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Cannabidiol found no better than placebo for hand arthritis pain
Use of cannabidiol (CBD) as an add-on pain management technique in patients with either hand osteoarthritis (OA) or psoriatic arthritis (PsA) did not significantly decrease pain intensity when compared with a placebo in a randomized, double-blind trial described as the first of its kind to investigate the effect of pure CBD as an add-on analgesic therapy in patients with joint disease.
Although data on the use of medical cannabis as a modulator of joint pain are limited, some studies suggest an effect from CBD without the addition of delta-9-tetrahydrocannabinol (THC), wrote Jonathan Vela, MD, of Aalborg (Denmark) University Hospital, and colleagues.
CBD is being used for pain conditions despite a lack of data on safety and effectiveness, the researchers emphasized. Notably, in a 2018 online survey, 62% of respondents reported using CBD for medical conditions, primarily for chronic pain and arthritis or joint pain, they wrote.
In a study published in the journal Pain, the researchers randomized 59 adults with PsA and 77 adults with hand OA to 20-30 mg of synthetic CBD or a placebo daily for 12 weeks in addition to conventional pain management. Patients initially received either oral CBD 10 mg or a placebo tablet once daily, increasing to 10 mg twice daily after 2 weeks, and once again up to 10 mg three times daily at 4 weeks if the patient did not experience more than 20-mm improvement on the visual analog scale (VAS).
The primary outcome in the trial was patient-reported pain intensity during the last 24 hours as assessed on a paper-based 100-mm VAS with the text, “How much pain have you experienced in the most symptomatic joint during the last 24 hours?” with 0 representing no pain and 100 representing the worst pain imaginable.
Overall, both CBD and placebo groups achieved significant reductions in pain intensity of 11-12 mm at 12 weeks. The mean between-group difference on the VAS was 0.23 mm (P = .96). Twenty-two percent of patients who received CBD and 21% who received placebo demonstrated a pain intensity reduction greater than 30 mm on the VAS. Pain reduction greater than 50% was reported by 17 patients (25%) in the CBD group and 16 (27%) in the placebo group. CBD had a similar effect in patients with either PsA or hand OA.
Four serious adverse events occurred during the 12-week study period, but none of these were deemed adverse drug reactions. Serious adverse events in the CBD patients included one case of ductal carcinoma and one case of lipotymia; serious adverse events in the placebo group included one case of acute shoulder fracture and one case of malignant hypertension. Fifty-nine patients reported adverse events during the study. The CBD group reported more ear-nose-throat adverse events, compared with the placebo group (8 vs. 0).
The researchers assessed the impact of CBD vs. placebo on sleep quality, depression, anxiety, or pain catastrophizing scores using the Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, and Health Assessment Questionnaire but found no differences in patients taking CBD vs. placebo.
The study findings were limited by several factors, including the potentially insufficient dose level to evoke a pain relief response, and a lack of data on additional daily use of analgesics or of the study drug beyond the prescribed dosage, the researchers noted.
The results were strengthened by the randomized, double-blind trial design and its relatively large sample size, they wrote. However, the researchers also cautioned that their study focused on CBD as a single ingredient, and the results might not generalize to other CBD formulations. They also noted that more research is needed to examine both higher doses of CBD and different types of pain disorders.
The study was supported by the Danish Psoriasis Foundation Grant and the Danish Rheumatism Foundation. The researchers had no financial conflicts to disclose.
Use of cannabidiol (CBD) as an add-on pain management technique in patients with either hand osteoarthritis (OA) or psoriatic arthritis (PsA) did not significantly decrease pain intensity when compared with a placebo in a randomized, double-blind trial described as the first of its kind to investigate the effect of pure CBD as an add-on analgesic therapy in patients with joint disease.
Although data on the use of medical cannabis as a modulator of joint pain are limited, some studies suggest an effect from CBD without the addition of delta-9-tetrahydrocannabinol (THC), wrote Jonathan Vela, MD, of Aalborg (Denmark) University Hospital, and colleagues.
CBD is being used for pain conditions despite a lack of data on safety and effectiveness, the researchers emphasized. Notably, in a 2018 online survey, 62% of respondents reported using CBD for medical conditions, primarily for chronic pain and arthritis or joint pain, they wrote.
In a study published in the journal Pain, the researchers randomized 59 adults with PsA and 77 adults with hand OA to 20-30 mg of synthetic CBD or a placebo daily for 12 weeks in addition to conventional pain management. Patients initially received either oral CBD 10 mg or a placebo tablet once daily, increasing to 10 mg twice daily after 2 weeks, and once again up to 10 mg three times daily at 4 weeks if the patient did not experience more than 20-mm improvement on the visual analog scale (VAS).
The primary outcome in the trial was patient-reported pain intensity during the last 24 hours as assessed on a paper-based 100-mm VAS with the text, “How much pain have you experienced in the most symptomatic joint during the last 24 hours?” with 0 representing no pain and 100 representing the worst pain imaginable.
Overall, both CBD and placebo groups achieved significant reductions in pain intensity of 11-12 mm at 12 weeks. The mean between-group difference on the VAS was 0.23 mm (P = .96). Twenty-two percent of patients who received CBD and 21% who received placebo demonstrated a pain intensity reduction greater than 30 mm on the VAS. Pain reduction greater than 50% was reported by 17 patients (25%) in the CBD group and 16 (27%) in the placebo group. CBD had a similar effect in patients with either PsA or hand OA.
Four serious adverse events occurred during the 12-week study period, but none of these were deemed adverse drug reactions. Serious adverse events in the CBD patients included one case of ductal carcinoma and one case of lipotymia; serious adverse events in the placebo group included one case of acute shoulder fracture and one case of malignant hypertension. Fifty-nine patients reported adverse events during the study. The CBD group reported more ear-nose-throat adverse events, compared with the placebo group (8 vs. 0).
The researchers assessed the impact of CBD vs. placebo on sleep quality, depression, anxiety, or pain catastrophizing scores using the Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, and Health Assessment Questionnaire but found no differences in patients taking CBD vs. placebo.
The study findings were limited by several factors, including the potentially insufficient dose level to evoke a pain relief response, and a lack of data on additional daily use of analgesics or of the study drug beyond the prescribed dosage, the researchers noted.
The results were strengthened by the randomized, double-blind trial design and its relatively large sample size, they wrote. However, the researchers also cautioned that their study focused on CBD as a single ingredient, and the results might not generalize to other CBD formulations. They also noted that more research is needed to examine both higher doses of CBD and different types of pain disorders.
The study was supported by the Danish Psoriasis Foundation Grant and the Danish Rheumatism Foundation. The researchers had no financial conflicts to disclose.
Use of cannabidiol (CBD) as an add-on pain management technique in patients with either hand osteoarthritis (OA) or psoriatic arthritis (PsA) did not significantly decrease pain intensity when compared with a placebo in a randomized, double-blind trial described as the first of its kind to investigate the effect of pure CBD as an add-on analgesic therapy in patients with joint disease.
Although data on the use of medical cannabis as a modulator of joint pain are limited, some studies suggest an effect from CBD without the addition of delta-9-tetrahydrocannabinol (THC), wrote Jonathan Vela, MD, of Aalborg (Denmark) University Hospital, and colleagues.
CBD is being used for pain conditions despite a lack of data on safety and effectiveness, the researchers emphasized. Notably, in a 2018 online survey, 62% of respondents reported using CBD for medical conditions, primarily for chronic pain and arthritis or joint pain, they wrote.
In a study published in the journal Pain, the researchers randomized 59 adults with PsA and 77 adults with hand OA to 20-30 mg of synthetic CBD or a placebo daily for 12 weeks in addition to conventional pain management. Patients initially received either oral CBD 10 mg or a placebo tablet once daily, increasing to 10 mg twice daily after 2 weeks, and once again up to 10 mg three times daily at 4 weeks if the patient did not experience more than 20-mm improvement on the visual analog scale (VAS).
The primary outcome in the trial was patient-reported pain intensity during the last 24 hours as assessed on a paper-based 100-mm VAS with the text, “How much pain have you experienced in the most symptomatic joint during the last 24 hours?” with 0 representing no pain and 100 representing the worst pain imaginable.
Overall, both CBD and placebo groups achieved significant reductions in pain intensity of 11-12 mm at 12 weeks. The mean between-group difference on the VAS was 0.23 mm (P = .96). Twenty-two percent of patients who received CBD and 21% who received placebo demonstrated a pain intensity reduction greater than 30 mm on the VAS. Pain reduction greater than 50% was reported by 17 patients (25%) in the CBD group and 16 (27%) in the placebo group. CBD had a similar effect in patients with either PsA or hand OA.
Four serious adverse events occurred during the 12-week study period, but none of these were deemed adverse drug reactions. Serious adverse events in the CBD patients included one case of ductal carcinoma and one case of lipotymia; serious adverse events in the placebo group included one case of acute shoulder fracture and one case of malignant hypertension. Fifty-nine patients reported adverse events during the study. The CBD group reported more ear-nose-throat adverse events, compared with the placebo group (8 vs. 0).
The researchers assessed the impact of CBD vs. placebo on sleep quality, depression, anxiety, or pain catastrophizing scores using the Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, and Health Assessment Questionnaire but found no differences in patients taking CBD vs. placebo.
The study findings were limited by several factors, including the potentially insufficient dose level to evoke a pain relief response, and a lack of data on additional daily use of analgesics or of the study drug beyond the prescribed dosage, the researchers noted.
The results were strengthened by the randomized, double-blind trial design and its relatively large sample size, they wrote. However, the researchers also cautioned that their study focused on CBD as a single ingredient, and the results might not generalize to other CBD formulations. They also noted that more research is needed to examine both higher doses of CBD and different types of pain disorders.
The study was supported by the Danish Psoriasis Foundation Grant and the Danish Rheumatism Foundation. The researchers had no financial conflicts to disclose.
FROM PAIN
Ask about itch and joint pain in pediatric psoriasis patients, expert advises
During the annual meeting of the Society for Pediatric Dermatology, Amy S. Paller, MD, MS, marveled on the remarkable advances in the treatment of inflammatory skin disorders during the past 2 decades.
“We’ve come a long way, from disease features being red, thick, and scaly and being treated with nonspecific therapy like topical steroids, keratolytics, and tar, to understanding disease pathogenesis and finding new targeted therapies for inflammatory skin disorders in children,” said Dr. Paller, professor and chair of the department of dermatology at Northwestern University, Chicago. “There are now studies moving forward with gene correction, gene replacement, the gene product replaced, or pathway inhibition to prevent the effects of genetic change.”
Technology is leading the way in generating new therapeutic advances, she continued, beyond traditional “omics” to lipidomics, metabolomics, glycomics, and kinomics. “This has enabled us to find new genetic disorders and their causes, to look at changes in gene expression patterns, and to look at changes in protein expression patterns that give us clues as to how to move forward with better therapy,” she said. “When we’re talking about new insights into pathogenesis-based therapy, we’re talking largely about understanding the pathways that lead to either inflammation or promoting cell proliferation and abnormal differentiation.”
