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FDA approves oral TYK2 inhibitor deucravacitinib for treating psoriasis
the manufacturer announced on Sept. 9.
Deucravacitinib targets TYK2, which inhibits signaling of interleukin-23, interleukin-12, and type 1 interferons, key cytokines involved in the pathogenesis of multiple immune-mediated diseases, according to Bristol Myers Squibb (BMS). This is the first approval for deucravacitinib, which will be marketed as Sotyktu, and the first drug in this class to be approved.
It is also currently under review for the same indication in Europe and Japan, and elsewhere, and for treating pustular psoriasis and erythrodermic psoriasis in Japan.
FDA approval was based on the results of POETYK PSO-1 and POETYK PSO-2, phase 3 trials of almost 1,700 adults with moderate to severe plaque psoriasis. In these studies, treatment with once-daily deucravacitinib showed significant and clinically meaningful improvements in skin clearance and symptoms, compared with placebo and with apremilast (Otezla), according to the company.
In the two studies, patients were randomly assigned to receive 6 mg daily of deucravacitinib, placebo, or a 30-mg twice-daily dose of apremilast, the oral phosphodiesterase 4 inhibitor approved for psoriasis. The primary endpoints were the percentage of patients who achieved a Psoriasis Area and Severity Index (PASI) 75 response and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear) at 16 weeks.
At 16 weeks, 58% and 53% of patients receiving deucravacitinib in the POETYK PSO-1 and POETYK PSO-2 studies, respectively, achieved PASI 75 response, compared with 13% and 9% of those receiving placebo (P < .0001 for both) and 35% and 40% receiving apremilast (P < .0001, P = .0004, respectively), according to the company’s announcement of the approval. PASI 75 responses were maintained through 52 weeks among the patients who remained on treatment, in both studies, according to BMS.
In the POETYK PSO-1 and PSO-2 studies, respectively, 54% and 50% of those on deucravacitinib achieved an sPGA of 0/1 at 16 weeks, compared with 7% and 9% of those receiving placebo (P < .0001 for both) and 32% and 34% of those receiving apremilast (P < .0001 for both).
Across the two studies, at 16 weeks, the most common adverse events that affected at least 1% of patients on deucravacitinib and that occurred at higher rates than in the placebo group were upper respiratory infections (19.2%), increases in serum creatine phosphokinase (2.7%), herpes simplex (2%), mouth ulcers (1.9%), folliculitis (1.7%), and acne (1.4%). Adverse events resulting in discontinuation of treatment were reported in 2.4% of persons receiving deucravacitinib and 5.2% of those receiving apremilast, compared with 3.8% of those receiving placebo.
Up to 16 weeks, according to the BMS statement, 28% of persons receiving deucravacitinib had infections, most of which were mild to moderate and not serious and did not result in stopping treatment, compared with 22% of those receiving placebo. In addition, five patients treated with deucravacitinib and five patients receiving placebo had serious infections, and three patients receiving deucravacitinib had cancer (not including nonmelanoma skin cancer).
Deucravacitinib is also being evaluated in clinical trials for psoriatic arthritis, lupus, and inflammatory bowel disease. It is not recommended for use in combination with other potent immunosuppressants, according to BMS.
The prescribing information and patient medication guide are available online.
The POETYK PSO-1 and POETYK PSO-2 studies were funded by Bristol Myers Squibb.
A version of this article first appeared on Medscape.com.
the manufacturer announced on Sept. 9.
Deucravacitinib targets TYK2, which inhibits signaling of interleukin-23, interleukin-12, and type 1 interferons, key cytokines involved in the pathogenesis of multiple immune-mediated diseases, according to Bristol Myers Squibb (BMS). This is the first approval for deucravacitinib, which will be marketed as Sotyktu, and the first drug in this class to be approved.
It is also currently under review for the same indication in Europe and Japan, and elsewhere, and for treating pustular psoriasis and erythrodermic psoriasis in Japan.
FDA approval was based on the results of POETYK PSO-1 and POETYK PSO-2, phase 3 trials of almost 1,700 adults with moderate to severe plaque psoriasis. In these studies, treatment with once-daily deucravacitinib showed significant and clinically meaningful improvements in skin clearance and symptoms, compared with placebo and with apremilast (Otezla), according to the company.
In the two studies, patients were randomly assigned to receive 6 mg daily of deucravacitinib, placebo, or a 30-mg twice-daily dose of apremilast, the oral phosphodiesterase 4 inhibitor approved for psoriasis. The primary endpoints were the percentage of patients who achieved a Psoriasis Area and Severity Index (PASI) 75 response and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear) at 16 weeks.
At 16 weeks, 58% and 53% of patients receiving deucravacitinib in the POETYK PSO-1 and POETYK PSO-2 studies, respectively, achieved PASI 75 response, compared with 13% and 9% of those receiving placebo (P < .0001 for both) and 35% and 40% receiving apremilast (P < .0001, P = .0004, respectively), according to the company’s announcement of the approval. PASI 75 responses were maintained through 52 weeks among the patients who remained on treatment, in both studies, according to BMS.
In the POETYK PSO-1 and PSO-2 studies, respectively, 54% and 50% of those on deucravacitinib achieved an sPGA of 0/1 at 16 weeks, compared with 7% and 9% of those receiving placebo (P < .0001 for both) and 32% and 34% of those receiving apremilast (P < .0001 for both).
Across the two studies, at 16 weeks, the most common adverse events that affected at least 1% of patients on deucravacitinib and that occurred at higher rates than in the placebo group were upper respiratory infections (19.2%), increases in serum creatine phosphokinase (2.7%), herpes simplex (2%), mouth ulcers (1.9%), folliculitis (1.7%), and acne (1.4%). Adverse events resulting in discontinuation of treatment were reported in 2.4% of persons receiving deucravacitinib and 5.2% of those receiving apremilast, compared with 3.8% of those receiving placebo.
Up to 16 weeks, according to the BMS statement, 28% of persons receiving deucravacitinib had infections, most of which were mild to moderate and not serious and did not result in stopping treatment, compared with 22% of those receiving placebo. In addition, five patients treated with deucravacitinib and five patients receiving placebo had serious infections, and three patients receiving deucravacitinib had cancer (not including nonmelanoma skin cancer).
Deucravacitinib is also being evaluated in clinical trials for psoriatic arthritis, lupus, and inflammatory bowel disease. It is not recommended for use in combination with other potent immunosuppressants, according to BMS.
The prescribing information and patient medication guide are available online.
The POETYK PSO-1 and POETYK PSO-2 studies were funded by Bristol Myers Squibb.
A version of this article first appeared on Medscape.com.
the manufacturer announced on Sept. 9.
Deucravacitinib targets TYK2, which inhibits signaling of interleukin-23, interleukin-12, and type 1 interferons, key cytokines involved in the pathogenesis of multiple immune-mediated diseases, according to Bristol Myers Squibb (BMS). This is the first approval for deucravacitinib, which will be marketed as Sotyktu, and the first drug in this class to be approved.
It is also currently under review for the same indication in Europe and Japan, and elsewhere, and for treating pustular psoriasis and erythrodermic psoriasis in Japan.
FDA approval was based on the results of POETYK PSO-1 and POETYK PSO-2, phase 3 trials of almost 1,700 adults with moderate to severe plaque psoriasis. In these studies, treatment with once-daily deucravacitinib showed significant and clinically meaningful improvements in skin clearance and symptoms, compared with placebo and with apremilast (Otezla), according to the company.
In the two studies, patients were randomly assigned to receive 6 mg daily of deucravacitinib, placebo, or a 30-mg twice-daily dose of apremilast, the oral phosphodiesterase 4 inhibitor approved for psoriasis. The primary endpoints were the percentage of patients who achieved a Psoriasis Area and Severity Index (PASI) 75 response and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear) at 16 weeks.
At 16 weeks, 58% and 53% of patients receiving deucravacitinib in the POETYK PSO-1 and POETYK PSO-2 studies, respectively, achieved PASI 75 response, compared with 13% and 9% of those receiving placebo (P < .0001 for both) and 35% and 40% receiving apremilast (P < .0001, P = .0004, respectively), according to the company’s announcement of the approval. PASI 75 responses were maintained through 52 weeks among the patients who remained on treatment, in both studies, according to BMS.
In the POETYK PSO-1 and PSO-2 studies, respectively, 54% and 50% of those on deucravacitinib achieved an sPGA of 0/1 at 16 weeks, compared with 7% and 9% of those receiving placebo (P < .0001 for both) and 32% and 34% of those receiving apremilast (P < .0001 for both).
Across the two studies, at 16 weeks, the most common adverse events that affected at least 1% of patients on deucravacitinib and that occurred at higher rates than in the placebo group were upper respiratory infections (19.2%), increases in serum creatine phosphokinase (2.7%), herpes simplex (2%), mouth ulcers (1.9%), folliculitis (1.7%), and acne (1.4%). Adverse events resulting in discontinuation of treatment were reported in 2.4% of persons receiving deucravacitinib and 5.2% of those receiving apremilast, compared with 3.8% of those receiving placebo.
Up to 16 weeks, according to the BMS statement, 28% of persons receiving deucravacitinib had infections, most of which were mild to moderate and not serious and did not result in stopping treatment, compared with 22% of those receiving placebo. In addition, five patients treated with deucravacitinib and five patients receiving placebo had serious infections, and three patients receiving deucravacitinib had cancer (not including nonmelanoma skin cancer).
Deucravacitinib is also being evaluated in clinical trials for psoriatic arthritis, lupus, and inflammatory bowel disease. It is not recommended for use in combination with other potent immunosuppressants, according to BMS.
The prescribing information and patient medication guide are available online.
The POETYK PSO-1 and POETYK PSO-2 studies were funded by Bristol Myers Squibb.
A version of this article first appeared on Medscape.com.
Should patients with PsA or ankylosing spondylitis with axial disease be ‘lumped’ or ‘split’?
A new study provides evidence that two conditions that fall under the umbrella of spondyloarthritis – isolated axial disease in patients with psoriatic arthritis (PsA) and isolated axial disease in patients with ankylosing spondylitis (AS) accompanied by psoriasis – are different clinical entities and may need different treatments. These relatively rare rheumatologic conditions, defined by their back involvement, have considerable clinical overlap and are often lumped together under the label axial spondyloarthritis.
This is a hot topic and current matter of debate within the scientific community: Are axial PsA and axial AS two separate diseases or just two phenotypes under the spondyloarthritis umbrella? said Fabian Proft, MD, a rheumatologist and researcher at Charité Universitätsmedizin Berlin, commenting on the new study, which was published online in Annals of the Rheumatic Diseases.
Both conditions belong to the spectrum of spondyloarthritis, but with varying viewpoints on nomenclature. They have intersections and overlaps, but not all treatments are equally effective for both. “We need to better understand their differences and similarities,” Dr. Proft said, adding that the new study is noteworthy for the size of the population included, its long-term follow-up data, and the researchers’ depth of experience treating these patients.
The researchers are based at the University of Toronto, which has separate clinics dedicated to PsA and to AS, said Dafna D. Gladman, MD, professor of medicine at the university, codirector of the PsA clinic, and corresponding author for the new study. The two clinics follow the same standardized protocols, including clinical, radiographic, genetic, and laboratory assessments. Even though the patients present quite similarly, she credits referring physicians for recognizing the distinctions by their referrals to the PsA or AS clinic.
According to previous research, pure axial PsA, without peripheral involvement, is rare, affecting about 2%-5% of patients with PsA. For this study, an observational cohort of 1,576 patients from the PsA clinic included 31% (n = 495) with axial disease, 2% (n = 32) with isolated axial PsA, and 29% (n = 463) with both axial and peripheral involvement. A total of 25 of the patients with isolated axial PsA ultimately developed peripheral disease by their most recent clinic follow-up visit. In a second cohort of 1,688 patients with AS, nearly 5% (n = 68) had isolated axial disease with psoriasis.
“In our logistic regression analysis, isolated axial PsA was found to be a different clinical entity than isolated AS with psoriasis. They are not the same patients,” Dr. Gladman said. The patients with isolated axial PsA were older at diagnosis, more likely to have psoriatic nail lesions, and less likely to have inflammatory back pain than were patients with isolated axial AS and accompanying psoriasis.
When interviewed in early September, Dr. Gladman was preparing to fly to Ghent, Belgium, to participate in a debate at the International Congress on Spondyloarthritides, taking the pro position on the thesis: Is axial inflammation in PsA distinct from axial spondyloarthritis? Taking the con position was to be Robert Landewé, MD, PhD, of Amsterdam University Medical Center in the Netherlands.
“This is an old debate, splitters versus lumpers,” Dr. Gladman told this news organization. “My message is that when you place patients in more homogeneous groups, you can learn more and perhaps find better opportunities for treating their disease.” For example, even with the similarities, do these patients need to be treated with different medications? Medications for psoriasis, including those targeting the interleukin-23 cytokine, may not be effective for AS, but patients with axial PsA may not get them because of the association with axial AS.
“Now is the opportunity to really understand what – if any – are the differences between various components of this disease group. If you lump people together, you may miss the forest for the trees,” Dr. Gladman said. “If, at the end of the day, we find out these patients essentially are the same, I will lump. But until we have proved that there are no important differences, I will split.” She added that it is important for practicing rheumatologists to make the correct diagnosis so that they know to access certain drugs.
Dr. Proft credited Dr. Gladman and colleagues’ study for adding another piece of the puzzle to better understand differences and similarities for these two axial diseases. He noted, however, that the study did not include MRI scans for every participating patient, which could have given a deeper picture.
“International efforts are being made to recruit patients for a multinational, multicenter study of axial involvement in PsA,” which will include MRI data, Dr. Gladman said. She and Dr. Proft are both part of AXIS, the Axial Involvement in Psoriatic Arthritis cohort, now recruiting patients for such a study. AXIS is a joint project of the Assessment of SpondyloArthritis international Society and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
“We don’t have final answers yet, although we have given evidence to support the differences.” The proof is in the pudding, she said, and that pudding will be the clinical trials.
The University of Toronto Psoriatic Arthritis Program is supported by a grant from the Krembil Foundation. The study authors declared no competing interests. Dr. Proft reported receiving research support from Novartis, Eli Lilly, and UCB, and fees for consulting and serving on speakers bureaus from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Hexal, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB.
A new study provides evidence that two conditions that fall under the umbrella of spondyloarthritis – isolated axial disease in patients with psoriatic arthritis (PsA) and isolated axial disease in patients with ankylosing spondylitis (AS) accompanied by psoriasis – are different clinical entities and may need different treatments. These relatively rare rheumatologic conditions, defined by their back involvement, have considerable clinical overlap and are often lumped together under the label axial spondyloarthritis.
This is a hot topic and current matter of debate within the scientific community: Are axial PsA and axial AS two separate diseases or just two phenotypes under the spondyloarthritis umbrella? said Fabian Proft, MD, a rheumatologist and researcher at Charité Universitätsmedizin Berlin, commenting on the new study, which was published online in Annals of the Rheumatic Diseases.
Both conditions belong to the spectrum of spondyloarthritis, but with varying viewpoints on nomenclature. They have intersections and overlaps, but not all treatments are equally effective for both. “We need to better understand their differences and similarities,” Dr. Proft said, adding that the new study is noteworthy for the size of the population included, its long-term follow-up data, and the researchers’ depth of experience treating these patients.
The researchers are based at the University of Toronto, which has separate clinics dedicated to PsA and to AS, said Dafna D. Gladman, MD, professor of medicine at the university, codirector of the PsA clinic, and corresponding author for the new study. The two clinics follow the same standardized protocols, including clinical, radiographic, genetic, and laboratory assessments. Even though the patients present quite similarly, she credits referring physicians for recognizing the distinctions by their referrals to the PsA or AS clinic.
According to previous research, pure axial PsA, without peripheral involvement, is rare, affecting about 2%-5% of patients with PsA. For this study, an observational cohort of 1,576 patients from the PsA clinic included 31% (n = 495) with axial disease, 2% (n = 32) with isolated axial PsA, and 29% (n = 463) with both axial and peripheral involvement. A total of 25 of the patients with isolated axial PsA ultimately developed peripheral disease by their most recent clinic follow-up visit. In a second cohort of 1,688 patients with AS, nearly 5% (n = 68) had isolated axial disease with psoriasis.
