MDedge Rheumatology

Hyperglycemia at hospital admission – regardless of diabetes status – is a key predictor of COVID-19-related death and severity among noncritical patients, new research from Spain finds.

The observational study, the largest to date to investigate this association, was published online Nov. 23 in Annals of Medicine by Francisco Javier Carrasco-Sánchez, MD, PhD, and colleagues.

Among more than 11,000 patients with confirmed COVID-19 from March to May 2020 in a nationwide Spanish registry involving 109 hospitals, admission hyperglycemia independently predicted progression from noncritical to critical condition and death, regardless of prior diabetes history. 

Those with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% vs 15.7%). They also had an increased need for a ventilator and intensive care unit (ICU) admission.

“These results provided a simple and practical way to stratify risk of death in hospitalized patients with COVID-19. Hence, admission hyperglycemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of COVID-19 patients with and without diabetes,” Dr. Carrasco-Sánchez and colleagues wrote.

The findings confirm those of previous retrospective observational studies, but the current study “has, by far, the biggest number of patients involved in this kind of study [to date]. All conclusions are consistent to other studies,” Dr. Carrasco-Sánchez, of University Hospital Juan Ramón Jiménez, Huelva, Spain, said in an interview.

However, a surprising finding, he said, “was how hyperglycemia works in the nondiabetic population and [that] glucose levels over 140 [mg/dL] ... increase the risk of death.”
 

Pay attention to even mild hyperglycemia from admission

The study also differs from some of the prior observational ones in that it examines outcome by admission glycemia rather than during the hospital stay, therefore eliminating the effect of any inpatient treatment, such as dexamethasone, he noted.

Although blood glucose measurement at admission is routine for all patients in Spain, as it is in the United States and elsewhere, a mildly elevated level in a person without a diagnosis of diabetes may not be recognized as important.

“In patients with diabetes we start the protocol to control and treat hyperglycemia during hospitalization. However, in nondiabetic patients blood glucose levels under 180 [mg/dL], and even greater, are usually overlooked. This means there is not a correct follow-up of the patients during hospitalization.

“After this study we learned that we need to pay attention to this population ... who develop hyperglycemia from the beginning,” he said.  

The study was limited in that patients who had previously undiagnosed diabetes couldn’t always be distinguished from those with acute “stress hyperglycemia.”

However, both need to be managed during hospitalization, he said. “Unfortunately, there is high variability in inpatient glucose management. The working group of diabetes of the Spanish Society of Internal Medicine is working on specific protocols,” said Dr. Carrasco-Sánchez.
 

All-cause death, progress to critical care higher with hyperglycemia

The retrospective, multicenter study was based on data from 11,312 adult patients with confirmed COVID-19 in 109 hospitals participating in Spain’s SEMI-COVID-19 registry as of May 29, 2020. They had a mean age of 67 years, 57% were male, and 19% had a diagnosis of diabetes. A total of 20% (n = 2,289) died during hospitalization.

Overall all-cause mortality was 41.1% among those with admission blood glucose levels above 180 mg/dL, 33.0% for those with glucose levels 140-180 mg/dL, and 15.7% for levels below 140 mg/dL. All differences were significant (P < .0001), but there were no differences in mortality rates within each blood glucose category between patients with or without a previous diagnosis of diabetes.

After adjustment for confounding factors, elevated admission blood glucose level remained a significant predictor of death. Compared to < 140 mg/dL, the hazard ratios for 140-180 mg/dL and > 180 mg/dL were 1.48 and 1.50, respectively (both P < .001). (Adjustments included age, gender, hypertension, diabetes, chronic obstructive pulmonary disease, lymphopenia, anemia (hemoglobin < 10 g/dL), serum creatinine, C-reactive protein > 60 mg/L, lactate dehydrogenase > 400 U/L and D-dimer >1000 ng/mL.)

Length of stay was 12, 11.5, and 11.1 days for those with admission blood glucose levels > 180, 140-180, and < 140 mg/dL, respectively (P = .011).

Use of mechanical ventilation and admission to intensive care also rose with higher admission blood glucose levels. For the composite of death, mechanical ventilation, and/or ICU admission, odds ratios for 140-180 mg/dL and > 180 mg/dL compared with < 140 mg/dL were 1.70 and 2.02, respectively (both P < .001). 

The study was supported by the Spanish Federation of Internal Medicine. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Hyperglycemia at hospital admission – regardless of diabetes status – is a key predictor of COVID-19-related death and severity among noncritical patients, new research from Spain finds.

The observational study, the largest to date to investigate this association, was published online Nov. 23 in Annals of Medicine by Francisco Javier Carrasco-Sánchez, MD, PhD, and colleagues.

Among more than 11,000 patients with confirmed COVID-19 from March to May 2020 in a nationwide Spanish registry involving 109 hospitals, admission hyperglycemia independently predicted progression from noncritical to critical condition and death, regardless of prior diabetes history. 

Those with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% vs 15.7%). They also had an increased need for a ventilator and intensive care unit (ICU) admission.

“These results provided a simple and practical way to stratify risk of death in hospitalized patients with COVID-19. Hence, admission hyperglycemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of COVID-19 patients with and without diabetes,” Dr. Carrasco-Sánchez and colleagues wrote.

The findings confirm those of previous retrospective observational studies, but the current study “has, by far, the biggest number of patients involved in this kind of study [to date]. All conclusions are consistent to other studies,” Dr. Carrasco-Sánchez, of University Hospital Juan Ramón Jiménez, Huelva, Spain, said in an interview.

However, a surprising finding, he said, “was how hyperglycemia works in the nondiabetic population and [that] glucose levels over 140 [mg/dL] ... increase the risk of death.”
 

Pay attention to even mild hyperglycemia from admission

The study also differs from some of the prior observational ones in that it examines outcome by admission glycemia rather than during the hospital stay, therefore eliminating the effect of any inpatient treatment, such as dexamethasone, he noted.

Although blood glucose measurement at admission is routine for all patients in Spain, as it is in the United States and elsewhere, a mildly elevated level in a person without a diagnosis of diabetes may not be recognized as important.

“In patients with diabetes we start the protocol to control and treat hyperglycemia during hospitalization. However, in nondiabetic patients blood glucose levels under 180 [mg/dL], and even greater, are usually overlooked. This means there is not a correct follow-up of the patients during hospitalization.

“After this study we learned that we need to pay attention to this population ... who develop hyperglycemia from the beginning,” he said.  

The study was limited in that patients who had previously undiagnosed diabetes couldn’t always be distinguished from those with acute “stress hyperglycemia.”

However, both need to be managed during hospitalization, he said. “Unfortunately, there is high variability in inpatient glucose management. The working group of diabetes of the Spanish Society of Internal Medicine is working on specific protocols,” said Dr. Carrasco-Sánchez.
 

