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The case for anti–IL-17 agents as first-line biologics in psoriatic arthritis
LAS VEGAS – at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
The 2018 joint American College of Rheumatology/National Psoriasis Association guidelines recommend the anti–tumor necrosis factor agents as first-line biologic therapy for PsA, with the anti–IL-17 biologics held in reserve as second-tier therapy for when the anti-TNFs don’t work. That’s largely because the guidance was developed before the compelling evidence for the anti–IL-17 agents as the biologics of choice was appreciated, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
“Many people go by these guidelines,” the dermatologist noted. “I think it’s really critical to look at the data and not just the guidelines because the guidelines don’t give full credit to the anti–IL-17 agents,” he added.
“Emerging psoriatic arthritis data may likely put this class of medications into the forefront of treatment for patients who have both psoriasis and psoriatic arthritis because you generally get higher responses for the skin disease than with anti-TNF therapy, and with similar responses in psoriatic arthritis.”
Two IL-17 inhibitors are approved for both PsA and psoriasis: secukinumab (Cosentyx) and ixekizumab (Taltz). In addition, brodalumab (Siliq), approved for psoriasis, is expected to receive an expanded indication for PsA based upon its strong showing in the AMVISION-1 and -2 trials. Data from those trials, as well as the FUTURE 2 trial for secukinumab and SPIRIT-P1 for ixekizumab, consistently document at least 20% improvement in the ACR criteria for PsA severity – that is, an ACR 20 response – in 50%-60% of patients on one of the three IL-17 inhibitors, as well as ACR 50 response rates of around 30%. Those outcomes are quite consistent with the impact of the anti-TNF biologics on joint disease. But the TNF inhibitors can’t touch the anti–IL-17 biologics when it comes to improvement in Psoriasis Area and Severity Index (PASI) scores: The anti–IL-17 agents have week-52 PASI 75 response rates in the range of 80%, PASI 90 response rates of 70%-75%, and PASI 100 response rates of 40%-55%, with the highest-end results being seen with brodalumab, he continued.
A point worth remembering when prescribing secukinumab is that the approved dose for PsA is 150 mg every 4 weeks, which is just half of the typical dose in psoriasis.
“I spend a lot of time convincing my rheumatology colleagues that if you’re treating both psoriasis and psoriatic arthritis, use the psoriasis dose. There’s some evidence that the higher dose provides some benefit in terms of prevention of permanent joint damage by x-ray,” Dr. Gordon said.
Evidence that TNF inhibitors inhibit permanent joint damage in patients with PsA has been considered a major advantage, establishing this medication class as first-line biologic therapy. But anti–IL-17 therapies appear to have a similar beneficial effect. That was demonstrated in the SPIRIT-P1 trial, where Sharp scores – a radiographic measure of progression of joint damage – were similar at 24 weeks in PsA patients randomized to ixekizumab as compared to adalimumab, with both biologics being superior to placebo. An Assessment of SpondyloArthritis International Society 20% improvement (ASAS 20) response or an ACR 50 response doesn’t capture what’s going on with regard to axial disease. That’s assessed through ASAS 20 and ASAS 40 responses – that is, at least 20% or 40% improvement, compared with baseline, in Assessment in Ankylosing Spondylitis scores. And in the MEASURE 1 and 2 trials, secukinumab achieved robust improvement in axial disease as reflected in favorable ASAS 20 and ASAS 40 responses through 52 weeks in patients with active ankylosing spondylitis.
“The anti–IL-17 agents do actually work in ankylosing spondylitis, which might be a surrogate for the treatment effect in axial psoriatic arthritis,” Dr. Gordon commented.
The phase 3b MAXIMISE trial presented at the 2019 EULAR meeting looked specifically at the impact of secukinumab in patients with psoriatic arthritis with axial involvement. An ASAS 20 response at week 12 was seen in 67% and 65% of patients randomized to secukinumab at 150 or 300 mg, respectively, if they were on concomitant methotrexate, and 64% and 61% if they were not, compared with ASAS 20 rates of 34% and 31% in placebo-treated controls.
“This is the only study of an anti–IL-17 agent that’s been done for axial disease to date in psoriatic arthritis. It’s very, very encouraging,” the dermatologist commented.
Durability of response and safety
“In terms of safety, the anti–IL-17s have been a truly remarkable success story. There are very low rates of things to be concerned about,” Dr. Gordon said.
Oral candidiasis occurs in 2%-4% of treated patients, but he noted, “It’s almost always very mild disease” that’s easily treatable with nystatin or, in the worst case, with some fluconazole.
Inflammatory bowel disease (IBD) as a side effect of anti–IL-17 therapy has been a controversial issue. Dr. Gordon’s interpretation of the evidence is that there probably is a very slight increase in the risk of developing ulcerative colitis, but not Crohn’s disease.
“This rate is extraordinarily low, so while it’s something that I consider, and if a patient has a personal history of IBD I will sometimes hesitate to use an anti–IL-17 agent, in patients who don’t have a personal history I’ll go ahead,” he explained.
There is a signal of a slight increase in risk of depression in patients on brodalumab, which isn’t the case for secukinumab or ixekizumab.
Importantly, large long-term extension studies with years of follow-up show that the initially low adverse event rates associated with the IL-17 inhibitors don’t increase over time; rather, they remain steady over years of use.
Long-term maintenance of response with these biologics is impressive. “It’s not perfect, but it’s still a tremendous advantage for patients, especially if you can get them through that initial period,” Dr. Gordon said.
For example, in the long-term extension of the UNCOVER-1 trial, psoriasis patients who had clear or almost clear skin at week 12 on ixekizumab and continued to take the medication open label for 5 years had PASI 75, 90, and 100 response rates of 94%, 82%, and 47%, respectively, at week 264.
What about IL-12/23 and IL-23 inhibitors in PsA?
In a separate presentation at the MedscapeLive seminar, Bruce E. Strober, MD, PhD, said that, although ustekinumab (Stelara) is approved for both psoriasis and PsA, the IL-12/-23 inhibitor’s efficacy in PsA is inconsistent and lower than other approved biologics. In contrast, the IL-23 inhibitor guselkumab (Tremfya), which also has the dual indications, is a strong performer in both. In the DISCOVER-2 trial, conducted in treatment-naive patients with PsA, guselkumab at the approved dose of 100 mg every 8 weeks achieved ACR 20, 50, and 70 rates of 64%, 31%, and 19%, respectively. It was also significantly better than placebo for resolution of enthesitis.
An important caveat: While radiographic inhibition of progression of joint disease occurred with guselkumab dosed at 100 mg every 4 weeks in DISCOVER-2, that’s not the approved dose. At 100 mg every 8 weeks – the FDA-approved dosing for both psoriatic arthritis and psoriasis – radiographic inhibition wasn’t better than with placebo, noted Dr. Strober, a dermatologist at Yale University, New Haven, Conn.
Dr. Gordon and Dr. Strober are clinical trialists who reported receiving research support and/or honoraria from more than a dozen pharmaceutical companies, including virtually all of those with biologics for dermatology.
MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
The 2018 joint American College of Rheumatology/National Psoriasis Association guidelines recommend the anti–tumor necrosis factor agents as first-line biologic therapy for PsA, with the anti–IL-17 biologics held in reserve as second-tier therapy for when the anti-TNFs don’t work. That’s largely because the guidance was developed before the compelling evidence for the anti–IL-17 agents as the biologics of choice was appreciated, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
“Many people go by these guidelines,” the dermatologist noted. “I think it’s really critical to look at the data and not just the guidelines because the guidelines don’t give full credit to the anti–IL-17 agents,” he added.
“Emerging psoriatic arthritis data may likely put this class of medications into the forefront of treatment for patients who have both psoriasis and psoriatic arthritis because you generally get higher responses for the skin disease than with anti-TNF therapy, and with similar responses in psoriatic arthritis.”
Two IL-17 inhibitors are approved for both PsA and psoriasis: secukinumab (Cosentyx) and ixekizumab (Taltz). In addition, brodalumab (Siliq), approved for psoriasis, is expected to receive an expanded indication for PsA based upon its strong showing in the AMVISION-1 and -2 trials. Data from those trials, as well as the FUTURE 2 trial for secukinumab and SPIRIT-P1 for ixekizumab, consistently document at least 20% improvement in the ACR criteria for PsA severity – that is, an ACR 20 response – in 50%-60% of patients on one of the three IL-17 inhibitors, as well as ACR 50 response rates of around 30%. Those outcomes are quite consistent with the impact of the anti-TNF biologics on joint disease. But the TNF inhibitors can’t touch the anti–IL-17 biologics when it comes to improvement in Psoriasis Area and Severity Index (PASI) scores: The anti–IL-17 agents have week-52 PASI 75 response rates in the range of 80%, PASI 90 response rates of 70%-75%, and PASI 100 response rates of 40%-55%, with the highest-end results being seen with brodalumab, he continued.
A point worth remembering when prescribing secukinumab is that the approved dose for PsA is 150 mg every 4 weeks, which is just half of the typical dose in psoriasis.
“I spend a lot of time convincing my rheumatology colleagues that if you’re treating both psoriasis and psoriatic arthritis, use the psoriasis dose. There’s some evidence that the higher dose provides some benefit in terms of prevention of permanent joint damage by x-ray,” Dr. Gordon said.
Evidence that TNF inhibitors inhibit permanent joint damage in patients with PsA has been considered a major advantage, establishing this medication class as first-line biologic therapy. But anti–IL-17 therapies appear to have a similar beneficial effect. That was demonstrated in the SPIRIT-P1 trial, where Sharp scores – a radiographic measure of progression of joint damage – were similar at 24 weeks in PsA patients randomized to ixekizumab as compared to adalimumab, with both biologics being superior to placebo. An Assessment of SpondyloArthritis International Society 20% improvement (ASAS 20) response or an ACR 50 response doesn’t capture what’s going on with regard to axial disease. That’s assessed through ASAS 20 and ASAS 40 responses – that is, at least 20% or 40% improvement, compared with baseline, in Assessment in Ankylosing Spondylitis scores. And in the MEASURE 1 and 2 trials, secukinumab achieved robust improvement in axial disease as reflected in favorable ASAS 20 and ASAS 40 responses through 52 weeks in patients with active ankylosing spondylitis.
“The anti–IL-17 agents do actually work in ankylosing spondylitis, which might be a surrogate for the treatment effect in axial psoriatic arthritis,” Dr. Gordon commented.
The phase 3b MAXIMISE trial presented at the 2019 EULAR meeting looked specifically at the impact of secukinumab in patients with psoriatic arthritis with axial involvement. An ASAS 20 response at week 12 was seen in 67% and 65% of patients randomized to secukinumab at 150 or 300 mg, respectively, if they were on concomitant methotrexate, and 64% and 61% if they were not, compared with ASAS 20 rates of 34% and 31% in placebo-treated controls.
“This is the only study of an anti–IL-17 agent that’s been done for axial disease to date in psoriatic arthritis. It’s very, very encouraging,” the dermatologist commented.
Durability of response and safety
“In terms of safety, the anti–IL-17s have been a truly remarkable success story. There are very low rates of things to be concerned about,” Dr. Gordon said.
Oral candidiasis occurs in 2%-4% of treated patients, but he noted, “It’s almost always very mild disease” that’s easily treatable with nystatin or, in the worst case, with some fluconazole.
Inflammatory bowel disease (IBD) as a side effect of anti–IL-17 therapy has been a controversial issue. Dr. Gordon’s interpretation of the evidence is that there probably is a very slight increase in the risk of developing ulcerative colitis, but not Crohn’s disease.
“This rate is extraordinarily low, so while it’s something that I consider, and if a patient has a personal history of IBD I will sometimes hesitate to use an anti–IL-17 agent, in patients who don’t have a personal history I’ll go ahead,” he explained.
There is a signal of a slight increase in risk of depression in patients on brodalumab, which isn’t the case for secukinumab or ixekizumab.
Importantly, large long-term extension studies with years of follow-up show that the initially low adverse event rates associated with the IL-17 inhibitors don’t increase over time; rather, they remain steady over years of use.
Long-term maintenance of response with these biologics is impressive. “It’s not perfect, but it’s still a tremendous advantage for patients, especially if you can get them through that initial period,” Dr. Gordon said.
For example, in the long-term extension of the UNCOVER-1 trial, psoriasis patients who had clear or almost clear skin at week 12 on ixekizumab and continued to take the medication open label for 5 years had PASI 75, 90, and 100 response rates of 94%, 82%, and 47%, respectively, at week 264.
What about IL-12/23 and IL-23 inhibitors in PsA?