“In our logistic regression analysis, isolated axial PsA was found to be a different clinical entity than isolated AS with psoriasis. They are not the same patients,” Dr. Gladman said. The patients with isolated axial PsA were older at diagnosis, more likely to have psoriatic nail lesions, and less likely to have inflammatory back pain than were patients with isolated axial AS and accompanying psoriasis.
When interviewed in early September, Dr. Gladman was preparing to fly to Ghent, Belgium, to participate in a debate at the International Congress on Spondyloarthritides, taking the pro position on the thesis: Is axial inflammation in PsA distinct from axial spondyloarthritis? Taking the con position was to be Robert Landewé, MD, PhD, of Amsterdam University Medical Center in the Netherlands.
“This is an old debate, splitters versus lumpers,” Dr. Gladman told this news organization. “My message is that when you place patients in more homogeneous groups, you can learn more and perhaps find better opportunities for treating their disease.” For example, even with the similarities, do these patients need to be treated with different medications? Medications for psoriasis, including those targeting the interleukin-23 cytokine, may not be effective for AS, but patients with axial PsA may not get them because of the association with axial AS.
“Now is the opportunity to really understand what – if any – are the differences between various components of this disease group. If you lump people together, you may miss the forest for the trees,” Dr. Gladman said. “If, at the end of the day, we find out these patients essentially are the same, I will lump. But until we have proved that there are no important differences, I will split.” She added that it is important for practicing rheumatologists to make the correct diagnosis so that they know to access certain drugs.
Dr. Proft credited Dr. Gladman and colleagues’ study for adding another piece of the puzzle to better understand differences and similarities for these two axial diseases. He noted, however, that the study did not include MRI scans for every participating patient, which could have given a deeper picture.
“International efforts are being made to recruit patients for a multinational, multicenter study of axial involvement in PsA,” which will include MRI data, Dr. Gladman said. She and Dr. Proft are both part of AXIS, the Axial Involvement in Psoriatic Arthritis cohort, now recruiting patients for such a study. AXIS is a joint project of the Assessment of SpondyloArthritis international Society and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
“We don’t have final answers yet, although we have given evidence to support the differences.” The proof is in the pudding, she said, and that pudding will be the clinical trials.
The University of Toronto Psoriatic Arthritis Program is supported by a grant from the Krembil Foundation. The study authors declared no competing interests. Dr. Proft reported receiving research support from Novartis, Eli Lilly, and UCB, and fees for consulting and serving on speakers bureaus from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Hexal, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB.
A new study provides evidence that two conditions that fall under the umbrella of spondyloarthritis – isolated axial disease in patients with psoriatic arthritis (PsA) and isolated axial disease in patients with ankylosing spondylitis (AS) accompanied by psoriasis – are different clinical entities and may need different treatments. These relatively rare rheumatologic conditions, defined by their back involvement, have considerable clinical overlap and are often lumped together under the label axial spondyloarthritis.
This is a hot topic and current matter of debate within the scientific community: Are axial PsA and axial AS two separate diseases or just two phenotypes under the spondyloarthritis umbrella? said Fabian Proft, MD, a rheumatologist and researcher at Charité Universitätsmedizin Berlin, commenting on the new study, which was published online in Annals of the Rheumatic Diseases.
Both conditions belong to the spectrum of spondyloarthritis, but with varying viewpoints on nomenclature. They have intersections and overlaps, but not all treatments are equally effective for both. “We need to better understand their differences and similarities,” Dr. Proft said, adding that the new study is noteworthy for the size of the population included, its long-term follow-up data, and the researchers’ depth of experience treating these patients.
The researchers are based at the University of Toronto, which has separate clinics dedicated to PsA and to AS, said Dafna D. Gladman, MD, professor of medicine at the university, codirector of the PsA clinic, and corresponding author for the new study. The two clinics follow the same standardized protocols, including clinical, radiographic, genetic, and laboratory assessments. Even though the patients present quite similarly, she credits referring physicians for recognizing the distinctions by their referrals to the PsA or AS clinic.
According to previous research, pure axial PsA, without peripheral involvement, is rare, affecting about 2%-5% of patients with PsA. For this study, an observational cohort of 1,576 patients from the PsA clinic included 31% (n = 495) with axial disease, 2% (n = 32) with isolated axial PsA, and 29% (n = 463) with both axial and peripheral involvement. A total of 25 of the patients with isolated axial PsA ultimately developed peripheral disease by their most recent clinic follow-up visit. In a second cohort of 1,688 patients with AS, nearly 5% (n = 68) had isolated axial disease with psoriasis.
“In our logistic regression analysis, isolated axial PsA was found to be a different clinical entity than isolated AS with psoriasis. They are not the same patients,” Dr. Gladman said. The patients with isolated axial PsA were older at diagnosis, more likely to have psoriatic nail lesions, and less likely to have inflammatory back pain than were patients with isolated axial AS and accompanying psoriasis.
When interviewed in early September, Dr. Gladman was preparing to fly to Ghent, Belgium, to participate in a debate at the International Congress on Spondyloarthritides, taking the pro position on the thesis: Is axial inflammation in PsA distinct from axial spondyloarthritis? Taking the con position was to be Robert Landewé, MD, PhD, of Amsterdam University Medical Center in the Netherlands.
“This is an old debate, splitters versus lumpers,” Dr. Gladman told this news organization. “My message is that when you place patients in more homogeneous groups, you can learn more and perhaps find better opportunities for treating their disease.” For example, even with the similarities, do these patients need to be treated with different medications? Medications for psoriasis, including those targeting the interleukin-23 cytokine, may not be effective for AS, but patients with axial PsA may not get them because of the association with axial AS.
“Now is the opportunity to really understand what – if any – are the differences between various components of this disease group. If you lump people together, you may miss the forest for the trees,” Dr. Gladman said. “If, at the end of the day, we find out these patients essentially are the same, I will lump. But until we have proved that there are no important differences, I will split.” She added that it is important for practicing rheumatologists to make the correct diagnosis so that they know to access certain drugs.
Dr. Proft credited Dr. Gladman and colleagues’ study for adding another piece of the puzzle to better understand differences and similarities for these two axial diseases. He noted, however, that the study did not include MRI scans for every participating patient, which could have given a deeper picture.
“International efforts are being made to recruit patients for a multinational, multicenter study of axial involvement in PsA,” which will include MRI data, Dr. Gladman said. She and Dr. Proft are both part of AXIS, the Axial Involvement in Psoriatic Arthritis cohort, now recruiting patients for such a study. AXIS is a joint project of the Assessment of SpondyloArthritis international Society and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
“We don’t have final answers yet, although we have given evidence to support the differences.” The proof is in the pudding, she said, and that pudding will be the clinical trials.
The University of Toronto Psoriatic Arthritis Program is supported by a grant from the Krembil Foundation. The study authors declared no competing interests. Dr. Proft reported receiving research support from Novartis, Eli Lilly, and UCB, and fees for consulting and serving on speakers bureaus from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Hexal, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB.
FROM ANNALS OF THE RHEUMATIC DISEASES
Commentary: IL-Targeted Therapies and Nail Dystrophy in PsA, September 2022
Recent publications on psoriatic arthritis (PsA) have focused on targeted therapies, particularly those targeting interleukin (IL) 17 and 23. Bimekizumab is a novel biologic that dually inhibits IL-17A and IL-17F. Coates and colleagues reported 3-year results from the phase 2b BE ACTIVE trial that included 206 adults with active PsA randomly assigned to receive bimekizumab or placebo for 48 weeks, of which 184 patients were enrolled in the open-label extension phase for a further 104 weeks of treatment. They report that at least 20% improvement in American College of Rheumatology score was maintained by 64.1% of patients at week 152 compared with 72.3% of patients at week 48. By week 152, 89.3% of patients had reported one or more treatment-emergent adverse event (TEAE), with serious TEAE being reported by 10.7% of patients. Fungal infections are of special interest when inhibiting both IL-17A and IL-17F. It was observed that 9.7% had fungal infections (all mild-to-moderate and localized), of which 4.6% had candidiasis. Thus, bimekizumab shows promise as a new therapy for PsA.
In addition to improving signs and symptoms, clinically meaningful improvement in health-related quality of life is an important goal of treatment. Two studies reported improvement in patient reported outcomes on treatment with IL-23 inhibitors.
An analysis of data from the phase 3 DISCOVER 2 trial included 738 biologic-naive patients with active PsA and inadequate response to standard treatments. These patients were randomly assigned to receive 100 mg guselkumab every 4 weeks (Q4W) or every 8 weeks (Q8W) or placebo. Curtis and colleagues showed that a significantly higher proportion of patients receiving guselkumab Q4W/Q8W vs placebo reported achieving minimally important differences (MID) in the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index (56.0%/56.0% vs 43.4%; P < .006) and Visual Analog Scale (EQ-VAS) score (62.8%/63.5% vs 44.4%; P < .0001) at week 24, with more than 60% of patients reporting improvements at week 52.
Similarly, analyses of data by Kristensen and colleagues from two phase 3 trials, KEEPsAKE-1 and KEEPsAKE-2, included adults with PsA and inadequate response/intolerance to disease-modifying antirheumatic drugs or biologics. The patients were randomly assigned to receive risankizumab or placebo for 24 weeks and only risankizumab during weeks 24-52. At week 24, patients receiving risankizumab vs placebo were significantly more likely to report achieving MID in Patient's Global Assessment of Disease Activity (PtGA) in both KEEPsAKE-1 (odds ratio [OR] 2.0; P < .001) and KEEPsAKE-2 (OR 1.9; P < .01) studies, with further improvement at week 52. Improvement was also seen on the Patient's Assessment of Pain, Health Assessment Questionnaire – Disability Index, Short-Form 36 Physical and Mental Component Summary scores, EQ-5D-5L, Functional Assessment of Chronic Illness Therapy – Fatigue, and Work Productivity and Activity Impairment.
An interesting insight from two studies showed the importance of nail disease in predicting treatment response. A post hoc analysis by Helliwell and colleagues of the phase 3 SEAM-PsA trial of 851 biologic/methotrexate-naive patients with active PsA who were randomly assigned to receive methotrexate monotherapy, etanercept monotherapy, or methotrexate + etanercept combination therapy showed that the presence of both dactylitis and nail disease at baseline were significantly associated with the achievement of minimal disease activity (OR 1.4; P = .0457; and OR 1.8; P = .0233, respectively), as well as low PsA Disease Activity Score (OR 1.8; P = .0014; and OR 1.8; P = .0168, respectively).
Similarly, a post hoc analysis by Baraliakos and colleagues of the phase 3b MAXIMISE trial of 473 adult patients with PsA and axial manifestations who were randomly assigned to receive secukinumab (150 or 300 mg) or placebo showed that the presence vs the absence of nail dystrophy was associated with the achievement of significantly better Assessment of SpondyloArthritis International Society 20 response in the 300 mg secukinumab group (OR 5.0; 95% CI 1.47-17.19).
Recent publications on psoriatic arthritis (PsA) have focused on targeted therapies, particularly those targeting interleukin (IL) 17 and 23. Bimekizumab is a novel biologic that dually inhibits IL-17A and IL-17F. Coates and colleagues reported 3-year results from the phase 2b BE ACTIVE trial that included 206 adults with active PsA randomly assigned to receive bimekizumab or placebo for 48 weeks, of which 184 patients were enrolled in the open-label extension phase for a further 104 weeks of treatment. They report that at least 20% improvement in American College of Rheumatology score was maintained by 64.1% of patients at week 152 compared with 72.3% of patients at week 48. By week 152, 89.3% of patients had reported one or more treatment-emergent adverse event (TEAE), with serious TEAE being reported by 10.7% of patients. Fungal infections are of special interest when inhibiting both IL-17A and IL-17F. It was observed that 9.7% had fungal infections (all mild-to-moderate and localized), of which 4.6% had candidiasis. Thus, bimekizumab shows promise as a new therapy for PsA.
In addition to improving signs and symptoms, clinically meaningful improvement in health-related quality of life is an important goal of treatment. Two studies reported improvement in patient reported outcomes on treatment with IL-23 inhibitors.
An analysis of data from the phase 3 DISCOVER 2 trial included 738 biologic-naive patients with active PsA and inadequate response to standard treatments. These patients were randomly assigned to receive 100 mg guselkumab every 4 weeks (Q4W) or every 8 weeks (Q8W) or placebo. Curtis and colleagues showed that a significantly higher proportion of patients receiving guselkumab Q4W/Q8W vs placebo reported achieving minimally important differences (MID) in the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index (56.0%/56.0% vs 43.4%; P < .006) and Visual Analog Scale (EQ-VAS) score (62.8%/63.5% vs 44.4%; P < .0001) at week 24, with more than 60% of patients reporting improvements at week 52.
Similarly, analyses of data by Kristensen and colleagues from two phase 3 trials, KEEPsAKE-1 and KEEPsAKE-2, included adults with PsA and inadequate response/intolerance to disease-modifying antirheumatic drugs or biologics. The patients were randomly assigned to receive risankizumab or placebo for 24 weeks and only risankizumab during weeks 24-52. At week 24, patients receiving risankizumab vs placebo were significantly more likely to report achieving MID in Patient's Global Assessment of Disease Activity (PtGA) in both KEEPsAKE-1 (odds ratio [OR] 2.0; P < .001) and KEEPsAKE-2 (OR 1.9; P < .01) studies, with further improvement at week 52. Improvement was also seen on the Patient's Assessment of Pain, Health Assessment Questionnaire – Disability Index, Short-Form 36 Physical and Mental Component Summary scores, EQ-5D-5L, Functional Assessment of Chronic Illness Therapy – Fatigue, and Work Productivity and Activity Impairment.
An interesting insight from two studies showed the importance of nail disease in predicting treatment response. A post hoc analysis by Helliwell and colleagues of the phase 3 SEAM-PsA trial of 851 biologic/methotrexate-naive patients with active PsA who were randomly assigned to receive methotrexate monotherapy, etanercept monotherapy, or methotrexate + etanercept combination therapy showed that the presence of both dactylitis and nail disease at baseline were significantly associated with the achievement of minimal disease activity (OR 1.4; P = .0457; and OR 1.8; P = .0233, respectively), as well as low PsA Disease Activity Score (OR 1.8; P = .0014; and OR 1.8; P = .0168, respectively).
Similarly, a post hoc analysis by Baraliakos and colleagues of the phase 3b MAXIMISE trial of 473 adult patients with PsA and axial manifestations who were randomly assigned to receive secukinumab (150 or 300 mg) or placebo showed that the presence vs the absence of nail dystrophy was associated with the achievement of significantly better Assessment of SpondyloArthritis International Society 20 response in the 300 mg secukinumab group (OR 5.0; 95% CI 1.47-17.19).
Recent publications on psoriatic arthritis (PsA) have focused on targeted therapies, particularly those targeting interleukin (IL) 17 and 23. Bimekizumab is a novel biologic that dually inhibits IL-17A and IL-17F. Coates and colleagues reported 3-year results from the phase 2b BE ACTIVE trial that included 206 adults with active PsA randomly assigned to receive bimekizumab or placebo for 48 weeks, of which 184 patients were enrolled in the open-label extension phase for a further 104 weeks of treatment. They report that at least 20% improvement in American College of Rheumatology score was maintained by 64.1% of patients at week 152 compared with 72.3% of patients at week 48. By week 152, 89.3% of patients had reported one or more treatment-emergent adverse event (TEAE), with serious TEAE being reported by 10.7% of patients. Fungal infections are of special interest when inhibiting both IL-17A and IL-17F. It was observed that 9.7% had fungal infections (all mild-to-moderate and localized), of which 4.6% had candidiasis. Thus, bimekizumab shows promise as a new therapy for PsA.
In addition to improving signs and symptoms, clinically meaningful improvement in health-related quality of life is an important goal of treatment. Two studies reported improvement in patient reported outcomes on treatment with IL-23 inhibitors.
An analysis of data from the phase 3 DISCOVER 2 trial included 738 biologic-naive patients with active PsA and inadequate response to standard treatments. These patients were randomly assigned to receive 100 mg guselkumab every 4 weeks (Q4W) or every 8 weeks (Q8W) or placebo. Curtis and colleagues showed that a significantly higher proportion of patients receiving guselkumab Q4W/Q8W vs placebo reported achieving minimally important differences (MID) in the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index (56.0%/56.0% vs 43.4%; P < .006) and Visual Analog Scale (EQ-VAS) score (62.8%/63.5% vs 44.4%; P < .0001) at week 24, with more than 60% of patients reporting improvements at week 52.
