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Psoriatic Arthritis Journal Scan: March 2019
A systematic review of herpes zoster incidence and consensus recommendations on vaccination in adult patients on systemic therapy for psoriasis or psoriatic arthritis: From the Medical Board of the National Psoriasis Foundation.
Baumrin E, Van Voorhees A, Garg A, Feldman SR, Merola JF. J Am Acad Dermatol. 2019 Mar 15
A systematic literature search was performed of HZ in patients with PsO/PsA. HZ vaccination guidelines were reviewed and the medical board of the National Psoriasis Foundation made consensus recommendations in PsO/PsA patients based on graded evidence. HZ risk depends on disease severity and treatment class. Recombinant zoster vaccine should be given to all PsO/PsA patients >50 years old and younger patients at increased risk.
Ultrasonographic and Clinical Assessment of Peripheral Enthesitis in Patients with Psoriatic Arthritis, Psoriasis, and Fibromyalgia Syndrome: The ULISSE Study.
Macchioni P, Salvarani C, Possemato N, et al. J Rheumatol. 2019 Mar 15.
The ULISSE study indicated that enthesitis is a common feature in patients with PsA, those with psoriasis, and in those with FMS if only clinical examination is used. US entheseal assessment showed findings more consistent with the 3 disorders.
The development of a modified Psoriatic Arthritis Disease Activity Score (mPASDAS) using SF-12 as a measure of quality of life.
Perruccio AV, Got M, Li S, Ye Y, Gladman DD, Chandran V. Arthritis Care Res (Hoboken). 2019 Mar 15.
The Psoriatic Arthritis Disease Activity Score (PASDAS) is a composite measure of psoriatic arthritis (PsA) disease activity. The length of its patient-reported components raises concern about questionnaire burden. The PASDAS includes the SF-36 measure. The study investigated the agreement between PASDAS and a modified PASDAS (mPASDAS) which substituted the SF-36 with the shortened SF-12.
The Impact of Intermittent Fasting (Ramadan Fasting) on Psoriatic Arthritis Disease Activity, Enthesitis, and Dactylitis: A Multicentre Study.
Adawi M, Damiani G, Bragazzi NL, et al. Nutrients. 2019 Mar 12;11(3).
Fasting was found to be a predictor of a decrease in PsA disease activity scores (DAPSA, BASDAI, LEI, DSS) even after adjustment for weight loss. IL-17 therapy was found to be an independent predictor of decreases in LEI after fasting.
Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition.
Scher JU, Ogdie A, Merola JF, Ritchlin C. Nat Rev Rheumatol. 2019 Mar;15(3):153-166.
The events responsible for progression to PsA are currently unclear. Genetic and clinical–demographic risk factors (most notably familial aggregation and psoriasis sub-phenotypes) provide relevant insights into the variables that promote transition.
A systematic review of herpes zoster incidence and consensus recommendations on vaccination in adult patients on systemic therapy for psoriasis or psoriatic arthritis: From the Medical Board of the National Psoriasis Foundation.
Baumrin E, Van Voorhees A, Garg A, Feldman SR, Merola JF. J Am Acad Dermatol. 2019 Mar 15
A systematic literature search was performed of HZ in patients with PsO/PsA. HZ vaccination guidelines were reviewed and the medical board of the National Psoriasis Foundation made consensus recommendations in PsO/PsA patients based on graded evidence. HZ risk depends on disease severity and treatment class. Recombinant zoster vaccine should be given to all PsO/PsA patients >50 years old and younger patients at increased risk.
Ultrasonographic and Clinical Assessment of Peripheral Enthesitis in Patients with Psoriatic Arthritis, Psoriasis, and Fibromyalgia Syndrome: The ULISSE Study.
Macchioni P, Salvarani C, Possemato N, et al. J Rheumatol. 2019 Mar 15.
The ULISSE study indicated that enthesitis is a common feature in patients with PsA, those with psoriasis, and in those with FMS if only clinical examination is used. US entheseal assessment showed findings more consistent with the 3 disorders.
The development of a modified Psoriatic Arthritis Disease Activity Score (mPASDAS) using SF-12 as a measure of quality of life.
Perruccio AV, Got M, Li S, Ye Y, Gladman DD, Chandran V. Arthritis Care Res (Hoboken). 2019 Mar 15.
The Psoriatic Arthritis Disease Activity Score (PASDAS) is a composite measure of psoriatic arthritis (PsA) disease activity. The length of its patient-reported components raises concern about questionnaire burden. The PASDAS includes the SF-36 measure. The study investigated the agreement between PASDAS and a modified PASDAS (mPASDAS) which substituted the SF-36 with the shortened SF-12.
The Impact of Intermittent Fasting (Ramadan Fasting) on Psoriatic Arthritis Disease Activity, Enthesitis, and Dactylitis: A Multicentre Study.
Adawi M, Damiani G, Bragazzi NL, et al. Nutrients. 2019 Mar 12;11(3).
Fasting was found to be a predictor of a decrease in PsA disease activity scores (DAPSA, BASDAI, LEI, DSS) even after adjustment for weight loss. IL-17 therapy was found to be an independent predictor of decreases in LEI after fasting.
Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition.
Scher JU, Ogdie A, Merola JF, Ritchlin C. Nat Rev Rheumatol. 2019 Mar;15(3):153-166.
The events responsible for progression to PsA are currently unclear. Genetic and clinical–demographic risk factors (most notably familial aggregation and psoriasis sub-phenotypes) provide relevant insights into the variables that promote transition.
A systematic review of herpes zoster incidence and consensus recommendations on vaccination in adult patients on systemic therapy for psoriasis or psoriatic arthritis: From the Medical Board of the National Psoriasis Foundation.
Baumrin E, Van Voorhees A, Garg A, Feldman SR, Merola JF. J Am Acad Dermatol. 2019 Mar 15
A systematic literature search was performed of HZ in patients with PsO/PsA. HZ vaccination guidelines were reviewed and the medical board of the National Psoriasis Foundation made consensus recommendations in PsO/PsA patients based on graded evidence. HZ risk depends on disease severity and treatment class. Recombinant zoster vaccine should be given to all PsO/PsA patients >50 years old and younger patients at increased risk.
Ultrasonographic and Clinical Assessment of Peripheral Enthesitis in Patients with Psoriatic Arthritis, Psoriasis, and Fibromyalgia Syndrome: The ULISSE Study.
Macchioni P, Salvarani C, Possemato N, et al. J Rheumatol. 2019 Mar 15.
The ULISSE study indicated that enthesitis is a common feature in patients with PsA, those with psoriasis, and in those with FMS if only clinical examination is used. US entheseal assessment showed findings more consistent with the 3 disorders.
The development of a modified Psoriatic Arthritis Disease Activity Score (mPASDAS) using SF-12 as a measure of quality of life.
Perruccio AV, Got M, Li S, Ye Y, Gladman DD, Chandran V. Arthritis Care Res (Hoboken). 2019 Mar 15.
The Psoriatic Arthritis Disease Activity Score (PASDAS) is a composite measure of psoriatic arthritis (PsA) disease activity. The length of its patient-reported components raises concern about questionnaire burden. The PASDAS includes the SF-36 measure. The study investigated the agreement between PASDAS and a modified PASDAS (mPASDAS) which substituted the SF-36 with the shortened SF-12.
The Impact of Intermittent Fasting (Ramadan Fasting) on Psoriatic Arthritis Disease Activity, Enthesitis, and Dactylitis: A Multicentre Study.
Adawi M, Damiani G, Bragazzi NL, et al. Nutrients. 2019 Mar 12;11(3).
Fasting was found to be a predictor of a decrease in PsA disease activity scores (DAPSA, BASDAI, LEI, DSS) even after adjustment for weight loss. IL-17 therapy was found to be an independent predictor of decreases in LEI after fasting.
Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition.
Scher JU, Ogdie A, Merola JF, Ritchlin C. Nat Rev Rheumatol. 2019 Mar;15(3):153-166.
The events responsible for progression to PsA are currently unclear. Genetic and clinical–demographic risk factors (most notably familial aggregation and psoriasis sub-phenotypes) provide relevant insights into the variables that promote transition.
Proinflammatory diet may not trigger adult psoriasis, PsA, or AD
reported Alanna C. Bridgman of Queen’s University, Kingston, Ont., and her associates.
In a large, retrospective cohort study among women from the Nurses’ Health Study II (NHS-II), including 85,185 psoriasis participants and 63,443 atopic dermatitis participants, Ms. Bridgman and her associates sought to determine whether proinflammatory diet increased the risk of incident psoriasis, psoriatic arthritis, or atopic dermatitis. Clinicians administered food frequency questionnaires every 4 years beginning in 1991 among female nurses aged 25-42 years.
Food groups included in the evaluation were those most predictive of three plasma markers of inflammation: interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor–alpha R2 (TNF-R2). Proinflammatory foods included processed meat, red meat, organ meat, white fish, vegetables other than leafy green and dark yellow, refined grains, low- and high-energy drinks, and tomatoes. Anti-inflammatory foods included beer, wine, tea, coffee, dark yellow and green leafy vegetables, snacks such as popcorn and crackers, fruit juice, and pizza.
No association was found between proinflammatory diet and increased likelihood for incident psoriasis, psoriatic arthritis, or atopic dermatitis. Although proinflammatory dietary patterns were associated with psoriatic arthritis in the age-adjusted model, the hazard ratio was attenuated and found to be no longer statistically significant after adjustment for important confounders such as body mass index. In addition, no significant relationship between atopic dermatitis and proinflammatory diet was observed, they reported. The study was published in the Journal of the American Academy of Dermatology.
Ms. Bridgman and her associates measured dietary patterns using the Empirical Dietary Inflammatory Pattern (EDIP); dietary patterns measuring high on the EDIP scale were associated with higher levels of TNF-alpha, TNF-alpha R1, TNF-alpha R2, CRP, IL-6, and adiponectin. Psoriasis and psoriatic arthritis are Th1- and Th17-mediated diseases that exhibit higher serum levels of IL-6, CRP, and TNF-alpha, unlike atopic dermatitis, which is primarily a Th2-mediated condition featuring reduced involvement of the Th1/Th17 inflammatory cytokines.
Because a goal of the EDIP score was to “account for the overall effect of dietary patterns,” the researchers included in their analysis only those food groups that “explain the maximal variation in the three noted inflammatory biomarkers.”
All patients included in the study were questioned at baseline regarding their height and race/ethnicity. Weight, smoking status, and physical activity, and diagnoses of hypercholesterolemia, type 2 diabetes, cardiovascular disease, and asthma were monitored biennially.
Overall, patients with higher EDIP scores were found to have higher BMI, lower physical activity, and alcohol use, as well as increased rates of hypercholesterolemia and hypertension.
“Though we found no convincing evidence for an association with EDIP score for any of the investigated diseases, the results followed an internal pattern consistent with our hypotheses that higher EDIP scores would have more of an association with psoriatic disease than with atopic dermatitis,” the researchers wrote.
Citing recent evidence gathered in studies, such as the French NutriNet-Santé study, which demonstrated proinflammatory effects similar to those measured with the EDIP in cases where there was low adherence to the Mediterranean diet, the authors attributed their contradictory findings to “important methodological differences.” Unlike the NutriNet-Santé study, which classified psoriasis by severity, Ms. Bridgman and her colleagues examined the overall risk of incident psoriasis. “It is possible that a dietary index associated with more Th-2 inflammation would yield different results,” they noted.
The large sample size, prospectively collected dietary, and psoriatic disease data, as well as the ability to adjust for important confounding factors, were included among the strengths of the study.
That the participants were limited to U.S. women could be considered a limitation because the results may not be generalizable to other populations. The results also may not be relevant to child-onset disease because the patient population included only cases of adult-onset atopic dermatitis. Questionnaire-based diagnoses increase the likelihood of misclassification, so “dilution of the case pool with false-positive cases would bias our results towards the null,” they added.
Ultimately, the authors noted that proinflammatory diet may be associated with other health risks, but these do not warrant counseling patients concerning their possible impact in cases of psoriatic disease or atopic dermatitis.
The study was funded by Brown University department of dermatology and from Regeneron, Sanofi, the National Institutes of Health, and the National Cancer Institute. Two coauthors, one of whom has a patent pending for the nix-tix tick remover, disclosed ties with various companies.
SOURCE: Bridgman AC et al. J Am Acad Dermatol. 2019 Feb 21. pii: S0190-9622(19)30329-9.
reported Alanna C. Bridgman of Queen’s University, Kingston, Ont., and her associates.
In a large, retrospective cohort study among women from the Nurses’ Health Study II (NHS-II), including 85,185 psoriasis participants and 63,443 atopic dermatitis participants, Ms. Bridgman and her associates sought to determine whether proinflammatory diet increased the risk of incident psoriasis, psoriatic arthritis, or atopic dermatitis. Clinicians administered food frequency questionnaires every 4 years beginning in 1991 among female nurses aged 25-42 years.
Food groups included in the evaluation were those most predictive of three plasma markers of inflammation: interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor–alpha R2 (TNF-R2). Proinflammatory foods included processed meat, red meat, organ meat, white fish, vegetables other than leafy green and dark yellow, refined grains, low- and high-energy drinks, and tomatoes. Anti-inflammatory foods included beer, wine, tea, coffee, dark yellow and green leafy vegetables, snacks such as popcorn and crackers, fruit juice, and pizza.
No association was found between proinflammatory diet and increased likelihood for incident psoriasis, psoriatic arthritis, or atopic dermatitis. Although proinflammatory dietary patterns were associated with psoriatic arthritis in the age-adjusted model, the hazard ratio was attenuated and found to be no longer statistically significant after adjustment for important confounders such as body mass index. In addition, no significant relationship between atopic dermatitis and proinflammatory diet was observed, they reported. The study was published in the Journal of the American Academy of Dermatology.