In a separate presentation at the MedscapeLive seminar, Bruce E. Strober, MD, PhD, said that, although ustekinumab (Stelara) is approved for both psoriasis and PsA, the IL-12/-23 inhibitor’s efficacy in PsA is inconsistent and lower than other approved biologics. In contrast, the IL-23 inhibitor guselkumab (Tremfya), which also has the dual indications, is a strong performer in both. In the DISCOVER-2 trial, conducted in treatment-naive patients with PsA, guselkumab at the approved dose of 100 mg every 8 weeks achieved ACR 20, 50, and 70 rates of 64%, 31%, and 19%, respectively. It was also significantly better than placebo for resolution of enthesitis.
An important caveat: While radiographic inhibition of progression of joint disease occurred with guselkumab dosed at 100 mg every 4 weeks in DISCOVER-2, that’s not the approved dose. At 100 mg every 8 weeks – the FDA-approved dosing for both psoriatic arthritis and psoriasis – radiographic inhibition wasn’t better than with placebo, noted Dr. Strober, a dermatologist at Yale University, New Haven, Conn.
Dr. Gordon and Dr. Strober are clinical trialists who reported receiving research support and/or honoraria from more than a dozen pharmaceutical companies, including virtually all of those with biologics for dermatology.
MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
The 2018 joint American College of Rheumatology/National Psoriasis Association guidelines recommend the anti–tumor necrosis factor agents as first-line biologic therapy for PsA, with the anti–IL-17 biologics held in reserve as second-tier therapy for when the anti-TNFs don’t work. That’s largely because the guidance was developed before the compelling evidence for the anti–IL-17 agents as the biologics of choice was appreciated, according to Dr. Gordon, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
“Many people go by these guidelines,” the dermatologist noted. “I think it’s really critical to look at the data and not just the guidelines because the guidelines don’t give full credit to the anti–IL-17 agents,” he added.
“Emerging psoriatic arthritis data may likely put this class of medications into the forefront of treatment for patients who have both psoriasis and psoriatic arthritis because you generally get higher responses for the skin disease than with anti-TNF therapy, and with similar responses in psoriatic arthritis.”
Two IL-17 inhibitors are approved for both PsA and psoriasis: secukinumab (Cosentyx) and ixekizumab (Taltz). In addition, brodalumab (Siliq), approved for psoriasis, is expected to receive an expanded indication for PsA based upon its strong showing in the AMVISION-1 and -2 trials. Data from those trials, as well as the FUTURE 2 trial for secukinumab and SPIRIT-P1 for ixekizumab, consistently document at least 20% improvement in the ACR criteria for PsA severity – that is, an ACR 20 response – in 50%-60% of patients on one of the three IL-17 inhibitors, as well as ACR 50 response rates of around 30%. Those outcomes are quite consistent with the impact of the anti-TNF biologics on joint disease. But the TNF inhibitors can’t touch the anti–IL-17 biologics when it comes to improvement in Psoriasis Area and Severity Index (PASI) scores: The anti–IL-17 agents have week-52 PASI 75 response rates in the range of 80%, PASI 90 response rates of 70%-75%, and PASI 100 response rates of 40%-55%, with the highest-end results being seen with brodalumab, he continued.
A point worth remembering when prescribing secukinumab is that the approved dose for PsA is 150 mg every 4 weeks, which is just half of the typical dose in psoriasis.
“I spend a lot of time convincing my rheumatology colleagues that if you’re treating both psoriasis and psoriatic arthritis, use the psoriasis dose. There’s some evidence that the higher dose provides some benefit in terms of prevention of permanent joint damage by x-ray,” Dr. Gordon said.
Evidence that TNF inhibitors inhibit permanent joint damage in patients with PsA has been considered a major advantage, establishing this medication class as first-line biologic therapy. But anti–IL-17 therapies appear to have a similar beneficial effect. That was demonstrated in the SPIRIT-P1 trial, where Sharp scores – a radiographic measure of progression of joint damage – were similar at 24 weeks in PsA patients randomized to ixekizumab as compared to adalimumab, with both biologics being superior to placebo. An Assessment of SpondyloArthritis International Society 20% improvement (ASAS 20) response or an ACR 50 response doesn’t capture what’s going on with regard to axial disease. That’s assessed through ASAS 20 and ASAS 40 responses – that is, at least 20% or 40% improvement, compared with baseline, in Assessment in Ankylosing Spondylitis scores. And in the MEASURE 1 and 2 trials, secukinumab achieved robust improvement in axial disease as reflected in favorable ASAS 20 and ASAS 40 responses through 52 weeks in patients with active ankylosing spondylitis.
“The anti–IL-17 agents do actually work in ankylosing spondylitis, which might be a surrogate for the treatment effect in axial psoriatic arthritis,” Dr. Gordon commented.
The phase 3b MAXIMISE trial presented at the 2019 EULAR meeting looked specifically at the impact of secukinumab in patients with psoriatic arthritis with axial involvement. An ASAS 20 response at week 12 was seen in 67% and 65% of patients randomized to secukinumab at 150 or 300 mg, respectively, if they were on concomitant methotrexate, and 64% and 61% if they were not, compared with ASAS 20 rates of 34% and 31% in placebo-treated controls.
“This is the only study of an anti–IL-17 agent that’s been done for axial disease to date in psoriatic arthritis. It’s very, very encouraging,” the dermatologist commented.
Durability of response and safety
“In terms of safety, the anti–IL-17s have been a truly remarkable success story. There are very low rates of things to be concerned about,” Dr. Gordon said.
Oral candidiasis occurs in 2%-4% of treated patients, but he noted, “It’s almost always very mild disease” that’s easily treatable with nystatin or, in the worst case, with some fluconazole.
Inflammatory bowel disease (IBD) as a side effect of anti–IL-17 therapy has been a controversial issue. Dr. Gordon’s interpretation of the evidence is that there probably is a very slight increase in the risk of developing ulcerative colitis, but not Crohn’s disease.
“This rate is extraordinarily low, so while it’s something that I consider, and if a patient has a personal history of IBD I will sometimes hesitate to use an anti–IL-17 agent, in patients who don’t have a personal history I’ll go ahead,” he explained.
There is a signal of a slight increase in risk of depression in patients on brodalumab, which isn’t the case for secukinumab or ixekizumab.
Importantly, large long-term extension studies with years of follow-up show that the initially low adverse event rates associated with the IL-17 inhibitors don’t increase over time; rather, they remain steady over years of use.
Long-term maintenance of response with these biologics is impressive. “It’s not perfect, but it’s still a tremendous advantage for patients, especially if you can get them through that initial period,” Dr. Gordon said.
For example, in the long-term extension of the UNCOVER-1 trial, psoriasis patients who had clear or almost clear skin at week 12 on ixekizumab and continued to take the medication open label for 5 years had PASI 75, 90, and 100 response rates of 94%, 82%, and 47%, respectively, at week 264.
What about IL-12/23 and IL-23 inhibitors in PsA?
In a separate presentation at the MedscapeLive seminar, Bruce E. Strober, MD, PhD, said that, although ustekinumab (Stelara) is approved for both psoriasis and PsA, the IL-12/-23 inhibitor’s efficacy in PsA is inconsistent and lower than other approved biologics. In contrast, the IL-23 inhibitor guselkumab (Tremfya), which also has the dual indications, is a strong performer in both. In the DISCOVER-2 trial, conducted in treatment-naive patients with PsA, guselkumab at the approved dose of 100 mg every 8 weeks achieved ACR 20, 50, and 70 rates of 64%, 31%, and 19%, respectively. It was also significantly better than placebo for resolution of enthesitis.
An important caveat: While radiographic inhibition of progression of joint disease occurred with guselkumab dosed at 100 mg every 4 weeks in DISCOVER-2, that’s not the approved dose. At 100 mg every 8 weeks – the FDA-approved dosing for both psoriatic arthritis and psoriasis – radiographic inhibition wasn’t better than with placebo, noted Dr. Strober, a dermatologist at Yale University, New Haven, Conn.
Dr. Gordon and Dr. Strober are clinical trialists who reported receiving research support and/or honoraria from more than a dozen pharmaceutical companies, including virtually all of those with biologics for dermatology.
MedscapeLive and this news organization are owned by the same parent company.
FROM MEDSCAPELIVE LAS VEGAS DERMATOLOGY SEMINAR
Several approaches recommended to reduce filler, neuromodulator complications
Katie Beleznay, MD, of the University of British Columbia, Vancouver, said in a virtual presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
The number of reported cases of vascular complications in patients receiving fillers has increased in recent years, said Dr. Beleznay, who also treats patients in private practice in Vancouver. However, knowing the facial anatomy and recognizing that there is no “one-size-fits-all” approach goes a long way in preventing and managing complications.
In terms of neuromodulators such as Botox, the upper face is the most common area for treatment, and potential complications include eyelid ptosis, brow ptosis, and the “Spock brow,” Dr. Beleznay noted. For example, patients won’t be able to engage elevator muscles, such as the frontalis, if too much neuromodulator is injected. But, a couple of units in the upper forehead can help make the effect look natural, soften the lines, without being too frozen.
To help avoid eyelid ptosis with neuromodulators, inject at least one centimeter above the supraorbital rim at the midpupillary line, Dr. Beleznay advised. “I will feel the muscle,” because some brows are drawn or microbladed on, she noted. Patients who develop eyelid ptosis can be treated with apraclonidine drops.
To avoid brow ptosis with neuromodulators, it is important to assess the anatomy at baseline, Dr. Beleznay said. Some patients like to be able to lift their brows, and too much Botox will prevent their doing so. In order to mitigate this, it is important to treat brow depressors to balance and provide lift, and staying above the first horizontal forehead rhytid when injecting can help reduce brow ptosis risk.
Remember when injecting the upper face there are several glabellar contraction patterns, so “be sure you are targeting the treatment for the muscle pulling pattern that you see,” she said.
Complications associated with fillers
When injecting fillers, there are rare complications, including blindness, that are worth acknowledging, said Dr. Beleznay, lead author of a study on global cases of blindness caused by fillers published in 2015, including 98 cases up to 2015, and another 48 cases in a study published in 2019.
The highest-risk areas for causing blindness with fillers are the glabella and the nose, but “anywhere you are injecting is at risk for this complication,” she commented.
Explaining the mechanism of action for blindness resulting from filler injections, she said: “When the tip of the needle gets into the vessel, if you put enough pressure on the plunger, the filler can travel retrograde in the vessel back into the ophthalmic artery system, and then travels distally and blocks blood supply to the retina,” causing vision complications.
Understanding the potential mechanism for these complications informs preventive strategies, Dr. Beleznay emphasized.
If vision complications from fillers occur, they are likely to happen immediately, she said. There could be skin involvement or stroke-like features in addition to vision complications, so it is important to screen for these conditions as well if patients complain of vision loss.
Tips for prevention
Knowing the anatomy is the first step to maximize safe placement of fillers, Dr. Beleznay said. For example, the glabella is a high-risk location and includes the supraorbital and supratrochlear arteries, which start deep and become more superficial as they travel up the forehead.
When Dr. Beleznay injects in the glabella area, “I will do a true intradermal injection using tiny microdroplets, because that feels safest to me.” A video with additional details on surface anatomy and safer planes for injecting is available online to members of the American Society of Dermatologic Surgery.
Other tips to reduce the risk of vascular complications include injecting slowly and with a minimal amount of pressure, Dr. Beleznay emphasized. Injecting in small increments, moving the needle tip between injections, and using a cannula also may help reduce risk.
Always ask and use caution if patients have had other recent surgical procedures, she added.
Vascular complications such as blindness can be devastating, but the overall risks remain low. It’s important that clinicians know their anatomy, educate patients, and have prepared treatment protocols in place in the event of serious complications, Dr. Beleznay noted.
Dr. Beleznay disclosed relationships as an investigator, speaker, and/or consultant with AbbVie, Actelion, Allergan, Almirall, Amgen, Bausch Health, Celgene, Cipher, Evolus, Galderma, Johnson & Johnson, L’Oreal, Leo, Merz, Novartis, Procter & Gamble, Prollenium, Revance, Sandoz, Sanofi, Valeant, Vichy, and Zeltiq.
MedscapeLive and this news organization are owned by the same parent company.
Katie Beleznay, MD, of the University of British Columbia, Vancouver, said in a virtual presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
The number of reported cases of vascular complications in patients receiving fillers has increased in recent years, said Dr. Beleznay, who also treats patients in private practice in Vancouver. However, knowing the facial anatomy and recognizing that there is no “one-size-fits-all” approach goes a long way in preventing and managing complications.
In terms of neuromodulators such as Botox, the upper face is the most common area for treatment, and potential complications include eyelid ptosis, brow ptosis, and the “Spock brow,” Dr. Beleznay noted. For example, patients won’t be able to engage elevator muscles, such as the frontalis, if too much neuromodulator is injected. But, a couple of units in the upper forehead can help make the effect look natural, soften the lines, without being too frozen.
To help avoid eyelid ptosis with neuromodulators, inject at least one centimeter above the supraorbital rim at the midpupillary line, Dr. Beleznay advised. “I will feel the muscle,” because some brows are drawn or microbladed on, she noted. Patients who develop eyelid ptosis can be treated with apraclonidine drops.
