown to work in about 75% of patients with genital psoriasis, he noted.
Another important area of research is the identification of biomarkers for predicting response and relapse, he said. For now, biomarker research has disappointed, he added, predicting that it will take at least 3-5 years before biomarkers to help guide treatment are identified.
Indeed, Dr. Gelfand, who also is director of the Psoriasis and Phototherapy Treatment Center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, agreed there is a need for research to improve treatment selection.
Advances are being made in genetics – with more than 80 different genes now identified as being related to psoriasis – and in medical informatics – which allow thousands of patients to be followed for years, he said, noting that this could elucidate immunopathological features that can improve treatments, predict and prevent comorbidity, and further improve outcomes.
“We also need care that is more patient centered,” he said, describing the ongoing pragmatic LITE trial of home- or office-based phototherapy for which he is the lead investigator, and other studies that he hopes will expand access to care.
Kenneth Brian Gordon, MD, chair and professor of dermatology at the Medical College of Wisconsin, Milwaukee, whose career started in the basic science immunology arena, added the need for expanding benefit to patients with more-moderate disease. Like Dr. Menter, he identified psoriasis as the area in medicine that has had the greatest degree of advancement, except perhaps for hepatitis C.
He described the process not as a “bench-to-bedside” story, but as a bedside-to-bench, then “back-to-bedside” story.
It was really about taking those early T-cell–targeted biologics and anti-TNF agents from bedside to bench with the realization of the importance of the IL-23 and IL-17 pathways, and that understanding led back to the bedside with the development of the newest agents – and to a “huge difference in patient’s lives.”
“But we’ve gotten so good at treating patients with severe disease ... the question now is how to take care of those with more-moderate disease,” he said, noting that a focus on cost and better delivery systems will be needed for that population.
That research is underway, and the future looks bright – and clear.
“I think with psoriasis therapy and where we’ve come in the last 20 years ... we have a hard time remembering what it was like before we had biologic agents” he said. “Our perspective has changed a lot, and sometimes we forget that.”
In fact, “psoriasis has sort of dragged dermatology into the world of modern clinical trial science, and we can now apply that to all sorts of other diseases,” he said. “The psoriasis trials were the first really well-done large-scale trials in dermatology, and I think that has given dermatology a real leg up in how we do clinical research and how we do evidence-based medicine.”
All of the doctors interviewed for this story have received funds and/or honoraria from, consulted with, are employed with, or served on the advisory boards of manufacturers of biologics. Dr. Gelfand is a copatent holder of resiquimod for treatment of cutaneous T-cell lymphoma and is deputy editor of the Journal of Investigative Dermatology.
Imagine a patient suffering with horrible psoriasis for decades having failed “every available treatment.” Imagine him living all that time with “flaking, cracking, painful, itchy skin,” only to develop cirrhosis after exposure to toxic therapies.
Then imagine the experience for that patient when, 2 weeks after initiating treatment with a new interleukin-17 inhibitor, his skin clears completely.
“Two weeks later it’s all gone – it was a moment to behold,” said Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, who had cared for the man for many years before a psoriasis treatment revolution of sorts took the field of dermatology by storm.
“The progress has been breathtaking – there’s no other way to describe it – and it feels like a miracle every time I see a new patient who has tough disease and I have all these things to offer them,” he continued. “For most patients, I can really help them and make a major difference in their life.”
said Mark Lebwohl, MD, Waldman professor of dermatology and chair of the Kimberly and Eric J. Waldman department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Lebwohl recounted some of his own experiences with psoriasis patients before the advent of treatments – particularly biologics – that have transformed practice.
There was a time when psoriasis patients had little more to turn to than the effective – but “disgusting” – Goeckerman Regimen involving cycles of UVB light exposure and topical crude coal tar application. Initially, the regimen, which was introduced in the 1920s, was used around the clock on an inpatient basis until the skin cleared, Dr. Lebwohl said.