All-cause death, progress to critical care higher with hyperglycemia

The retrospective, multicenter study was based on data from 11,312 adult patients with confirmed COVID-19 in 109 hospitals participating in Spain’s SEMI-COVID-19 registry as of May 29, 2020. They had a mean age of 67 years, 57% were male, and 19% had a diagnosis of diabetes. A total of 20% (n = 2,289) died during hospitalization.

Overall all-cause mortality was 41.1% among those with admission blood glucose levels above 180 mg/dL, 33.0% for those with glucose levels 140-180 mg/dL, and 15.7% for levels below 140 mg/dL. All differences were significant (P < .0001), but there were no differences in mortality rates within each blood glucose category between patients with or without a previous diagnosis of diabetes.

After adjustment for confounding factors, elevated admission blood glucose level remained a significant predictor of death. Compared to < 140 mg/dL, the hazard ratios for 140-180 mg/dL and > 180 mg/dL were 1.48 and 1.50, respectively (both P < .001). (Adjustments included age, gender, hypertension, diabetes, chronic obstructive pulmonary disease, lymphopenia, anemia (hemoglobin < 10 g/dL), serum creatinine, C-reactive protein > 60 mg/L, lactate dehydrogenase > 400 U/L and D-dimer >1000 ng/mL.)

Length of stay was 12, 11.5, and 11.1 days for those with admission blood glucose levels > 180, 140-180, and < 140 mg/dL, respectively (P = .011).

Use of mechanical ventilation and admission to intensive care also rose with higher admission blood glucose levels. For the composite of death, mechanical ventilation, and/or ICU admission, odds ratios for 140-180 mg/dL and > 180 mg/dL compared with < 140 mg/dL were 1.70 and 2.02, respectively (both P < .001). 

The study was supported by the Spanish Federation of Internal Medicine. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Hyperglycemia at hospital admission – regardless of diabetes status – is a key predictor of COVID-19-related death and severity among noncritical patients, new research from Spain finds.

The observational study, the largest to date to investigate this association, was published online Nov. 23 in Annals of Medicine by Francisco Javier Carrasco-Sánchez, MD, PhD, and colleagues.

Among more than 11,000 patients with confirmed COVID-19 from March to May 2020 in a nationwide Spanish registry involving 109 hospitals, admission hyperglycemia independently predicted progression from noncritical to critical condition and death, regardless of prior diabetes history. 

Those with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% vs 15.7%). They also had an increased need for a ventilator and intensive care unit (ICU) admission.

“These results provided a simple and practical way to stratify risk of death in hospitalized patients with COVID-19. Hence, admission hyperglycemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of COVID-19 patients with and without diabetes,” Dr. Carrasco-Sánchez and colleagues wrote.

The findings confirm those of previous retrospective observational studies, but the current study “has, by far, the biggest number of patients involved in this kind of study [to date]. All conclusions are consistent to other studies,” Dr. Carrasco-Sánchez, of University Hospital Juan Ramón Jiménez, Huelva, Spain, said in an interview.

However, a surprising finding, he said, “was how hyperglycemia works in the nondiabetic population and [that] glucose levels over 140 [mg/dL] ... increase the risk of death.”
 

Pay attention to even mild hyperglycemia from admission

The study also differs from some of the prior observational ones in that it examines outcome by admission glycemia rather than during the hospital stay, therefore eliminating the effect of any inpatient treatment, such as dexamethasone, he noted.

Although blood glucose measurement at admission is routine for all patients in Spain, as it is in the United States and elsewhere, a mildly elevated level in a person without a diagnosis of diabetes may not be recognized as important.

“In patients with diabetes we start the protocol to control and treat hyperglycemia during hospitalization. However, in nondiabetic patients blood glucose levels under 180 [mg/dL], and even greater, are usually overlooked. This means there is not a correct follow-up of the patients during hospitalization.

“After this study we learned that we need to pay attention to this population ... who develop hyperglycemia from the beginning,” he said.  

The study was limited in that patients who had previously undiagnosed diabetes couldn’t always be distinguished from those with acute “stress hyperglycemia.”

However, both need to be managed during hospitalization, he said. “Unfortunately, there is high variability in inpatient glucose management. The working group of diabetes of the Spanish Society of Internal Medicine is working on specific protocols,” said Dr. Carrasco-Sánchez.
 

All-cause death, progress to critical care higher with hyperglycemia

The retrospective, multicenter study was based on data from 11,312 adult patients with confirmed COVID-19 in 109 hospitals participating in Spain’s SEMI-COVID-19 registry as of May 29, 2020. They had a mean age of 67 years, 57% were male, and 19% had a diagnosis of diabetes. A total of 20% (n = 2,289) died during hospitalization.

Overall all-cause mortality was 41.1% among those with admission blood glucose levels above 180 mg/dL, 33.0% for those with glucose levels 140-180 mg/dL, and 15.7% for levels below 140 mg/dL. All differences were significant (P < .0001), but there were no differences in mortality rates within each blood glucose category between patients with or without a previous diagnosis of diabetes.

After adjustment for confounding factors, elevated admission blood glucose level remained a significant predictor of death. Compared to < 140 mg/dL, the hazard ratios for 140-180 mg/dL and > 180 mg/dL were 1.48 and 1.50, respectively (both P < .001). (Adjustments included age, gender, hypertension, diabetes, chronic obstructive pulmonary disease, lymphopenia, anemia (hemoglobin < 10 g/dL), serum creatinine, C-reactive protein > 60 mg/L, lactate dehydrogenase > 400 U/L and D-dimer >1000 ng/mL.)

Length of stay was 12, 11.5, and 11.1 days for those with admission blood glucose levels > 180, 140-180, and < 140 mg/dL, respectively (P = .011).

Use of mechanical ventilation and admission to intensive care also rose with higher admission blood glucose levels. For the composite of death, mechanical ventilation, and/or ICU admission, odds ratios for 140-180 mg/dL and > 180 mg/dL compared with < 140 mg/dL were 1.70 and 2.02, respectively (both P < .001). 

The study was supported by the Spanish Federation of Internal Medicine. The authors have reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

LAS VEGAS – Current major guidelines for treatment of psoriatic arthritis (PsA) shortchange the value of the anti–interleukin-17 biologics for this disease, Kenneth B. Gordon, MD, said 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.

[email protected]

LAS VEGAS – Current major guidelines for treatment of psoriatic arthritis (PsA) shortchange the value of the anti–interleukin-17 biologics for this disease, Kenneth B. Gordon, MD, said 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.

[email protected]

LAS VEGAS – Current major guidelines for treatment of psoriatic arthritis (PsA) shortchange the value of the anti–interleukin-17 biologics for this disease, Kenneth B. Gordon, MD, said 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.

[email protected]

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 a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, 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.

[email protected]

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 a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, 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.

[email protected]

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 a pediatric indication for apremilast in psoriasis down the line, and probably a mild to moderate indication for psoriasis, 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.

[email protected]

On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.

An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.

ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.

“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”

There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.

But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.

ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.

In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.

ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.

“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.

ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.

“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.

Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.

“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
 

Broader access

Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.

The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.

Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.

Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.

At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.

In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.

“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”

In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.

“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.

Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.

“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.

Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.

There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.

Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.

The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.

“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.

Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.

“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.

ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.

“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.

This article first appeared on Medscape.com.

On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.

An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.

ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.

“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”

There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.

But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.

ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.

In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.

ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.

“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.

ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.

“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.

Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.

“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
 

Broader access

Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.

The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.

Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.

Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.

At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.

In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.

“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”

In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.

“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.

Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.

“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.

Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.

There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.

Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.

The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.

“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.

Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.

“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.

ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.

“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.

This article first appeared on Medscape.com.

On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.

An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.

ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.

“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”

There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.

But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.

ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.

In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.

ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.

“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.

ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.

“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.

Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.

“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
 

Broader access

Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.

The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.

Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.

Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.

At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.

In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.

“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”

In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.

“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.

Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.

“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.

Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.

There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.

Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.

The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.

“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.

Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.

“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.

ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.

“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.

This article first appeared on Medscape.com.

New study results from British researchers show that dactylitis may be a clinical indicator of an aggressive phenotype of psoriatic arthritis (PsA). That phenotype is marked by a significantly greater swollen joint count, tender joint count, C-reactive protein, erosive damage, and ultrasound synovitis in very early disease-modifying antirheumatic drug (DMARD)-naive PsA.

The dactylitis study is noted by Dr Saakshi Khattri, assistant professor of rheumatology and dermatology at the Icahn School of Medicine at Mount Sinai, as one of the key findings on PsA presented at ACR Convergence 2020, the American College of Rheumatology's first all-virtual annual meeting. Researchers from Leeds, United Kingdom, concluded that dactylitis may help differentiate risk among patients in an early disease stage.

Another study from researchers in the UK also addresses very early DMARD-naive PsA patients. It found that clinically, swollen joints are linked to power Doppler‒detected synovitis, but tender, nonswollen joints are not.

Also in this ReCAP, Dr Khattri discusses a population-based study from the Mayo Clinic that shows that patients with a family history of psoriasis and severe psoriasis experience a delay in transitioning to PsA. She highlights an interim report about an emerging risk-prediction model that may improve early detection of PsA. Finally, Dr Khattri shares a quality-of-life survey from the National Psoriasis Foundation about the prevalence of unacceptable symptom states in PsA, which reinforces that PsA is far from adequately treated.
--

Saakshi Khattri, MBBS, MD, Assistant Professor, Department of Internal Medicine, Divisions of Rheumatology and Dermatology, Icahn School of Medicine at Mount Sinai; Director, Center for Connective Tissue Diseases at Mount Sinai, New York, NY. 

Saakshi Khattri, MBBS, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Novartis
Serve(d) as a speaker or a member of a speakers bureau for: Janssen
Received research grant from: Pfizer
Received income in an amount equal to or greater than $250 from: Pfizer; Novartis.

New study results from British researchers show that dactylitis may be a clinical indicator of an aggressive phenotype of psoriatic arthritis (PsA). That phenotype is marked by a significantly greater swollen joint count, tender joint count, C-reactive protein, erosive damage, and ultrasound synovitis in very early disease-modifying antirheumatic drug (DMARD)-naive PsA.

The dactylitis study is noted by Dr Saakshi Khattri, assistant professor of rheumatology and dermatology at the Icahn School of Medicine at Mount Sinai, as one of the key findings on PsA presented at ACR Convergence 2020, the American College of Rheumatology's first all-virtual annual meeting. Researchers from Leeds, United Kingdom, concluded that dactylitis may help differentiate risk among patients in an early disease stage.

Another study from researchers in the UK also addresses very early DMARD-naive PsA patients. It found that clinically, swollen joints are linked to power Doppler‒detected synovitis, but tender, nonswollen joints are not.

Also in this ReCAP, Dr Khattri discusses a population-based study from the Mayo Clinic that shows that patients with a family history of psoriasis and severe psoriasis experience a delay in transitioning to PsA. She highlights an interim report about an emerging risk-prediction model that may improve early detection of PsA. Finally, Dr Khattri shares a quality-of-life survey from the National Psoriasis Foundation about the prevalence of unacceptable symptom states in PsA, which reinforces that PsA is far from adequately treated.
--

Saakshi Khattri, MBBS, MD, Assistant Professor, Department of Internal Medicine, Divisions of Rheumatology and Dermatology, Icahn School of Medicine at Mount Sinai; Director, Center for Connective Tissue Diseases at Mount Sinai, New York, NY. 

Saakshi Khattri, MBBS, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Novartis
Serve(d) as a speaker or a member of a speakers bureau for: Janssen
Received research grant from: Pfizer
Received income in an amount equal to or greater than $250 from: Pfizer; Novartis.

New study results from British researchers show that dactylitis may be a clinical indicator of an aggressive phenotype of psoriatic arthritis (PsA). That phenotype is marked by a significantly greater swollen joint count, tender joint count, C-reactive protein, erosive damage, and ultrasound synovitis in very early disease-modifying antirheumatic drug (DMARD)-naive PsA.

The dactylitis study is noted by Dr Saakshi Khattri, assistant professor of rheumatology and dermatology at the Icahn School of Medicine at Mount Sinai, as one of the key findings on PsA presented at ACR Convergence 2020, the American College of Rheumatology's first all-virtual annual meeting. Researchers from Leeds, United Kingdom, concluded that dactylitis may help differentiate risk among patients in an early disease stage.

Another study from researchers in the UK also addresses very early DMARD-naive PsA patients. It found that clinically, swollen joints are linked to power Doppler‒detected synovitis, but tender, nonswollen joints are not.

Also in this ReCAP, Dr Khattri discusses a population-based study from the Mayo Clinic that shows that patients with a family history of psoriasis and severe psoriasis experience a delay in transitioning to PsA. She highlights an interim report about an emerging risk-prediction model that may improve early detection of PsA. Finally, Dr Khattri shares a quality-of-life survey from the National Psoriasis Foundation about the prevalence of unacceptable symptom states in PsA, which reinforces that PsA is far from adequately treated.
--

Saakshi Khattri, MBBS, MD, Assistant Professor, Department of Internal Medicine, Divisions of Rheumatology and Dermatology, Icahn School of Medicine at Mount Sinai; Director, Center for Connective Tissue Diseases at Mount Sinai, New York, NY. 

Saakshi Khattri, MBBS, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Novartis
Serve(d) as a speaker or a member of a speakers bureau for: Janssen
Received research grant from: Pfizer
Received income in an amount equal to or greater than $250 from: Pfizer; Novartis.

The American College of Rheumatology hosted its first-ever all-virtual annual meeting this year. Convergence 2020 highlighted several important treatment abstracts related to systemic lupus erythematosus. 