To avoid brow ptosis with neuromodulators, it is important to assess the anatomy at baseline, Dr. Beleznay said. Some patients like to be able to lift their brows, and too much Botox will prevent their doing so. In order to mitigate this, it is important to treat brow depressors to balance and provide lift, and staying above the first horizontal forehead rhytid when injecting can help reduce brow ptosis risk.
Remember when injecting the upper face there are several glabellar contraction patterns, so “be sure you are targeting the treatment for the muscle pulling pattern that you see,” she said.
Complications associated with fillers
When injecting fillers, there are rare complications, including blindness, that are worth acknowledging, said Dr. Beleznay, lead author of a study on global cases of blindness caused by fillers published in 2015, including 98 cases up to 2015, and another 48 cases in a study published in 2019.
The highest-risk areas for causing blindness with fillers are the glabella and the nose, but “anywhere you are injecting is at risk for this complication,” she commented.
Explaining the mechanism of action for blindness resulting from filler injections, she said: “When the tip of the needle gets into the vessel, if you put enough pressure on the plunger, the filler can travel retrograde in the vessel back into the ophthalmic artery system, and then travels distally and blocks blood supply to the retina,” causing vision complications.
Understanding the potential mechanism for these complications informs preventive strategies, Dr. Beleznay emphasized.
If vision complications from fillers occur, they are likely to happen immediately, she said. There could be skin involvement or stroke-like features in addition to vision complications, so it is important to screen for these conditions as well if patients complain of vision loss.
Tips for prevention
Knowing the anatomy is the first step to maximize safe placement of fillers, Dr. Beleznay said. For example, the glabella is a high-risk location and includes the supraorbital and supratrochlear arteries, which start deep and become more superficial as they travel up the forehead.
When Dr. Beleznay injects in the glabella area, “I will do a true intradermal injection using tiny microdroplets, because that feels safest to me.” A video with additional details on surface anatomy and safer planes for injecting is available online to members of the American Society of Dermatologic Surgery.
Other tips to reduce the risk of vascular complications include injecting slowly and with a minimal amount of pressure, Dr. Beleznay emphasized. Injecting in small increments, moving the needle tip between injections, and using a cannula also may help reduce risk.
Always ask and use caution if patients have had other recent surgical procedures, she added.
Vascular complications such as blindness can be devastating, but the overall risks remain low. It’s important that clinicians know their anatomy, educate patients, and have prepared treatment protocols in place in the event of serious complications, Dr. Beleznay noted.
Dr. Beleznay disclosed relationships as an investigator, speaker, and/or consultant with AbbVie, Actelion, Allergan, Almirall, Amgen, Bausch Health, Celgene, Cipher, Evolus, Galderma, Johnson & Johnson, L’Oreal, Leo, Merz, Novartis, Procter & Gamble, Prollenium, Revance, Sandoz, Sanofi, Valeant, Vichy, and Zeltiq.
MedscapeLive and this news organization are owned by the same parent company.
Katie Beleznay, MD, of the University of British Columbia, Vancouver, said in a virtual presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
The number of reported cases of vascular complications in patients receiving fillers has increased in recent years, said Dr. Beleznay, who also treats patients in private practice in Vancouver. However, knowing the facial anatomy and recognizing that there is no “one-size-fits-all” approach goes a long way in preventing and managing complications.
In terms of neuromodulators such as Botox, the upper face is the most common area for treatment, and potential complications include eyelid ptosis, brow ptosis, and the “Spock brow,” Dr. Beleznay noted. For example, patients won’t be able to engage elevator muscles, such as the frontalis, if too much neuromodulator is injected. But, a couple of units in the upper forehead can help make the effect look natural, soften the lines, without being too frozen.
To help avoid eyelid ptosis with neuromodulators, inject at least one centimeter above the supraorbital rim at the midpupillary line, Dr. Beleznay advised. “I will feel the muscle,” because some brows are drawn or microbladed on, she noted. Patients who develop eyelid ptosis can be treated with apraclonidine drops.
To avoid brow ptosis with neuromodulators, it is important to assess the anatomy at baseline, Dr. Beleznay said. Some patients like to be able to lift their brows, and too much Botox will prevent their doing so. In order to mitigate this, it is important to treat brow depressors to balance and provide lift, and staying above the first horizontal forehead rhytid when injecting can help reduce brow ptosis risk.
Remember when injecting the upper face there are several glabellar contraction patterns, so “be sure you are targeting the treatment for the muscle pulling pattern that you see,” she said.
Complications associated with fillers
When injecting fillers, there are rare complications, including blindness, that are worth acknowledging, said Dr. Beleznay, lead author of a study on global cases of blindness caused by fillers published in 2015, including 98 cases up to 2015, and another 48 cases in a study published in 2019.
The highest-risk areas for causing blindness with fillers are the glabella and the nose, but “anywhere you are injecting is at risk for this complication,” she commented.
Explaining the mechanism of action for blindness resulting from filler injections, she said: “When the tip of the needle gets into the vessel, if you put enough pressure on the plunger, the filler can travel retrograde in the vessel back into the ophthalmic artery system, and then travels distally and blocks blood supply to the retina,” causing vision complications.
Understanding the potential mechanism for these complications informs preventive strategies, Dr. Beleznay emphasized.
If vision complications from fillers occur, they are likely to happen immediately, she said. There could be skin involvement or stroke-like features in addition to vision complications, so it is important to screen for these conditions as well if patients complain of vision loss.
Tips for prevention
Knowing the anatomy is the first step to maximize safe placement of fillers, Dr. Beleznay said. For example, the glabella is a high-risk location and includes the supraorbital and supratrochlear arteries, which start deep and become more superficial as they travel up the forehead.
When Dr. Beleznay injects in the glabella area, “I will do a true intradermal injection using tiny microdroplets, because that feels safest to me.” A video with additional details on surface anatomy and safer planes for injecting is available online to members of the American Society of Dermatologic Surgery.
Other tips to reduce the risk of vascular complications include injecting slowly and with a minimal amount of pressure, Dr. Beleznay emphasized. Injecting in small increments, moving the needle tip between injections, and using a cannula also may help reduce risk.
Always ask and use caution if patients have had other recent surgical procedures, she added.
Vascular complications such as blindness can be devastating, but the overall risks remain low. It’s important that clinicians know their anatomy, educate patients, and have prepared treatment protocols in place in the event of serious complications, Dr. Beleznay noted.
Dr. Beleznay disclosed relationships as an investigator, speaker, and/or consultant with AbbVie, Actelion, Allergan, Almirall, Amgen, Bausch Health, Celgene, Cipher, Evolus, Galderma, Johnson & Johnson, L’Oreal, Leo, Merz, Novartis, Procter & Gamble, Prollenium, Revance, Sandoz, Sanofi, Valeant, Vichy, and Zeltiq.
MedscapeLive and this news organization are owned by the same parent company.
FROM MEDSCAPELIVE LAS VEGAS DERMATOLOGY SEMINAR
Black patients with ES-SCLC get less chemo but have better survival
Black patients with extensive-stage small cell lung cancer (ES-SCLC) are less likely to receive chemotherapy but have better survival, compared with White patients, according to a study published in JTO Clinical Research and Reports.
This study provides a large-scale analysis of real-world data identifying racial and socioeconomic factors impacting systemic therapy delivery and survival in ES-SCLC.
“The most important finding was the significant disparity in receipt of chemotherapy,” said study author Umit Tapan, MD, of Boston Medical Center.
“Black individuals with ES-SCLC were less likely to receive chemotherapy compared to Whites and other racial groups. Similarly, elderly, uninsured patients, patients with nonprivate health insurance, and those with lower education levels were less likely to be treated with chemotherapy,” Dr. Tapan said.
Using the National Cancer Data Base (NCDB), Dr. Tapan and colleagues identified 148,961 patients who were diagnosed with stage IV ES-SCLC during 2004-2016. In all, 82,592 patients were included in the study.
Results: Treatment and survival
Compared with White patients, Black patients (adjusted odds ratio, 0.85; P = .0004) and patients from other racial groups (aOR, 0.87; P = .126) had lower odds of receiving chemotherapy on multivariate analysis.
However, survival was superior in Black patients (adjusted hazard ratio, 0.92; P < .0001) and other non-White patients (aHR 0.86; P < .0001).
“We speculate that additional factors, such as performance status, which is not captured by NCDB, might have accounted for better survival for Black patients,” Dr. Tapan said, noting that the analysis was adjusted for known possible confounding factors, such as age, gender, and comorbidity status.
Black patients had higher odds of receiving chemotherapy between 2010 and 2016 compared with 2004 and 2009. “This suggests a positive impact of the Patient Protection and Affordable Care Act (ACA) in 2010,” Dr. Tapan said.
Another surprising finding pertained to patients with nonprivate insurance. These patients had even lower odds of getting chemotherapy after the implementation of ACA, Dr. Tapan said. Patients who had private insurance had higher survival compared with those who were uninsured.
Higher level of education, measured by percentage of residents with a high school degree, increased the odds of receiving chemotherapy.
Age also had a significant impact on receipt of chemotherapy. About 83% of patients over age 80 years received chemotherapy, compared with 94% of patients aged 40-64 years.
Real-world data
Minorities are underrepresented in cancer clinical trials in the United States, with only 2% of National Cancer Institute trials having sufficient minority participants, Dr. Tapan said. A study published in Academic Medicine in 2018 showed that only 13% of 782 National Institute of Health–sponsored clinical trials reported outcomes by race and ethnicity.
As a result, we are missing data on patient care in minority populations, Dr. Tapan said. “Collecting and analyzing real-world data becomes critical to study treatment patterns and outcomes,” he added.
The current real-world study had a somewhat diverse patient population, but 90.6% of patients were White, 7.8% were Black, and 1.7% were other races.
“We would have expected a higher percentage of Black patients considering the most recent U.S. Census Bureau estimates that 76.3% of the U.S. population is White and 13.4% is Black,” Dr. Tapan said. “There are conflicting results in the literature regarding racial disparities in SCLC and survival. Many of these studies were performed via state-based cancer registries instead of on a national level, making prior reports less generalizable.”
‘More work to do’
While the new study showed patients with nonprivate insurance or those with no insurance were less likely to receive chemotherapy, studies have shown that chemotherapy administration was not impacted by insurance status in limited-stage SCLC.
This is in contrast to radiotherapy delivery. Studies have revealed a lower likelihood of radiotherapy delivery in limited-stage SCLC for patients with government health insurance such as Medicare/Medicaid, Dr. Tapan said.
“Access to cancer care has been shown to be one of the most important barriers in racial disparity. Studies analyzing outcomes in the equal access health systems, such as the Veteran Administration, have revealed less racial disparities,” Dr. Tapan said.
Even when Black patients have equal access to care, they might receive suboptimal treatment, Dr. Tapan noted.
“Studies have shown that Black patients are not only more likely to refuse surgery, but also are more likely to be given a negative recommendation by a surgeon as compared to Whites, suggesting potential involvement of miscommunication or bias during patient-physician encounters,” Dr. Tapan said. “In the same vein, physicians would need to acknowledge their patients’ beliefs. Not doing so may lead to unsatisfactory physician-patient interactions and suboptimal decision-making.”
“Measures to reduce physician bias are an important step to reduce disparities,” Dr. Tapan continued. “Studies have shown that Black patients are perceived to be less intelligent and educated, less likely to have social support, and more likely to be at risk of noncompliance. For some patients and oncologists, extra effort is needed so that every patient can access the best possible treatments and outcomes. It is the oncologist’s responsibility to advocate for patients, but, ultimately, further legislative actions are needed to mitigate the disparities around cancer care.”
Dr. Tapan noted that, in 1966, Martin Luther King Jr., PhD, stated that “of all the forms of inequality, injustice in health care is the most shocking and inhumane.”
Dr. Tapan said: “We have overcome some barriers since 1966, but we have more work to do.” He and colleagues had no disclosures related to this study.
SOURCE: Tapan U et al. JTO Clin Res Rep. 2020. doi: 10.1016/j.jtocrr.2020.100109.
Black patients with extensive-stage small cell lung cancer (ES-SCLC) are less likely to receive chemotherapy but have better survival, compared with White patients, according to a study published in JTO Clinical Research and Reports.
This study provides a large-scale analysis of real-world data identifying racial and socioeconomic factors impacting systemic therapy delivery and survival in ES-SCLC.
“The most important finding was the significant disparity in receipt of chemotherapy,” said study author Umit Tapan, MD, of Boston Medical Center.
“Black individuals with ES-SCLC were less likely to receive chemotherapy compared to Whites and other racial groups. Similarly, elderly, uninsured patients, patients with nonprivate health insurance, and those with lower education levels were less likely to be treated with chemotherapy,” Dr. Tapan said.