Ms. Bridgman and her associates measured dietary patterns using the Empirical Dietary Inflammatory Pattern (EDIP); dietary patterns measuring high on the EDIP scale were associated with higher levels of TNF-alpha, TNF-alpha R1, TNF-alpha R2, CRP, IL-6, and adiponectin. Psoriasis and psoriatic arthritis are Th1- and Th17-mediated diseases that exhibit higher serum levels of IL-6, CRP, and TNF-alpha, unlike atopic dermatitis, which is primarily a Th2-mediated condition featuring reduced involvement of the Th1/Th17 inflammatory cytokines.
Because a goal of the EDIP score was to “account for the overall effect of dietary patterns,” the researchers included in their analysis only those food groups that “explain the maximal variation in the three noted inflammatory biomarkers.”
All patients included in the study were questioned at baseline regarding their height and race/ethnicity. Weight, smoking status, and physical activity, and diagnoses of hypercholesterolemia, type 2 diabetes, cardiovascular disease, and asthma were monitored biennially.
Overall, patients with higher EDIP scores were found to have higher BMI, lower physical activity, and alcohol use, as well as increased rates of hypercholesterolemia and hypertension.
“Though we found no convincing evidence for an association with EDIP score for any of the investigated diseases, the results followed an internal pattern consistent with our hypotheses that higher EDIP scores would have more of an association with psoriatic disease than with atopic dermatitis,” the researchers wrote.
Citing recent evidence gathered in studies, such as the French NutriNet-Santé study, which demonstrated proinflammatory effects similar to those measured with the EDIP in cases where there was low adherence to the Mediterranean diet, the authors attributed their contradictory findings to “important methodological differences.” Unlike the NutriNet-Santé study, which classified psoriasis by severity, Ms. Bridgman and her colleagues examined the overall risk of incident psoriasis. “It is possible that a dietary index associated with more Th-2 inflammation would yield different results,” they noted.
The large sample size, prospectively collected dietary, and psoriatic disease data, as well as the ability to adjust for important confounding factors, were included among the strengths of the study.
That the participants were limited to U.S. women could be considered a limitation because the results may not be generalizable to other populations. The results also may not be relevant to child-onset disease because the patient population included only cases of adult-onset atopic dermatitis. Questionnaire-based diagnoses increase the likelihood of misclassification, so “dilution of the case pool with false-positive cases would bias our results towards the null,” they added.
Ultimately, the authors noted that proinflammatory diet may be associated with other health risks, but these do not warrant counseling patients concerning their possible impact in cases of psoriatic disease or atopic dermatitis.
The study was funded by Brown University department of dermatology and from Regeneron, Sanofi, the National Institutes of Health, and the National Cancer Institute. Two coauthors, one of whom has a patent pending for the nix-tix tick remover, disclosed ties with various companies.
SOURCE: Bridgman AC et al. J Am Acad Dermatol. 2019 Feb 21. pii: S0190-9622(19)30329-9.
reported Alanna C. Bridgman of Queen’s University, Kingston, Ont., and her associates.
In a large, retrospective cohort study among women from the Nurses’ Health Study II (NHS-II), including 85,185 psoriasis participants and 63,443 atopic dermatitis participants, Ms. Bridgman and her associates sought to determine whether proinflammatory diet increased the risk of incident psoriasis, psoriatic arthritis, or atopic dermatitis. Clinicians administered food frequency questionnaires every 4 years beginning in 1991 among female nurses aged 25-42 years.
Food groups included in the evaluation were those most predictive of three plasma markers of inflammation: interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor–alpha R2 (TNF-R2). Proinflammatory foods included processed meat, red meat, organ meat, white fish, vegetables other than leafy green and dark yellow, refined grains, low- and high-energy drinks, and tomatoes. Anti-inflammatory foods included beer, wine, tea, coffee, dark yellow and green leafy vegetables, snacks such as popcorn and crackers, fruit juice, and pizza.
No association was found between proinflammatory diet and increased likelihood for incident psoriasis, psoriatic arthritis, or atopic dermatitis. Although proinflammatory dietary patterns were associated with psoriatic arthritis in the age-adjusted model, the hazard ratio was attenuated and found to be no longer statistically significant after adjustment for important confounders such as body mass index. In addition, no significant relationship between atopic dermatitis and proinflammatory diet was observed, they reported. The study was published in the Journal of the American Academy of Dermatology.
Ms. Bridgman and her associates measured dietary patterns using the Empirical Dietary Inflammatory Pattern (EDIP); dietary patterns measuring high on the EDIP scale were associated with higher levels of TNF-alpha, TNF-alpha R1, TNF-alpha R2, CRP, IL-6, and adiponectin. Psoriasis and psoriatic arthritis are Th1- and Th17-mediated diseases that exhibit higher serum levels of IL-6, CRP, and TNF-alpha, unlike atopic dermatitis, which is primarily a Th2-mediated condition featuring reduced involvement of the Th1/Th17 inflammatory cytokines.
Because a goal of the EDIP score was to “account for the overall effect of dietary patterns,” the researchers included in their analysis only those food groups that “explain the maximal variation in the three noted inflammatory biomarkers.”
All patients included in the study were questioned at baseline regarding their height and race/ethnicity. Weight, smoking status, and physical activity, and diagnoses of hypercholesterolemia, type 2 diabetes, cardiovascular disease, and asthma were monitored biennially.
Overall, patients with higher EDIP scores were found to have higher BMI, lower physical activity, and alcohol use, as well as increased rates of hypercholesterolemia and hypertension.
“Though we found no convincing evidence for an association with EDIP score for any of the investigated diseases, the results followed an internal pattern consistent with our hypotheses that higher EDIP scores would have more of an association with psoriatic disease than with atopic dermatitis,” the researchers wrote.
Citing recent evidence gathered in studies, such as the French NutriNet-Santé study, which demonstrated proinflammatory effects similar to those measured with the EDIP in cases where there was low adherence to the Mediterranean diet, the authors attributed their contradictory findings to “important methodological differences.” Unlike the NutriNet-Santé study, which classified psoriasis by severity, Ms. Bridgman and her colleagues examined the overall risk of incident psoriasis. “It is possible that a dietary index associated with more Th-2 inflammation would yield different results,” they noted.
The large sample size, prospectively collected dietary, and psoriatic disease data, as well as the ability to adjust for important confounding factors, were included among the strengths of the study.
That the participants were limited to U.S. women could be considered a limitation because the results may not be generalizable to other populations. The results also may not be relevant to child-onset disease because the patient population included only cases of adult-onset atopic dermatitis. Questionnaire-based diagnoses increase the likelihood of misclassification, so “dilution of the case pool with false-positive cases would bias our results towards the null,” they added.
Ultimately, the authors noted that proinflammatory diet may be associated with other health risks, but these do not warrant counseling patients concerning their possible impact in cases of psoriatic disease or atopic dermatitis.
The study was funded by Brown University department of dermatology and from Regeneron, Sanofi, the National Institutes of Health, and the National Cancer Institute. Two coauthors, one of whom has a patent pending for the nix-tix tick remover, disclosed ties with various companies.
SOURCE: Bridgman AC et al. J Am Acad Dermatol. 2019 Feb 21. pii: S0190-9622(19)30329-9.
FROM JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Key clinical point: Study results may not be generalizable to other study populations.
Major finding: No association was found between proinflammatory diet and increased likelihood for incident psoriasis, psoriatic arthritis, or atopic dermatitis in adult women.
Study details: Large retrospective cohort study of 85,185 psoriasis subjects and 63,443 atopic dermatitis subjects.
Disclosures: The study was funded by Brown University department of dermatology and from Regeneron, Sanofi, the National Institutes of Health, and the National Cancer Institute. Two coauthors, one of whom has a patent pending for the nix-tix tick remover, disclosed ties with various companies. Source: Bridgman AC et al. J Am Acad Dermatol. 2019 Feb 21. pii: S0190-9622(19)30329-9.
Four biomarkers could distinguish psoriatic arthritis from osteoarthritis
A panel of four biomarkers of cartilage metabolism, metabolic syndrome, and inflammation could help physicians to distinguish between osteoarthritis and psoriatic arthritis, new research suggests.
Such a test for distinguishing between the two conditions, which have “similarities in the distribution of joints involved,” could offer a way to make earlier diagnoses and avoid inappropriate treatment, according to Vinod Chandran, MD, PhD, of the department of medicine at the University of Toronto and Toronto Western Hospital and his colleagues. Dr. Chandran was first author on a study published online in Annals of the Rheumatic Diseases that analyzed serum samples from the University of Toronto Psoriatic Arthritis Program and University Health Network Arthritis Program for differences in certain biomarkers from 201 individuals with osteoarthritis, 77 with psoriatic arthritis, and 76 healthy controls.
The samples were tested for 15 biomarkers, including those related to cartilage metabolism (cartilage oligomeric matrix protein and hyaluronan), to metabolic syndrome (adiponectin, adipsin, resistin, hepatocyte growth factor, insulin, and leptin), and to inflammation (C-reactive protein, interleukin-1-beta, interleukin-6, interleukin-8, tumor necrosis factor alpha, monocyte chemoattractant protein–1, and nerve growth factor).
Researchers found that levels of 12 of these markers were different in patients with psoriatic arthritis, osteoarthritis, or controls, and 9 markers showed altered expression in psoriatic arthritis, compared with osteoarthritis.
Further analysis showed that levels of cartilage oligomeric matrix protein, resistin, monocyte chemoattractant protein–1, and nerve growth factor were significantly different between patients with psoriatic arthritis and those with osteoarthritis. The ROC curve for a model based on these four biomarkers that also incorporated age and sex had an area under the curve of 0.9984.
Researchers then validated the four biomarkers in an independent set of 75 patients with osteoarthritis and 73 with psoriatic arthritis and found these biomarkers were able to discriminate between the two conditions beyond what would be achieved based on age and sex alone.
The authors noted that previous research has observed high expression of monocyte chemoattractant protein–1 and resistin in patients with psoriatic arthritis when compared with those with osteoarthritis.
Nerve growth factor has been seen at elevated levels in the synovial fluid of individuals with osteoarthritis and is known to play a role in the chronic pain associated with that disease.
Similarly, higher cartilage oligomeric matrix protein levels are associated with a higher risk of knee osteoarthritis.
However, the authors noted that individuals with osteoarthritis in the study were all undergoing joint replacement surgery and therefore may not be typical of patients presenting to family practices or rheumatology clinics.
The University of Toronto Psoriatic Arthritis Program is supported by the Krembil Foundation. No conflicts of interest were declared.
SOURCE: Chandran V et al. Ann Rheum Dis. 2019 Mar 25. doi: 10.1136/annrheumdis-2018-214737.
A panel of four biomarkers of cartilage metabolism, metabolic syndrome, and inflammation could help physicians to distinguish between osteoarthritis and psoriatic arthritis, new research suggests.
Such a test for distinguishing between the two conditions, which have “similarities in the distribution of joints involved,” could offer a way to make earlier diagnoses and avoid inappropriate treatment, according to Vinod Chandran, MD, PhD, of the department of medicine at the University of Toronto and Toronto Western Hospital and his colleagues. Dr. Chandran was first author on a study published online in Annals of the Rheumatic Diseases that analyzed serum samples from the University of Toronto Psoriatic Arthritis Program and University Health Network Arthritis Program for differences in certain biomarkers from 201 individuals with osteoarthritis, 77 with psoriatic arthritis, and 76 healthy controls.
The samples were tested for 15 biomarkers, including those related to cartilage metabolism (cartilage oligomeric matrix protein and hyaluronan), to metabolic syndrome (adiponectin, adipsin, resistin, hepatocyte growth factor, insulin, and leptin), and to inflammation (C-reactive protein, interleukin-1-beta, interleukin-6, interleukin-8, tumor necrosis factor alpha, monocyte chemoattractant protein–1, and nerve growth factor).
Researchers found that levels of 12 of these markers were different in patients with psoriatic arthritis, osteoarthritis, or controls, and 9 markers showed altered expression in psoriatic arthritis, compared with osteoarthritis.
Further analysis showed that levels of cartilage oligomeric matrix protein, resistin, monocyte chemoattractant protein–1, and nerve growth factor were significantly different between patients with psoriatic arthritis and those with osteoarthritis. The ROC curve for a model based on these four biomarkers that also incorporated age and sex had an area under the curve of 0.9984.
Researchers then validated the four biomarkers in an independent set of 75 patients with osteoarthritis and 73 with psoriatic arthritis and found these biomarkers were able to discriminate between the two conditions beyond what would be achieved based on age and sex alone.
The authors noted that previous research has observed high expression of monocyte chemoattractant protein–1 and resistin in patients with psoriatic arthritis when compared with those with osteoarthritis.
Nerve growth factor has been seen at elevated levels in the synovial fluid of individuals with osteoarthritis and is known to play a role in the chronic pain associated with that disease.
Similarly, higher cartilage oligomeric matrix protein levels are associated with a higher risk of knee osteoarthritis.
However, the authors noted that individuals with osteoarthritis in the study were all undergoing joint replacement surgery and therefore may not be typical of patients presenting to family practices or rheumatology clinics.
The University of Toronto Psoriatic Arthritis Program is supported by the Krembil Foundation. No conflicts of interest were declared.
SOURCE: Chandran V et al. Ann Rheum Dis. 2019 Mar 25. doi: 10.1136/annrheumdis-2018-214737.
A panel of four biomarkers of cartilage metabolism, metabolic syndrome, and inflammation could help physicians to distinguish between osteoarthritis and psoriatic arthritis, new research suggests.
Such a test for distinguishing between the two conditions, which have “similarities in the distribution of joints involved,” could offer a way to make earlier diagnoses and avoid inappropriate treatment, according to Vinod Chandran, MD, PhD, of the department of medicine at the University of Toronto and Toronto Western Hospital and his colleagues. Dr. Chandran was first author on a study published online in Annals of the Rheumatic Diseases that analyzed serum samples from the University of Toronto Psoriatic Arthritis Program and University Health Network Arthritis Program for differences in certain biomarkers from 201 individuals with osteoarthritis, 77 with psoriatic arthritis, and 76 healthy controls.