Dr Michelle Petri, of Johns Hopkins University, reports on the use of hydroxychloroquine, which was not found to be associated with QTc length in a large cohort of patients with lupus and rheumatoid arthritis. This is notable because hydroxychloroquine was implicated in ventricular arrhythmias in patients with COVID-19 who were also given azithromycin.

Dr Petri also looks at the results of two trials focusing on the effects of belimumab and obinutuzumab on renal outcomes.

In the belimumab trial, the primary outcome was a 700-mg reduction in the urine protein to creatinine ratio, and it met that outcome with a 10.8% delta that was statistically significant. It also met the complete renal response outcome of less than 500 mg with a 10% delta, which is statistically significant.

In the other study, obinutuzumab showed a marked improvement over rituximab as a B-cell depleter.

The completion of the phase 2 trial means that there are now 2 years of data showing a 19% delta between obinutuzumab and standard-of-care treatment.  

Finally, Dr Petri highlights two studies focusing on nonrenal lupus and the use of both BIIB059 and iberdomide.

--

Michelle Petri, MD, MPH, Professor, Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; Director, Johns Hopkins Lupus Center, Johns Hopkins Hospital, Baltimore, Maryland.

Michelle Petri, MD, MPH, has disclosed the following relevant financial relationships:
Received research grant from: GlaxoSmithKline; Eli Lilly and Company; Thermo Fisher; Hexagen; AstraZeneca
Received income in an amount equal to or greater than $250 from: AbbVie; Amgen; AstraZeneca; Blackrock; Bristol-Myers Squibb; Hexagen; Glenmark; GlaxoSmithKline; IQVIA; Janssen; Eli Lilly and Company; Merck; EMD Serono; Novartis; Sanofi; Thermo Fisher; UCB

The American College of Rheumatology hosted its first-ever all-virtual annual meeting this year. Convergence 2020 highlighted several important treatment abstracts related to systemic lupus erythematosus. 

Dr Michelle Petri, of Johns Hopkins University, reports on the use of hydroxychloroquine, which was not found to be associated with QTc length in a large cohort of patients with lupus and rheumatoid arthritis. This is notable because hydroxychloroquine was implicated in ventricular arrhythmias in patients with COVID-19 who were also given azithromycin.

Dr Petri also looks at the results of two trials focusing on the effects of belimumab and obinutuzumab on renal outcomes.

In the belimumab trial, the primary outcome was a 700-mg reduction in the urine protein to creatinine ratio, and it met that outcome with a 10.8% delta that was statistically significant. It also met the complete renal response outcome of less than 500 mg with a 10% delta, which is statistically significant.

In the other study, obinutuzumab showed a marked improvement over rituximab as a B-cell depleter.

The completion of the phase 2 trial means that there are now 2 years of data showing a 19% delta between obinutuzumab and standard-of-care treatment.  

Finally, Dr Petri highlights two studies focusing on nonrenal lupus and the use of both BIIB059 and iberdomide.

--

Michelle Petri, MD, MPH, Professor, Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; Director, Johns Hopkins Lupus Center, Johns Hopkins Hospital, Baltimore, Maryland.

Michelle Petri, MD, MPH, has disclosed the following relevant financial relationships:
Received research grant from: GlaxoSmithKline; Eli Lilly and Company; Thermo Fisher; Hexagen; AstraZeneca
Received income in an amount equal to or greater than $250 from: AbbVie; Amgen; AstraZeneca; Blackrock; Bristol-Myers Squibb; Hexagen; Glenmark; GlaxoSmithKline; IQVIA; Janssen; Eli Lilly and Company; Merck; EMD Serono; Novartis; Sanofi; Thermo Fisher; UCB

The American College of Rheumatology hosted its first-ever all-virtual annual meeting this year. Convergence 2020 highlighted several important treatment abstracts related to systemic lupus erythematosus. 

Dr Michelle Petri, of Johns Hopkins University, reports on the use of hydroxychloroquine, which was not found to be associated with QTc length in a large cohort of patients with lupus and rheumatoid arthritis. This is notable because hydroxychloroquine was implicated in ventricular arrhythmias in patients with COVID-19 who were also given azithromycin.

Dr Petri also looks at the results of two trials focusing on the effects of belimumab and obinutuzumab on renal outcomes.

In the belimumab trial, the primary outcome was a 700-mg reduction in the urine protein to creatinine ratio, and it met that outcome with a 10.8% delta that was statistically significant. It also met the complete renal response outcome of less than 500 mg with a 10% delta, which is statistically significant.

In the other study, obinutuzumab showed a marked improvement over rituximab as a B-cell depleter.

The completion of the phase 2 trial means that there are now 2 years of data showing a 19% delta between obinutuzumab and standard-of-care treatment.  

Finally, Dr Petri highlights two studies focusing on nonrenal lupus and the use of both BIIB059 and iberdomide.

--

Michelle Petri, MD, MPH, Professor, Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine; Director, Johns Hopkins Lupus Center, Johns Hopkins Hospital, Baltimore, Maryland.

Michelle Petri, MD, MPH, has disclosed the following relevant financial relationships:
Received research grant from: GlaxoSmithKline; Eli Lilly and Company; Thermo Fisher; Hexagen; AstraZeneca
Received income in an amount equal to or greater than $250 from: AbbVie; Amgen; AstraZeneca; Blackrock; Bristol-Myers Squibb; Hexagen; Glenmark; GlaxoSmithKline; IQVIA; Janssen; Eli Lilly and Company; Merck; EMD Serono; Novartis; Sanofi; Thermo Fisher; UCB

In a single-center retrospective analysis of 102 patients with psoriasis induced by tumor necrosis factor (TNF) inhibitors, most cases improved or resolved with use of topical medications or with discontinuation of the inciting TNF inhibitor, with or without other interventions. All patients were treated and diagnosed by dermatologists.

While TNF inhibitors have revolutionized management of numerous debilitating chronic inflammatory diseases, they are associated with mild and potentially serious adverse reactions, including de novo psoriasiform eruptions, noted Sean E. Mazloom, MD, and colleagues, at the Cleveland Clinic, Cleveland, Ohio, in the Journal of the American Academy of Dermatology. Despite the fact that it has been more than 15 years since the first reports of TNF inhibitor-induced psoriasis, optimal treatment strategies still remain poorly understood.
 

IBD and RA most common

Dr. Mazloom and colleagues identified 102 patients (median onset, 41 years; 72.5% female) with TNF inhibitor-induced psoriasis seen at a single tertiary care institution (the Cleveland Clinic) over a 10-year period. The authors proposed a treatment algorithm based on their findings.

Inciting TNF inhibitors were prescribed most commonly for inflammatory bowel disease (IBD) (52%) and rheumatoid arthritis (RA) (24.5%). The most common inciting TNF inhibitor was infliximab (52%). TNF inhibitor-induced psoriasis improved or resolved with topical medications alone in 63.5% of patients, and cyclosporine and methotrexate (10 mg weekly) were often effective (cyclosporine in five of five patients; methotrexate in 7 of 13) if topicals failed.