Using the National Cancer Data Base (NCDB), Dr. Tapan and colleagues identified 148,961 patients who were diagnosed with stage IV ES-SCLC during 2004-2016. In all, 82,592 patients were included in the study.
Results: Treatment and survival
Compared with White patients, Black patients (adjusted odds ratio, 0.85; P = .0004) and patients from other racial groups (aOR, 0.87; P = .126) had lower odds of receiving chemotherapy on multivariate analysis.
However, survival was superior in Black patients (adjusted hazard ratio, 0.92; P < .0001) and other non-White patients (aHR 0.86; P < .0001).
“We speculate that additional factors, such as performance status, which is not captured by NCDB, might have accounted for better survival for Black patients,” Dr. Tapan said, noting that the analysis was adjusted for known possible confounding factors, such as age, gender, and comorbidity status.
Black patients had higher odds of receiving chemotherapy between 2010 and 2016 compared with 2004 and 2009. “This suggests a positive impact of the Patient Protection and Affordable Care Act (ACA) in 2010,” Dr. Tapan said.
Another surprising finding pertained to patients with nonprivate insurance. These patients had even lower odds of getting chemotherapy after the implementation of ACA, Dr. Tapan said. Patients who had private insurance had higher survival compared with those who were uninsured.
Higher level of education, measured by percentage of residents with a high school degree, increased the odds of receiving chemotherapy.
Age also had a significant impact on receipt of chemotherapy. About 83% of patients over age 80 years received chemotherapy, compared with 94% of patients aged 40-64 years.
Real-world data
Minorities are underrepresented in cancer clinical trials in the United States, with only 2% of National Cancer Institute trials having sufficient minority participants, Dr. Tapan said. A study published in Academic Medicine in 2018 showed that only 13% of 782 National Institute of Health–sponsored clinical trials reported outcomes by race and ethnicity.
As a result, we are missing data on patient care in minority populations, Dr. Tapan said. “Collecting and analyzing real-world data becomes critical to study treatment patterns and outcomes,” he added.
The current real-world study had a somewhat diverse patient population, but 90.6% of patients were White, 7.8% were Black, and 1.7% were other races.
“We would have expected a higher percentage of Black patients considering the most recent U.S. Census Bureau estimates that 76.3% of the U.S. population is White and 13.4% is Black,” Dr. Tapan said. “There are conflicting results in the literature regarding racial disparities in SCLC and survival. Many of these studies were performed via state-based cancer registries instead of on a national level, making prior reports less generalizable.”
‘More work to do’
While the new study showed patients with nonprivate insurance or those with no insurance were less likely to receive chemotherapy, studies have shown that chemotherapy administration was not impacted by insurance status in limited-stage SCLC.
This is in contrast to radiotherapy delivery. Studies have revealed a lower likelihood of radiotherapy delivery in limited-stage SCLC for patients with government health insurance such as Medicare/Medicaid, Dr. Tapan said.
“Access to cancer care has been shown to be one of the most important barriers in racial disparity. Studies analyzing outcomes in the equal access health systems, such as the Veteran Administration, have revealed less racial disparities,” Dr. Tapan said.
Even when Black patients have equal access to care, they might receive suboptimal treatment, Dr. Tapan noted.
“Studies have shown that Black patients are not only more likely to refuse surgery, but also are more likely to be given a negative recommendation by a surgeon as compared to Whites, suggesting potential involvement of miscommunication or bias during patient-physician encounters,” Dr. Tapan said. “In the same vein, physicians would need to acknowledge their patients’ beliefs. Not doing so may lead to unsatisfactory physician-patient interactions and suboptimal decision-making.”
“Measures to reduce physician bias are an important step to reduce disparities,” Dr. Tapan continued. “Studies have shown that Black patients are perceived to be less intelligent and educated, less likely to have social support, and more likely to be at risk of noncompliance. For some patients and oncologists, extra effort is needed so that every patient can access the best possible treatments and outcomes. It is the oncologist’s responsibility to advocate for patients, but, ultimately, further legislative actions are needed to mitigate the disparities around cancer care.”
Dr. Tapan noted that, in 1966, Martin Luther King Jr., PhD, stated that “of all the forms of inequality, injustice in health care is the most shocking and inhumane.”
Dr. Tapan said: “We have overcome some barriers since 1966, but we have more work to do.” He and colleagues had no disclosures related to this study.
SOURCE: Tapan U et al. JTO Clin Res Rep. 2020. doi: 10.1016/j.jtocrr.2020.100109.
Black patients with extensive-stage small cell lung cancer (ES-SCLC) are less likely to receive chemotherapy but have better survival, compared with White patients, according to a study published in JTO Clinical Research and Reports.
This study provides a large-scale analysis of real-world data identifying racial and socioeconomic factors impacting systemic therapy delivery and survival in ES-SCLC.
“The most important finding was the significant disparity in receipt of chemotherapy,” said study author Umit Tapan, MD, of Boston Medical Center.
“Black individuals with ES-SCLC were less likely to receive chemotherapy compared to Whites and other racial groups. Similarly, elderly, uninsured patients, patients with nonprivate health insurance, and those with lower education levels were less likely to be treated with chemotherapy,” Dr. Tapan said.
Using the National Cancer Data Base (NCDB), Dr. Tapan and colleagues identified 148,961 patients who were diagnosed with stage IV ES-SCLC during 2004-2016. In all, 82,592 patients were included in the study.
Results: Treatment and survival
Compared with White patients, Black patients (adjusted odds ratio, 0.85; P = .0004) and patients from other racial groups (aOR, 0.87; P = .126) had lower odds of receiving chemotherapy on multivariate analysis.
However, survival was superior in Black patients (adjusted hazard ratio, 0.92; P < .0001) and other non-White patients (aHR 0.86; P < .0001).
“We speculate that additional factors, such as performance status, which is not captured by NCDB, might have accounted for better survival for Black patients,” Dr. Tapan said, noting that the analysis was adjusted for known possible confounding factors, such as age, gender, and comorbidity status.
Black patients had higher odds of receiving chemotherapy between 2010 and 2016 compared with 2004 and 2009. “This suggests a positive impact of the Patient Protection and Affordable Care Act (ACA) in 2010,” Dr. Tapan said.
Another surprising finding pertained to patients with nonprivate insurance. These patients had even lower odds of getting chemotherapy after the implementation of ACA, Dr. Tapan said. Patients who had private insurance had higher survival compared with those who were uninsured.
Higher level of education, measured by percentage of residents with a high school degree, increased the odds of receiving chemotherapy.
Age also had a significant impact on receipt of chemotherapy. About 83% of patients over age 80 years received chemotherapy, compared with 94% of patients aged 40-64 years.
Real-world data
Minorities are underrepresented in cancer clinical trials in the United States, with only 2% of National Cancer Institute trials having sufficient minority participants, Dr. Tapan said. A study published in Academic Medicine in 2018 showed that only 13% of 782 National Institute of Health–sponsored clinical trials reported outcomes by race and ethnicity.
As a result, we are missing data on patient care in minority populations, Dr. Tapan said. “Collecting and analyzing real-world data becomes critical to study treatment patterns and outcomes,” he added.
The current real-world study had a somewhat diverse patient population, but 90.6% of patients were White, 7.8% were Black, and 1.7% were other races.
“We would have expected a higher percentage of Black patients considering the most recent U.S. Census Bureau estimates that 76.3% of the U.S. population is White and 13.4% is Black,” Dr. Tapan said. “There are conflicting results in the literature regarding racial disparities in SCLC and survival. Many of these studies were performed via state-based cancer registries instead of on a national level, making prior reports less generalizable.”
‘More work to do’
While the new study showed patients with nonprivate insurance or those with no insurance were less likely to receive chemotherapy, studies have shown that chemotherapy administration was not impacted by insurance status in limited-stage SCLC.
This is in contrast to radiotherapy delivery. Studies have revealed a lower likelihood of radiotherapy delivery in limited-stage SCLC for patients with government health insurance such as Medicare/Medicaid, Dr. Tapan said.
“Access to cancer care has been shown to be one of the most important barriers in racial disparity. Studies analyzing outcomes in the equal access health systems, such as the Veteran Administration, have revealed less racial disparities,” Dr. Tapan said.
Even when Black patients have equal access to care, they might receive suboptimal treatment, Dr. Tapan noted.
“Studies have shown that Black patients are not only more likely to refuse surgery, but also are more likely to be given a negative recommendation by a surgeon as compared to Whites, suggesting potential involvement of miscommunication or bias during patient-physician encounters,” Dr. Tapan said. “In the same vein, physicians would need to acknowledge their patients’ beliefs. Not doing so may lead to unsatisfactory physician-patient interactions and suboptimal decision-making.”
“Measures to reduce physician bias are an important step to reduce disparities,” Dr. Tapan continued. “Studies have shown that Black patients are perceived to be less intelligent and educated, less likely to have social support, and more likely to be at risk of noncompliance. For some patients and oncologists, extra effort is needed so that every patient can access the best possible treatments and outcomes. It is the oncologist’s responsibility to advocate for patients, but, ultimately, further legislative actions are needed to mitigate the disparities around cancer care.”
Dr. Tapan noted that, in 1966, Martin Luther King Jr., PhD, stated that “of all the forms of inequality, injustice in health care is the most shocking and inhumane.”
Dr. Tapan said: “We have overcome some barriers since 1966, but we have more work to do.” He and colleagues had no disclosures related to this study.
SOURCE: Tapan U et al. JTO Clin Res Rep. 2020. doi: 10.1016/j.jtocrr.2020.100109.
FROM JTO CLINICAL AND RESEARCH REPORTS
Twenty years later, two gambles that paid off
Amidst the pandemic and election, two anniversaries passed almost unnoticed in early November.
On Nov. 2, 2020, we reached 20 years since the first crew moved into the International Space Station (ISS). This may seem like a minor anniversary to some, but it means a lot if you think about it. From humble beginnings, and scattered launches in different craft between 1961 and 1999, it’s now been over a generation since people weren’t living in space. We certainly aren’t on the starship Enterprise yet, or even going to Mars, but today’s college kids have never known a world where people didn’t live and work in the void upstairs. That’s something to think about.
Equally important, but of significance to far fewer, is that on Nov. 6, 2020, my little solo practice also reached its 20-year anniversary.
To the central person involved, me, this is a pretty big deal. In early 2000, when I made the decision to leave a large practice, I was confident but still nervous. I’d developed a decent referral base while working for the other group, but still didn’t know what would happen. I was 33. My oldest kid was 1 and my wife and I had twins on the way.
Now, it’s 20 years later. All three kids grew up and went off to college, but in the strange circle of the pandemic, they are now back home. Granted they’re not waking us up at night when they’re hungry (they have microwave popcorn – lots of it – for that).
Some things have changed. I’m now across the street from the office I started in. My hospital work, which in 2000 was about 50% of my practice, is now down to 0% for the time being. My medical assistant is still the same one, and my secretary has been with me since 2004. I’m lucky to have such a long-lasting team. Even in 2020, when they’re working from home, we’re still doing a great job of keeping it running.
After 20 years I’m heavier and my hair is thinning and gray, but I still like this job. I still try to do the very best I can for my patients. I sometimes read the personal statement I wrote in the summer of 1987 for my medical school application, trying to keep in touch with who I was then when I started out.
Looking back after 20 years, going solo, like building the ISS, was a big gamble. But both have worked out. My job has allowed me to support and raise a family, to care for patients (contrary to the impression one gets from medical blogs, the vast majority of them are good, decent, people) and get to know them for who they are, and to work with my two terrific long-time office staff who, like my wife, kids, and dogs, still put up with me and my quirks. And all the while I am still doing something that I found I loved in my first week of residency.
Looking forward another 20 years, who knows where I (or the ISS) will be? I probably won’t want to be working full time then, but if I still enjoy medicine I doubt I’ll want to be completely retired, either. Looking back, I’ve been fortunate that I found this one.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Amidst the pandemic and election, two anniversaries passed almost unnoticed in early November.
On Nov. 2, 2020, we reached 20 years since the first crew moved into the International Space Station (ISS). This may seem like a minor anniversary to some, but it means a lot if you think about it. From humble beginnings, and scattered launches in different craft between 1961 and 1999, it’s now been over a generation since people weren’t living in space. We certainly aren’t on the starship Enterprise yet, or even going to Mars, but today’s college kids have never known a world where people didn’t live and work in the void upstairs. That’s something to think about.
Equally important, but of significance to far fewer, is that on Nov. 6, 2020, my little solo practice also reached its 20-year anniversary.
To the central person involved, me, this is a pretty big deal. In early 2000, when I made the decision to leave a large practice, I was confident but still nervous. I’d developed a decent referral base while working for the other group, but still didn’t know what would happen. I was 33. My oldest kid was 1 and my wife and I had twins on the way.