The samples were tested for 15 biomarkers, including those related to cartilage metabolism (cartilage oligomeric matrix protein and hyaluronan), to metabolic syndrome (adiponectin, adipsin, resistin, hepatocyte growth factor, insulin, and leptin), and to inflammation (C-reactive protein, interleukin-1-beta, interleukin-6, interleukin-8, tumor necrosis factor alpha, monocyte chemoattractant protein–1, and nerve growth factor).
Researchers found that levels of 12 of these markers were different in patients with psoriatic arthritis, osteoarthritis, or controls, and 9 markers showed altered expression in psoriatic arthritis, compared with osteoarthritis.
Further analysis showed that levels of cartilage oligomeric matrix protein, resistin, monocyte chemoattractant protein–1, and nerve growth factor were significantly different between patients with psoriatic arthritis and those with osteoarthritis. The ROC curve for a model based on these four biomarkers that also incorporated age and sex had an area under the curve of 0.9984.
Researchers then validated the four biomarkers in an independent set of 75 patients with osteoarthritis and 73 with psoriatic arthritis and found these biomarkers were able to discriminate between the two conditions beyond what would be achieved based on age and sex alone.
The authors noted that previous research has observed high expression of monocyte chemoattractant protein–1 and resistin in patients with psoriatic arthritis when compared with those with osteoarthritis.
Nerve growth factor has been seen at elevated levels in the synovial fluid of individuals with osteoarthritis and is known to play a role in the chronic pain associated with that disease.
Similarly, higher cartilage oligomeric matrix protein levels are associated with a higher risk of knee osteoarthritis.
However, the authors noted that individuals with osteoarthritis in the study were all undergoing joint replacement surgery and therefore may not be typical of patients presenting to family practices or rheumatology clinics.
The University of Toronto Psoriatic Arthritis Program is supported by the Krembil Foundation. No conflicts of interest were declared.
SOURCE: Chandran V et al. Ann Rheum Dis. 2019 Mar 25. doi: 10.1136/annrheumdis-2018-214737.
FROM ANNALS OF THE RHEUMATIC DISEASES
Herpes zoster risk increased with some psoriasis, psoriatic arthritis treatments
All individuals with psoriasis or psoriatic arthritis aged over 50 years should receive the recombinant herpes zoster vaccine, according to a systematic review and consensus recommendations from the National Psoriasis Foundation.
Emily Baumrin, MD, of Brigham and Women’s Hospital, Boston, and her coauthors reviewed 41 studies of herpes zoster in people with psoriasis or psoriatic arthritis according to treatment modality. Their report is in the Journal of the American Academy of Dermatology.
Overall, psoriasis was associated with an increased rate of herpes zoster when compared with the general population: 13.3 cases per 1,000 patient-years for psoriasis and 15.9 for psoriatic arthritis, compared with 8.5 in healthy controls after adjustment for age, sex, and systemic medications. Most of this increased incidence was seen in patients with more severe disease: Those with mild disease who were not receiving systemic therapy had a risk similar to that of healthy controls.
However, one study suggested much of the increased risk of herpes zoster in psoriasis was accounted for by immunosuppressive therapy; when those patients were excluded, there was an 8% increase in risk.
The authors found that people whose psoriasis was treated with tofacitinib (Xeljanz) had a two- to threefold increased risk of herpes zoster, compared with those treated with tumor necrosis factor (TNF) inhibitors or conventional synthetic disease-modifying antirheumatic drugs (DMARDs).
Corticosteroids – either alone or in combination with DMARDs – were also associated with significant increases in the risk of herpes zoster. Patients treated with TNF inhibitor monotherapy had a risk of herpes zoster similar to that of those treated with conventional synthetic DMARDs or no synthetic therapy.
On the question of immunization, the authors pointed to guidelines recommending use of the live attenuated zoster vaccine (Zostavax) in immunocompetent patients or those on low-dose immunosuppression, although they noted that the vaccine is currently contraindicated for patients on biologic DMARDs.
They also examined the evidence for the use of the recently-released non-live recombinant herpes zoster vaccine (Shingrix) in immunocompromised patients, which found no evidence of vaccine-related serious adverse events in individuals with HIV and low CD4 cell counts and in autologous hematopoietic stem cell transplant recipients.
Given this, they recommended that the recombinant vaccine be administered to all patients aged over 50 years with psoriasis or psoriatic arthritis, and to those aged under 50 years who were being treated with tofacitinib, systemic corticosteroids, or combination systemic therapy.
There were insufficient data to draw conclusions about the impact of treatment with the interleukin-12/23 blocker ustekinumab (Stelara) on herpes zoster risk, but the authors noted that there was a trend toward an increased risk. They found no increase in the risk of herpes zoster with interleukin-17 inhibitors (ixekizumab [Taltz], secukinumab [Cosentyx], and brodalumab [Siliq]) and interleukin-23 (p19 subunit) inhibitors (guselkumab [Tremfya], tildrakizumab [Ilumya], and risankizumab) but noted an absence of long-term safety data for these drugs.
Four authors declared advisory, consultancy, or speaker positions with the pharmaceutical sector.
SOURCE: Baumrin E et al. J Am Acad Dermatol. 2019 March 15. doi: 10.1016/j.jaad.2019.03.017.
All individuals with psoriasis or psoriatic arthritis aged over 50 years should receive the recombinant herpes zoster vaccine, according to a systematic review and consensus recommendations from the National Psoriasis Foundation.
Emily Baumrin, MD, of Brigham and Women’s Hospital, Boston, and her coauthors reviewed 41 studies of herpes zoster in people with psoriasis or psoriatic arthritis according to treatment modality. Their report is in the Journal of the American Academy of Dermatology.
Overall, psoriasis was associated with an increased rate of herpes zoster when compared with the general population: 13.3 cases per 1,000 patient-years for psoriasis and 15.9 for psoriatic arthritis, compared with 8.5 in healthy controls after adjustment for age, sex, and systemic medications. Most of this increased incidence was seen in patients with more severe disease: Those with mild disease who were not receiving systemic therapy had a risk similar to that of healthy controls.
However, one study suggested much of the increased risk of herpes zoster in psoriasis was accounted for by immunosuppressive therapy; when those patients were excluded, there was an 8% increase in risk.
The authors found that people whose psoriasis was treated with tofacitinib (Xeljanz) had a two- to threefold increased risk of herpes zoster, compared with those treated with tumor necrosis factor (TNF) inhibitors or conventional synthetic disease-modifying antirheumatic drugs (DMARDs).
Corticosteroids – either alone or in combination with DMARDs – were also associated with significant increases in the risk of herpes zoster. Patients treated with TNF inhibitor monotherapy had a risk of herpes zoster similar to that of those treated with conventional synthetic DMARDs or no synthetic therapy.
On the question of immunization, the authors pointed to guidelines recommending use of the live attenuated zoster vaccine (Zostavax) in immunocompetent patients or those on low-dose immunosuppression, although they noted that the vaccine is currently contraindicated for patients on biologic DMARDs.
They also examined the evidence for the use of the recently-released non-live recombinant herpes zoster vaccine (Shingrix) in immunocompromised patients, which found no evidence of vaccine-related serious adverse events in individuals with HIV and low CD4 cell counts and in autologous hematopoietic stem cell transplant recipients.
Given this, they recommended that the recombinant vaccine be administered to all patients aged over 50 years with psoriasis or psoriatic arthritis, and to those aged under 50 years who were being treated with tofacitinib, systemic corticosteroids, or combination systemic therapy.
There were insufficient data to draw conclusions about the impact of treatment with the interleukin-12/23 blocker ustekinumab (Stelara) on herpes zoster risk, but the authors noted that there was a trend toward an increased risk. They found no increase in the risk of herpes zoster with interleukin-17 inhibitors (ixekizumab [Taltz], secukinumab [Cosentyx], and brodalumab [Siliq]) and interleukin-23 (p19 subunit) inhibitors (guselkumab [Tremfya], tildrakizumab [Ilumya], and risankizumab) but noted an absence of long-term safety data for these drugs.
Four authors declared advisory, consultancy, or speaker positions with the pharmaceutical sector.
SOURCE: Baumrin E et al. J Am Acad Dermatol. 2019 March 15. doi: 10.1016/j.jaad.2019.03.017.
All individuals with psoriasis or psoriatic arthritis aged over 50 years should receive the recombinant herpes zoster vaccine, according to a systematic review and consensus recommendations from the National Psoriasis Foundation.
Emily Baumrin, MD, of Brigham and Women’s Hospital, Boston, and her coauthors reviewed 41 studies of herpes zoster in people with psoriasis or psoriatic arthritis according to treatment modality. Their report is in the Journal of the American Academy of Dermatology.
Overall, psoriasis was associated with an increased rate of herpes zoster when compared with the general population: 13.3 cases per 1,000 patient-years for psoriasis and 15.9 for psoriatic arthritis, compared with 8.5 in healthy controls after adjustment for age, sex, and systemic medications. Most of this increased incidence was seen in patients with more severe disease: Those with mild disease who were not receiving systemic therapy had a risk similar to that of healthy controls.
However, one study suggested much of the increased risk of herpes zoster in psoriasis was accounted for by immunosuppressive therapy; when those patients were excluded, there was an 8% increase in risk.
The authors found that people whose psoriasis was treated with tofacitinib (Xeljanz) had a two- to threefold increased risk of herpes zoster, compared with those treated with tumor necrosis factor (TNF) inhibitors or conventional synthetic disease-modifying antirheumatic drugs (DMARDs).
Corticosteroids – either alone or in combination with DMARDs – were also associated with significant increases in the risk of herpes zoster. Patients treated with TNF inhibitor monotherapy had a risk of herpes zoster similar to that of those treated with conventional synthetic DMARDs or no synthetic therapy.
On the question of immunization, the authors pointed to guidelines recommending use of the live attenuated zoster vaccine (Zostavax) in immunocompetent patients or those on low-dose immunosuppression, although they noted that the vaccine is currently contraindicated for patients on biologic DMARDs.
They also examined the evidence for the use of the recently-released non-live recombinant herpes zoster vaccine (Shingrix) in immunocompromised patients, which found no evidence of vaccine-related serious adverse events in individuals with HIV and low CD4 cell counts and in autologous hematopoietic stem cell transplant recipients.
Given this, they recommended that the recombinant vaccine be administered to all patients aged over 50 years with psoriasis or psoriatic arthritis, and to those aged under 50 years who were being treated with tofacitinib, systemic corticosteroids, or combination systemic therapy.
There were insufficient data to draw conclusions about the impact of treatment with the interleukin-12/23 blocker ustekinumab (Stelara) on herpes zoster risk, but the authors noted that there was a trend toward an increased risk. They found no increase in the risk of herpes zoster with interleukin-17 inhibitors (ixekizumab [Taltz], secukinumab [Cosentyx], and brodalumab [Siliq]) and interleukin-23 (p19 subunit) inhibitors (guselkumab [Tremfya], tildrakizumab [Ilumya], and risankizumab) but noted an absence of long-term safety data for these drugs.
Four authors declared advisory, consultancy, or speaker positions with the pharmaceutical sector.
SOURCE: Baumrin E et al. J Am Acad Dermatol. 2019 March 15. doi: 10.1016/j.jaad.2019.03.017.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
FDA approves patient-controlled injector for guselkumab
The Food and Drug Administration has in adults, the manufacturer announced.
FDA approval is based on results from the phase 3, multicenter, randomized ORION trial, according to a press release issued by Janssen. In a Self-Injection Assessment Questionnaire, patients who received the One-Press injection rated their satisfaction with self-injection a mean score of 9.18 (0 indicated least satisfaction, 10 indicated highest satisfaction) and rated ease of use at 9.24 (10 indicated “very easy”).
In addition, 81% of patients who received One-Press achieved a Investigator’s Global Assessment score of 0 or 1, and 76% achieved a Psoriasis Area Severity Index (PASI) 90 response after 16 weeks; no patients who received the placebo achieved either.
The most common adverse event during the ORION study was injection-site reaction; the most common adverse events associated with guselkumab, an interleukin-23 blocker, include upper respiratory infections, headache, injection-site reactions, joint pain, diarrhea, gastroenteritis, fungal skin infections, and herpes simplex infections.
The Food and Drug Administration has in adults, the manufacturer announced.
FDA approval is based on results from the phase 3, multicenter, randomized ORION trial, according to a press release issued by Janssen. In a Self-Injection Assessment Questionnaire, patients who received the One-Press injection rated their satisfaction with self-injection a mean score of 9.18 (0 indicated least satisfaction, 10 indicated highest satisfaction) and rated ease of use at 9.24 (10 indicated “very easy”).
In addition, 81% of patients who received One-Press achieved a Investigator’s Global Assessment score of 0 or 1, and 76% achieved a Psoriasis Area Severity Index (PASI) 90 response after 16 weeks; no patients who received the placebo achieved either.
The most common adverse event during the ORION study was injection-site reaction; the most common adverse events associated with guselkumab, an interleukin-23 blocker, include upper respiratory infections, headache, injection-site reactions, joint pain, diarrhea, gastroenteritis, fungal skin infections, and herpes simplex infections.
The Food and Drug Administration has in adults, the manufacturer announced.
FDA approval is based on results from the phase 3, multicenter, randomized ORION trial, according to a press release issued by Janssen. In a Self-Injection Assessment Questionnaire, patients who received the One-Press injection rated their satisfaction with self-injection a mean score of 9.18 (0 indicated least satisfaction, 10 indicated highest satisfaction) and rated ease of use at 9.24 (10 indicated “very easy”).
In addition, 81% of patients who received One-Press achieved a Investigator’s Global Assessment score of 0 or 1, and 76% achieved a Psoriasis Area Severity Index (PASI) 90 response after 16 weeks; no patients who received the placebo achieved either.
The most common adverse event during the ORION study was injection-site reaction; the most common adverse events associated with guselkumab, an interleukin-23 blocker, include upper respiratory infections, headache, injection-site reactions, joint pain, diarrhea, gastroenteritis, fungal skin infections, and herpes simplex infections.
