Psoriatic Arthritis

Measuring success with a treat-to-target strategy in psoriatic arthritis patients proved to be more comprehensive with the Psoriatic Arthritis Disease Activity Score (PASDAS) than it was with the Disease Activity Score in 28 joints (DAS28), according to findings from a prospective cohort study.

Fewer patients had a low disease activity score according to DAS28, and a higher percentage of patients deemed adequately treated according to DAS28 were found to have residual disease activity, compared with the number of patients so categorized according to PASDAS, researcher Michelle Mulder reported in her presentation of the study at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

“PASDAS implementation in a tightly monitored PsA [psoriatic arthritis] cohort suggests relevant residual disease burden, even though DAS28 was measured at every visit previously,” said Ms. Mulder, an MD/PhD student at Sint Maartenskliniek in Nijmegen, The Netherlands.

The presentation was convincing to Philip Helliwell, MD, PhD, who is a professor of clinical rheumatology at Leeds (England) University, and was also one of the developers of PASDAS. “We know it can be used in clinical practice with a certain amount of organization and clinical staff to help you,” he said during another presentation at GRAPPA.

Treat to target is a widely accepted therapeutic strategy. It’s particularly common in rheumatoid arthritis, but increasing evidence suggests that it improves patient outcomes in psoriatic arthritis. DAS28 is frequently used in treat-to-target approaches in rheumatoid arthritis, and often gets applied to psoriatic arthritis since rheumatologists are already comfortable with it, according to Ms. Mulder. “However, DAS28 has shown some limitations when used in psoriatic arthritis. For example, its joint count is limited to only 28 joints, and it does not take all PsA domains into account,” she said.

DAS28 was previously used at Sint Maartenskliniek in combination with psoriatic arthritis–specific assessment recommendations, but the institution opted in 2019 to switch to PASDAS, which was developed by GRAPPA and the European League Against Rheumatism. “To better adhere to international PsA guidelines, we chose to implement PASDAS in our cohort with the assumption that it might improve patient care,” Ms. Mulder said.

With DAS28, clinicians measured the C-reactive protein (CRP) and Patient Global Visual Analog Scale (VAS) domains and were advised to examine 28 joints for tender and swollen joint count domains. Under the PASDAS guidance, clinicians examined 68 joints for tenderness, 66 joints for swelling, CRP, Patient Global VAS, Physician Global VAS, Leeds Enthesitis Index, dactylitis, and the 12-item Short Form Physical Composite Scale. They also examined the skin, nails, and axial disease.

To examine the effects of the switch from DAS28 to PASDAS, the researchers compared outcomes in 855 patients before and after the change during March to December 2019. The mean age of patients was 55 years, and 46% were female. The mean disease duration was 10 years, and the mean PASDAS score was 3.1. A total of 96% of participants were negative for anti-cyclic citrullinated peptide. Overall, 30% had arthritis, 9% had axial disease, 3% had dactylitis, 21% had enthesitis, 51% had skin disease, and 42% had nail disease.

About three-quarters (77.4%) of patients reached the threshold of low disease activity (LDA) according to the DAS28 measure, while 53.1% did so using the PASDAS. High disease activity occurred in 7.8% of patients according to DAS28, compared with 2.7% as measured by PASDAS. Patients who reached only the DAS28 LDA target but not the PASDAS target, compared with patients who reached the LDA target in both measures, had significantly worse counts for swelling in 66 joints (0.7 vs. 0.2; P < .001) and tenderness in 68 joints (2.1 vs. 0.7; P < .001), as well as worse scores for enthesitis (0.5 vs. 0.1; P < .001), dactylitis (4% vs. 1%; P = .005), patient global VAS (44.0 vs. 14.4; P < .001), Health Assessment Questionnaire (0.8 vs. 0.4; P < .001) and Patient Acceptable Symptom State (unacceptable score in 17% vs. 3%; P < .001).

Ms. Mulder acknowledged that PASDAS imposes a significant burden on clinicians, and noted that Sint Maartenskliniek created patient infrastructure to handle the load. “It’s very important that you set up your clinic in a specific way. When the patient comes in, we draw blood immediately and we ask them to fill in the questionnaires, and then they go to a specialized nurse who measures all the different components of the PASDAS. It took a lot of time to train the specialized nurses and to implement the PASDAS score in our electronic health records. After we did those things, it was quite easy because we have this whole setup. It takes time and it is difficult, but it is definitely possible to do it,” Ms. Mulder said during a live Q&A following her prerecorded presentation.

The study received no funding. Ms. Mulder had no relevant financial disclosures. Dr. Helliwell has financial ties to AbbVie, Amgen, Celgen, Galapagos, Janssen, Novartis, Pfizer, and UCB.

SOURCE: Mulder M et al. GRAPPA 2020 Virtual Annual Meeting.

Measuring success with a treat-to-target strategy in psoriatic arthritis patients proved to be more comprehensive with the Psoriatic Arthritis Disease Activity Score (PASDAS) than it was with the Disease Activity Score in 28 joints (DAS28), according to findings from a prospective cohort study.

Fewer patients had a low disease activity score according to DAS28, and a higher percentage of patients deemed adequately treated according to DAS28 were found to have residual disease activity, compared with the number of patients so categorized according to PASDAS, researcher Michelle Mulder reported in her presentation of the study at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

“PASDAS implementation in a tightly monitored PsA [psoriatic arthritis] cohort suggests relevant residual disease burden, even though DAS28 was measured at every visit previously,” said Ms. Mulder, an MD/PhD student at Sint Maartenskliniek in Nijmegen, The Netherlands.

The presentation was convincing to Philip Helliwell, MD, PhD, who is a professor of clinical rheumatology at Leeds (England) University, and was also one of the developers of PASDAS. “We know it can be used in clinical practice with a certain amount of organization and clinical staff to help you,” he said during another presentation at GRAPPA.

Treat to target is a widely accepted therapeutic strategy. It’s particularly common in rheumatoid arthritis, but increasing evidence suggests that it improves patient outcomes in psoriatic arthritis. DAS28 is frequently used in treat-to-target approaches in rheumatoid arthritis, and often gets applied to psoriatic arthritis since rheumatologists are already comfortable with it, according to Ms. Mulder. “However, DAS28 has shown some limitations when used in psoriatic arthritis. For example, its joint count is limited to only 28 joints, and it does not take all PsA domains into account,” she said.

DAS28 was previously used at Sint Maartenskliniek in combination with psoriatic arthritis–specific assessment recommendations, but the institution opted in 2019 to switch to PASDAS, which was developed by GRAPPA and the European League Against Rheumatism. “To better adhere to international PsA guidelines, we chose to implement PASDAS in our cohort with the assumption that it might improve patient care,” Ms. Mulder said.

With DAS28, clinicians measured the C-reactive protein (CRP) and Patient Global Visual Analog Scale (VAS) domains and were advised to examine 28 joints for tender and swollen joint count domains. Under the PASDAS guidance, clinicians examined 68 joints for tenderness, 66 joints for swelling, CRP, Patient Global VAS, Physician Global VAS, Leeds Enthesitis Index, dactylitis, and the 12-item Short Form Physical Composite Scale. They also examined the skin, nails, and axial disease.

To examine the effects of the switch from DAS28 to PASDAS, the researchers compared outcomes in 855 patients before and after the change during March to December 2019. The mean age of patients was 55 years, and 46% were female. The mean disease duration was 10 years, and the mean PASDAS score was 3.1. A total of 96% of participants were negative for anti-cyclic citrullinated peptide. Overall, 30% had arthritis, 9% had axial disease, 3% had dactylitis, 21% had enthesitis, 51% had skin disease, and 42% had nail disease.

About three-quarters (77.4%) of patients reached the threshold of low disease activity (LDA) according to the DAS28 measure, while 53.1% did so using the PASDAS. High disease activity occurred in 7.8% of patients according to DAS28, compared with 2.7% as measured by PASDAS. Patients who reached only the DAS28 LDA target but not the PASDAS target, compared with patients who reached the LDA target in both measures, had significantly worse counts for swelling in 66 joints (0.7 vs. 0.2; P < .001) and tenderness in 68 joints (2.1 vs. 0.7; P < .001), as well as worse scores for enthesitis (0.5 vs. 0.1; P < .001), dactylitis (4% vs. 1%; P = .005), patient global VAS (44.0 vs. 14.4; P < .001), Health Assessment Questionnaire (0.8 vs. 0.4; P < .001) and Patient Acceptable Symptom State (unacceptable score in 17% vs. 3%; P < .001).

Ms. Mulder acknowledged that PASDAS imposes a significant burden on clinicians, and noted that Sint Maartenskliniek created patient infrastructure to handle the load. “It’s very important that you set up your clinic in a specific way. When the patient comes in, we draw blood immediately and we ask them to fill in the questionnaires, and then they go to a specialized nurse who measures all the different components of the PASDAS. It took a lot of time to train the specialized nurses and to implement the PASDAS score in our electronic health records. After we did those things, it was quite easy because we have this whole setup. It takes time and it is difficult, but it is definitely possible to do it,” Ms. Mulder said during a live Q&A following her prerecorded presentation.

The study received no funding. Ms. Mulder had no relevant financial disclosures. Dr. Helliwell has financial ties to AbbVie, Amgen, Celgen, Galapagos, Janssen, Novartis, Pfizer, and UCB.

SOURCE: Mulder M et al. GRAPPA 2020 Virtual Annual Meeting.

Measuring success with a treat-to-target strategy in psoriatic arthritis patients proved to be more comprehensive with the Psoriatic Arthritis Disease Activity Score (PASDAS) than it was with the Disease Activity Score in 28 joints (DAS28), according to findings from a prospective cohort study.

Fewer patients had a low disease activity score according to DAS28, and a higher percentage of patients deemed adequately treated according to DAS28 were found to have residual disease activity, compared with the number of patients so categorized according to PASDAS, researcher Michelle Mulder reported in her presentation of the study at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

“PASDAS implementation in a tightly monitored PsA [psoriatic arthritis] cohort suggests relevant residual disease burden, even though DAS28 was measured at every visit previously,” said Ms. Mulder, an MD/PhD student at Sint Maartenskliniek in Nijmegen, The Netherlands.

The presentation was convincing to Philip Helliwell, MD, PhD, who is a professor of clinical rheumatology at Leeds (England) University, and was also one of the developers of PASDAS. “We know it can be used in clinical practice with a certain amount of organization and clinical staff to help you,” he said during another presentation at GRAPPA.

Treat to target is a widely accepted therapeutic strategy. It’s particularly common in rheumatoid arthritis, but increasing evidence suggests that it improves patient outcomes in psoriatic arthritis. DAS28 is frequently used in treat-to-target approaches in rheumatoid arthritis, and often gets applied to psoriatic arthritis since rheumatologists are already comfortable with it, according to Ms. Mulder. “However, DAS28 has shown some limitations when used in psoriatic arthritis. For example, its joint count is limited to only 28 joints, and it does not take all PsA domains into account,” she said.

DAS28 was previously used at Sint Maartenskliniek in combination with psoriatic arthritis–specific assessment recommendations, but the institution opted in 2019 to switch to PASDAS, which was developed by GRAPPA and the European League Against Rheumatism. “To better adhere to international PsA guidelines, we chose to implement PASDAS in our cohort with the assumption that it might improve patient care,” Ms. Mulder said.

With DAS28, clinicians measured the C-reactive protein (CRP) and Patient Global Visual Analog Scale (VAS) domains and were advised to examine 28 joints for tender and swollen joint count domains. Under the PASDAS guidance, clinicians examined 68 joints for tenderness, 66 joints for swelling, CRP, Patient Global VAS, Physician Global VAS, Leeds Enthesitis Index, dactylitis, and the 12-item Short Form Physical Composite Scale. They also examined the skin, nails, and axial disease.

To examine the effects of the switch from DAS28 to PASDAS, the researchers compared outcomes in 855 patients before and after the change during March to December 2019. The mean age of patients was 55 years, and 46% were female. The mean disease duration was 10 years, and the mean PASDAS score was 3.1. A total of 96% of participants were negative for anti-cyclic citrullinated peptide. Overall, 30% had arthritis, 9% had axial disease, 3% had dactylitis, 21% had enthesitis, 51% had skin disease, and 42% had nail disease.

About three-quarters (77.4%) of patients reached the threshold of low disease activity (LDA) according to the DAS28 measure, while 53.1% did so using the PASDAS. High disease activity occurred in 7.8% of patients according to DAS28, compared with 2.7% as measured by PASDAS. Patients who reached only the DAS28 LDA target but not the PASDAS target, compared with patients who reached the LDA target in both measures, had significantly worse counts for swelling in 66 joints (0.7 vs. 0.2; P < .001) and tenderness in 68 joints (2.1 vs. 0.7; P < .001), as well as worse scores for enthesitis (0.5 vs. 0.1; P < .001), dactylitis (4% vs. 1%; P = .005), patient global VAS (44.0 vs. 14.4; P < .001), Health Assessment Questionnaire (0.8 vs. 0.4; P < .001) and Patient Acceptable Symptom State (unacceptable score in 17% vs. 3%; P < .001).

Ms. Mulder acknowledged that PASDAS imposes a significant burden on clinicians, and noted that Sint Maartenskliniek created patient infrastructure to handle the load. “It’s very important that you set up your clinic in a specific way. When the patient comes in, we draw blood immediately and we ask them to fill in the questionnaires, and then they go to a specialized nurse who measures all the different components of the PASDAS. It took a lot of time to train the specialized nurses and to implement the PASDAS score in our electronic health records. After we did those things, it was quite easy because we have this whole setup. It takes time and it is difficult, but it is definitely possible to do it,” Ms. Mulder said during a live Q&A following her prerecorded presentation.

The study received no funding. Ms. Mulder had no relevant financial disclosures. Dr. Helliwell has financial ties to AbbVie, Amgen, Celgen, Galapagos, Janssen, Novartis, Pfizer, and UCB.

SOURCE: Mulder M et al. GRAPPA 2020 Virtual Annual Meeting.

Extended use of corticosteroids for chronic inflammatory conditions puts patients at risk for serious adverse events (AEs), including cardiovascular disease, osteoporosis, cataracts, and diabetes. Now, a growing body of evidence suggests that even short bursts of these drugs are associated with serious risks.

Most recently, a population-based study of more than 2.6 million people found that taking corticosteroids for 14 days or less was associated with a substantially greater risk for gastrointestinal (GI) bleeding, sepsis, and heart failure, particularly within the first 30 days after therapy.

In the study, Tsung-Chieh Yao, MD, PhD, a professor in the division of allergy, asthma, and rheumatology in the department of pediatrics at Chang Gung Memorial Hospital in Taoyuan, Taiwan, and colleagues used a self-controlled case series to analyze data from Taiwan’s National Health Insurance Research Database of medical claims. They compared patients’ conditions in the period from 5 to 90 days before treatment to conditions from the periods from 5 to 30 days and from 31 to 90 days after therapy.

With a median duration of 3 days of treatment, the incidence rate ratios (IRRs) were 1.80 (95% confidence interval, 1.75-1.84) for GI bleeding, 1.99 (95% CI, 1.70-2.32) for sepsis, and 2.37 (95% CI, 2.13-2.63) for heart failure.

Given the findings, physicians should weigh the benefits against the risks of rare but potentially serious consequences of these anti-inflammatory drugs, according to the authors.

“After initiating patients on oral steroid bursts, physicians should be on the lookout for these severe adverse events, particularly within the first month after initiation of steroid therapy,” Dr. Yao said in an interview.

The findings were published online July 6 in Annals of Internal Medicine.

Of the 15,859,129 adult Asians in the Taiwanese database, the study included 2,623,327 adults aged 20-64 years who received single steroid bursts (14 days or less) between Jan. 1, 2013, and Dec. 31, 2015.

Almost 60% of the indications were for skin disorders, such as eczema and urticaria, and for respiratory tract infections, such as sinusitis and acute pharyngitis. Among specialties, dermatology, otolaryngology, family practice, internal medicine, and pediatrics accounted for 88% of prescriptions.

“Our findings are important for physicians and guideline developers because short-term use of oral corticosteroids is common and the real-world safety of this approach remains unclear,” the authors wrote. They acknowledged that the database did not provide information on such potential confounders as disease severity and lifestyle factors, nor did it include children and vulnerable individuals, which may limit the generalizability of the results.

The findings echo those of a 2017 cohort study conducted by researchers at the University of Michigan in Ann Arbor. That study, by Akbar K. Waljee, MD, assistant professor of gastroenterology, University of Michigan, Ann Arbor, and colleagues, included data on more than 1.5 million privately insured U.S. adults. The researchers included somewhat longer steroid bursts of up to 30 days’ duration and found that use of the drugs was associated with a greater than fivefold increased risk for sepsis, a more than threefold increased risk for venous thromboembolism, and a nearly twofold increased risk for fracture within 30 days of starting treatment.

Furthermore, the elevated risk persisted at prednisone-equivalent doses of less than 20 mg/d (IRR, 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture; all P < .001).

The U.S. study also found that during the 3-year period from 2012 to 2014, more than 20% of patients were prescribed short-term oral corticosteroids.

“Both studies indicate that these short-term regimens are more common in the real world than was previously thought and are not risk free,” Dr. Yao said.

Recognition that corticosteroids are associated with adverse events has been building for decades, according to the authors of an editorial that accompanies the new study.

