Psoriatic Arthritis Resource Center

MADRID – Secukinumab was superior to placebo for the primary endpoint of 20% improvement in Assessment of SpondyloArthritis international Society criteria (ASAS20), based on the initial 12-week data from the ongoing phase 3b MAXIMISE trial, the first randomized, controlled trial to evaluate a biologic therapy for the treatment of the axial manifestations of psoriatic arthritis (PsA).

Ted Bosworth/MDedge News

“There was rapid and significant clinical improvement as measured with ASAS20 with both of the study doses of secukinumab,” an anti–interleukin-17 monoclonal antibody, reported Xenofon Baraliakos, MD, of Rheumazentrum Ruhrgebliet, Ruhr-University Bochum in Herne, Germany.

At the European Congress of Rheumatology, Dr. Baraliakos said that the 1-year data will be complete before the end of 2019.

In this primary analysis, 498 patients with established PsA were randomized to 150 mg secukinumab, 300 mg secukinumab, or placebo. For enrollment, all patients were required to have substantial axial pain and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score greater than 4 despite treatment with at least two NSAIDs.

For the first 4 weeks of the trial, patients received their assigned therapies weekly by subcutaneous administration. Treatment thereafter was every 4 weeks.

Almost all patients had active psoriasis and axial symptoms of at least several years duration. The median patient age was 46 years. Approximately one-third were HLA B27 positive.

At baseline, the median back pain score on a visual analog scale of 100 was 73, and the median BASDAI score was greater than 7.0. More than 90% of patients reported back pain worsening with rest.

The proportion of patients achieving ASAS20 at 12 weeks was 63.1% in the group assigned to 300 mg secukinumab, 66.3% in those assigned 150 mg, and 31.1% for those assigned placebo (P less than .0001 for either active therapy versus placebo).

Analyses conducted with multiple imputations and comparing those who were and were not taking methotrexate produced almost the same relative advantage for secukinumab. ASAS20 responses in patients using concomitant methotrexate were 65.1% with 300 mg secukinumab, 67.3% with 150 mg secukinumab, and 33.9% with placebo. Corresponding values in the no-methotrexate group were 60.5%, 64.4%, and 27.1%, respectively.

“There was a good response from either dose of secukinumab no matter what analysis was employed,” reported Dr. Baraliakos, citing an odds ratio of 3.81 for reaching the primary endpoint with secukinumab versus placebo. There were no significant differences in efficacy between the doses of secukinumab.

There was “not much to say about safety,” according to Dr. Baraliakos, as no significant differences in any adverse events were observed between study arms. However, he did caution that longer-term exposure is needed for a more complete analysis of tolerability and safety.

Most patients with PsA are thought to eventually develop axial involvement, which has a major adverse affect on quality of life, according to Dr. Baraliakos. He considers this primary 12-week analysis encouraging, but said the 1-year data will provide more information about whether this therapy should be considered routinely in PsA patients with persistent axial symptoms.

Axial imaging was conducted at study entry even though it was not a criterion for enrollment. Dr. Baraliakos reported that the impact of secukinumab on objective imaging measures of disease activity, if any, is forthcoming.

Imaging data might be needed to establish benefit objectively, judging from a criticism of the study design that arose during discussion after the data were presented. Specifically, it was pointed out that improvement in ASAS20 and BASDAI could occur as a result of improvement in peripheral symptoms, such as enthesitis. The lack of axial-specific outcomes was called a potential weakness of this study.

Dr. Baraliakos countered that BASDAI evaluations did include axial-specific questions, but also confirmed that spine-specific outcomes are included among outcomes to be presented with longer-term analyses.

“These data will come,” said Dr. Baraliakos, referring to imaging as well as other outcomes that will provide more information on the impact of secukinumab in treating the axial involvement of PsA.

Dr. Baraliakos reported multiple financial relationships with pharmaceutical companies, including Novartis, which sponsored this trial.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl2):195-6. Abstract OPO235. doi: 10.1136/annrheumdis-2019-eular.2932.

MADRID – Secukinumab was superior to placebo for the primary endpoint of 20% improvement in Assessment of SpondyloArthritis international Society criteria (ASAS20), based on the initial 12-week data from the ongoing phase 3b MAXIMISE trial, the first randomized, controlled trial to evaluate a biologic therapy for the treatment of the axial manifestations of psoriatic arthritis (PsA).

Ted Bosworth/MDedge News

“There was rapid and significant clinical improvement as measured with ASAS20 with both of the study doses of secukinumab,” an anti–interleukin-17 monoclonal antibody, reported Xenofon Baraliakos, MD, of Rheumazentrum Ruhrgebliet, Ruhr-University Bochum in Herne, Germany.

At the European Congress of Rheumatology, Dr. Baraliakos said that the 1-year data will be complete before the end of 2019.

In this primary analysis, 498 patients with established PsA were randomized to 150 mg secukinumab, 300 mg secukinumab, or placebo. For enrollment, all patients were required to have substantial axial pain and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score greater than 4 despite treatment with at least two NSAIDs.

For the first 4 weeks of the trial, patients received their assigned therapies weekly by subcutaneous administration. Treatment thereafter was every 4 weeks.