Golimumab plus methotrexate looks good in early psoriatic arthritis
For patients with early psoriatic arthritis, starting the tumor necrosis factor inhibitor golimumab (Simponi) at the same time as methotrexate nearly doubled the chances of remission, compared with methotrexate monotherapy, researchers reported in Annals of the Rheumatic Diseases.
In this multicenter, double-blind trial, 51 adults with CASPAR-defined psoriatic arthritis who were naive to methotrexate and biologic disease-modifying antirheumatic drugs were randomly assigned to receive monthly golimumab (50 mg subcutaneously) or placebo, in addition to methotrexate (15 mg/week, increased to 25 mg/week over 8 weeks). All patients had current active disease: At baseline, most had at least five swollen joints and at least nine tender joints.
Among 45 patients who completed the study, rates of Disease Activity Score (DAS) remission (DAS C-reactive protein score less than 1.6) at week 22 were 81% for golimumab-methotrexate and 42% for methotrexate-placebo (P = .004). “This difference in DAS remission was already observed at week 8,” wrote Leonieke J.J. van Mens, MD, of AMC/University of Amsterdam and her colleagues.
Golimumab-methotrexate also topped methotrexate monotherapy on secondary outcome measures. By week 22, median swollen joint counts were 0 with combined therapy versus 3 with methotrexate monotherapy (P = .04). Median tender joint counts were 0 and 2, respectively (P = .02). Combined golimumab-methotrexate therapy also produced significantly higher rates of low disease activity based on Disease Activity in Psoriatic Arthritis score (92% vs. 54%, respectively), Minimal Disease Activity (81% vs. 29%), and ACR20, 50, or 70 response (85% vs. 58%, 81% vs. 33%, and 58% vs. 13%, respectively).
Most differences were already statistically significant by week 8, and many were more pronounced by week 22, the researchers said. “It remains unknown if the responses – in particular the stringent responses such as remission – have already plateaued at week 22 or could even further increase over time,” they added. “Similarly, it remains to be determined if the combination of tumor necrosis factor inhibitor and methotrexate is only needed for the induction of remission or is also needed to maintain this state of remission over time.”
They explained that golimumab (or placebo) was stopped at week 22 in patients who achieved DAS CRP remission. An extension of the current study will assess whether methotrexate monotherapy can maintain responses for up to 50 weeks.
The only serious adverse event in the study occurred in the methotrexate arm and consisted of spinal stenosis that was not seen as treatment related. Rates of other adverse events were similar between arms, and those that required a dose halt or dose reduction were related to methotrexate, not golimumab. There were no deaths on trial.
Merck Sharp & Dohme provided medication and unrestricted funding for the study. Dr. van Mens and two coinvestigators reported having no disclosures. Several other coinvestigators disclosed ties to UCB, AbbVie, Novartis, Janssen, Eli Lilly, and other pharmaceutical companies.
SOURCE: van Mens LJJ et al. Ann Rheum Dis. 2019 Feb 26. doi: 10.1136/annrheumdis-2018-214746.
For patients with early psoriatic arthritis, starting the tumor necrosis factor inhibitor golimumab (Simponi) at the same time as methotrexate nearly doubled the chances of remission, compared with methotrexate monotherapy, researchers reported in Annals of the Rheumatic Diseases.
In this multicenter, double-blind trial, 51 adults with CASPAR-defined psoriatic arthritis who were naive to methotrexate and biologic disease-modifying antirheumatic drugs were randomly assigned to receive monthly golimumab (50 mg subcutaneously) or placebo, in addition to methotrexate (15 mg/week, increased to 25 mg/week over 8 weeks). All patients had current active disease: At baseline, most had at least five swollen joints and at least nine tender joints.
Among 45 patients who completed the study, rates of Disease Activity Score (DAS) remission (DAS C-reactive protein score less than 1.6) at week 22 were 81% for golimumab-methotrexate and 42% for methotrexate-placebo (P = .004). “This difference in DAS remission was already observed at week 8,” wrote Leonieke J.J. van Mens, MD, of AMC/University of Amsterdam and her colleagues.
Golimumab-methotrexate also topped methotrexate monotherapy on secondary outcome measures. By week 22, median swollen joint counts were 0 with combined therapy versus 3 with methotrexate monotherapy (P = .04). Median tender joint counts were 0 and 2, respectively (P = .02). Combined golimumab-methotrexate therapy also produced significantly higher rates of low disease activity based on Disease Activity in Psoriatic Arthritis score (92% vs. 54%, respectively), Minimal Disease Activity (81% vs. 29%), and ACR20, 50, or 70 response (85% vs. 58%, 81% vs. 33%, and 58% vs. 13%, respectively).
Most differences were already statistically significant by week 8, and many were more pronounced by week 22, the researchers said. “It remains unknown if the responses – in particular the stringent responses such as remission – have already plateaued at week 22 or could even further increase over time,” they added. “Similarly, it remains to be determined if the combination of tumor necrosis factor inhibitor and methotrexate is only needed for the induction of remission or is also needed to maintain this state of remission over time.”
They explained that golimumab (or placebo) was stopped at week 22 in patients who achieved DAS CRP remission. An extension of the current study will assess whether methotrexate monotherapy can maintain responses for up to 50 weeks.
The only serious adverse event in the study occurred in the methotrexate arm and consisted of spinal stenosis that was not seen as treatment related. Rates of other adverse events were similar between arms, and those that required a dose halt or dose reduction were related to methotrexate, not golimumab. There were no deaths on trial.
Merck Sharp & Dohme provided medication and unrestricted funding for the study. Dr. van Mens and two coinvestigators reported having no disclosures. Several other coinvestigators disclosed ties to UCB, AbbVie, Novartis, Janssen, Eli Lilly, and other pharmaceutical companies.
SOURCE: van Mens LJJ et al. Ann Rheum Dis. 2019 Feb 26. doi: 10.1136/annrheumdis-2018-214746.
For patients with early psoriatic arthritis, starting the tumor necrosis factor inhibitor golimumab (Simponi) at the same time as methotrexate nearly doubled the chances of remission, compared with methotrexate monotherapy, researchers reported in Annals of the Rheumatic Diseases.
In this multicenter, double-blind trial, 51 adults with CASPAR-defined psoriatic arthritis who were naive to methotrexate and biologic disease-modifying antirheumatic drugs were randomly assigned to receive monthly golimumab (50 mg subcutaneously) or placebo, in addition to methotrexate (15 mg/week, increased to 25 mg/week over 8 weeks). All patients had current active disease: At baseline, most had at least five swollen joints and at least nine tender joints.
Among 45 patients who completed the study, rates of Disease Activity Score (DAS) remission (DAS C-reactive protein score less than 1.6) at week 22 were 81% for golimumab-methotrexate and 42% for methotrexate-placebo (P = .004). “This difference in DAS remission was already observed at week 8,” wrote Leonieke J.J. van Mens, MD, of AMC/University of Amsterdam and her colleagues.
Golimumab-methotrexate also topped methotrexate monotherapy on secondary outcome measures. By week 22, median swollen joint counts were 0 with combined therapy versus 3 with methotrexate monotherapy (P = .04). Median tender joint counts were 0 and 2, respectively (P = .02). Combined golimumab-methotrexate therapy also produced significantly higher rates of low disease activity based on Disease Activity in Psoriatic Arthritis score (92% vs. 54%, respectively), Minimal Disease Activity (81% vs. 29%), and ACR20, 50, or 70 response (85% vs. 58%, 81% vs. 33%, and 58% vs. 13%, respectively).
Most differences were already statistically significant by week 8, and many were more pronounced by week 22, the researchers said. “It remains unknown if the responses – in particular the stringent responses such as remission – have already plateaued at week 22 or could even further increase over time,” they added. “Similarly, it remains to be determined if the combination of tumor necrosis factor inhibitor and methotrexate is only needed for the induction of remission or is also needed to maintain this state of remission over time.”
They explained that golimumab (or placebo) was stopped at week 22 in patients who achieved DAS CRP remission. An extension of the current study will assess whether methotrexate monotherapy can maintain responses for up to 50 weeks.
The only serious adverse event in the study occurred in the methotrexate arm and consisted of spinal stenosis that was not seen as treatment related. Rates of other adverse events were similar between arms, and those that required a dose halt or dose reduction were related to methotrexate, not golimumab. There were no deaths on trial.
Merck Sharp & Dohme provided medication and unrestricted funding for the study. Dr. van Mens and two coinvestigators reported having no disclosures. Several other coinvestigators disclosed ties to UCB, AbbVie, Novartis, Janssen, Eli Lilly, and other pharmaceutical companies.
SOURCE: van Mens LJJ et al. Ann Rheum Dis. 2019 Feb 26. doi: 10.1136/annrheumdis-2018-214746.
FROM ANNALS OF THE RHEUMATIC DISEASES
FDA: Safety signal emerged with higher dose of tofacitinib in RA study
the Food and Drug Administration reported.
The trial’s Data Safety and Monitoring Board identified the signal in patients taking a 10-mg dose of tofacitinib twice daily, the FDA said in a safety announcement.
Pfizer, the trial’s sponsor, took “immediate action” to transition patients in the ongoing trial from the 10-mg, twice-daily dose to 5 mg twice daily, which is the approved dose for adult patients with moderate to severe rheumatoid arthritis, the agency said. The 10-mg, twice-daily dose is approved only in the dosing regimen for patients with ulcerative colitis. Xeljanz is also approved to treat psoriatic arthritis. The 11-mg, once-daily dose of Xeljanz XR that is approved to treat rheumatoid arthritis and psoriatic arthritis was not tested in the trial.
The ongoing study was designed to assess risks of cardiovascular events, cancer, and opportunistic infections with tofacitinib 10 mg twice daily or 5 mg twice daily versus the risks in a control group treated with a tumor necrosis factor (TNF) inhibitor, according to the statement.
Patients had to be 50 years of age or older and have at least one cardiovascular risk factor to be eligible for the study, which was required by the agency in 2012 when it approved tofacitinib, the statement says.
The FDA is reviewing trial data and working with Pfizer to better understand the safety signal, its effect on patients, and how tofacitinib should be used, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a news release. The trial will continue and is expected to be completed by the end of 2019.
“The agency will take appropriate action, as warranted, to ensure patients enrolled in this and other trials are protected and that health care professionals and clinical trial researchers understand the risks associated with this use,” she added.
Health care professionals should follow tofacitinib prescribing information, monitor patients for the signs and symptoms of pulmonary embolism, and advise patients to seek medical attention immediately if they experience those signs and symptoms, according to the statement.
“We are communicating now, given the serious nature of the safety issue, to ensure that patients taking tofacitinib are aware that the FDA still believes the benefits of taking tofacitinib for its approved uses continue to outweigh the risks,” Dr. Woodcock said in the release.
While not approved in rheumatoid arthritis, the 10-mg, twice-daily dose of tofacitinib is approved in the dosing regimen for patients with ulcerative colitis, the release says.
the Food and Drug Administration reported.
The trial’s Data Safety and Monitoring Board identified the signal in patients taking a 10-mg dose of tofacitinib twice daily, the FDA said in a safety announcement.
Pfizer, the trial’s sponsor, took “immediate action” to transition patients in the ongoing trial from the 10-mg, twice-daily dose to 5 mg twice daily, which is the approved dose for adult patients with moderate to severe rheumatoid arthritis, the agency said. The 10-mg, twice-daily dose is approved only in the dosing regimen for patients with ulcerative colitis. Xeljanz is also approved to treat psoriatic arthritis. The 11-mg, once-daily dose of Xeljanz XR that is approved to treat rheumatoid arthritis and psoriatic arthritis was not tested in the trial.
The ongoing study was designed to assess risks of cardiovascular events, cancer, and opportunistic infections with tofacitinib 10 mg twice daily or 5 mg twice daily versus the risks in a control group treated with a tumor necrosis factor (TNF) inhibitor, according to the statement.
Patients had to be 50 years of age or older and have at least one cardiovascular risk factor to be eligible for the study, which was required by the agency in 2012 when it approved tofacitinib, the statement says.
The FDA is reviewing trial data and working with Pfizer to better understand the safety signal, its effect on patients, and how tofacitinib should be used, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a news release. The trial will continue and is expected to be completed by the end of 2019.
“The agency will take appropriate action, as warranted, to ensure patients enrolled in this and other trials are protected and that health care professionals and clinical trial researchers understand the risks associated with this use,” she added.
Health care professionals should follow tofacitinib prescribing information, monitor patients for the signs and symptoms of pulmonary embolism, and advise patients to seek medical attention immediately if they experience those signs and symptoms, according to the statement.
“We are communicating now, given the serious nature of the safety issue, to ensure that patients taking tofacitinib are aware that the FDA still believes the benefits of taking tofacitinib for its approved uses continue to outweigh the risks,” Dr. Woodcock said in the release.
While not approved in rheumatoid arthritis, the 10-mg, twice-daily dose of tofacitinib is approved in the dosing regimen for patients with ulcerative colitis, the release says.
the Food and Drug Administration reported.
The trial’s Data Safety and Monitoring Board identified the signal in patients taking a 10-mg dose of tofacitinib twice daily, the FDA said in a safety announcement.
Pfizer, the trial’s sponsor, took “immediate action” to transition patients in the ongoing trial from the 10-mg, twice-daily dose to 5 mg twice daily, which is the approved dose for adult patients with moderate to severe rheumatoid arthritis, the agency said. The 10-mg, twice-daily dose is approved only in the dosing regimen for patients with ulcerative colitis. Xeljanz is also approved to treat psoriatic arthritis. The 11-mg, once-daily dose of Xeljanz XR that is approved to treat rheumatoid arthritis and psoriatic arthritis was not tested in the trial.
The ongoing study was designed to assess risks of cardiovascular events, cancer, and opportunistic infections with tofacitinib 10 mg twice daily or 5 mg twice daily versus the risks in a control group treated with a tumor necrosis factor (TNF) inhibitor, according to the statement.