In the 1970s, the immunosuppressive chemotherapy drug methotrexate became the first oral systemic therapy approved for severe psoriasis. For those with disabling disease, it offered some hope for relief, but only about 40% of patients achieved at least a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75), he said, adding that they did so at the expense of the liver and bone marrow. “But it was the only thing we had for severe psoriasis other than light treatments.”
In the 1980s and 1990s, oral retinoids emerged as a treatment for psoriasis, and the immunosuppressive drug cyclosporine used to prevent organ rejection in some transplant patients was found to clear psoriasis in affected transplant recipients. Although they brought relief to some patients with severe, disabling disease, these also came with a high price. “It’s not that effective, and it has lots of side effects ... and causes kidney damage in essentially 100% of patients,” Dr. Lebwohl said of cyclosporine.
“So we had treatments that worked, but because the side effects were sufficiently severe, a lot of patients were not treated,” he said.
Enter the biologics era
The early 2000s brought the first two approvals for psoriasis: alefacept (Amevive), a “modestly effective, but quite safe” immunosuppressive dimeric fusion protein approved in early 2003 for moderate to severe plaque psoriasis, and efalizumab (Raptiva), a recombinant humanized monoclonal antibody approved in October 2003; both were T-cell–targeted therapies. The former was withdrawn from the market voluntarily as newer agents became available, and the latter was withdrawn in 2009 because of a link with development of progressive multifocal leukoencephalopathy.
Tumor necrosis factor (TNF) blockers, which had been used effectively for RA and Crohn’s disease, emerged next, and were highly effective, much safer than the systemic treatments, and gained “very widespread use,” Dr. Lebwohl said.
His colleague Alice B. Gottlieb, MD, PhD, was among the pioneers in the development of TNF blockers for the treatment of psoriasis. Her seminal, investigator-initiated paper on the efficacy and safety of infliximab (Remicade) monotherapy for plaque-type psoriasis published in the Lancet in 2001 helped launch the current era in which many psoriasis patients achieve 100% PASI responses with limited side effects, he said, explaining that subsequent research elucidated the role of IL-12 and -23 – leading to effective treatments like ustekinumab (Stelara), and later IL-17, which is, “in fact, the molecule closest to the pathogenesis of psoriasis.”
“If you block IL-17, you get rid of psoriasis,” he said, noting that there are now several companies with approved antibodies to IL-17. “Taltz [ixekizumab] and Cosentyx [secukinumab] are the leading ones, and Siliq [brodalumab] blocks the receptor for IL-17, so it is very effective.”
Another novel biologic – bimekizumab – is on the horizon. It blocks both IL-17a and IL-17f, and appears highly effective in psoriasis and psoriatic arthritis (PsA). “Biologics were the real start of the [psoriasis treatment] revolution,” he said. “When I started out I would speak at patient meetings and the patients were angry at their physicians; they thought they weren’t aggressive enough, they were very frustrated.”
Dr. Lebwohl described patients he would see at annual National Psoriasis Foundation meetings: “There were patients in wheel chairs, because they couldn’t walk. They would be red and scaly all over ... you could have literally swept up scale like it was snow after one of those meetings.
“You go forward to around 2010 – nobody’s in wheelchairs anymore, everybody has clear skin, and it’s become a party; patients are no longer angry – they are thrilled with the results they are getting from much safer and much more effective drugs,” he said. “So it’s been a pleasure taking care of those patients and going from a very difficult time of treating them, to a time where we’ve done a great job treating them.”
Dr. Lebwohl noted that a “large number of dermatologists have been involved with the development of these drugs and making sure they succeed, and that has also been a pleasure to see.”
Dr. Gottlieb, who Dr. Lebwohl has described as “a superstar” in the fields of dermatology and rheumatology, is one such researcher. In an interview, she looked back on her work and the ways that her work “opened the field,” led to many of her trainees also doing “great work,” and changed the lives of patients.