Almost all patients had active psoriasis and axial symptoms of at least several years duration. The median patient age was 46 years. Approximately one-third were HLA B27 positive.

At baseline, the median back pain score on a visual analog scale of 100 was 73, and the median BASDAI score was greater than 7.0. More than 90% of patients reported back pain worsening with rest.

The proportion of patients achieving ASAS20 at 12 weeks was 63.1% in the group assigned to 300 mg secukinumab, 66.3% in those assigned 150 mg, and 31.1% for those assigned placebo (P less than .0001 for either active therapy versus placebo).

Analyses conducted with multiple imputations and comparing those who were and were not taking methotrexate produced almost the same relative advantage for secukinumab. ASAS20 responses in patients using concomitant methotrexate were 65.1% with 300 mg secukinumab, 67.3% with 150 mg secukinumab, and 33.9% with placebo. Corresponding values in the no-methotrexate group were 60.5%, 64.4%, and 27.1%, respectively.

“There was a good response from either dose of secukinumab no matter what analysis was employed,” reported Dr. Baraliakos, citing an odds ratio of 3.81 for reaching the primary endpoint with secukinumab versus placebo. There were no significant differences in efficacy between the doses of secukinumab.

There was “not much to say about safety,” according to Dr. Baraliakos, as no significant differences in any adverse events were observed between study arms. However, he did caution that longer-term exposure is needed for a more complete analysis of tolerability and safety.

Most patients with PsA are thought to eventually develop axial involvement, which has a major adverse affect on quality of life, according to Dr. Baraliakos. He considers this primary 12-week analysis encouraging, but said the 1-year data will provide more information about whether this therapy should be considered routinely in PsA patients with persistent axial symptoms.

Axial imaging was conducted at study entry even though it was not a criterion for enrollment. Dr. Baraliakos reported that the impact of secukinumab on objective imaging measures of disease activity, if any, is forthcoming.

Imaging data might be needed to establish benefit objectively, judging from a criticism of the study design that arose during discussion after the data were presented. Specifically, it was pointed out that improvement in ASAS20 and BASDAI could occur as a result of improvement in peripheral symptoms, such as enthesitis. The lack of axial-specific outcomes was called a potential weakness of this study.

Dr. Baraliakos countered that BASDAI evaluations did include axial-specific questions, but also confirmed that spine-specific outcomes are included among outcomes to be presented with longer-term analyses.

“These data will come,” said Dr. Baraliakos, referring to imaging as well as other outcomes that will provide more information on the impact of secukinumab in treating the axial involvement of PsA.

Dr. Baraliakos reported multiple financial relationships with pharmaceutical companies, including Novartis, which sponsored this trial.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl2):195-6. Abstract OPO235. doi: 10.1136/annrheumdis-2019-eular.2932.

MADRID – Secukinumab was superior to placebo for the primary endpoint of 20% improvement in Assessment of SpondyloArthritis international Society criteria (ASAS20), based on the initial 12-week data from the ongoing phase 3b MAXIMISE trial, the first randomized, controlled trial to evaluate a biologic therapy for the treatment of the axial manifestations of psoriatic arthritis (PsA).

Ted Bosworth/MDedge News

“There was rapid and significant clinical improvement as measured with ASAS20 with both of the study doses of secukinumab,” an anti–interleukin-17 monoclonal antibody, reported Xenofon Baraliakos, MD, of Rheumazentrum Ruhrgebliet, Ruhr-University Bochum in Herne, Germany.

At the European Congress of Rheumatology, Dr. Baraliakos said that the 1-year data will be complete before the end of 2019.

In this primary analysis, 498 patients with established PsA were randomized to 150 mg secukinumab, 300 mg secukinumab, or placebo. For enrollment, all patients were required to have substantial axial pain and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score greater than 4 despite treatment with at least two NSAIDs.

For the first 4 weeks of the trial, patients received their assigned therapies weekly by subcutaneous administration. Treatment thereafter was every 4 weeks.

Almost all patients had active psoriasis and axial symptoms of at least several years duration. The median patient age was 46 years. Approximately one-third were HLA B27 positive.

At baseline, the median back pain score on a visual analog scale of 100 was 73, and the median BASDAI score was greater than 7.0. More than 90% of patients reported back pain worsening with rest.

The proportion of patients achieving ASAS20 at 12 weeks was 63.1% in the group assigned to 300 mg secukinumab, 66.3% in those assigned 150 mg, and 31.1% for those assigned placebo (P less than .0001 for either active therapy versus placebo).

Analyses conducted with multiple imputations and comparing those who were and were not taking methotrexate produced almost the same relative advantage for secukinumab. ASAS20 responses in patients using concomitant methotrexate were 65.1% with 300 mg secukinumab, 67.3% with 150 mg secukinumab, and 33.9% with placebo. Corresponding values in the no-methotrexate group were 60.5%, 64.4%, and 27.1%, respectively.

“There was a good response from either dose of secukinumab no matter what analysis was employed,” reported Dr. Baraliakos, citing an odds ratio of 3.81 for reaching the primary endpoint with secukinumab versus placebo. There were no significant differences in efficacy between the doses of secukinumab.