“However, we commonly use short corticosteroid ‘bursts’ for minor ailments despite a lack of evidence for meaningful benefit. We are now learning that bursts as short as 3 days may increase risk for serious AEs, even in young and healthy people,” wrote editorialists Beth I. Wallace, MD, of the Center for Clinical Management Research at the VA Ann Arbor Healthcare System and the Institute for Healthcare Policy and Innovation at Michigan Medicine, Ann Arbor, and Dr. Waljee, who led the 2017 study.

Dr. Wallace and Dr. Waljee drew parallels between corticosteroid bursts and other short-term regimens, such as of antibiotics and opiates, in which prescriber preference and sometimes patient pressure play a role. “All of these treatments have well-defined indications but can cause net harm when used. We can thus conceive of a corticosteroid stewardship model of targeted interventions that aims to reduce inappropriate prescribing,” they wrote.

In an interview, Dr. Wallace, a rheumatologist who prescribes oral steroids fairly frequently, noted that the Taiwan study is the first to investigate steroid bursts. “Up till now, these very short courses have flown under the radar. Clinicians very commonly prescribe short courses to help relieve symptoms of self-limited conditions like bronchitis, and we assume that because the exposure duration is short, the risks are low, especially for patients who are otherwise healthy.”

She warned that the data in the current study indicate that these short bursts – even at the lower end of the 1- to 2-week courses American physicians prescribe most often – carry small but real increases in risk for serious AEs. “And these increases were seen in young, healthy people, not just in people with preexisting conditions,” she said. “So, we might need to start thinking harder about how we are prescribing even these very short courses of steroids and try to use steroids only when their meaningful benefits really outweigh the risk.”

She noted that a patient with a chronic inflammatory condition such as rheumatoid arthritis may benefit substantially from short-term steroids to treat a disease flare. In that specific case, the benefits of short-term steroids may outweigh the risks, Dr. Wallace said.

But not everyone thinks a new strategy is needed. For Whitney A. High, MD, associate professor of dermatology and pathology at the University of Colorado at Denver, Aurora, the overprescribing of short-term corticosteroids is not a problem, and dermatologists are already exercising caution.

Bruce Jancin/MDedge News

“I only prescribe these drugs short term to, at a guess, about 1 in 40 patients and only when a patient is miserable and quality of life is being seriously affected,” he said in an interview. “And that’s something that can’t be measured in a database study like the one from Taiwan but only in a risk-benefit analysis,” he said.

Furthermore, dermatologists have other drugs and technologies in their armamentarium, including topical steroids with occlusion or with wet wraps, phototherapy, phosphodiesterase inhibitors, calcipotriene, methotrexate and other immunosuppressive agents, and biologics. “In fact, many of these agents are specifically referred to as steroid-sparing,” Dr. High said.

Nor does he experience much pressure from patients to prescribe these drugs. “While occasionally I may encounter a patient who places pressure on me for oral steroids, it’s probably not nearly as frequently as providers in other fields are pressured to prescribe antibiotics or narcotics,” he said.

According to the Taiwanese researchers, the next step is to conduct more studies, including clinical trials, to determine optimal use of corticosteroids by monitoring adverse events. In the meantime, for practitioners such as Dr. Wallace and Dr. High, there is ample evidence from several recent studies of the harms of short-term corticosteroids, whereas the benefits for patients with self-limiting conditions remain uncertain. “This and other studies like it quite appropriately remind providers to avoid oral steroids when they’re not necessary and to seek alternatives where possible,” Dr. High said.

The study was supported by the National Health Research Institutes of Taiwan, the Ministry of Science and Technology of Taiwan, the Chang Gung Medical Foundation, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH). Dr. Yao has disclosed no relevant financial relationships. Dr. Wu has received grants from GlaxoSmithKline outside the submitted work. The editorialists and Dr. High have disclosed no relevant financial relationships. Dr. Wallace received an NIH grant during the writing of the editorial.
 

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

Extended use of corticosteroids for chronic inflammatory conditions puts patients at risk for serious adverse events (AEs), including cardiovascular disease, osteoporosis, cataracts, and diabetes. Now, a growing body of evidence suggests that even short bursts of these drugs are associated with serious risks.

Most recently, a population-based study of more than 2.6 million people found that taking corticosteroids for 14 days or less was associated with a substantially greater risk for gastrointestinal (GI) bleeding, sepsis, and heart failure, particularly within the first 30 days after therapy.

In the study, Tsung-Chieh Yao, MD, PhD, a professor in the division of allergy, asthma, and rheumatology in the department of pediatrics at Chang Gung Memorial Hospital in Taoyuan, Taiwan, and colleagues used a self-controlled case series to analyze data from Taiwan’s National Health Insurance Research Database of medical claims. They compared patients’ conditions in the period from 5 to 90 days before treatment to conditions from the periods from 5 to 30 days and from 31 to 90 days after therapy.

With a median duration of 3 days of treatment, the incidence rate ratios (IRRs) were 1.80 (95% confidence interval, 1.75-1.84) for GI bleeding, 1.99 (95% CI, 1.70-2.32) for sepsis, and 2.37 (95% CI, 2.13-2.63) for heart failure.

Given the findings, physicians should weigh the benefits against the risks of rare but potentially serious consequences of these anti-inflammatory drugs, according to the authors.

“After initiating patients on oral steroid bursts, physicians should be on the lookout for these severe adverse events, particularly within the first month after initiation of steroid therapy,” Dr. Yao said in an interview.

The findings were published online July 6 in Annals of Internal Medicine.

Of the 15,859,129 adult Asians in the Taiwanese database, the study included 2,623,327 adults aged 20-64 years who received single steroid bursts (14 days or less) between Jan. 1, 2013, and Dec. 31, 2015.

Almost 60% of the indications were for skin disorders, such as eczema and urticaria, and for respiratory tract infections, such as sinusitis and acute pharyngitis. Among specialties, dermatology, otolaryngology, family practice, internal medicine, and pediatrics accounted for 88% of prescriptions.

“Our findings are important for physicians and guideline developers because short-term use of oral corticosteroids is common and the real-world safety of this approach remains unclear,” the authors wrote. They acknowledged that the database did not provide information on such potential confounders as disease severity and lifestyle factors, nor did it include children and vulnerable individuals, which may limit the generalizability of the results.

The findings echo those of a 2017 cohort study conducted by researchers at the University of Michigan in Ann Arbor. That study, by Akbar K. Waljee, MD, assistant professor of gastroenterology, University of Michigan, Ann Arbor, and colleagues, included data on more than 1.5 million privately insured U.S. adults. The researchers included somewhat longer steroid bursts of up to 30 days’ duration and found that use of the drugs was associated with a greater than fivefold increased risk for sepsis, a more than threefold increased risk for venous thromboembolism, and a nearly twofold increased risk for fracture within 30 days of starting treatment.

Furthermore, the elevated risk persisted at prednisone-equivalent doses of less than 20 mg/d (IRR, 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture; all P < .001).

The U.S. study also found that during the 3-year period from 2012 to 2014, more than 20% of patients were prescribed short-term oral corticosteroids.

“Both studies indicate that these short-term regimens are more common in the real world than was previously thought and are not risk free,” Dr. Yao said.

Recognition that corticosteroids are associated with adverse events has been building for decades, according to the authors of an editorial that accompanies the new study.

“However, we commonly use short corticosteroid ‘bursts’ for minor ailments despite a lack of evidence for meaningful benefit. We are now learning that bursts as short as 3 days may increase risk for serious AEs, even in young and healthy people,” wrote editorialists Beth I. Wallace, MD, of the Center for Clinical Management Research at the VA Ann Arbor Healthcare System and the Institute for Healthcare Policy and Innovation at Michigan Medicine, Ann Arbor, and Dr. Waljee, who led the 2017 study.

Dr. Wallace and Dr. Waljee drew parallels between corticosteroid bursts and other short-term regimens, such as of antibiotics and opiates, in which prescriber preference and sometimes patient pressure play a role. “All of these treatments have well-defined indications but can cause net harm when used. We can thus conceive of a corticosteroid stewardship model of targeted interventions that aims to reduce inappropriate prescribing,” they wrote.

In an interview, Dr. Wallace, a rheumatologist who prescribes oral steroids fairly frequently, noted that the Taiwan study is the first to investigate steroid bursts. “Up till now, these very short courses have flown under the radar. Clinicians very commonly prescribe short courses to help relieve symptoms of self-limited conditions like bronchitis, and we assume that because the exposure duration is short, the risks are low, especially for patients who are otherwise healthy.”

She warned that the data in the current study indicate that these short bursts – even at the lower end of the 1- to 2-week courses American physicians prescribe most often – carry small but real increases in risk for serious AEs. “And these increases were seen in young, healthy people, not just in people with preexisting conditions,” she said. “So, we might need to start thinking harder about how we are prescribing even these very short courses of steroids and try to use steroids only when their meaningful benefits really outweigh the risk.”

She noted that a patient with a chronic inflammatory condition such as rheumatoid arthritis may benefit substantially from short-term steroids to treat a disease flare. In that specific case, the benefits of short-term steroids may outweigh the risks, Dr. Wallace said.

But not everyone thinks a new strategy is needed. For Whitney A. High, MD, associate professor of dermatology and pathology at the University of Colorado at Denver, Aurora, the overprescribing of short-term corticosteroids is not a problem, and dermatologists are already exercising caution.

Bruce Jancin/MDedge News

“I only prescribe these drugs short term to, at a guess, about 1 in 40 patients and only when a patient is miserable and quality of life is being seriously affected,” he said in an interview. “And that’s something that can’t be measured in a database study like the one from Taiwan but only in a risk-benefit analysis,” he said.

Furthermore, dermatologists have other drugs and technologies in their armamentarium, including topical steroids with occlusion or with wet wraps, phototherapy, phosphodiesterase inhibitors, calcipotriene, methotrexate and other immunosuppressive agents, and biologics. “In fact, many of these agents are specifically referred to as steroid-sparing,” Dr. High said.

Nor does he experience much pressure from patients to prescribe these drugs. “While occasionally I may encounter a patient who places pressure on me for oral steroids, it’s probably not nearly as frequently as providers in other fields are pressured to prescribe antibiotics or narcotics,” he said.

According to the Taiwanese researchers, the next step is to conduct more studies, including clinical trials, to determine optimal use of corticosteroids by monitoring adverse events. In the meantime, for practitioners such as Dr. Wallace and Dr. High, there is ample evidence from several recent studies of the harms of short-term corticosteroids, whereas the benefits for patients with self-limiting conditions remain uncertain. “This and other studies like it quite appropriately remind providers to avoid oral steroids when they’re not necessary and to seek alternatives where possible,” Dr. High said.

The study was supported by the National Health Research Institutes of Taiwan, the Ministry of Science and Technology of Taiwan, the Chang Gung Medical Foundation, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH). Dr. Yao has disclosed no relevant financial relationships. Dr. Wu has received grants from GlaxoSmithKline outside the submitted work. The editorialists and Dr. High have disclosed no relevant financial relationships. Dr. Wallace received an NIH grant during the writing of the editorial.
 

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

Extended use of corticosteroids for chronic inflammatory conditions puts patients at risk for serious adverse events (AEs), including cardiovascular disease, osteoporosis, cataracts, and diabetes. Now, a growing body of evidence suggests that even short bursts of these drugs are associated with serious risks.

Most recently, a population-based study of more than 2.6 million people found that taking corticosteroids for 14 days or less was associated with a substantially greater risk for gastrointestinal (GI) bleeding, sepsis, and heart failure, particularly within the first 30 days after therapy.

In the study, Tsung-Chieh Yao, MD, PhD, a professor in the division of allergy, asthma, and rheumatology in the department of pediatrics at Chang Gung Memorial Hospital in Taoyuan, Taiwan, and colleagues used a self-controlled case series to analyze data from Taiwan’s National Health Insurance Research Database of medical claims. They compared patients’ conditions in the period from 5 to 90 days before treatment to conditions from the periods from 5 to 30 days and from 31 to 90 days after therapy.

With a median duration of 3 days of treatment, the incidence rate ratios (IRRs) were 1.80 (95% confidence interval, 1.75-1.84) for GI bleeding, 1.99 (95% CI, 1.70-2.32) for sepsis, and 2.37 (95% CI, 2.13-2.63) for heart failure.

Given the findings, physicians should weigh the benefits against the risks of rare but potentially serious consequences of these anti-inflammatory drugs, according to the authors.

“After initiating patients on oral steroid bursts, physicians should be on the lookout for these severe adverse events, particularly within the first month after initiation of steroid therapy,” Dr. Yao said in an interview.

The findings were published online July 6 in Annals of Internal Medicine.

Of the 15,859,129 adult Asians in the Taiwanese database, the study included 2,623,327 adults aged 20-64 years who received single steroid bursts (14 days or less) between Jan. 1, 2013, and Dec. 31, 2015.

Almost 60% of the indications were for skin disorders, such as eczema and urticaria, and for respiratory tract infections, such as sinusitis and acute pharyngitis. Among specialties, dermatology, otolaryngology, family practice, internal medicine, and pediatrics accounted for 88% of prescriptions.

“Our findings are important for physicians and guideline developers because short-term use of oral corticosteroids is common and the real-world safety of this approach remains unclear,” the authors wrote. They acknowledged that the database did not provide information on such potential confounders as disease severity and lifestyle factors, nor did it include children and vulnerable individuals, which may limit the generalizability of the results.

The findings echo those of a 2017 cohort study conducted by researchers at the University of Michigan in Ann Arbor. That study, by Akbar K. Waljee, MD, assistant professor of gastroenterology, University of Michigan, Ann Arbor, and colleagues, included data on more than 1.5 million privately insured U.S. adults. The researchers included somewhat longer steroid bursts of up to 30 days’ duration and found that use of the drugs was associated with a greater than fivefold increased risk for sepsis, a more than threefold increased risk for venous thromboembolism, and a nearly twofold increased risk for fracture within 30 days of starting treatment.

Furthermore, the elevated risk persisted at prednisone-equivalent doses of less than 20 mg/d (IRR, 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture; all P < .001).

The U.S. study also found that during the 3-year period from 2012 to 2014, more than 20% of patients were prescribed short-term oral corticosteroids.

“Both studies indicate that these short-term regimens are more common in the real world than was previously thought and are not risk free,” Dr. Yao said.

Recognition that corticosteroids are associated with adverse events has been building for decades, according to the authors of an editorial that accompanies the new study.

“However, we commonly use short corticosteroid ‘bursts’ for minor ailments despite a lack of evidence for meaningful benefit. We are now learning that bursts as short as 3 days may increase risk for serious AEs, even in young and healthy people,” wrote editorialists Beth I. Wallace, MD, of the Center for Clinical Management Research at the VA Ann Arbor Healthcare System and the Institute for Healthcare Policy and Innovation at Michigan Medicine, Ann Arbor, and Dr. Waljee, who led the 2017 study.

Dr. Wallace and Dr. Waljee drew parallels between corticosteroid bursts and other short-term regimens, such as of antibiotics and opiates, in which prescriber preference and sometimes patient pressure play a role. “All of these treatments have well-defined indications but can cause net harm when used. We can thus conceive of a corticosteroid stewardship model of targeted interventions that aims to reduce inappropriate prescribing,” they wrote.

In an interview, Dr. Wallace, a rheumatologist who prescribes oral steroids fairly frequently, noted that the Taiwan study is the first to investigate steroid bursts. “Up till now, these very short courses have flown under the radar. Clinicians very commonly prescribe short courses to help relieve symptoms of self-limited conditions like bronchitis, and we assume that because the exposure duration is short, the risks are low, especially for patients who are otherwise healthy.”

She warned that the data in the current study indicate that these short bursts – even at the lower end of the 1- to 2-week courses American physicians prescribe most often – carry small but real increases in risk for serious AEs. “And these increases were seen in young, healthy people, not just in people with preexisting conditions,” she said. “So, we might need to start thinking harder about how we are prescribing even these very short courses of steroids and try to use steroids only when their meaningful benefits really outweigh the risk.”

She noted that a patient with a chronic inflammatory condition such as rheumatoid arthritis may benefit substantially from short-term steroids to treat a disease flare. In that specific case, the benefits of short-term steroids may outweigh the risks, Dr. Wallace said.

But not everyone thinks a new strategy is needed. For Whitney A. High, MD, associate professor of dermatology and pathology at the University of Colorado at Denver, Aurora, the overprescribing of short-term corticosteroids is not a problem, and dermatologists are already exercising caution.

Bruce Jancin/MDedge News

“I only prescribe these drugs short term to, at a guess, about 1 in 40 patients and only when a patient is miserable and quality of life is being seriously affected,” he said in an interview. “And that’s something that can’t be measured in a database study like the one from Taiwan but only in a risk-benefit analysis,” he said.

Furthermore, dermatologists have other drugs and technologies in their armamentarium, including topical steroids with occlusion or with wet wraps, phototherapy, phosphodiesterase inhibitors, calcipotriene, methotrexate and other immunosuppressive agents, and biologics. “In fact, many of these agents are specifically referred to as steroid-sparing,” Dr. High said.

Nor does he experience much pressure from patients to prescribe these drugs. “While occasionally I may encounter a patient who places pressure on me for oral steroids, it’s probably not nearly as frequently as providers in other fields are pressured to prescribe antibiotics or narcotics,” he said.