Patients had to be 50 years of age or older and have at least one cardiovascular risk factor to be eligible for the study, which was required by the agency in 2012 when it approved tofacitinib, the statement says.
The FDA is reviewing trial data and working with Pfizer to better understand the safety signal, its effect on patients, and how tofacitinib should be used, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in a news release. The trial will continue and is expected to be completed by the end of 2019.
“The agency will take appropriate action, as warranted, to ensure patients enrolled in this and other trials are protected and that health care professionals and clinical trial researchers understand the risks associated with this use,” she added.
Health care professionals should follow tofacitinib prescribing information, monitor patients for the signs and symptoms of pulmonary embolism, and advise patients to seek medical attention immediately if they experience those signs and symptoms, according to the statement.
“We are communicating now, given the serious nature of the safety issue, to ensure that patients taking tofacitinib are aware that the FDA still believes the benefits of taking tofacitinib for its approved uses continue to outweigh the risks,” Dr. Woodcock said in the release.
While not approved in rheumatoid arthritis, the 10-mg, twice-daily dose of tofacitinib is approved in the dosing regimen for patients with ulcerative colitis, the release says.
Ixekizumab psoriasis outcomes, sliced and diced
WAIKOLOA, HAWAII – The highly selective interleukin-17A subunit inhibitor in the long-term extension phase of the randomized, controlled UNCOVER-3 (NCT01646177) trial, Craig L. Leonardi, MD, reported at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
However, the strict inclusion and exclusion criteria employed in randomized trials such as this raise questions about the broader applicability of the results in real-world clinical practice. So separately at the Hawaii seminar, Dr. Leonardi presented a single-center retrospective observational cohort study of the rapidity and duration of response to ixekizumab in his own clinical practice after the biologic received Food and Drug Administration marketing approval. Those results, too, were impressive and, in his view, highly generalizable.
“It is expected that this study cohort is generally representative of patients who are routinely seen at dermatology referral practices in the U.S.,” commented Dr. Leonardi, of Saint Louis University.
UNCOVER-3 included 1,346 psoriasis patients initially randomized 2:2:2:1 to double-blind subcutaneous ixekizumab (Taltz) at 80 mg either every 2 weeks or every 4 weeks after a 160-mg loading dose; subcutaneous etanercept at 50 mg twice weekly; or placebo for 12 weeks, followed by a switch to ixekizumab at 80 mg every 4 weeks from week 12 out to 3 years. The long-term efficacy analysis was restricted to patients who received the biologic according to what ultimately became the approved dosing schedule: a 160-mg loading dose, followed by 80 mg every 2 weeks through week 12, then 80 mg every 4 weeks. The safety analysis, in contrast, included everybody.
Dr. Leonardi presented the efficacy data using several different statistical methodologies, thereby providing an instructive lesson regarding the importance of examining the fine print when viewing clinical trial results. At one extreme is the as-observed analysis. Under this methodology, if a patient dropped out of UNCOVER-3 at, for example, week 11, the last measurement of treatment response, recorded at week 8, is carried forward by investigators and assumed to be valid for the rest of the study. Since week 8 may have been the last time the patient was doing well on the drug, the as-observed analysis can create a distorted overly favorable picture of the drug’s performance.
“Patients fall out because the drug isn’t working well or they’re having a side effect, so over time, you tend to enrich for patients who are doing very well with the as-observed analysis,” the dermatologist explained.
Historically, many industry-sponsored clinical trials reported efficacy outcomes using the as-observed analysis; however, the FDA is increasingly unwilling to accept that approach as the sole analytic method.
At the other extreme is the nonresponder imputation method.
“This is the most stringent statistical package that exists. In fact, when a patient isn’t observed at one of the observation points – for example, at week 8 say the patient has a flat tire and can’t make it to the clinic – they’re counted as a treatment failure. So it’s a very tough statistical package,” according to Dr. Leonardi.
Seventy-seven percent of the initial 1,346 randomized patients in UNCOVER-3 completed 156 weeks of follow-up. To illustrate the importance of paying attention to the details of statistical methodology utilized in reporting efficacy outcomes, he noted that the PASI 75 rate at 156 weeks in study completers on the approved dosing regimen was 97% by the as-observed method, dropping to a still robust 81% by nonresponder imputation. The PASI 90 and -100 rates and static Physician’s Global Assessment (sPGA) results followed suit (see graphic).
Real-world performance
Dr. Leonard’s analysis of ixekizumab’s performance in his own practice included 106 patients placed on the drug following its FDA approval in March 2016, 74% of whom were still on the drug 12 months later. The cohort had a mean disease duration of 15 years. Three-quarters of them had previously received biologic therapy for their psoriasis, most often a tumor necrosis factor inhibitor. The study efficacy endpoints were the sPGA and Dermatology Life Quality Index (DLQI).
Already at 1 month, 30% of ixekizumab-treated patients had an sPGA score of 0, meaning their skin was totally clear. Another 29% had an sPGA of 1, meaning almost clear. At 3 months, 53% of patients had an sPGA of 0 and 21% had an sPGA of 1. Among patients on treatment at 12 months, the rates were 39% and 24% for sPGAs of 0 and 1, respectively. And in patients with an sPGA of 0/1 at 3 months, 73% maintained that score at 12 months, including 47% with an sPGA of 0.
A DLQI score of 0/1, indicative of little or no disease effect upon a patient’s life, was present in 63% of ixekizumab-treated patients at 1 month, 84% at 3 months, and 73% at 12 months.
The value in pushing for PASI 100
The ixekizumab experience in the phase-3 UNCOVER clinical trial program provided the first-ever evidence that incrementally improving psoriasis also provides stepwise improvement in DLQI, a key patient-reported outcome. At week 12 under double-blind conditions, only 4% of ixekizumab-treated patients with less than a PASI 50 response had a DLQI of 0/1. The rate rose to 18.8% in those with a PASI 50 to less than PASI 75 response. In patients with a week-12 PASI 75 to less than PASI 90 response, the DLQI 0/1 rate climbed to 52.3%. At a PASI 90 to less than PASI 100 response, the rate was 66.9%. And 82.9% of patients with a PASI 100 had a DLQI of 0/1. Every step of the way, those DLQI rates were significantly different from each other.
These data are “fascinating,” Dr. Leonardi commented. “If you ever get any inquiries from the friendly insurance carrier and they want to know if you’re improving your patient’s life, this is the kind of data that supports that they’re being improved dramatically.”
Dr. Leonardi noted that ixekizumab isn’t unique in its high rate of clinical effectiveness. That distinction is shared by the other approved IL-17 inhibitors, secukinumab (Cosentyx) and brodalumab (Siliq), as well as the IL-23 inhibitor guselkumab (Tremfya). He refers to these biologics collectively as “high-performance skin-clearance drugs.” He has calculated the number needed to treat (NNT) to achieve a PASI 100 response – complete clearance of the disease – based upon clinical trial data filed with the FDA and/or in the package inserts. The numbers are eye-opening: an NTT of 2.6 for ixekizumab based upon data from the UNCOVER-2 trial, 2.4 for brodalumab, 2.7 for guselkumab, and 3.6 for secukinumab. To help put that into perspective, the NNTs for methotrexate and etanercept (Enbrel) – not so long ago considered state of the art medications for moderate to severe psoriasis – are 25 and 23.3, respectively.
The UNCOVER trial portfolio and Dr. Leonardi’s single-center retrospective study were funded by Eli Lilly, which markets ixekizumab. He reported serving as a consultant to and receiving research funding from that company and more than a dozen others.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – The highly selective interleukin-17A subunit inhibitor in the long-term extension phase of the randomized, controlled UNCOVER-3 (NCT01646177) trial, Craig L. Leonardi, MD, reported at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
However, the strict inclusion and exclusion criteria employed in randomized trials such as this raise questions about the broader applicability of the results in real-world clinical practice. So separately at the Hawaii seminar, Dr. Leonardi presented a single-center retrospective observational cohort study of the rapidity and duration of response to ixekizumab in his own clinical practice after the biologic received Food and Drug Administration marketing approval. Those results, too, were impressive and, in his view, highly generalizable.
“It is expected that this study cohort is generally representative of patients who are routinely seen at dermatology referral practices in the U.S.,” commented Dr. Leonardi, of Saint Louis University.
UNCOVER-3 included 1,346 psoriasis patients initially randomized 2:2:2:1 to double-blind subcutaneous ixekizumab (Taltz) at 80 mg either every 2 weeks or every 4 weeks after a 160-mg loading dose; subcutaneous etanercept at 50 mg twice weekly; or placebo for 12 weeks, followed by a switch to ixekizumab at 80 mg every 4 weeks from week 12 out to 3 years. The long-term efficacy analysis was restricted to patients who received the biologic according to what ultimately became the approved dosing schedule: a 160-mg loading dose, followed by 80 mg every 2 weeks through week 12, then 80 mg every 4 weeks. The safety analysis, in contrast, included everybody.
Dr. Leonardi presented the efficacy data using several different statistical methodologies, thereby providing an instructive lesson regarding the importance of examining the fine print when viewing clinical trial results. At one extreme is the as-observed analysis. Under this methodology, if a patient dropped out of UNCOVER-3 at, for example, week 11, the last measurement of treatment response, recorded at week 8, is carried forward by investigators and assumed to be valid for the rest of the study. Since week 8 may have been the last time the patient was doing well on the drug, the as-observed analysis can create a distorted overly favorable picture of the drug’s performance.
“Patients fall out because the drug isn’t working well or they’re having a side effect, so over time, you tend to enrich for patients who are doing very well with the as-observed analysis,” the dermatologist explained.
Historically, many industry-sponsored clinical trials reported efficacy outcomes using the as-observed analysis; however, the FDA is increasingly unwilling to accept that approach as the sole analytic method.
At the other extreme is the nonresponder imputation method.
“This is the most stringent statistical package that exists. In fact, when a patient isn’t observed at one of the observation points – for example, at week 8 say the patient has a flat tire and can’t make it to the clinic – they’re counted as a treatment failure. So it’s a very tough statistical package,” according to Dr. Leonardi.
Seventy-seven percent of the initial 1,346 randomized patients in UNCOVER-3 completed 156 weeks of follow-up. To illustrate the importance of paying attention to the details of statistical methodology utilized in reporting efficacy outcomes, he noted that the PASI 75 rate at 156 weeks in study completers on the approved dosing regimen was 97% by the as-observed method, dropping to a still robust 81% by nonresponder imputation. The PASI 90 and -100 rates and static Physician’s Global Assessment (sPGA) results followed suit (see graphic).
Real-world performance
Dr. Leonard’s analysis of ixekizumab’s performance in his own practice included 106 patients placed on the drug following its FDA approval in March 2016, 74% of whom were still on the drug 12 months later. The cohort had a mean disease duration of 15 years. Three-quarters of them had previously received biologic therapy for their psoriasis, most often a tumor necrosis factor inhibitor. The study efficacy endpoints were the sPGA and Dermatology Life Quality Index (DLQI).
Already at 1 month, 30% of ixekizumab-treated patients had an sPGA score of 0, meaning their skin was totally clear. Another 29% had an sPGA of 1, meaning almost clear. At 3 months, 53% of patients had an sPGA of 0 and 21% had an sPGA of 1. Among patients on treatment at 12 months, the rates were 39% and 24% for sPGAs of 0 and 1, respectively. And in patients with an sPGA of 0/1 at 3 months, 73% maintained that score at 12 months, including 47% with an sPGA of 0.
A DLQI score of 0/1, indicative of little or no disease effect upon a patient’s life, was present in 63% of ixekizumab-treated patients at 1 month, 84% at 3 months, and 73% at 12 months.
The value in pushing for PASI 100
The ixekizumab experience in the phase-3 UNCOVER clinical trial program provided the first-ever evidence that incrementally improving psoriasis also provides stepwise improvement in DLQI, a key patient-reported outcome. At week 12 under double-blind conditions, only 4% of ixekizumab-treated patients with less than a PASI 50 response had a DLQI of 0/1. The rate rose to 18.8% in those with a PASI 50 to less than PASI 75 response. In patients with a week-12 PASI 75 to less than PASI 90 response, the DLQI 0/1 rate climbed to 52.3%. At a PASI 90 to less than PASI 100 response, the rate was 66.9%. And 82.9% of patients with a PASI 100 had a DLQI of 0/1. Every step of the way, those DLQI rates were significantly different from each other.
These data are “fascinating,” Dr. Leonardi commented. “If you ever get any inquiries from the friendly insurance carrier and they want to know if you’re improving your patient’s life, this is the kind of data that supports that they’re being improved dramatically.”
Dr. Leonardi noted that ixekizumab isn’t unique in its high rate of clinical effectiveness. That distinction is shared by the other approved IL-17 inhibitors, secukinumab (Cosentyx) and brodalumab (Siliq), as well as the IL-23 inhibitor guselkumab (Tremfya). He refers to these biologics collectively as “high-performance skin-clearance drugs.” He has calculated the number needed to treat (NNT) to achieve a PASI 100 response – complete clearance of the disease – based upon clinical trial data filed with the FDA and/or in the package inserts. The numbers are eye-opening: an NTT of 2.6 for ixekizumab based upon data from the UNCOVER-2 trial, 2.4 for brodalumab, 2.7 for guselkumab, and 3.6 for secukinumab. To help put that into perspective, the NNTs for methotrexate and etanercept (Enbrel) – not so long ago considered state of the art medications for moderate to severe psoriasis – are 25 and 23.3, respectively.
The UNCOVER trial portfolio and Dr. Leonardi’s single-center retrospective study were funded by Eli Lilly, which markets ixekizumab. He reported serving as a consultant to and receiving research funding from that company and more than a dozen others.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – The highly selective interleukin-17A subunit inhibitor in the long-term extension phase of the randomized, controlled UNCOVER-3 (NCT01646177) trial, Craig L. Leonardi, MD, reported at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
However, the strict inclusion and exclusion criteria employed in randomized trials such as this raise questions about the broader applicability of the results in real-world clinical practice. So separately at the Hawaii seminar, Dr. Leonardi presented a single-center retrospective observational cohort study of the rapidity and duration of response to ixekizumab in his own clinical practice after the biologic received Food and Drug Administration marketing approval. Those results, too, were impressive and, in his view, highly generalizable.