Now, it’s 20 years later. All three kids grew up and went off to college, but in the strange circle of the pandemic, they are now back home. Granted they’re not waking us up at night when they’re hungry (they have microwave popcorn – lots of it – for that).
Some things have changed. I’m now across the street from the office I started in. My hospital work, which in 2000 was about 50% of my practice, is now down to 0% for the time being. My medical assistant is still the same one, and my secretary has been with me since 2004. I’m lucky to have such a long-lasting team. Even in 2020, when they’re working from home, we’re still doing a great job of keeping it running.
After 20 years I’m heavier and my hair is thinning and gray, but I still like this job. I still try to do the very best I can for my patients. I sometimes read the personal statement I wrote in the summer of 1987 for my medical school application, trying to keep in touch with who I was then when I started out.
Looking back after 20 years, going solo, like building the ISS, was a big gamble. But both have worked out. My job has allowed me to support and raise a family, to care for patients (contrary to the impression one gets from medical blogs, the vast majority of them are good, decent, people) and get to know them for who they are, and to work with my two terrific long-time office staff who, like my wife, kids, and dogs, still put up with me and my quirks. And all the while I am still doing something that I found I loved in my first week of residency.
Looking forward another 20 years, who knows where I (or the ISS) will be? I probably won’t want to be working full time then, but if I still enjoy medicine I doubt I’ll want to be completely retired, either. Looking back, I’ve been fortunate that I found this one.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Amidst the pandemic and election, two anniversaries passed almost unnoticed in early November.
On Nov. 2, 2020, we reached 20 years since the first crew moved into the International Space Station (ISS). This may seem like a minor anniversary to some, but it means a lot if you think about it. From humble beginnings, and scattered launches in different craft between 1961 and 1999, it’s now been over a generation since people weren’t living in space. We certainly aren’t on the starship Enterprise yet, or even going to Mars, but today’s college kids have never known a world where people didn’t live and work in the void upstairs. That’s something to think about.
Equally important, but of significance to far fewer, is that on Nov. 6, 2020, my little solo practice also reached its 20-year anniversary.
To the central person involved, me, this is a pretty big deal. In early 2000, when I made the decision to leave a large practice, I was confident but still nervous. I’d developed a decent referral base while working for the other group, but still didn’t know what would happen. I was 33. My oldest kid was 1 and my wife and I had twins on the way.
Now, it’s 20 years later. All three kids grew up and went off to college, but in the strange circle of the pandemic, they are now back home. Granted they’re not waking us up at night when they’re hungry (they have microwave popcorn – lots of it – for that).
Some things have changed. I’m now across the street from the office I started in. My hospital work, which in 2000 was about 50% of my practice, is now down to 0% for the time being. My medical assistant is still the same one, and my secretary has been with me since 2004. I’m lucky to have such a long-lasting team. Even in 2020, when they’re working from home, we’re still doing a great job of keeping it running.
After 20 years I’m heavier and my hair is thinning and gray, but I still like this job. I still try to do the very best I can for my patients. I sometimes read the personal statement I wrote in the summer of 1987 for my medical school application, trying to keep in touch with who I was then when I started out.
Looking back after 20 years, going solo, like building the ISS, was a big gamble. But both have worked out. My job has allowed me to support and raise a family, to care for patients (contrary to the impression one gets from medical blogs, the vast majority of them are good, decent, people) and get to know them for who they are, and to work with my two terrific long-time office staff who, like my wife, kids, and dogs, still put up with me and my quirks. And all the while I am still doing something that I found I loved in my first week of residency.
Looking forward another 20 years, who knows where I (or the ISS) will be? I probably won’t want to be working full time then, but if I still enjoy medicine I doubt I’ll want to be completely retired, either. Looking back, I’ve been fortunate that I found this one.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Adverse events occur in LTC residents transitioning from hospital to nursing home
Background: Adverse events in the immediate posthospitalization period are a serious threat to patients 65 years and older who are residents of long-term care facilities. Changes during hospitalization – such as fasting for procedures, immobility, change in surroundings, disruption of sleep, and medication adjustments – can lead to adverse events such as falls, pressure ulcers, adverse drug reactions, and health care–acquired infections. However, the frequency and preventability of these adverse events has not been measured.
Study design: Prospective cohort study.
Setting: Nursing homes in the New England states.
Synopsis: This study sampled 762 hospital discharges for 555 long-term care residents of 32 nursing homes who were discharged from the hospital back to their same long-term care facility and followed for 45 days. A trained nurse reviewed records using a trigger tool developed by the Institute for Healthcare Improvement. Each trigger linked to a possible harm was reviewed by two physicians. Adverse events were categorized into health care–acquired infections and events related to resident care, medications, and procedures. The severity and preventability of each event was assessed.
Of the 555 residents, 65.5% were female and the mean age was 82.2. There were 379 adverse events identified; 52% involved pressure ulcers, skin tears, and falls with injury, which were deemed preventable. Healthcare-acquired infections totaled 28.5% and adverse drug events were 16.5%. Close to half of the events were serious, life threatening, or fatal. The study was limited by subjectivity in classifying the adverse events.
Hospitalists should ensure proper coordination and handoff when transitioning patients back to their nursing home.
Bottom line: Adverse events occur in 4 of 10 discharges from the hospital to long-term care facilities, and most events are preventable.
Citation: Kapoor A et al. Adverse events in long-term care residents transitioning from hospital back to nursing home. JAMA Intern Med. 2019 Jul 22;179(9):1254-61.
Dr. Ali is assistant professor of internal medicine and section chief of hospital medicine at St. Louis University School of Medicine.
Background: Adverse events in the immediate posthospitalization period are a serious threat to patients 65 years and older who are residents of long-term care facilities. Changes during hospitalization – such as fasting for procedures, immobility, change in surroundings, disruption of sleep, and medication adjustments – can lead to adverse events such as falls, pressure ulcers, adverse drug reactions, and health care–acquired infections. However, the frequency and preventability of these adverse events has not been measured.
Study design: Prospective cohort study.
Setting: Nursing homes in the New England states.
Synopsis: This study sampled 762 hospital discharges for 555 long-term care residents of 32 nursing homes who were discharged from the hospital back to their same long-term care facility and followed for 45 days. A trained nurse reviewed records using a trigger tool developed by the Institute for Healthcare Improvement. Each trigger linked to a possible harm was reviewed by two physicians. Adverse events were categorized into health care–acquired infections and events related to resident care, medications, and procedures. The severity and preventability of each event was assessed.
Of the 555 residents, 65.5% were female and the mean age was 82.2. There were 379 adverse events identified; 52% involved pressure ulcers, skin tears, and falls with injury, which were deemed preventable. Healthcare-acquired infections totaled 28.5% and adverse drug events were 16.5%. Close to half of the events were serious, life threatening, or fatal. The study was limited by subjectivity in classifying the adverse events.
Hospitalists should ensure proper coordination and handoff when transitioning patients back to their nursing home.
Bottom line: Adverse events occur in 4 of 10 discharges from the hospital to long-term care facilities, and most events are preventable.
Citation: Kapoor A et al. Adverse events in long-term care residents transitioning from hospital back to nursing home. JAMA Intern Med. 2019 Jul 22;179(9):1254-61.
Dr. Ali is assistant professor of internal medicine and section chief of hospital medicine at St. Louis University School of Medicine.
Background: Adverse events in the immediate posthospitalization period are a serious threat to patients 65 years and older who are residents of long-term care facilities. Changes during hospitalization – such as fasting for procedures, immobility, change in surroundings, disruption of sleep, and medication adjustments – can lead to adverse events such as falls, pressure ulcers, adverse drug reactions, and health care–acquired infections. However, the frequency and preventability of these adverse events has not been measured.
Study design: Prospective cohort study.
Setting: Nursing homes in the New England states.
Synopsis: This study sampled 762 hospital discharges for 555 long-term care residents of 32 nursing homes who were discharged from the hospital back to their same long-term care facility and followed for 45 days. A trained nurse reviewed records using a trigger tool developed by the Institute for Healthcare Improvement. Each trigger linked to a possible harm was reviewed by two physicians. Adverse events were categorized into health care–acquired infections and events related to resident care, medications, and procedures. The severity and preventability of each event was assessed.
Of the 555 residents, 65.5% were female and the mean age was 82.2. There were 379 adverse events identified; 52% involved pressure ulcers, skin tears, and falls with injury, which were deemed preventable. Healthcare-acquired infections totaled 28.5% and adverse drug events were 16.5%. Close to half of the events were serious, life threatening, or fatal. The study was limited by subjectivity in classifying the adverse events.
Hospitalists should ensure proper coordination and handoff when transitioning patients back to their nursing home.
Bottom line: Adverse events occur in 4 of 10 discharges from the hospital to long-term care facilities, and most events are preventable.
Citation: Kapoor A et al. Adverse events in long-term care residents transitioning from hospital back to nursing home. JAMA Intern Med. 2019 Jul 22;179(9):1254-61.
Dr. Ali is assistant professor of internal medicine and section chief of hospital medicine at St. Louis University School of Medicine.
December 2020 - Quick Quiz Question 2
Q2. Correct answer: D
Rationale
Deficient intake of fiber and folate may originate in the food choice of the individual, whereas some deficiencies of intake, such as thiamine, appear to be celiac specific. The provider should encourage intake of nutrient-dense foods including wholegrain foods, enriched if possible, legumes, fruits, vegetables, lean meat, fish, chicken, and eggs. It is not necessary to prioritize micronutrient supplements over achieving nutritional adequacy through dietary intake. Iron deficiency is an effect of untreated celiac disease.
Reference
1. Shepherd SJ, Gibson PR. J Human Nutr Dietet. 2012;26:349-58.
Q2. Correct answer: D
Rationale
Deficient intake of fiber and folate may originate in the food choice of the individual, whereas some deficiencies of intake, such as thiamine, appear to be celiac specific. The provider should encourage intake of nutrient-dense foods including wholegrain foods, enriched if possible, legumes, fruits, vegetables, lean meat, fish, chicken, and eggs. It is not necessary to prioritize micronutrient supplements over achieving nutritional adequacy through dietary intake. Iron deficiency is an effect of untreated celiac disease.
Reference
1. Shepherd SJ, Gibson PR. J Human Nutr Dietet. 2012;26:349-58.
Q2. Correct answer: D
Rationale
Deficient intake of fiber and folate may originate in the food choice of the individual, whereas some deficiencies of intake, such as thiamine, appear to be celiac specific. The provider should encourage intake of nutrient-dense foods including wholegrain foods, enriched if possible, legumes, fruits, vegetables, lean meat, fish, chicken, and eggs. It is not necessary to prioritize micronutrient supplements over achieving nutritional adequacy through dietary intake. Iron deficiency is an effect of untreated celiac disease.
Reference
1. Shepherd SJ, Gibson PR. J Human Nutr Dietet. 2012;26:349-58.
Question 2
December 2020 - Quick Quiz Question 1
Correct answer: C
Rationale
According to the Multi-Society Task Force on Colorectal Cancer, colonoscopy should be performed 1 year after resection, and again 3 years later, in order to decrease the risk of metachronous colorectal cancer.
Reference
1. Kahi CJ, Boland CR, Dominitz JA. Gastroenterology. 2016. 150(3):758-68.e11.
Correct answer: C
Rationale
According to the Multi-Society Task Force on Colorectal Cancer, colonoscopy should be performed 1 year after resection, and again 3 years later, in order to decrease the risk of metachronous colorectal cancer.
Reference
1. Kahi CJ, Boland CR, Dominitz JA. Gastroenterology. 2016. 150(3):758-68.e11.
Correct answer: C
Rationale
According to the Multi-Society Task Force on Colorectal Cancer, colonoscopy should be performed 1 year after resection, and again 3 years later, in order to decrease the risk of metachronous colorectal cancer.
Reference
1. Kahi CJ, Boland CR, Dominitz JA. Gastroenterology. 2016. 150(3):758-68.e11.
You perform a colonoscopy for a patient who underwent sigmoid resection for stage 2 colorectal cancer 1 year ago. The colonoscopy reveals one diminutive adenoma in the cecum, which you remove with a cold snare.
Hemochromatosis variants may confer 10-fold higher risk of liver cancer
Hereditary hemochromatosis is primarily caused by HFE gene variants. Past research suggested that 81% of patients with hereditary hemochromatosis carry the p.C282Y variant and 5% carry the p.C282Y/p.H63D compound heterozygote genotype.
In a new study, the presence of HFE p.C282Y and p.H63D genotypes was associated with a 10-fold greater risk of developing a hepatic malignancy among men of European ancestry aged 40-70 years. In addition, men with HFE variants were 1.2 times more likely to die of any cause, compared with men who had neither pathogenic variant.
Janice L. Atkins, PhD, of the University of Exeter (England), and colleagues reported these findings in JAMA.
For this study, Dr. Atkins and colleagues used follow-up data from a large genotyped community sample to estimate the incidence of primary hepatic carcinomas and deaths by HFE variant status in participants of European descent.