According to the Taiwanese researchers, the next step is to conduct more studies, including clinical trials, to determine optimal use of corticosteroids by monitoring adverse events. In the meantime, for practitioners such as Dr. Wallace and Dr. High, there is ample evidence from several recent studies of the harms of short-term corticosteroids, whereas the benefits for patients with self-limiting conditions remain uncertain. “This and other studies like it quite appropriately remind providers to avoid oral steroids when they’re not necessary and to seek alternatives where possible,” Dr. High said.

The study was supported by the National Health Research Institutes of Taiwan, the Ministry of Science and Technology of Taiwan, the Chang Gung Medical Foundation, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH). Dr. Yao has disclosed no relevant financial relationships. Dr. Wu has received grants from GlaxoSmithKline outside the submitted work. The editorialists and Dr. High have disclosed no relevant financial relationships. Dr. Wallace received an NIH grant during the writing of the editorial.
 

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

A pair of new vaccines for adults aged 65 years and older will be available for the 2020-2021 flu season – Fluzone high-dose quadrivalent, which replaces the trivalent Fluzone high-dose and Fluad quadrivalent (Seqirus), according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

At a virtual meeting on June 24, the committee voted unanimously to approve the vaccine recommendations for annual influenza immunization of all individuals aged 6 months and older. They also voted to accept some guidance and language changes to the recommendations.

The past flu season was unique in its overlap with the emergence of the COVID-19 coronavirus, which likely contributed to a third peak in reported cases of influenza-like illness at approximately week 14 of last season, said Lisa Grohskopf, MD, of the CDC’s influenza division, who presented data on last year’s activity and the updates for next season.

The CDC estimates that 39,000,000-56,000,000 flu illnesses occurred in the United States from Oct. 1, 2019, to April 4, 2020, said Dr. Grohskopf. Estimates also suggest as many as 740,000 hospitalizations and 62,000 deaths related to the seasonal flu.

Preliminary results of vaccine effectiveness showed 39% overall for the 2019-2020 season, with more substantial protection against influenza B and lower protection against A/H1N1pmd09.

Vaccine safety data from the Vaccine Adverse Event Reporting System and Vaccine Safety Datalink showed no new safety concerns for any flu vaccine types used last year, Dr. Grohskopf noted.

Based on this information, three components (A/H1N1pdm09, A/H3N2, and B/Victoria) have been updated for the 2020-2021 vaccines, said Dr. Grohskopf. The egg-based influenza vaccines will include hemagglutinin derived from an A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09–like virus, an A/Hong Kong/2671/2019(H3N2)–like virus and a B/Washington/02/2019 (Victoria lineage)–like virus, and (for quadrivalent vaccines) a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

Nonegg vaccines will contain hemagglutinin derived from an A/Hawaii/70/2019 (H1N1)pdm09–like virus, an A/Hong Kong/45/2019 (H3N2)–like virus, a B/Washington/02/2019 (Victoria lineage)–like virus, and a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

New guidance for next year’s flu season includes a change to the language in the contraindications and precautions table to simply read “Contraindications,” with more details in the text explaining package insert contraindications and ACIP recommendations, Dr. Grohskopf said. In addition, updated guidance clarifies that live-attenuated influenza vaccine quadravalents (LAIV4) should not be used in patients with cochlear implants, active cerebrospinal fluid leaks, and anatomical or functional asplenia, based on ACIP’s review of the latest evidence and the availability of alternative vaccines.

ACIP also updated guidance on the use of antivirals and LAIV4. Based on half-lives, language was added indicating that clinicians should assume interference if antivirals are given within certain intervals of LAIV4, Dr. Grohskopf explained. “Newer antivirals peramivir and baloxavir have longer half-lives than oseltamivir and zanamivir, and insufficient data are available on the use of LAIV4 in the setting of antiviral use.”

The ACIP members had no financial conflicts to disclose.
 

A pair of new vaccines for adults aged 65 years and older will be available for the 2020-2021 flu season – Fluzone high-dose quadrivalent, which replaces the trivalent Fluzone high-dose and Fluad quadrivalent (Seqirus), according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

At a virtual meeting on June 24, the committee voted unanimously to approve the vaccine recommendations for annual influenza immunization of all individuals aged 6 months and older. They also voted to accept some guidance and language changes to the recommendations.

The past flu season was unique in its overlap with the emergence of the COVID-19 coronavirus, which likely contributed to a third peak in reported cases of influenza-like illness at approximately week 14 of last season, said Lisa Grohskopf, MD, of the CDC’s influenza division, who presented data on last year’s activity and the updates for next season.

The CDC estimates that 39,000,000-56,000,000 flu illnesses occurred in the United States from Oct. 1, 2019, to April 4, 2020, said Dr. Grohskopf. Estimates also suggest as many as 740,000 hospitalizations and 62,000 deaths related to the seasonal flu.

Preliminary results of vaccine effectiveness showed 39% overall for the 2019-2020 season, with more substantial protection against influenza B and lower protection against A/H1N1pmd09.

Vaccine safety data from the Vaccine Adverse Event Reporting System and Vaccine Safety Datalink showed no new safety concerns for any flu vaccine types used last year, Dr. Grohskopf noted.

Based on this information, three components (A/H1N1pdm09, A/H3N2, and B/Victoria) have been updated for the 2020-2021 vaccines, said Dr. Grohskopf. The egg-based influenza vaccines will include hemagglutinin derived from an A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09–like virus, an A/Hong Kong/2671/2019(H3N2)–like virus and a B/Washington/02/2019 (Victoria lineage)–like virus, and (for quadrivalent vaccines) a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

Nonegg vaccines will contain hemagglutinin derived from an A/Hawaii/70/2019 (H1N1)pdm09–like virus, an A/Hong Kong/45/2019 (H3N2)–like virus, a B/Washington/02/2019 (Victoria lineage)–like virus, and a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

New guidance for next year’s flu season includes a change to the language in the contraindications and precautions table to simply read “Contraindications,” with more details in the text explaining package insert contraindications and ACIP recommendations, Dr. Grohskopf said. In addition, updated guidance clarifies that live-attenuated influenza vaccine quadravalents (LAIV4) should not be used in patients with cochlear implants, active cerebrospinal fluid leaks, and anatomical or functional asplenia, based on ACIP’s review of the latest evidence and the availability of alternative vaccines.

ACIP also updated guidance on the use of antivirals and LAIV4. Based on half-lives, language was added indicating that clinicians should assume interference if antivirals are given within certain intervals of LAIV4, Dr. Grohskopf explained. “Newer antivirals peramivir and baloxavir have longer half-lives than oseltamivir and zanamivir, and insufficient data are available on the use of LAIV4 in the setting of antiviral use.”

The ACIP members had no financial conflicts to disclose.
 

A pair of new vaccines for adults aged 65 years and older will be available for the 2020-2021 flu season – Fluzone high-dose quadrivalent, which replaces the trivalent Fluzone high-dose and Fluad quadrivalent (Seqirus), according to the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.

At a virtual meeting on June 24, the committee voted unanimously to approve the vaccine recommendations for annual influenza immunization of all individuals aged 6 months and older. They also voted to accept some guidance and language changes to the recommendations.

The past flu season was unique in its overlap with the emergence of the COVID-19 coronavirus, which likely contributed to a third peak in reported cases of influenza-like illness at approximately week 14 of last season, said Lisa Grohskopf, MD, of the CDC’s influenza division, who presented data on last year’s activity and the updates for next season.

The CDC estimates that 39,000,000-56,000,000 flu illnesses occurred in the United States from Oct. 1, 2019, to April 4, 2020, said Dr. Grohskopf. Estimates also suggest as many as 740,000 hospitalizations and 62,000 deaths related to the seasonal flu.

Preliminary results of vaccine effectiveness showed 39% overall for the 2019-2020 season, with more substantial protection against influenza B and lower protection against A/H1N1pmd09.

Vaccine safety data from the Vaccine Adverse Event Reporting System and Vaccine Safety Datalink showed no new safety concerns for any flu vaccine types used last year, Dr. Grohskopf noted.

Based on this information, three components (A/H1N1pdm09, A/H3N2, and B/Victoria) have been updated for the 2020-2021 vaccines, said Dr. Grohskopf. The egg-based influenza vaccines will include hemagglutinin derived from an A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09–like virus, an A/Hong Kong/2671/2019(H3N2)–like virus and a B/Washington/02/2019 (Victoria lineage)–like virus, and (for quadrivalent vaccines) a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

Nonegg vaccines will contain hemagglutinin derived from an A/Hawaii/70/2019 (H1N1)pdm09–like virus, an A/Hong Kong/45/2019 (H3N2)–like virus, a B/Washington/02/2019 (Victoria lineage)–like virus, and a B/Phuket/3073/2013 (Yamagata lineage)–like virus.

New guidance for next year’s flu season includes a change to the language in the contraindications and precautions table to simply read “Contraindications,” with more details in the text explaining package insert contraindications and ACIP recommendations, Dr. Grohskopf said. In addition, updated guidance clarifies that live-attenuated influenza vaccine quadravalents (LAIV4) should not be used in patients with cochlear implants, active cerebrospinal fluid leaks, and anatomical or functional asplenia, based on ACIP’s review of the latest evidence and the availability of alternative vaccines.

ACIP also updated guidance on the use of antivirals and LAIV4. Based on half-lives, language was added indicating that clinicians should assume interference if antivirals are given within certain intervals of LAIV4, Dr. Grohskopf explained. “Newer antivirals peramivir and baloxavir have longer half-lives than oseltamivir and zanamivir, and insufficient data are available on the use of LAIV4 in the setting of antiviral use.”

The ACIP members had no financial conflicts to disclose.
 

The interleukin (IL)-23 inhibitor risankizumab was decisively more effective than the IL-17A inhibitor secukinumab at 52 weeks in a multinational randomized head-to-head trial in patients with moderate to severe psoriasis.

Risankizumab was better tolerated, with a significantly lower rate of treatment-emergent adverse events and a lower study dropout rate, Richard B. Warren, MBChB, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.

In addition, the dosing schedule for risankizumab (Skyrizi) is more convenient, with maintenance dosing by subcutaneous injection once every 12 weeks, compared with monthly for secukinumab (Cosentyx), a biologic for psoriasis considered state-of-the-art not long ago, noted Dr. Warren, a dermatologist at the Salford (England) Royal NHS Foundation Trust and the Manchester NIHR Biomedical Research Center as well as professor of dermatology at the University of Manchester.

The phase 3 IMMERGE trial included 327 patients with moderate to severe psoriasis randomized to risankizumab or secukinumab for 52 weeks at their approved dosing. The trial, conducted mainly in the United States, Canada, and Europe, was open label, but evaluator blinded.

The coprimary endpoints were a 90% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 90) at weeks 16 and 52. The week 52 PASI 90 response rates were 87% in the risankizumab group and 57% with secukinumab, for a highly significant absolute 30% difference. The week 16 result was a prespecified noninferiority analysis, and here again risankizumab met its mark, with a PASI 90 rate of 74%, statistically noninferior to the 66% rate with secukinumab, even though at that point patients had received only two doses of risankizumab, versus seven doses of secukinumab.

The PASI 100 response rate at 52 weeks, a key secondary endpoint, was 66% with risankizumab and 40% with secukinumab. Another secondary endpoint was achievement of a static Physician Global Assessment score of 0 or 1 – clear or almost clear – at week 52; the rates were 88% with risankizumab, 58% with secukinumab.

Ninety-two percent of participants randomized to risankizumab completed the full 52-week study, as did 82.8% of the secukinumab group. The nearly 10% absolute lower completion rate in the secukinumab group was driven by a higher rate of lack of efficacy – 4.3%, compared to 0.6% for risankizumab – and a greater incidence of adverse events. Indeed, treatment-emergent adverse events were fourfold more common in the secukinumab arm, with a rate of 4.9%, versus 1.2% with risankizumab, according to Dr. Warren.

He reported receiving research grants from and serving as a consultant to the study sponsor, AbbVie, as well as roughly a dozen other pharmaceutical companies.

[email protected]

The interleukin (IL)-23 inhibitor risankizumab was decisively more effective than the IL-17A inhibitor secukinumab at 52 weeks in a multinational randomized head-to-head trial in patients with moderate to severe psoriasis.

Risankizumab was better tolerated, with a significantly lower rate of treatment-emergent adverse events and a lower study dropout rate, Richard B. Warren, MBChB, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.

In addition, the dosing schedule for risankizumab (Skyrizi) is more convenient, with maintenance dosing by subcutaneous injection once every 12 weeks, compared with monthly for secukinumab (Cosentyx), a biologic for psoriasis considered state-of-the-art not long ago, noted Dr. Warren, a dermatologist at the Salford (England) Royal NHS Foundation Trust and the Manchester NIHR Biomedical Research Center as well as professor of dermatology at the University of Manchester.

The phase 3 IMMERGE trial included 327 patients with moderate to severe psoriasis randomized to risankizumab or secukinumab for 52 weeks at their approved dosing. The trial, conducted mainly in the United States, Canada, and Europe, was open label, but evaluator blinded.

The coprimary endpoints were a 90% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 90) at weeks 16 and 52. The week 52 PASI 90 response rates were 87% in the risankizumab group and 57% with secukinumab, for a highly significant absolute 30% difference. The week 16 result was a prespecified noninferiority analysis, and here again risankizumab met its mark, with a PASI 90 rate of 74%, statistically noninferior to the 66% rate with secukinumab, even though at that point patients had received only two doses of risankizumab, versus seven doses of secukinumab.

The PASI 100 response rate at 52 weeks, a key secondary endpoint, was 66% with risankizumab and 40% with secukinumab. Another secondary endpoint was achievement of a static Physician Global Assessment score of 0 or 1 – clear or almost clear – at week 52; the rates were 88% with risankizumab, 58% with secukinumab.

Ninety-two percent of participants randomized to risankizumab completed the full 52-week study, as did 82.8% of the secukinumab group. The nearly 10% absolute lower completion rate in the secukinumab group was driven by a higher rate of lack of efficacy – 4.3%, compared to 0.6% for risankizumab – and a greater incidence of adverse events. Indeed, treatment-emergent adverse events were fourfold more common in the secukinumab arm, with a rate of 4.9%, versus 1.2% with risankizumab, according to Dr. Warren.

He reported receiving research grants from and serving as a consultant to the study sponsor, AbbVie, as well as roughly a dozen other pharmaceutical companies.

[email protected]

The interleukin (IL)-23 inhibitor risankizumab was decisively more effective than the IL-17A inhibitor secukinumab at 52 weeks in a multinational randomized head-to-head trial in patients with moderate to severe psoriasis.

Risankizumab was better tolerated, with a significantly lower rate of treatment-emergent adverse events and a lower study dropout rate, Richard B. Warren, MBChB, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.

In addition, the dosing schedule for risankizumab (Skyrizi) is more convenient, with maintenance dosing by subcutaneous injection once every 12 weeks, compared with monthly for secukinumab (Cosentyx), a biologic for psoriasis considered state-of-the-art not long ago, noted Dr. Warren, a dermatologist at the Salford (England) Royal NHS Foundation Trust and the Manchester NIHR Biomedical Research Center as well as professor of dermatology at the University of Manchester.

The phase 3 IMMERGE trial included 327 patients with moderate to severe psoriasis randomized to risankizumab or secukinumab for 52 weeks at their approved dosing. The trial, conducted mainly in the United States, Canada, and Europe, was open label, but evaluator blinded.

The coprimary endpoints were a 90% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 90) at weeks 16 and 52. The week 52 PASI 90 response rates were 87% in the risankizumab group and 57% with secukinumab, for a highly significant absolute 30% difference. The week 16 result was a prespecified noninferiority analysis, and here again risankizumab met its mark, with a PASI 90 rate of 74%, statistically noninferior to the 66% rate with secukinumab, even though at that point patients had received only two doses of risankizumab, versus seven doses of secukinumab.

The PASI 100 response rate at 52 weeks, a key secondary endpoint, was 66% with risankizumab and 40% with secukinumab. Another secondary endpoint was achievement of a static Physician Global Assessment score of 0 or 1 – clear or almost clear – at week 52; the rates were 88% with risankizumab, 58% with secukinumab.

Ninety-two percent of participants randomized to risankizumab completed the full 52-week study, as did 82.8% of the secukinumab group. The nearly 10% absolute lower completion rate in the secukinumab group was driven by a higher rate of lack of efficacy – 4.3%, compared to 0.6% for risankizumab – and a greater incidence of adverse events. Indeed, treatment-emergent adverse events were fourfold more common in the secukinumab arm, with a rate of 4.9%, versus 1.2% with risankizumab, according to Dr. Warren.

He reported receiving research grants from and serving as a consultant to the study sponsor, AbbVie, as well as roughly a dozen other pharmaceutical companies.

[email protected]

New EULAR recommendations for the intra-articular (IA) treatment of arthropathies aim to facilitate uniformity and quality of care for this mainstay of rheumatologic practice, according to a report on the new guidance that was presented at the annual European Congress of Rheumatology, held online this year due to COVID-19.

Until now there were no official recommendations on how best to use it in everyday practice. “This is the first time that there’s been a joint effort to develop evidence-based recommendations,” Jacqueline Usón, MD, PhD, associate professor medicine at Rey Juan Carlos University in Madrid, said in an interview. “Everything that we are saying is pretty logical, but it’s nice to see it put in recommendations based on evidence.”