Treating pediatric psoriasis
. “First of all, ask about itch and pain with these patients,” she advised. “Interviews have shown that 61% of children experience some itch, 39% have pain or stinging, and in the ixekizumab trials, 72% had what’s considered meaningful itch, with at least 4 out of 10 (mean intensity 5.3) on the itch numeric rating scale. Little is known about the itch associated with psoriasis and its underlying cause – unrelated to the IL-4/IL-13 pathway activation of atopic dermatitis – but it’s worth asking about. I find that itch of the scalp is especially a problem in psoriasis.”
Physicians should also ask pediatric psoriasis patients about joint pain, because about 1% of them have psoriatic arthritis, which is much less common than in adults, “but important to find and manage,” she added. Dr. Paller recommends the new R-JET rapid joint exam technique, which is accompanied by a three-question survey and body diagram that facilitates identification of true arthritis, “so you can know how quickly to refer”.
Several studies have described an increased risk of metabolic syndrome in adolescents with pediatric psoriasis and now in prepubertal children with the disease. In a recent study of 60 consecutive prepubertal children with psoriasis, 70% of whom had mild disease, 40% were overweight or obese, 53% had central obesity, 27% had high levels of the HOMA-IR (homeostasis model assessment of insulin resistance) despite generally normal levels of fasting glucose, and 30% met criteria for metabolic syndrome.
“This really struck me because our AAD [American Academy of Dermatology] guidelines did not recommend screening for type 2 diabetes in prepubertal children, even if overweight, because the risk is so small,” Dr. Paller said. “This report suggests that we may need to reconsider this recommendation in prepubertal children with psoriasis.”
Meanwhile, the number of medications approved by the Food and Drug Administration and the European Medicines Agency for children with psoriasis who are 6 years of age and above continues to expand, including tumor necrosis factor (TNF) inhibitors, interleukin (IL)-23 inhibitors, and IL-17 inhibitors. Most children can now achieve a PASI 90 within 12 weeks with the IL-23 inhibitor ustekinumab and the IL-17 inhibitors ixekizumab and secukinumab, Dr. Paller said.
In the ixekizumab trial, there are head-to-head comparison data in a European arm that involved the use of etanercept, she said. “What’s most noticeable is the significant difference in those who were able to achieve PASI 90 or above with this IL-17 inhibitor, versus etanercept,” which she added, raises the question of whether aiming for a PASI 75 is adequate, "or should we strive for PASI 90?” A pediatric psoriasis study published in 2020 found that the greatest improvement in quality of life was associated with a PASI 90 and use of systemic treatments.
Looking forward, phase 3 clinical trials are underway in pediatric patients with moderate to severe psoriasis for guselkumab, tildrakizumab, risankizumab, certolizumab, bimekizumab, and brodalumab. “The cost of all of these biologics is high, however. I remind everyone that we still have methotrexate,” she said. “The risk of side effects with our low-dose methotrexate treatment for psoriasis remains low, but methotrexate doesn’t hit these [high] PASI numbers and it’s much slower in its onset than biologics.”
Dr. Paller disclosed that she is a consultant to and/or an investigator for AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, RAPT Therapeutics, Regeneron, and Sanofi.
Commentary by Robert Sidbury, MD, MPH
Dr. Paller reminds us of some essential features of pediatric psoriasis:
• It can hurt. Ask your patients if it does.
• It can itch. Look for excoriations, especially in the scalp.
• It is often associated with metabolic syndrome, so check relevant biometrics and labs, and consider coincident insulin resistance.
• Our traditional clinical trial target of PASI75, or a 75% reduction in body surface area involvement, is just not good enough. Studies have shown that the most meaningful quality-of-life gains come at PASI90 or above.
• With our newer biologics, such as IL-12/23 blockers (for instance, ustekinumab) and IL-17 blockers (for example, ixekizumab and secukinumab), PASI90 and better is a reasonable expectation, not a pipe dream.
Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.
This article was updated 6/16/22.
During the annual meeting of the Society for Pediatric Dermatology, Amy S. Paller, MD, MS, marveled on the remarkable advances in the treatment of inflammatory skin disorders during the past 2 decades.
“We’ve come a long way, from disease features being red, thick, and scaly and being treated with nonspecific therapy like topical steroids, keratolytics, and tar, to understanding disease pathogenesis and finding new targeted therapies for inflammatory skin disorders in children,” said Dr. Paller, professor and chair of the department of dermatology at Northwestern University, Chicago. “There are now studies moving forward with gene correction, gene replacement, the gene product replaced, or pathway inhibition to prevent the effects of genetic change.”
Technology is leading the way in generating new therapeutic advances, she continued, beyond traditional “omics” to lipidomics, metabolomics, glycomics, and kinomics. “This has enabled us to find new genetic disorders and their causes, to look at changes in gene expression patterns, and to look at changes in protein expression patterns that give us clues as to how to move forward with better therapy,” she said. “When we’re talking about new insights into pathogenesis-based therapy, we’re talking largely about understanding the pathways that lead to either inflammation or promoting cell proliferation and abnormal differentiation.”
Treating pediatric psoriasis
. “First of all, ask about itch and pain with these patients,” she advised. “Interviews have shown that 61% of children experience some itch, 39% have pain or stinging, and in the ixekizumab trials, 72% had what’s considered meaningful itch, with at least 4 out of 10 (mean intensity 5.3) on the itch numeric rating scale. Little is known about the itch associated with psoriasis and its underlying cause – unrelated to the IL-4/IL-13 pathway activation of atopic dermatitis – but it’s worth asking about. I find that itch of the scalp is especially a problem in psoriasis.”
Physicians should also ask pediatric psoriasis patients about joint pain, because about 1% of them have psoriatic arthritis, which is much less common than in adults, “but important to find and manage,” she added. Dr. Paller recommends the new R-JET rapid joint exam technique, which is accompanied by a three-question survey and body diagram that facilitates identification of true arthritis, “so you can know how quickly to refer”.
Several studies have described an increased risk of metabolic syndrome in adolescents with pediatric psoriasis and now in prepubertal children with the disease. In a recent study of 60 consecutive prepubertal children with psoriasis, 70% of whom had mild disease, 40% were overweight or obese, 53% had central obesity, 27% had high levels of the HOMA-IR (homeostasis model assessment of insulin resistance) despite generally normal levels of fasting glucose, and 30% met criteria for metabolic syndrome.
“This really struck me because our AAD [American Academy of Dermatology] guidelines did not recommend screening for type 2 diabetes in prepubertal children, even if overweight, because the risk is so small,” Dr. Paller said. “This report suggests that we may need to reconsider this recommendation in prepubertal children with psoriasis.”
Meanwhile, the number of medications approved by the Food and Drug Administration and the European Medicines Agency for children with psoriasis who are 6 years of age and above continues to expand, including tumor necrosis factor (TNF) inhibitors, interleukin (IL)-23 inhibitors, and IL-17 inhibitors. Most children can now achieve a PASI 90 within 12 weeks with the IL-23 inhibitor ustekinumab and the IL-17 inhibitors ixekizumab and secukinumab, Dr. Paller said.
In the ixekizumab trial, there are head-to-head comparison data in a European arm that involved the use of etanercept, she said. “What’s most noticeable is the significant difference in those who were able to achieve PASI 90 or above with this IL-17 inhibitor, versus etanercept,” which she added, raises the question of whether aiming for a PASI 75 is adequate, "or should we strive for PASI 90?” A pediatric psoriasis study published in 2020 found that the greatest improvement in quality of life was associated with a PASI 90 and use of systemic treatments.
Looking forward, phase 3 clinical trials are underway in pediatric patients with moderate to severe psoriasis for guselkumab, tildrakizumab, risankizumab, certolizumab, bimekizumab, and brodalumab. “The cost of all of these biologics is high, however. I remind everyone that we still have methotrexate,” she said. “The risk of side effects with our low-dose methotrexate treatment for psoriasis remains low, but methotrexate doesn’t hit these [high] PASI numbers and it’s much slower in its onset than biologics.”
Dr. Paller disclosed that she is a consultant to and/or an investigator for AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, RAPT Therapeutics, Regeneron, and Sanofi.
Commentary by Robert Sidbury, MD, MPH
Dr. Paller reminds us of some essential features of pediatric psoriasis:
• It can hurt. Ask your patients if it does.
• It can itch. Look for excoriations, especially in the scalp.
• It is often associated with metabolic syndrome, so check relevant biometrics and labs, and consider coincident insulin resistance.
• Our traditional clinical trial target of PASI75, or a 75% reduction in body surface area involvement, is just not good enough. Studies have shown that the most meaningful quality-of-life gains come at PASI90 or above.
• With our newer biologics, such as IL-12/23 blockers (for instance, ustekinumab) and IL-17 blockers (for example, ixekizumab and secukinumab), PASI90 and better is a reasonable expectation, not a pipe dream.
Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.
This article was updated 6/16/22.
During the annual meeting of the Society for Pediatric Dermatology, Amy S. Paller, MD, MS, marveled on the remarkable advances in the treatment of inflammatory skin disorders during the past 2 decades.
“We’ve come a long way, from disease features being red, thick, and scaly and being treated with nonspecific therapy like topical steroids, keratolytics, and tar, to understanding disease pathogenesis and finding new targeted therapies for inflammatory skin disorders in children,” said Dr. Paller, professor and chair of the department of dermatology at Northwestern University, Chicago. “There are now studies moving forward with gene correction, gene replacement, the gene product replaced, or pathway inhibition to prevent the effects of genetic change.”
Technology is leading the way in generating new therapeutic advances, she continued, beyond traditional “omics” to lipidomics, metabolomics, glycomics, and kinomics. “This has enabled us to find new genetic disorders and their causes, to look at changes in gene expression patterns, and to look at changes in protein expression patterns that give us clues as to how to move forward with better therapy,” she said. “When we’re talking about new insights into pathogenesis-based therapy, we’re talking largely about understanding the pathways that lead to either inflammation or promoting cell proliferation and abnormal differentiation.”
Treating pediatric psoriasis
. “First of all, ask about itch and pain with these patients,” she advised. “Interviews have shown that 61% of children experience some itch, 39% have pain or stinging, and in the ixekizumab trials, 72% had what’s considered meaningful itch, with at least 4 out of 10 (mean intensity 5.3) on the itch numeric rating scale. Little is known about the itch associated with psoriasis and its underlying cause – unrelated to the IL-4/IL-13 pathway activation of atopic dermatitis – but it’s worth asking about. I find that itch of the scalp is especially a problem in psoriasis.”
Physicians should also ask pediatric psoriasis patients about joint pain, because about 1% of them have psoriatic arthritis, which is much less common than in adults, “but important to find and manage,” she added. Dr. Paller recommends the new R-JET rapid joint exam technique, which is accompanied by a three-question survey and body diagram that facilitates identification of true arthritis, “so you can know how quickly to refer”.
Several studies have described an increased risk of metabolic syndrome in adolescents with pediatric psoriasis and now in prepubertal children with the disease. In a recent study of 60 consecutive prepubertal children with psoriasis, 70% of whom had mild disease, 40% were overweight or obese, 53% had central obesity, 27% had high levels of the HOMA-IR (homeostasis model assessment of insulin resistance) despite generally normal levels of fasting glucose, and 30% met criteria for metabolic syndrome.