Similarly, analyses of data by Kristensen and colleagues from two phase 3 trials, KEEPsAKE-1 and KEEPsAKE-2, included adults with PsA and inadequate response/intolerance to disease-modifying antirheumatic drugs or biologics. The patients were randomly assigned to receive risankizumab or placebo for 24 weeks and only risankizumab during weeks 24-52. At week 24, patients receiving risankizumab vs placebo were significantly more likely to report achieving MID in Patient's Global Assessment of Disease Activity (PtGA) in both KEEPsAKE-1 (odds ratio [OR] 2.0; P < .001) and KEEPsAKE-2 (OR 1.9; P < .01) studies, with further improvement at week 52. Improvement was also seen on the Patient's Assessment of Pain, Health Assessment Questionnaire – Disability Index, Short-Form 36 Physical and Mental Component Summary scores, EQ-5D-5L, Functional Assessment of Chronic Illness Therapy – Fatigue, and Work Productivity and Activity Impairment.
An interesting insight from two studies showed the importance of nail disease in predicting treatment response. A post hoc analysis by Helliwell and colleagues of the phase 3 SEAM-PsA trial of 851 biologic/methotrexate-naive patients with active PsA who were randomly assigned to receive methotrexate monotherapy, etanercept monotherapy, or methotrexate + etanercept combination therapy showed that the presence of both dactylitis and nail disease at baseline were significantly associated with the achievement of minimal disease activity (OR 1.4; P = .0457; and OR 1.8; P = .0233, respectively), as well as low PsA Disease Activity Score (OR 1.8; P = .0014; and OR 1.8; P = .0168, respectively).
Similarly, a post hoc analysis by Baraliakos and colleagues of the phase 3b MAXIMISE trial of 473 adult patients with PsA and axial manifestations who were randomly assigned to receive secukinumab (150 or 300 mg) or placebo showed that the presence vs the absence of nail dystrophy was associated with the achievement of significantly better Assessment of SpondyloArthritis International Society 20 response in the 300 mg secukinumab group (OR 5.0; 95% CI 1.47-17.19).
Inhaled, systemic steroids linked to changes in brain structure
New research links the use of glucocorticoids with changes in white matter microstructure – which may explain the development of anxiety, depression, and other neuropsychiatric side effects related to these drugs, investigators say.
Results from a cross-sectional study showed that use of both systemic and inhaled glucocorticoids was associated with widespread reductions in fractional anisotropy (FA) and increases in mean diffusivity.
Glucocorticoids have “a whole catalogue” of adverse events, and effects on brain structure “adds to the list,” co-investigator Onno C. Meijer, PhD, professor of molecular neuroendocrinology of corticosteroids, department of medicine, Leiden University Medical Center, the Netherlands, told this news organization.
The findings should encourage clinicians to consider whether doses they are prescribing are too high, said Dr. Meijer. He added that the negative effect of glucocorticoids on the brain was also found in those using inhalers, such as patients with asthma.
The findings were published online in the BMJ Open.
Serious side effects
Glucocorticoids, a class of synthetic steroids with immunosuppressive properties, are prescribed for a wide range of conditions, including rheumatoid arthritis and asthma.
However, they are also associated with potentially serious metabolic, cardiovascular, and musculoskeletal side effects as well as neuropsychiatric side effects such as depression, mania, and cognitive impairment.
About 1 in 3 patients exposed to “quite a lot of these drugs” will experience neuropsychiatric symptoms, Dr. Meijer said.
Most previous studies that investigated effects from high levels of glucocorticoids on brain structure have been small and involved selected populations, such as those with Cushing disease.
The new study included participants from the UK Biobank, a large population-based cohort. Participants had undergone imaging and did not have a history of psychiatric disease – although they could have conditions associated with glucocorticoid use, including anxiety, depression, mania, or delirium.
The analysis included 222 patients using oral or parenteral glucocorticoids at the time of imaging (systemic group), 557 using inhaled glucocorticoids, and 24,106 not using glucocorticoids (the control group).
Inhaled steroids target the lungs, whereas a steroid in pill form “travels in the blood and reaches each and every organ and cell in the body and typically requires higher doses,” Dr. Meijer noted.
The groups were similar with respect to sex, education, and smoking status. However, the systemic glucocorticoid group was slightly older (mean age, 66.1 years vs. 63.3 years for inhaled glucocorticoid users and 63.5 years for the control group).
In addition to age, researchers adjusted for sex, education level, head position in the scanner, head size, assessment center, and year of imaging.
Imaging analyses
Imaging analyses showed systemic glucocorticoid use was associated with reduced global FA (adjusted mean difference, -3.7e-3; 95% confidence interval, -6.4e-3 to 1.0e-3), and reductions in regional FA in the body and genu of the corpus callosum versus the control group.
Inhaled glucocorticoid use was associated with reduced global FA (AMD, -2.3e-3; 95% CI, -4.0e-3 to -5.7e-4), and lower FA in the splenium of the corpus callosum and the cingulum of the hippocampus.
Global mean diffusivity was higher in systemic glucocorticoid users (AMD, 7.2e-6; 95% CI, 3.2e-6 to 1.1e-5) and inhaled glucocorticoid users (AMD, 2.7e-6; 95% CI, 1.7e-7 to 5.2e-6), compared with the control group.
The effects of glucocorticoids on white matter were “pervasive,” and the “most important finding” of the study, Dr. Meijer said. “We were impressed by the fact white matter is so sensitive to these drugs.”
He noted that it is likely that functional connectivity between brain regions is affected by use of glucocorticoids. “You could say communication between brain regions is probably somewhat impaired or challenged,” he said.
Subgroup analyses among participants using glucocorticoids chronically, defined as reported at two consecutive visits, suggested a potential dose-dependent or duration-dependent effect of glucocorticoids on white matter microstructure.
Systemic glucocorticoid use was also associated with an increase in total and grey matter volume of the caudate nucleus.
In addition, there was a significant association between inhaled glucocorticoid use and decreased grey matter volume of the amygdala, which Dr. Meijer said was surprising because studies have shown that glucocorticoids “can drive amygdala big time.”
Move away from ‘one dose for all’?
Another surprise was that the results showed no hippocampal volume differences with steroid use, Dr. Meijer noted.
The modest association between glucocorticoid use and brain volumes could indicate that white matter integrity is more sensitive to glucocorticoids than is grey matter volume, “at least at the structural level,” he said.
He added that longer use or higher doses may be necessary to also induce volumetric changes.
Participants also completed a questionnaire to assess mood over the previous 2 weeks. Systemic glucocorticoid users had more depressive symptoms, disinterest, tenseness/restlessness, and tiredness/lethargy, compared with the control group. Inhaled glucocorticoid users only reported more tiredness/lethargy.
The investigators note that mood-related effects could be linked to the condition for which glucocorticoids were prescribed: for example, rheumatoid arthritis or chronic obstructive pulmonary disease.
In terms of cognition, systemic glucocorticoid users performed significantly worse on the symbol digit substitution task, compared with participants in the control group.
In light of these findings, pharmaceutical companies that make inhaled corticosteroids “should perhaps find out if glucocorticoids can be dosed by kilogram body weight rather than simply one dose fits all,” which is currently the case, Dr. Meijer said.
Impressive, but several limitations
Commenting on the findings, E. Sherwood Brown, MD, PhD, Distinguished Chair in Psychiatric Research and professor and vice chair for clinical research, department of psychiatry, The University of Texas Southwestern Medical Center, Dallas, called the study sample size “impressive.”
In addition, the study is the first to look at systemic as well as inhaled corticosteroids, said Dr. Brown, who was not involved with the research. He noted that previously, there had been only case reports of psychiatric symptoms with inhaled corticosteroids.
That results are in the same direction but greater with systemic, compared with inhaled corticosteroids, is “particularly interesting” because this might suggest dose-dependent effects, Dr. Brown said.
He noted that cognitive differences were also only observed with systemic corticosteroids.
Some study observations, such as smaller amygdala volume with inhaled but not systemic corticosteroids, “are harder to understand,” said Dr. Brown.
However, he pointed out some study limitations. For example, data were apparently unavailable for verbal and declarative memory test data, despite corticosteroids probably affecting the hippocampus and causing memory changes.
Other drawbacks were that the dose and duration of corticosteroid use, as well as the medical histories of study participants, were not available, Dr. Brown said.
No study funding was reported. Dr. Meijer has received research grants and honorariums from Corcept Therapeutics and a speakers’ fee from Ipsen. Dr. Brown is on an advisory board for Sage Pharmaceuticals, which is developing neurosteroids (not corticosteroids) for mood disorders. He is also on a Medscape advisory board related to bipolar disorder.
A version of this article first appeared on Medscape.com.
New research links the use of glucocorticoids with changes in white matter microstructure – which may explain the development of anxiety, depression, and other neuropsychiatric side effects related to these drugs, investigators say.
Results from a cross-sectional study showed that use of both systemic and inhaled glucocorticoids was associated with widespread reductions in fractional anisotropy (FA) and increases in mean diffusivity.
Glucocorticoids have “a whole catalogue” of adverse events, and effects on brain structure “adds to the list,” co-investigator Onno C. Meijer, PhD, professor of molecular neuroendocrinology of corticosteroids, department of medicine, Leiden University Medical Center, the Netherlands, told this news organization.
The findings should encourage clinicians to consider whether doses they are prescribing are too high, said Dr. Meijer. He added that the negative effect of glucocorticoids on the brain was also found in those using inhalers, such as patients with asthma.
The findings were published online in the BMJ Open.
Serious side effects
Glucocorticoids, a class of synthetic steroids with immunosuppressive properties, are prescribed for a wide range of conditions, including rheumatoid arthritis and asthma.
However, they are also associated with potentially serious metabolic, cardiovascular, and musculoskeletal side effects as well as neuropsychiatric side effects such as depression, mania, and cognitive impairment.
About 1 in 3 patients exposed to “quite a lot of these drugs” will experience neuropsychiatric symptoms, Dr. Meijer said.
Most previous studies that investigated effects from high levels of glucocorticoids on brain structure have been small and involved selected populations, such as those with Cushing disease.
The new study included participants from the UK Biobank, a large population-based cohort. Participants had undergone imaging and did not have a history of psychiatric disease – although they could have conditions associated with glucocorticoid use, including anxiety, depression, mania, or delirium.
The analysis included 222 patients using oral or parenteral glucocorticoids at the time of imaging (systemic group), 557 using inhaled glucocorticoids, and 24,106 not using glucocorticoids (the control group).
Inhaled steroids target the lungs, whereas a steroid in pill form “travels in the blood and reaches each and every organ and cell in the body and typically requires higher doses,” Dr. Meijer noted.
The groups were similar with respect to sex, education, and smoking status. However, the systemic glucocorticoid group was slightly older (mean age, 66.1 years vs. 63.3 years for inhaled glucocorticoid users and 63.5 years for the control group).
In addition to age, researchers adjusted for sex, education level, head position in the scanner, head size, assessment center, and year of imaging.
Imaging analyses
Imaging analyses showed systemic glucocorticoid use was associated with reduced global FA (adjusted mean difference, -3.7e-3; 95% confidence interval, -6.4e-3 to 1.0e-3), and reductions in regional FA in the body and genu of the corpus callosum versus the control group.
Inhaled glucocorticoid use was associated with reduced global FA (AMD, -2.3e-3; 95% CI, -4.0e-3 to -5.7e-4), and lower FA in the splenium of the corpus callosum and the cingulum of the hippocampus.
Global mean diffusivity was higher in systemic glucocorticoid users (AMD, 7.2e-6; 95% CI, 3.2e-6 to 1.1e-5) and inhaled glucocorticoid users (AMD, 2.7e-6; 95% CI, 1.7e-7 to 5.2e-6), compared with the control group.
The effects of glucocorticoids on white matter were “pervasive,” and the “most important finding” of the study, Dr. Meijer said. “We were impressed by the fact white matter is so sensitive to these drugs.”
He noted that it is likely that functional connectivity between brain regions is affected by use of glucocorticoids. “You could say communication between brain regions is probably somewhat impaired or challenged,” he said.
Subgroup analyses among participants using glucocorticoids chronically, defined as reported at two consecutive visits, suggested a potential dose-dependent or duration-dependent effect of glucocorticoids on white matter microstructure.
Systemic glucocorticoid use was also associated with an increase in total and grey matter volume of the caudate nucleus.
In addition, there was a significant association between inhaled glucocorticoid use and decreased grey matter volume of the amygdala, which Dr. Meijer said was surprising because studies have shown that glucocorticoids “can drive amygdala big time.”
Move away from ‘one dose for all’?
Another surprise was that the results showed no hippocampal volume differences with steroid use, Dr. Meijer noted.
The modest association between glucocorticoid use and brain volumes could indicate that white matter integrity is more sensitive to glucocorticoids than is grey matter volume, “at least at the structural level,” he said.
He added that longer use or higher doses may be necessary to also induce volumetric changes.
Participants also completed a questionnaire to assess mood over the previous 2 weeks. Systemic glucocorticoid users had more depressive symptoms, disinterest, tenseness/restlessness, and tiredness/lethargy, compared with the control group. Inhaled glucocorticoid users only reported more tiredness/lethargy.
The investigators note that mood-related effects could be linked to the condition for which glucocorticoids were prescribed: for example, rheumatoid arthritis or chronic obstructive pulmonary disease.
In terms of cognition, systemic glucocorticoid users performed significantly worse on the symbol digit substitution task, compared with participants in the control group.
In light of these findings, pharmaceutical companies that make inhaled corticosteroids “should perhaps find out if glucocorticoids can be dosed by kilogram body weight rather than simply one dose fits all,” which is currently the case, Dr. Meijer said.
Impressive, but several limitations
Commenting on the findings, E. Sherwood Brown, MD, PhD, Distinguished Chair in Psychiatric Research and professor and vice chair for clinical research, department of psychiatry, The University of Texas Southwestern Medical Center, Dallas, called the study sample size “impressive.”
In addition, the study is the first to look at systemic as well as inhaled corticosteroids, said Dr. Brown, who was not involved with the research. He noted that previously, there had been only case reports of psychiatric symptoms with inhaled corticosteroids.
That results are in the same direction but greater with systemic, compared with inhaled corticosteroids, is “particularly interesting” because this might suggest dose-dependent effects, Dr. Brown said.
He noted that cognitive differences were also only observed with systemic corticosteroids.
Some study observations, such as smaller amygdala volume with inhaled but not systemic corticosteroids, “are harder to understand,” said Dr. Brown.
However, he pointed out some study limitations. For example, data were apparently unavailable for verbal and declarative memory test data, despite corticosteroids probably affecting the hippocampus and causing memory changes.
Other drawbacks were that the dose and duration of corticosteroid use, as well as the medical histories of study participants, were not available, Dr. Brown said.
No study funding was reported. Dr. Meijer has received research grants and honorariums from Corcept Therapeutics and a speakers’ fee from Ipsen. Dr. Brown is on an advisory board for Sage Pharmaceuticals, which is developing neurosteroids (not corticosteroids) for mood disorders. He is also on a Medscape advisory board related to bipolar disorder.
A version of this article first appeared on Medscape.com.
New research links the use of glucocorticoids with changes in white matter microstructure – which may explain the development of anxiety, depression, and other neuropsychiatric side effects related to these drugs, investigators say.
Results from a cross-sectional study showed that use of both systemic and inhaled glucocorticoids was associated with widespread reductions in fractional anisotropy (FA) and increases in mean diffusivity.
Glucocorticoids have “a whole catalogue” of adverse events, and effects on brain structure “adds to the list,” co-investigator Onno C. Meijer, PhD, professor of molecular neuroendocrinology of corticosteroids, department of medicine, Leiden University Medical Center, the Netherlands, told this news organization.
The findings should encourage clinicians to consider whether doses they are prescribing are too high, said Dr. Meijer. He added that the negative effect of glucocorticoids on the brain was also found in those using inhalers, such as patients with asthma.
The findings were published online in the BMJ Open.
Serious side effects
Glucocorticoids, a class of synthetic steroids with immunosuppressive properties, are prescribed for a wide range of conditions, including rheumatoid arthritis and asthma.
However, they are also associated with potentially serious metabolic, cardiovascular, and musculoskeletal side effects as well as neuropsychiatric side effects such as depression, mania, and cognitive impairment.