IA therapy has been around for decades and is key for treating adults with a number of different conditions where synovitis, effusion, pain, or all three, are present, such as inflammatory arthritis and osteoarthritis, Dr. Usón observed during her presentation.

“Today, commonly used injectables are not only corticosteroids but also local anesthetics, hyaluronic acid, blood products, and maybe pharmaceuticals,” she said, adding that “there is a wide variation in the way intra-articular therapies are used and delivered to patients.” Health professionals also have very different views and habits depending on geographic locations and health care systems, she observed. Ironing out the variation was one of the main objectives of the recommendations.

As one of the two conveners of the EULAR task force behind the recommendations, Dr. Usón, herself a rheumatologist at University Hospital of Móstoles, pointed out that the task force brought together a range of specialties – rheumatologists, orthopedic surgeons, radiologists, nuclear medicine specialists, among others, as well as patients – to ensure that the best advice could be given.

The task force followed EULAR standard operating procedures for developing recommendations, with discussion groups, systematic literature reviews, and Delphi technique-based consensus all being employed. The literature search considered publications from 1946 up until 2019.

“We agreed on the need for more background information from health professionals and patients, so we developed two surveys: One for health professionals with 160 items, [for which] we obtained 186 responses from 26 countries; and the patient survey was made up of 44 items, translated into 10 different languages, and we obtained 200 responses,” she said.

The results of the systematic literature review and surveys were used to help form expert consensus, leading to 5 overarching principles and 11 recommendations that look at before, during, and after intra-articular therapy.
 

Five overarching principles

The first overarching principle recognizes the widespread use of IA therapies and that their use is specific to the disease that is being treated and “may not be interchangeable across indications,” Dr. Usón said. The second principle concerns improving patient-centered outcomes, which are “those that are relevant to the patient,” and include the benefits, harms, preferences, or implications for self-management.

“Contextual factors are important and contribute to the effect of IAT [intra-articular treatment],” she said, discussing the third principle. “These include effective communication, patient expectations, or settings [where the procedure takes place]. In addition, one should take into account that the route of delivery has in itself a placebo effect. We found that in different RCTs [randomized controlled trials], the pooled placebo effect of IA saline is moderate to large.”

The fourth principle looks at ensuring that patients and clinicians make an informed and shared decision, which is again highlighted by the first recommendation. The fifth, and last, overarching principle acknowledges that IA injections may be given by a range of health care professionals.
 

Advice for before, during, and after injection

Patients need to be “fully informed of the nature of the procedure, the injectable used, and potential effects – benefits and risks – [and] informed consent should be obtained and documented,” said Dr. Usón, outlining the first recommendation. “That seems common,” she said in the interview, “but when we did the survey, we realize that many patients didn’t [give consent], and the doctors didn’t even ask for it. This is why it’s a very general statement, and it’s our first recommendation. The agreement was 99%!”

The recommendations also look at the optimal settings for performing injections, such as providing a professional and private, well-lighted room, and having a resuscitation kit nearby in case patients faint. Accuracy is important, Dr. Usón said, and imaging, such as ultrasound, should be used where available to ensure accurate injection into the joint. This is an area where further research could be performed, she said, urging young rheumatologists and health professionals to consider this. “Intra-articular therapy is something that you learn and do, but you never really investigate in it,” she said.

One recommendation states that when intra-articular injections are being given to pregnant patients, the safety of injected compound must be considered, both for the mother and for the fetus. There is another recommendation on the need to perform IA injections under aseptic conditions, and another stating that patients should be offered local anesthetics, after explaining the pros and cons.

Special populations of patients are also considered, Dr. Usón said. For example, the guidance advises warning patients with diabetes of the risk of transient glycemia after IA glucocorticoids and the need to monitor their blood glucose levels carefully for a couple of days afterward.

As a rule, “IAT is not a contraindication to people with clotting or bleeding disorders, or taking antithrombotic medications,” she said, unless they are at a high risk of bleeding.

Importantly, the recommendations cover when IAT can be performed after joint replacement surgery (after at least 3 months), and the need to “avoid overuse of injected joints” while also avoiding complete immobilization for at least 24 hours afterward. The recommendations very generally cover re-injections, but not how long intervals between injections should be. When asked about interval duration after her presentation, Dr. Usón said that the usual advice is to give IA injections no more than 2-3 times a year, but it depends on the injectable.

“It wasn’t our intention to review the efficacy and the safety of the different injectables, nor to review the use of IAT in different types of joint diseases,” she said. “We do lack a lot of information, a lot of evidence in this, and I really would hope that new rheumatologists start looking into and start investigating in this topic,” she added.
 

Recommendations will increase awareness of good clinical practice

“IA injections are commonly administered in the rheumatology setting. This is because [IA injection] is often a useful treatment for acute flare of arthritis, particularly when it is limited to a few joints,” observed Ai Lyn Tan, MD, associate professor and honorary consultant rheumatologist at the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine.

IA injection “also relieves symptoms relatively quickly for patients; however, the response can be variable, and there are side effects associated with IA injections,” Dr. Tan added in an interview.

There is a lack of universally accepted recommendations, Dr. Tan observed, noting that while there might be some local guidelines on how to safely perform IA injections these were often not standardized and were subject to being continually updated to try to improve the experience for patients.

“It is therefore timely to learn about the new EULAR recommendations for IA injections. The advantage of this will be to increase awareness of good clinical practice for performing IA injections.”

Dr. Tan had no relevant conflicts of interest.

SOURCE: EULAR COVID-19 Recommendations. E-congress content available until Sept. 1, 2020.

New EULAR recommendations for the intra-articular (IA) treatment of arthropathies aim to facilitate uniformity and quality of care for this mainstay of rheumatologic practice, according to a report on the new guidance that was presented at the annual European Congress of Rheumatology, held online this year due to COVID-19.

Until now there were no official recommendations on how best to use it in everyday practice. “This is the first time that there’s been a joint effort to develop evidence-based recommendations,” Jacqueline Usón, MD, PhD, associate professor medicine at Rey Juan Carlos University in Madrid, said in an interview. “Everything that we are saying is pretty logical, but it’s nice to see it put in recommendations based on evidence.”

IA therapy has been around for decades and is key for treating adults with a number of different conditions where synovitis, effusion, pain, or all three, are present, such as inflammatory arthritis and osteoarthritis, Dr. Usón observed during her presentation.

“Today, commonly used injectables are not only corticosteroids but also local anesthetics, hyaluronic acid, blood products, and maybe pharmaceuticals,” she said, adding that “there is a wide variation in the way intra-articular therapies are used and delivered to patients.” Health professionals also have very different views and habits depending on geographic locations and health care systems, she observed. Ironing out the variation was one of the main objectives of the recommendations.

As one of the two conveners of the EULAR task force behind the recommendations, Dr. Usón, herself a rheumatologist at University Hospital of Móstoles, pointed out that the task force brought together a range of specialties – rheumatologists, orthopedic surgeons, radiologists, nuclear medicine specialists, among others, as well as patients – to ensure that the best advice could be given.

The task force followed EULAR standard operating procedures for developing recommendations, with discussion groups, systematic literature reviews, and Delphi technique-based consensus all being employed. The literature search considered publications from 1946 up until 2019.

“We agreed on the need for more background information from health professionals and patients, so we developed two surveys: One for health professionals with 160 items, [for which] we obtained 186 responses from 26 countries; and the patient survey was made up of 44 items, translated into 10 different languages, and we obtained 200 responses,” she said.

The results of the systematic literature review and surveys were used to help form expert consensus, leading to 5 overarching principles and 11 recommendations that look at before, during, and after intra-articular therapy.
 

Five overarching principles

The first overarching principle recognizes the widespread use of IA therapies and that their use is specific to the disease that is being treated and “may not be interchangeable across indications,” Dr. Usón said. The second principle concerns improving patient-centered outcomes, which are “those that are relevant to the patient,” and include the benefits, harms, preferences, or implications for self-management.

“Contextual factors are important and contribute to the effect of IAT [intra-articular treatment],” she said, discussing the third principle. “These include effective communication, patient expectations, or settings [where the procedure takes place]. In addition, one should take into account that the route of delivery has in itself a placebo effect. We found that in different RCTs [randomized controlled trials], the pooled placebo effect of IA saline is moderate to large.”

The fourth principle looks at ensuring that patients and clinicians make an informed and shared decision, which is again highlighted by the first recommendation. The fifth, and last, overarching principle acknowledges that IA injections may be given by a range of health care professionals.
 

Advice for before, during, and after injection

Patients need to be “fully informed of the nature of the procedure, the injectable used, and potential effects – benefits and risks – [and] informed consent should be obtained and documented,” said Dr. Usón, outlining the first recommendation. “That seems common,” she said in the interview, “but when we did the survey, we realize that many patients didn’t [give consent], and the doctors didn’t even ask for it. This is why it’s a very general statement, and it’s our first recommendation. The agreement was 99%!”

The recommendations also look at the optimal settings for performing injections, such as providing a professional and private, well-lighted room, and having a resuscitation kit nearby in case patients faint. Accuracy is important, Dr. Usón said, and imaging, such as ultrasound, should be used where available to ensure accurate injection into the joint. This is an area where further research could be performed, she said, urging young rheumatologists and health professionals to consider this. “Intra-articular therapy is something that you learn and do, but you never really investigate in it,” she said.

One recommendation states that when intra-articular injections are being given to pregnant patients, the safety of injected compound must be considered, both for the mother and for the fetus. There is another recommendation on the need to perform IA injections under aseptic conditions, and another stating that patients should be offered local anesthetics, after explaining the pros and cons.

Special populations of patients are also considered, Dr. Usón said. For example, the guidance advises warning patients with diabetes of the risk of transient glycemia after IA glucocorticoids and the need to monitor their blood glucose levels carefully for a couple of days afterward.

As a rule, “IAT is not a contraindication to people with clotting or bleeding disorders, or taking antithrombotic medications,” she said, unless they are at a high risk of bleeding.

Importantly, the recommendations cover when IAT can be performed after joint replacement surgery (after at least 3 months), and the need to “avoid overuse of injected joints” while also avoiding complete immobilization for at least 24 hours afterward. The recommendations very generally cover re-injections, but not how long intervals between injections should be. When asked about interval duration after her presentation, Dr. Usón said that the usual advice is to give IA injections no more than 2-3 times a year, but it depends on the injectable.

“It wasn’t our intention to review the efficacy and the safety of the different injectables, nor to review the use of IAT in different types of joint diseases,” she said. “We do lack a lot of information, a lot of evidence in this, and I really would hope that new rheumatologists start looking into and start investigating in this topic,” she added.
 

Recommendations will increase awareness of good clinical practice

“IA injections are commonly administered in the rheumatology setting. This is because [IA injection] is often a useful treatment for acute flare of arthritis, particularly when it is limited to a few joints,” observed Ai Lyn Tan, MD, associate professor and honorary consultant rheumatologist at the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine.

IA injection “also relieves symptoms relatively quickly for patients; however, the response can be variable, and there are side effects associated with IA injections,” Dr. Tan added in an interview.

There is a lack of universally accepted recommendations, Dr. Tan observed, noting that while there might be some local guidelines on how to safely perform IA injections these were often not standardized and were subject to being continually updated to try to improve the experience for patients.

“It is therefore timely to learn about the new EULAR recommendations for IA injections. The advantage of this will be to increase awareness of good clinical practice for performing IA injections.”

Dr. Tan had no relevant conflicts of interest.

SOURCE: EULAR COVID-19 Recommendations. E-congress content available until Sept. 1, 2020.

New EULAR recommendations for the intra-articular (IA) treatment of arthropathies aim to facilitate uniformity and quality of care for this mainstay of rheumatologic practice, according to a report on the new guidance that was presented at the annual European Congress of Rheumatology, held online this year due to COVID-19.

Until now there were no official recommendations on how best to use it in everyday practice. “This is the first time that there’s been a joint effort to develop evidence-based recommendations,” Jacqueline Usón, MD, PhD, associate professor medicine at Rey Juan Carlos University in Madrid, said in an interview. “Everything that we are saying is pretty logical, but it’s nice to see it put in recommendations based on evidence.”

IA therapy has been around for decades and is key for treating adults with a number of different conditions where synovitis, effusion, pain, or all three, are present, such as inflammatory arthritis and osteoarthritis, Dr. Usón observed during her presentation.

“Today, commonly used injectables are not only corticosteroids but also local anesthetics, hyaluronic acid, blood products, and maybe pharmaceuticals,” she said, adding that “there is a wide variation in the way intra-articular therapies are used and delivered to patients.” Health professionals also have very different views and habits depending on geographic locations and health care systems, she observed. Ironing out the variation was one of the main objectives of the recommendations.

As one of the two conveners of the EULAR task force behind the recommendations, Dr. Usón, herself a rheumatologist at University Hospital of Móstoles, pointed out that the task force brought together a range of specialties – rheumatologists, orthopedic surgeons, radiologists, nuclear medicine specialists, among others, as well as patients – to ensure that the best advice could be given.

The task force followed EULAR standard operating procedures for developing recommendations, with discussion groups, systematic literature reviews, and Delphi technique-based consensus all being employed. The literature search considered publications from 1946 up until 2019.

“We agreed on the need for more background information from health professionals and patients, so we developed two surveys: One for health professionals with 160 items, [for which] we obtained 186 responses from 26 countries; and the patient survey was made up of 44 items, translated into 10 different languages, and we obtained 200 responses,” she said.

The results of the systematic literature review and surveys were used to help form expert consensus, leading to 5 overarching principles and 11 recommendations that look at before, during, and after intra-articular therapy.
 

Five overarching principles

The first overarching principle recognizes the widespread use of IA therapies and that their use is specific to the disease that is being treated and “may not be interchangeable across indications,” Dr. Usón said. The second principle concerns improving patient-centered outcomes, which are “those that are relevant to the patient,” and include the benefits, harms, preferences, or implications for self-management.

“Contextual factors are important and contribute to the effect of IAT [intra-articular treatment],” she said, discussing the third principle. “These include effective communication, patient expectations, or settings [where the procedure takes place]. In addition, one should take into account that the route of delivery has in itself a placebo effect. We found that in different RCTs [randomized controlled trials], the pooled placebo effect of IA saline is moderate to large.”

The fourth principle looks at ensuring that patients and clinicians make an informed and shared decision, which is again highlighted by the first recommendation. The fifth, and last, overarching principle acknowledges that IA injections may be given by a range of health care professionals.
 

Advice for before, during, and after injection

Patients need to be “fully informed of the nature of the procedure, the injectable used, and potential effects – benefits and risks – [and] informed consent should be obtained and documented,” said Dr. Usón, outlining the first recommendation. “That seems common,” she said in the interview, “but when we did the survey, we realize that many patients didn’t [give consent], and the doctors didn’t even ask for it. This is why it’s a very general statement, and it’s our first recommendation. The agreement was 99%!”

The recommendations also look at the optimal settings for performing injections, such as providing a professional and private, well-lighted room, and having a resuscitation kit nearby in case patients faint. Accuracy is important, Dr. Usón said, and imaging, such as ultrasound, should be used where available to ensure accurate injection into the joint. This is an area where further research could be performed, she said, urging young rheumatologists and health professionals to consider this. “Intra-articular therapy is something that you learn and do, but you never really investigate in it,” she said.

One recommendation states that when intra-articular injections are being given to pregnant patients, the safety of injected compound must be considered, both for the mother and for the fetus. There is another recommendation on the need to perform IA injections under aseptic conditions, and another stating that patients should be offered local anesthetics, after explaining the pros and cons.

Special populations of patients are also considered, Dr. Usón said. For example, the guidance advises warning patients with diabetes of the risk of transient glycemia after IA glucocorticoids and the need to monitor their blood glucose levels carefully for a couple of days afterward.

As a rule, “IAT is not a contraindication to people with clotting or bleeding disorders, or taking antithrombotic medications,” she said, unless they are at a high risk of bleeding.

Importantly, the recommendations cover when IAT can be performed after joint replacement surgery (after at least 3 months), and the need to “avoid overuse of injected joints” while also avoiding complete immobilization for at least 24 hours afterward. The recommendations very generally cover re-injections, but not how long intervals between injections should be. When asked about interval duration after her presentation, Dr. Usón said that the usual advice is to give IA injections no more than 2-3 times a year, but it depends on the injectable.

“It wasn’t our intention to review the efficacy and the safety of the different injectables, nor to review the use of IAT in different types of joint diseases,” she said. “We do lack a lot of information, a lot of evidence in this, and I really would hope that new rheumatologists start looking into and start investigating in this topic,” she added.
 

Recommendations will increase awareness of good clinical practice

“IA injections are commonly administered in the rheumatology setting. This is because [IA injection] is often a useful treatment for acute flare of arthritis, particularly when it is limited to a few joints,” observed Ai Lyn Tan, MD, associate professor and honorary consultant rheumatologist at the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine.

IA injection “also relieves symptoms relatively quickly for patients; however, the response can be variable, and there are side effects associated with IA injections,” Dr. Tan added in an interview.

There is a lack of universally accepted recommendations, Dr. Tan observed, noting that while there might be some local guidelines on how to safely perform IA injections these were often not standardized and were subject to being continually updated to try to improve the experience for patients.