“It’s nice to feel that I really did change, fundamentally, how psoriasis patients are treated,” said Dr. Gottlieb, who is a clinical professor in the department of dermatology at the Icahn School of Medicine at Mount Sinai. “That obviously feels great.”
She recalled a patient – “a 6-foot-5 biker with bad psoriasis” – who “literally, the minute the door closed, he was crying about how horrible his disease was.”
“And I cleared him ... and then you get big hugs – it just feels extremely good ... giving somebody their life back,” she said.
Dr. Gottlieb has been involved in much of the work in developing biologics for psoriasis, including the ongoing work with bimekizumab for PsA as mentioned by Dr. Lebwohl.
If the phase 2 data with bimekizumab are replicated in the ongoing phase 3 trials now underway at her center, “that can really raise the bar ... so if it’s reproducible, it’s very exciting.”
“It’s exciting to have an IL-23 blocker that, at least in clinical trials, showed inhibition of radiographic progression [in PsA],” she said. “That’s guselkumab those data are already out, and I was involved with that.”
The early work of Dr. Gottlieb and others has also “spread to other diseases,” like hidradenitis suppurativa and atopic dermatitis, she said, noting that numerous studies are underway.
Aside from curing all patients, her ultimate goal is getting to a point where psoriasis has no effect on patients’ quality of life.
“And I see it already,” she said. “It’s happening, and it’s nice to see that it’s happening in children now, too; several of the drugs are approved in kids.”
Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, also a prolific researcher – and chair of the guidelines committee that published two new sets of guidelines for psoriasis treatment in 2019 – said that the field of dermatology was “late to the biologic evolution,” as many of the early biologics were first approved for PsA.
“But over the last 10 years, things have changed dramatically,” he said. “After that we suddenly leapt ahead of everybody. ... We now have 11 biologic drugs approved for psoriasis, which is more than any other disease has available.”
It’s been “highly exciting” to see this “evolution and revolution,” he commented, adding that one of the next challenges is to address the comorbidities, such as cardiovascular disease, associated with psoriasis.
“The big question now ... is if you improve skin and you improve joints, can you potentially reduce the risk of coronary artery disease,” he said. “Everybody is looking at that, and to me it’s one of the most exciting things that we’re doing.”
Work is ongoing to look at whether the IL-17s and IL-23s have “other indications outside of the skin and joints,” both within and outside of dermatology.
Like Dr. Gottlieb, Dr. Menter also mentioned the potential for hidradenitis suppurativa, and also for a condition that is rarely discussed or studied: genital psoriasis. Ixekizumab has recently been shown to work in about 75% of patients with genital psoriasis, he noted.
Another important area of research is the identification of biomarkers for predicting response and relapse, he said. For now, biomarker research has disappointed, he added, predicting that it will take at least 3-5 years before biomarkers to help guide treatment are identified.
Indeed, Dr. Gelfand, who also is director of the Psoriasis and Phototherapy Treatment Center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, agreed there is a need for research to improve treatment selection.
Advances are being made in genetics – with more than 80 different genes now identified as being related to psoriasis – and in medical informatics – which allow thousands of patients to be followed for years, he said, noting that this could elucidate immunopathological features that can improve treatments, predict and prevent comorbidity, and further improve outcomes.
“We also need care that is more patient centered,” he said, describing the ongoing pragmatic LITE trial of home- or office-based phototherapy for which he is the lead investigator, and other studies that he hopes will expand access to care.
Kenneth Brian Gordon, MD, chair and professor of dermatology at the Medical College of Wisconsin, Milwaukee, whose career started in the basic science immunology arena, added the need for expanding benefit to patients with more-moderate disease. Like Dr. Menter, he identified psoriasis as the area in medicine that has had the greatest degree of advancement, except perhaps for hepatitis C.
He described the process not as a “bench-to-bedside” story, but as a bedside-to-bench, then “back-to-bedside” story.