About 1 in 3 patients exposed to “quite a lot of these drugs” will experience neuropsychiatric symptoms, Dr. Meijer said.
Most previous studies that investigated effects from high levels of glucocorticoids on brain structure have been small and involved selected populations, such as those with Cushing disease.
The new study included participants from the UK Biobank, a large population-based cohort. Participants had undergone imaging and did not have a history of psychiatric disease – although they could have conditions associated with glucocorticoid use, including anxiety, depression, mania, or delirium.
The analysis included 222 patients using oral or parenteral glucocorticoids at the time of imaging (systemic group), 557 using inhaled glucocorticoids, and 24,106 not using glucocorticoids (the control group).
Inhaled steroids target the lungs, whereas a steroid in pill form “travels in the blood and reaches each and every organ and cell in the body and typically requires higher doses,” Dr. Meijer noted.
The groups were similar with respect to sex, education, and smoking status. However, the systemic glucocorticoid group was slightly older (mean age, 66.1 years vs. 63.3 years for inhaled glucocorticoid users and 63.5 years for the control group).
In addition to age, researchers adjusted for sex, education level, head position in the scanner, head size, assessment center, and year of imaging.
Imaging analyses
Imaging analyses showed systemic glucocorticoid use was associated with reduced global FA (adjusted mean difference, -3.7e-3; 95% confidence interval, -6.4e-3 to 1.0e-3), and reductions in regional FA in the body and genu of the corpus callosum versus the control group.
Inhaled glucocorticoid use was associated with reduced global FA (AMD, -2.3e-3; 95% CI, -4.0e-3 to -5.7e-4), and lower FA in the splenium of the corpus callosum and the cingulum of the hippocampus.
Global mean diffusivity was higher in systemic glucocorticoid users (AMD, 7.2e-6; 95% CI, 3.2e-6 to 1.1e-5) and inhaled glucocorticoid users (AMD, 2.7e-6; 95% CI, 1.7e-7 to 5.2e-6), compared with the control group.
The effects of glucocorticoids on white matter were “pervasive,” and the “most important finding” of the study, Dr. Meijer said. “We were impressed by the fact white matter is so sensitive to these drugs.”
He noted that it is likely that functional connectivity between brain regions is affected by use of glucocorticoids. “You could say communication between brain regions is probably somewhat impaired or challenged,” he said.
Subgroup analyses among participants using glucocorticoids chronically, defined as reported at two consecutive visits, suggested a potential dose-dependent or duration-dependent effect of glucocorticoids on white matter microstructure.
Systemic glucocorticoid use was also associated with an increase in total and grey matter volume of the caudate nucleus.
In addition, there was a significant association between inhaled glucocorticoid use and decreased grey matter volume of the amygdala, which Dr. Meijer said was surprising because studies have shown that glucocorticoids “can drive amygdala big time.”
Move away from ‘one dose for all’?
Another surprise was that the results showed no hippocampal volume differences with steroid use, Dr. Meijer noted.
The modest association between glucocorticoid use and brain volumes could indicate that white matter integrity is more sensitive to glucocorticoids than is grey matter volume, “at least at the structural level,” he said.
He added that longer use or higher doses may be necessary to also induce volumetric changes.
Participants also completed a questionnaire to assess mood over the previous 2 weeks. Systemic glucocorticoid users had more depressive symptoms, disinterest, tenseness/restlessness, and tiredness/lethargy, compared with the control group. Inhaled glucocorticoid users only reported more tiredness/lethargy.
The investigators note that mood-related effects could be linked to the condition for which glucocorticoids were prescribed: for example, rheumatoid arthritis or chronic obstructive pulmonary disease.
In terms of cognition, systemic glucocorticoid users performed significantly worse on the symbol digit substitution task, compared with participants in the control group.
In light of these findings, pharmaceutical companies that make inhaled corticosteroids “should perhaps find out if glucocorticoids can be dosed by kilogram body weight rather than simply one dose fits all,” which is currently the case, Dr. Meijer said.
Impressive, but several limitations
Commenting on the findings, E. Sherwood Brown, MD, PhD, Distinguished Chair in Psychiatric Research and professor and vice chair for clinical research, department of psychiatry, The University of Texas Southwestern Medical Center, Dallas, called the study sample size “impressive.”
In addition, the study is the first to look at systemic as well as inhaled corticosteroids, said Dr. Brown, who was not involved with the research. He noted that previously, there had been only case reports of psychiatric symptoms with inhaled corticosteroids.
That results are in the same direction but greater with systemic, compared with inhaled corticosteroids, is “particularly interesting” because this might suggest dose-dependent effects, Dr. Brown said.
He noted that cognitive differences were also only observed with systemic corticosteroids.
Some study observations, such as smaller amygdala volume with inhaled but not systemic corticosteroids, “are harder to understand,” said Dr. Brown.
However, he pointed out some study limitations. For example, data were apparently unavailable for verbal and declarative memory test data, despite corticosteroids probably affecting the hippocampus and causing memory changes.
Other drawbacks were that the dose and duration of corticosteroid use, as well as the medical histories of study participants, were not available, Dr. Brown said.
No study funding was reported. Dr. Meijer has received research grants and honorariums from Corcept Therapeutics and a speakers’ fee from Ipsen. Dr. Brown is on an advisory board for Sage Pharmaceuticals, which is developing neurosteroids (not corticosteroids) for mood disorders. He is also on a Medscape advisory board related to bipolar disorder.
A version of this article first appeared on Medscape.com.
FROM BMJ OPEN
OMERACT continues to set standards on research outcomes, enhancing the patient voice
Clinical research in rheumatology was suffering from an identity crisis of sorts 40 years ago. A lack of consensus across continents resulted in differing views about clinical outcome measures and judgments about treatments.
Patients were not allowed to be the generating source of a clinical outcome, according to Peter Tugwell, MSc, MD. “The only outcomes that were acceptable were clinician assessments, blood tests, and imaging,” said Dr. Tugwell, professor of medicine, epidemiology, and public health at the University of Ottawa (Ont.) and a practicing rheumatologist at Ottawa Hospital.
Clinicians were coming to different conclusions about patient responses to treatment when managing rheumatoid arthritis in clinical practice.
OMERACT sought to address this lack of uniformity. This international group, formed in 1992, leverages stakeholder groups to improve outcome measurement in rheumatology endpoints through a consensus-building, data-driven format.
It was originally known as “Outcome Measures in Rheumatoid Arthritis Clinical Trials,” but its leaders have since broadened its scope to “Outcome Measures in Rheumatology.” Over the years, it has evolved into an international network that assesses measurement across a wide variety of intervention studies. Now 30 years old, the network spans 40 active working groups and has influenced work in patient outcomes across 500 peer-reviewed publications.
The network meets every 2 years to address what is always a challenging agenda, said Dr. Tugwell, one of its founding members and chair. “There’s lots of strong opinions.” Participating in the discussions are individuals from all stages of seniority in rheumatology and clinical epidemiology, patient research partners, industry, approval agencies, and many countries who are committed to the spirit of OMERACT.
“The secret to our success has been getting world leaders to come together and have those discussions, work them through, and identify common ground in such a way that the approval agencies accept these outcome measures in clinical trials,” he added.
“My impression was the founders perceived a problem in the early 1990s and devised a consensus method in an attempt to quantify clinical parameters to define disease activity in rheumatoid arthritis – an important first step to do clinical trials and allow comparisons between them,” said Patricia Woo, CBE, FMedSci, FRCP, emeritus professor of pediatric rheumatology and previous head of the Centre for Paediatric and Adolescent Rheumatology at UCL, London. At that time, even disease definitions varied between the United States and Europe and other parts of the world, said Dr. Woo, who is not a part of OMERACT. “This was especially true for pediatric rheumatology.”
Fusing the continental divide
OMERACT arose from a need to streamline clinical outcome measures in rheumatology. Research papers during the 1980s demonstrated a lack of coherence in managing patients with rheumatoid arthritis in routine practice. In addition, the measures used to define clinical endpoints in clinical trials operated in silos – they were either too specific to a certain trial, overlapped with other concepts, or didn’t reflect changes in treatment.
Approval agencies in Europe and North America were approving only outcomes measures developed by their respective researchers. This was also true of patients they tested on. “This seemed crazy,” Dr. Tugwell said.
Dr. Tugwell was involved in the Cochrane collaboration, which conducts systematic reviews of best evidence across the world that assesses the magnitude of benefits versus harms.
To achieve this goal, “you need to pull studies from around the world,” he said. Maarten Boers, MD, PhD, a rheumatologist (and later professor of clinical epidemiology at Amsterdam University Medical Center) from the Netherlands, spent a year in Ontario, Canada, to train as a clinical epidemiologist. Together, Dr. Tugwell and Dr. Boers began discussing options to develop more streamlined outcome measures.
They initiated the first OMERACT conference in Maastricht, the Netherlands, in 1992. The Food and Drug Administration and European Medicines Agency participated, along with leaders of outcomes measurement in Europe and in North America.
Discussions centered on methods to develop outcomes in a meaningful fashion. During the first meeting, North American and European approval agencies agreed to accept each other’s studies and endpoints and patient reported outcomes.
Agreement was achieved on a preliminary set of outcome domains and measures that later became known as the WHO-ILAR (World Health Organization–International League of Associations for Rheumatology) core set. The set included seven outcome domains: tender joints, swollen joints, pain, physician global assessment, patient global assessment, physical disability, and acute phase reactants, and one additional outcome domain for studies lasting 1 year or more: radiographs of the joints.
“A proactive program was planned to test not only the validity of these endpoints, but also the methods for their measurement. This was the start of a continuing process,” OMERACT members said in a joint statement for this article. Meetings have since taken place every 2 years.
OMERACT accomplishments
OMERACT now requires buy-in from four continents: Asia, Australia, Europe, and North America.
Its leaders have developed an explicit process for gaining endorsement of core outcome domains and instrument measurement sets. To fully capture the possibilities of “what to measure,” i.e., “measurable aspects of health conditions,” OMERACT has developed a framework of concepts, core areas, and outcome domains. The key concepts are pathophysiology (with a core area termed “manifestations/abnormalities”) and impact (with core areas of “death/lifespan,” and “life impact,” and the optional area of “societal/resource use”). An outcome domain defines an element of a core area to measure the effects of a treatment, such as blood markers, pain intensity, physical function, or emotional well-being.
A core outcome domain set is developed by agreeing to at least one outcome domain within one of the three core areas. Subsequently, a core outcome measurement set is developed by agreeing to at least one applicable measurement instrument for each core outcome domain. This requires documentation of validity, summarized under three metrics: truth, discrimination, and feasibility.
OMERACT’s handbook provides tutelage on establishing and implementing core outcomes, and several workbooks offer guidance on developing core outcome domain sets, selecting instruments for core outcome measurement sets, and OMERACT methodology.
All this work has led to widespread adoption.
Approval agencies have accepted OMERACT’s filter and methods advances, which have been adopted by many research groups in rheumatology and among nonrheumatology research groups. Organizations such as the U.S. National Institutes of Health’s National Institute of Neurological Disorders and Stroke have sought its advice.
Its core outcomes have been adopted and used for approval in the great majority of studies on rheumatoid arthritis, Dr. Tugwell said.
Several BMJ articles underscore the influence and uptake of OMERACT’s core outcome set. One 2017 paper, which analyzed 273 randomized trials of rheumatoid arthritis drug treatments on ClinicalTrials.gov, found that the WHO-ILAR arthritis core outcome set was reported in 81% of the studies. “The adoption of a core outcome set has the potential to increase consistency in outcomes measured across trials and ensure that trials are more likely to measure appropriate outcomes,” the authors concluded.
Since the initial 1992 meeting, OMERACT has broadened its focus from rheumatoid arthritis to 25 other musculoskeletal conditions.
For example, other OMERACT conferences have led to consensus on core sets of measures for osteoarthritis and osteoporosis, psoriasis/psoriatic arthritis, psychosocial measures, and a core set of data for cost-effectiveness evaluations.
‘Speed is a limitation’
OMERACT is a bottom-up volunteer organization. It doesn’t represent any official organization of any clinical society. “We’ve not asked to be adopted by the American College of Rheumatology, EULAR [European Alliance of Associations for Rheumatology], or other international organizations,” Dr. Tugwell said. It offers a chance for patients, users, and doers of research to work together to agree on rigorous criteria accepted by the approval agencies and take the necessary time to work things through.
This is not a fast process, usually taking 4-6 years to initiate and establish an outcome domain set, he emphasized. “It would be beneficial to do it faster if we had the resources to meet every year. The fact is we’re a volunteer organization that meets every 2 years.”
Speed is a limitation, he acknowledged, but it’s an acceptable trade-off for doing things correctly.
The group has faced other challenges during the COVID-19 pandemic, pivoting to a virtual format that had benefits and limitations.
In one respect, moving to a virtual meeting increased uptake in participation and voting, Dr. Tugwell said. Patient participants with severe rheumatoid arthritis no longer faced the challenges of travel. “On the other hand, we didn’t have the same opportunity to achieve common ground virtually,” he said. “Where there are strong disagreements, I’m a great believer that people need to know one another. There needs to be relationship building.”
OMERACT’s emerging leader program has been a cornerstone of its in-person meetings, engaging young rheumatologists to interact with some of the leaders of outcome measurement. The virtual format dampened this process somewhat, eliminating those important “café chats” between the stakeholders.
The hope is to bring people face-to-face once more at the next meeting in May 2023. The agenda will focus on relationship building, identifying controversial areas, and bringing younger people to develop relationships, Dr. Tugwell said. OMERACT will retain a virtual option for the worldwide voting, “which will allow for more buy-in from so many more people,” he added.
A consensus on pain
The onus of developing outcome measures that move with the times is sometimes too great for one group to manage. In 2018, OMERACT became a part of the Red Hat Group (RHG), an organization conceived at the COMET (Core Outcome Measures in Effectiveness Trials) VII meeting in Amsterdam.
RHG aims to improve the choice of outcomes in health research. It includes eight groups: COMET; OMERACT; the Cochrane Skin Core Outcome Set Initiative; Grading of Recommendations, Assessment, Development and Evaluations; Center for Medical Technology Policy; COnsensus-based Standards for the selection of health Measurement Instruments; Clinical Data Interchange Standards Consortium; and Standardized Outcomes in Nephrology.
The collaboration between groups offers a “very interesting interface between consensus building as well as hard evidence,” Dr. Tugwell said. The focus goes beyond rheumatology to other clinical areas of common interest, exploring how one classifies outcome domains in terms of symptoms, life impact, or death.
Pain is an important common denominator that the RHG has evaluated.
“We believe it’s too general. We’re trying to define pain across all Red Hat Groups because it’s clear that the research community has all these different scales for defining pain severity,” Dr. Tugwell said. “We have to find a way to make ruthless decisions and rules for doing it. And of course, it has to be transparent.”
Looking ahead
As part of its ongoing work, OMERACT is evaluating the robustness of instruments that rheumatologists use as outcome measures in clinical trials, which can be a laborious process. The OMERACT Filter 2.0, part of the latest iteration of the handbook, offers strong guidance for researchers but needs a long-term strategy and key methodological support. “To that end, we set up a technical advisory group to help people in the instrument selection work and that remains an ongoing process,” OMERACT leaders said in their joint statement.
OMERACT is looking at opportunities to create benchmark processes for developing core sets outside of rheumatology and a methodology around outcome measures such as contextual factors, composites, and surrogates.
It will also be taking a step back to solicit opinions from the approval agencies represented by the OMERACT membership on the OMERACT handbook.
The goal is to make sure the handbook aligns with everyone else’s approval and labeling requirements.
OMERACT’s patient participants bring important perspectives
OMERACT over the years has sought to become a more patient-centered group. Patients have been involved in OMERACT activities since its sixth meeting, forming an independent, yet integrated, group within the network. They have their own steering committee and produced and helped to update a glossary for OMERACT patients and professionals.
Catherine (McGowan) Hofstetter, who was diagnosed with rheumatoid arthritis 30 years ago, chairs OMERACT’s Patient Research Partners Support Team. In a Q&A, she discussed the importance of patient voices and OMERACT’s plans to further educate and include patients in the dialogue on outcomes.
Question: Have patients always been a part of OMERACT meetings?
Answer: Patients have been involved with OMERACT since 2002. The patient voice adds relevance to all the work that OMERACT does. You can’t begin to talk about outcomes unless there is a patient at the table with lived experience.