“This really struck me because our AAD [American Academy of Dermatology] guidelines did not recommend screening for type 2 diabetes in prepubertal children, even if overweight, because the risk is so small,” Dr. Paller said. “This report suggests that we may need to reconsider this recommendation in prepubertal children with psoriasis.”
Meanwhile, the number of medications approved by the Food and Drug Administration and the European Medicines Agency for children with psoriasis who are 6 years of age and above continues to expand, including tumor necrosis factor (TNF) inhibitors, interleukin (IL)-23 inhibitors, and IL-17 inhibitors. Most children can now achieve a PASI 90 within 12 weeks with the IL-23 inhibitor ustekinumab and the IL-17 inhibitors ixekizumab and secukinumab, Dr. Paller said.
In the ixekizumab trial, there are head-to-head comparison data in a European arm that involved the use of etanercept, she said. “What’s most noticeable is the significant difference in those who were able to achieve PASI 90 or above with this IL-17 inhibitor, versus etanercept,” which she added, raises the question of whether aiming for a PASI 75 is adequate, "or should we strive for PASI 90?” A pediatric psoriasis study published in 2020 found that the greatest improvement in quality of life was associated with a PASI 90 and use of systemic treatments.
Looking forward, phase 3 clinical trials are underway in pediatric patients with moderate to severe psoriasis for guselkumab, tildrakizumab, risankizumab, certolizumab, bimekizumab, and brodalumab. “The cost of all of these biologics is high, however. I remind everyone that we still have methotrexate,” she said. “The risk of side effects with our low-dose methotrexate treatment for psoriasis remains low, but methotrexate doesn’t hit these [high] PASI numbers and it’s much slower in its onset than biologics.”
Dr. Paller disclosed that she is a consultant to and/or an investigator for AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, RAPT Therapeutics, Regeneron, and Sanofi.
Commentary by Robert Sidbury, MD, MPH
Dr. Paller reminds us of some essential features of pediatric psoriasis:
• It can hurt. Ask your patients if it does.
• It can itch. Look for excoriations, especially in the scalp.
• It is often associated with metabolic syndrome, so check relevant biometrics and labs, and consider coincident insulin resistance.
• Our traditional clinical trial target of PASI75, or a 75% reduction in body surface area involvement, is just not good enough. Studies have shown that the most meaningful quality-of-life gains come at PASI90 or above.
• With our newer biologics, such as IL-12/23 blockers (for instance, ustekinumab) and IL-17 blockers (for example, ixekizumab and secukinumab), PASI90 and better is a reasonable expectation, not a pipe dream.
Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.
This article was updated 6/16/22.
FROM SPD 2021
Three JAK inhibitors get boxed warnings, modified indications
The arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR) poses an increased risk of serious cardiac events such as heart attack or stroke, cancer, blood clots, and death, the Food and Drug Administration announced Sept 1.
Manufacturers of this drug along with other Janus kinase (JAK) inhibitors baricitinib (Olumiant) and upadacitinib (Rinvoq) must update their boxed warnings to include information about these health risks. The FDA made the determination after new study data from Pfizer, which manufacturers Xeljanz, found an association between a lower dose of Xeljanz and increased risk of blood clots and death.
“Recommendations for healthcare professionals will include consideration of the benefits and risks for the individual patient prior to initiating or continuing therapy,” the agency stated.
The FDA is limiting all approved uses of these three medications to patients who have not responded well to tumor necrosis factor (TNF) blockers to ensure their benefits outweigh their risks. Tofacitinib is indicated for rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis. Baricitinib and upadacitinib are approved only for RA. The FDA included baricitinib and upadacitinib in the warning because of the similar properties they share with tofacitinib, even though they haven’t been studied as extensively.
“We believe this update will bring important clarity for healthcare plans on the risk/benefit profile of Xeljanz, which is a medicine informed by more clinical data than any other JAK inhibitor,” Pfizer said in a statement.
Investigators for the ORAL Surveillance trial compared two doses of tofacitinib (5 mg twice daily and 10 mg twice daily) with TNF blockers in patients with rheumatoid arthritis who were aged 50 years or older with at least one additional cardiovascular risk factor.
For both dose regimens of tofacitinib, they found an increased risk of major adverse cardiovascular events, malignancies, thrombosis, and death compared with the TNF blocker regimen. In addition, rates of lung cancers and lymphomas were higher with tofacitinib. In trial data released earlier this year, Pfizer revealed that the tofacitinib group had a much higher incidence of adjudicated malignancies compared with the TNF blocker group (1.13 vs. 0.77 per 100 person-years; hazard ratio, 1.48; 95% confidence interval, 1.04-2.09).
Impact on clinical practice
Physicians treating patients who have rheumatoid arthritis with tofacitinib may initially decrease prescriptions following the FDA’s drug safety communication, said Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy) – particularly those with a principal mechanism of action slightly different from that of tofacitinib, he added.
“Tofacitinib is principally a JAK 1,3 inhibitor at usual concentrations, whereas upadacitinib and baricitinib are JAK 1,2 inhibitors. Thus, I speculate that the tofacitinib prescriptions will go down more than the upadacitinib and baricitinib prescriptions,” he said in an interview.
Some patients may also be worried about taking tofacitinib, particularly those with previous events or predisposing conditions, Dr. Furst noted.
“First and foremost, I think we need to actually look at the data in a publication rather than just an FDA statement before making huge changes in our practice,” he advised.
“I am looking forward to the data finally being published ... It’s interesting that the full data still isn’t really out there beyond the press releases and an abstract. I think there’s a lot more to learn about how these drugs work and who is really at risk for harmful events,” said Alexis R. Ogdie, MD, MSCE, associate professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia.
Pfizer’s data also may be affecting FDA approvals of other JAK inhibitors. This past summer, AbbVie and Eli Lilly stated that the FDA’s ongoing assessment of the safety trial was delaying the agency’s decisions about expanding use of their respective drugs upadacitinib and baricitinib.
“I think many rheumatologists have already taken this information in, and begun to incorporate it into their discussions with their patients” since it has been over a year since the first public release of information about the ORAL Surveillance trial, said Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego. “I don’t know that it will affect the approvals, but it will impact their labels.”
Wariness to prescribing tofacitinib may be lower for patients younger than those in the ORAL Surveillance trial without additional cardiovascular risk factors who are taking tofacitinib for non-RA indications, said gastroenterologist Miguel Regueiro, MD.
“The JAK inhibitor warning by the FDA is an important consideration for any prescriber or patient. The risk of cardiovascular disease and venous thromboembolism with this class of medicine appears higher in older rheumatoid arthritis patients with underlying cardiovascular disease. While the warning applies to all JAK inhibitors and likely the newer selective JAK inhibitors to come, we need to weigh the risk and benefit based on the indication for prescribing,” said Dr. Regueiro, chair of the Digestive Disease and Surgery Institute and of the department of gastroenterology, hepatology and nutrition at the Cleveland Clinic in Ohio.
“I do think that there will be a heightened awareness and wariness for older RA patients and for the prescribers. However, for inflammatory bowel disease (and other non-RA indications), it does not appear that the risk for cardiovascular disease and VTE are significantly increased. To that end, in my own practice, I still use tofacitinib for ulcerative colitis and will do the same for the selective JAK inhibitors to come for IBD. Of course, as with any medication, we need to have discussions with our patients, alert them to potential side effects and have an open line of communication for any questions or concerns.”
Gastroenterologist Stephen Hanauer, MD, professor of medicine at Northwestern University, Chicago, thought that while patients with RA have many other treatment options besides JAK inhibitors, fewer options available to patients with IBD “may motivate the use of oral [sphingosine-1-phosphate receptor modulator] agents such as ozanimod, although IBD patients are younger and [have fewer] MACE risk factors than RA patients, so absolute risk is very small in the ulcerative colitis population.”
Pfizer’s data may be affecting FDA approvals of other JAK inhibitors. This past summer, AbbVie and Eli Lilly stated that the FDA’s ongoing assessment of the safety trial was delaying the agency’s decisions about expanding use of their respective drugs upadacitinib and baricitinib.
The agency’s decision corroborates an earlier 2019 warning about the increased risk of blood clots and of death in patients with ulcerative colitis taking 10 mg tofacitinib twice daily.
The FDA said that two other JAK inhibitors, ruxolitinib (Jakafi) and fedratinib (Inrebic), are not indicated for the treatment of arthritis and other inflammatory conditions, and so are not a part of the updates being required.
Baricitinib, abrocitinib, and upadacitinib are currently under FDA review for treating atopic dermatitis (AD); a topical formulation of the JAK1/2 inhibitor ruxolitinib is under review for treating AD. Reviews for all 4 have been extended. In September 2020, baricitinib was approved for treating moderate to severe AD in Europe, at a dose of 4 mg once a day, with recommendations that the dose can be reduced to 2 mg once a day when the disease is under control, and that the dose may need to be reduced in patients with impaired kidney function, those with an increased risk of infections, and those older than aged 75 years.
In an interview, Jacob Thyssen, MD, PhD, professor of dermatology at the University of Copenhagen, said that in the EU, there has been “extensive education” about cardiovascular risks with baricitinib “and it is my impression that payers and dermatologists in Europe are confident that it is safe to use in AD.” In addition, there has been an emphasis on the differences in cardiovascular risk factors between RA and AD patients, “given that the latter group is generally young and lean.” In the United States, he added, it will be interesting to see which doses of the JAK inhibitors will be approved for AD.
Dr. Thyssen disclosed that he is a speaker, advisory board member and/or investigator for Regeneron, Sanofi-Genzyme, Eli Lilly, Pfizer, LEO Pharma, AbbVie, and Almirall.
*This story was updated 9/3/21 and 9/6/2021.
A version of this article first appeared on Medscape.com.
The arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR) poses an increased risk of serious cardiac events such as heart attack or stroke, cancer, blood clots, and death, the Food and Drug Administration announced Sept 1.
Manufacturers of this drug along with other Janus kinase (JAK) inhibitors baricitinib (Olumiant) and upadacitinib (Rinvoq) must update their boxed warnings to include information about these health risks. The FDA made the determination after new study data from Pfizer, which manufacturers Xeljanz, found an association between a lower dose of Xeljanz and increased risk of blood clots and death.
“Recommendations for healthcare professionals will include consideration of the benefits and risks for the individual patient prior to initiating or continuing therapy,” the agency stated.
The FDA is limiting all approved uses of these three medications to patients who have not responded well to tumor necrosis factor (TNF) blockers to ensure their benefits outweigh their risks. Tofacitinib is indicated for rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis. Baricitinib and upadacitinib are approved only for RA. The FDA included baricitinib and upadacitinib in the warning because of the similar properties they share with tofacitinib, even though they haven’t been studied as extensively.
“We believe this update will bring important clarity for healthcare plans on the risk/benefit profile of Xeljanz, which is a medicine informed by more clinical data than any other JAK inhibitor,” Pfizer said in a statement.