There was “not much to say about safety,” according to Dr. Baraliakos, as no significant differences in any adverse events were observed between study arms. However, he did caution that longer-term exposure is needed for a more complete analysis of tolerability and safety.

Most patients with PsA are thought to eventually develop axial involvement, which has a major adverse affect on quality of life, according to Dr. Baraliakos. He considers this primary 12-week analysis encouraging, but said the 1-year data will provide more information about whether this therapy should be considered routinely in PsA patients with persistent axial symptoms.

Axial imaging was conducted at study entry even though it was not a criterion for enrollment. Dr. Baraliakos reported that the impact of secukinumab on objective imaging measures of disease activity, if any, is forthcoming.

Imaging data might be needed to establish benefit objectively, judging from a criticism of the study design that arose during discussion after the data were presented. Specifically, it was pointed out that improvement in ASAS20 and BASDAI could occur as a result of improvement in peripheral symptoms, such as enthesitis. The lack of axial-specific outcomes was called a potential weakness of this study.

Dr. Baraliakos countered that BASDAI evaluations did include axial-specific questions, but also confirmed that spine-specific outcomes are included among outcomes to be presented with longer-term analyses.

“These data will come,” said Dr. Baraliakos, referring to imaging as well as other outcomes that will provide more information on the impact of secukinumab in treating the axial involvement of PsA.

Dr. Baraliakos reported multiple financial relationships with pharmaceutical companies, including Novartis, which sponsored this trial.

SOURCE: Ann Rheum Dis. Jun 2019;78(Suppl2):195-6. Abstract OPO235. doi: 10.1136/annrheumdis-2019-eular.2932.

MILAN – A novel topical nonsteroidal treatment for psoriasis showed sufficient efficacy in phase 2b clinical trials to proceed to phase 3 studies, with improvements in severity, pain, and burning in adults with mild to moderate psoriasis.

At the end of 12 weeks of treatment, 29% of patients receiving the medication – which targets nerve pathways – experienced a decrease of at least 2 grades on the 5-point Investigator’s Global Assessment (IGA) scale, compared with 13% of those receiving the topical vehicle only (P = .036). A similar proportion of patients achieved 75% improvement on the Psoriasis Area and Severity Index (PASI-75)compared with those on vehicle alone (27% versus 13%; P = .045).

These findings were seen only with the less concentrated formulation of pegcantratinib, known as SNA-120 in the clinical trial program, said Paul F. Lizzul, MD, PhD, presenting the findings during a late-breaking abstract session at the World Congress of Dermatology.

Pruritus severity also dropped by about 60%, but the decrease did not differ significantly from the change seen with vehicle alone, said Dr. Lizzul, chief medical officer for Sienna Biopharmaceuticals, Westlake Village, Calif., which funded the study. He and his coinvestigators found this “interesting, surprising, and different from what we had seen previously,” he said. “We think a few things happened here,” including intensive querying on itch by means of daily diaries, a different approach than had been taken in the investigator’s earlier SNA-120 trials. “We think in this way we probably biased patients’ expectations, altering reporting on this subjective measure,” he added.

“There’s been really a lack of innovation in the topical world in developing nonsteroidal therapies for the majority of patients who are treated with topicals, said Dr. Lizzul. Keratinocytes within psoriatic plaques are known to have elevated levels of nerve growth factor (NGF), he explained. Together with tropomyosin receptor kinase A (TrkA), NGF is implicated in the pathogenesis of psoriasis; it stimulates keratinocyte hyperproliferation, is a factor in neurogenic inflammation, and contributes to pruritus. Upregulation of TrkA expression is seen in nerve fibers within pruritic psoriasis plaques as well, said Dr. Lizzul, senior author of the study. (The first author was Kristina Callis Duffin, MD, cochair of the dermatology department at the University of Utah, Salt Lake City.)

In fact, the pruritus that plagues many psoriasis patients, said Dr. Lizzul, may “serve as a clinical biomarker for elevated NGF/TrkA expression.” And certain clinical phenomena observed in psoriasis, such as the Koebner phenomenon and plaque resolution along the path of damaged nerves, provide other clues. “Clearly, astute clinicians going back many, many years have recognized the very important role that nerves and neuropeptides play in psoriasis,” he added.

SNA-120 targets NGF TrKA activity, and “achieves high local drug concentration in the skin, with low systemic availability,” he said.

The randomized, double-blind, vehicle-controlled study enrolled 208 adults with mild to moderate psoriasis (scores of 2 or 3 on the IGA), with pruritus of at least moderate intensity (5 or higher on a 10-point itch numeric rating scale, or I-NRS). The mean age of the patients was 50 years, and about half were male. Most (84%-90% across study arms) were white. At baseline, the mean I-NRS was 7.3-7.4, and the mean PASI score at baseline ranged from 5.9 to 6.5.


Patients were randomized to receive SNA-120 twice daily at either 0.05% (70 patients) or 0.5% (69 patients) in an ointment formulation, or vehicle alone twice daily (69 patients). Efficacy was tracked by measuring decrease in IGA by one or two grades, the number of patients achieving PASI-50 and PASI-75, reduction in itch, and a composite of a decrease of at least 2 grades on the IGA and having clear or almost clear skin.