“It is therefore timely to learn about the new EULAR recommendations for IA injections. The advantage of this will be to increase awareness of good clinical practice for performing IA injections.”

Dr. Tan had no relevant conflicts of interest.

SOURCE: EULAR COVID-19 Recommendations. E-congress content available until Sept. 1, 2020.

A German registry is providing new insight into the characteristics and real-world diagnosis and management of rheumatic immune-related adverse events of cancer therapy. Its first findings were reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.

“We have limited knowledge on the interrelationships between malignant and rheumatic diseases on both the clinical and molecular level, and we have a large unmet need for management guidelines in the case of the coincidence of both disease entities,” noted lead author Karolina Benesova, MD, of the department of hematology, oncology, and rheumatology at University Hospital Heidelberg (Germany).

The TRheuMa registry – Therapy-Induced Rheumatic Symptoms in Patients with Malignancy – is one of three registries in a multicenter observational project exploring various contexts between malignant and rheumatic diseases. Over its first 22 months, the registry recruited 69 patients having rheumatic symptoms as a result of immune checkpoint inhibitor therapy or other cancer therapies.
 

Registry findings

The largest shares of patients had non–small cell lung cancer (38%) or melanoma (33%), Dr. Benesova reported. The immune checkpoint inhibitors most commonly received were pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy).

The immune-related adverse events usually presented with symptoms of de novo spondyloarthritis or psoriatic arthritis (42%), late-onset RA (17%), or polymyalgia rheumatica (14%). But 16% of the patients were experiencing a flare of a preexisting rheumatic and musculoskeletal disease.

Laboratory findings differed somewhat from those of classical rheumatic and musculoskeletal diseases, according to Dr. Benesova. Specific findings were rare; in particular, most patients did not have detectable autoantibodies. However, 76% had an elevated C-reactive protein level and 39% had an elevated soluble CD25 level. In addition, nearly all patients (96%) undergoing joint ultrasound had pathologic findings.

“Based on our experiences from interdisciplinary care together with our local oncologists, we have developed a therapeutic algorithm for rheumatic immune-related adverse events,” she reported, noting that the algorithm is consistent with recently published recommendations in this area.

The large majority of patients were adequately treated with prednisone at a dose greater than 10 mg (40%) or at a dose of 10 mg or less with or without an NSAID (40%), while some received NSAID monotherapy (14%).

“We have a growing proportion of patients on conventional or biological [disease-modifying antirheumatic drugs],” Dr. Benesova noted. “These are mostly patients with preexisting rheumatic and musculoskeletal disease or highly suspected de novo classical rheumatic and musculoskeletal disease under checkpoint inhibitor therapy.”

Patients with melanoma having a rheumatic immune-related adverse event had a better response to their therapy than historical counterparts who did not have such events: 39% of the former had a complete response, relative to merely 4% of the latter.

Only a small proportion of patients overall (9%) had to discontinue immune checkpoint inhibitor therapy because of their adverse event, and some of them may be eligible for rechallenge if their cancer progresses, Dr. Benesova noted.

“There is still a lot to be done,” she stated, such as better elucidating the nature of these adverse events [whether transient side effects or a triggering of chronic rheumatic and musculoskeletal diseases], the need for a defensive treatment strategy, and the advisability of closer monitoring of high-risk patients given immune checkpoint inhibitors. “We are aiming at solving these questions in the next few years,” she concluded.

Findings in context

“Registries are important to gain prospective data on patient outcomes,” Sabina Sandigursky, MD, an instructor in the division of rheumatology at the Laura and Isaac Perlmutter Cancer Center at New York University, commented in an interview. “One must be careful, while interpreting these data, especially since they are not randomized, controlled trials.”

Patterns may differ at other centers, too, she pointed out. “The German registry reported a predominance of spondyloarthritis-like disease; however, our patients have a predominance of small-joint involvement. It is unclear what accounts for this difference.”

Individual institutions in North America are similarly collecting data on this patient population, with efforts underway to compile those data to provide a larger picture, according to Dr. Sandigursky.

“Many of the syndromes that we consider to be rheumatic immune-related adverse events have been well described by groups from the U.S., Canada, Australia, and European Union,” she concluded. “From this registry, we can observe how patients are being treated in real time since this information is largely consensus based.”

The study did not receive any specific funding. Dr. Benesova disclosed grant/research support from AbbVie, Novartis, Rheumaliga Baden-Wurttemberg, and the University of Heidelberg, and consultancies, speaker fees, and/or travel reimbursements from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Medac, Merck Sharp & Dohme, Mundipharma, Novartis, Pfizer, Roche, and UCB. Some of her coauthors also disclosed financial relationships with industry. Dr. Sandigursky disclosed having no relevant conflicts of interest.

SOURCE: Benesova K et al. Ann Rheum Dis 2020;79[suppl 1]:168-9, Abstract OP0270.

A German registry is providing new insight into the characteristics and real-world diagnosis and management of rheumatic immune-related adverse events of cancer therapy. Its first findings were reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.

“We have limited knowledge on the interrelationships between malignant and rheumatic diseases on both the clinical and molecular level, and we have a large unmet need for management guidelines in the case of the coincidence of both disease entities,” noted lead author Karolina Benesova, MD, of the department of hematology, oncology, and rheumatology at University Hospital Heidelberg (Germany).

The TRheuMa registry – Therapy-Induced Rheumatic Symptoms in Patients with Malignancy – is one of three registries in a multicenter observational project exploring various contexts between malignant and rheumatic diseases. Over its first 22 months, the registry recruited 69 patients having rheumatic symptoms as a result of immune checkpoint inhibitor therapy or other cancer therapies.
 

Registry findings

The largest shares of patients had non–small cell lung cancer (38%) or melanoma (33%), Dr. Benesova reported. The immune checkpoint inhibitors most commonly received were pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy).

The immune-related adverse events usually presented with symptoms of de novo spondyloarthritis or psoriatic arthritis (42%), late-onset RA (17%), or polymyalgia rheumatica (14%). But 16% of the patients were experiencing a flare of a preexisting rheumatic and musculoskeletal disease.

Laboratory findings differed somewhat from those of classical rheumatic and musculoskeletal diseases, according to Dr. Benesova. Specific findings were rare; in particular, most patients did not have detectable autoantibodies. However, 76% had an elevated C-reactive protein level and 39% had an elevated soluble CD25 level. In addition, nearly all patients (96%) undergoing joint ultrasound had pathologic findings.

“Based on our experiences from interdisciplinary care together with our local oncologists, we have developed a therapeutic algorithm for rheumatic immune-related adverse events,” she reported, noting that the algorithm is consistent with recently published recommendations in this area.

The large majority of patients were adequately treated with prednisone at a dose greater than 10 mg (40%) or at a dose of 10 mg or less with or without an NSAID (40%), while some received NSAID monotherapy (14%).

“We have a growing proportion of patients on conventional or biological [disease-modifying antirheumatic drugs],” Dr. Benesova noted. “These are mostly patients with preexisting rheumatic and musculoskeletal disease or highly suspected de novo classical rheumatic and musculoskeletal disease under checkpoint inhibitor therapy.”

Patients with melanoma having a rheumatic immune-related adverse event had a better response to their therapy than historical counterparts who did not have such events: 39% of the former had a complete response, relative to merely 4% of the latter.

Only a small proportion of patients overall (9%) had to discontinue immune checkpoint inhibitor therapy because of their adverse event, and some of them may be eligible for rechallenge if their cancer progresses, Dr. Benesova noted.

“There is still a lot to be done,” she stated, such as better elucidating the nature of these adverse events [whether transient side effects or a triggering of chronic rheumatic and musculoskeletal diseases], the need for a defensive treatment strategy, and the advisability of closer monitoring of high-risk patients given immune checkpoint inhibitors. “We are aiming at solving these questions in the next few years,” she concluded.

Findings in context

“Registries are important to gain prospective data on patient outcomes,” Sabina Sandigursky, MD, an instructor in the division of rheumatology at the Laura and Isaac Perlmutter Cancer Center at New York University, commented in an interview. “One must be careful, while interpreting these data, especially since they are not randomized, controlled trials.”

Patterns may differ at other centers, too, she pointed out. “The German registry reported a predominance of spondyloarthritis-like disease; however, our patients have a predominance of small-joint involvement. It is unclear what accounts for this difference.”

Individual institutions in North America are similarly collecting data on this patient population, with efforts underway to compile those data to provide a larger picture, according to Dr. Sandigursky.

“Many of the syndromes that we consider to be rheumatic immune-related adverse events have been well described by groups from the U.S., Canada, Australia, and European Union,” she concluded. “From this registry, we can observe how patients are being treated in real time since this information is largely consensus based.”

The study did not receive any specific funding. Dr. Benesova disclosed grant/research support from AbbVie, Novartis, Rheumaliga Baden-Wurttemberg, and the University of Heidelberg, and consultancies, speaker fees, and/or travel reimbursements from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Medac, Merck Sharp & Dohme, Mundipharma, Novartis, Pfizer, Roche, and UCB. Some of her coauthors also disclosed financial relationships with industry. Dr. Sandigursky disclosed having no relevant conflicts of interest.

SOURCE: Benesova K et al. Ann Rheum Dis 2020;79[suppl 1]:168-9, Abstract OP0270.

A German registry is providing new insight into the characteristics and real-world diagnosis and management of rheumatic immune-related adverse events of cancer therapy. Its first findings were reported at the annual European Congress of Rheumatology, held online this year due to COVID-19.

“We have limited knowledge on the interrelationships between malignant and rheumatic diseases on both the clinical and molecular level, and we have a large unmet need for management guidelines in the case of the coincidence of both disease entities,” noted lead author Karolina Benesova, MD, of the department of hematology, oncology, and rheumatology at University Hospital Heidelberg (Germany).

The TRheuMa registry – Therapy-Induced Rheumatic Symptoms in Patients with Malignancy – is one of three registries in a multicenter observational project exploring various contexts between malignant and rheumatic diseases. Over its first 22 months, the registry recruited 69 patients having rheumatic symptoms as a result of immune checkpoint inhibitor therapy or other cancer therapies.
 

Registry findings

The largest shares of patients had non–small cell lung cancer (38%) or melanoma (33%), Dr. Benesova reported. The immune checkpoint inhibitors most commonly received were pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy).

The immune-related adverse events usually presented with symptoms of de novo spondyloarthritis or psoriatic arthritis (42%), late-onset RA (17%), or polymyalgia rheumatica (14%). But 16% of the patients were experiencing a flare of a preexisting rheumatic and musculoskeletal disease.

Laboratory findings differed somewhat from those of classical rheumatic and musculoskeletal diseases, according to Dr. Benesova. Specific findings were rare; in particular, most patients did not have detectable autoantibodies. However, 76% had an elevated C-reactive protein level and 39% had an elevated soluble CD25 level. In addition, nearly all patients (96%) undergoing joint ultrasound had pathologic findings.

“Based on our experiences from interdisciplinary care together with our local oncologists, we have developed a therapeutic algorithm for rheumatic immune-related adverse events,” she reported, noting that the algorithm is consistent with recently published recommendations in this area.

The large majority of patients were adequately treated with prednisone at a dose greater than 10 mg (40%) or at a dose of 10 mg or less with or without an NSAID (40%), while some received NSAID monotherapy (14%).

“We have a growing proportion of patients on conventional or biological [disease-modifying antirheumatic drugs],” Dr. Benesova noted. “These are mostly patients with preexisting rheumatic and musculoskeletal disease or highly suspected de novo classical rheumatic and musculoskeletal disease under checkpoint inhibitor therapy.”

Patients with melanoma having a rheumatic immune-related adverse event had a better response to their therapy than historical counterparts who did not have such events: 39% of the former had a complete response, relative to merely 4% of the latter.

Only a small proportion of patients overall (9%) had to discontinue immune checkpoint inhibitor therapy because of their adverse event, and some of them may be eligible for rechallenge if their cancer progresses, Dr. Benesova noted.

“There is still a lot to be done,” she stated, such as better elucidating the nature of these adverse events [whether transient side effects or a triggering of chronic rheumatic and musculoskeletal diseases], the need for a defensive treatment strategy, and the advisability of closer monitoring of high-risk patients given immune checkpoint inhibitors. “We are aiming at solving these questions in the next few years,” she concluded.

Findings in context

“Registries are important to gain prospective data on patient outcomes,” Sabina Sandigursky, MD, an instructor in the division of rheumatology at the Laura and Isaac Perlmutter Cancer Center at New York University, commented in an interview. “One must be careful, while interpreting these data, especially since they are not randomized, controlled trials.”

Patterns may differ at other centers, too, she pointed out. “The German registry reported a predominance of spondyloarthritis-like disease; however, our patients have a predominance of small-joint involvement. It is unclear what accounts for this difference.”

Individual institutions in North America are similarly collecting data on this patient population, with efforts underway to compile those data to provide a larger picture, according to Dr. Sandigursky.

“Many of the syndromes that we consider to be rheumatic immune-related adverse events have been well described by groups from the U.S., Canada, Australia, and European Union,” she concluded. “From this registry, we can observe how patients are being treated in real time since this information is largely consensus based.”

The study did not receive any specific funding. Dr. Benesova disclosed grant/research support from AbbVie, Novartis, Rheumaliga Baden-Wurttemberg, and the University of Heidelberg, and consultancies, speaker fees, and/or travel reimbursements from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Medac, Merck Sharp & Dohme, Mundipharma, Novartis, Pfizer, Roche, and UCB. Some of her coauthors also disclosed financial relationships with industry. Dr. Sandigursky disclosed having no relevant conflicts of interest.

SOURCE: Benesova K et al. Ann Rheum Dis 2020;79[suppl 1]:168-9, Abstract OP0270.

A proactive long-term strategy of maintenance therapy involving twice-weekly application of combined calcipotriene and betamethasone dipropionate spray foam was safe and effective in patients with moderate plaque psoriasis in the international, randomized PSO-LONG clinical trial, Mark Lebwohl, MD, reported at the virtual annual meeting of the American Academy of Dermatology.

The median time to first relapse – the primary study endpoint – was 56 days in patients randomized to the twice-weekly fixed-dose combination calcipotriene 0.005% and betamethasone dipropionate 0.064% foam (Enstilar), a significantly better outcome than the median 30 days for controls assigned to foam vehicle. Moreover, it took 169 days for 75% of patients on the combination foam to experience their first relapse: three times longer than in controls, added Dr. Lebwohl, principal investigator for PSO-LONG and professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

The positive results “could have been predicted,” he said in an interview. “But what really distinguishes this study from others is that no one before has ever done a placebo-controlled, double-blind trial with a topical steroid that lasted a year. This is a first, and we’ve shown that if you limit treatment to twice a week you get dramatic improvements in efficacy at no cost in terms of safety.”

The combination spray foam is approved by the Food and Drug Administration as once-daily therapy in psoriasis patients aged 12 years and older, but only for up to 4 weeks because of safety concerns regarding longer use of the potent topical steroid. However, psoriasis is a chronic disease. The PSO-LONG trial was designed to study the impact of a for-now still-investigational long-term maintenance treatment strategy.

The open-label run-in period of the study included 640 adults with plaque psoriasis, 82% of whom had moderate disease at baseline as rated by Physician Global Assessment (PGA). Participants applied the combination foam once daily for 4 weeks. At that point, 80% of them had achieved a PGA rating of clear or almost clear with at least a two-grade improvement from baseline; these 521 responders were then randomized to 52 weeks of double-blind treatment with the combination foam or vehicle foam. Anyone who relapsed went on 4 weeks of once-daily active treatment with the combination foam, then returned to their original treatment arm.

The risk of a first relapse during the course of 1 year was 43% lower with the combination foam than in controls. The relapse rate over the year was 46% lower. Patients in the active treatment arm spent an average of 256.5 days in remission during the year, compared with 222 days in controls.

“That’s more than 1 month more time in remission during the year with active treatment. And remember, if patients flared, they went on daily therapy for a month,” the dermatologist noted.

The rate of treatment-related adverse events was similar in the two groups at 2.8 events per 100 patient-years in the combination foam arm and 4.5 per 100 patient-years in controls. The twice-weekly active treatment group had no increase in stretch marks, telangiectasias, skin atrophy, serum calcium, or abnormalities of the hypothalamic-pituitary-adrenal axis.

Although the combination foam is approved for daily use for a maximum of 1 month in adolescents and adults, PSO-LONG was restricted to adults.

“I think that what will happen in the marketplace is that the data obtained from this adult study will likely be applied to younger patients,” Dr. Lebwohl predicted.

He reported receiving an institutional research grant to conduct the trial from LEO Pharma, the study sponsor, as well as serving as a consultant to and researcher for the company.

[email protected]

A proactive long-term strategy of maintenance therapy involving twice-weekly application of combined calcipotriene and betamethasone dipropionate spray foam was safe and effective in patients with moderate plaque psoriasis in the international, randomized PSO-LONG clinical trial, Mark Lebwohl, MD, reported at the virtual annual meeting of the American Academy of Dermatology.