Noting that the success with topicals in this cohort exceeded that of earlier reports, the authors suggested that more accurate diagnoses and optimal strategies attributable to the involvement of dermatologists may be explanatory.

In 67% of refractory cases, discontinuation of the inciting TNF inhibitor with or without other interventions improved or resolved TNF inhibitor-induced psoriasis. With switching of TNF inhibitors, persistence or worsening of TNF inhibitor-induced psoriasis was reported in 16 of 25 patients (64%).

Algorithm aims at balancing control

The treatment algorithm proposed by Dr. Mazloom and colleagues aims at balancing control of the primary disease with minimization of skin symptom discomfort and continuation of the inciting TNF inhibitor if possible. Only with cyclosporine or methotrexate failure amid severe symptoms and less-than-optimal primary disease control should TNF inhibitors be discontinued and biologics and/or small-molecule inhibitors with alternative mechanisms of action be introduced. Transitioning to other TNF inhibitors may be tried before alternative strategies when the underlying disease is well-controlled but TNF inhibitor-induced psoriasis remains severe.

“Most dermatologists who see TNF-induced psoriasis often are likely already using strategies like the one proposed in the algorithm,” commented senior author Anthony Fernandez, MD, PhD, of the Cleveland (Ohio) Clinic, in an interview. “The concern is over those who may not see TNF inhibitor-induced psoriasis very often, and who may, as a knee-jerk response to TNF-induced psoriasis, stop the inciting medication. When strong side effects occur in IBD and RA, it’s critical to know how well the TNF inhibitor is controlling the underlying disease because lack of control can lead to permanent damage.”

Risk to benefit ratio favors retaining TNF inhibitors

The dermatologist’s goal, if the TNF inhibitor is working well, should be to exhaust all reasonable options to control the psoriasiform eruption and keep the patient on the TNF inhibitor rather than turn to potentially less effective alternatives, Dr. Fernandez added. “The risk:benefit ratio still usually favors adding more immune therapies to treat these reactions in order to enable patients to stay” on their TNF inhibitors.

Study authors disclosed no direct funding for the study. Dr Fernandez, the senior author, receives research funding from Pfizer, Mallinckrodt, and Novartis, consults for AbbVie and Celgene, and is a speaker for AbbVie and Mallinckrodt.

SOURCE: Mazloom SE et al. J Am Acad Dermatol. 2020 Dec;83(6):1590-8.

In a single-center retrospective analysis of 102 patients with psoriasis induced by tumor necrosis factor (TNF) inhibitors, most cases improved or resolved with use of topical medications or with discontinuation of the inciting TNF inhibitor, with or without other interventions. All patients were treated and diagnosed by dermatologists.

While TNF inhibitors have revolutionized management of numerous debilitating chronic inflammatory diseases, they are associated with mild and potentially serious adverse reactions, including de novo psoriasiform eruptions, noted Sean E. Mazloom, MD, and colleagues, at the Cleveland Clinic, Cleveland, Ohio, in the Journal of the American Academy of Dermatology. Despite the fact that it has been more than 15 years since the first reports of TNF inhibitor-induced psoriasis, optimal treatment strategies still remain poorly understood.
 

IBD and RA most common

Dr. Mazloom and colleagues identified 102 patients (median onset, 41 years; 72.5% female) with TNF inhibitor-induced psoriasis seen at a single tertiary care institution (the Cleveland Clinic) over a 10-year period. The authors proposed a treatment algorithm based on their findings.

Inciting TNF inhibitors were prescribed most commonly for inflammatory bowel disease (IBD) (52%) and rheumatoid arthritis (RA) (24.5%). The most common inciting TNF inhibitor was infliximab (52%). TNF inhibitor-induced psoriasis improved or resolved with topical medications alone in 63.5% of patients, and cyclosporine and methotrexate (10 mg weekly) were often effective (cyclosporine in five of five patients; methotrexate in 7 of 13) if topicals failed.

Noting that the success with topicals in this cohort exceeded that of earlier reports, the authors suggested that more accurate diagnoses and optimal strategies attributable to the involvement of dermatologists may be explanatory.

In 67% of refractory cases, discontinuation of the inciting TNF inhibitor with or without other interventions improved or resolved TNF inhibitor-induced psoriasis. With switching of TNF inhibitors, persistence or worsening of TNF inhibitor-induced psoriasis was reported in 16 of 25 patients (64%).

Algorithm aims at balancing control

The treatment algorithm proposed by Dr. Mazloom and colleagues aims at balancing control of the primary disease with minimization of skin symptom discomfort and continuation of the inciting TNF inhibitor if possible. Only with cyclosporine or methotrexate failure amid severe symptoms and less-than-optimal primary disease control should TNF inhibitors be discontinued and biologics and/or small-molecule inhibitors with alternative mechanisms of action be introduced. Transitioning to other TNF inhibitors may be tried before alternative strategies when the underlying disease is well-controlled but TNF inhibitor-induced psoriasis remains severe.

“Most dermatologists who see TNF-induced psoriasis often are likely already using strategies like the one proposed in the algorithm,” commented senior author Anthony Fernandez, MD, PhD, of the Cleveland (Ohio) Clinic, in an interview. “The concern is over those who may not see TNF inhibitor-induced psoriasis very often, and who may, as a knee-jerk response to TNF-induced psoriasis, stop the inciting medication. When strong side effects occur in IBD and RA, it’s critical to know how well the TNF inhibitor is controlling the underlying disease because lack of control can lead to permanent damage.”

Risk to benefit ratio favors retaining TNF inhibitors

The dermatologist’s goal, if the TNF inhibitor is working well, should be to exhaust all reasonable options to control the psoriasiform eruption and keep the patient on the TNF inhibitor rather than turn to potentially less effective alternatives, Dr. Fernandez added. “The risk:benefit ratio still usually favors adding more immune therapies to treat these reactions in order to enable patients to stay” on their TNF inhibitors.

Study authors disclosed no direct funding for the study. Dr Fernandez, the senior author, receives research funding from Pfizer, Mallinckrodt, and Novartis, consults for AbbVie and Celgene, and is a speaker for AbbVie and Mallinckrodt.

SOURCE: Mazloom SE et al. J Am Acad Dermatol. 2020 Dec;83(6):1590-8.

In a single-center retrospective analysis of 102 patients with psoriasis induced by tumor necrosis factor (TNF) inhibitors, most cases improved or resolved with use of topical medications or with discontinuation of the inciting TNF inhibitor, with or without other interventions. All patients were treated and diagnosed by dermatologists.

While TNF inhibitors have revolutionized management of numerous debilitating chronic inflammatory diseases, they are associated with mild and potentially serious adverse reactions, including de novo psoriasiform eruptions, noted Sean E. Mazloom, MD, and colleagues, at the Cleveland Clinic, Cleveland, Ohio, in the Journal of the American Academy of Dermatology. Despite the fact that it has been more than 15 years since the first reports of TNF inhibitor-induced psoriasis, optimal treatment strategies still remain poorly understood.
 