Investigators for the ORAL Surveillance trial compared two doses of tofacitinib (5 mg twice daily and 10 mg twice daily) with TNF blockers in patients with rheumatoid arthritis who were aged 50 years or older with at least one additional cardiovascular risk factor.
For both dose regimens of tofacitinib, they found an increased risk of major adverse cardiovascular events, malignancies, thrombosis, and death compared with the TNF blocker regimen. In addition, rates of lung cancers and lymphomas were higher with tofacitinib. In trial data released earlier this year, Pfizer revealed that the tofacitinib group had a much higher incidence of adjudicated malignancies compared with the TNF blocker group (1.13 vs. 0.77 per 100 person-years; hazard ratio, 1.48; 95% confidence interval, 1.04-2.09).
Impact on clinical practice
Physicians treating patients who have rheumatoid arthritis with tofacitinib may initially decrease prescriptions following the FDA’s drug safety communication, said Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy) – particularly those with a principal mechanism of action slightly different from that of tofacitinib, he added.
“Tofacitinib is principally a JAK 1,3 inhibitor at usual concentrations, whereas upadacitinib and baricitinib are JAK 1,2 inhibitors. Thus, I speculate that the tofacitinib prescriptions will go down more than the upadacitinib and baricitinib prescriptions,” he said in an interview.
Some patients may also be worried about taking tofacitinib, particularly those with previous events or predisposing conditions, Dr. Furst noted.
“First and foremost, I think we need to actually look at the data in a publication rather than just an FDA statement before making huge changes in our practice,” he advised.
“I am looking forward to the data finally being published ... It’s interesting that the full data still isn’t really out there beyond the press releases and an abstract. I think there’s a lot more to learn about how these drugs work and who is really at risk for harmful events,” said Alexis R. Ogdie, MD, MSCE, associate professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia.
Pfizer’s data also may be affecting FDA approvals of other JAK inhibitors. This past summer, AbbVie and Eli Lilly stated that the FDA’s ongoing assessment of the safety trial was delaying the agency’s decisions about expanding use of their respective drugs upadacitinib and baricitinib.
“I think many rheumatologists have already taken this information in, and begun to incorporate it into their discussions with their patients” since it has been over a year since the first public release of information about the ORAL Surveillance trial, said Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego. “I don’t know that it will affect the approvals, but it will impact their labels.”
Wariness to prescribing tofacitinib may be lower for patients younger than those in the ORAL Surveillance trial without additional cardiovascular risk factors who are taking tofacitinib for non-RA indications, said gastroenterologist Miguel Regueiro, MD.
“The JAK inhibitor warning by the FDA is an important consideration for any prescriber or patient. The risk of cardiovascular disease and venous thromboembolism with this class of medicine appears higher in older rheumatoid arthritis patients with underlying cardiovascular disease. While the warning applies to all JAK inhibitors and likely the newer selective JAK inhibitors to come, we need to weigh the risk and benefit based on the indication for prescribing,” said Dr. Regueiro, chair of the Digestive Disease and Surgery Institute and of the department of gastroenterology, hepatology and nutrition at the Cleveland Clinic in Ohio.
“I do think that there will be a heightened awareness and wariness for older RA patients and for the prescribers. However, for inflammatory bowel disease (and other non-RA indications), it does not appear that the risk for cardiovascular disease and VTE are significantly increased. To that end, in my own practice, I still use tofacitinib for ulcerative colitis and will do the same for the selective JAK inhibitors to come for IBD. Of course, as with any medication, we need to have discussions with our patients, alert them to potential side effects and have an open line of communication for any questions or concerns.”
Gastroenterologist Stephen Hanauer, MD, professor of medicine at Northwestern University, Chicago, thought that while patients with RA have many other treatment options besides JAK inhibitors, fewer options available to patients with IBD “may motivate the use of oral [sphingosine-1-phosphate receptor modulator] agents such as ozanimod, although IBD patients are younger and [have fewer] MACE risk factors than RA patients, so absolute risk is very small in the ulcerative colitis population.”
Pfizer’s data may be affecting FDA approvals of other JAK inhibitors. This past summer, AbbVie and Eli Lilly stated that the FDA’s ongoing assessment of the safety trial was delaying the agency’s decisions about expanding use of their respective drugs upadacitinib and baricitinib.
The agency’s decision corroborates an earlier 2019 warning about the increased risk of blood clots and of death in patients with ulcerative colitis taking 10 mg tofacitinib twice daily.
The FDA said that two other JAK inhibitors, ruxolitinib (Jakafi) and fedratinib (Inrebic), are not indicated for the treatment of arthritis and other inflammatory conditions, and so are not a part of the updates being required.
Baricitinib, abrocitinib, and upadacitinib are currently under FDA review for treating atopic dermatitis (AD); a topical formulation of the JAK1/2 inhibitor ruxolitinib is under review for treating AD. Reviews for all 4 have been extended. In September 2020, baricitinib was approved for treating moderate to severe AD in Europe, at a dose of 4 mg once a day, with recommendations that the dose can be reduced to 2 mg once a day when the disease is under control, and that the dose may need to be reduced in patients with impaired kidney function, those with an increased risk of infections, and those older than aged 75 years.
In an interview, Jacob Thyssen, MD, PhD, professor of dermatology at the University of Copenhagen, said that in the EU, there has been “extensive education” about cardiovascular risks with baricitinib “and it is my impression that payers and dermatologists in Europe are confident that it is safe to use in AD.” In addition, there has been an emphasis on the differences in cardiovascular risk factors between RA and AD patients, “given that the latter group is generally young and lean.” In the United States, he added, it will be interesting to see which doses of the JAK inhibitors will be approved for AD.
Dr. Thyssen disclosed that he is a speaker, advisory board member and/or investigator for Regeneron, Sanofi-Genzyme, Eli Lilly, Pfizer, LEO Pharma, AbbVie, and Almirall.
*This story was updated 9/3/21 and 9/6/2021.
A version of this article first appeared on Medscape.com.
The arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR) poses an increased risk of serious cardiac events such as heart attack or stroke, cancer, blood clots, and death, the Food and Drug Administration announced Sept 1.
Manufacturers of this drug along with other Janus kinase (JAK) inhibitors baricitinib (Olumiant) and upadacitinib (Rinvoq) must update their boxed warnings to include information about these health risks. The FDA made the determination after new study data from Pfizer, which manufacturers Xeljanz, found an association between a lower dose of Xeljanz and increased risk of blood clots and death.
“Recommendations for healthcare professionals will include consideration of the benefits and risks for the individual patient prior to initiating or continuing therapy,” the agency stated.
The FDA is limiting all approved uses of these three medications to patients who have not responded well to tumor necrosis factor (TNF) blockers to ensure their benefits outweigh their risks. Tofacitinib is indicated for rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis. Baricitinib and upadacitinib are approved only for RA. The FDA included baricitinib and upadacitinib in the warning because of the similar properties they share with tofacitinib, even though they haven’t been studied as extensively.
“We believe this update will bring important clarity for healthcare plans on the risk/benefit profile of Xeljanz, which is a medicine informed by more clinical data than any other JAK inhibitor,” Pfizer said in a statement.
Investigators for the ORAL Surveillance trial compared two doses of tofacitinib (5 mg twice daily and 10 mg twice daily) with TNF blockers in patients with rheumatoid arthritis who were aged 50 years or older with at least one additional cardiovascular risk factor.
For both dose regimens of tofacitinib, they found an increased risk of major adverse cardiovascular events, malignancies, thrombosis, and death compared with the TNF blocker regimen. In addition, rates of lung cancers and lymphomas were higher with tofacitinib. In trial data released earlier this year, Pfizer revealed that the tofacitinib group had a much higher incidence of adjudicated malignancies compared with the TNF blocker group (1.13 vs. 0.77 per 100 person-years; hazard ratio, 1.48; 95% confidence interval, 1.04-2.09).
Impact on clinical practice
Physicians treating patients who have rheumatoid arthritis with tofacitinib may initially decrease prescriptions following the FDA’s drug safety communication, said Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, adjunct professor at the University of Washington, Seattle, and a research professor at the University of Florence (Italy) – particularly those with a principal mechanism of action slightly different from that of tofacitinib, he added.
“Tofacitinib is principally a JAK 1,3 inhibitor at usual concentrations, whereas upadacitinib and baricitinib are JAK 1,2 inhibitors. Thus, I speculate that the tofacitinib prescriptions will go down more than the upadacitinib and baricitinib prescriptions,” he said in an interview.
Some patients may also be worried about taking tofacitinib, particularly those with previous events or predisposing conditions, Dr. Furst noted.
“First and foremost, I think we need to actually look at the data in a publication rather than just an FDA statement before making huge changes in our practice,” he advised.
“I am looking forward to the data finally being published ... It’s interesting that the full data still isn’t really out there beyond the press releases and an abstract. I think there’s a lot more to learn about how these drugs work and who is really at risk for harmful events,” said Alexis R. Ogdie, MD, MSCE, associate professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia.
Pfizer’s data also may be affecting FDA approvals of other JAK inhibitors. This past summer, AbbVie and Eli Lilly stated that the FDA’s ongoing assessment of the safety trial was delaying the agency’s decisions about expanding use of their respective drugs upadacitinib and baricitinib.
“I think many rheumatologists have already taken this information in, and begun to incorporate it into their discussions with their patients” since it has been over a year since the first public release of information about the ORAL Surveillance trial, said Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego. “I don’t know that it will affect the approvals, but it will impact their labels.”
Wariness to prescribing tofacitinib may be lower for patients younger than those in the ORAL Surveillance trial without additional cardiovascular risk factors who are taking tofacitinib for non-RA indications, said gastroenterologist Miguel Regueiro, MD.
“The JAK inhibitor warning by the FDA is an important consideration for any prescriber or patient. The risk of cardiovascular disease and venous thromboembolism with this class of medicine appears higher in older rheumatoid arthritis patients with underlying cardiovascular disease. While the warning applies to all JAK inhibitors and likely the newer selective JAK inhibitors to come, we need to weigh the risk and benefit based on the indication for prescribing,” said Dr. Regueiro, chair of the Digestive Disease and Surgery Institute and of the department of gastroenterology, hepatology and nutrition at the Cleveland Clinic in Ohio.
“I do think that there will be a heightened awareness and wariness for older RA patients and for the prescribers. However, for inflammatory bowel disease (and other non-RA indications), it does not appear that the risk for cardiovascular disease and VTE are significantly increased. To that end, in my own practice, I still use tofacitinib for ulcerative colitis and will do the same for the selective JAK inhibitors to come for IBD. Of course, as with any medication, we need to have discussions with our patients, alert them to potential side effects and have an open line of communication for any questions or concerns.”
Gastroenterologist Stephen Hanauer, MD, professor of medicine at Northwestern University, Chicago, thought that while patients with RA have many other treatment options besides JAK inhibitors, fewer options available to patients with IBD “may motivate the use of oral [sphingosine-1-phosphate receptor modulator] agents such as ozanimod, although IBD patients are younger and [have fewer] MACE risk factors than RA patients, so absolute risk is very small in the ulcerative colitis population.”