The median time to first relapse – the primary study endpoint – was 56 days in patients randomized to the twice-weekly fixed-dose combination calcipotriene 0.005% and betamethasone dipropionate 0.064% foam (Enstilar), a significantly better outcome than the median 30 days for controls assigned to foam vehicle. Moreover, it took 169 days for 75% of patients on the combination foam to experience their first relapse: three times longer than in controls, added Dr. Lebwohl, principal investigator for PSO-LONG and professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

The positive results “could have been predicted,” he said in an interview. “But what really distinguishes this study from others is that no one before has ever done a placebo-controlled, double-blind trial with a topical steroid that lasted a year. This is a first, and we’ve shown that if you limit treatment to twice a week you get dramatic improvements in efficacy at no cost in terms of safety.”

The combination spray foam is approved by the Food and Drug Administration as once-daily therapy in psoriasis patients aged 12 years and older, but only for up to 4 weeks because of safety concerns regarding longer use of the potent topical steroid. However, psoriasis is a chronic disease. The PSO-LONG trial was designed to study the impact of a for-now still-investigational long-term maintenance treatment strategy.

The open-label run-in period of the study included 640 adults with plaque psoriasis, 82% of whom had moderate disease at baseline as rated by Physician Global Assessment (PGA). Participants applied the combination foam once daily for 4 weeks. At that point, 80% of them had achieved a PGA rating of clear or almost clear with at least a two-grade improvement from baseline; these 521 responders were then randomized to 52 weeks of double-blind treatment with the combination foam or vehicle foam. Anyone who relapsed went on 4 weeks of once-daily active treatment with the combination foam, then returned to their original treatment arm.

The risk of a first relapse during the course of 1 year was 43% lower with the combination foam than in controls. The relapse rate over the year was 46% lower. Patients in the active treatment arm spent an average of 256.5 days in remission during the year, compared with 222 days in controls.

“That’s more than 1 month more time in remission during the year with active treatment. And remember, if patients flared, they went on daily therapy for a month,” the dermatologist noted.

The rate of treatment-related adverse events was similar in the two groups at 2.8 events per 100 patient-years in the combination foam arm and 4.5 per 100 patient-years in controls. The twice-weekly active treatment group had no increase in stretch marks, telangiectasias, skin atrophy, serum calcium, or abnormalities of the hypothalamic-pituitary-adrenal axis.

Although the combination foam is approved for daily use for a maximum of 1 month in adolescents and adults, PSO-LONG was restricted to adults.

“I think that what will happen in the marketplace is that the data obtained from this adult study will likely be applied to younger patients,” Dr. Lebwohl predicted.

He reported receiving an institutional research grant to conduct the trial from LEO Pharma, the study sponsor, as well as serving as a consultant to and researcher for the company.

[email protected]

A proactive long-term strategy of maintenance therapy involving twice-weekly application of combined calcipotriene and betamethasone dipropionate spray foam was safe and effective in patients with moderate plaque psoriasis in the international, randomized PSO-LONG clinical trial, Mark Lebwohl, MD, reported at the virtual annual meeting of the American Academy of Dermatology.

The median time to first relapse – the primary study endpoint – was 56 days in patients randomized to the twice-weekly fixed-dose combination calcipotriene 0.005% and betamethasone dipropionate 0.064% foam (Enstilar), a significantly better outcome than the median 30 days for controls assigned to foam vehicle. Moreover, it took 169 days for 75% of patients on the combination foam to experience their first relapse: three times longer than in controls, added Dr. Lebwohl, principal investigator for PSO-LONG and professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York.

The positive results “could have been predicted,” he said in an interview. “But what really distinguishes this study from others is that no one before has ever done a placebo-controlled, double-blind trial with a topical steroid that lasted a year. This is a first, and we’ve shown that if you limit treatment to twice a week you get dramatic improvements in efficacy at no cost in terms of safety.”

The combination spray foam is approved by the Food and Drug Administration as once-daily therapy in psoriasis patients aged 12 years and older, but only for up to 4 weeks because of safety concerns regarding longer use of the potent topical steroid. However, psoriasis is a chronic disease. The PSO-LONG trial was designed to study the impact of a for-now still-investigational long-term maintenance treatment strategy.

The open-label run-in period of the study included 640 adults with plaque psoriasis, 82% of whom had moderate disease at baseline as rated by Physician Global Assessment (PGA). Participants applied the combination foam once daily for 4 weeks. At that point, 80% of them had achieved a PGA rating of clear or almost clear with at least a two-grade improvement from baseline; these 521 responders were then randomized to 52 weeks of double-blind treatment with the combination foam or vehicle foam. Anyone who relapsed went on 4 weeks of once-daily active treatment with the combination foam, then returned to their original treatment arm.

The risk of a first relapse during the course of 1 year was 43% lower with the combination foam than in controls. The relapse rate over the year was 46% lower. Patients in the active treatment arm spent an average of 256.5 days in remission during the year, compared with 222 days in controls.

“That’s more than 1 month more time in remission during the year with active treatment. And remember, if patients flared, they went on daily therapy for a month,” the dermatologist noted.

The rate of treatment-related adverse events was similar in the two groups at 2.8 events per 100 patient-years in the combination foam arm and 4.5 per 100 patient-years in controls. The twice-weekly active treatment group had no increase in stretch marks, telangiectasias, skin atrophy, serum calcium, or abnormalities of the hypothalamic-pituitary-adrenal axis.

Although the combination foam is approved for daily use for a maximum of 1 month in adolescents and adults, PSO-LONG was restricted to adults.

“I think that what will happen in the marketplace is that the data obtained from this adult study will likely be applied to younger patients,” Dr. Lebwohl predicted.

He reported receiving an institutional research grant to conduct the trial from LEO Pharma, the study sponsor, as well as serving as a consultant to and researcher for the company.

[email protected]

Results from two late-breaking phase 3 trials of bimekizumab, an investigational interleukin-17A and IL-17F inhibitor, showed that most patients with moderate to severe psoriasis achieved clearance at week 16 and maintained their clinical response at 1 year.

“The rapid and lasting skin clearance observed in the majority of patients in both clinical studies demonstrate bimekizumab’s strong potential to deliver across three key areas: speed, depth and durability,” Kristian Reich, MD, said in an interview during the virtual annual meeting of the American Academy of Dermatology.

Bimekizumab selectively inhibits IL-17A and IL-17F, two key cytokines that drive inflammation and tissue damage across multiple diseases. In BE VIVID, Dr. Reich, of the Center for Translational Research in Inflammatory Skin Diseases at the University Medical Center Hamburg-Eppendorf (Germany), and colleagues randomized 567 patients with moderate to severe psoriasis to bimekizumab 320 mg every 4 weeks (Q4W), ustekinumab (45/90 mg weight-based dosing at baseline and week 4, then every 12 weeks), or placebo (Q4W through week 16 then bimekizumab 320 mg Q4W). Coprimary endpoints were a Psoriasis Area and Severity Index (PASI) of at least 90 and an Investigator Global Assessment (IGA) response of 0 or 1. Secondary/other outcomes included PASI 100 at week 16; PASI 90, IGA 0/1, and PASI 100 at week 52; and safety. (Ustekinumab is an IL-12 and IL-23 antagonist.)

The mean age of patients was 46 years and 72% were male. The researchers found that the proportion of patients who achieved PASI 90 and an IGA of 0/1 was higher in the bimekizumab arm at week 16 (85.0% and 84.1%, respectively), compared with those in the ustekinumab arm (49.7% and 53.4%) and those on placebo (4.8% and 4.8%; P < .001 for all associations). In addition, 58.6% of patients in the bimekizumab arm achieved PASI 100, compared with 20.9% of those in the ustekinumab arm and none of those on placebo.

At week 52, patients in the bimekizumab arm achieved PASI 90, IGA 0/1, and PASI 100 response rates of 81.6%, 77.9%, and 64.2%, respectively, compared with 55.8%, 60.7%, and 38.0% of those in the ustekinumab arm. Over 52 weeks, incidence of serious treatment-emergent adverse events was 6.1% with bimekizumab arm, compared with 7.4% in the ustekinumab arm. Four deaths occurred (two in the bimekizumab arm, and one each in the ustekinumab and placebo arms), all considered unrelated to treatment. The most common reported adverse events in the bimekizumab arm through week 52 were nasopharyngitis (21.8%), oral candidiasis (15.2%), and upper respiratory tract infections (9.1%).

“The rapid and lasting skin clearance observed in the majority of patients treated with bimekizumab provide support for inhibiting IL-17F, in addition to IL-17A, to inhibit the IL-17 pathway,” Dr. Reich said. “This can make a meaningful difference for people living with psoriasis.” He added that the results of the head-to-head study of bimekizumab with secukinumab (an IL-17A antagonist) are expected later this year. “It will be very interesting to see if the marked differences in treatment effect seen in the BE VIVID study remain when comparing to an IL-17.”

In BE READY, a pivotal phase 3, randomized, withdrawal study, investigators led by Kenneth Gordon, MD, randomized 435 patients with moderate to severe psoriasis 4:1 to receive 320 mg Q4W or placebo, and followed them for 16 weeks. In a second part of the study, patients who had achieved at least a PASI 90 response at week 16 were rerandomized to receive continuous bimekizumab at two different dosing regimens: 320 mg Q4W or 320 mg every 8 weeks (Q8W), or to be withdrawn from treatment (placebo Q4W), and followed through week 56. Relapse was defined as a PASI score of less than 75 from week 20.

The mean age of patients was 44 years and 72% were male. At week 16, the proportion of patients who achieved a PASI 90 and an IGA of 0/1 was greatest in the bimekizumab arm (90.8% and 92.6%, respectively), compared with those on placebo. In addition, 68.2% of patients in the bimekizumab arm achieved PASI 100 at week 16, compared with only 1.2% of those on placebo (P < .001 for all associations). In the second part of the study, the researchers found that 86.8% of patients who received continuous bimekizumab 320 mg Q4W maintained PASI 90 at week 56, compared with 91% who were switched to bimekizumab 320 mg Q8W, and 16.2% of patients who were withdrawn from the trial.

“The speed of response and the number of patients who achieved clearance are extremely high, especially in a phase 3 trial,” Dr. Gordon, professor and Thomas R. Russell Family Chair of Dermatology at the Medical College of Wisconsin, Milwaukee, said in an interview. “However, the most surprising aspect may be the impressive maintenance of response in patients, even those who were treated with every-8-week dosing in the maintenance phase. While it is possible that there are some patients who may benefit from more frequent dosing in the long term, the possibility of every-8-week dosing would be a tremendous benefit for patients.”

As in the BE VIVID trial, the most frequently reported adverse events with bimekizumab between week 16 and week 56 in BE READY were nasopharyngitis (10.4% in the Q4W arm vs. 23% in the Q8W arm), oral candidiasis (11.3% Q4W vs. 9% Q8W), and upper respiratory tract infections (11.3% Q4W vs. 8% Q8W). The incidence of serious treatment-emergent adverse events with bimekizumab was 4.7% in the Q4W arm and 3% in the Q8W arm versus 3.8% in the placebo arm at week 56.

“The results from BE READY demonstrate that bimekizumab has the potential to deliver rapid and lasting skin improvement for psoriasis patients,” Dr. Gordon said. “The findings also support the hypothesis that inhibiting IL-17F, in addition to IL-17A, may be more effective in suppressing inflammation in suppressing inflammation in psoriasis than IL-17A inhibition alone.”

Both studies were funded by UCB Pharma. Dr. Reich disclosed that he has served as adviser and/or paid speaker for and/or participated in clinical trials sponsored by companies that include UCB. Dr. Gordon disclosed that he has received honoraria and/or research support from companies that include UCB..

[email protected]

Results from two late-breaking phase 3 trials of bimekizumab, an investigational interleukin-17A and IL-17F inhibitor, showed that most patients with moderate to severe psoriasis achieved clearance at week 16 and maintained their clinical response at 1 year.

“The rapid and lasting skin clearance observed in the majority of patients in both clinical studies demonstrate bimekizumab’s strong potential to deliver across three key areas: speed, depth and durability,” Kristian Reich, MD, said in an interview during the virtual annual meeting of the American Academy of Dermatology.

Bimekizumab selectively inhibits IL-17A and IL-17F, two key cytokines that drive inflammation and tissue damage across multiple diseases. In BE VIVID, Dr. Reich, of the Center for Translational Research in Inflammatory Skin Diseases at the University Medical Center Hamburg-Eppendorf (Germany), and colleagues randomized 567 patients with moderate to severe psoriasis to bimekizumab 320 mg every 4 weeks (Q4W), ustekinumab (45/90 mg weight-based dosing at baseline and week 4, then every 12 weeks), or placebo (Q4W through week 16 then bimekizumab 320 mg Q4W). Coprimary endpoints were a Psoriasis Area and Severity Index (PASI) of at least 90 and an Investigator Global Assessment (IGA) response of 0 or 1. Secondary/other outcomes included PASI 100 at week 16; PASI 90, IGA 0/1, and PASI 100 at week 52; and safety. (Ustekinumab is an IL-12 and IL-23 antagonist.)

The mean age of patients was 46 years and 72% were male. The researchers found that the proportion of patients who achieved PASI 90 and an IGA of 0/1 was higher in the bimekizumab arm at week 16 (85.0% and 84.1%, respectively), compared with those in the ustekinumab arm (49.7% and 53.4%) and those on placebo (4.8% and 4.8%; P < .001 for all associations). In addition, 58.6% of patients in the bimekizumab arm achieved PASI 100, compared with 20.9% of those in the ustekinumab arm and none of those on placebo.

At week 52, patients in the bimekizumab arm achieved PASI 90, IGA 0/1, and PASI 100 response rates of 81.6%, 77.9%, and 64.2%, respectively, compared with 55.8%, 60.7%, and 38.0% of those in the ustekinumab arm. Over 52 weeks, incidence of serious treatment-emergent adverse events was 6.1% with bimekizumab arm, compared with 7.4% in the ustekinumab arm. Four deaths occurred (two in the bimekizumab arm, and one each in the ustekinumab and placebo arms), all considered unrelated to treatment. The most common reported adverse events in the bimekizumab arm through week 52 were nasopharyngitis (21.8%), oral candidiasis (15.2%), and upper respiratory tract infections (9.1%).

“The rapid and lasting skin clearance observed in the majority of patients treated with bimekizumab provide support for inhibiting IL-17F, in addition to IL-17A, to inhibit the IL-17 pathway,” Dr. Reich said. “This can make a meaningful difference for people living with psoriasis.” He added that the results of the head-to-head study of bimekizumab with secukinumab (an IL-17A antagonist) are expected later this year. “It will be very interesting to see if the marked differences in treatment effect seen in the BE VIVID study remain when comparing to an IL-17.”

In BE READY, a pivotal phase 3, randomized, withdrawal study, investigators led by Kenneth Gordon, MD, randomized 435 patients with moderate to severe psoriasis 4:1 to receive 320 mg Q4W or placebo, and followed them for 16 weeks. In a second part of the study, patients who had achieved at least a PASI 90 response at week 16 were rerandomized to receive continuous bimekizumab at two different dosing regimens: 320 mg Q4W or 320 mg every 8 weeks (Q8W), or to be withdrawn from treatment (placebo Q4W), and followed through week 56. Relapse was defined as a PASI score of less than 75 from week 20.

The mean age of patients was 44 years and 72% were male. At week 16, the proportion of patients who achieved a PASI 90 and an IGA of 0/1 was greatest in the bimekizumab arm (90.8% and 92.6%, respectively), compared with those on placebo. In addition, 68.2% of patients in the bimekizumab arm achieved PASI 100 at week 16, compared with only 1.2% of those on placebo (P < .001 for all associations). In the second part of the study, the researchers found that 86.8% of patients who received continuous bimekizumab 320 mg Q4W maintained PASI 90 at week 56, compared with 91% who were switched to bimekizumab 320 mg Q8W, and 16.2% of patients who were withdrawn from the trial.

“The speed of response and the number of patients who achieved clearance are extremely high, especially in a phase 3 trial,” Dr. Gordon, professor and Thomas R. Russell Family Chair of Dermatology at the Medical College of Wisconsin, Milwaukee, said in an interview. “However, the most surprising aspect may be the impressive maintenance of response in patients, even those who were treated with every-8-week dosing in the maintenance phase. While it is possible that there are some patients who may benefit from more frequent dosing in the long term, the possibility of every-8-week dosing would be a tremendous benefit for patients.”

As in the BE VIVID trial, the most frequently reported adverse events with bimekizumab between week 16 and week 56 in BE READY were nasopharyngitis (10.4% in the Q4W arm vs. 23% in the Q8W arm), oral candidiasis (11.3% Q4W vs. 9% Q8W), and upper respiratory tract infections (11.3% Q4W vs. 8% Q8W). The incidence of serious treatment-emergent adverse events with bimekizumab was 4.7% in the Q4W arm and 3% in the Q8W arm versus 3.8% in the placebo arm at week 56.

“The results from BE READY demonstrate that bimekizumab has the potential to deliver rapid and lasting skin improvement for psoriasis patients,” Dr. Gordon said. “The findings also support the hypothesis that inhibiting IL-17F, in addition to IL-17A, may be more effective in suppressing inflammation in suppressing inflammation in psoriasis than IL-17A inhibition alone.”

Both studies were funded by UCB Pharma. Dr. Reich disclosed that he has served as adviser and/or paid speaker for and/or participated in clinical trials sponsored by companies that include UCB. Dr. Gordon disclosed that he has received honoraria and/or research support from companies that include UCB..