The investigators also tracked reduction in burning and pain as measured on a 10-point numeric rating scale. Though itch scores didn’t differ significantly from reductions seen with the topical vehicle alone, pain and burning were both reduced significantly compared with vehicle by week 12 of the study (P = .033 for pain; P = .043 for burning).

All improvements were seen only with the lower dose, not the 0.5% dose of SNA-120, noted Dr. Lizzul, adding: “This is not necessarily surprising in the world of kinase inhibitors, where you can see these J-shaped or inverse dose-response curves.”

In addition to recording adverse events, the researchers assessed safety by obtaining laboratory values and electrocardiograms. Plasma SNA-120 levels at study weeks 2, 4, and 8 were obtained for pharmacokinetic analysis. Systemic uptake was virtually nil, and the safety profile overall was good, said Dr. Lizzul.

Next steps are phase 3 clinical trials that will evaluate global improvement as well as pain, burning, and itch in psoriasis, he noted.

Dr. Lizzul is an employee of Sienna Biopharmaceuticals, which is developing SNA-120.

[email protected]

MILAN – A novel topical nonsteroidal treatment for psoriasis showed sufficient efficacy in phase 2b clinical trials to proceed to phase 3 studies, with improvements in severity, pain, and burning in adults with mild to moderate psoriasis.

At the end of 12 weeks of treatment, 29% of patients receiving the medication – which targets nerve pathways – experienced a decrease of at least 2 grades on the 5-point Investigator’s Global Assessment (IGA) scale, compared with 13% of those receiving the topical vehicle only (P = .036). A similar proportion of patients achieved 75% improvement on the Psoriasis Area and Severity Index (PASI-75)compared with those on vehicle alone (27% versus 13%; P = .045).

These findings were seen only with the less concentrated formulation of pegcantratinib, known as SNA-120 in the clinical trial program, said Paul F. Lizzul, MD, PhD, presenting the findings during a late-breaking abstract session at the World Congress of Dermatology.

Pruritus severity also dropped by about 60%, but the decrease did not differ significantly from the change seen with vehicle alone, said Dr. Lizzul, chief medical officer for Sienna Biopharmaceuticals, Westlake Village, Calif., which funded the study. He and his coinvestigators found this “interesting, surprising, and different from what we had seen previously,” he said. “We think a few things happened here,” including intensive querying on itch by means of daily diaries, a different approach than had been taken in the investigator’s earlier SNA-120 trials. “We think in this way we probably biased patients’ expectations, altering reporting on this subjective measure,” he added.

“There’s been really a lack of innovation in the topical world in developing nonsteroidal therapies for the majority of patients who are treated with topicals, said Dr. Lizzul. Keratinocytes within psoriatic plaques are known to have elevated levels of nerve growth factor (NGF), he explained. Together with tropomyosin receptor kinase A (TrkA), NGF is implicated in the pathogenesis of psoriasis; it stimulates keratinocyte hyperproliferation, is a factor in neurogenic inflammation, and contributes to pruritus. Upregulation of TrkA expression is seen in nerve fibers within pruritic psoriasis plaques as well, said Dr. Lizzul, senior author of the study. (The first author was Kristina Callis Duffin, MD, cochair of the dermatology department at the University of Utah, Salt Lake City.)

In fact, the pruritus that plagues many psoriasis patients, said Dr. Lizzul, may “serve as a clinical biomarker for elevated NGF/TrkA expression.” And certain clinical phenomena observed in psoriasis, such as the Koebner phenomenon and plaque resolution along the path of damaged nerves, provide other clues. “Clearly, astute clinicians going back many, many years have recognized the very important role that nerves and neuropeptides play in psoriasis,” he added.

SNA-120 targets NGF TrKA activity, and “achieves high local drug concentration in the skin, with low systemic availability,” he said.

The randomized, double-blind, vehicle-controlled study enrolled 208 adults with mild to moderate psoriasis (scores of 2 or 3 on the IGA), with pruritus of at least moderate intensity (5 or higher on a 10-point itch numeric rating scale, or I-NRS). The mean age of the patients was 50 years, and about half were male. Most (84%-90% across study arms) were white. At baseline, the mean I-NRS was 7.3-7.4, and the mean PASI score at baseline ranged from 5.9 to 6.5.


Patients were randomized to receive SNA-120 twice daily at either 0.05% (70 patients) or 0.5% (69 patients) in an ointment formulation, or vehicle alone twice daily (69 patients). Efficacy was tracked by measuring decrease in IGA by one or two grades, the number of patients achieving PASI-50 and PASI-75, reduction in itch, and a composite of a decrease of at least 2 grades on the IGA and having clear or almost clear skin.

The investigators also tracked reduction in burning and pain as measured on a 10-point numeric rating scale. Though itch scores didn’t differ significantly from reductions seen with the topical vehicle alone, pain and burning were both reduced significantly compared with vehicle by week 12 of the study (P = .033 for pain; P = .043 for burning).