It was really about taking those early T-cell–targeted biologics and anti-TNF agents from bedside to bench with the realization of the importance of the IL-23 and IL-17 pathways, and that understanding led back to the bedside with the development of the newest agents – and to a “huge difference in patient’s lives.”
“But we’ve gotten so good at treating patients with severe disease ... the question now is how to take care of those with more-moderate disease,” he said, noting that a focus on cost and better delivery systems will be needed for that population.
That research is underway, and the future looks bright – and clear.
“I think with psoriasis therapy and where we’ve come in the last 20 years ... we have a hard time remembering what it was like before we had biologic agents” he said. “Our perspective has changed a lot, and sometimes we forget that.”
In fact, “psoriasis has sort of dragged dermatology into the world of modern clinical trial science, and we can now apply that to all sorts of other diseases,” he said. “The psoriasis trials were the first really well-done large-scale trials in dermatology, and I think that has given dermatology a real leg up in how we do clinical research and how we do evidence-based medicine.”
All of the doctors interviewed for this story have received funds and/or honoraria from, consulted with, are employed with, or served on the advisory boards of manufacturers of biologics. Dr. Gelfand is a copatent holder of resiquimod for treatment of cutaneous T-cell lymphoma and is deputy editor of the Journal of Investigative Dermatology.
Imagine a patient suffering with horrible psoriasis for decades having failed “every available treatment.” Imagine him living all that time with “flaking, cracking, painful, itchy skin,” only to develop cirrhosis after exposure to toxic therapies.
Then imagine the experience for that patient when, 2 weeks after initiating treatment with a new interleukin-17 inhibitor, his skin clears completely.
“Two weeks later it’s all gone – it was a moment to behold,” said Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, who had cared for the man for many years before a psoriasis treatment revolution of sorts took the field of dermatology by storm.
“The progress has been breathtaking – there’s no other way to describe it – and it feels like a miracle every time I see a new patient who has tough disease and I have all these things to offer them,” he continued. “For most patients, I can really help them and make a major difference in their life.”
said Mark Lebwohl, MD, Waldman professor of dermatology and chair of the Kimberly and Eric J. Waldman department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Lebwohl recounted some of his own experiences with psoriasis patients before the advent of treatments – particularly biologics – that have transformed practice.
There was a time when psoriasis patients had little more to turn to than the effective – but “disgusting” – Goeckerman Regimen involving cycles of UVB light exposure and topical crude coal tar application. Initially, the regimen, which was introduced in the 1920s, was used around the clock on an inpatient basis until the skin cleared, Dr. Lebwohl said.
In the 1970s, the immunosuppressive chemotherapy drug methotrexate became the first oral systemic therapy approved for severe psoriasis. For those with disabling disease, it offered some hope for relief, but only about 40% of patients achieved at least a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75), he said, adding that they did so at the expense of the liver and bone marrow. “But it was the only thing we had for severe psoriasis other than light treatments.”
In the 1980s and 1990s, oral retinoids emerged as a treatment for psoriasis, and the immunosuppressive drug cyclosporine used to prevent organ rejection in some transplant patients was found to clear psoriasis in affected transplant recipients. Although they brought relief to some patients with severe, disabling disease, these also came with a high price. “It’s not that effective, and it has lots of side effects ... and causes kidney damage in essentially 100% of patients,” Dr. Lebwohl said of cyclosporine.
“So we had treatments that worked, but because the side effects were sufficiently severe, a lot of patients were not treated,” he said.
Enter the biologics era
The early 2000s brought the first two approvals for psoriasis: alefacept (Amevive), a “modestly effective, but quite safe” immunosuppressive dimeric fusion protein approved in early 2003 for moderate to severe plaque psoriasis, and efalizumab (Raptiva), a recombinant humanized monoclonal antibody approved in October 2003; both were T-cell–targeted therapies. The former was withdrawn from the market voluntarily as newer agents became available, and the latter was withdrawn in 2009 because of a link with development of progressive multifocal leukoencephalopathy.