[email protected]

Results from two late-breaking phase 3 trials of bimekizumab, an investigational interleukin-17A and IL-17F inhibitor, showed that most patients with moderate to severe psoriasis achieved clearance at week 16 and maintained their clinical response at 1 year.

“The rapid and lasting skin clearance observed in the majority of patients in both clinical studies demonstrate bimekizumab’s strong potential to deliver across three key areas: speed, depth and durability,” Kristian Reich, MD, said in an interview during the virtual annual meeting of the American Academy of Dermatology.

Bimekizumab selectively inhibits IL-17A and IL-17F, two key cytokines that drive inflammation and tissue damage across multiple diseases. In BE VIVID, Dr. Reich, of the Center for Translational Research in Inflammatory Skin Diseases at the University Medical Center Hamburg-Eppendorf (Germany), and colleagues randomized 567 patients with moderate to severe psoriasis to bimekizumab 320 mg every 4 weeks (Q4W), ustekinumab (45/90 mg weight-based dosing at baseline and week 4, then every 12 weeks), or placebo (Q4W through week 16 then bimekizumab 320 mg Q4W). Coprimary endpoints were a Psoriasis Area and Severity Index (PASI) of at least 90 and an Investigator Global Assessment (IGA) response of 0 or 1. Secondary/other outcomes included PASI 100 at week 16; PASI 90, IGA 0/1, and PASI 100 at week 52; and safety. (Ustekinumab is an IL-12 and IL-23 antagonist.)

The mean age of patients was 46 years and 72% were male. The researchers found that the proportion of patients who achieved PASI 90 and an IGA of 0/1 was higher in the bimekizumab arm at week 16 (85.0% and 84.1%, respectively), compared with those in the ustekinumab arm (49.7% and 53.4%) and those on placebo (4.8% and 4.8%; P < .001 for all associations). In addition, 58.6% of patients in the bimekizumab arm achieved PASI 100, compared with 20.9% of those in the ustekinumab arm and none of those on placebo.

At week 52, patients in the bimekizumab arm achieved PASI 90, IGA 0/1, and PASI 100 response rates of 81.6%, 77.9%, and 64.2%, respectively, compared with 55.8%, 60.7%, and 38.0% of those in the ustekinumab arm. Over 52 weeks, incidence of serious treatment-emergent adverse events was 6.1% with bimekizumab arm, compared with 7.4% in the ustekinumab arm. Four deaths occurred (two in the bimekizumab arm, and one each in the ustekinumab and placebo arms), all considered unrelated to treatment. The most common reported adverse events in the bimekizumab arm through week 52 were nasopharyngitis (21.8%), oral candidiasis (15.2%), and upper respiratory tract infections (9.1%).

“The rapid and lasting skin clearance observed in the majority of patients treated with bimekizumab provide support for inhibiting IL-17F, in addition to IL-17A, to inhibit the IL-17 pathway,” Dr. Reich said. “This can make a meaningful difference for people living with psoriasis.” He added that the results of the head-to-head study of bimekizumab with secukinumab (an IL-17A antagonist) are expected later this year. “It will be very interesting to see if the marked differences in treatment effect seen in the BE VIVID study remain when comparing to an IL-17.”

In BE READY, a pivotal phase 3, randomized, withdrawal study, investigators led by Kenneth Gordon, MD, randomized 435 patients with moderate to severe psoriasis 4:1 to receive 320 mg Q4W or placebo, and followed them for 16 weeks. In a second part of the study, patients who had achieved at least a PASI 90 response at week 16 were rerandomized to receive continuous bimekizumab at two different dosing regimens: 320 mg Q4W or 320 mg every 8 weeks (Q8W), or to be withdrawn from treatment (placebo Q4W), and followed through week 56. Relapse was defined as a PASI score of less than 75 from week 20.

The mean age of patients was 44 years and 72% were male. At week 16, the proportion of patients who achieved a PASI 90 and an IGA of 0/1 was greatest in the bimekizumab arm (90.8% and 92.6%, respectively), compared with those on placebo. In addition, 68.2% of patients in the bimekizumab arm achieved PASI 100 at week 16, compared with only 1.2% of those on placebo (P < .001 for all associations). In the second part of the study, the researchers found that 86.8% of patients who received continuous bimekizumab 320 mg Q4W maintained PASI 90 at week 56, compared with 91% who were switched to bimekizumab 320 mg Q8W, and 16.2% of patients who were withdrawn from the trial.

“The speed of response and the number of patients who achieved clearance are extremely high, especially in a phase 3 trial,” Dr. Gordon, professor and Thomas R. Russell Family Chair of Dermatology at the Medical College of Wisconsin, Milwaukee, said in an interview. “However, the most surprising aspect may be the impressive maintenance of response in patients, even those who were treated with every-8-week dosing in the maintenance phase. While it is possible that there are some patients who may benefit from more frequent dosing in the long term, the possibility of every-8-week dosing would be a tremendous benefit for patients.”

As in the BE VIVID trial, the most frequently reported adverse events with bimekizumab between week 16 and week 56 in BE READY were nasopharyngitis (10.4% in the Q4W arm vs. 23% in the Q8W arm), oral candidiasis (11.3% Q4W vs. 9% Q8W), and upper respiratory tract infections (11.3% Q4W vs. 8% Q8W). The incidence of serious treatment-emergent adverse events with bimekizumab was 4.7% in the Q4W arm and 3% in the Q8W arm versus 3.8% in the placebo arm at week 56.

“The results from BE READY demonstrate that bimekizumab has the potential to deliver rapid and lasting skin improvement for psoriasis patients,” Dr. Gordon said. “The findings also support the hypothesis that inhibiting IL-17F, in addition to IL-17A, may be more effective in suppressing inflammation in suppressing inflammation in psoriasis than IL-17A inhibition alone.”

Both studies were funded by UCB Pharma. Dr. Reich disclosed that he has served as adviser and/or paid speaker for and/or participated in clinical trials sponsored by companies that include UCB. Dr. Gordon disclosed that he has received honoraria and/or research support from companies that include UCB..

[email protected]

Structural entheseal lesions and reduced bone mineral density detected using high-resolution CT imaging of a pair of knuckle joints in patients with psoriasis strongly linked with subsequent development of psoriatic arthritis (PsA) in a single-center study with 114 patients followed for an average of 2.3 years.

“These findings substantiate the concept of mechano-inflammation in the pathogenesis of psoriatic disease,” and suggest that interventions with high efficacy for controlling entheseal inflammation may be a “particularly valuable strategy in interfering with the onset of PsA in patients with psoriatic disease,” David Simon, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.

The study, which is now published in Arthritis & Rheumatology, began with 377 patients with psoriasis who had been referred to the University Hospital in Erlangen, Germany, during 2011-2018, and who tested positive on the German Psoriasis Arthritis Diagnostic questionnaire. The researchers excluded patients with existing signs of PsA, any arthritis or enthesitis or other signs of inflammatory rheumatic disease, and they also excluded patients who had not undergoing a high-resolution peripheral quantitative CT (HR-pQCT) examination of the second and third metacarpal joints of the patient’s nondominant hand, which left 114 patients for their analysis. During a mean follow-up of 28 months, 24 patients (27%) developed PsA. The study patients were an average age of 45 years, and they had been diagnosed with psoriasis for an average of about 16 years.

Dr. Simon and associates used the baseline HR-pQCT scans to make two assessments of each patient: the presence of structural entheseal lesions (SEL) in the two metacarpal joints and the calculated volumetric bone mineral density (vBMD). Their analysis showed that the number and severity of SEL were increased among patients who later developed PsA. In a multivariable model that adjusted for age, sex, body mass index, duration of psoriasis, and arthralgia, patients with any SEL had a fivefold higher rate of developing PsA, compared with patients with no SEL, reported Dr. Simon, a rheumatologist at Erlangen University Hospital.

The analysis of vBMD also showed a strong link between bone density at the entheseal sites of the two studied joints and subsequent PsA development. For every standard deviation increase in vBMD at these sites the subsequent rate of PsA incidence fell by about 67% in an analysis that controlled for the same covariants as well as presence of SEL. The same relationship between higher vBMD and a lower risk for PsA held for both total vBMD measurement and for cortical vBMD, but only at the entheseal site. Levels of vBMD at the intra-articular site of the joints had no statistically significant relationship with subsequent PsA development.

The two metrics also appeared to identify additive risks. Nearly 90% of patients with at least one SEL who also had low vBMD at the entheseal site developed PsA during follow-up, compared with about a 50% rate among patients with at least one SEL but high vBMD.

courtesy EULAR

The imaging method used to run these analyses, HR-pQCT, remains for the time being a “research technique” that “is not generalizable for routine practice,” but further development of this method or of a surrogate measure might make it feasible for future widespread practice, commented Iain McInnes, MD, PhD, president of the European League Against Rheumatism and professor of rheumatology and director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow.

“We’ve thought for many years that psoriasis and psoriatic arthritis are on a spectrum, and this work is consistent with the idea that some patients with psoriasis develop tissue involvement at entheses and joints,” Dr. McInnes said in an interview. The higher incidence of PsA seen in patients with adverse SEL and vBMD markers was in an “interesting range” that warrants further study. A next step is to run an intervention study in which patients with these adverse markers would receive an intervention randomized against placebo to see if it improved their outcomes, he suggested. Good candidate agents to study in psoriasis patients who have these adverse markers include drugs that inhibit the action of interleukin-17, drugs that target the p19 cytokine subunit of IL-23, and possibly Janus kinase inhibitor drugs.

Dr. Simon has been a consultant to AbbVie and Eli Lilly, a speaker on behalf of Eli Lilly, Janssen, and Novartis, and has received research funding from Eli Lilly and Novartis. Dr. McInnes has been a consultant to AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, and he has received research funding from Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, and UCB.

[email protected]

SOURCE: Simon D et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:33-4, Abstract OP0051.

Structural entheseal lesions and reduced bone mineral density detected using high-resolution CT imaging of a pair of knuckle joints in patients with psoriasis strongly linked with subsequent development of psoriatic arthritis (PsA) in a single-center study with 114 patients followed for an average of 2.3 years.

“These findings substantiate the concept of mechano-inflammation in the pathogenesis of psoriatic disease,” and suggest that interventions with high efficacy for controlling entheseal inflammation may be a “particularly valuable strategy in interfering with the onset of PsA in patients with psoriatic disease,” David Simon, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.

The study, which is now published in Arthritis & Rheumatology, began with 377 patients with psoriasis who had been referred to the University Hospital in Erlangen, Germany, during 2011-2018, and who tested positive on the German Psoriasis Arthritis Diagnostic questionnaire. The researchers excluded patients with existing signs of PsA, any arthritis or enthesitis or other signs of inflammatory rheumatic disease, and they also excluded patients who had not undergoing a high-resolution peripheral quantitative CT (HR-pQCT) examination of the second and third metacarpal joints of the patient’s nondominant hand, which left 114 patients for their analysis. During a mean follow-up of 28 months, 24 patients (27%) developed PsA. The study patients were an average age of 45 years, and they had been diagnosed with psoriasis for an average of about 16 years.

Dr. Simon and associates used the baseline HR-pQCT scans to make two assessments of each patient: the presence of structural entheseal lesions (SEL) in the two metacarpal joints and the calculated volumetric bone mineral density (vBMD). Their analysis showed that the number and severity of SEL were increased among patients who later developed PsA. In a multivariable model that adjusted for age, sex, body mass index, duration of psoriasis, and arthralgia, patients with any SEL had a fivefold higher rate of developing PsA, compared with patients with no SEL, reported Dr. Simon, a rheumatologist at Erlangen University Hospital.

The analysis of vBMD also showed a strong link between bone density at the entheseal sites of the two studied joints and subsequent PsA development. For every standard deviation increase in vBMD at these sites the subsequent rate of PsA incidence fell by about 67% in an analysis that controlled for the same covariants as well as presence of SEL. The same relationship between higher vBMD and a lower risk for PsA held for both total vBMD measurement and for cortical vBMD, but only at the entheseal site. Levels of vBMD at the intra-articular site of the joints had no statistically significant relationship with subsequent PsA development.

The two metrics also appeared to identify additive risks. Nearly 90% of patients with at least one SEL who also had low vBMD at the entheseal site developed PsA during follow-up, compared with about a 50% rate among patients with at least one SEL but high vBMD.

courtesy EULAR

The imaging method used to run these analyses, HR-pQCT, remains for the time being a “research technique” that “is not generalizable for routine practice,” but further development of this method or of a surrogate measure might make it feasible for future widespread practice, commented Iain McInnes, MD, PhD, president of the European League Against Rheumatism and professor of rheumatology and director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow.

“We’ve thought for many years that psoriasis and psoriatic arthritis are on a spectrum, and this work is consistent with the idea that some patients with psoriasis develop tissue involvement at entheses and joints,” Dr. McInnes said in an interview. The higher incidence of PsA seen in patients with adverse SEL and vBMD markers was in an “interesting range” that warrants further study. A next step is to run an intervention study in which patients with these adverse markers would receive an intervention randomized against placebo to see if it improved their outcomes, he suggested. Good candidate agents to study in psoriasis patients who have these adverse markers include drugs that inhibit the action of interleukin-17, drugs that target the p19 cytokine subunit of IL-23, and possibly Janus kinase inhibitor drugs.

Dr. Simon has been a consultant to AbbVie and Eli Lilly, a speaker on behalf of Eli Lilly, Janssen, and Novartis, and has received research funding from Eli Lilly and Novartis. Dr. McInnes has been a consultant to AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, and he has received research funding from Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, and UCB.

[email protected]

SOURCE: Simon D et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:33-4, Abstract OP0051.

Structural entheseal lesions and reduced bone mineral density detected using high-resolution CT imaging of a pair of knuckle joints in patients with psoriasis strongly linked with subsequent development of psoriatic arthritis (PsA) in a single-center study with 114 patients followed for an average of 2.3 years.

“These findings substantiate the concept of mechano-inflammation in the pathogenesis of psoriatic disease,” and suggest that interventions with high efficacy for controlling entheseal inflammation may be a “particularly valuable strategy in interfering with the onset of PsA in patients with psoriatic disease,” David Simon, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.

The study, which is now published in Arthritis & Rheumatology, began with 377 patients with psoriasis who had been referred to the University Hospital in Erlangen, Germany, during 2011-2018, and who tested positive on the German Psoriasis Arthritis Diagnostic questionnaire. The researchers excluded patients with existing signs of PsA, any arthritis or enthesitis or other signs of inflammatory rheumatic disease, and they also excluded patients who had not undergoing a high-resolution peripheral quantitative CT (HR-pQCT) examination of the second and third metacarpal joints of the patient’s nondominant hand, which left 114 patients for their analysis. During a mean follow-up of 28 months, 24 patients (27%) developed PsA. The study patients were an average age of 45 years, and they had been diagnosed with psoriasis for an average of about 16 years.

Dr. Simon and associates used the baseline HR-pQCT scans to make two assessments of each patient: the presence of structural entheseal lesions (SEL) in the two metacarpal joints and the calculated volumetric bone mineral density (vBMD). Their analysis showed that the number and severity of SEL were increased among patients who later developed PsA. In a multivariable model that adjusted for age, sex, body mass index, duration of psoriasis, and arthralgia, patients with any SEL had a fivefold higher rate of developing PsA, compared with patients with no SEL, reported Dr. Simon, a rheumatologist at Erlangen University Hospital.

The analysis of vBMD also showed a strong link between bone density at the entheseal sites of the two studied joints and subsequent PsA development. For every standard deviation increase in vBMD at these sites the subsequent rate of PsA incidence fell by about 67% in an analysis that controlled for the same covariants as well as presence of SEL. The same relationship between higher vBMD and a lower risk for PsA held for both total vBMD measurement and for cortical vBMD, but only at the entheseal site. Levels of vBMD at the intra-articular site of the joints had no statistically significant relationship with subsequent PsA development.

The two metrics also appeared to identify additive risks. Nearly 90% of patients with at least one SEL who also had low vBMD at the entheseal site developed PsA during follow-up, compared with about a 50% rate among patients with at least one SEL but high vBMD.

courtesy EULAR

The imaging method used to run these analyses, HR-pQCT, remains for the time being a “research technique” that “is not generalizable for routine practice,” but further development of this method or of a surrogate measure might make it feasible for future widespread practice, commented Iain McInnes, MD, PhD, president of the European League Against Rheumatism and professor of rheumatology and director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow.

“We’ve thought for many years that psoriasis and psoriatic arthritis are on a spectrum, and this work is consistent with the idea that some patients with psoriasis develop tissue involvement at entheses and joints,” Dr. McInnes said in an interview. The higher incidence of PsA seen in patients with adverse SEL and vBMD markers was in an “interesting range” that warrants further study. A next step is to run an intervention study in which patients with these adverse markers would receive an intervention randomized against placebo to see if it improved their outcomes, he suggested. Good candidate agents to study in psoriasis patients who have these adverse markers include drugs that inhibit the action of interleukin-17, drugs that target the p19 cytokine subunit of IL-23, and possibly Janus kinase inhibitor drugs.

Dr. Simon has been a consultant to AbbVie and Eli Lilly, a speaker on behalf of Eli Lilly, Janssen, and Novartis, and has received research funding from Eli Lilly and Novartis. Dr. McInnes has been a consultant to AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, and he has received research funding from Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, and UCB.