All improvements were seen only with the lower dose, not the 0.5% dose of SNA-120, noted Dr. Lizzul, adding: “This is not necessarily surprising in the world of kinase inhibitors, where you can see these J-shaped or inverse dose-response curves.”

In addition to recording adverse events, the researchers assessed safety by obtaining laboratory values and electrocardiograms. Plasma SNA-120 levels at study weeks 2, 4, and 8 were obtained for pharmacokinetic analysis. Systemic uptake was virtually nil, and the safety profile overall was good, said Dr. Lizzul.

Next steps are phase 3 clinical trials that will evaluate global improvement as well as pain, burning, and itch in psoriasis, he noted.

Dr. Lizzul is an employee of Sienna Biopharmaceuticals, which is developing SNA-120.

[email protected]

MILAN – A novel topical nonsteroidal treatment for psoriasis showed sufficient efficacy in phase 2b clinical trials to proceed to phase 3 studies, with improvements in severity, pain, and burning in adults with mild to moderate psoriasis.

At the end of 12 weeks of treatment, 29% of patients receiving the medication – which targets nerve pathways – experienced a decrease of at least 2 grades on the 5-point Investigator’s Global Assessment (IGA) scale, compared with 13% of those receiving the topical vehicle only (P = .036). A similar proportion of patients achieved 75% improvement on the Psoriasis Area and Severity Index (PASI-75)compared with those on vehicle alone (27% versus 13%; P = .045).

These findings were seen only with the less concentrated formulation of pegcantratinib, known as SNA-120 in the clinical trial program, said Paul F. Lizzul, MD, PhD, presenting the findings during a late-breaking abstract session at the World Congress of Dermatology.

Pruritus severity also dropped by about 60%, but the decrease did not differ significantly from the change seen with vehicle alone, said Dr. Lizzul, chief medical officer for Sienna Biopharmaceuticals, Westlake Village, Calif., which funded the study. He and his coinvestigators found this “interesting, surprising, and different from what we had seen previously,” he said. “We think a few things happened here,” including intensive querying on itch by means of daily diaries, a different approach than had been taken in the investigator’s earlier SNA-120 trials. “We think in this way we probably biased patients’ expectations, altering reporting on this subjective measure,” he added.

“There’s been really a lack of innovation in the topical world in developing nonsteroidal therapies for the majority of patients who are treated with topicals, said Dr. Lizzul. Keratinocytes within psoriatic plaques are known to have elevated levels of nerve growth factor (NGF), he explained. Together with tropomyosin receptor kinase A (TrkA), NGF is implicated in the pathogenesis of psoriasis; it stimulates keratinocyte hyperproliferation, is a factor in neurogenic inflammation, and contributes to pruritus. Upregulation of TrkA expression is seen in nerve fibers within pruritic psoriasis plaques as well, said Dr. Lizzul, senior author of the study. (The first author was Kristina Callis Duffin, MD, cochair of the dermatology department at the University of Utah, Salt Lake City.)

In fact, the pruritus that plagues many psoriasis patients, said Dr. Lizzul, may “serve as a clinical biomarker for elevated NGF/TrkA expression.” And certain clinical phenomena observed in psoriasis, such as the Koebner phenomenon and plaque resolution along the path of damaged nerves, provide other clues. “Clearly, astute clinicians going back many, many years have recognized the very important role that nerves and neuropeptides play in psoriasis,” he added.

SNA-120 targets NGF TrKA activity, and “achieves high local drug concentration in the skin, with low systemic availability,” he said.

The randomized, double-blind, vehicle-controlled study enrolled 208 adults with mild to moderate psoriasis (scores of 2 or 3 on the IGA), with pruritus of at least moderate intensity (5 or higher on a 10-point itch numeric rating scale, or I-NRS). The mean age of the patients was 50 years, and about half were male. Most (84%-90% across study arms) were white. At baseline, the mean I-NRS was 7.3-7.4, and the mean PASI score at baseline ranged from 5.9 to 6.5.


Patients were randomized to receive SNA-120 twice daily at either 0.05% (70 patients) or 0.5% (69 patients) in an ointment formulation, or vehicle alone twice daily (69 patients). Efficacy was tracked by measuring decrease in IGA by one or two grades, the number of patients achieving PASI-50 and PASI-75, reduction in itch, and a composite of a decrease of at least 2 grades on the IGA and having clear or almost clear skin.

The investigators also tracked reduction in burning and pain as measured on a 10-point numeric rating scale. Though itch scores didn’t differ significantly from reductions seen with the topical vehicle alone, pain and burning were both reduced significantly compared with vehicle by week 12 of the study (P = .033 for pain; P = .043 for burning).

All improvements were seen only with the lower dose, not the 0.5% dose of SNA-120, noted Dr. Lizzul, adding: “This is not necessarily surprising in the world of kinase inhibitors, where you can see these J-shaped or inverse dose-response curves.”

In addition to recording adverse events, the researchers assessed safety by obtaining laboratory values and electrocardiograms. Plasma SNA-120 levels at study weeks 2, 4, and 8 were obtained for pharmacokinetic analysis. Systemic uptake was virtually nil, and the safety profile overall was good, said Dr. Lizzul.