Tumor necrosis factor (TNF) blockers, which had been used effectively for RA and Crohn’s disease, emerged next, and were highly effective, much safer than the systemic treatments, and gained “very widespread use,” Dr. Lebwohl said.
His colleague Alice B. Gottlieb, MD, PhD, was among the pioneers in the development of TNF blockers for the treatment of psoriasis. Her seminal, investigator-initiated paper on the efficacy and safety of infliximab (Remicade) monotherapy for plaque-type psoriasis published in the Lancet in 2001 helped launch the current era in which many psoriasis patients achieve 100% PASI responses with limited side effects, he said, explaining that subsequent research elucidated the role of IL-12 and -23 – leading to effective treatments like ustekinumab (Stelara), and later IL-17, which is, “in fact, the molecule closest to the pathogenesis of psoriasis.”
“If you block IL-17, you get rid of psoriasis,” he said, noting that there are now several companies with approved antibodies to IL-17. “Taltz [ixekizumab] and Cosentyx [secukinumab] are the leading ones, and Siliq [brodalumab] blocks the receptor for IL-17, so it is very effective.”
Another novel biologic – bimekizumab – is on the horizon. It blocks both IL-17a and IL-17f, and appears highly effective in psoriasis and psoriatic arthritis (PsA). “Biologics were the real start of the [psoriasis treatment] revolution,” he said. “When I started out I would speak at patient meetings and the patients were angry at their physicians; they thought they weren’t aggressive enough, they were very frustrated.”
Dr. Lebwohl described patients he would see at annual National Psoriasis Foundation meetings: “There were patients in wheel chairs, because they couldn’t walk. They would be red and scaly all over ... you could have literally swept up scale like it was snow after one of those meetings.
“You go forward to around 2010 – nobody’s in wheelchairs anymore, everybody has clear skin, and it’s become a party; patients are no longer angry – they are thrilled with the results they are getting from much safer and much more effective drugs,” he said. “So it’s been a pleasure taking care of those patients and going from a very difficult time of treating them, to a time where we’ve done a great job treating them.”
Dr. Lebwohl noted that a “large number of dermatologists have been involved with the development of these drugs and making sure they succeed, and that has also been a pleasure to see.”
Dr. Gottlieb, who Dr. Lebwohl has described as “a superstar” in the fields of dermatology and rheumatology, is one such researcher. In an interview, she looked back on her work and the ways that her work “opened the field,” led to many of her trainees also doing “great work,” and changed the lives of patients.
“It’s nice to feel that I really did change, fundamentally, how psoriasis patients are treated,” said Dr. Gottlieb, who is a clinical professor in the department of dermatology at the Icahn School of Medicine at Mount Sinai. “That obviously feels great.”
She recalled a patient – “a 6-foot-5 biker with bad psoriasis” – who “literally, the minute the door closed, he was crying about how horrible his disease was.”
“And I cleared him ... and then you get big hugs – it just feels extremely good ... giving somebody their life back,” she said.
Dr. Gottlieb has been involved in much of the work in developing biologics for psoriasis, including the ongoing work with bimekizumab for PsA as mentioned by Dr. Lebwohl.
If the phase 2 data with bimekizumab are replicated in the ongoing phase 3 trials now underway at her center, “that can really raise the bar ... so if it’s reproducible, it’s very exciting.”
“It’s exciting to have an IL-23 blocker that, at least in clinical trials, showed inhibition of radiographic progression [in PsA],” she said. “That’s guselkumab those data are already out, and I was involved with that.”
The early work of Dr. Gottlieb and others has also “spread to other diseases,” like hidradenitis suppurativa and atopic dermatitis, she said, noting that numerous studies are underway.
Aside from curing all patients, her ultimate goal is getting to a point where psoriasis has no effect on patients’ quality of life.
“And I see it already,” she said. “It’s happening, and it’s nice to see that it’s happening in children now, too; several of the drugs are approved in kids.”