Q: Can you cite a few examples of how the patient voice enriches the conversation on outcomes research?
A: Outcomes and priorities that are important to patients are often completely different than those of the clinician. For instance, a work outcome is important to someone who doesn’t have any medical insurance or disability insurance, so that you can ensure that there is food on the table and a roof over your head. Or it may be important to someone because the employment provides medical and disability insurance to provide security for them and their family. These are two different perspectives on work and therefore work priorities and outcomes.
Q: What have been some of the challenges of getting patients to participate?
A: Training patients is one challenge. OMERACT’s work has a very steep learning curve, and while the basics are the same between the groups in terms of looking at what we measure and how we measure it, the nuances of different working groups require a lot of time and energy to be comfortable enough with the work, and then be confident enough to bring your perspective and lived experience to the table. It’s also a very accomplished group, which can be quite intimidating. Self-disclosure is a very personal and intimate undertaking that requires patience, compassion, and respect.
Q: Are there any plans to enhance patient engagement?
A: When we had OMERACT 2020 it was a virtual conference that took place over about 6 months. We had far more patient research partners [PRPs] participate than we have ever had at any OMERACT face-to-face meeting. There is a desire and passion on the part of patients to lend their voices to the work. The working groups meet virtually throughout the year to advance their agendas, and PRPs are a part of each of the working groups.
Hopefully, we can start working toward including more voices at the conferences by enabling a hybrid model. The PRP Support Team will begin engaging patients this fall with education, mentoring, and team-building exercises so by the time we meet in person in May 2023, they will have enough background knowledge and information to give them the confidence that will enhance their experience at the face-to-face meeting.
We also need to ensure that those patients who want to stay engaged can. This means that the education and training should continue long after the face-to-face meeting is over. We need to build capacity in the PRP group and look to succession planning and be a resource to working groups struggling to find PRPs to work with them on a longer-term basis.
Clinical research in rheumatology was suffering from an identity crisis of sorts 40 years ago. A lack of consensus across continents resulted in differing views about clinical outcome measures and judgments about treatments.
Patients were not allowed to be the generating source of a clinical outcome, according to Peter Tugwell, MSc, MD. “The only outcomes that were acceptable were clinician assessments, blood tests, and imaging,” said Dr. Tugwell, professor of medicine, epidemiology, and public health at the University of Ottawa (Ont.) and a practicing rheumatologist at Ottawa Hospital.
Clinicians were coming to different conclusions about patient responses to treatment when managing rheumatoid arthritis in clinical practice.
OMERACT sought to address this lack of uniformity. This international group, formed in 1992, leverages stakeholder groups to improve outcome measurement in rheumatology endpoints through a consensus-building, data-driven format.
It was originally known as “Outcome Measures in Rheumatoid Arthritis Clinical Trials,” but its leaders have since broadened its scope to “Outcome Measures in Rheumatology.” Over the years, it has evolved into an international network that assesses measurement across a wide variety of intervention studies. Now 30 years old, the network spans 40 active working groups and has influenced work in patient outcomes across 500 peer-reviewed publications.
The network meets every 2 years to address what is always a challenging agenda, said Dr. Tugwell, one of its founding members and chair. “There’s lots of strong opinions.” Participating in the discussions are individuals from all stages of seniority in rheumatology and clinical epidemiology, patient research partners, industry, approval agencies, and many countries who are committed to the spirit of OMERACT.
“The secret to our success has been getting world leaders to come together and have those discussions, work them through, and identify common ground in such a way that the approval agencies accept these outcome measures in clinical trials,” he added.
“My impression was the founders perceived a problem in the early 1990s and devised a consensus method in an attempt to quantify clinical parameters to define disease activity in rheumatoid arthritis – an important first step to do clinical trials and allow comparisons between them,” said Patricia Woo, CBE, FMedSci, FRCP, emeritus professor of pediatric rheumatology and previous head of the Centre for Paediatric and Adolescent Rheumatology at UCL, London. At that time, even disease definitions varied between the United States and Europe and other parts of the world, said Dr. Woo, who is not a part of OMERACT. “This was especially true for pediatric rheumatology.”
Fusing the continental divide
OMERACT arose from a need to streamline clinical outcome measures in rheumatology. Research papers during the 1980s demonstrated a lack of coherence in managing patients with rheumatoid arthritis in routine practice. In addition, the measures used to define clinical endpoints in clinical trials operated in silos – they were either too specific to a certain trial, overlapped with other concepts, or didn’t reflect changes in treatment.
Approval agencies in Europe and North America were approving only outcomes measures developed by their respective researchers. This was also true of patients they tested on. “This seemed crazy,” Dr. Tugwell said.
Dr. Tugwell was involved in the Cochrane collaboration, which conducts systematic reviews of best evidence across the world that assesses the magnitude of benefits versus harms.
To achieve this goal, “you need to pull studies from around the world,” he said. Maarten Boers, MD, PhD, a rheumatologist (and later professor of clinical epidemiology at Amsterdam University Medical Center) from the Netherlands, spent a year in Ontario, Canada, to train as a clinical epidemiologist. Together, Dr. Tugwell and Dr. Boers began discussing options to develop more streamlined outcome measures.
They initiated the first OMERACT conference in Maastricht, the Netherlands, in 1992. The Food and Drug Administration and European Medicines Agency participated, along with leaders of outcomes measurement in Europe and in North America.
Discussions centered on methods to develop outcomes in a meaningful fashion. During the first meeting, North American and European approval agencies agreed to accept each other’s studies and endpoints and patient reported outcomes.
Agreement was achieved on a preliminary set of outcome domains and measures that later became known as the WHO-ILAR (World Health Organization–International League of Associations for Rheumatology) core set. The set included seven outcome domains: tender joints, swollen joints, pain, physician global assessment, patient global assessment, physical disability, and acute phase reactants, and one additional outcome domain for studies lasting 1 year or more: radiographs of the joints.
“A proactive program was planned to test not only the validity of these endpoints, but also the methods for their measurement. This was the start of a continuing process,” OMERACT members said in a joint statement for this article. Meetings have since taken place every 2 years.
OMERACT accomplishments
OMERACT now requires buy-in from four continents: Asia, Australia, Europe, and North America.
Its leaders have developed an explicit process for gaining endorsement of core outcome domains and instrument measurement sets. To fully capture the possibilities of “what to measure,” i.e., “measurable aspects of health conditions,” OMERACT has developed a framework of concepts, core areas, and outcome domains. The key concepts are pathophysiology (with a core area termed “manifestations/abnormalities”) and impact (with core areas of “death/lifespan,” and “life impact,” and the optional area of “societal/resource use”). An outcome domain defines an element of a core area to measure the effects of a treatment, such as blood markers, pain intensity, physical function, or emotional well-being.
A core outcome domain set is developed by agreeing to at least one outcome domain within one of the three core areas. Subsequently, a core outcome measurement set is developed by agreeing to at least one applicable measurement instrument for each core outcome domain. This requires documentation of validity, summarized under three metrics: truth, discrimination, and feasibility.
OMERACT’s handbook provides tutelage on establishing and implementing core outcomes, and several workbooks offer guidance on developing core outcome domain sets, selecting instruments for core outcome measurement sets, and OMERACT methodology.
All this work has led to widespread adoption.
Approval agencies have accepted OMERACT’s filter and methods advances, which have been adopted by many research groups in rheumatology and among nonrheumatology research groups. Organizations such as the U.S. National Institutes of Health’s National Institute of Neurological Disorders and Stroke have sought its advice.
Its core outcomes have been adopted and used for approval in the great majority of studies on rheumatoid arthritis, Dr. Tugwell said.
Several BMJ articles underscore the influence and uptake of OMERACT’s core outcome set. One 2017 paper, which analyzed 273 randomized trials of rheumatoid arthritis drug treatments on ClinicalTrials.gov, found that the WHO-ILAR arthritis core outcome set was reported in 81% of the studies. “The adoption of a core outcome set has the potential to increase consistency in outcomes measured across trials and ensure that trials are more likely to measure appropriate outcomes,” the authors concluded.
Since the initial 1992 meeting, OMERACT has broadened its focus from rheumatoid arthritis to 25 other musculoskeletal conditions.
For example, other OMERACT conferences have led to consensus on core sets of measures for osteoarthritis and osteoporosis, psoriasis/psoriatic arthritis, psychosocial measures, and a core set of data for cost-effectiveness evaluations.
‘Speed is a limitation’
OMERACT is a bottom-up volunteer organization. It doesn’t represent any official organization of any clinical society. “We’ve not asked to be adopted by the American College of Rheumatology, EULAR [European Alliance of Associations for Rheumatology], or other international organizations,” Dr. Tugwell said. It offers a chance for patients, users, and doers of research to work together to agree on rigorous criteria accepted by the approval agencies and take the necessary time to work things through.
This is not a fast process, usually taking 4-6 years to initiate and establish an outcome domain set, he emphasized. “It would be beneficial to do it faster if we had the resources to meet every year. The fact is we’re a volunteer organization that meets every 2 years.”
Speed is a limitation, he acknowledged, but it’s an acceptable trade-off for doing things correctly.
The group has faced other challenges during the COVID-19 pandemic, pivoting to a virtual format that had benefits and limitations.
In one respect, moving to a virtual meeting increased uptake in participation and voting, Dr. Tugwell said. Patient participants with severe rheumatoid arthritis no longer faced the challenges of travel. “On the other hand, we didn’t have the same opportunity to achieve common ground virtually,” he said. “Where there are strong disagreements, I’m a great believer that people need to know one another. There needs to be relationship building.”
OMERACT’s emerging leader program has been a cornerstone of its in-person meetings, engaging young rheumatologists to interact with some of the leaders of outcome measurement. The virtual format dampened this process somewhat, eliminating those important “café chats” between the stakeholders.
The hope is to bring people face-to-face once more at the next meeting in May 2023. The agenda will focus on relationship building, identifying controversial areas, and bringing younger people to develop relationships, Dr. Tugwell said. OMERACT will retain a virtual option for the worldwide voting, “which will allow for more buy-in from so many more people,” he added.
A consensus on pain
The onus of developing outcome measures that move with the times is sometimes too great for one group to manage. In 2018, OMERACT became a part of the Red Hat Group (RHG), an organization conceived at the COMET (Core Outcome Measures in Effectiveness Trials) VII meeting in Amsterdam.
RHG aims to improve the choice of outcomes in health research. It includes eight groups: COMET; OMERACT; the Cochrane Skin Core Outcome Set Initiative; Grading of Recommendations, Assessment, Development and Evaluations; Center for Medical Technology Policy; COnsensus-based Standards for the selection of health Measurement Instruments; Clinical Data Interchange Standards Consortium; and Standardized Outcomes in Nephrology.
The collaboration between groups offers a “very interesting interface between consensus building as well as hard evidence,” Dr. Tugwell said. The focus goes beyond rheumatology to other clinical areas of common interest, exploring how one classifies outcome domains in terms of symptoms, life impact, or death.
Pain is an important common denominator that the RHG has evaluated.
“We believe it’s too general. We’re trying to define pain across all Red Hat Groups because it’s clear that the research community has all these different scales for defining pain severity,” Dr. Tugwell said. “We have to find a way to make ruthless decisions and rules for doing it. And of course, it has to be transparent.”
Looking ahead
As part of its ongoing work, OMERACT is evaluating the robustness of instruments that rheumatologists use as outcome measures in clinical trials, which can be a laborious process. The OMERACT Filter 2.0, part of the latest iteration of the handbook, offers strong guidance for researchers but needs a long-term strategy and key methodological support. “To that end, we set up a technical advisory group to help people in the instrument selection work and that remains an ongoing process,” OMERACT leaders said in their joint statement.
OMERACT is looking at opportunities to create benchmark processes for developing core sets outside of rheumatology and a methodology around outcome measures such as contextual factors, composites, and surrogates.
It will also be taking a step back to solicit opinions from the approval agencies represented by the OMERACT membership on the OMERACT handbook.
The goal is to make sure the handbook aligns with everyone else’s approval and labeling requirements.
OMERACT’s patient participants bring important perspectives
OMERACT over the years has sought to become a more patient-centered group. Patients have been involved in OMERACT activities since its sixth meeting, forming an independent, yet integrated, group within the network. They have their own steering committee and produced and helped to update a glossary for OMERACT patients and professionals.
Catherine (McGowan) Hofstetter, who was diagnosed with rheumatoid arthritis 30 years ago, chairs OMERACT’s Patient Research Partners Support Team. In a Q&A, she discussed the importance of patient voices and OMERACT’s plans to further educate and include patients in the dialogue on outcomes.
Question: Have patients always been a part of OMERACT meetings?
Answer: Patients have been involved with OMERACT since 2002. The patient voice adds relevance to all the work that OMERACT does. You can’t begin to talk about outcomes unless there is a patient at the table with lived experience.
Q: Can you cite a few examples of how the patient voice enriches the conversation on outcomes research?
A: Outcomes and priorities that are important to patients are often completely different than those of the clinician. For instance, a work outcome is important to someone who doesn’t have any medical insurance or disability insurance, so that you can ensure that there is food on the table and a roof over your head. Or it may be important to someone because the employment provides medical and disability insurance to provide security for them and their family. These are two different perspectives on work and therefore work priorities and outcomes.
Q: What have been some of the challenges of getting patients to participate?
A: Training patients is one challenge. OMERACT’s work has a very steep learning curve, and while the basics are the same between the groups in terms of looking at what we measure and how we measure it, the nuances of different working groups require a lot of time and energy to be comfortable enough with the work, and then be confident enough to bring your perspective and lived experience to the table. It’s also a very accomplished group, which can be quite intimidating. Self-disclosure is a very personal and intimate undertaking that requires patience, compassion, and respect.
Q: Are there any plans to enhance patient engagement?
A: When we had OMERACT 2020 it was a virtual conference that took place over about 6 months. We had far more patient research partners [PRPs] participate than we have ever had at any OMERACT face-to-face meeting. There is a desire and passion on the part of patients to lend their voices to the work. The working groups meet virtually throughout the year to advance their agendas, and PRPs are a part of each of the working groups.
Hopefully, we can start working toward including more voices at the conferences by enabling a hybrid model. The PRP Support Team will begin engaging patients this fall with education, mentoring, and team-building exercises so by the time we meet in person in May 2023, they will have enough background knowledge and information to give them the confidence that will enhance their experience at the face-to-face meeting.
We also need to ensure that those patients who want to stay engaged can. This means that the education and training should continue long after the face-to-face meeting is over. We need to build capacity in the PRP group and look to succession planning and be a resource to working groups struggling to find PRPs to work with them on a longer-term basis.
Clinical research in rheumatology was suffering from an identity crisis of sorts 40 years ago. A lack of consensus across continents resulted in differing views about clinical outcome measures and judgments about treatments.
Patients were not allowed to be the generating source of a clinical outcome, according to Peter Tugwell, MSc, MD. “The only outcomes that were acceptable were clinician assessments, blood tests, and imaging,” said Dr. Tugwell, professor of medicine, epidemiology, and public health at the University of Ottawa (Ont.) and a practicing rheumatologist at Ottawa Hospital.
Clinicians were coming to different conclusions about patient responses to treatment when managing rheumatoid arthritis in clinical practice.
OMERACT sought to address this lack of uniformity. This international group, formed in 1992, leverages stakeholder groups to improve outcome measurement in rheumatology endpoints through a consensus-building, data-driven format.
It was originally known as “Outcome Measures in Rheumatoid Arthritis Clinical Trials,” but its leaders have since broadened its scope to “Outcome Measures in Rheumatology.” Over the years, it has evolved into an international network that assesses measurement across a wide variety of intervention studies. Now 30 years old, the network spans 40 active working groups and has influenced work in patient outcomes across 500 peer-reviewed publications.
The network meets every 2 years to address what is always a challenging agenda, said Dr. Tugwell, one of its founding members and chair. “There’s lots of strong opinions.” Participating in the discussions are individuals from all stages of seniority in rheumatology and clinical epidemiology, patient research partners, industry, approval agencies, and many countries who are committed to the spirit of OMERACT.
“The secret to our success has been getting world leaders to come together and have those discussions, work them through, and identify common ground in such a way that the approval agencies accept these outcome measures in clinical trials,” he added.