Data for the two linked coprimary endpoints, incident primary liver carcinoma and all-cause mortality, were derived from hospital and death certificate records. Where available, primary care data was also included.
Results: Increased risks for men, not women
The researchers analyzed data from 451,186 men and women, aged 40-70 years, from the UK Biobank. There were 2,890 (0.9%) patients who were p.C282Y homozygous, 1,294 of whom were men.
Among the 1,294 men with HFE p.C282Y homozygosity, 21 were diagnosed with a primary hepatic malignancy. Ten of these patients were not diagnosed with hemochromatosis at baseline.
At a median follow-up of 8.9 years, the risk of primary hepatic malignancy was significantly higher in men with HFE p.C282Y homozygosity, compared with men without HFE pathogenic variants (hazard ratio, 10.5; 95% confidence interval, 6.6-16.7; P < .001).
The risk of all-cause death was significantly higher in men with HFE p.C282Y homozygosity as well (HR, 1.2; 95% CI, 1.0-1.5; P = .046).
In contrast, female HFE p.C282Y homozygotes had no significant increases in the risk of incident primary hepatic malignancy or all-cause mortality.
Life table projections estimated that 7.2% of men with HFE p.C282Y homozygosity will develop a primary hepatic malignancy by age 75, compared with 0.6% of men without p.C282Y or p.H63D variants.
The researchers acknowledged that a key limitation of this study was the ancestral homogeneity of the cohort. Thus, the findings may not be generalizable to all patient populations.
Implications: Earlier diagnosis and treatment
The results of this study underline the importance of early diagnosis and genetic testing, according to the researchers.
“Tragically, men with the hemochromatosis faulty genes have been dying of liver cancer for many years, but this was thought to be rare,” study author David Melzer, MBBCh, PhD, of University of Exeter, said in a press release.
“The large scale of the UK Biobank study allowed us to measure cancer risk accurately. We were shocked to find that more than 7% of men with two faulty genes are likely to develop liver cancer by age 75, particularly considering that the U.K. has the second-highest rate of these faulty genes in the world. Fortunately, most of these cancers could be prevented with early treatment,” Dr. Melzer added.
“Physicians and scientists have long acknowledged that iron overload is an important cofactor fueling the development of many serious diseases, including cancer,” said study author Jeremy Shearman, MBChB, DPhil, of Nuffield Health and South Warwickshire NHS Foundation Trust in the United Kingdom.
“This research is a vital step towards quantifying that risk and should raise awareness of the importance of iron in the minds of both clinicians and patients. Measurement of iron stores and recognition of the genetic risk of iron overload needs to become a routine part of health assessment and monitoring in the U.K.,” Dr. Shearman added.
“The UK Biobank project is a glimpse into the future of medicine where all known genes are tested and then treatable conditions are offered treatment before serious complications develop,” said study author Paul Adams, MD, of the University of Western Ontario in London.
This research was funded by the UK Medical Research Council. Dr. Melzer disclosed financial affiliations with the UK Medical Research Council during the conduct of the study.
SOURCE: Atkins JL et al. JAMA. 2020 Nov 24. doi: 10.1001/jama.2020.21566.
Hereditary hemochromatosis is primarily caused by HFE gene variants. Past research suggested that 81% of patients with hereditary hemochromatosis carry the p.C282Y variant and 5% carry the p.C282Y/p.H63D compound heterozygote genotype.
In a new study, the presence of HFE p.C282Y and p.H63D genotypes was associated with a 10-fold greater risk of developing a hepatic malignancy among men of European ancestry aged 40-70 years. In addition, men with HFE variants were 1.2 times more likely to die of any cause, compared with men who had neither pathogenic variant.
Janice L. Atkins, PhD, of the University of Exeter (England), and colleagues reported these findings in JAMA.
For this study, Dr. Atkins and colleagues used follow-up data from a large genotyped community sample to estimate the incidence of primary hepatic carcinomas and deaths by HFE variant status in participants of European descent.
Data for the two linked coprimary endpoints, incident primary liver carcinoma and all-cause mortality, were derived from hospital and death certificate records. Where available, primary care data was also included.
Results: Increased risks for men, not women
The researchers analyzed data from 451,186 men and women, aged 40-70 years, from the UK Biobank. There were 2,890 (0.9%) patients who were p.C282Y homozygous, 1,294 of whom were men.
Among the 1,294 men with HFE p.C282Y homozygosity, 21 were diagnosed with a primary hepatic malignancy. Ten of these patients were not diagnosed with hemochromatosis at baseline.
At a median follow-up of 8.9 years, the risk of primary hepatic malignancy was significantly higher in men with HFE p.C282Y homozygosity, compared with men without HFE pathogenic variants (hazard ratio, 10.5; 95% confidence interval, 6.6-16.7; P < .001).
The risk of all-cause death was significantly higher in men with HFE p.C282Y homozygosity as well (HR, 1.2; 95% CI, 1.0-1.5; P = .046).
In contrast, female HFE p.C282Y homozygotes had no significant increases in the risk of incident primary hepatic malignancy or all-cause mortality.
Life table projections estimated that 7.2% of men with HFE p.C282Y homozygosity will develop a primary hepatic malignancy by age 75, compared with 0.6% of men without p.C282Y or p.H63D variants.
The researchers acknowledged that a key limitation of this study was the ancestral homogeneity of the cohort. Thus, the findings may not be generalizable to all patient populations.
Implications: Earlier diagnosis and treatment
The results of this study underline the importance of early diagnosis and genetic testing, according to the researchers.
“Tragically, men with the hemochromatosis faulty genes have been dying of liver cancer for many years, but this was thought to be rare,” study author David Melzer, MBBCh, PhD, of University of Exeter, said in a press release.
“The large scale of the UK Biobank study allowed us to measure cancer risk accurately. We were shocked to find that more than 7% of men with two faulty genes are likely to develop liver cancer by age 75, particularly considering that the U.K. has the second-highest rate of these faulty genes in the world. Fortunately, most of these cancers could be prevented with early treatment,” Dr. Melzer added.
“Physicians and scientists have long acknowledged that iron overload is an important cofactor fueling the development of many serious diseases, including cancer,” said study author Jeremy Shearman, MBChB, DPhil, of Nuffield Health and South Warwickshire NHS Foundation Trust in the United Kingdom.
“This research is a vital step towards quantifying that risk and should raise awareness of the importance of iron in the minds of both clinicians and patients. Measurement of iron stores and recognition of the genetic risk of iron overload needs to become a routine part of health assessment and monitoring in the U.K.,” Dr. Shearman added.
“The UK Biobank project is a glimpse into the future of medicine where all known genes are tested and then treatable conditions are offered treatment before serious complications develop,” said study author Paul Adams, MD, of the University of Western Ontario in London.
This research was funded by the UK Medical Research Council. Dr. Melzer disclosed financial affiliations with the UK Medical Research Council during the conduct of the study.
SOURCE: Atkins JL et al. JAMA. 2020 Nov 24. doi: 10.1001/jama.2020.21566.
Hereditary hemochromatosis is primarily caused by HFE gene variants. Past research suggested that 81% of patients with hereditary hemochromatosis carry the p.C282Y variant and 5% carry the p.C282Y/p.H63D compound heterozygote genotype.
In a new study, the presence of HFE p.C282Y and p.H63D genotypes was associated with a 10-fold greater risk of developing a hepatic malignancy among men of European ancestry aged 40-70 years. In addition, men with HFE variants were 1.2 times more likely to die of any cause, compared with men who had neither pathogenic variant.
Janice L. Atkins, PhD, of the University of Exeter (England), and colleagues reported these findings in JAMA.
For this study, Dr. Atkins and colleagues used follow-up data from a large genotyped community sample to estimate the incidence of primary hepatic carcinomas and deaths by HFE variant status in participants of European descent.
Data for the two linked coprimary endpoints, incident primary liver carcinoma and all-cause mortality, were derived from hospital and death certificate records. Where available, primary care data was also included.
Results: Increased risks for men, not women
The researchers analyzed data from 451,186 men and women, aged 40-70 years, from the UK Biobank. There were 2,890 (0.9%) patients who were p.C282Y homozygous, 1,294 of whom were men.
Among the 1,294 men with HFE p.C282Y homozygosity, 21 were diagnosed with a primary hepatic malignancy. Ten of these patients were not diagnosed with hemochromatosis at baseline.
At a median follow-up of 8.9 years, the risk of primary hepatic malignancy was significantly higher in men with HFE p.C282Y homozygosity, compared with men without HFE pathogenic variants (hazard ratio, 10.5; 95% confidence interval, 6.6-16.7; P < .001).
The risk of all-cause death was significantly higher in men with HFE p.C282Y homozygosity as well (HR, 1.2; 95% CI, 1.0-1.5; P = .046).
In contrast, female HFE p.C282Y homozygotes had no significant increases in the risk of incident primary hepatic malignancy or all-cause mortality.
Life table projections estimated that 7.2% of men with HFE p.C282Y homozygosity will develop a primary hepatic malignancy by age 75, compared with 0.6% of men without p.C282Y or p.H63D variants.
The researchers acknowledged that a key limitation of this study was the ancestral homogeneity of the cohort. Thus, the findings may not be generalizable to all patient populations.
Implications: Earlier diagnosis and treatment
The results of this study underline the importance of early diagnosis and genetic testing, according to the researchers.
“Tragically, men with the hemochromatosis faulty genes have been dying of liver cancer for many years, but this was thought to be rare,” study author David Melzer, MBBCh, PhD, of University of Exeter, said in a press release.
“The large scale of the UK Biobank study allowed us to measure cancer risk accurately. We were shocked to find that more than 7% of men with two faulty genes are likely to develop liver cancer by age 75, particularly considering that the U.K. has the second-highest rate of these faulty genes in the world. Fortunately, most of these cancers could be prevented with early treatment,” Dr. Melzer added.
“Physicians and scientists have long acknowledged that iron overload is an important cofactor fueling the development of many serious diseases, including cancer,” said study author Jeremy Shearman, MBChB, DPhil, of Nuffield Health and South Warwickshire NHS Foundation Trust in the United Kingdom.
“This research is a vital step towards quantifying that risk and should raise awareness of the importance of iron in the minds of both clinicians and patients. Measurement of iron stores and recognition of the genetic risk of iron overload needs to become a routine part of health assessment and monitoring in the U.K.,” Dr. Shearman added.
“The UK Biobank project is a glimpse into the future of medicine where all known genes are tested and then treatable conditions are offered treatment before serious complications develop,” said study author Paul Adams, MD, of the University of Western Ontario in London.
This research was funded by the UK Medical Research Council. Dr. Melzer disclosed financial affiliations with the UK Medical Research Council during the conduct of the study.
SOURCE: Atkins JL et al. JAMA. 2020 Nov 24. doi: 10.1001/jama.2020.21566.
FROM JAMA
Approval of COVID-19 vaccines will change nature of clinical trials
While stressing the urgent need to vaccinate the whole U.S. population, infectious disease experts and medical ethicists are raising questions about the clinical trials needed to answer important questions about the new COVID-19 vaccines.
In a statement released on Nov. 20, Barbara Alexander, MD, president of the Infectious Diseases Society of America (IDSA) and a professor at Duke University, Durham, N.C., commented on Pfizer and BioNTech’s application to the Food and Drug Administration for an emergency use authorization (EUA) for its COVID-19 vaccine. Besides emphasizing the need for a transparent review of the companies’ trial data prior to the FDA’s granting an EUA, she said, “If emergency use authorization is granted, clinical trials and data collection must continue.”
In an interview, Dr. Alexander said she is convinced that both Pfizer and Moderna, which is also expected to seek an EUA soon, will continue their clinical trials to monitor the long-term safety and efficacy of their vaccines.
“The EUA guidance for COVID vaccine authorization is very clear that clinical trials will move forward,” she said. “Any EUA request would have to include a strategy to ensure that the long-term safety and efficacy of a vaccine could be monitored. I see no evidence that either Pfizer or Moderna is not prepared to follow those regulations.”
Eventually, she added, the drug makers will have to seek full FDA approval to replace an EUA, which as its name signifies, is designed for public health emergencies. “The EUA is a tool to help us get the vaccine into circulation and have it start working as quickly as possible in the current health crisis,” she said. “But once the crisis is over, if the sponsors want to continue to market their vaccines, they have to go forward and get full approval.”
Medical ethicists, however, point out there may be ethical and practical dilemmas involved in continuing or initiating clinical trials once a vaccine has been approved for use even on an emergency basis.
In a commentary in Annals of Internal Medicine, Rafael Dal-Re, MD, PhD, Arthur L. Caplan, PhD, and two other ethicists stipulated that the pandemic requires early licensing and deployment of COVID-19 vaccines. Nevertheless, they noted, additional months of data are required to establish the long-term efficacy and safety of the vaccines. “Moreover, early deployment could interfere with the acquisition of long-term data,” both on these vaccines and on others coming through the pipeline, they wrote.