[email protected]

SOURCE: Simon D et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:33-4, Abstract OP0051.

As might be expected, the “EULAR [European League Against Rheumatism] provisional recommendations for the management of rheumatic and musculoskeletal diseases [RMDs] in the context of SARS-CoV-2” concur with much of the guidance already released on how best to manage patients during the current pandemic.

Highlights of the five overarching principles are that, contrary to earlier expectations, “there is no indication that patients with RMDs have an additional, or have a higher, risk of contracting the virus, or that they fare a worse course” than the general population, said the task force convener Robert Landewé, MD, PhD, professor of rheumatology at the University of Amsterdam.

“The second pertinent highlight is that, when it comes to managerial discussions, whether or not to stop or to start treatment for RMDs, rheumatologists should definitely be involved,” Dr. Landewé said during a live session at the annual European Congress of Rheumatology, held online this year due to COVID-19. “In practice, something that happens very often is that immunosuppressive drugs are stopped by medical specialists involved in the care of COVID but without any expertise in treating patients with rheumatic diseases. We should try to avoid that situation.”

The third highlight, something many rheumatologists may already be well aware of, is that rheumatology drugs are being used to treat COVID-19 patients without RMDs and a shortage of disease-modifying antirheumatic drugs (DMARDs) agents is a real possibility. As such, the fifth overarching highlight states that the availability of both synthetic and biologic DMARDs is “a delicate societal responsibility” and that “the off-label use of DMARDs in COVID-19 outside the context of clinical trials should be discouraged.”

The EULAR recommendation are now published online in Annals of the Rheumatic Diseases and they are “what you could call an unprecedented set of recommendations,” Dr. Landewé said. “We have never done this before,” he added, referring to the speed and way in which they had to be put together, remotely, and with little scientific evidence currently available. “Three months ago we hadn’t even heard about the virus.”

From the first patient being identified in the Hubei province of China in November 2019, to the first U.S. patient in the state of Washington on Jan. 20, 2020, and to the first European patient identified a little over 10 days later, the COVID-19 pandemic has taken the world by storm. It was only declared a pandemic on March 11, 2020, however, and Dr. Landewé noted that the response to the pandemic had been very variable – some countries locking down their borders early, while others took their time to make an appropriate response, if at all.

The rheumatology community was particularly concerned, Dr. Landewé said, because people with autoimmune diseases who were taking immunosuppressant drugs might be at higher risk for becoming infected with SARS-CoV-2, and may be at higher risk than others for a worse disease course. Thankfully, that seems not to be the case according to data that are emerging from new registries that have been set up, including EULAR’s own COVID-19 registry.

There are 13 recommendations that cover 4 themes: general measures and prevention of SARS-CoV-2 infection; the management of RMD patients during the pandemic; the management of RMD patients who have COVID-19; and the prevention of other pulmonary infections in RMD patients.

Highlighting the first three general recommendations, Dr. Landewé said: “Follow the regular guidelines in your country; if a patient with RMD does not have symptoms of COVID-19, simply continue RMD treatments,” albeit with a couple of exceptions.

The next four recommendation highlights are to avoid visits to the hospital or to the office; use remote monitoring via the telephone, for example; and if visits cannot be avoided, then take appropriate precautions. Finally, if you suspect a patient has COVID-19, do a test.

If patients test positive, then the next four recommendations cover what to do, such as continuing use of RMD treatments, but in the case of glucocorticoids this should be the lowest possible dose necessary. There is no consensus on what to do in cases of mild symptoms; the recommendation is to “decide on a case-by-case basis,” said Dr. Landewé. If a patient’s symptoms worsen, then “seek expert advice immediately and follow local treatment recommendations. The rheumatologist is not the expert to treat COVID-19,” he added. That responsibility lies with the pulmonologist, infectious disease specialist, or maybe the intensive care specialist, depending on local situations.

On the whole, the EULAR recommendations are pretty similar to those already released by the American College of Rheumatology, said Ted Mikuls, MD, of the University of Nebraska Medical Center, Omaha. The ACR recommendations are “slightly more prescriptive”, he suggested, with 25 final guidance statements. For example, general statements focused not only on the use of glucocorticoids, but also other medicines, such as antihypertensives.

“There’s really not a [lot of], I would say, major differences in the two efforts and that’s ... somewhat reassuring that we’re approaching the unknown from very different parts of the world, and driving in a very similar place,” commented Dr. Mikuls, who is a member of the ACR COVID-19 recommendations task force.

“I think one of the very important similarities that I would highlight is that, in the absence of known exposure, in the absence of COVID-19 infection, our panel felt very strongly about the importance of continuing rheumatic disease treatments,” Dr. Mikuls observed. The ACR guidelines also touch upon societal perspectives, including “some statements that were made very specific to lupus, and the use of antimalarials, given supply chain issues that we have encountered.”

Dr. Mikuls also said that the American recommendations emphasized that “you really have to manage active inflammatory rheumatic disease. Even in the context of the COVID-19 pandemic, given what we saw as the potential risk of unchecked inflammation and unchecked rheumatic disease.”

One notable difference, however, is that the European recommendations advise on immunizations and pneumonia prophylaxis, saying that all patients without COVID-19 symptoms should make sure they are up to date with any recommended vaccinations, “with a particular focus on pneumococcal and influenza vaccinations,” Dr. Landewé said.

Another difference is that the ACR recommendations are a living document and could potentially be updated monthly if the evidence arrives to allow that. In that sense, the American guidance is more agile, with EULAR expecting to update its recommendations every 3 months.

“The current evidence is extremely sparse and fragmented,” Dr. Landewé said. “We, as a task force are essentially flying blindly. We also have to cover many jurisdictions within Europe, with many conflicting opinions. So the last word to say is that updates are truly necessary, but we have to wait a while.”

SOURCE: Landewé RB et al. Ann Rheum Dis. 2020 Jun 5. doi: 10.1136/annrheumdis-2020-217877.

As might be expected, the “EULAR [European League Against Rheumatism] provisional recommendations for the management of rheumatic and musculoskeletal diseases [RMDs] in the context of SARS-CoV-2” concur with much of the guidance already released on how best to manage patients during the current pandemic.

Highlights of the five overarching principles are that, contrary to earlier expectations, “there is no indication that patients with RMDs have an additional, or have a higher, risk of contracting the virus, or that they fare a worse course” than the general population, said the task force convener Robert Landewé, MD, PhD, professor of rheumatology at the University of Amsterdam.

“The second pertinent highlight is that, when it comes to managerial discussions, whether or not to stop or to start treatment for RMDs, rheumatologists should definitely be involved,” Dr. Landewé said during a live session at the annual European Congress of Rheumatology, held online this year due to COVID-19. “In practice, something that happens very often is that immunosuppressive drugs are stopped by medical specialists involved in the care of COVID but without any expertise in treating patients with rheumatic diseases. We should try to avoid that situation.”

The third highlight, something many rheumatologists may already be well aware of, is that rheumatology drugs are being used to treat COVID-19 patients without RMDs and a shortage of disease-modifying antirheumatic drugs (DMARDs) agents is a real possibility. As such, the fifth overarching highlight states that the availability of both synthetic and biologic DMARDs is “a delicate societal responsibility” and that “the off-label use of DMARDs in COVID-19 outside the context of clinical trials should be discouraged.”

The EULAR recommendation are now published online in Annals of the Rheumatic Diseases and they are “what you could call an unprecedented set of recommendations,” Dr. Landewé said. “We have never done this before,” he added, referring to the speed and way in which they had to be put together, remotely, and with little scientific evidence currently available. “Three months ago we hadn’t even heard about the virus.”

From the first patient being identified in the Hubei province of China in November 2019, to the first U.S. patient in the state of Washington on Jan. 20, 2020, and to the first European patient identified a little over 10 days later, the COVID-19 pandemic has taken the world by storm. It was only declared a pandemic on March 11, 2020, however, and Dr. Landewé noted that the response to the pandemic had been very variable – some countries locking down their borders early, while others took their time to make an appropriate response, if at all.

The rheumatology community was particularly concerned, Dr. Landewé said, because people with autoimmune diseases who were taking immunosuppressant drugs might be at higher risk for becoming infected with SARS-CoV-2, and may be at higher risk than others for a worse disease course. Thankfully, that seems not to be the case according to data that are emerging from new registries that have been set up, including EULAR’s own COVID-19 registry.

There are 13 recommendations that cover 4 themes: general measures and prevention of SARS-CoV-2 infection; the management of RMD patients during the pandemic; the management of RMD patients who have COVID-19; and the prevention of other pulmonary infections in RMD patients.

Highlighting the first three general recommendations, Dr. Landewé said: “Follow the regular guidelines in your country; if a patient with RMD does not have symptoms of COVID-19, simply continue RMD treatments,” albeit with a couple of exceptions.

The next four recommendation highlights are to avoid visits to the hospital or to the office; use remote monitoring via the telephone, for example; and if visits cannot be avoided, then take appropriate precautions. Finally, if you suspect a patient has COVID-19, do a test.

If patients test positive, then the next four recommendations cover what to do, such as continuing use of RMD treatments, but in the case of glucocorticoids this should be the lowest possible dose necessary. There is no consensus on what to do in cases of mild symptoms; the recommendation is to “decide on a case-by-case basis,” said Dr. Landewé. If a patient’s symptoms worsen, then “seek expert advice immediately and follow local treatment recommendations. The rheumatologist is not the expert to treat COVID-19,” he added. That responsibility lies with the pulmonologist, infectious disease specialist, or maybe the intensive care specialist, depending on local situations.

On the whole, the EULAR recommendations are pretty similar to those already released by the American College of Rheumatology, said Ted Mikuls, MD, of the University of Nebraska Medical Center, Omaha. The ACR recommendations are “slightly more prescriptive”, he suggested, with 25 final guidance statements. For example, general statements focused not only on the use of glucocorticoids, but also other medicines, such as antihypertensives.

“There’s really not a [lot of], I would say, major differences in the two efforts and that’s ... somewhat reassuring that we’re approaching the unknown from very different parts of the world, and driving in a very similar place,” commented Dr. Mikuls, who is a member of the ACR COVID-19 recommendations task force.

“I think one of the very important similarities that I would highlight is that, in the absence of known exposure, in the absence of COVID-19 infection, our panel felt very strongly about the importance of continuing rheumatic disease treatments,” Dr. Mikuls observed. The ACR guidelines also touch upon societal perspectives, including “some statements that were made very specific to lupus, and the use of antimalarials, given supply chain issues that we have encountered.”

Dr. Mikuls also said that the American recommendations emphasized that “you really have to manage active inflammatory rheumatic disease. Even in the context of the COVID-19 pandemic, given what we saw as the potential risk of unchecked inflammation and unchecked rheumatic disease.”

One notable difference, however, is that the European recommendations advise on immunizations and pneumonia prophylaxis, saying that all patients without COVID-19 symptoms should make sure they are up to date with any recommended vaccinations, “with a particular focus on pneumococcal and influenza vaccinations,” Dr. Landewé said.

Another difference is that the ACR recommendations are a living document and could potentially be updated monthly if the evidence arrives to allow that. In that sense, the American guidance is more agile, with EULAR expecting to update its recommendations every 3 months.

“The current evidence is extremely sparse and fragmented,” Dr. Landewé said. “We, as a task force are essentially flying blindly. We also have to cover many jurisdictions within Europe, with many conflicting opinions. So the last word to say is that updates are truly necessary, but we have to wait a while.”

SOURCE: Landewé RB et al. Ann Rheum Dis. 2020 Jun 5. doi: 10.1136/annrheumdis-2020-217877.

As might be expected, the “EULAR [European League Against Rheumatism] provisional recommendations for the management of rheumatic and musculoskeletal diseases [RMDs] in the context of SARS-CoV-2” concur with much of the guidance already released on how best to manage patients during the current pandemic.

Highlights of the five overarching principles are that, contrary to earlier expectations, “there is no indication that patients with RMDs have an additional, or have a higher, risk of contracting the virus, or that they fare a worse course” than the general population, said the task force convener Robert Landewé, MD, PhD, professor of rheumatology at the University of Amsterdam.

“The second pertinent highlight is that, when it comes to managerial discussions, whether or not to stop or to start treatment for RMDs, rheumatologists should definitely be involved,” Dr. Landewé said during a live session at the annual European Congress of Rheumatology, held online this year due to COVID-19. “In practice, something that happens very often is that immunosuppressive drugs are stopped by medical specialists involved in the care of COVID but without any expertise in treating patients with rheumatic diseases. We should try to avoid that situation.”

The third highlight, something many rheumatologists may already be well aware of, is that rheumatology drugs are being used to treat COVID-19 patients without RMDs and a shortage of disease-modifying antirheumatic drugs (DMARDs) agents is a real possibility. As such, the fifth overarching highlight states that the availability of both synthetic and biologic DMARDs is “a delicate societal responsibility” and that “the off-label use of DMARDs in COVID-19 outside the context of clinical trials should be discouraged.”

The EULAR recommendation are now published online in Annals of the Rheumatic Diseases and they are “what you could call an unprecedented set of recommendations,” Dr. Landewé said. “We have never done this before,” he added, referring to the speed and way in which they had to be put together, remotely, and with little scientific evidence currently available. “Three months ago we hadn’t even heard about the virus.”

From the first patient being identified in the Hubei province of China in November 2019, to the first U.S. patient in the state of Washington on Jan. 20, 2020, and to the first European patient identified a little over 10 days later, the COVID-19 pandemic has taken the world by storm. It was only declared a pandemic on March 11, 2020, however, and Dr. Landewé noted that the response to the pandemic had been very variable – some countries locking down their borders early, while others took their time to make an appropriate response, if at all.

The rheumatology community was particularly concerned, Dr. Landewé said, because people with autoimmune diseases who were taking immunosuppressant drugs might be at higher risk for becoming infected with SARS-CoV-2, and may be at higher risk than others for a worse disease course. Thankfully, that seems not to be the case according to data that are emerging from new registries that have been set up, including EULAR’s own COVID-19 registry.

There are 13 recommendations that cover 4 themes: general measures and prevention of SARS-CoV-2 infection; the management of RMD patients during the pandemic; the management of RMD patients who have COVID-19; and the prevention of other pulmonary infections in RMD patients.

Highlighting the first three general recommendations, Dr. Landewé said: “Follow the regular guidelines in your country; if a patient with RMD does not have symptoms of COVID-19, simply continue RMD treatments,” albeit with a couple of exceptions.

The next four recommendation highlights are to avoid visits to the hospital or to the office; use remote monitoring via the telephone, for example; and if visits cannot be avoided, then take appropriate precautions. Finally, if you suspect a patient has COVID-19, do a test.

If patients test positive, then the next four recommendations cover what to do, such as continuing use of RMD treatments, but in the case of glucocorticoids this should be the lowest possible dose necessary. There is no consensus on what to do in cases of mild symptoms; the recommendation is to “decide on a case-by-case basis,” said Dr. Landewé. If a patient’s symptoms worsen, then “seek expert advice immediately and follow local treatment recommendations. The rheumatologist is not the expert to treat COVID-19,” he added. That responsibility lies with the pulmonologist, infectious disease specialist, or maybe the intensive care specialist, depending on local situations.

On the whole, the EULAR recommendations are pretty similar to those already released by the American College of Rheumatology, said Ted Mikuls, MD, of the University of Nebraska Medical Center, Omaha. The ACR recommendations are “slightly more prescriptive”, he suggested, with 25 final guidance statements. For example, general statements focused not only on the use of glucocorticoids, but also other medicines, such as antihypertensives.

“There’s really not a [lot of], I would say, major differences in the two efforts and that’s ... somewhat reassuring that we’re approaching the unknown from very different parts of the world, and driving in a very similar place,” commented Dr. Mikuls, who is a member of the ACR COVID-19 recommendations task force.

“I think one of the very important similarities that I would highlight is that, in the absence of known exposure, in the absence of COVID-19 infection, our panel felt very strongly about the importance of continuing rheumatic disease treatments,” Dr. Mikuls observed. The ACR guidelines also touch upon societal perspectives, including “some statements that were made very specific to lupus, and the use of antimalarials, given supply chain issues that we have encountered.”

Dr. Mikuls also said that the American recommendations emphasized that “you really have to manage active inflammatory rheumatic disease. Even in the context of the COVID-19 pandemic, given what we saw as the potential risk of unchecked inflammation and unchecked rheumatic disease.”

One notable difference, however, is that the European recommendations advise on immunizations and pneumonia prophylaxis, saying that all patients without COVID-19 symptoms should make sure they are up to date with any recommended vaccinations, “with a particular focus on pneumococcal and influenza vaccinations,” Dr. Landewé said.

Another difference is that the ACR recommendations are a living document and could potentially be updated monthly if the evidence arrives to allow that. In that sense, the American guidance is more agile, with EULAR expecting to update its recommendations every 3 months.

“The current evidence is extremely sparse and fragmented,” Dr. Landewé said. “We, as a task force are essentially flying blindly. We also have to cover many jurisdictions within Europe, with many conflicting opinions. So the last word to say is that updates are truly necessary, but we have to wait a while.”

SOURCE: Landewé RB et al. Ann Rheum Dis. 2020 Jun 5. doi: 10.1136/annrheumdis-2020-217877.