Pfizer’s data may be affecting FDA approvals of other JAK inhibitors. This past summer, AbbVie and Eli Lilly stated that the FDA’s ongoing assessment of the safety trial was delaying the agency’s decisions about expanding use of their respective drugs upadacitinib and baricitinib.
The agency’s decision corroborates an earlier 2019 warning about the increased risk of blood clots and of death in patients with ulcerative colitis taking 10 mg tofacitinib twice daily.
The FDA said that two other JAK inhibitors, ruxolitinib (Jakafi) and fedratinib (Inrebic), are not indicated for the treatment of arthritis and other inflammatory conditions, and so are not a part of the updates being required.
Baricitinib, abrocitinib, and upadacitinib are currently under FDA review for treating atopic dermatitis (AD); a topical formulation of the JAK1/2 inhibitor ruxolitinib is under review for treating AD. Reviews for all 4 have been extended. In September 2020, baricitinib was approved for treating moderate to severe AD in Europe, at a dose of 4 mg once a day, with recommendations that the dose can be reduced to 2 mg once a day when the disease is under control, and that the dose may need to be reduced in patients with impaired kidney function, those with an increased risk of infections, and those older than aged 75 years.
In an interview, Jacob Thyssen, MD, PhD, professor of dermatology at the University of Copenhagen, said that in the EU, there has been “extensive education” about cardiovascular risks with baricitinib “and it is my impression that payers and dermatologists in Europe are confident that it is safe to use in AD.” In addition, there has been an emphasis on the differences in cardiovascular risk factors between RA and AD patients, “given that the latter group is generally young and lean.” In the United States, he added, it will be interesting to see which doses of the JAK inhibitors will be approved for AD.
Dr. Thyssen disclosed that he is a speaker, advisory board member and/or investigator for Regeneron, Sanofi-Genzyme, Eli Lilly, Pfizer, LEO Pharma, AbbVie, and Almirall.
*This story was updated 9/3/21 and 9/6/2021.
A version of this article first appeared on Medscape.com.
Clinical Edge Journal Scan Commentary: PsA September 2021
Identifying risk factors for onset of Psoriatic Arthritis (PsA) is a major unmet need. Comparing potential risk factors for the diagnosis of PsA, rheumatoid arthritis (RA), and ankylosing spondylitis (AS) is of interest. Such studies may help us identify shared and unique risk factors of onset of chronic inflammatory arthritis. Meer E et al compared potential risk factors for the diagnosis of PsA, psoriasis, RA, and AS. They conducted four parallel case-control studies using data collected between 1994 and 2015 in The Health Improvement Network, an anonymized longitudinal patient dataset collected at primary care clinics throughout the United Kingdom. PsA was associated with obesity, pharyngitis, skin infections, moderate alcohol intake, gout, and uveitis. As expected, PsA and AS were associated with uveitis. Interestingly, PsA and RA were associated with preceding gout. Smoking was a risk factor for all disease and statin use was inversely associated with all 4 diseases. This study has identified potential risk factors for inflammatory diseases including PsA and may help in early identification as well as risk mitigation.
Most patients develop psoriatic arthritis (PsA) after or simultaneously with cutaneous psoriasis. The mechanisms underlying progression from cutaneous psoriasis to arthritis psoriasis are currently unclear. An important question is whether modern targeted treatment of cutaneous psoriasis reduces the risk of developing PsA. To address this, Acosta Felquer ML et al conducted a retrospective cohort study to compare the incidence of PsA in 1719 patients with psoriasis (14,721 patient/years of follow up) grouped according to different treatments for their skin psoriasis: topicals, phototherapy or no treatment (n= 1387), conventional disease-modifying antirheumatic drugs (cDMARDs) or biological DMARDs (bDMARDs). During follow-up, 239 patients (14%) developed PsA. The risk of developing PsA in patients treated with bDMARDs was significantly lower (incidence rate ratio (IRR)=0.26; 95% CI 0.03 to 0.94), compared with topicals, but not compared with cDMARDs (IRR=0.35; 95% CI 0.035 to 1.96). Male sex, nail involvement and higher body mass index were associated with increased risk of developing PsA, while bDMARD use was protective. Thus, this study provides some evidence that systemic treatment might ‘protect’ against development if PsA. Appropriately designed prospective studies are required.
One important clinical question is whether patients with oligoarthritis (involvement of <5 joints) progress to polyarthritis. In an observational study Gladman DD et al reported that in 407 patients evaluated within 12 months of diagnosis, 192 (47%) presented with oligoarthritis. More patients with polyarthritis presented with dactylitis, enthesitis, higher HAQ and lower SF-36 scores. Of the 192 patients with oligoarthritis, 75 (39%) progressed to polyarthritis. Lower SF-36 mental component summary score was the predictor for progressing to polyarthritis. Thus, except for the burden of musculoskeletal involvement, oligoarticular PsA resembles polyarticular PsA and therefore the two PsA subclasses should simply be classified together as peripheral arthritis.
Identifying risk factors for onset of Psoriatic Arthritis (PsA) is a major unmet need. Comparing potential risk factors for the diagnosis of PsA, rheumatoid arthritis (RA), and ankylosing spondylitis (AS) is of interest. Such studies may help us identify shared and unique risk factors of onset of chronic inflammatory arthritis. Meer E et al compared potential risk factors for the diagnosis of PsA, psoriasis, RA, and AS. They conducted four parallel case-control studies using data collected between 1994 and 2015 in The Health Improvement Network, an anonymized longitudinal patient dataset collected at primary care clinics throughout the United Kingdom. PsA was associated with obesity, pharyngitis, skin infections, moderate alcohol intake, gout, and uveitis. As expected, PsA and AS were associated with uveitis. Interestingly, PsA and RA were associated with preceding gout. Smoking was a risk factor for all disease and statin use was inversely associated with all 4 diseases. This study has identified potential risk factors for inflammatory diseases including PsA and may help in early identification as well as risk mitigation.
Most patients develop psoriatic arthritis (PsA) after or simultaneously with cutaneous psoriasis. The mechanisms underlying progression from cutaneous psoriasis to arthritis psoriasis are currently unclear. An important question is whether modern targeted treatment of cutaneous psoriasis reduces the risk of developing PsA. To address this, Acosta Felquer ML et al conducted a retrospective cohort study to compare the incidence of PsA in 1719 patients with psoriasis (14,721 patient/years of follow up) grouped according to different treatments for their skin psoriasis: topicals, phototherapy or no treatment (n= 1387), conventional disease-modifying antirheumatic drugs (cDMARDs) or biological DMARDs (bDMARDs). During follow-up, 239 patients (14%) developed PsA. The risk of developing PsA in patients treated with bDMARDs was significantly lower (incidence rate ratio (IRR)=0.26; 95% CI 0.03 to 0.94), compared with topicals, but not compared with cDMARDs (IRR=0.35; 95% CI 0.035 to 1.96). Male sex, nail involvement and higher body mass index were associated with increased risk of developing PsA, while bDMARD use was protective. Thus, this study provides some evidence that systemic treatment might ‘protect’ against development if PsA. Appropriately designed prospective studies are required.
One important clinical question is whether patients with oligoarthritis (involvement of <5 joints) progress to polyarthritis. In an observational study Gladman DD et al reported that in 407 patients evaluated within 12 months of diagnosis, 192 (47%) presented with oligoarthritis. More patients with polyarthritis presented with dactylitis, enthesitis, higher HAQ and lower SF-36 scores. Of the 192 patients with oligoarthritis, 75 (39%) progressed to polyarthritis. Lower SF-36 mental component summary score was the predictor for progressing to polyarthritis. Thus, except for the burden of musculoskeletal involvement, oligoarticular PsA resembles polyarticular PsA and therefore the two PsA subclasses should simply be classified together as peripheral arthritis.
Identifying risk factors for onset of Psoriatic Arthritis (PsA) is a major unmet need. Comparing potential risk factors for the diagnosis of PsA, rheumatoid arthritis (RA), and ankylosing spondylitis (AS) is of interest. Such studies may help us identify shared and unique risk factors of onset of chronic inflammatory arthritis. Meer E et al compared potential risk factors for the diagnosis of PsA, psoriasis, RA, and AS. They conducted four parallel case-control studies using data collected between 1994 and 2015 in The Health Improvement Network, an anonymized longitudinal patient dataset collected at primary care clinics throughout the United Kingdom. PsA was associated with obesity, pharyngitis, skin infections, moderate alcohol intake, gout, and uveitis. As expected, PsA and AS were associated with uveitis. Interestingly, PsA and RA were associated with preceding gout. Smoking was a risk factor for all disease and statin use was inversely associated with all 4 diseases. This study has identified potential risk factors for inflammatory diseases including PsA and may help in early identification as well as risk mitigation.
Most patients develop psoriatic arthritis (PsA) after or simultaneously with cutaneous psoriasis. The mechanisms underlying progression from cutaneous psoriasis to arthritis psoriasis are currently unclear. An important question is whether modern targeted treatment of cutaneous psoriasis reduces the risk of developing PsA. To address this, Acosta Felquer ML et al conducted a retrospective cohort study to compare the incidence of PsA in 1719 patients with psoriasis (14,721 patient/years of follow up) grouped according to different treatments for their skin psoriasis: topicals, phototherapy or no treatment (n= 1387), conventional disease-modifying antirheumatic drugs (cDMARDs) or biological DMARDs (bDMARDs). During follow-up, 239 patients (14%) developed PsA. The risk of developing PsA in patients treated with bDMARDs was significantly lower (incidence rate ratio (IRR)=0.26; 95% CI 0.03 to 0.94), compared with topicals, but not compared with cDMARDs (IRR=0.35; 95% CI 0.035 to 1.96). Male sex, nail involvement and higher body mass index were associated with increased risk of developing PsA, while bDMARD use was protective. Thus, this study provides some evidence that systemic treatment might ‘protect’ against development if PsA. Appropriately designed prospective studies are required.
One important clinical question is whether patients with oligoarthritis (involvement of <5 joints) progress to polyarthritis. In an observational study Gladman DD et al reported that in 407 patients evaluated within 12 months of diagnosis, 192 (47%) presented with oligoarthritis. More patients with polyarthritis presented with dactylitis, enthesitis, higher HAQ and lower SF-36 scores. Of the 192 patients with oligoarthritis, 75 (39%) progressed to polyarthritis. Lower SF-36 mental component summary score was the predictor for progressing to polyarthritis. Thus, except for the burden of musculoskeletal involvement, oligoarticular PsA resembles polyarticular PsA and therefore the two PsA subclasses should simply be classified together as peripheral arthritis.
Biologic benefit in psoriasis might extend to arthritis prevention
Receiving treatment with a biologic medication, compared with no biologic treatment, appeared to be associated with a lower risk for developing psoriatic arthritis (PsA) in patients with psoriasis.
That’s according to the results of a nested case-control study involving electronic medical record data from an Israeli health maintenance organization in Arthritis & Rheumatology. Compared with no biologic treatment, the risk for developing PsA among PsO patients was reduced by 39%.