In countries where an approved vaccine is deployed, the ethicists noted, investigators must inform participants in an ongoing trial about the approved vaccine’s status and ask if they want to continue in the study. If enough participants decline, the trial might have to be terminated early. At that point, researchers may not have sufficient long-term data to identify late-term safety issues, determine how long efficacy lasts, determine whether waning immunity is associated with reduced levels of antibodies, or identify the level of neutralizing antibodies that correlates with immunity.
Moreover, they observed, long-term trials are especially important for vaccines that use mRNA technology, because less is known about them than about traditional kinds of vaccines.
The authors also pointed out that early licensing of any vaccine might make it harder to evaluate vaccines that haven’t yet been approved. “Once a vaccine is licensed, new placebo-controlled RCTs [randomized controlled trials] of other vaccines will not be acceptable ethically, and noninferiority RCTs will be the most likely alternative.
“The goal of noninferiority trials will be to demonstrate that the immune response (that is, neutralizing antibody titers or levels) of the candidate vaccine is not inferior to that of the approved vaccine within a prespecified margin, which the FDA has established as less than 10% for COVID-19 vaccines,” the authors noted.
More data with more study designs
Dial Hewlett Jr., MD, medical director for disease control services, Westchester County Department of Health, White Plains, N.Y., said in an interview that the ethicists raise important issues that have been discussed in other forums, including a recent webinar of the National Academy of Medicine.
“As the authors point out, once you have a vaccine that has been shown to be effective and safe, it’s no longer ethical to enroll people in placebo trials,” he said.
Therefore, he said, Pfizer and Moderna will undoubtedly offer their vaccines to the people in their studies’ placebo groups after the vaccines receive an EUA. Then they will follow everyone who has been vaccinated for 2 years to determine long-term safety. Efficacy will also continue to be measured as an adjunct of safety, he said.
With regard to the difficulty of reconsenting individuals to enter a new clinical trial after a vaccine has been approved, he said, “I’d agree that trying to get all the same participants to come into another study would be a challenge. You can, however, design studies that will allow you to obtain the same information. You will have a large number of people out there who haven’t been vaccinated, and you can do single-arm longitudinal studies and measure a number of things in the individuals who are enrolled in those studies,” he said.
“You can look at the immunologic markers, both antibody and T-cell. You can follow these individuals longitudinally to see if they do develop disease over a period of time. If they do, you can determine what their levels of response were,” he added. “So there are opportunities to design studies that would give you some of the same information, although it would not be in the same population that was in the randomized trials.”
For newer vaccines that have yet to be tested, he said, developers can compare “historical controls” from the trials of approved vaccines, i.e., data from the unvaccinated participants in those studies, with the data from inoculating people with the novel agents. The historical data can be sex- and age-matched, among other things, to individuals in the new trials. Moreover, because the study protocols have been harmonized for all trials under Operation Warp Speed, it doesn’t matter what kind of vaccine they’re testing, he said.
It may be necessary to do additional studies to find out how long immunity lasts after people have been vaccinated, Dr. Hewlett pointed out.
“You may have a different trial design. You don’t need a control arm to determine how long immunity lasts. You’re just comparing the patients who were vaccinated to nothing,” he said. “So you could have a single-arm trial on a group of people who consent to be immunized and followed. You can see what their antibody levels are and other surrogate markers, and you can see when they might develop disease, if they do. You’d need a large sample, but you can do that.”
Dr. Hewlett noted that additional studies will be required to determine whether the new vaccines stop transmission of the coronavirus or just prevent symptoms of COVID-19. Until it’s established that a vaccine halts transmission or the country achieves herd immunity, he said, “we’ll still have to wear masks and take other precautions, because a significant portion of people will still be at risk.”
‘A lot of redundancy’
Dr. Alexander emphasized that any safety or efficacy issues with the first COVID-19 vaccines must be identified before the vaccine is offered to a large portion of the U.S. population.
“While the data from the Pfizer and Moderna trials are said to be favorable, we at IDSA want to make sure that whatever vaccine comes to market is safe,” she said. “Having an unsafe vaccine on the market would be worse than no vaccine, because you’re compromising the public confidence. We have to make sure the public trusts the process and that sufficient data have been evaluated to ensure the vaccine is safe and efficacious.
“I believe the FDA is being very careful and thoughtful in [its] response,” Dr. Alexander said. “They realize how important it is to get a vaccine and save lives. While they’re doing things differently and moving much faster than before, they’re still trying to be thoughtful and reasonable. They don’t seem to be putting people at risk or circumventing the regulatory standards.”
Moreover, she pointed out, the FDA’s Vaccines and Related Biological Products Advisory Committee, which is expected to meet on Dec. 10, will review the trial data before the agency grants an EUA to Pfizer or Moderna. Then the FDA will post the data publicly.
The next step is for the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention to look at the data and decide who in the United States should receive the vaccine first, she pointed out. And both Pfizer and Moderna have shown their data to advisory panels of outside experts.
“There’s a lot of redundancy, and a lot of people are looking at the data,” Dr. Alexander said. “So I don’t think we’re cutting corners to get it out there more quickly.”
A version of this article originally appeared on Medscape.com.
While stressing the urgent need to vaccinate the whole U.S. population, infectious disease experts and medical ethicists are raising questions about the clinical trials needed to answer important questions about the new COVID-19 vaccines.
In a statement released on Nov. 20, Barbara Alexander, MD, president of the Infectious Diseases Society of America (IDSA) and a professor at Duke University, Durham, N.C., commented on Pfizer and BioNTech’s application to the Food and Drug Administration for an emergency use authorization (EUA) for its COVID-19 vaccine. Besides emphasizing the need for a transparent review of the companies’ trial data prior to the FDA’s granting an EUA, she said, “If emergency use authorization is granted, clinical trials and data collection must continue.”
In an interview, Dr. Alexander said she is convinced that both Pfizer and Moderna, which is also expected to seek an EUA soon, will continue their clinical trials to monitor the long-term safety and efficacy of their vaccines.
“The EUA guidance for COVID vaccine authorization is very clear that clinical trials will move forward,” she said. “Any EUA request would have to include a strategy to ensure that the long-term safety and efficacy of a vaccine could be monitored. I see no evidence that either Pfizer or Moderna is not prepared to follow those regulations.”
Eventually, she added, the drug makers will have to seek full FDA approval to replace an EUA, which as its name signifies, is designed for public health emergencies. “The EUA is a tool to help us get the vaccine into circulation and have it start working as quickly as possible in the current health crisis,” she said. “But once the crisis is over, if the sponsors want to continue to market their vaccines, they have to go forward and get full approval.”
Medical ethicists, however, point out there may be ethical and practical dilemmas involved in continuing or initiating clinical trials once a vaccine has been approved for use even on an emergency basis.
In a commentary in Annals of Internal Medicine, Rafael Dal-Re, MD, PhD, Arthur L. Caplan, PhD, and two other ethicists stipulated that the pandemic requires early licensing and deployment of COVID-19 vaccines. Nevertheless, they noted, additional months of data are required to establish the long-term efficacy and safety of the vaccines. “Moreover, early deployment could interfere with the acquisition of long-term data,” both on these vaccines and on others coming through the pipeline, they wrote.
In countries where an approved vaccine is deployed, the ethicists noted, investigators must inform participants in an ongoing trial about the approved vaccine’s status and ask if they want to continue in the study. If enough participants decline, the trial might have to be terminated early. At that point, researchers may not have sufficient long-term data to identify late-term safety issues, determine how long efficacy lasts, determine whether waning immunity is associated with reduced levels of antibodies, or identify the level of neutralizing antibodies that correlates with immunity.
Moreover, they observed, long-term trials are especially important for vaccines that use mRNA technology, because less is known about them than about traditional kinds of vaccines.
The authors also pointed out that early licensing of any vaccine might make it harder to evaluate vaccines that haven’t yet been approved. “Once a vaccine is licensed, new placebo-controlled RCTs [randomized controlled trials] of other vaccines will not be acceptable ethically, and noninferiority RCTs will be the most likely alternative.
“The goal of noninferiority trials will be to demonstrate that the immune response (that is, neutralizing antibody titers or levels) of the candidate vaccine is not inferior to that of the approved vaccine within a prespecified margin, which the FDA has established as less than 10% for COVID-19 vaccines,” the authors noted.
More data with more study designs
Dial Hewlett Jr., MD, medical director for disease control services, Westchester County Department of Health, White Plains, N.Y., said in an interview that the ethicists raise important issues that have been discussed in other forums, including a recent webinar of the National Academy of Medicine.
“As the authors point out, once you have a vaccine that has been shown to be effective and safe, it’s no longer ethical to enroll people in placebo trials,” he said.
Therefore, he said, Pfizer and Moderna will undoubtedly offer their vaccines to the people in their studies’ placebo groups after the vaccines receive an EUA. Then they will follow everyone who has been vaccinated for 2 years to determine long-term safety. Efficacy will also continue to be measured as an adjunct of safety, he said.
With regard to the difficulty of reconsenting individuals to enter a new clinical trial after a vaccine has been approved, he said, “I’d agree that trying to get all the same participants to come into another study would be a challenge. You can, however, design studies that will allow you to obtain the same information. You will have a large number of people out there who haven’t been vaccinated, and you can do single-arm longitudinal studies and measure a number of things in the individuals who are enrolled in those studies,” he said.
“You can look at the immunologic markers, both antibody and T-cell. You can follow these individuals longitudinally to see if they do develop disease over a period of time. If they do, you can determine what their levels of response were,” he added. “So there are opportunities to design studies that would give you some of the same information, although it would not be in the same population that was in the randomized trials.”
For newer vaccines that have yet to be tested, he said, developers can compare “historical controls” from the trials of approved vaccines, i.e., data from the unvaccinated participants in those studies, with the data from inoculating people with the novel agents. The historical data can be sex- and age-matched, among other things, to individuals in the new trials. Moreover, because the study protocols have been harmonized for all trials under Operation Warp Speed, it doesn’t matter what kind of vaccine they’re testing, he said.
It may be necessary to do additional studies to find out how long immunity lasts after people have been vaccinated, Dr. Hewlett pointed out.
“You may have a different trial design. You don’t need a control arm to determine how long immunity lasts. You’re just comparing the patients who were vaccinated to nothing,” he said. “So you could have a single-arm trial on a group of people who consent to be immunized and followed. You can see what their antibody levels are and other surrogate markers, and you can see when they might develop disease, if they do. You’d need a large sample, but you can do that.”
Dr. Hewlett noted that additional studies will be required to determine whether the new vaccines stop transmission of the coronavirus or just prevent symptoms of COVID-19. Until it’s established that a vaccine halts transmission or the country achieves herd immunity, he said, “we’ll still have to wear masks and take other precautions, because a significant portion of people will still be at risk.”
‘A lot of redundancy’
Dr. Alexander emphasized that any safety or efficacy issues with the first COVID-19 vaccines must be identified before the vaccine is offered to a large portion of the U.S. population.
“While the data from the Pfizer and Moderna trials are said to be favorable, we at IDSA want to make sure that whatever vaccine comes to market is safe,” she said. “Having an unsafe vaccine on the market would be worse than no vaccine, because you’re compromising the public confidence. We have to make sure the public trusts the process and that sufficient data have been evaluated to ensure the vaccine is safe and efficacious.
“I believe the FDA is being very careful and thoughtful in [its] response,” Dr. Alexander said. “They realize how important it is to get a vaccine and save lives. While they’re doing things differently and moving much faster than before, they’re still trying to be thoughtful and reasonable. They don’t seem to be putting people at risk or circumventing the regulatory standards.”
Moreover, she pointed out, the FDA’s Vaccines and Related Biological Products Advisory Committee, which is expected to meet on Dec. 10, will review the trial data before the agency grants an EUA to Pfizer or Moderna. Then the FDA will post the data publicly.
The next step is for the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention to look at the data and decide who in the United States should receive the vaccine first, she pointed out. And both Pfizer and Moderna have shown their data to advisory panels of outside experts.
“There’s a lot of redundancy, and a lot of people are looking at the data,” Dr. Alexander said. “So I don’t think we’re cutting corners to get it out there more quickly.”
A version of this article originally appeared on Medscape.com.
While stressing the urgent need to vaccinate the whole U.S. population, infectious disease experts and medical ethicists are raising questions about the clinical trials needed to answer important questions about the new COVID-19 vaccines.
In a statement released on Nov. 20, Barbara Alexander, MD, president of the Infectious Diseases Society of America (IDSA) and a professor at Duke University, Durham, N.C., commented on Pfizer and BioNTech’s application to the Food and Drug Administration for an emergency use authorization (EUA) for its COVID-19 vaccine. Besides emphasizing the need for a transparent review of the companies’ trial data prior to the FDA’s granting an EUA, she said, “If emergency use authorization is granted, clinical trials and data collection must continue.”