“It is expected that this study cohort is generally representative of patients who are routinely seen at dermatology referral practices in the U.S.,” commented Dr. Leonardi, of Saint Louis University.
UNCOVER-3 included 1,346 psoriasis patients initially randomized 2:2:2:1 to double-blind subcutaneous ixekizumab (Taltz) at 80 mg either every 2 weeks or every 4 weeks after a 160-mg loading dose; subcutaneous etanercept at 50 mg twice weekly; or placebo for 12 weeks, followed by a switch to ixekizumab at 80 mg every 4 weeks from week 12 out to 3 years. The long-term efficacy analysis was restricted to patients who received the biologic according to what ultimately became the approved dosing schedule: a 160-mg loading dose, followed by 80 mg every 2 weeks through week 12, then 80 mg every 4 weeks. The safety analysis, in contrast, included everybody.
Dr. Leonardi presented the efficacy data using several different statistical methodologies, thereby providing an instructive lesson regarding the importance of examining the fine print when viewing clinical trial results. At one extreme is the as-observed analysis. Under this methodology, if a patient dropped out of UNCOVER-3 at, for example, week 11, the last measurement of treatment response, recorded at week 8, is carried forward by investigators and assumed to be valid for the rest of the study. Since week 8 may have been the last time the patient was doing well on the drug, the as-observed analysis can create a distorted overly favorable picture of the drug’s performance.
“Patients fall out because the drug isn’t working well or they’re having a side effect, so over time, you tend to enrich for patients who are doing very well with the as-observed analysis,” the dermatologist explained.
Historically, many industry-sponsored clinical trials reported efficacy outcomes using the as-observed analysis; however, the FDA is increasingly unwilling to accept that approach as the sole analytic method.
At the other extreme is the nonresponder imputation method.
“This is the most stringent statistical package that exists. In fact, when a patient isn’t observed at one of the observation points – for example, at week 8 say the patient has a flat tire and can’t make it to the clinic – they’re counted as a treatment failure. So it’s a very tough statistical package,” according to Dr. Leonardi.
Seventy-seven percent of the initial 1,346 randomized patients in UNCOVER-3 completed 156 weeks of follow-up. To illustrate the importance of paying attention to the details of statistical methodology utilized in reporting efficacy outcomes, he noted that the PASI 75 rate at 156 weeks in study completers on the approved dosing regimen was 97% by the as-observed method, dropping to a still robust 81% by nonresponder imputation. The PASI 90 and -100 rates and static Physician’s Global Assessment (sPGA) results followed suit (see graphic).
Real-world performance
Dr. Leonard’s analysis of ixekizumab’s performance in his own practice included 106 patients placed on the drug following its FDA approval in March 2016, 74% of whom were still on the drug 12 months later. The cohort had a mean disease duration of 15 years. Three-quarters of them had previously received biologic therapy for their psoriasis, most often a tumor necrosis factor inhibitor. The study efficacy endpoints were the sPGA and Dermatology Life Quality Index (DLQI).
Already at 1 month, 30% of ixekizumab-treated patients had an sPGA score of 0, meaning their skin was totally clear. Another 29% had an sPGA of 1, meaning almost clear. At 3 months, 53% of patients had an sPGA of 0 and 21% had an sPGA of 1. Among patients on treatment at 12 months, the rates were 39% and 24% for sPGAs of 0 and 1, respectively. And in patients with an sPGA of 0/1 at 3 months, 73% maintained that score at 12 months, including 47% with an sPGA of 0.
A DLQI score of 0/1, indicative of little or no disease effect upon a patient’s life, was present in 63% of ixekizumab-treated patients at 1 month, 84% at 3 months, and 73% at 12 months.
The value in pushing for PASI 100
The ixekizumab experience in the phase-3 UNCOVER clinical trial program provided the first-ever evidence that incrementally improving psoriasis also provides stepwise improvement in DLQI, a key patient-reported outcome. At week 12 under double-blind conditions, only 4% of ixekizumab-treated patients with less than a PASI 50 response had a DLQI of 0/1. The rate rose to 18.8% in those with a PASI 50 to less than PASI 75 response. In patients with a week-12 PASI 75 to less than PASI 90 response, the DLQI 0/1 rate climbed to 52.3%. At a PASI 90 to less than PASI 100 response, the rate was 66.9%. And 82.9% of patients with a PASI 100 had a DLQI of 0/1. Every step of the way, those DLQI rates were significantly different from each other.
These data are “fascinating,” Dr. Leonardi commented. “If you ever get any inquiries from the friendly insurance carrier and they want to know if you’re improving your patient’s life, this is the kind of data that supports that they’re being improved dramatically.”
Dr. Leonardi noted that ixekizumab isn’t unique in its high rate of clinical effectiveness. That distinction is shared by the other approved IL-17 inhibitors, secukinumab (Cosentyx) and brodalumab (Siliq), as well as the IL-23 inhibitor guselkumab (Tremfya). He refers to these biologics collectively as “high-performance skin-clearance drugs.” He has calculated the number needed to treat (NNT) to achieve a PASI 100 response – complete clearance of the disease – based upon clinical trial data filed with the FDA and/or in the package inserts. The numbers are eye-opening: an NTT of 2.6 for ixekizumab based upon data from the UNCOVER-2 trial, 2.4 for brodalumab, 2.7 for guselkumab, and 3.6 for secukinumab. To help put that into perspective, the NNTs for methotrexate and etanercept (Enbrel) – not so long ago considered state of the art medications for moderate to severe psoriasis – are 25 and 23.3, respectively.
The UNCOVER trial portfolio and Dr. Leonardi’s single-center retrospective study were funded by Eli Lilly, which markets ixekizumab. He reported serving as a consultant to and receiving research funding from that company and more than a dozen others.
SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM SDEF HAWAII DERMATOLOGY SEMINAR
AAD, NPF release two joint guidelines on treatment, management of psoriasis
The .
These guidelines are the first of two papers to be published in the Journal of the American Academy of Dermatology (JAAD), with four more guidelines on psoriasis to be published later this year in JAAD on phototherapy, topical therapy, nonbiologic systemic medications, and treatment of pediatric patients.
The guideline on biologics updates the 2008 AAD guidelines on psoriasis. In an interview, Alan Menter, MD, cochair of the guidelines work group and lead author of the biologics paper, said the guidelines for biologics were needed because of major advances with the availability of new biologics over the last decade. For example, three tumor necrosis factor–alpha (TNF-alpha) inhibitors were available in 2008, but that number has increased to 10 biologics and now includes agents such as those targeting interleukin (IL)-12/IL-23, IL-17 and IL-23.
In addition, the new guidelines from AAD were developed to represent improvements in the management of patients with moderate to severe psoriasis as well as the relationship between psoriasis and related comorbidities.
“Major advances in new biologic drugs [are] now available to patients, plus [there have been] significant advances in our understanding of comorbid conditions,” such as cardiovascular comorbidities, said Dr. Menter, chairman of the division of dermatology, Baylor University Medical Center, and clinical professor of dermatology, University of Texas, both in Dallas.
The working group for each set of guidelines consisted of dermatologists, patient representatives, a cardiologist, and a rheumatologist. The biologic guidelines working group analyzed studies published between January 2008 and December 2018 and issued a series of recommendations based on published evidence for the effectiveness, adverse events, and switching for Food and Drug Administration–approved TNF-alpha inhibitors (etanercept, infliximab, adalimumab, certolizumab, and TNF-alpha biosimilars); IL-12/IL-23 inhibitors (ustekinumab); IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab); and IL-23 inhibitors (guselkumab and tildrakizumab, and risankizumab, which is still under FDA review) for monotherapy or combination therapy in patients with moderate to severe psoriasis.
The biologic guidelines noted that, while FDA-approved biologics were deemed safe overall for patients with moderate to severe psoriasis, dermatologists should recognize the adverse effects of these therapies, monitor for infections, and counsel their patients against modifying or discontinuing therapy without first consulting a dermatologist. In general, the working group noted that failure with one biologic does not necessarily mean that a patient will experience failure with a different biologic, even among TNF-alpha and IL-12/IL-23 inhibitors. However, reduced efficacy for a patient receiving a specific TNF-alpha inhibitor may predict reduced efficacy when switching to a different TNF-alpha inhibitor, they said.
In the psoriasis comorbidity guideline, the working group examined the therapeutic interventions for psoriasis-related comorbidities such as psoriatic arthritis (PsA), cardiovascular disease, metabolic syndrome, and inflammatory bowel disease. They also provided recommendations on the effect of psoriasis on mental health, quality of life, and lifestyle choices such as smoking and alcohol use.
With respect to cardiovascular disease, the dermatologist should ensure that patients are aware of the association between risk factors for cardiovascular disease and psoriasis, and that they undergo screening for these risk factors, consider lifestyle changes to reduce risk of cardiovascular disease, and consult with cardiologists and primary care providers based on individual risk, the guideline states. The working group recommended that patients with psoriasis undergo screening for hypertension, diabetes, and hyperlipidemia based on national guidelines, with more frequent screening recommended for patients with psoriasis greater than 10% body surface area or who are eligible for systemic or phototherapy.
In both the biologic and the comorbidity guidelines, the working groups stressed the importance of patient education and the role of the dermatologist in educating patients so that shared decision-making can occur. They noted that education was related to improved quality of life for these patients.
“Both the comorbidities guidelines and the biologic guidelines will help educate the psoriasis population with input from dermatologists in clinical practices,” Dr. Menter said.
However, both working groups noted there are still significant gaps in research, such as the effects of treatment combinations for new biologics and the lack of biomarkers that would identify which biologics are best suited for individual psoriasis patients.
There is also little known about the complex relationship between psoriasis and its comorbidities, and how psoriasis treatment can potentially prevent future disease. To ensure treatment of psoriasis-related comorbidities, dermatologists should consider psoriasis as a systemic disease with multiple comorbidities and interact with primary care doctors, cardiologists, and other providers involved in the care of the patients, Dr. Menter said.
There were no specific funding sources reported for the guidelines. Several authors reported relationships with industry, including pharmaceutical companies with drugs and products involving psoriasis, during the development of the guidelines. If a potential conflict was noted, the working group member recused himself or herself from discussion and drafting of recommendations, according to the paper. Dr. Menter’s disclosure includes serving as a consultant, speaker, investigator, and adviser, and receiving honoraria, from multiple pharmaceutical companies.
SOURCE: Menter A et al. J Am Acad Dermatol. 2019 Feb 13. doi: 10.1016/j.jaad.2018.11.057. Elmets CA et al. J Am Acad Dermatol. 2019 Feb 13. doi: 10.1016/j.jaad.2018.11.058.
The .
These guidelines are the first of two papers to be published in the Journal of the American Academy of Dermatology (JAAD), with four more guidelines on psoriasis to be published later this year in JAAD on phototherapy, topical therapy, nonbiologic systemic medications, and treatment of pediatric patients.
The guideline on biologics updates the 2008 AAD guidelines on psoriasis. In an interview, Alan Menter, MD, cochair of the guidelines work group and lead author of the biologics paper, said the guidelines for biologics were needed because of major advances with the availability of new biologics over the last decade. For example, three tumor necrosis factor–alpha (TNF-alpha) inhibitors were available in 2008, but that number has increased to 10 biologics and now includes agents such as those targeting interleukin (IL)-12/IL-23, IL-17 and IL-23.
In addition, the new guidelines from AAD were developed to represent improvements in the management of patients with moderate to severe psoriasis as well as the relationship between psoriasis and related comorbidities.
“Major advances in new biologic drugs [are] now available to patients, plus [there have been] significant advances in our understanding of comorbid conditions,” such as cardiovascular comorbidities, said Dr. Menter, chairman of the division of dermatology, Baylor University Medical Center, and clinical professor of dermatology, University of Texas, both in Dallas.
The working group for each set of guidelines consisted of dermatologists, patient representatives, a cardiologist, and a rheumatologist. The biologic guidelines working group analyzed studies published between January 2008 and December 2018 and issued a series of recommendations based on published evidence for the effectiveness, adverse events, and switching for Food and Drug Administration–approved TNF-alpha inhibitors (etanercept, infliximab, adalimumab, certolizumab, and TNF-alpha biosimilars); IL-12/IL-23 inhibitors (ustekinumab); IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab); and IL-23 inhibitors (guselkumab and tildrakizumab, and risankizumab, which is still under FDA review) for monotherapy or combination therapy in patients with moderate to severe psoriasis.
The biologic guidelines noted that, while FDA-approved biologics were deemed safe overall for patients with moderate to severe psoriasis, dermatologists should recognize the adverse effects of these therapies, monitor for infections, and counsel their patients against modifying or discontinuing therapy without first consulting a dermatologist. In general, the working group noted that failure with one biologic does not necessarily mean that a patient will experience failure with a different biologic, even among TNF-alpha and IL-12/IL-23 inhibitors. However, reduced efficacy for a patient receiving a specific TNF-alpha inhibitor may predict reduced efficacy when switching to a different TNF-alpha inhibitor, they said.
In the psoriasis comorbidity guideline, the working group examined the therapeutic interventions for psoriasis-related comorbidities such as psoriatic arthritis (PsA), cardiovascular disease, metabolic syndrome, and inflammatory bowel disease. They also provided recommendations on the effect of psoriasis on mental health, quality of life, and lifestyle choices such as smoking and alcohol use.
With respect to cardiovascular disease, the dermatologist should ensure that patients are aware of the association between risk factors for cardiovascular disease and psoriasis, and that they undergo screening for these risk factors, consider lifestyle changes to reduce risk of cardiovascular disease, and consult with cardiologists and primary care providers based on individual risk, the guideline states. The working group recommended that patients with psoriasis undergo screening for hypertension, diabetes, and hyperlipidemia based on national guidelines, with more frequent screening recommended for patients with psoriasis greater than 10% body surface area or who are eligible for systemic or phototherapy.