This study shows “a statistically and clinically significant lower risk for developing PsA among patients receiving biologic medications for psoriasis treatment,” wrote Yael Shalev Rosenthal, MPH, of the Sackler Faculty of Medicine, Tel Aviv University and colleagues. “The results suggest considering treatment with biologic medications in patients [who] present with significant risk factors for PsA at an earlier stage of treatment.”
“It would be nice to believe this story, but I don’t think we can based on the evidence we’ve got so far,” commented Philip Helliwell, PhD, DM, in an interview.
Dr. Helliwell, who is professor of clinical rheumatology at the University of Leeds (England) and an Honorary Consultant Rheumatologist for the Leeds Teaching Hospitals and Bradford Teaching Hospitals NHS Trust, noted that there were several issues with the current evidence.
Aside from their often retrospective or nonrandomized nature, prior analyses, including the current one, were based on EMR data.
“There’s actually no face-to-face patient contact going on here. It’s all done on coding, and coding can be unreliable,” Dr. Helliwell said.
While the study’s findings are “in line with other studies that have looked at this, and suggest that if you get a biologic, you’re less likely to get PsA with your psoriasis, there could be lots of reasons why.”
The big problem here is confounding by indication. “You don’t get on a biologic unless you’ve got bad psoriasis,” Dr. Helliwell explained. The Israeli criteria for starting a biologic are much higher than in the United Kingdom, he added, requiring more than 50% of patients’ body surface area to be affected, or a Psoriasis Area and Severity Index score of more than 50. Moreover, people with bad psoriasis are more likely to get PsA. This, however, makes the results more impressive.
Confounding by indication is an issue with this study, agreed consultant rheumatologist Adewale Adebajo, PhD, in a separate interview. He acknowledged, however, that the study’s authors did try to account for this by limiting the timescale of their analysis to the first 10 years of biologic therapy. They also used the usual methods of propensity score matching and multivariate Cox regression analysis to hopefully iron out any differences between the two groups of patients.
Study details and results
Ms. Rosenthal and coauthors analyzed EMR data on patients with psoriasis but not PsA that were logged in the Maccabi Healthcare Services (MHS) database. The MHS is the second-largest health maintenance organization in Israel, insuring over 2 million members, the researchers said.
In all, 663 patients with psoriasis but not PsA before or at initiation of biologic treatment were included in their analysis and matched to a control group of 663 patients with psoriasis who had not received biologic treatment. Propensity score matching was used to iron out some differences in baseline characteristics that had been seen between the groups, such as older age at diagnosis, higher body mass index, and a longer time between diagnosis and treatment seen in patients treated without biologics.
After adjusting for multiple risk factors and confounders, “the control group still had a significantly higher risk for PsA, compared to the biological treatment group,” the researchers wrote. Indeed, the adjusted hazard ratio was 1.39, with a 95% confidence interval between 1.03 and 1.87.
An ‘intriguing study’
“This is a retrospective study, and it has all the faults of a retrospective study,” said Dr. Adebajo, associate medical director for research and development at Barnsley (England) NHS Foundation Trust. But “these were patients who hopefully hadn’t yet developed psoriatic arthritis, although it is difficult to exclude subclinical psoriatic arthritis.”
The ideal would of course be to look at patients prospectively, but a randomized clinical trial would be unlikely to ever be conducted, Dr. Helliwell noted. “It would be unfair to randomize people who have got bad psoriasis and need a biologic to placebo just to prove the point really,” he said. “Getting control groups in this arena is very difficult.”
That doesn’t mean that prospective evaluation is not possible. Dr. Adebajo noted that there were already cohorts of newly diagnosed patients who were being prospectively followed up and those could perhaps be used to look at the question again in the future.
“You’re then looking at the natural history, the natural outcome, and you don’t need to worry about confounding because you’re just collecting all of the information as you go along.”
The idea that biologics might slow or even prevent the onset of PsA is “an interesting and enchanting hypothesis,” Dr. Adebajo said. “The study doesn’t prove the hypothesis, but it’s an intriguing study because it doesn’t disprove the hypothesis either.
“It gives us food for thought and a basis for further studies,” as well as some “encouragement to perhaps use biologics earlier because there may be additional benefits of doing so.”
That’s still to be proven of course, as it has been reported that patients with psoriasis can develop PsA while taking biologics.
“Clinically, that’s what we see in the combined clinic. We get people referred with psoriasis [who are] already on a biologic who developed musculoskeletal problems,” Dr. Helliwell said.
“It would be nice to believe” that biologics prevent or slow PsA in patients with psoriasis, Dr. Helliwell added, but I’m not sure these data are conclusive. From this study we know nothing about the phenotype of psoriasis, which is important in the development of PsA. In addition, we know that of the 30% of people with psoriasis who develop PsA, about half of these are undiagnosed at the time of such studies. In that case, what the biologic is doing is just treating preexisting PsA. If you count those numbers up, some of the differences between the two groups seen in this study are accounted for. From registry data there is no way of checking this.”
No external funding was used for the study. One author acknowledged acting as an investigator, adviser, or consultant to several pharmaceutical companies including AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Coherus, Dexcel Pharma, Eli Lilly, Janssen, Novartis, and Pfizer. All other authors had nothing to disclose.
Dr. Helliwell and Dr. Adebajo had no conflicts of interest.
Receiving treatment with a biologic medication, compared with no biologic treatment, appeared to be associated with a lower risk for developing psoriatic arthritis (PsA) in patients with psoriasis.
That’s according to the results of a nested case-control study involving electronic medical record data from an Israeli health maintenance organization in Arthritis & Rheumatology. Compared with no biologic treatment, the risk for developing PsA among PsO patients was reduced by 39%.
This study shows “a statistically and clinically significant lower risk for developing PsA among patients receiving biologic medications for psoriasis treatment,” wrote Yael Shalev Rosenthal, MPH, of the Sackler Faculty of Medicine, Tel Aviv University and colleagues. “The results suggest considering treatment with biologic medications in patients [who] present with significant risk factors for PsA at an earlier stage of treatment.”
“It would be nice to believe this story, but I don’t think we can based on the evidence we’ve got so far,” commented Philip Helliwell, PhD, DM, in an interview.
Dr. Helliwell, who is professor of clinical rheumatology at the University of Leeds (England) and an Honorary Consultant Rheumatologist for the Leeds Teaching Hospitals and Bradford Teaching Hospitals NHS Trust, noted that there were several issues with the current evidence.
Aside from their often retrospective or nonrandomized nature, prior analyses, including the current one, were based on EMR data.
“There’s actually no face-to-face patient contact going on here. It’s all done on coding, and coding can be unreliable,” Dr. Helliwell said.
While the study’s findings are “in line with other studies that have looked at this, and suggest that if you get a biologic, you’re less likely to get PsA with your psoriasis, there could be lots of reasons why.”
The big problem here is confounding by indication. “You don’t get on a biologic unless you’ve got bad psoriasis,” Dr. Helliwell explained. The Israeli criteria for starting a biologic are much higher than in the United Kingdom, he added, requiring more than 50% of patients’ body surface area to be affected, or a Psoriasis Area and Severity Index score of more than 50. Moreover, people with bad psoriasis are more likely to get PsA. This, however, makes the results more impressive.
Confounding by indication is an issue with this study, agreed consultant rheumatologist Adewale Adebajo, PhD, in a separate interview. He acknowledged, however, that the study’s authors did try to account for this by limiting the timescale of their analysis to the first 10 years of biologic therapy. They also used the usual methods of propensity score matching and multivariate Cox regression analysis to hopefully iron out any differences between the two groups of patients.
Study details and results
Ms. Rosenthal and coauthors analyzed EMR data on patients with psoriasis but not PsA that were logged in the Maccabi Healthcare Services (MHS) database. The MHS is the second-largest health maintenance organization in Israel, insuring over 2 million members, the researchers said.
In all, 663 patients with psoriasis but not PsA before or at initiation of biologic treatment were included in their analysis and matched to a control group of 663 patients with psoriasis who had not received biologic treatment. Propensity score matching was used to iron out some differences in baseline characteristics that had been seen between the groups, such as older age at diagnosis, higher body mass index, and a longer time between diagnosis and treatment seen in patients treated without biologics.
After adjusting for multiple risk factors and confounders, “the control group still had a significantly higher risk for PsA, compared to the biological treatment group,” the researchers wrote. Indeed, the adjusted hazard ratio was 1.39, with a 95% confidence interval between 1.03 and 1.87.
An ‘intriguing study’
“This is a retrospective study, and it has all the faults of a retrospective study,” said Dr. Adebajo, associate medical director for research and development at Barnsley (England) NHS Foundation Trust. But “these were patients who hopefully hadn’t yet developed psoriatic arthritis, although it is difficult to exclude subclinical psoriatic arthritis.”
The ideal would of course be to look at patients prospectively, but a randomized clinical trial would be unlikely to ever be conducted, Dr. Helliwell noted. “It would be unfair to randomize people who have got bad psoriasis and need a biologic to placebo just to prove the point really,” he said. “Getting control groups in this arena is very difficult.”
That doesn’t mean that prospective evaluation is not possible. Dr. Adebajo noted that there were already cohorts of newly diagnosed patients who were being prospectively followed up and those could perhaps be used to look at the question again in the future.
“You’re then looking at the natural history, the natural outcome, and you don’t need to worry about confounding because you’re just collecting all of the information as you go along.”
The idea that biologics might slow or even prevent the onset of PsA is “an interesting and enchanting hypothesis,” Dr. Adebajo said. “The study doesn’t prove the hypothesis, but it’s an intriguing study because it doesn’t disprove the hypothesis either.
“It gives us food for thought and a basis for further studies,” as well as some “encouragement to perhaps use biologics earlier because there may be additional benefits of doing so.”
That’s still to be proven of course, as it has been reported that patients with psoriasis can develop PsA while taking biologics.
“Clinically, that’s what we see in the combined clinic. We get people referred with psoriasis [who are] already on a biologic who developed musculoskeletal problems,” Dr. Helliwell said.
“It would be nice to believe” that biologics prevent or slow PsA in patients with psoriasis, Dr. Helliwell added, but I’m not sure these data are conclusive. From this study we know nothing about the phenotype of psoriasis, which is important in the development of PsA. In addition, we know that of the 30% of people with psoriasis who develop PsA, about half of these are undiagnosed at the time of such studies. In that case, what the biologic is doing is just treating preexisting PsA. If you count those numbers up, some of the differences between the two groups seen in this study are accounted for. From registry data there is no way of checking this.”
No external funding was used for the study. One author acknowledged acting as an investigator, adviser, or consultant to several pharmaceutical companies including AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Coherus, Dexcel Pharma, Eli Lilly, Janssen, Novartis, and Pfizer. All other authors had nothing to disclose.
Dr. Helliwell and Dr. Adebajo had no conflicts of interest.
Receiving treatment with a biologic medication, compared with no biologic treatment, appeared to be associated with a lower risk for developing psoriatic arthritis (PsA) in patients with psoriasis.