“My impression was the founders perceived a problem in the early 1990s and devised a consensus method in an attempt to quantify clinical parameters to define disease activity in rheumatoid arthritis – an important first step to do clinical trials and allow comparisons between them,” said Patricia Woo, CBE, FMedSci, FRCP, emeritus professor of pediatric rheumatology and previous head of the Centre for Paediatric and Adolescent Rheumatology at UCL, London. At that time, even disease definitions varied between the United States and Europe and other parts of the world, said Dr. Woo, who is not a part of OMERACT. “This was especially true for pediatric rheumatology.”
Fusing the continental divide
OMERACT arose from a need to streamline clinical outcome measures in rheumatology. Research papers during the 1980s demonstrated a lack of coherence in managing patients with rheumatoid arthritis in routine practice. In addition, the measures used to define clinical endpoints in clinical trials operated in silos – they were either too specific to a certain trial, overlapped with other concepts, or didn’t reflect changes in treatment.
Approval agencies in Europe and North America were approving only outcomes measures developed by their respective researchers. This was also true of patients they tested on. “This seemed crazy,” Dr. Tugwell said.
Dr. Tugwell was involved in the Cochrane collaboration, which conducts systematic reviews of best evidence across the world that assesses the magnitude of benefits versus harms.
To achieve this goal, “you need to pull studies from around the world,” he said. Maarten Boers, MD, PhD, a rheumatologist (and later professor of clinical epidemiology at Amsterdam University Medical Center) from the Netherlands, spent a year in Ontario, Canada, to train as a clinical epidemiologist. Together, Dr. Tugwell and Dr. Boers began discussing options to develop more streamlined outcome measures.
They initiated the first OMERACT conference in Maastricht, the Netherlands, in 1992. The Food and Drug Administration and European Medicines Agency participated, along with leaders of outcomes measurement in Europe and in North America.
Discussions centered on methods to develop outcomes in a meaningful fashion. During the first meeting, North American and European approval agencies agreed to accept each other’s studies and endpoints and patient reported outcomes.
Agreement was achieved on a preliminary set of outcome domains and measures that later became known as the WHO-ILAR (World Health Organization–International League of Associations for Rheumatology) core set. The set included seven outcome domains: tender joints, swollen joints, pain, physician global assessment, patient global assessment, physical disability, and acute phase reactants, and one additional outcome domain for studies lasting 1 year or more: radiographs of the joints.
“A proactive program was planned to test not only the validity of these endpoints, but also the methods for their measurement. This was the start of a continuing process,” OMERACT members said in a joint statement for this article. Meetings have since taken place every 2 years.
OMERACT accomplishments
OMERACT now requires buy-in from four continents: Asia, Australia, Europe, and North America.
Its leaders have developed an explicit process for gaining endorsement of core outcome domains and instrument measurement sets. To fully capture the possibilities of “what to measure,” i.e., “measurable aspects of health conditions,” OMERACT has developed a framework of concepts, core areas, and outcome domains. The key concepts are pathophysiology (with a core area termed “manifestations/abnormalities”) and impact (with core areas of “death/lifespan,” and “life impact,” and the optional area of “societal/resource use”). An outcome domain defines an element of a core area to measure the effects of a treatment, such as blood markers, pain intensity, physical function, or emotional well-being.
A core outcome domain set is developed by agreeing to at least one outcome domain within one of the three core areas. Subsequently, a core outcome measurement set is developed by agreeing to at least one applicable measurement instrument for each core outcome domain. This requires documentation of validity, summarized under three metrics: truth, discrimination, and feasibility.
OMERACT’s handbook provides tutelage on establishing and implementing core outcomes, and several workbooks offer guidance on developing core outcome domain sets, selecting instruments for core outcome measurement sets, and OMERACT methodology.
All this work has led to widespread adoption.
Approval agencies have accepted OMERACT’s filter and methods advances, which have been adopted by many research groups in rheumatology and among nonrheumatology research groups. Organizations such as the U.S. National Institutes of Health’s National Institute of Neurological Disorders and Stroke have sought its advice.
Its core outcomes have been adopted and used for approval in the great majority of studies on rheumatoid arthritis, Dr. Tugwell said.
Several BMJ articles underscore the influence and uptake of OMERACT’s core outcome set. One 2017 paper, which analyzed 273 randomized trials of rheumatoid arthritis drug treatments on ClinicalTrials.gov, found that the WHO-ILAR arthritis core outcome set was reported in 81% of the studies. “The adoption of a core outcome set has the potential to increase consistency in outcomes measured across trials and ensure that trials are more likely to measure appropriate outcomes,” the authors concluded.
Since the initial 1992 meeting, OMERACT has broadened its focus from rheumatoid arthritis to 25 other musculoskeletal conditions.
For example, other OMERACT conferences have led to consensus on core sets of measures for osteoarthritis and osteoporosis, psoriasis/psoriatic arthritis, psychosocial measures, and a core set of data for cost-effectiveness evaluations.
‘Speed is a limitation’
OMERACT is a bottom-up volunteer organization. It doesn’t represent any official organization of any clinical society. “We’ve not asked to be adopted by the American College of Rheumatology, EULAR [European Alliance of Associations for Rheumatology], or other international organizations,” Dr. Tugwell said. It offers a chance for patients, users, and doers of research to work together to agree on rigorous criteria accepted by the approval agencies and take the necessary time to work things through.
This is not a fast process, usually taking 4-6 years to initiate and establish an outcome domain set, he emphasized. “It would be beneficial to do it faster if we had the resources to meet every year. The fact is we’re a volunteer organization that meets every 2 years.”
Speed is a limitation, he acknowledged, but it’s an acceptable trade-off for doing things correctly.
The group has faced other challenges during the COVID-19 pandemic, pivoting to a virtual format that had benefits and limitations.
In one respect, moving to a virtual meeting increased uptake in participation and voting, Dr. Tugwell said. Patient participants with severe rheumatoid arthritis no longer faced the challenges of travel. “On the other hand, we didn’t have the same opportunity to achieve common ground virtually,” he said. “Where there are strong disagreements, I’m a great believer that people need to know one another. There needs to be relationship building.”
OMERACT’s emerging leader program has been a cornerstone of its in-person meetings, engaging young rheumatologists to interact with some of the leaders of outcome measurement. The virtual format dampened this process somewhat, eliminating those important “café chats” between the stakeholders.
The hope is to bring people face-to-face once more at the next meeting in May 2023. The agenda will focus on relationship building, identifying controversial areas, and bringing younger people to develop relationships, Dr. Tugwell said. OMERACT will retain a virtual option for the worldwide voting, “which will allow for more buy-in from so many more people,” he added.
A consensus on pain
The onus of developing outcome measures that move with the times is sometimes too great for one group to manage. In 2018, OMERACT became a part of the Red Hat Group (RHG), an organization conceived at the COMET (Core Outcome Measures in Effectiveness Trials) VII meeting in Amsterdam.
RHG aims to improve the choice of outcomes in health research. It includes eight groups: COMET; OMERACT; the Cochrane Skin Core Outcome Set Initiative; Grading of Recommendations, Assessment, Development and Evaluations; Center for Medical Technology Policy; COnsensus-based Standards for the selection of health Measurement Instruments; Clinical Data Interchange Standards Consortium; and Standardized Outcomes in Nephrology.
The collaboration between groups offers a “very interesting interface between consensus building as well as hard evidence,” Dr. Tugwell said. The focus goes beyond rheumatology to other clinical areas of common interest, exploring how one classifies outcome domains in terms of symptoms, life impact, or death.
Pain is an important common denominator that the RHG has evaluated.
“We believe it’s too general. We’re trying to define pain across all Red Hat Groups because it’s clear that the research community has all these different scales for defining pain severity,” Dr. Tugwell said. “We have to find a way to make ruthless decisions and rules for doing it. And of course, it has to be transparent.”
Looking ahead
As part of its ongoing work, OMERACT is evaluating the robustness of instruments that rheumatologists use as outcome measures in clinical trials, which can be a laborious process. The OMERACT Filter 2.0, part of the latest iteration of the handbook, offers strong guidance for researchers but needs a long-term strategy and key methodological support. “To that end, we set up a technical advisory group to help people in the instrument selection work and that remains an ongoing process,” OMERACT leaders said in their joint statement.
OMERACT is looking at opportunities to create benchmark processes for developing core sets outside of rheumatology and a methodology around outcome measures such as contextual factors, composites, and surrogates.
It will also be taking a step back to solicit opinions from the approval agencies represented by the OMERACT membership on the OMERACT handbook.
The goal is to make sure the handbook aligns with everyone else’s approval and labeling requirements.
OMERACT’s patient participants bring important perspectives
OMERACT over the years has sought to become a more patient-centered group. Patients have been involved in OMERACT activities since its sixth meeting, forming an independent, yet integrated, group within the network. They have their own steering committee and produced and helped to update a glossary for OMERACT patients and professionals.
Catherine (McGowan) Hofstetter, who was diagnosed with rheumatoid arthritis 30 years ago, chairs OMERACT’s Patient Research Partners Support Team. In a Q&A, she discussed the importance of patient voices and OMERACT’s plans to further educate and include patients in the dialogue on outcomes.
Question: Have patients always been a part of OMERACT meetings?
Answer: Patients have been involved with OMERACT since 2002. The patient voice adds relevance to all the work that OMERACT does. You can’t begin to talk about outcomes unless there is a patient at the table with lived experience.
Q: Can you cite a few examples of how the patient voice enriches the conversation on outcomes research?
A: Outcomes and priorities that are important to patients are often completely different than those of the clinician. For instance, a work outcome is important to someone who doesn’t have any medical insurance or disability insurance, so that you can ensure that there is food on the table and a roof over your head. Or it may be important to someone because the employment provides medical and disability insurance to provide security for them and their family. These are two different perspectives on work and therefore work priorities and outcomes.
Q: What have been some of the challenges of getting patients to participate?
A: Training patients is one challenge. OMERACT’s work has a very steep learning curve, and while the basics are the same between the groups in terms of looking at what we measure and how we measure it, the nuances of different working groups require a lot of time and energy to be comfortable enough with the work, and then be confident enough to bring your perspective and lived experience to the table. It’s also a very accomplished group, which can be quite intimidating. Self-disclosure is a very personal and intimate undertaking that requires patience, compassion, and respect.
Q: Are there any plans to enhance patient engagement?
A: When we had OMERACT 2020 it was a virtual conference that took place over about 6 months. We had far more patient research partners [PRPs] participate than we have ever had at any OMERACT face-to-face meeting. There is a desire and passion on the part of patients to lend their voices to the work. The working groups meet virtually throughout the year to advance their agendas, and PRPs are a part of each of the working groups.
Hopefully, we can start working toward including more voices at the conferences by enabling a hybrid model. The PRP Support Team will begin engaging patients this fall with education, mentoring, and team-building exercises so by the time we meet in person in May 2023, they will have enough background knowledge and information to give them the confidence that will enhance their experience at the face-to-face meeting.
We also need to ensure that those patients who want to stay engaged can. This means that the education and training should continue long after the face-to-face meeting is over. We need to build capacity in the PRP group and look to succession planning and be a resource to working groups struggling to find PRPs to work with them on a longer-term basis.
Autoimmune disease patients’ waxing, waning response to COVID vaccination studied in-depth
A new study in The Lancet Rheumatology examines the strength and duration of SARS-CoV-2 vaccine–induced immunoglobulin-G antibody responses over time for patients with a variety of autoimmune diseases, compared with healthy controls.
The presence of humoral antibodies to SARS-CoV-2 has been shown to correlate with protection against COVID infection. But for patients with immune-mediated inflammatory diseases (IMIDs), host response to COVID infection or to vaccination is affected by the immune dysfunction imposed by the IMID and by the use of immune-modulating drugs to treat it.
This new study finds a weaker – as shown previously – and less sustained immune response to SARS-CoV-2 vaccines in patients with a variety of IMIDs, including rheumatoid arthritis, spondyloarthritis, psoriasis, inflammatory bowel diseases, and other systemic autoimmune diseases such as lupus. It also points toward the possibility of adjusting treatment and vaccination schedules and strategies for these patients based on their antibody levels, among other factors, to preserve best protection against severe COVID.
“It is important to assess immune response in these patients to see if they still have protection against severe COVID infection,” said lead author David Simon, MD, senior clinical scientist in clinical immunology and rheumatology at University Hospital Erlangen (Germany). “We know that antibody response is an immune correlate. Therefore, it is important to see how large and durable the immune response is to the coronavirus vaccine in these IMID patients, and whether specific drugs or therapies have negative effects on their immune response.”
What was studied?
For this large prospective cohort study, researchers registered 5076 coronavirus-vaccinated individuals. They analyzed serum samples obtained between December 15, 2020, and December 1, 2021, from 2,535 patients diagnosed with IMIDs and participating in a prospective coronavirus study program at the Deutsches Zentrum Immuntherapie in Erlangen. The IMID patients had a mean age of 55.0 years, and 58.9% were women.
A healthy control group of 1,198 individuals without IMID who had a mean age of 40.7 years, including 53.8% men, was also recruited for the analysis. All approved coronavirus vaccines were included, following standard vaccination schedules. Antibody response was measured over time by an enzyme-linked immunosorbent assay from 8 weeks after first vaccination to week 40.
Among the findings, the healthy controls had higher postvaccine antibody levels than did those with IMIDs. But the majority of vaccinated patients with IMID were able to build up a humoral immune response to SARS-CoV-2. Patients who were taking B-cell inhibitors like rituximab (Rituxan, Genentech; and biosimilars) and T-cell inhibitors like abatacept (Orencia, Bristol Myers Squibb) for IMIDs had significantly poorer antibody response.
Greater age and the use of combination therapies for IMIDs, compared with monotherapy, further reduced immune response to the vaccine. In terms of vaccination modality, messenger RNA–based vaccines induced higher antibody levels than did vector-based vaccines. The researchers noted that patients with IMID who were given a third vaccine dose could actually catch up well with the antibody responses observed in healthy controls.
“We looked at whether different IMIDs had a different humoral response, and we also assessed if there are effects from different therapeutic strategies,” Dr. Simon explained. “It doesn’t matter so much what kind of IMID patients have; much more important is the specific drug treatment and its impact on their antibody response.” Some participants were advised to briefly stop taking some immunosuppressive treatments before or after vaccination.
One of Dr. Simon’s coauthors, statistician and rheumatologist Koray Tascilar, MD, added, “This research is important because we looked not only at who responded less, which has been previously established, but who are at greater risk of losing their immune response, and how quickly.”
Need to take care
“Most treatments we as rheumatologists give to our patients don’t affect their SARS-CoV-2 humoral response,” Dr. Simon said. “However, there are specific drugs that are associated with lower antibody response. With respect to those drugs, we have to be more careful.”
It is important to be able to tell patients which drugs are safe and won’t have a negative impact on their immune response to vaccinations, Dr. Tascilar said. “But it would be too strong to say we’re ready to choose therapies based on their potential impact on protection against COVID. Yes, there is a risk from catching COVID, but we need to balance that risk with the risk of not giving patients the medications that are necessary to treat their rheumatologic condition.”
These diseases are serious, sometimes life-threatening. “We might think of strategies for how to mitigate the risk of underprotection from COVID that is brought about by these treatments,” he said. For example, offering boosters sooner or more frequently, or prophylactically treating with monoclonal antibodies.
“This study, along other recent studies, has found that antibody levels in patients with immune-mediated diseases wane more rapidly than in healthy controls, and this is especially true of those on medications that interfere with the B and T cells and anticytokine therapies,” Rebecca Haberman, MD, assistant professor, division of rheumatology, New York University Langone Health, noted in an email to this news organization.
“While there is no known antibody level that specifically correlates with clinical protection, and each patient needs to be thought of individually, these findings support the use of supplemental booster dosing in patients with immune-mediated inflammatory diseases,” Dr. Haberman said, adding that her own research in this area has shown similar results.
“As a rheumatologist, I would be more likely to encourage my patients – especially those on immunomodulatory medications – to get boosted.”
Dr. Tascilar said his study does not directly answer the question of whether an earlier booster shot would be an effective strategy for patients with IMID. “In our department, we have an early boosting strategy, based on level of immune response.” But the decision of revaccination or not, and when, is based on a number of factors, not only on the level of antibodies. “It’s just part of the instruments we are using.”
The study was supported by the Deutsche Forschungsgemeinschaft. Dr. Simon and Dr. Tascilar declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new study in The Lancet Rheumatology examines the strength and duration of SARS-CoV-2 vaccine–induced immunoglobulin-G antibody responses over time for patients with a variety of autoimmune diseases, compared with healthy controls.