IBD and RA most common

Dr. Mazloom and colleagues identified 102 patients (median onset, 41 years; 72.5% female) with TNF inhibitor-induced psoriasis seen at a single tertiary care institution (the Cleveland Clinic) over a 10-year period. The authors proposed a treatment algorithm based on their findings.

Inciting TNF inhibitors were prescribed most commonly for inflammatory bowel disease (IBD) (52%) and rheumatoid arthritis (RA) (24.5%). The most common inciting TNF inhibitor was infliximab (52%). TNF inhibitor-induced psoriasis improved or resolved with topical medications alone in 63.5% of patients, and cyclosporine and methotrexate (10 mg weekly) were often effective (cyclosporine in five of five patients; methotrexate in 7 of 13) if topicals failed.

Noting that the success with topicals in this cohort exceeded that of earlier reports, the authors suggested that more accurate diagnoses and optimal strategies attributable to the involvement of dermatologists may be explanatory.

In 67% of refractory cases, discontinuation of the inciting TNF inhibitor with or without other interventions improved or resolved TNF inhibitor-induced psoriasis. With switching of TNF inhibitors, persistence or worsening of TNF inhibitor-induced psoriasis was reported in 16 of 25 patients (64%).

Algorithm aims at balancing control

The treatment algorithm proposed by Dr. Mazloom and colleagues aims at balancing control of the primary disease with minimization of skin symptom discomfort and continuation of the inciting TNF inhibitor if possible. Only with cyclosporine or methotrexate failure amid severe symptoms and less-than-optimal primary disease control should TNF inhibitors be discontinued and biologics and/or small-molecule inhibitors with alternative mechanisms of action be introduced. Transitioning to other TNF inhibitors may be tried before alternative strategies when the underlying disease is well-controlled but TNF inhibitor-induced psoriasis remains severe.

“Most dermatologists who see TNF-induced psoriasis often are likely already using strategies like the one proposed in the algorithm,” commented senior author Anthony Fernandez, MD, PhD, of the Cleveland (Ohio) Clinic, in an interview. “The concern is over those who may not see TNF inhibitor-induced psoriasis very often, and who may, as a knee-jerk response to TNF-induced psoriasis, stop the inciting medication. When strong side effects occur in IBD and RA, it’s critical to know how well the TNF inhibitor is controlling the underlying disease because lack of control can lead to permanent damage.”

Risk to benefit ratio favors retaining TNF inhibitors

The dermatologist’s goal, if the TNF inhibitor is working well, should be to exhaust all reasonable options to control the psoriasiform eruption and keep the patient on the TNF inhibitor rather than turn to potentially less effective alternatives, Dr. Fernandez added. “The risk:benefit ratio still usually favors adding more immune therapies to treat these reactions in order to enable patients to stay” on their TNF inhibitors.

Study authors disclosed no direct funding for the study. Dr Fernandez, the senior author, receives research funding from Pfizer, Mallinckrodt, and Novartis, consults for AbbVie and Celgene, and is a speaker for AbbVie and Mallinckrodt.

SOURCE: Mazloom SE et al. J Am Acad Dermatol. 2020 Dec;83(6):1590-8.

The human monoclonal antibody golimumab (Simponi) preserved endogenous insulin secretion in patients with new-onset type 1 diabetes and reduced their exogenous insulin requirements at 1 year, newly published phase 2 data indicate.

Results from the multicenter, double-blind, placebo-controlled trial were first reported as a poster at the virtual American Diabetes Association 80th Scientific Sessions in June. They were published online Nov. 18 in the New England Journal of Medicine.

In the 52-week study of 84 children and adults with new-onset type 1 diabetes, those given golimumab injections every 2 weeks had significantly higher levels of C-peptide, a marker of insulin secretion, and required less injected or infused insulin than did those who received placebo injections. There were no treatment-associated serious adverse events.

Golimumab is a human monoclonal antibody specific for tumor necrosis factor–alpha. It is approved for the treatment of several autoimmune diseases, including rheumatoid arthritis and ulcerative colitis, in the United States, Europe, and elsewhere.
 

An intermediate step toward a cure

Although none of the patients were able to stop taking insulin entirely, the results have important clinical implications, lead author Teresa Quattrin, MD, said in an interview.

“People want a cure, but the fact is, a cure is not available yet. So, this is an intermediate step towards a cure.... There are advantages to being on a small insulin dose,” including lower rates of hypoglycemia and maintenance of intraportal insulin, said Dr. Quattrin, of the State University of New York at Buffalo.

But in an accompanying editorial, Domenico Accili, MD, points to potential risks from immunotherapy and from attempting additional interventions at an “emotionally fraught” time when patients and families are coping with the new diabetes diagnosis.

He said of golimumab, “the effect is actually very small. ... There’s nothing wrong in and of itself with improving those outcomes. I just wouldn’t assign them as game changers.”

If this or a similar immunotherapeutic intervention were approved for this indication, “I would tell patients it exists and let them make the decision whether they want to try it. I wouldn’t say you must try it,” said Dr. Accili, of the Columbia University Diabetes and Endocrinology Research Center, New York.
 

With golimumab, higher C-peptide, lower insulin requirement

Of the 84 patients, who ranged in age from 6 to 21 years, 56 were randomly assigned within 100 days of being diagnosed with type 1 diabetes to receive golimumab, and 28 were assigned to receive placebo injections, given every 2 weeks.

The drug resulted in lower insulin use (0.51U/Kg per day vs. 0.69 U/kg per day), and the increase in insulin use over 52 weeks was less with golimumab than with placebo (0.07 vs. 0.24 U/kg per day; P = .001).

The mean percent decrease of C-peptide production from baseline was 12% with golimumab versus 56% with placebo.

Although the mean number of overall hypoglycemic events was similar, the mean number of level 2 hypoglycemic events (<54 mg/dL) was 36% lower with golimumab (11.5 vs. 17.6). There were no severe cases of hypoglycemia in either group.

No severe or serious infections occurred in either group, although mild to moderate infections were reported in 71% with golimumab versus 61% with placebo. More patients in the golimumab group experienced a decrease in neutrophils (29% vs. 19%).
 

Immunotherapy: Which one, and when should it start?

These findings come on the heels of the 2019 landmark results with another monoclonal antibody, the investigational anti-CD3 teplizumab (PRV-031). Among patients at risk, a diagnosis of type 1 diabetes was delayed by 2 years, and continued benefit was seen at 3 years.

However, Dr. Quattrin said teplizumab is limited by the fact that it must be administered via a 14-day infusion, whereas golimumab can be injected by patients themselves at home.