That’s according to the results of a nested case-control study involving electronic medical record data from an Israeli health maintenance organization in Arthritis & Rheumatology. Compared with no biologic treatment, the risk for developing PsA among PsO patients was reduced by 39%.
This study shows “a statistically and clinically significant lower risk for developing PsA among patients receiving biologic medications for psoriasis treatment,” wrote Yael Shalev Rosenthal, MPH, of the Sackler Faculty of Medicine, Tel Aviv University and colleagues. “The results suggest considering treatment with biologic medications in patients [who] present with significant risk factors for PsA at an earlier stage of treatment.”
“It would be nice to believe this story, but I don’t think we can based on the evidence we’ve got so far,” commented Philip Helliwell, PhD, DM, in an interview.
Dr. Helliwell, who is professor of clinical rheumatology at the University of Leeds (England) and an Honorary Consultant Rheumatologist for the Leeds Teaching Hospitals and Bradford Teaching Hospitals NHS Trust, noted that there were several issues with the current evidence.
Aside from their often retrospective or nonrandomized nature, prior analyses, including the current one, were based on EMR data.
“There’s actually no face-to-face patient contact going on here. It’s all done on coding, and coding can be unreliable,” Dr. Helliwell said.
While the study’s findings are “in line with other studies that have looked at this, and suggest that if you get a biologic, you’re less likely to get PsA with your psoriasis, there could be lots of reasons why.”
The big problem here is confounding by indication. “You don’t get on a biologic unless you’ve got bad psoriasis,” Dr. Helliwell explained. The Israeli criteria for starting a biologic are much higher than in the United Kingdom, he added, requiring more than 50% of patients’ body surface area to be affected, or a Psoriasis Area and Severity Index score of more than 50. Moreover, people with bad psoriasis are more likely to get PsA. This, however, makes the results more impressive.
Confounding by indication is an issue with this study, agreed consultant rheumatologist Adewale Adebajo, PhD, in a separate interview. He acknowledged, however, that the study’s authors did try to account for this by limiting the timescale of their analysis to the first 10 years of biologic therapy. They also used the usual methods of propensity score matching and multivariate Cox regression analysis to hopefully iron out any differences between the two groups of patients.
Study details and results
Ms. Rosenthal and coauthors analyzed EMR data on patients with psoriasis but not PsA that were logged in the Maccabi Healthcare Services (MHS) database. The MHS is the second-largest health maintenance organization in Israel, insuring over 2 million members, the researchers said.
In all, 663 patients with psoriasis but not PsA before or at initiation of biologic treatment were included in their analysis and matched to a control group of 663 patients with psoriasis who had not received biologic treatment. Propensity score matching was used to iron out some differences in baseline characteristics that had been seen between the groups, such as older age at diagnosis, higher body mass index, and a longer time between diagnosis and treatment seen in patients treated without biologics.
After adjusting for multiple risk factors and confounders, “the control group still had a significantly higher risk for PsA, compared to the biological treatment group,” the researchers wrote. Indeed, the adjusted hazard ratio was 1.39, with a 95% confidence interval between 1.03 and 1.87.
An ‘intriguing study’
“This is a retrospective study, and it has all the faults of a retrospective study,” said Dr. Adebajo, associate medical director for research and development at Barnsley (England) NHS Foundation Trust. But “these were patients who hopefully hadn’t yet developed psoriatic arthritis, although it is difficult to exclude subclinical psoriatic arthritis.”
The ideal would of course be to look at patients prospectively, but a randomized clinical trial would be unlikely to ever be conducted, Dr. Helliwell noted. “It would be unfair to randomize people who have got bad psoriasis and need a biologic to placebo just to prove the point really,” he said. “Getting control groups in this arena is very difficult.”
That doesn’t mean that prospective evaluation is not possible. Dr. Adebajo noted that there were already cohorts of newly diagnosed patients who were being prospectively followed up and those could perhaps be used to look at the question again in the future.
“You’re then looking at the natural history, the natural outcome, and you don’t need to worry about confounding because you’re just collecting all of the information as you go along.”
The idea that biologics might slow or even prevent the onset of PsA is “an interesting and enchanting hypothesis,” Dr. Adebajo said. “The study doesn’t prove the hypothesis, but it’s an intriguing study because it doesn’t disprove the hypothesis either.
“It gives us food for thought and a basis for further studies,” as well as some “encouragement to perhaps use biologics earlier because there may be additional benefits of doing so.”
That’s still to be proven of course, as it has been reported that patients with psoriasis can develop PsA while taking biologics.
“Clinically, that’s what we see in the combined clinic. We get people referred with psoriasis [who are] already on a biologic who developed musculoskeletal problems,” Dr. Helliwell said.
“It would be nice to believe” that biologics prevent or slow PsA in patients with psoriasis, Dr. Helliwell added, but I’m not sure these data are conclusive. From this study we know nothing about the phenotype of psoriasis, which is important in the development of PsA. In addition, we know that of the 30% of people with psoriasis who develop PsA, about half of these are undiagnosed at the time of such studies. In that case, what the biologic is doing is just treating preexisting PsA. If you count those numbers up, some of the differences between the two groups seen in this study are accounted for. From registry data there is no way of checking this.”
No external funding was used for the study. One author acknowledged acting as an investigator, adviser, or consultant to several pharmaceutical companies including AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Coherus, Dexcel Pharma, Eli Lilly, Janssen, Novartis, and Pfizer. All other authors had nothing to disclose.
Dr. Helliwell and Dr. Adebajo had no conflicts of interest.
FROM ARTHRITIS & RHEUMATOLOGY
Circulating miR-140 and serum leptin could help discriminate PsA from RA
Key clinical point: Increased expression levels of circulating microRNA (miRNA) like miR-140 and serum levels of few adipokines like leptin could serve as biomarkers for psoriatic arthritis (PsA) and could be particularly helpful in the differential diagnosis of peripheral PsA from other rheumatic diseases like rheumatoid arthritis (RA).
Major finding: MiR-140 and serum leptin levels were significantly higher in patients with PsA vs those with RA and healthy controls (HCs; both P < .001) and served as predictors of RA vs PsA (area under the receiver-operating characteristic curve, 0.91 and 0.83, respectively).
Study details: Findings are from a case-control study including 50 patients with peripheral PsA, 50 patients with RA, and 50 HCs.
Disclosures: No specific funding was received for this study. The authors declared no conflict of interests.
Source: Cheleschi S et al. Transl Res. 2021 Aug 8. doi: 10.1016/j.trsl.2021.08.001.
Key clinical point: Increased expression levels of circulating microRNA (miRNA) like miR-140 and serum levels of few adipokines like leptin could serve as biomarkers for psoriatic arthritis (PsA) and could be particularly helpful in the differential diagnosis of peripheral PsA from other rheumatic diseases like rheumatoid arthritis (RA).
Major finding: MiR-140 and serum leptin levels were significantly higher in patients with PsA vs those with RA and healthy controls (HCs; both P < .001) and served as predictors of RA vs PsA (area under the receiver-operating characteristic curve, 0.91 and 0.83, respectively).
Study details: Findings are from a case-control study including 50 patients with peripheral PsA, 50 patients with RA, and 50 HCs.
Disclosures: No specific funding was received for this study. The authors declared no conflict of interests.
Source: Cheleschi S et al. Transl Res. 2021 Aug 8. doi: 10.1016/j.trsl.2021.08.001.
Key clinical point: Increased expression levels of circulating microRNA (miRNA) like miR-140 and serum levels of few adipokines like leptin could serve as biomarkers for psoriatic arthritis (PsA) and could be particularly helpful in the differential diagnosis of peripheral PsA from other rheumatic diseases like rheumatoid arthritis (RA).
Major finding: MiR-140 and serum leptin levels were significantly higher in patients with PsA vs those with RA and healthy controls (HCs; both P < .001) and served as predictors of RA vs PsA (area under the receiver-operating characteristic curve, 0.91 and 0.83, respectively).
Study details: Findings are from a case-control study including 50 patients with peripheral PsA, 50 patients with RA, and 50 HCs.
Disclosures: No specific funding was received for this study. The authors declared no conflict of interests.
Source: Cheleschi S et al. Transl Res. 2021 Aug 8. doi: 10.1016/j.trsl.2021.08.001.
Identifying potential risks factors for PsA
Key clinical point: A previous diagnosis of gout, uveitis, metabolic and lifestyle factors like obesity, alcohol consumption, and infections like pharyngitis and skin infections were potential risk factors for psoriatic arthritis (PsA), whereas statin use showed a negative association with PsA.
Major finding: A previous diagnosis of gout (odds ratio [OR], 2.19), uveitis (OR, 3.79), alcohol use (OR, 1.67), obesity (OR, 1.64), pharyngitis (OR, 1.23), and skin infection (OR, 1.37; all P < .001) were significant risk factors for PsA. The use of statin was negatively associated with PsA (OR, 0.53; P < .001).
Study details: This was a set of 4 separate case-control studies conducted in parallel and included cases of incident PsA (n=7,594), psoriasis (n=111,375), rheumatoid arthritis (RA; n=28,341), and ankylosing spondylitis (AS; n=3,253) matched to control participants (PsA, n=75,930; psoriasis, n=1113,345; RA, n=283,226; and AS, n=32,530).
Disclosures: This work was supported by grants from the National Institute of Health and internal grants from the University of Pennsylvania. Dr. Gelfand, Dr. Love, and Dr. Ogdie declared receiving research grants, honoraria, and reimbursement from and/or serving as a consultant for various sources.
Source: Meer E et al. J Rheumatol. 2021 Aug 1. doi: 10.3899/jrheum.210006.
Key clinical point: A previous diagnosis of gout, uveitis, metabolic and lifestyle factors like obesity, alcohol consumption, and infections like pharyngitis and skin infections were potential risk factors for psoriatic arthritis (PsA), whereas statin use showed a negative association with PsA.
Major finding: A previous diagnosis of gout (odds ratio [OR], 2.19), uveitis (OR, 3.79), alcohol use (OR, 1.67), obesity (OR, 1.64), pharyngitis (OR, 1.23), and skin infection (OR, 1.37; all P < .001) were significant risk factors for PsA. The use of statin was negatively associated with PsA (OR, 0.53; P < .001).
Study details: This was a set of 4 separate case-control studies conducted in parallel and included cases of incident PsA (n=7,594), psoriasis (n=111,375), rheumatoid arthritis (RA; n=28,341), and ankylosing spondylitis (AS; n=3,253) matched to control participants (PsA, n=75,930; psoriasis, n=1113,345; RA, n=283,226; and AS, n=32,530).
Disclosures: This work was supported by grants from the National Institute of Health and internal grants from the University of Pennsylvania. Dr. Gelfand, Dr. Love, and Dr. Ogdie declared receiving research grants, honoraria, and reimbursement from and/or serving as a consultant for various sources.
Source: Meer E et al. J Rheumatol. 2021 Aug 1. doi: 10.3899/jrheum.210006.