Next steps are phase 3 clinical trials that will evaluate global improvement as well as pain, burning, and itch in psoriasis, he noted.

Dr. Lizzul is an employee of Sienna Biopharmaceuticals, which is developing SNA-120.

[email protected]

MADRID – Tildrakizumab, a high-affinity anti–interleukin-23p19 monoclonal antibody, significantly improved joint and skin manifestations in patients with psoriatic arthritis in an ongoing phase 2b study.

Sara Freeman/MDedge News

“By week 24, all four doses of tildrakizumab were significantly more efficacious than placebo,” Philip J. Mease, MD, director of the division of rheumatology clinical research at Swedish Medical Center, Seattle, reported at the European Congress of Rheumatology. This included patient-rated pain, he observed.

Furthermore, “there was a clear separation between tildrakizumab and placebo as early as 8 weeks” for the trial’s primary endpoint, a 20% response rate on American College of Rheumatology criteria (ACR20) at 24 weeks.

The study (NCT02980692), which is projected to complete next year, was conducted to demonstrate the safety and efficacy of tildrakizumab in patients with active psoriatic arthritis. Tildrakizumab is already approved for the treatment of moderate to severe plaque psoriasis in multiple countries, Dr. Mease pointed out. Indeed, the drug – which is marketed as Ilumya in the United States and as Ilumetri in the Europe Union – was approved by the Food and Drug Administration in March last year based on the positive results of the phase 3 reSURFACE clinical trials program (Drugs. 2018;78[8]:845-9).

In presenting interim findings from the study, Dr. Mease observed that “it looked like shortening the dosing interval from Q12 to Q4 weeks for the 200-mg dose did not result in a measurable difference in skin or joint responses.”

The trial included 391 of 500 adult patients who were screened and then randomized to one of four tildrakizumab dosing groups or placebo; there were 78 patients treated with tildrakizumab 200 mg once every 4 weeks (Q4W) and 79 who were treated with tildrakizumab 200 mg once every 12 weeks (Q12W). A further 77 patients were treated with a 100 mg tildrakizumab dose Q12W, 78 patients with a 20 mg tildrakizumab dose Q12W, and 79 patients were treated with a placebo Q4W.

The mean age of patients included in the study was around 48 years. A total of 55% were female, and more than 96% were white. Across the groups, patients had a median of 7-8 tender joints and about 14-19 swollen joints, and 53%-70% had at least 3% psoriasis body surface area involvement.

The primary endpoint of ACR20 at 24 weeks was met by 79.5%, 77.2%, 71.4%, and 73.1% of patients in the tildrakizumab 200-mg Q4W, 200-mg Q12W, 100-mg Q12W, and 20-mg Q12W groups, and by 50.6% of the placebo-treated patients. “So even the very low dose had an effect,” Dr. Mease observed, also acknowledging the “very high placebo response.”

An ACR50 response was achieved by a respective 53.6%, 50.6%, 45.5%, 39.7%, 19.7%, and 24.1% of patients. ACR70 response rates were also “proportionately lower” than the ACR20 responses at around 25%-29% for the tildrakizumab groups and 16% for placebo.

“The skin scores were as expected quite high,” Dr. Mease said. The Psoriasis Area and Severity Index (PASI) 75 response rate was 79.6% in the tildrakizumab 200-mg Q12W group, 64.2% in the 200-mg Q4W group, 55.6% in the 100-mg Q12W group, 46.3% in the 20-mg Q12W group, and just 16.7% in the placebo group. The respective percentages of patients achieving a PASI 90 response rate were 50%, 47.2%, 38.9%, 36.6%, and 7.1%.

Patient pain assessment showed a clear reduction with tildrakizumab versus placebo treatment. “We see statistical separation between all of the tildrakizumab arms and placebo,” Dr. Mease said. “A greater than 50% response in pain is considered major clinical improvement, and that was achieved by all of the tildrakizumab arms.”

As for enthesitis, the mean change in Leeds Enthesitis Scores from baseline to week 24 were greater with all tildrakizumab doses than with placebo, although a high placebo response was again apparent.

“In general, the safety profile was very good for this agent,” Dr. Mease said. Any treatment-emergent adverse event (TEAE) occurred in 156 of 317 (49%) tildrakizumab-treated patients and in 34 of 70 (49%) placebo-treated patients. The rates of any severe TEAE were 2.2% for the tildrakizumab arms and 2.5% for placebo. Any TEAE related to treatment occurred in a respective 11.2% and 12.7%, but there were no discontinuations because of adverse events, nor were there any major cardiac adverse events, cases of malignancy, or deaths caused by TEAEs. There was a single serious infection, a case of tonsillitis, which occurred with tildrakizumab treatment.

In response to a question after his presentation, Dr. Measure noted: “In the psoriasis trials with this agent, even a single dose yielded a fairly meaningful PASI 75 responses out for extremely long periods of time, 6–12 months. So, it looks like the Q12 dosing is going to be reasonable and convenient for patients”. He also agreed with a comment that the more frequent dosing seemed to be linked to inferior responses in the skin.