Moreover, the phase 2 teplizumab study was conducted in people who had antibodies that placed them at high risk for type 1 diabetes, but those patients did not yet have the condition. They were identified because they had close relatives with type 1 diabetes and were enrolled in the federally funded TrialNet screening program.

Dr. Quattrin is now participating in an ongoing phase 3 study of teplizumab that involves patients newly diagnosed with type 1 diabetes.

A Janssen spokesperson said in an interview that the company isn’t planning to further develop golimumab for use in type 1 diabetes.

“Our focus is to apply insights from the phase 2 ... proof-of-concept study to progress what we believe are novel, immunologically targeted pipeline candidates in stage 2 disease or presymptomatic stages of type 1 diabetes, which is consistent with our mission to intercept and prevent type 1 diabetes,” the spokesperson said.

To identify more individuals at risk for type 1 diabetes beyond the close relatives of those who already have it, so as to be able to intervene at a presymptomatic stage, Janssen is organizing a public-private effort to advocate for routine population screening for type 1 diabetes–related autoantibodies.

Dr. Quattrin said: “Preserving some insulin is key. Having somebody with beta cell functioning still is an intermediate step to a cure and will make their life easier, and that’s what people should care about.”

Dr. Accili, who cofounded and leads a company working on a novel approach to type 1 diabetes treatment, writes in his editorial: “We should also be mindful that this treatment debate is first world–centric.

“Current treatments for type 1 diabetes require resources not readily available in most parts of the world, where something as simple as refrigeration of insulin can become a logistic nightmare. While combinations of [approaches] tailored to individual risk and potential benefits are likely to make inroads in clinical practice, the need for a simpler, safer, and equally effective alternative to insulin remains,” he wrote.

Dr. Quattrin is a researcher and consultant for Janssen and conducts clinical trials for Provention Bio, Opko, and Ascendis. Dr. Accili is founder and director of Forkhead Therapeutics.

A version of this article originally appeared on Medscape.com.

The human monoclonal antibody golimumab (Simponi) preserved endogenous insulin secretion in patients with new-onset type 1 diabetes and reduced their exogenous insulin requirements at 1 year, newly published phase 2 data indicate.

Results from the multicenter, double-blind, placebo-controlled trial were first reported as a poster at the virtual American Diabetes Association 80th Scientific Sessions in June. They were published online Nov. 18 in the New England Journal of Medicine.

In the 52-week study of 84 children and adults with new-onset type 1 diabetes, those given golimumab injections every 2 weeks had significantly higher levels of C-peptide, a marker of insulin secretion, and required less injected or infused insulin than did those who received placebo injections. There were no treatment-associated serious adverse events.

Golimumab is a human monoclonal antibody specific for tumor necrosis factor–alpha. It is approved for the treatment of several autoimmune diseases, including rheumatoid arthritis and ulcerative colitis, in the United States, Europe, and elsewhere.
 

An intermediate step toward a cure

Although none of the patients were able to stop taking insulin entirely, the results have important clinical implications, lead author Teresa Quattrin, MD, said in an interview.

“People want a cure, but the fact is, a cure is not available yet. So, this is an intermediate step towards a cure.... There are advantages to being on a small insulin dose,” including lower rates of hypoglycemia and maintenance of intraportal insulin, said Dr. Quattrin, of the State University of New York at Buffalo.

But in an accompanying editorial, Domenico Accili, MD, points to potential risks from immunotherapy and from attempting additional interventions at an “emotionally fraught” time when patients and families are coping with the new diabetes diagnosis.

He said of golimumab, “the effect is actually very small. ... There’s nothing wrong in and of itself with improving those outcomes. I just wouldn’t assign them as game changers.”

If this or a similar immunotherapeutic intervention were approved for this indication, “I would tell patients it exists and let them make the decision whether they want to try it. I wouldn’t say you must try it,” said Dr. Accili, of the Columbia University Diabetes and Endocrinology Research Center, New York.
 

With golimumab, higher C-peptide, lower insulin requirement

Of the 84 patients, who ranged in age from 6 to 21 years, 56 were randomly assigned within 100 days of being diagnosed with type 1 diabetes to receive golimumab, and 28 were assigned to receive placebo injections, given every 2 weeks.

The drug resulted in lower insulin use (0.51U/Kg per day vs. 0.69 U/kg per day), and the increase in insulin use over 52 weeks was less with golimumab than with placebo (0.07 vs. 0.24 U/kg per day; P = .001).

The mean percent decrease of C-peptide production from baseline was 12% with golimumab versus 56% with placebo.

Although the mean number of overall hypoglycemic events was similar, the mean number of level 2 hypoglycemic events (<54 mg/dL) was 36% lower with golimumab (11.5 vs. 17.6). There were no severe cases of hypoglycemia in either group.

No severe or serious infections occurred in either group, although mild to moderate infections were reported in 71% with golimumab versus 61% with placebo. More patients in the golimumab group experienced a decrease in neutrophils (29% vs. 19%).
 

Immunotherapy: Which one, and when should it start?

These findings come on the heels of the 2019 landmark results with another monoclonal antibody, the investigational anti-CD3 teplizumab (PRV-031). Among patients at risk, a diagnosis of type 1 diabetes was delayed by 2 years, and continued benefit was seen at 3 years.

However, Dr. Quattrin said teplizumab is limited by the fact that it must be administered via a 14-day infusion, whereas golimumab can be injected by patients themselves at home.

Moreover, the phase 2 teplizumab study was conducted in people who had antibodies that placed them at high risk for type 1 diabetes, but those patients did not yet have the condition. They were identified because they had close relatives with type 1 diabetes and were enrolled in the federally funded TrialNet screening program.

Dr. Quattrin is now participating in an ongoing phase 3 study of teplizumab that involves patients newly diagnosed with type 1 diabetes.

A Janssen spokesperson said in an interview that the company isn’t planning to further develop golimumab for use in type 1 diabetes.

“Our focus is to apply insights from the phase 2 ... proof-of-concept study to progress what we believe are novel, immunologically targeted pipeline candidates in stage 2 disease or presymptomatic stages of type 1 diabetes, which is consistent with our mission to intercept and prevent type 1 diabetes,” the spokesperson said.

To identify more individuals at risk for type 1 diabetes beyond the close relatives of those who already have it, so as to be able to intervene at a presymptomatic stage, Janssen is organizing a public-private effort to advocate for routine population screening for type 1 diabetes–related autoantibodies.

Dr. Quattrin said: “Preserving some insulin is key. Having somebody with beta cell functioning still is an intermediate step to a cure and will make their life easier, and that’s what people should care about.”

Dr. Accili, who cofounded and leads a company working on a novel approach to type 1 diabetes treatment, writes in his editorial: “We should also be mindful that this treatment debate is first world–centric.

“Current treatments for type 1 diabetes require resources not readily available in most parts of the world, where something as simple as refrigeration of insulin can become a logistic nightmare. While combinations of [approaches] tailored to individual risk and potential benefits are likely to make inroads in clinical practice, the need for a simpler, safer, and equally effective alternative to insulin remains,” he wrote.