Key clinical point: A previous diagnosis of gout, uveitis, metabolic and lifestyle factors like obesity, alcohol consumption, and infections like pharyngitis and skin infections were potential risk factors for psoriatic arthritis (PsA), whereas statin use showed a negative association with PsA.
Major finding: A previous diagnosis of gout (odds ratio [OR], 2.19), uveitis (OR, 3.79), alcohol use (OR, 1.67), obesity (OR, 1.64), pharyngitis (OR, 1.23), and skin infection (OR, 1.37; all P < .001) were significant risk factors for PsA. The use of statin was negatively associated with PsA (OR, 0.53; P < .001).
Study details: This was a set of 4 separate case-control studies conducted in parallel and included cases of incident PsA (n=7,594), psoriasis (n=111,375), rheumatoid arthritis (RA; n=28,341), and ankylosing spondylitis (AS; n=3,253) matched to control participants (PsA, n=75,930; psoriasis, n=1113,345; RA, n=283,226; and AS, n=32,530).
Disclosures: This work was supported by grants from the National Institute of Health and internal grants from the University of Pennsylvania. Dr. Gelfand, Dr. Love, and Dr. Ogdie declared receiving research grants, honoraria, and reimbursement from and/or serving as a consultant for various sources.
Source: Meer E et al. J Rheumatol. 2021 Aug 1. doi: 10.3899/jrheum.210006.
No clinically relevant increase in mortality in patients with PsA
Key clinical point: Psoriatic arthritis (PsA) was not associated with a significant increase in risk for all-cause mortality in the more recent era between 2003 and 2018. Moreover, the major causes of death in PsA were not different than those commonly reported in the general population.
Major finding: The number of deaths was similar in PsA and control groups (8.9% and 7.9%, respectively), and the association between PsA and a higher risk for all-cause mortality was not significant (hazard ratio, 1.02; 95% confidence interval, 0.90-1.15). In the general population, malignancy (26.0%) and ischemic heart disease (15.8%) were the leading causes of death in patients with PsA.
Study details: Findings are from an analysis of a cohort of 5,275 adults newly diagnosed with PsA between 2003 and 2018, matched with 21,011 control participants and followed for 7.2±4.4 years.
Disclosures: The study did not report any source of funding. No conflict of interests was reported.
Source: Haddad A et al. J Rheumatol. 2021 Jul 15. doi: 10.3899/jrheum.210159.
Key clinical point: Psoriatic arthritis (PsA) was not associated with a significant increase in risk for all-cause mortality in the more recent era between 2003 and 2018. Moreover, the major causes of death in PsA were not different than those commonly reported in the general population.
Major finding: The number of deaths was similar in PsA and control groups (8.9% and 7.9%, respectively), and the association between PsA and a higher risk for all-cause mortality was not significant (hazard ratio, 1.02; 95% confidence interval, 0.90-1.15). In the general population, malignancy (26.0%) and ischemic heart disease (15.8%) were the leading causes of death in patients with PsA.
Study details: Findings are from an analysis of a cohort of 5,275 adults newly diagnosed with PsA between 2003 and 2018, matched with 21,011 control participants and followed for 7.2±4.4 years.
Disclosures: The study did not report any source of funding. No conflict of interests was reported.
Source: Haddad A et al. J Rheumatol. 2021 Jul 15. doi: 10.3899/jrheum.210159.
Key clinical point: Psoriatic arthritis (PsA) was not associated with a significant increase in risk for all-cause mortality in the more recent era between 2003 and 2018. Moreover, the major causes of death in PsA were not different than those commonly reported in the general population.
Major finding: The number of deaths was similar in PsA and control groups (8.9% and 7.9%, respectively), and the association between PsA and a higher risk for all-cause mortality was not significant (hazard ratio, 1.02; 95% confidence interval, 0.90-1.15). In the general population, malignancy (26.0%) and ischemic heart disease (15.8%) were the leading causes of death in patients with PsA.
Study details: Findings are from an analysis of a cohort of 5,275 adults newly diagnosed with PsA between 2003 and 2018, matched with 21,011 control participants and followed for 7.2±4.4 years.
Disclosures: The study did not report any source of funding. No conflict of interests was reported.
Source: Haddad A et al. J Rheumatol. 2021 Jul 15. doi: 10.3899/jrheum.210159.
Oligoarticular PsA similar to polyarticular PsA with few exceptions
Key clinical point: Oligoarticular psoriatic arthritis (PsA) is similar to polyarticular disease. However, involvement of lower extremity small joint had the highest chances of polyarticular presentation, whereas low Short Form-36 (SF-36) Mental Component Summary (MCS) score was significantly associated with progression from oligoarthritis to polyarthritis.
Major finding: Demographics and clinical characteristics were similar between the oligoarticular and polyarticular PsA groups. However, polyarticular PsA was associated with higher odds of lower extremity small joints (odds ratio, 17.15; P < .001). Among patients with oligoarticular PsA, 39% developed polyarticular PsA with lower SF-36 MCS being the only predictor for progression (hazard ratio, 0.97; P = .01).
Study details: Findings are from a longitudinal study including 407 patients with PsA who entered the University of Toronto PsA clinic within 12 months of diagnosis between 1978 and 2018, of which 47% presented with oligoarthritis and 53% with polyarthritis.
Disclosures: The University of Toronto PsA program was funded by the Krembil Foundation. The authors declared no conflict of interests.
Source: Gladman DD et al. J Rheumatol. 2021 Aug 1. doi: 10.3899/jrheum.210434.
Key clinical point: Oligoarticular psoriatic arthritis (PsA) is similar to polyarticular disease. However, involvement of lower extremity small joint had the highest chances of polyarticular presentation, whereas low Short Form-36 (SF-36) Mental Component Summary (MCS) score was significantly associated with progression from oligoarthritis to polyarthritis.
Major finding: Demographics and clinical characteristics were similar between the oligoarticular and polyarticular PsA groups. However, polyarticular PsA was associated with higher odds of lower extremity small joints (odds ratio, 17.15; P < .001). Among patients with oligoarticular PsA, 39% developed polyarticular PsA with lower SF-36 MCS being the only predictor for progression (hazard ratio, 0.97; P = .01).
Study details: Findings are from a longitudinal study including 407 patients with PsA who entered the University of Toronto PsA clinic within 12 months of diagnosis between 1978 and 2018, of which 47% presented with oligoarthritis and 53% with polyarthritis.
Disclosures: The University of Toronto PsA program was funded by the Krembil Foundation. The authors declared no conflict of interests.
Source: Gladman DD et al. J Rheumatol. 2021 Aug 1. doi: 10.3899/jrheum.210434.
Key clinical point: Oligoarticular psoriatic arthritis (PsA) is similar to polyarticular disease. However, involvement of lower extremity small joint had the highest chances of polyarticular presentation, whereas low Short Form-36 (SF-36) Mental Component Summary (MCS) score was significantly associated with progression from oligoarthritis to polyarthritis.
Major finding: Demographics and clinical characteristics were similar between the oligoarticular and polyarticular PsA groups. However, polyarticular PsA was associated with higher odds of lower extremity small joints (odds ratio, 17.15; P < .001). Among patients with oligoarticular PsA, 39% developed polyarticular PsA with lower SF-36 MCS being the only predictor for progression (hazard ratio, 0.97; P = .01).
Study details: Findings are from a longitudinal study including 407 patients with PsA who entered the University of Toronto PsA clinic within 12 months of diagnosis between 1978 and 2018, of which 47% presented with oligoarthritis and 53% with polyarthritis.
Disclosures: The University of Toronto PsA program was funded by the Krembil Foundation. The authors declared no conflict of interests.
Source: Gladman DD et al. J Rheumatol. 2021 Aug 1. doi: 10.3899/jrheum.210434.
Secukinumab effective for PsA, with high patient satisfaction in the real world
Key clinical point: Secukinumab was effective in treating patients with psoriatic arthritis (PsA) in real-world clinical settings and generated high levels of satisfaction among physicians.
Major finding: At treatment initiation, 5.6%, 16.3%, and 8.7% of patients were categorized with mild disease, skin, and joint severity, which increased to 75.5%, 83.6%, and 77.6%, respectively, at the current consultation. Patients with Psoriasis Area Severity Index scores of less than 3 increased from 7.1% at treatment initiation to 64.3% at the current consultation. Physician satisfaction with secukinumab treatment was greater than 90% irrespective of disease severity at initiation and several other clinical parameters.
Study details: Findings are from a retrospective analysis of data collected for 572 patients with mild-to-severe PsA from 294 rheumatologists and 144 dermatologists. Included patients received either secukinumab 300 mg or 150 mg for at least 4 months.
Disclosures: This study was funded by Novartis. Dr. Conaghan and Dr. Kiltz declared receiving consultancy or speaker fees and/or research support from several sources including Novartis.
Source: Conaghan PG et al. Curr Med Res Opin. 2021 Jul 23. doi: 10.1080/03007995.2021.1954500.
Key clinical point: Secukinumab was effective in treating patients with psoriatic arthritis (PsA) in real-world clinical settings and generated high levels of satisfaction among physicians.
Major finding: At treatment initiation, 5.6%, 16.3%, and 8.7% of patients were categorized with mild disease, skin, and joint severity, which increased to 75.5%, 83.6%, and 77.6%, respectively, at the current consultation. Patients with Psoriasis Area Severity Index scores of less than 3 increased from 7.1% at treatment initiation to 64.3% at the current consultation. Physician satisfaction with secukinumab treatment was greater than 90% irrespective of disease severity at initiation and several other clinical parameters.
Study details: Findings are from a retrospective analysis of data collected for 572 patients with mild-to-severe PsA from 294 rheumatologists and 144 dermatologists. Included patients received either secukinumab 300 mg or 150 mg for at least 4 months.
Disclosures: This study was funded by Novartis. Dr. Conaghan and Dr. Kiltz declared receiving consultancy or speaker fees and/or research support from several sources including Novartis.
Source: Conaghan PG et al. Curr Med Res Opin. 2021 Jul 23. doi: 10.1080/03007995.2021.1954500.
Key clinical point: Secukinumab was effective in treating patients with psoriatic arthritis (PsA) in real-world clinical settings and generated high levels of satisfaction among physicians.
Major finding: At treatment initiation, 5.6%, 16.3%, and 8.7% of patients were categorized with mild disease, skin, and joint severity, which increased to 75.5%, 83.6%, and 77.6%, respectively, at the current consultation. Patients with Psoriasis Area Severity Index scores of less than 3 increased from 7.1% at treatment initiation to 64.3% at the current consultation. Physician satisfaction with secukinumab treatment was greater than 90% irrespective of disease severity at initiation and several other clinical parameters.
Study details: Findings are from a retrospective analysis of data collected for 572 patients with mild-to-severe PsA from 294 rheumatologists and 144 dermatologists. Included patients received either secukinumab 300 mg or 150 mg for at least 4 months.
Disclosures: This study was funded by Novartis. Dr. Conaghan and Dr. Kiltz declared receiving consultancy or speaker fees and/or research support from several sources including Novartis.
Source: Conaghan PG et al. Curr Med Res Opin. 2021 Jul 23. doi: 10.1080/03007995.2021.1954500.