Alan Menter, MD, chairman of the division of dermatology at Baylor University Medical Center, Dallas, also a prolific researcher – and chair of the guidelines committee that published two new sets of guidelines for psoriasis treatment in 2019 – said that the field of dermatology was “late to the biologic evolution,” as many of the early biologics were first approved for PsA.
“But over the last 10 years, things have changed dramatically,” he said. “After that we suddenly leapt ahead of everybody. ... We now have 11 biologic drugs approved for psoriasis, which is more than any other disease has available.”
It’s been “highly exciting” to see this “evolution and revolution,” he commented, adding that one of the next challenges is to address the comorbidities, such as cardiovascular disease, associated with psoriasis.
“The big question now ... is if you improve skin and you improve joints, can you potentially reduce the risk of coronary artery disease,” he said. “Everybody is looking at that, and to me it’s one of the most exciting things that we’re doing.”
Work is ongoing to look at whether the IL-17s and IL-23s have “other indications outside of the skin and joints,” both within and outside of dermatology.
Like Dr. Gottlieb, Dr. Menter also mentioned the potential for hidradenitis suppurativa, and also for a condition that is rarely discussed or studied: genital psoriasis. Ixekizumab has recently been shown to work in about 75% of patients with genital psoriasis, he noted.
Another important area of research is the identification of biomarkers for predicting response and relapse, he said. For now, biomarker research has disappointed, he added, predicting that it will take at least 3-5 years before biomarkers to help guide treatment are identified.
Indeed, Dr. Gelfand, who also is director of the Psoriasis and Phototherapy Treatment Center, vice chair of clinical research, and medical director of the dermatology clinical studies unit at the University of Pennsylvania, agreed there is a need for research to improve treatment selection.
Advances are being made in genetics – with more than 80 different genes now identified as being related to psoriasis – and in medical informatics – which allow thousands of patients to be followed for years, he said, noting that this could elucidate immunopathological features that can improve treatments, predict and prevent comorbidity, and further improve outcomes.
“We also need care that is more patient centered,” he said, describing the ongoing pragmatic LITE trial of home- or office-based phototherapy for which he is the lead investigator, and other studies that he hopes will expand access to care.
Kenneth Brian Gordon, MD, chair and professor of dermatology at the Medical College of Wisconsin, Milwaukee, whose career started in the basic science immunology arena, added the need for expanding benefit to patients with more-moderate disease. Like Dr. Menter, he identified psoriasis as the area in medicine that has had the greatest degree of advancement, except perhaps for hepatitis C.
He described the process not as a “bench-to-bedside” story, but as a bedside-to-bench, then “back-to-bedside” story.
It was really about taking those early T-cell–targeted biologics and anti-TNF agents from bedside to bench with the realization of the importance of the IL-23 and IL-17 pathways, and that understanding led back to the bedside with the development of the newest agents – and to a “huge difference in patient’s lives.”
“But we’ve gotten so good at treating patients with severe disease ... the question now is how to take care of those with more-moderate disease,” he said, noting that a focus on cost and better delivery systems will be needed for that population.
That research is underway, and the future looks bright – and clear.
“I think with psoriasis therapy and where we’ve come in the last 20 years ... we have a hard time remembering what it was like before we had biologic agents” he said. “Our perspective has changed a lot, and sometimes we forget that.”
In fact, “psoriasis has sort of dragged dermatology into the world of modern clinical trial science, and we can now apply that to all sorts of other diseases,” he said. “The psoriasis trials were the first really well-done large-scale trials in dermatology, and I think that has given dermatology a real leg up in how we do clinical research and how we do evidence-based medicine.”
All of the doctors interviewed for this story have received funds and/or honoraria from, consulted with, are employed with, or served on the advisory boards of manufacturers of biologics. Dr. Gelfand is a copatent holder of resiquimod for treatment of cutaneous T-cell lymphoma and is deputy editor of the Journal of Investigative Dermatology.