Dr. Quattrin is a researcher and consultant for Janssen and conducts clinical trials for Provention Bio, Opko, and Ascendis. Dr. Accili is founder and director of Forkhead Therapeutics.

A version of this article originally appeared on Medscape.com.

The human monoclonal antibody golimumab (Simponi) preserved endogenous insulin secretion in patients with new-onset type 1 diabetes and reduced their exogenous insulin requirements at 1 year, newly published phase 2 data indicate.

Results from the multicenter, double-blind, placebo-controlled trial were first reported as a poster at the virtual American Diabetes Association 80th Scientific Sessions in June. They were published online Nov. 18 in the New England Journal of Medicine.

In the 52-week study of 84 children and adults with new-onset type 1 diabetes, those given golimumab injections every 2 weeks had significantly higher levels of C-peptide, a marker of insulin secretion, and required less injected or infused insulin than did those who received placebo injections. There were no treatment-associated serious adverse events.

Golimumab is a human monoclonal antibody specific for tumor necrosis factor–alpha. It is approved for the treatment of several autoimmune diseases, including rheumatoid arthritis and ulcerative colitis, in the United States, Europe, and elsewhere.
 

An intermediate step toward a cure

Although none of the patients were able to stop taking insulin entirely, the results have important clinical implications, lead author Teresa Quattrin, MD, said in an interview.

“People want a cure, but the fact is, a cure is not available yet. So, this is an intermediate step towards a cure.... There are advantages to being on a small insulin dose,” including lower rates of hypoglycemia and maintenance of intraportal insulin, said Dr. Quattrin, of the State University of New York at Buffalo.

But in an accompanying editorial, Domenico Accili, MD, points to potential risks from immunotherapy and from attempting additional interventions at an “emotionally fraught” time when patients and families are coping with the new diabetes diagnosis.

He said of golimumab, “the effect is actually very small. ... There’s nothing wrong in and of itself with improving those outcomes. I just wouldn’t assign them as game changers.”

If this or a similar immunotherapeutic intervention were approved for this indication, “I would tell patients it exists and let them make the decision whether they want to try it. I wouldn’t say you must try it,” said Dr. Accili, of the Columbia University Diabetes and Endocrinology Research Center, New York.
 

With golimumab, higher C-peptide, lower insulin requirement

Of the 84 patients, who ranged in age from 6 to 21 years, 56 were randomly assigned within 100 days of being diagnosed with type 1 diabetes to receive golimumab, and 28 were assigned to receive placebo injections, given every 2 weeks.

The drug resulted in lower insulin use (0.51U/Kg per day vs. 0.69 U/kg per day), and the increase in insulin use over 52 weeks was less with golimumab than with placebo (0.07 vs. 0.24 U/kg per day; P = .001).

The mean percent decrease of C-peptide production from baseline was 12% with golimumab versus 56% with placebo.

Although the mean number of overall hypoglycemic events was similar, the mean number of level 2 hypoglycemic events (<54 mg/dL) was 36% lower with golimumab (11.5 vs. 17.6). There were no severe cases of hypoglycemia in either group.

No severe or serious infections occurred in either group, although mild to moderate infections were reported in 71% with golimumab versus 61% with placebo. More patients in the golimumab group experienced a decrease in neutrophils (29% vs. 19%).
 

Immunotherapy: Which one, and when should it start?

These findings come on the heels of the 2019 landmark results with another monoclonal antibody, the investigational anti-CD3 teplizumab (PRV-031). Among patients at risk, a diagnosis of type 1 diabetes was delayed by 2 years, and continued benefit was seen at 3 years.

However, Dr. Quattrin said teplizumab is limited by the fact that it must be administered via a 14-day infusion, whereas golimumab can be injected by patients themselves at home.

Moreover, the phase 2 teplizumab study was conducted in people who had antibodies that placed them at high risk for type 1 diabetes, but those patients did not yet have the condition. They were identified because they had close relatives with type 1 diabetes and were enrolled in the federally funded TrialNet screening program.

Dr. Quattrin is now participating in an ongoing phase 3 study of teplizumab that involves patients newly diagnosed with type 1 diabetes.

A Janssen spokesperson said in an interview that the company isn’t planning to further develop golimumab for use in type 1 diabetes.

“Our focus is to apply insights from the phase 2 ... proof-of-concept study to progress what we believe are novel, immunologically targeted pipeline candidates in stage 2 disease or presymptomatic stages of type 1 diabetes, which is consistent with our mission to intercept and prevent type 1 diabetes,” the spokesperson said.

To identify more individuals at risk for type 1 diabetes beyond the close relatives of those who already have it, so as to be able to intervene at a presymptomatic stage, Janssen is organizing a public-private effort to advocate for routine population screening for type 1 diabetes–related autoantibodies.

Dr. Quattrin said: “Preserving some insulin is key. Having somebody with beta cell functioning still is an intermediate step to a cure and will make their life easier, and that’s what people should care about.”

Dr. Accili, who cofounded and leads a company working on a novel approach to type 1 diabetes treatment, writes in his editorial: “We should also be mindful that this treatment debate is first world–centric.

“Current treatments for type 1 diabetes require resources not readily available in most parts of the world, where something as simple as refrigeration of insulin can become a logistic nightmare. While combinations of [approaches] tailored to individual risk and potential benefits are likely to make inroads in clinical practice, the need for a simpler, safer, and equally effective alternative to insulin remains,” he wrote.

Dr. Quattrin is a researcher and consultant for Janssen and conducts clinical trials for Provention Bio, Opko, and Ascendis. Dr. Accili is founder and director of Forkhead Therapeutics.

A version of this article originally appeared on Medscape.com.

• Survey reveals special impact of COVID-19 on persons with rare disorders
• Topical treatment tackles oral ulcers in Behçet’s syndrome
• Managing the risk of congenital heart block in anti-Ro/SSA-positive women
• Newly described lung disorder strikes children with systemic juvenile idiopathic arthritis

Read the report here.

• Survey reveals special impact of COVID-19 on persons with rare disorders
• Topical treatment tackles oral ulcers in Behçet’s syndrome
• Managing the risk of congenital heart block in anti-Ro/SSA-positive women
• Newly described lung disorder strikes children with systemic juvenile idiopathic arthritis

Read the report here.

• Survey reveals special impact of COVID-19 on persons with rare disorders
• Topical treatment tackles oral ulcers in Behçet’s syndrome
• Managing the risk of congenital heart block in anti-Ro/SSA-positive women
• Newly described lung disorder strikes children with systemic juvenile idiopathic arthritis

Read the report here.

As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.

In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.

The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.

Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.

Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.

[email protected]

As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.

In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.

The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.

Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.

Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.

[email protected]

As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.

In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.

The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.

Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.

Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.

[email protected]