The study was sponsored by Sun Pharmaceutical Industries. Dr. Mease has received research grants, consulting fees, and/or speaker fees from 15 pharmaceutical companies, including Sun Pharmaceutical Industries.

SOURCE: Mease PJ et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):77-9. Abstract LB0002, doi: 10.1136/annrheumdis-2019-eular.8669

MADRID – Tildrakizumab, a high-affinity anti–interleukin-23p19 monoclonal antibody, significantly improved joint and skin manifestations in patients with psoriatic arthritis in an ongoing phase 2b study.

Sara Freeman/MDedge News

“By week 24, all four doses of tildrakizumab were significantly more efficacious than placebo,” Philip J. Mease, MD, director of the division of rheumatology clinical research at Swedish Medical Center, Seattle, reported at the European Congress of Rheumatology. This included patient-rated pain, he observed.

Furthermore, “there was a clear separation between tildrakizumab and placebo as early as 8 weeks” for the trial’s primary endpoint, a 20% response rate on American College of Rheumatology criteria (ACR20) at 24 weeks.

The study (NCT02980692), which is projected to complete next year, was conducted to demonstrate the safety and efficacy of tildrakizumab in patients with active psoriatic arthritis. Tildrakizumab is already approved for the treatment of moderate to severe plaque psoriasis in multiple countries, Dr. Mease pointed out. Indeed, the drug – which is marketed as Ilumya in the United States and as Ilumetri in the Europe Union – was approved by the Food and Drug Administration in March last year based on the positive results of the phase 3 reSURFACE clinical trials program (Drugs. 2018;78[8]:845-9).

In presenting interim findings from the study, Dr. Mease observed that “it looked like shortening the dosing interval from Q12 to Q4 weeks for the 200-mg dose did not result in a measurable difference in skin or joint responses.”

The trial included 391 of 500 adult patients who were screened and then randomized to one of four tildrakizumab dosing groups or placebo; there were 78 patients treated with tildrakizumab 200 mg once every 4 weeks (Q4W) and 79 who were treated with tildrakizumab 200 mg once every 12 weeks (Q12W). A further 77 patients were treated with a 100 mg tildrakizumab dose Q12W, 78 patients with a 20 mg tildrakizumab dose Q12W, and 79 patients were treated with a placebo Q4W.

The mean age of patients included in the study was around 48 years. A total of 55% were female, and more than 96% were white. Across the groups, patients had a median of 7-8 tender joints and about 14-19 swollen joints, and 53%-70% had at least 3% psoriasis body surface area involvement.

The primary endpoint of ACR20 at 24 weeks was met by 79.5%, 77.2%, 71.4%, and 73.1% of patients in the tildrakizumab 200-mg Q4W, 200-mg Q12W, 100-mg Q12W, and 20-mg Q12W groups, and by 50.6% of the placebo-treated patients. “So even the very low dose had an effect,” Dr. Mease observed, also acknowledging the “very high placebo response.”

An ACR50 response was achieved by a respective 53.6%, 50.6%, 45.5%, 39.7%, 19.7%, and 24.1% of patients. ACR70 response rates were also “proportionately lower” than the ACR20 responses at around 25%-29% for the tildrakizumab groups and 16% for placebo.

“The skin scores were as expected quite high,” Dr. Mease said. The Psoriasis Area and Severity Index (PASI) 75 response rate was 79.6% in the tildrakizumab 200-mg Q12W group, 64.2% in the 200-mg Q4W group, 55.6% in the 100-mg Q12W group, 46.3% in the 20-mg Q12W group, and just 16.7% in the placebo group. The respective percentages of patients achieving a PASI 90 response rate were 50%, 47.2%, 38.9%, 36.6%, and 7.1%.

Patient pain assessment showed a clear reduction with tildrakizumab versus placebo treatment. “We see statistical separation between all of the tildrakizumab arms and placebo,” Dr. Mease said. “A greater than 50% response in pain is considered major clinical improvement, and that was achieved by all of the tildrakizumab arms.”

As for enthesitis, the mean change in Leeds Enthesitis Scores from baseline to week 24 were greater with all tildrakizumab doses than with placebo, although a high placebo response was again apparent.

“In general, the safety profile was very good for this agent,” Dr. Mease said. Any treatment-emergent adverse event (TEAE) occurred in 156 of 317 (49%) tildrakizumab-treated patients and in 34 of 70 (49%) placebo-treated patients. The rates of any severe TEAE were 2.2% for the tildrakizumab arms and 2.5% for placebo. Any TEAE related to treatment occurred in a respective 11.2% and 12.7%, but there were no discontinuations because of adverse events, nor were there any major cardiac adverse events, cases of malignancy, or deaths caused by TEAEs. There was a single serious infection, a case of tonsillitis, which occurred with tildrakizumab treatment.

In response to a question after his presentation, Dr. Measure noted: “In the psoriasis trials with this agent, even a single dose yielded a fairly meaningful PASI 75 responses out for extremely long periods of time, 6–12 months. So, it looks like the Q12 dosing is going to be reasonable and convenient for patients”. He also agreed with a comment that the more frequent dosing seemed to be linked to inferior responses in the skin.