In both the biologic and the comorbidity guidelines, the working groups stressed the importance of patient education and the role of the dermatologist in educating patients so that shared decision-making can occur. They noted that education was related to improved quality of life for these patients.
“Both the comorbidities guidelines and the biologic guidelines will help educate the psoriasis population with input from dermatologists in clinical practices,” Dr. Menter said.
However, both working groups noted there are still significant gaps in research, such as the effects of treatment combinations for new biologics and the lack of biomarkers that would identify which biologics are best suited for individual psoriasis patients.
There is also little known about the complex relationship between psoriasis and its comorbidities, and how psoriasis treatment can potentially prevent future disease. To ensure treatment of psoriasis-related comorbidities, dermatologists should consider psoriasis as a systemic disease with multiple comorbidities and interact with primary care doctors, cardiologists, and other providers involved in the care of the patients, Dr. Menter said.
There were no specific funding sources reported for the guidelines. Several authors reported relationships with industry, including pharmaceutical companies with drugs and products involving psoriasis, during the development of the guidelines. If a potential conflict was noted, the working group member recused himself or herself from discussion and drafting of recommendations, according to the paper. Dr. Menter’s disclosure includes serving as a consultant, speaker, investigator, and adviser, and receiving honoraria, from multiple pharmaceutical companies.
SOURCE: Menter A et al. J Am Acad Dermatol. 2019 Feb 13. doi: 10.1016/j.jaad.2018.11.057. Elmets CA et al. J Am Acad Dermatol. 2019 Feb 13. doi: 10.1016/j.jaad.2018.11.058.
The .
These guidelines are the first of two papers to be published in the Journal of the American Academy of Dermatology (JAAD), with four more guidelines on psoriasis to be published later this year in JAAD on phototherapy, topical therapy, nonbiologic systemic medications, and treatment of pediatric patients.
The guideline on biologics updates the 2008 AAD guidelines on psoriasis. In an interview, Alan Menter, MD, cochair of the guidelines work group and lead author of the biologics paper, said the guidelines for biologics were needed because of major advances with the availability of new biologics over the last decade. For example, three tumor necrosis factor–alpha (TNF-alpha) inhibitors were available in 2008, but that number has increased to 10 biologics and now includes agents such as those targeting interleukin (IL)-12/IL-23, IL-17 and IL-23.
In addition, the new guidelines from AAD were developed to represent improvements in the management of patients with moderate to severe psoriasis as well as the relationship between psoriasis and related comorbidities.
“Major advances in new biologic drugs [are] now available to patients, plus [there have been] significant advances in our understanding of comorbid conditions,” such as cardiovascular comorbidities, said Dr. Menter, chairman of the division of dermatology, Baylor University Medical Center, and clinical professor of dermatology, University of Texas, both in Dallas.
The working group for each set of guidelines consisted of dermatologists, patient representatives, a cardiologist, and a rheumatologist. The biologic guidelines working group analyzed studies published between January 2008 and December 2018 and issued a series of recommendations based on published evidence for the effectiveness, adverse events, and switching for Food and Drug Administration–approved TNF-alpha inhibitors (etanercept, infliximab, adalimumab, certolizumab, and TNF-alpha biosimilars); IL-12/IL-23 inhibitors (ustekinumab); IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab); and IL-23 inhibitors (guselkumab and tildrakizumab, and risankizumab, which is still under FDA review) for monotherapy or combination therapy in patients with moderate to severe psoriasis.
The biologic guidelines noted that, while FDA-approved biologics were deemed safe overall for patients with moderate to severe psoriasis, dermatologists should recognize the adverse effects of these therapies, monitor for infections, and counsel their patients against modifying or discontinuing therapy without first consulting a dermatologist. In general, the working group noted that failure with one biologic does not necessarily mean that a patient will experience failure with a different biologic, even among TNF-alpha and IL-12/IL-23 inhibitors. However, reduced efficacy for a patient receiving a specific TNF-alpha inhibitor may predict reduced efficacy when switching to a different TNF-alpha inhibitor, they said.
In the psoriasis comorbidity guideline, the working group examined the therapeutic interventions for psoriasis-related comorbidities such as psoriatic arthritis (PsA), cardiovascular disease, metabolic syndrome, and inflammatory bowel disease. They also provided recommendations on the effect of psoriasis on mental health, quality of life, and lifestyle choices such as smoking and alcohol use.
With respect to cardiovascular disease, the dermatologist should ensure that patients are aware of the association between risk factors for cardiovascular disease and psoriasis, and that they undergo screening for these risk factors, consider lifestyle changes to reduce risk of cardiovascular disease, and consult with cardiologists and primary care providers based on individual risk, the guideline states. The working group recommended that patients with psoriasis undergo screening for hypertension, diabetes, and hyperlipidemia based on national guidelines, with more frequent screening recommended for patients with psoriasis greater than 10% body surface area or who are eligible for systemic or phototherapy.
In both the biologic and the comorbidity guidelines, the working groups stressed the importance of patient education and the role of the dermatologist in educating patients so that shared decision-making can occur. They noted that education was related to improved quality of life for these patients.
“Both the comorbidities guidelines and the biologic guidelines will help educate the psoriasis population with input from dermatologists in clinical practices,” Dr. Menter said.
However, both working groups noted there are still significant gaps in research, such as the effects of treatment combinations for new biologics and the lack of biomarkers that would identify which biologics are best suited for individual psoriasis patients.
There is also little known about the complex relationship between psoriasis and its comorbidities, and how psoriasis treatment can potentially prevent future disease. To ensure treatment of psoriasis-related comorbidities, dermatologists should consider psoriasis as a systemic disease with multiple comorbidities and interact with primary care doctors, cardiologists, and other providers involved in the care of the patients, Dr. Menter said.
There were no specific funding sources reported for the guidelines. Several authors reported relationships with industry, including pharmaceutical companies with drugs and products involving psoriasis, during the development of the guidelines. If a potential conflict was noted, the working group member recused himself or herself from discussion and drafting of recommendations, according to the paper. Dr. Menter’s disclosure includes serving as a consultant, speaker, investigator, and adviser, and receiving honoraria, from multiple pharmaceutical companies.
SOURCE: Menter A et al. J Am Acad Dermatol. 2019 Feb 13. doi: 10.1016/j.jaad.2018.11.057. Elmets CA et al. J Am Acad Dermatol. 2019 Feb 13. doi: 10.1016/j.jaad.2018.11.058.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
What’s new with adalimumab? Plenty
WAIKOLOA, HAWAII – A flurry of recent impressive , identifies a simple biomarker predictive of the likelihood of a favorable PASI 75 response, and highlights a disconnect in psoriatic arthritis (PsA) patients between clinical response as reflected in disease activity and radiographic progression of joint disease, according to Kristina C. Duffin, MD.
Also, a new citrate-free version of adalimumab (Humira) is available. It requires a new prescription, and an additional prior authorization is mandated by some insurers. But this is a welcome innovation for patients bothered by significant burning and stinging with their injections of classic adalimumab, Dr. Duffin, cochair of the department of dermatology at the University of Utah, Salt Lake City, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
New long-term safety data
Adalimumab is a market leader in biologic therapy for psoriasis. But the long-term experience with biologics in dermatology is still relatively limited, so the recent publication of two large studies providing encouraging evidence of the long-term safety of adalimumab is noteworthy.
Craig L. Leonardi, MD, of Saint Louis University, St. Louis, Mo., was first author of an analysis of long-term safety data from 18 clinical trials in adults with moderate to severe plaque psoriasis. The key takeaway, in Dr. Duffin’s view, was that the rate of adverse events, including serious infections and malignancies other than nonmelanoma skin cancer, remained stable over time out to 240 weeks of follow-up in patients on continuous treatment, with no new safety signals emerging (Br J Dermatol. 2019 Jan;180[1]:76-85).
However, randomized clinical trials often paint an overly rosy safety picture because of their strict inclusion and exclusion criteria.
“We single out patients for clinical trials because they’re especially healthy. That doesn’t happen in real-world registries,” she noted.
That’s why a systematic review of adalimumab’s safety performance in 10 real-world registries of adalimumab-treated psoriasis patients is particularly informative. The registries included in the systematic review, led by Bruce E. Strober, MD, PhD, professor of dermatology at the University of Connecticut, Farmington, didn’t all measure the same outcomes. But the three registries that documented major adverse cardiovascular events showed rates of less than 0.1 to less than 1 per 100 patient-years. Rates of malignancies other than nonmelanoma skin cancer were consistently in the 0.3-0.6 events per 100 patient-years range, similar to what has been reported in studies of other systemic psoriasis therapies, biologic as well as nonbiologic (J Eur Acad Dermatol Venereol. 2018 Dec;32[12]:2126-33).
Overall infection rates reported in the real-world registries ranged from 7.7 to 14.7 events per 100 patient-years, which is actually considerably lower than in the clinical trials. Rates of serious infections ranged from less than one up to two events per 100 patient-years, with the most common ones being cellulitis and pneumonia, consistent with the randomized trial experience.
Predicting response to adalimumab
A prospective, multicenter, observational cohort study of 544 psoriasis patients on adalimumab monotherapy conducted by U.K. investigators concluded that a patient’s serum drug level is the single most important predictor of treatment response. A cut point of 3.2 mcg/mL, which is considered the minimal effective circulating drug level, was associated with a 65% probability of a 75% improvement in Psoriasis Area and Severity Index from baseline, or PASI 75 response. The higher the serum drug level, the greater the likelihood of a PASI 75 response, up to a serum level of 7 mcg/mL, which was associated with an 81% probability of achieving PASI 75. Beyond 7 mcg/mL, however, the relationship with treatment response plateaued. Importantly, drug levels measured early on – at 1-12 weeks into therapy – were predictive of response 6 months later. So were steady-state levels (J Invest Dermatol. 2019 Jan;139[1]:115-23).
This is clinically useful information, Dr. Duffin observed.
“I’m hoping we’re going to see more real-world use of checking drug levels,” she said.
Indeed, even though the approved dosing of adalimumab for psoriasis is 40 mg by subcutaneous injection every 2 weeks, the new American Academy of Dermatology/National Psoriasis Foundation joint guidelines for treatment of psoriasis with biologics declare that “a maintenance dose of adalimumab at 40 mg/week is recommended for better disease control in some patients” (J Am Acad Dermatol. 2019 Feb 7. doi: 10.1016/j.jaad.2018.11.057. [Epub ahead of print]).
The new guidelines provide support for dermatologists who decide weekly therapy is best for a given patient, and adalimumab drug levels could prove useful in identifying the patient subgroup likely to benefit.
Dr. Duffin is often consulted by other physicians as to whether they should check for neutralizing antibodies in patients who appear to be losing therapeutic efficacy on a given biologic. She’s not a fan of the practice.
“There are commercial assays out there, but it’s very hard to interpret them because we don’t really know if they’re truly measuring neutralizing antibodies. And the cost is not insignificant; it can be hundreds of dollars,” she noted.
She believes a straightforward measurement of the serum biologic level is a better strategy.
“It makes sense: This is an indirect way of determining if there’s been neutralization of the drug, rather than trying to check the antibody that’s doing it, which is fraught with problems,” Dr. Duffin said.
Radiographic progression and clinical PsA activity on adalimumab don’t always correlate
A post hoc analysis of the randomized, double-blind, placebo-controlled ADEPT trial in PsA patients demonstrated that inhibition of radiographic progression as measured by change in modified total Sharp score from baseline through 24 weeks of adalimumab therapy was greater than expected based upon control of clinical disease activity (Rheumatology [Oxford]. 2019 Jan 3. doi: 10.1093/rheumatology/key417. [Epub ahead of print]).
One implication of the disconnect between radiographic progression and clinical disease documented in this study is that a dermatologist shouldn’t be too quick to change from adalimumab to another biologic just because a patient with PsA reports continued but bearable joint pain. And the converse is also true.
“I think that we as dermatologists probably shouldn’t be reassured when a patient says, ‘My joints feel great!” That’s because you may not necessarily be able to predict lack of progression in Sharp score based upon clinical response,” Dr. Duffin cautioned. “I think you should still have a rheumatologist check in with the patient and do x-rays periodically. The rheumatologist I work with does that, usually about on a yearly basis.”
Another key finding in the ADEPT analysis was that concomitant methotrexate had no added effect in terms of preventing joint destruction. This underscores the prescience of the first-ever collaborative American College of Rheumatology/National Psoriasis Foundation guidelines for the treatment of PsA (Arthritis Care Res (Hoboken). 2019 Jan;71[1]:2-29).
The new guidelines recommend that, in a psoriasis patient with confirmed PsA, the first-line treatment is a tumor necrosis factor (TNF) inhibitor. Agents from this class are preferred over other biologics because they are backed by a larger body of data regarding inhibition of joint disease progression. If the patient fails on the first TNF inhibitor prescribed, second-line therapy is another TNF inhibitor. So is third-line therapy.
Adalimumab citrate free
Not only does this new iteration of adalimumab do away with citrate as a buffer because it can cause pain and burning, it also utilizes a thinner 29-gauge needle rather than the standard 27-gauge. And the needle cover isn’t made with natural rubber latex. Also, both the pen and prefilled syringe contain half the volume of liquid, compared with the classic version of the biologic, so it’s 40 mg of drug in 0.4 mL rather than in 0.8 mL.
The packaging of adalimumab citrate free is different. It comes in a blue box to distinguish the product from the classic version.
Dr. Duffin reported receiving research grants from and serving as a consultant to AbbVie, which markets adalimumab, as well as close to a dozen other pharmaceutical companies.
The SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – A flurry of recent impressive , identifies a simple biomarker predictive of the likelihood of a favorable PASI 75 response, and highlights a disconnect in psoriatic arthritis (PsA) patients between clinical response as reflected in disease activity and radiographic progression of joint disease, according to Kristina C. Duffin, MD.