The presence of humoral antibodies to SARS-CoV-2 has been shown to correlate with protection against COVID infection. But for patients with immune-mediated inflammatory diseases (IMIDs), host response to COVID infection or to vaccination is affected by the immune dysfunction imposed by the IMID and by the use of immune-modulating drugs to treat it.
This new study finds a weaker – as shown previously – and less sustained immune response to SARS-CoV-2 vaccines in patients with a variety of IMIDs, including rheumatoid arthritis, spondyloarthritis, psoriasis, inflammatory bowel diseases, and other systemic autoimmune diseases such as lupus. It also points toward the possibility of adjusting treatment and vaccination schedules and strategies for these patients based on their antibody levels, among other factors, to preserve best protection against severe COVID.
“It is important to assess immune response in these patients to see if they still have protection against severe COVID infection,” said lead author David Simon, MD, senior clinical scientist in clinical immunology and rheumatology at University Hospital Erlangen (Germany). “We know that antibody response is an immune correlate. Therefore, it is important to see how large and durable the immune response is to the coronavirus vaccine in these IMID patients, and whether specific drugs or therapies have negative effects on their immune response.”
What was studied?
For this large prospective cohort study, researchers registered 5076 coronavirus-vaccinated individuals. They analyzed serum samples obtained between December 15, 2020, and December 1, 2021, from 2,535 patients diagnosed with IMIDs and participating in a prospective coronavirus study program at the Deutsches Zentrum Immuntherapie in Erlangen. The IMID patients had a mean age of 55.0 years, and 58.9% were women.
A healthy control group of 1,198 individuals without IMID who had a mean age of 40.7 years, including 53.8% men, was also recruited for the analysis. All approved coronavirus vaccines were included, following standard vaccination schedules. Antibody response was measured over time by an enzyme-linked immunosorbent assay from 8 weeks after first vaccination to week 40.
Among the findings, the healthy controls had higher postvaccine antibody levels than did those with IMIDs. But the majority of vaccinated patients with IMID were able to build up a humoral immune response to SARS-CoV-2. Patients who were taking B-cell inhibitors like rituximab (Rituxan, Genentech; and biosimilars) and T-cell inhibitors like abatacept (Orencia, Bristol Myers Squibb) for IMIDs had significantly poorer antibody response.
Greater age and the use of combination therapies for IMIDs, compared with monotherapy, further reduced immune response to the vaccine. In terms of vaccination modality, messenger RNA–based vaccines induced higher antibody levels than did vector-based vaccines. The researchers noted that patients with IMID who were given a third vaccine dose could actually catch up well with the antibody responses observed in healthy controls.
“We looked at whether different IMIDs had a different humoral response, and we also assessed if there are effects from different therapeutic strategies,” Dr. Simon explained. “It doesn’t matter so much what kind of IMID patients have; much more important is the specific drug treatment and its impact on their antibody response.” Some participants were advised to briefly stop taking some immunosuppressive treatments before or after vaccination.
One of Dr. Simon’s coauthors, statistician and rheumatologist Koray Tascilar, MD, added, “This research is important because we looked not only at who responded less, which has been previously established, but who are at greater risk of losing their immune response, and how quickly.”
Need to take care
“Most treatments we as rheumatologists give to our patients don’t affect their SARS-CoV-2 humoral response,” Dr. Simon said. “However, there are specific drugs that are associated with lower antibody response. With respect to those drugs, we have to be more careful.”
It is important to be able to tell patients which drugs are safe and won’t have a negative impact on their immune response to vaccinations, Dr. Tascilar said. “But it would be too strong to say we’re ready to choose therapies based on their potential impact on protection against COVID. Yes, there is a risk from catching COVID, but we need to balance that risk with the risk of not giving patients the medications that are necessary to treat their rheumatologic condition.”
These diseases are serious, sometimes life-threatening. “We might think of strategies for how to mitigate the risk of underprotection from COVID that is brought about by these treatments,” he said. For example, offering boosters sooner or more frequently, or prophylactically treating with monoclonal antibodies.
“This study, along other recent studies, has found that antibody levels in patients with immune-mediated diseases wane more rapidly than in healthy controls, and this is especially true of those on medications that interfere with the B and T cells and anticytokine therapies,” Rebecca Haberman, MD, assistant professor, division of rheumatology, New York University Langone Health, noted in an email to this news organization.
“While there is no known antibody level that specifically correlates with clinical protection, and each patient needs to be thought of individually, these findings support the use of supplemental booster dosing in patients with immune-mediated inflammatory diseases,” Dr. Haberman said, adding that her own research in this area has shown similar results.
“As a rheumatologist, I would be more likely to encourage my patients – especially those on immunomodulatory medications – to get boosted.”
Dr. Tascilar said his study does not directly answer the question of whether an earlier booster shot would be an effective strategy for patients with IMID. “In our department, we have an early boosting strategy, based on level of immune response.” But the decision of revaccination or not, and when, is based on a number of factors, not only on the level of antibodies. “It’s just part of the instruments we are using.”
The study was supported by the Deutsche Forschungsgemeinschaft. Dr. Simon and Dr. Tascilar declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new study in The Lancet Rheumatology examines the strength and duration of SARS-CoV-2 vaccine–induced immunoglobulin-G antibody responses over time for patients with a variety of autoimmune diseases, compared with healthy controls.
The presence of humoral antibodies to SARS-CoV-2 has been shown to correlate with protection against COVID infection. But for patients with immune-mediated inflammatory diseases (IMIDs), host response to COVID infection or to vaccination is affected by the immune dysfunction imposed by the IMID and by the use of immune-modulating drugs to treat it.
This new study finds a weaker – as shown previously – and less sustained immune response to SARS-CoV-2 vaccines in patients with a variety of IMIDs, including rheumatoid arthritis, spondyloarthritis, psoriasis, inflammatory bowel diseases, and other systemic autoimmune diseases such as lupus. It also points toward the possibility of adjusting treatment and vaccination schedules and strategies for these patients based on their antibody levels, among other factors, to preserve best protection against severe COVID.
“It is important to assess immune response in these patients to see if they still have protection against severe COVID infection,” said lead author David Simon, MD, senior clinical scientist in clinical immunology and rheumatology at University Hospital Erlangen (Germany). “We know that antibody response is an immune correlate. Therefore, it is important to see how large and durable the immune response is to the coronavirus vaccine in these IMID patients, and whether specific drugs or therapies have negative effects on their immune response.”
What was studied?
For this large prospective cohort study, researchers registered 5076 coronavirus-vaccinated individuals. They analyzed serum samples obtained between December 15, 2020, and December 1, 2021, from 2,535 patients diagnosed with IMIDs and participating in a prospective coronavirus study program at the Deutsches Zentrum Immuntherapie in Erlangen. The IMID patients had a mean age of 55.0 years, and 58.9% were women.
A healthy control group of 1,198 individuals without IMID who had a mean age of 40.7 years, including 53.8% men, was also recruited for the analysis. All approved coronavirus vaccines were included, following standard vaccination schedules. Antibody response was measured over time by an enzyme-linked immunosorbent assay from 8 weeks after first vaccination to week 40.
Among the findings, the healthy controls had higher postvaccine antibody levels than did those with IMIDs. But the majority of vaccinated patients with IMID were able to build up a humoral immune response to SARS-CoV-2. Patients who were taking B-cell inhibitors like rituximab (Rituxan, Genentech; and biosimilars) and T-cell inhibitors like abatacept (Orencia, Bristol Myers Squibb) for IMIDs had significantly poorer antibody response.
Greater age and the use of combination therapies for IMIDs, compared with monotherapy, further reduced immune response to the vaccine. In terms of vaccination modality, messenger RNA–based vaccines induced higher antibody levels than did vector-based vaccines. The researchers noted that patients with IMID who were given a third vaccine dose could actually catch up well with the antibody responses observed in healthy controls.
“We looked at whether different IMIDs had a different humoral response, and we also assessed if there are effects from different therapeutic strategies,” Dr. Simon explained. “It doesn’t matter so much what kind of IMID patients have; much more important is the specific drug treatment and its impact on their antibody response.” Some participants were advised to briefly stop taking some immunosuppressive treatments before or after vaccination.
One of Dr. Simon’s coauthors, statistician and rheumatologist Koray Tascilar, MD, added, “This research is important because we looked not only at who responded less, which has been previously established, but who are at greater risk of losing their immune response, and how quickly.”
Need to take care
“Most treatments we as rheumatologists give to our patients don’t affect their SARS-CoV-2 humoral response,” Dr. Simon said. “However, there are specific drugs that are associated with lower antibody response. With respect to those drugs, we have to be more careful.”
It is important to be able to tell patients which drugs are safe and won’t have a negative impact on their immune response to vaccinations, Dr. Tascilar said. “But it would be too strong to say we’re ready to choose therapies based on their potential impact on protection against COVID. Yes, there is a risk from catching COVID, but we need to balance that risk with the risk of not giving patients the medications that are necessary to treat their rheumatologic condition.”
These diseases are serious, sometimes life-threatening. “We might think of strategies for how to mitigate the risk of underprotection from COVID that is brought about by these treatments,” he said. For example, offering boosters sooner or more frequently, or prophylactically treating with monoclonal antibodies.
“This study, along other recent studies, has found that antibody levels in patients with immune-mediated diseases wane more rapidly than in healthy controls, and this is especially true of those on medications that interfere with the B and T cells and anticytokine therapies,” Rebecca Haberman, MD, assistant professor, division of rheumatology, New York University Langone Health, noted in an email to this news organization.
“While there is no known antibody level that specifically correlates with clinical protection, and each patient needs to be thought of individually, these findings support the use of supplemental booster dosing in patients with immune-mediated inflammatory diseases,” Dr. Haberman said, adding that her own research in this area has shown similar results.
“As a rheumatologist, I would be more likely to encourage my patients – especially those on immunomodulatory medications – to get boosted.”
Dr. Tascilar said his study does not directly answer the question of whether an earlier booster shot would be an effective strategy for patients with IMID. “In our department, we have an early boosting strategy, based on level of immune response.” But the decision of revaccination or not, and when, is based on a number of factors, not only on the level of antibodies. “It’s just part of the instruments we are using.”
The study was supported by the Deutsche Forschungsgemeinschaft. Dr. Simon and Dr. Tascilar declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE LANCET RHEUMATOLOGY
Asian patients with psoriasis have shortest visits, study shows
(NAMCS) from 2010 to 2016.
Yet the reasons for the difference are unclear and in need of further research, said the investigators and dermatologists who were asked to comment on the research.
The study covered over 4 million visits for psoriasis and found that the mean duration of visits for Asian patients was 9.2 minutes, compared with 15.7 minutes for Hispanic or Latino patients, 20.7 minutes for non-Hispanic Black patients, and 15.4 minutes for non-Hispanic White patients.
The mean duration of visits with Asian patients was 39.9% shorter, compared with visits with White patients (beta coefficient, –5,747; 95% confidence interval, –11.026 to –0.469; P = .03), and 40.6% shorter, compared with visits with non-Asian patients combined (beta coefficient, –5.908; 95% CI, –11.147 to –0.669, P = .03), April W. Armstrong, MD, MPH, professor of dermatology and director of the psoriasis program at the University of Southern California, Los Angeles, and Kevin K. Wu, MD, a dermatology resident at USC, said in a research letter published in JAMA Dermatology.
“The etiology of these differences is unclear,” they wrote. “It is possible that factors such as unconscious bias, cultural differences in communication, or residual confounding may be responsible for the observed findings.”
Their findings came from multivariable linear regression analyses that adjusted for age, sex, type of visit (new or follow-up), visit complexity based on the number of reasons for the visit, insurance status (such as private insurance or Medicaid), psoriasis severity on the basis of systemic psoriasis treatment or phototherapy, and complex topical regimens (three or more topical agents).
Commenting on the results, Deborah A. Scott, MD, codirector of the skin of color dermatology program at Brigham and Women’s Hospital and assistant professor at Harvard Medical School, both in Boston, said in an interview that visit length “is a reasonable parameter to look at among many others” when investigating potential disparities in care.
“They’re equating [shorter visit times] with lack of time spent counseling patients,” said Dr. Scott, who was not involved in the research. But there are “many variables” that can affect visit time, such as language differences, time spent with interpreters, and differences in patient educational levels.
Clarissa Yang, MD, dermatologist-in-chief at Tufts Medical Center, Boston, agreed. “We’re worried about there being a quality of care issue. However, there could also be differences culturally in how [the patients] interact with their physicians – their styles and the questions they ask,” she said in an interview. “The study is a good first step to noting that there may be a disparity,” and there is a need to break down the differences “into more granularity.”
Previous research, the authors wrote, has found that Asian patients were less likely to receive counseling from physicians, compared with White patients. And “paradoxically,” they noted, Asian individuals tend to present with more severe psoriasis than patients of other races and ethnicities.
Dr. Scott said the tendency to present with more severe psoriasis has been documented in patients with skin of color broadly – likely because of delays in recognition and treatment.
Race and ethnicity in the study were self-reported by patients, and missing data were imputed by NAMCS researchers using a sequential regression method. Patients who did not report race and ethnicity may have different characteristics affecting visit duration than those who did report the information, Dr. Armstrong and Dr. Wu said in describing their study’s limitations.
Other differences found
In addition to visit length, they found significant differences in mean age and in the use of complex topical regimens. The mean ages of Asian, Hispanic or Latino, and non-Hispanic Black patients were 37.2, 44.7, and 33.3 years, respectively. Complex topical regimens were prescribed to 11.8% of Asian patients, compared with 1.5% of Black and 1.1% of White patients.
For practicing dermatologists, knowing for now that Asian patients have shorter visits “may bring to light some consciousness to how we practice,” Dr. Yang noted. “We may counsel differently, we may spend differing amounts of time – for reasons still unknown. But being generally aware can help us to shift any unconscious bias that may be there.”
Dermatologists, Dr. Armstrong and Dr. Wu wrote, “need to allow sufficient time to develop strong physician-patient communication regardless of patient background.”
The NAMCS – administered by the Center for Disease Control and Prevention’s National Center for Health Statistics – collects data on a sample of visits provided by non–federally employed office-based physicians.
Dr. Armstrong disclosed receiving personal fees from AbbVie and Regeneron for research funding and serving as a scientific adviser and speaker for additional pharmaceutical and therapeutic companies. Dr. Wu, Dr. Scott, and Dr. Yang did not report any disclosures.
(NAMCS) from 2010 to 2016.
Yet the reasons for the difference are unclear and in need of further research, said the investigators and dermatologists who were asked to comment on the research.
The study covered over 4 million visits for psoriasis and found that the mean duration of visits for Asian patients was 9.2 minutes, compared with 15.7 minutes for Hispanic or Latino patients, 20.7 minutes for non-Hispanic Black patients, and 15.4 minutes for non-Hispanic White patients.
The mean duration of visits with Asian patients was 39.9% shorter, compared with visits with White patients (beta coefficient, –5,747; 95% confidence interval, –11.026 to –0.469; P = .03), and 40.6% shorter, compared with visits with non-Asian patients combined (beta coefficient, –5.908; 95% CI, –11.147 to –0.669, P = .03), April W. Armstrong, MD, MPH, professor of dermatology and director of the psoriasis program at the University of Southern California, Los Angeles, and Kevin K. Wu, MD, a dermatology resident at USC, said in a research letter published in JAMA Dermatology.
“The etiology of these differences is unclear,” they wrote. “It is possible that factors such as unconscious bias, cultural differences in communication, or residual confounding may be responsible for the observed findings.”
Their findings came from multivariable linear regression analyses that adjusted for age, sex, type of visit (new or follow-up), visit complexity based on the number of reasons for the visit, insurance status (such as private insurance or Medicaid), psoriasis severity on the basis of systemic psoriasis treatment or phototherapy, and complex topical regimens (three or more topical agents).
Commenting on the results, Deborah A. Scott, MD, codirector of the skin of color dermatology program at Brigham and Women’s Hospital and assistant professor at Harvard Medical School, both in Boston, said in an interview that visit length “is a reasonable parameter to look at among many others” when investigating potential disparities in care.
“They’re equating [shorter visit times] with lack of time spent counseling patients,” said Dr. Scott, who was not involved in the research. But there are “many variables” that can affect visit time, such as language differences, time spent with interpreters, and differences in patient educational levels.