In an interview, Dr. Alexander said she is convinced that both Pfizer and Moderna, which is also expected to seek an EUA soon, will continue their clinical trials to monitor the long-term safety and efficacy of their vaccines.
“The EUA guidance for COVID vaccine authorization is very clear that clinical trials will move forward,” she said. “Any EUA request would have to include a strategy to ensure that the long-term safety and efficacy of a vaccine could be monitored. I see no evidence that either Pfizer or Moderna is not prepared to follow those regulations.”
Eventually, she added, the drug makers will have to seek full FDA approval to replace an EUA, which as its name signifies, is designed for public health emergencies. “The EUA is a tool to help us get the vaccine into circulation and have it start working as quickly as possible in the current health crisis,” she said. “But once the crisis is over, if the sponsors want to continue to market their vaccines, they have to go forward and get full approval.”
Medical ethicists, however, point out there may be ethical and practical dilemmas involved in continuing or initiating clinical trials once a vaccine has been approved for use even on an emergency basis.
In a commentary in Annals of Internal Medicine, Rafael Dal-Re, MD, PhD, Arthur L. Caplan, PhD, and two other ethicists stipulated that the pandemic requires early licensing and deployment of COVID-19 vaccines. Nevertheless, they noted, additional months of data are required to establish the long-term efficacy and safety of the vaccines. “Moreover, early deployment could interfere with the acquisition of long-term data,” both on these vaccines and on others coming through the pipeline, they wrote.
In countries where an approved vaccine is deployed, the ethicists noted, investigators must inform participants in an ongoing trial about the approved vaccine’s status and ask if they want to continue in the study. If enough participants decline, the trial might have to be terminated early. At that point, researchers may not have sufficient long-term data to identify late-term safety issues, determine how long efficacy lasts, determine whether waning immunity is associated with reduced levels of antibodies, or identify the level of neutralizing antibodies that correlates with immunity.
Moreover, they observed, long-term trials are especially important for vaccines that use mRNA technology, because less is known about them than about traditional kinds of vaccines.
The authors also pointed out that early licensing of any vaccine might make it harder to evaluate vaccines that haven’t yet been approved. “Once a vaccine is licensed, new placebo-controlled RCTs [randomized controlled trials] of other vaccines will not be acceptable ethically, and noninferiority RCTs will be the most likely alternative.
“The goal of noninferiority trials will be to demonstrate that the immune response (that is, neutralizing antibody titers or levels) of the candidate vaccine is not inferior to that of the approved vaccine within a prespecified margin, which the FDA has established as less than 10% for COVID-19 vaccines,” the authors noted.
More data with more study designs
Dial Hewlett Jr., MD, medical director for disease control services, Westchester County Department of Health, White Plains, N.Y., said in an interview that the ethicists raise important issues that have been discussed in other forums, including a recent webinar of the National Academy of Medicine.
“As the authors point out, once you have a vaccine that has been shown to be effective and safe, it’s no longer ethical to enroll people in placebo trials,” he said.
Therefore, he said, Pfizer and Moderna will undoubtedly offer their vaccines to the people in their studies’ placebo groups after the vaccines receive an EUA. Then they will follow everyone who has been vaccinated for 2 years to determine long-term safety. Efficacy will also continue to be measured as an adjunct of safety, he said.
With regard to the difficulty of reconsenting individuals to enter a new clinical trial after a vaccine has been approved, he said, “I’d agree that trying to get all the same participants to come into another study would be a challenge. You can, however, design studies that will allow you to obtain the same information. You will have a large number of people out there who haven’t been vaccinated, and you can do single-arm longitudinal studies and measure a number of things in the individuals who are enrolled in those studies,” he said.
“You can look at the immunologic markers, both antibody and T-cell. You can follow these individuals longitudinally to see if they do develop disease over a period of time. If they do, you can determine what their levels of response were,” he added. “So there are opportunities to design studies that would give you some of the same information, although it would not be in the same population that was in the randomized trials.”
For newer vaccines that have yet to be tested, he said, developers can compare “historical controls” from the trials of approved vaccines, i.e., data from the unvaccinated participants in those studies, with the data from inoculating people with the novel agents. The historical data can be sex- and age-matched, among other things, to individuals in the new trials. Moreover, because the study protocols have been harmonized for all trials under Operation Warp Speed, it doesn’t matter what kind of vaccine they’re testing, he said.
It may be necessary to do additional studies to find out how long immunity lasts after people have been vaccinated, Dr. Hewlett pointed out.
“You may have a different trial design. You don’t need a control arm to determine how long immunity lasts. You’re just comparing the patients who were vaccinated to nothing,” he said. “So you could have a single-arm trial on a group of people who consent to be immunized and followed. You can see what their antibody levels are and other surrogate markers, and you can see when they might develop disease, if they do. You’d need a large sample, but you can do that.”
Dr. Hewlett noted that additional studies will be required to determine whether the new vaccines stop transmission of the coronavirus or just prevent symptoms of COVID-19. Until it’s established that a vaccine halts transmission or the country achieves herd immunity, he said, “we’ll still have to wear masks and take other precautions, because a significant portion of people will still be at risk.”
‘A lot of redundancy’
Dr. Alexander emphasized that any safety or efficacy issues with the first COVID-19 vaccines must be identified before the vaccine is offered to a large portion of the U.S. population.
“While the data from the Pfizer and Moderna trials are said to be favorable, we at IDSA want to make sure that whatever vaccine comes to market is safe,” she said. “Having an unsafe vaccine on the market would be worse than no vaccine, because you’re compromising the public confidence. We have to make sure the public trusts the process and that sufficient data have been evaluated to ensure the vaccine is safe and efficacious.
“I believe the FDA is being very careful and thoughtful in [its] response,” Dr. Alexander said. “They realize how important it is to get a vaccine and save lives. While they’re doing things differently and moving much faster than before, they’re still trying to be thoughtful and reasonable. They don’t seem to be putting people at risk or circumventing the regulatory standards.”
Moreover, she pointed out, the FDA’s Vaccines and Related Biological Products Advisory Committee, which is expected to meet on Dec. 10, will review the trial data before the agency grants an EUA to Pfizer or Moderna. Then the FDA will post the data publicly.
The next step is for the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention to look at the data and decide who in the United States should receive the vaccine first, she pointed out. And both Pfizer and Moderna have shown their data to advisory panels of outside experts.
“There’s a lot of redundancy, and a lot of people are looking at the data,” Dr. Alexander said. “So I don’t think we’re cutting corners to get it out there more quickly.”
A version of this article originally appeared on Medscape.com.
Expanded indications likely for apremilast
Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
“We’ll have , meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
Mild or moderate psoriasis
Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.
Pediatric studies
A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.
“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.
Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.
Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.
“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.
Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.
One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
Topical PDE-4 inhibitor shows promise
Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.
“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.
The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.
A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.
The phase 3 program is now recruiting participants.
Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.
MedscapeLive and this news organization are owned by the same parent company.
Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
“We’ll have , meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
Mild or moderate psoriasis
Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.
Pediatric studies
A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.
“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.
Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.
Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.
“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.
Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.
One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
Topical PDE-4 inhibitor shows promise
Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.
“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.
The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.
A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.
The phase 3 program is now recruiting participants.
Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.
MedscapeLive and this news organization are owned by the same parent company.
Big changes are coming in the use of oral apremilast, currently approved for moderate to severe psoriasis and plaque psoriasis in adults, Bruce E. Strober, MD, PhD, predicted at MedscapeLive’s annual Las Vegas Dermatology Seminar, held virtually this year.
“We’ll have , meaning we can use this drug in patients in whom we typically think about using only topical therapies. Keep on the lookout: I think the mild to moderate indication may be coming next year, and that’s going to really shake up the whole landscape of psoriasis therapy,” said Dr. Strober, a dermatologist at Yale University in New Haven, Conn., and Central Connecticut Dermatology in Cromwell, Conn.
Mild or moderate psoriasis
Apremilast manufacturer Amgen has announced positive topline results from the phase 3 ADVANCE trial, a multicenter, placebo-controlled, double-blind, study of 595 patients with mild or moderate psoriasis as defined by an involved body surface area of 2%-15% and a Psoriasis Area and Severity Index score of 2-15. Participants were randomized to the approved dose of apremilast (Otezla) – 30 mg twice daily – or placebo for 16 weeks, followed by 16 weeks of open-label apremilast for all. The full study findings haven’t yet been published or presented at a medical conference, but Amgen announced that the results were positive for all primary and secondary endpoints, and the company plans to file a request with the Food and Drug Administration for an expanded indication for the oral agent.
Pediatric studies
A recently published phase 2, open-label, 1-year study of apremilast in 42 children and adolescents with moderate to severe plaque psoriasis demonstrated that weight-based dosing is the best approach in the pediatric population. The study, which serves as the template for coming phase 3 trials, showed that dosing apremilast at 20 mg twice daily in youths weighing not more than 35 kg and 30 mg twice daily in those who weighed more provided pharmacokinetic exposure similar to that achieved with apremilast at the standard adult dose of 30 mg twice daily. Most participants liked the taste of the tablet.
“My prediction is apremilast will have efficacy in children and teenagers comparable to what it has in adults, with a similar safety and adverse event profile,” Dr. Strober said.
Apremilast works by blocking phosphodiesterase type 4, thereby reducing cyclic AMP metabolism, with a resultant increase in cyclic AMP levels. Cyclic AMP is a regulator of inflammation. Boosting its level has the effect of decreasing tumor necrosis factor and other proinflammatory cytokines while increasing anti-inflammatory mediators, such as interleukin-10.
Dr. Strober characterized apremilast’s efficacy as “modest” by contemporary standards in adults with moderate to severe psoriasis, with week 16 PASI 75 rates of about 30% in randomized trials, compared with 5% in placebo-treated controls. He considers it a good option in patients with moderate disease who are needle phobic and in those averse to the inconvenience of laboratory monitoring. The drug is useful in treating psoriasis in especially challenging locations. Apremilast is specifically approved for scalp psoriasis, and Dr. Strober has anecdotally found it helpful in patients with palmoplantar psoriasis or genital psoriasis.
“Apremilast has tolerability issues: first and foremost diarrhea, nausea, and headache. Probably 15%-20% of patients have nausea or diarrhea ranging from mild to severe, and 1 in 20 have headache. You have to warn patients,” he said.
Roughly 1% of patients experience depressed mood. “I’ve seen it in a few patients. I definitely believe it’s real, so query patients about mood changes while taking apremilast,” the dermatologist advised.
One in 5 patients loses 5% of body weight during the first 6 months on apremilast, but there’s no additional weight loss thereafter. It’s wrong to characterize the oral agent as a weight-loss drug, though, since 80% of patients don’t lose weight, Dr. Strober noted.
Topical PDE-4 inhibitor shows promise
Separately at the Las Vegas meeting, Linda Stein Gold, MD, provided highlights of a phase 2b randomized trial of a topical cream formulation of an extremely potent PDE-4 inhibitor, roflumilast, in patients with chronic plaque psoriasis. This molecule is a couple hundred times more effective at inhibiting the PDE-4 receptor than either oral apremilast or topical crisaborole (Eucrisa). And as a once-daily topical agent with very little systemic absorption, roflumilast cream sidesteps the tolerability issues that accompany apremilast.
“Roflumilast is currently available as an oral formulation for treatment of [chronic obstructive pulmonary disease], so it has a fairly well-established safety profile,” noted Dr. Stein Gold, director of dermatology clinical research at the Henry Ford Health System in Detroit.
The 12-week, multicenter, phase 2b study sponsored by Arcutis Biotherapeutics included 331 patients with chronic plaque psoriasis who were randomized to once-daily 0.3% roflumilast cream, 0.15% roflumilast cream, or vehicle. Three-quarters of participants had baseline moderate disease.
A week-8 Investigator’s Global Assessment (IGA) score of 0 or 1, meaning clear skin or almost clear, plus at least a 2-grade improvement from baseline occurred in 32% of the high-dose roflumilast group, 25% of those on the 0.15% formulation, and 10% of controls. On the secondary endpoint of improvement in tough-to-treat intertriginous psoriasis, at week 12 an intertriginous IGA score of 0 or 1 plus at least a 2-point improvement from baseline was seen in 86% of the 0.3% roflumilast cream group, 50% on low-dose therapy, and 29% of controls. Moreover, the clinical improvements in IGA and itch kicked in quickly, with significant separation from placebo by week 2, Dr. Stein Gold noted.
The phase 3 program is now recruiting participants.
Dr. Strober and Dr. Stein Gold reported receiving research funding from and serving as consultants to Amgen and numerous other pharmaceutical companies.
MedscapeLive and this news organization are owned by the same parent company.
FROM MEDSCAPELIVE LAS VEGAS DERMATOLOGY SEMINAR