Also, a new citrate-free version of adalimumab (Humira) is available. It requires a new prescription, and an additional prior authorization is mandated by some insurers. But this is a welcome innovation for patients bothered by significant burning and stinging with their injections of classic adalimumab, Dr. Duffin, cochair of the department of dermatology at the University of Utah, Salt Lake City, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
New long-term safety data
Adalimumab is a market leader in biologic therapy for psoriasis. But the long-term experience with biologics in dermatology is still relatively limited, so the recent publication of two large studies providing encouraging evidence of the long-term safety of adalimumab is noteworthy.
Craig L. Leonardi, MD, of Saint Louis University, St. Louis, Mo., was first author of an analysis of long-term safety data from 18 clinical trials in adults with moderate to severe plaque psoriasis. The key takeaway, in Dr. Duffin’s view, was that the rate of adverse events, including serious infections and malignancies other than nonmelanoma skin cancer, remained stable over time out to 240 weeks of follow-up in patients on continuous treatment, with no new safety signals emerging (Br J Dermatol. 2019 Jan;180[1]:76-85).
However, randomized clinical trials often paint an overly rosy safety picture because of their strict inclusion and exclusion criteria.
“We single out patients for clinical trials because they’re especially healthy. That doesn’t happen in real-world registries,” she noted.
That’s why a systematic review of adalimumab’s safety performance in 10 real-world registries of adalimumab-treated psoriasis patients is particularly informative. The registries included in the systematic review, led by Bruce E. Strober, MD, PhD, professor of dermatology at the University of Connecticut, Farmington, didn’t all measure the same outcomes. But the three registries that documented major adverse cardiovascular events showed rates of less than 0.1 to less than 1 per 100 patient-years. Rates of malignancies other than nonmelanoma skin cancer were consistently in the 0.3-0.6 events per 100 patient-years range, similar to what has been reported in studies of other systemic psoriasis therapies, biologic as well as nonbiologic (J Eur Acad Dermatol Venereol. 2018 Dec;32[12]:2126-33).
Overall infection rates reported in the real-world registries ranged from 7.7 to 14.7 events per 100 patient-years, which is actually considerably lower than in the clinical trials. Rates of serious infections ranged from less than one up to two events per 100 patient-years, with the most common ones being cellulitis and pneumonia, consistent with the randomized trial experience.
Predicting response to adalimumab
A prospective, multicenter, observational cohort study of 544 psoriasis patients on adalimumab monotherapy conducted by U.K. investigators concluded that a patient’s serum drug level is the single most important predictor of treatment response. A cut point of 3.2 mcg/mL, which is considered the minimal effective circulating drug level, was associated with a 65% probability of a 75% improvement in Psoriasis Area and Severity Index from baseline, or PASI 75 response. The higher the serum drug level, the greater the likelihood of a PASI 75 response, up to a serum level of 7 mcg/mL, which was associated with an 81% probability of achieving PASI 75. Beyond 7 mcg/mL, however, the relationship with treatment response plateaued. Importantly, drug levels measured early on – at 1-12 weeks into therapy – were predictive of response 6 months later. So were steady-state levels (J Invest Dermatol. 2019 Jan;139[1]:115-23).
This is clinically useful information, Dr. Duffin observed.
“I’m hoping we’re going to see more real-world use of checking drug levels,” she said.
Indeed, even though the approved dosing of adalimumab for psoriasis is 40 mg by subcutaneous injection every 2 weeks, the new American Academy of Dermatology/National Psoriasis Foundation joint guidelines for treatment of psoriasis with biologics declare that “a maintenance dose of adalimumab at 40 mg/week is recommended for better disease control in some patients” (J Am Acad Dermatol. 2019 Feb 7. doi: 10.1016/j.jaad.2018.11.057. [Epub ahead of print]).
The new guidelines provide support for dermatologists who decide weekly therapy is best for a given patient, and adalimumab drug levels could prove useful in identifying the patient subgroup likely to benefit.
Dr. Duffin is often consulted by other physicians as to whether they should check for neutralizing antibodies in patients who appear to be losing therapeutic efficacy on a given biologic. She’s not a fan of the practice.
“There are commercial assays out there, but it’s very hard to interpret them because we don’t really know if they’re truly measuring neutralizing antibodies. And the cost is not insignificant; it can be hundreds of dollars,” she noted.
She believes a straightforward measurement of the serum biologic level is a better strategy.
“It makes sense: This is an indirect way of determining if there’s been neutralization of the drug, rather than trying to check the antibody that’s doing it, which is fraught with problems,” Dr. Duffin said.
Radiographic progression and clinical PsA activity on adalimumab don’t always correlate
A post hoc analysis of the randomized, double-blind, placebo-controlled ADEPT trial in PsA patients demonstrated that inhibition of radiographic progression as measured by change in modified total Sharp score from baseline through 24 weeks of adalimumab therapy was greater than expected based upon control of clinical disease activity (Rheumatology [Oxford]. 2019 Jan 3. doi: 10.1093/rheumatology/key417. [Epub ahead of print]).
One implication of the disconnect between radiographic progression and clinical disease documented in this study is that a dermatologist shouldn’t be too quick to change from adalimumab to another biologic just because a patient with PsA reports continued but bearable joint pain. And the converse is also true.
“I think that we as dermatologists probably shouldn’t be reassured when a patient says, ‘My joints feel great!” That’s because you may not necessarily be able to predict lack of progression in Sharp score based upon clinical response,” Dr. Duffin cautioned. “I think you should still have a rheumatologist check in with the patient and do x-rays periodically. The rheumatologist I work with does that, usually about on a yearly basis.”
Another key finding in the ADEPT analysis was that concomitant methotrexate had no added effect in terms of preventing joint destruction. This underscores the prescience of the first-ever collaborative American College of Rheumatology/National Psoriasis Foundation guidelines for the treatment of PsA (Arthritis Care Res (Hoboken). 2019 Jan;71[1]:2-29).
The new guidelines recommend that, in a psoriasis patient with confirmed PsA, the first-line treatment is a tumor necrosis factor (TNF) inhibitor. Agents from this class are preferred over other biologics because they are backed by a larger body of data regarding inhibition of joint disease progression. If the patient fails on the first TNF inhibitor prescribed, second-line therapy is another TNF inhibitor. So is third-line therapy.
Adalimumab citrate free
Not only does this new iteration of adalimumab do away with citrate as a buffer because it can cause pain and burning, it also utilizes a thinner 29-gauge needle rather than the standard 27-gauge. And the needle cover isn’t made with natural rubber latex. Also, both the pen and prefilled syringe contain half the volume of liquid, compared with the classic version of the biologic, so it’s 40 mg of drug in 0.4 mL rather than in 0.8 mL.
The packaging of adalimumab citrate free is different. It comes in a blue box to distinguish the product from the classic version.
Dr. Duffin reported receiving research grants from and serving as a consultant to AbbVie, which markets adalimumab, as well as close to a dozen other pharmaceutical companies.
The SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
WAIKOLOA, HAWAII – A flurry of recent impressive , identifies a simple biomarker predictive of the likelihood of a favorable PASI 75 response, and highlights a disconnect in psoriatic arthritis (PsA) patients between clinical response as reflected in disease activity and radiographic progression of joint disease, according to Kristina C. Duffin, MD.
Also, a new citrate-free version of adalimumab (Humira) is available. It requires a new prescription, and an additional prior authorization is mandated by some insurers. But this is a welcome innovation for patients bothered by significant burning and stinging with their injections of classic adalimumab, Dr. Duffin, cochair of the department of dermatology at the University of Utah, Salt Lake City, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.
New long-term safety data
Adalimumab is a market leader in biologic therapy for psoriasis. But the long-term experience with biologics in dermatology is still relatively limited, so the recent publication of two large studies providing encouraging evidence of the long-term safety of adalimumab is noteworthy.
Craig L. Leonardi, MD, of Saint Louis University, St. Louis, Mo., was first author of an analysis of long-term safety data from 18 clinical trials in adults with moderate to severe plaque psoriasis. The key takeaway, in Dr. Duffin’s view, was that the rate of adverse events, including serious infections and malignancies other than nonmelanoma skin cancer, remained stable over time out to 240 weeks of follow-up in patients on continuous treatment, with no new safety signals emerging (Br J Dermatol. 2019 Jan;180[1]:76-85).
However, randomized clinical trials often paint an overly rosy safety picture because of their strict inclusion and exclusion criteria.
“We single out patients for clinical trials because they’re especially healthy. That doesn’t happen in real-world registries,” she noted.
That’s why a systematic review of adalimumab’s safety performance in 10 real-world registries of adalimumab-treated psoriasis patients is particularly informative. The registries included in the systematic review, led by Bruce E. Strober, MD, PhD, professor of dermatology at the University of Connecticut, Farmington, didn’t all measure the same outcomes. But the three registries that documented major adverse cardiovascular events showed rates of less than 0.1 to less than 1 per 100 patient-years. Rates of malignancies other than nonmelanoma skin cancer were consistently in the 0.3-0.6 events per 100 patient-years range, similar to what has been reported in studies of other systemic psoriasis therapies, biologic as well as nonbiologic (J Eur Acad Dermatol Venereol. 2018 Dec;32[12]:2126-33).
Overall infection rates reported in the real-world registries ranged from 7.7 to 14.7 events per 100 patient-years, which is actually considerably lower than in the clinical trials. Rates of serious infections ranged from less than one up to two events per 100 patient-years, with the most common ones being cellulitis and pneumonia, consistent with the randomized trial experience.
Predicting response to adalimumab
A prospective, multicenter, observational cohort study of 544 psoriasis patients on adalimumab monotherapy conducted by U.K. investigators concluded that a patient’s serum drug level is the single most important predictor of treatment response. A cut point of 3.2 mcg/mL, which is considered the minimal effective circulating drug level, was associated with a 65% probability of a 75% improvement in Psoriasis Area and Severity Index from baseline, or PASI 75 response. The higher the serum drug level, the greater the likelihood of a PASI 75 response, up to a serum level of 7 mcg/mL, which was associated with an 81% probability of achieving PASI 75. Beyond 7 mcg/mL, however, the relationship with treatment response plateaued. Importantly, drug levels measured early on – at 1-12 weeks into therapy – were predictive of response 6 months later. So were steady-state levels (J Invest Dermatol. 2019 Jan;139[1]:115-23).
This is clinically useful information, Dr. Duffin observed.
“I’m hoping we’re going to see more real-world use of checking drug levels,” she said.
Indeed, even though the approved dosing of adalimumab for psoriasis is 40 mg by subcutaneous injection every 2 weeks, the new American Academy of Dermatology/National Psoriasis Foundation joint guidelines for treatment of psoriasis with biologics declare that “a maintenance dose of adalimumab at 40 mg/week is recommended for better disease control in some patients” (J Am Acad Dermatol. 2019 Feb 7. doi: 10.1016/j.jaad.2018.11.057. [Epub ahead of print]).
The new guidelines provide support for dermatologists who decide weekly therapy is best for a given patient, and adalimumab drug levels could prove useful in identifying the patient subgroup likely to benefit.
Dr. Duffin is often consulted by other physicians as to whether they should check for neutralizing antibodies in patients who appear to be losing therapeutic efficacy on a given biologic. She’s not a fan of the practice.
“There are commercial assays out there, but it’s very hard to interpret them because we don’t really know if they’re truly measuring neutralizing antibodies. And the cost is not insignificant; it can be hundreds of dollars,” she noted.
She believes a straightforward measurement of the serum biologic level is a better strategy.
“It makes sense: This is an indirect way of determining if there’s been neutralization of the drug, rather than trying to check the antibody that’s doing it, which is fraught with problems,” Dr. Duffin said.
Radiographic progression and clinical PsA activity on adalimumab don’t always correlate
A post hoc analysis of the randomized, double-blind, placebo-controlled ADEPT trial in PsA patients demonstrated that inhibition of radiographic progression as measured by change in modified total Sharp score from baseline through 24 weeks of adalimumab therapy was greater than expected based upon control of clinical disease activity (Rheumatology [Oxford]. 2019 Jan 3. doi: 10.1093/rheumatology/key417. [Epub ahead of print]).
One implication of the disconnect between radiographic progression and clinical disease documented in this study is that a dermatologist shouldn’t be too quick to change from adalimumab to another biologic just because a patient with PsA reports continued but bearable joint pain. And the converse is also true.
“I think that we as dermatologists probably shouldn’t be reassured when a patient says, ‘My joints feel great!” That’s because you may not necessarily be able to predict lack of progression in Sharp score based upon clinical response,” Dr. Duffin cautioned. “I think you should still have a rheumatologist check in with the patient and do x-rays periodically. The rheumatologist I work with does that, usually about on a yearly basis.”
Another key finding in the ADEPT analysis was that concomitant methotrexate had no added effect in terms of preventing joint destruction. This underscores the prescience of the first-ever collaborative American College of Rheumatology/National Psoriasis Foundation guidelines for the treatment of PsA (Arthritis Care Res (Hoboken). 2019 Jan;71[1]:2-29).
The new guidelines recommend that, in a psoriasis patient with confirmed PsA, the first-line treatment is a tumor necrosis factor (TNF) inhibitor. Agents from this class are preferred over other biologics because they are backed by a larger body of data regarding inhibition of joint disease progression. If the patient fails on the first TNF inhibitor prescribed, second-line therapy is another TNF inhibitor. So is third-line therapy.
Adalimumab citrate free
Not only does this new iteration of adalimumab do away with citrate as a buffer because it can cause pain and burning, it also utilizes a thinner 29-gauge needle rather than the standard 27-gauge. And the needle cover isn’t made with natural rubber latex. Also, both the pen and prefilled syringe contain half the volume of liquid, compared with the classic version of the biologic, so it’s 40 mg of drug in 0.4 mL rather than in 0.8 mL.
The packaging of adalimumab citrate free is different. It comes in a blue box to distinguish the product from the classic version.
Dr. Duffin reported receiving research grants from and serving as a consultant to AbbVie, which markets adalimumab, as well as close to a dozen other pharmaceutical companies.
The SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
REPORTING FROM SDEF HAWAII DERMATOLOGY SEMINAR