Clarissa Yang, MD, dermatologist-in-chief at Tufts Medical Center, Boston, agreed. “We’re worried about there being a quality of care issue. However, there could also be differences culturally in how [the patients] interact with their physicians – their styles and the questions they ask,” she said in an interview. “The study is a good first step to noting that there may be a disparity,” and there is a need to break down the differences “into more granularity.”
Previous research, the authors wrote, has found that Asian patients were less likely to receive counseling from physicians, compared with White patients. And “paradoxically,” they noted, Asian individuals tend to present with more severe psoriasis than patients of other races and ethnicities.
Dr. Scott said the tendency to present with more severe psoriasis has been documented in patients with skin of color broadly – likely because of delays in recognition and treatment.
Race and ethnicity in the study were self-reported by patients, and missing data were imputed by NAMCS researchers using a sequential regression method. Patients who did not report race and ethnicity may have different characteristics affecting visit duration than those who did report the information, Dr. Armstrong and Dr. Wu said in describing their study’s limitations.
Other differences found
In addition to visit length, they found significant differences in mean age and in the use of complex topical regimens. The mean ages of Asian, Hispanic or Latino, and non-Hispanic Black patients were 37.2, 44.7, and 33.3 years, respectively. Complex topical regimens were prescribed to 11.8% of Asian patients, compared with 1.5% of Black and 1.1% of White patients.
For practicing dermatologists, knowing for now that Asian patients have shorter visits “may bring to light some consciousness to how we practice,” Dr. Yang noted. “We may counsel differently, we may spend differing amounts of time – for reasons still unknown. But being generally aware can help us to shift any unconscious bias that may be there.”
Dermatologists, Dr. Armstrong and Dr. Wu wrote, “need to allow sufficient time to develop strong physician-patient communication regardless of patient background.”
The NAMCS – administered by the Center for Disease Control and Prevention’s National Center for Health Statistics – collects data on a sample of visits provided by non–federally employed office-based physicians.
Dr. Armstrong disclosed receiving personal fees from AbbVie and Regeneron for research funding and serving as a scientific adviser and speaker for additional pharmaceutical and therapeutic companies. Dr. Wu, Dr. Scott, and Dr. Yang did not report any disclosures.
(NAMCS) from 2010 to 2016.
Yet the reasons for the difference are unclear and in need of further research, said the investigators and dermatologists who were asked to comment on the research.
The study covered over 4 million visits for psoriasis and found that the mean duration of visits for Asian patients was 9.2 minutes, compared with 15.7 minutes for Hispanic or Latino patients, 20.7 minutes for non-Hispanic Black patients, and 15.4 minutes for non-Hispanic White patients.
The mean duration of visits with Asian patients was 39.9% shorter, compared with visits with White patients (beta coefficient, –5,747; 95% confidence interval, –11.026 to –0.469; P = .03), and 40.6% shorter, compared with visits with non-Asian patients combined (beta coefficient, –5.908; 95% CI, –11.147 to –0.669, P = .03), April W. Armstrong, MD, MPH, professor of dermatology and director of the psoriasis program at the University of Southern California, Los Angeles, and Kevin K. Wu, MD, a dermatology resident at USC, said in a research letter published in JAMA Dermatology.
“The etiology of these differences is unclear,” they wrote. “It is possible that factors such as unconscious bias, cultural differences in communication, or residual confounding may be responsible for the observed findings.”
Their findings came from multivariable linear regression analyses that adjusted for age, sex, type of visit (new or follow-up), visit complexity based on the number of reasons for the visit, insurance status (such as private insurance or Medicaid), psoriasis severity on the basis of systemic psoriasis treatment or phototherapy, and complex topical regimens (three or more topical agents).
Commenting on the results, Deborah A. Scott, MD, codirector of the skin of color dermatology program at Brigham and Women’s Hospital and assistant professor at Harvard Medical School, both in Boston, said in an interview that visit length “is a reasonable parameter to look at among many others” when investigating potential disparities in care.
“They’re equating [shorter visit times] with lack of time spent counseling patients,” said Dr. Scott, who was not involved in the research. But there are “many variables” that can affect visit time, such as language differences, time spent with interpreters, and differences in patient educational levels.
Clarissa Yang, MD, dermatologist-in-chief at Tufts Medical Center, Boston, agreed. “We’re worried about there being a quality of care issue. However, there could also be differences culturally in how [the patients] interact with their physicians – their styles and the questions they ask,” she said in an interview. “The study is a good first step to noting that there may be a disparity,” and there is a need to break down the differences “into more granularity.”
Previous research, the authors wrote, has found that Asian patients were less likely to receive counseling from physicians, compared with White patients. And “paradoxically,” they noted, Asian individuals tend to present with more severe psoriasis than patients of other races and ethnicities.
Dr. Scott said the tendency to present with more severe psoriasis has been documented in patients with skin of color broadly – likely because of delays in recognition and treatment.
Race and ethnicity in the study were self-reported by patients, and missing data were imputed by NAMCS researchers using a sequential regression method. Patients who did not report race and ethnicity may have different characteristics affecting visit duration than those who did report the information, Dr. Armstrong and Dr. Wu said in describing their study’s limitations.
Other differences found
In addition to visit length, they found significant differences in mean age and in the use of complex topical regimens. The mean ages of Asian, Hispanic or Latino, and non-Hispanic Black patients were 37.2, 44.7, and 33.3 years, respectively. Complex topical regimens were prescribed to 11.8% of Asian patients, compared with 1.5% of Black and 1.1% of White patients.
For practicing dermatologists, knowing for now that Asian patients have shorter visits “may bring to light some consciousness to how we practice,” Dr. Yang noted. “We may counsel differently, we may spend differing amounts of time – for reasons still unknown. But being generally aware can help us to shift any unconscious bias that may be there.”
Dermatologists, Dr. Armstrong and Dr. Wu wrote, “need to allow sufficient time to develop strong physician-patient communication regardless of patient background.”
The NAMCS – administered by the Center for Disease Control and Prevention’s National Center for Health Statistics – collects data on a sample of visits provided by non–federally employed office-based physicians.
Dr. Armstrong disclosed receiving personal fees from AbbVie and Regeneron for research funding and serving as a scientific adviser and speaker for additional pharmaceutical and therapeutic companies. Dr. Wu, Dr. Scott, and Dr. Yang did not report any disclosures.
FROM JAMA DERMATOLOGY
Fatigue impairs general health outcomes in PsA
Key clinical point: A substantial proportion of patients with psoriatic arthritis (PsA) reported fatigue, and the degree of fatigue had a significant impact on their disease severity and physical functionality.
Major finding: The majority of patients with PsA (78.3%) reported fatigue. Patients with higher fatigue scores reported more severe disease, greater pain levels, and higher tender/swollen joint count (all P < .001). Higher fatigue scores were associated with worse physical functioning and higher overall work impairment (both P < .001).
Study details: Findings are from an analysis of an independent, cross-sectional, multinational, real-world survey, Adelphi Real World Spondyloarthritis (SpA) IV Disease Specific Programme, including 831 patients with PsA.
Disclosures: The Adelphi SpA IV Disease Specific Programme was funded by Janssen. Three authors declared being employees of Janssen and shareholders of Janssen/Johnson & Johnson. Four authors declared being employees of Adelphi Real World. Other authors declared receiving grants of serving as consultants for several sources, including Janssen.
Source: Gossec L et al. Impact of fatigue on health-related quality of life and work productivity in psoriatic arthritis: Findings from a real-world survey. J Rheumatol. 2022 (Jul 15). Doi: 10.3899/jrheum.211288
Key clinical point: A substantial proportion of patients with psoriatic arthritis (PsA) reported fatigue, and the degree of fatigue had a significant impact on their disease severity and physical functionality.
Major finding: The majority of patients with PsA (78.3%) reported fatigue. Patients with higher fatigue scores reported more severe disease, greater pain levels, and higher tender/swollen joint count (all P < .001). Higher fatigue scores were associated with worse physical functioning and higher overall work impairment (both P < .001).
Study details: Findings are from an analysis of an independent, cross-sectional, multinational, real-world survey, Adelphi Real World Spondyloarthritis (SpA) IV Disease Specific Programme, including 831 patients with PsA.
Disclosures: The Adelphi SpA IV Disease Specific Programme was funded by Janssen. Three authors declared being employees of Janssen and shareholders of Janssen/Johnson & Johnson. Four authors declared being employees of Adelphi Real World. Other authors declared receiving grants of serving as consultants for several sources, including Janssen.
Source: Gossec L et al. Impact of fatigue on health-related quality of life and work productivity in psoriatic arthritis: Findings from a real-world survey. J Rheumatol. 2022 (Jul 15). Doi: 10.3899/jrheum.211288
Key clinical point: A substantial proportion of patients with psoriatic arthritis (PsA) reported fatigue, and the degree of fatigue had a significant impact on their disease severity and physical functionality.
Major finding: The majority of patients with PsA (78.3%) reported fatigue. Patients with higher fatigue scores reported more severe disease, greater pain levels, and higher tender/swollen joint count (all P < .001). Higher fatigue scores were associated with worse physical functioning and higher overall work impairment (both P < .001).
Study details: Findings are from an analysis of an independent, cross-sectional, multinational, real-world survey, Adelphi Real World Spondyloarthritis (SpA) IV Disease Specific Programme, including 831 patients with PsA.
Disclosures: The Adelphi SpA IV Disease Specific Programme was funded by Janssen. Three authors declared being employees of Janssen and shareholders of Janssen/Johnson & Johnson. Four authors declared being employees of Adelphi Real World. Other authors declared receiving grants of serving as consultants for several sources, including Janssen.
Source: Gossec L et al. Impact of fatigue on health-related quality of life and work productivity in psoriatic arthritis: Findings from a real-world survey. J Rheumatol. 2022 (Jul 15). Doi: 10.3899/jrheum.211288
Elevated IL-23 levels associated with psychiatric disorders in PsA
Key clinical point: In patients with psoriatic arthritis (PsA), serum interleukin-23 (IL-23) levels were elevated and significantly correlated with disease activity (DA), depression, and anxiety.
Major finding: Serum IL-23 levels were higher in patients with PsA vs healthy volunteers without PsA (225.19 vs 118.12 pg/mL; P < .0001), and a significantly higher proportion of patients vs volunteers reported anxiety (45% vs 20%) and depression (35% vs 15%; both P < .0001). Serum IL-23 levels were positively correlated with Disease Activity Index for Psoriatic Arthritis (correlation coefficient [r] 0.959), Hospital Anxiety and Depression Scale (HADS) anxiety (r 0.932), and HADS depression (r 0.934; all P = .0001) scores.
Study details: Findings are from an observational case-control study including 80 patients with PsA and 80 matched healthy volunteers.
Disclosures: This study was funded by The Science, Technology & Innovation Funding Authority, Egypt, in cooperation with The Egyptian Knowledge Bank. The authors declared no conflicts of interest.
Source: Tabra SA et al. Serum interleukin-23 levels: Relation to depression, anxiety, and disease activity in psoriatic arthritis patients. Clin Rheumatol. 2022 (Jul 21). Doi: 10.1007/s10067-022-06300-1
Key clinical point: In patients with psoriatic arthritis (PsA), serum interleukin-23 (IL-23) levels were elevated and significantly correlated with disease activity (DA), depression, and anxiety.
Major finding: Serum IL-23 levels were higher in patients with PsA vs healthy volunteers without PsA (225.19 vs 118.12 pg/mL; P < .0001), and a significantly higher proportion of patients vs volunteers reported anxiety (45% vs 20%) and depression (35% vs 15%; both P < .0001). Serum IL-23 levels were positively correlated with Disease Activity Index for Psoriatic Arthritis (correlation coefficient [r] 0.959), Hospital Anxiety and Depression Scale (HADS) anxiety (r 0.932), and HADS depression (r 0.934; all P = .0001) scores.
Study details: Findings are from an observational case-control study including 80 patients with PsA and 80 matched healthy volunteers.
Disclosures: This study was funded by The Science, Technology & Innovation Funding Authority, Egypt, in cooperation with The Egyptian Knowledge Bank. The authors declared no conflicts of interest.
Source: Tabra SA et al. Serum interleukin-23 levels: Relation to depression, anxiety, and disease activity in psoriatic arthritis patients. Clin Rheumatol. 2022 (Jul 21). Doi: 10.1007/s10067-022-06300-1
Key clinical point: In patients with psoriatic arthritis (PsA), serum interleukin-23 (IL-23) levels were elevated and significantly correlated with disease activity (DA), depression, and anxiety.
Major finding: Serum IL-23 levels were higher in patients with PsA vs healthy volunteers without PsA (225.19 vs 118.12 pg/mL; P < .0001), and a significantly higher proportion of patients vs volunteers reported anxiety (45% vs 20%) and depression (35% vs 15%; both P < .0001). Serum IL-23 levels were positively correlated with Disease Activity Index for Psoriatic Arthritis (correlation coefficient [r] 0.959), Hospital Anxiety and Depression Scale (HADS) anxiety (r 0.932), and HADS depression (r 0.934; all P = .0001) scores.
Study details: Findings are from an observational case-control study including 80 patients with PsA and 80 matched healthy volunteers.
Disclosures: This study was funded by The Science, Technology & Innovation Funding Authority, Egypt, in cooperation with The Egyptian Knowledge Bank. The authors declared no conflicts of interest.
Source: Tabra SA et al. Serum interleukin-23 levels: Relation to depression, anxiety, and disease activity in psoriatic arthritis patients. Clin Rheumatol. 2022 (Jul 21). Doi: 10.1007/s10067-022-06300-1
PsA remission depends on patient perception and is multidimensional
Key clinical point: Patients with psoriatic arthritis (PsA) were more likely to report remission if they perceived an acceptable disease state, psoriasis remission, and a lower impact of PsA on global quality of life.
Major finding: Patient-reported PsA remission was associated with the achievement of 9-question Psoriatic Arthritis Impact of Disease score of ≤4 (odds ratio [OR] 4.58; P < .05), perception of psoriasis remission (OR 4.51; P < .05), and global quality of life score (OR 0.55; P < .001).
Study details: Findings are from a cross-sectional survey by the National Psoriasis Foundation including 834 patients with psoriasis or PsA.
Disclosures: This study did not receive any funding. Several authors declared serving as research or principal investigators, advisors, or consultants for several sources.
Source: Gondo G et al. Demographic and clinical factors associated with patient-reported remission in psoriatic arthritis. Dermatol Ther (Heidelb). 2022;12(8):1885-1895 (Jul 21). Doi: 10.1007/s13555-022-00770-6
Key clinical point: Patients with psoriatic arthritis (PsA) were more likely to report remission if they perceived an acceptable disease state, psoriasis remission, and a lower impact of PsA on global quality of life.
Major finding: Patient-reported PsA remission was associated with the achievement of 9-question Psoriatic Arthritis Impact of Disease score of ≤4 (odds ratio [OR] 4.58; P < .05), perception of psoriasis remission (OR 4.51; P < .05), and global quality of life score (OR 0.55; P < .001).
Study details: Findings are from a cross-sectional survey by the National Psoriasis Foundation including 834 patients with psoriasis or PsA.
Disclosures: This study did not receive any funding. Several authors declared serving as research or principal investigators, advisors, or consultants for several sources.
Source: Gondo G et al. Demographic and clinical factors associated with patient-reported remission in psoriatic arthritis. Dermatol Ther (Heidelb). 2022;12(8):1885-1895 (Jul 21). Doi: 10.1007/s13555-022-00770-6
Key clinical point: Patients with psoriatic arthritis (PsA) were more likely to report remission if they perceived an acceptable disease state, psoriasis remission, and a lower impact of PsA on global quality of life.
Major finding: Patient-reported PsA remission was associated with the achievement of 9-question Psoriatic Arthritis Impact of Disease score of ≤4 (odds ratio [OR] 4.58; P < .05), perception of psoriasis remission (OR 4.51; P < .05), and global quality of life score (OR 0.55; P < .001).
Study details: Findings are from a cross-sectional survey by the National Psoriasis Foundation including 834 patients with psoriasis or PsA.
Disclosures: This study did not receive any funding. Several authors declared serving as research or principal investigators, advisors, or consultants for several sources.
Source: Gondo G et al. Demographic and clinical factors associated with patient-reported remission in psoriatic arthritis. Dermatol Ther (Heidelb). 2022;12(8):1885-1895 (Jul 21). Doi: 10.1007/s13555-022-00770-6