The study was sponsored by Sun Pharmaceutical Industries. Dr. Mease has received research grants, consulting fees, and/or speaker fees from 15 pharmaceutical companies, including Sun Pharmaceutical Industries.

SOURCE: Mease PJ et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):77-9. Abstract LB0002, doi: 10.1136/annrheumdis-2019-eular.8669

MADRID – Tildrakizumab, a high-affinity anti–interleukin-23p19 monoclonal antibody, significantly improved joint and skin manifestations in patients with psoriatic arthritis in an ongoing phase 2b study.

Sara Freeman/MDedge News

“By week 24, all four doses of tildrakizumab were significantly more efficacious than placebo,” Philip J. Mease, MD, director of the division of rheumatology clinical research at Swedish Medical Center, Seattle, reported at the European Congress of Rheumatology. This included patient-rated pain, he observed.

Furthermore, “there was a clear separation between tildrakizumab and placebo as early as 8 weeks” for the trial’s primary endpoint, a 20% response rate on American College of Rheumatology criteria (ACR20) at 24 weeks.

The study (NCT02980692), which is projected to complete next year, was conducted to demonstrate the safety and efficacy of tildrakizumab in patients with active psoriatic arthritis. Tildrakizumab is already approved for the treatment of moderate to severe plaque psoriasis in multiple countries, Dr. Mease pointed out. Indeed, the drug – which is marketed as Ilumya in the United States and as Ilumetri in the Europe Union – was approved by the Food and Drug Administration in March last year based on the positive results of the phase 3 reSURFACE clinical trials program (Drugs. 2018;78[8]:845-9).

In presenting interim findings from the study, Dr. Mease observed that “it looked like shortening the dosing interval from Q12 to Q4 weeks for the 200-mg dose did not result in a measurable difference in skin or joint responses.”

The trial included 391 of 500 adult patients who were screened and then randomized to one of four tildrakizumab dosing groups or placebo; there were 78 patients treated with tildrakizumab 200 mg once every 4 weeks (Q4W) and 79 who were treated with tildrakizumab 200 mg once every 12 weeks (Q12W). A further 77 patients were treated with a 100 mg tildrakizumab dose Q12W, 78 patients with a 20 mg tildrakizumab dose Q12W, and 79 patients were treated with a placebo Q4W.

The mean age of patients included in the study was around 48 years. A total of 55% were female, and more than 96% were white. Across the groups, patients had a median of 7-8 tender joints and about 14-19 swollen joints, and 53%-70% had at least 3% psoriasis body surface area involvement.

The primary endpoint of ACR20 at 24 weeks was met by 79.5%, 77.2%, 71.4%, and 73.1% of patients in the tildrakizumab 200-mg Q4W, 200-mg Q12W, 100-mg Q12W, and 20-mg Q12W groups, and by 50.6% of the placebo-treated patients. “So even the very low dose had an effect,” Dr. Mease observed, also acknowledging the “very high placebo response.”

An ACR50 response was achieved by a respective 53.6%, 50.6%, 45.5%, 39.7%, 19.7%, and 24.1% of patients. ACR70 response rates were also “proportionately lower” than the ACR20 responses at around 25%-29% for the tildrakizumab groups and 16% for placebo.

“The skin scores were as expected quite high,” Dr. Mease said. The Psoriasis Area and Severity Index (PASI) 75 response rate was 79.6% in the tildrakizumab 200-mg Q12W group, 64.2% in the 200-mg Q4W group, 55.6% in the 100-mg Q12W group, 46.3% in the 20-mg Q12W group, and just 16.7% in the placebo group. The respective percentages of patients achieving a PASI 90 response rate were 50%, 47.2%, 38.9%, 36.6%, and 7.1%.

Patient pain assessment showed a clear reduction with tildrakizumab versus placebo treatment. “We see statistical separation between all of the tildrakizumab arms and placebo,” Dr. Mease said. “A greater than 50% response in pain is considered major clinical improvement, and that was achieved by all of the tildrakizumab arms.”

As for enthesitis, the mean change in Leeds Enthesitis Scores from baseline to week 24 were greater with all tildrakizumab doses than with placebo, although a high placebo response was again apparent.

“In general, the safety profile was very good for this agent,” Dr. Mease said. Any treatment-emergent adverse event (TEAE) occurred in 156 of 317 (49%) tildrakizumab-treated patients and in 34 of 70 (49%) placebo-treated patients. The rates of any severe TEAE were 2.2% for the tildrakizumab arms and 2.5% for placebo. Any TEAE related to treatment occurred in a respective 11.2% and 12.7%, but there were no discontinuations because of adverse events, nor were there any major cardiac adverse events, cases of malignancy, or deaths caused by TEAEs. There was a single serious infection, a case of tonsillitis, which occurred with tildrakizumab treatment.

In response to a question after his presentation, Dr. Measure noted: “In the psoriasis trials with this agent, even a single dose yielded a fairly meaningful PASI 75 responses out for extremely long periods of time, 6–12 months. So, it looks like the Q12 dosing is going to be reasonable and convenient for patients”. He also agreed with a comment that the more frequent dosing seemed to be linked to inferior responses in the skin.

The study was sponsored by Sun Pharmaceutical Industries. Dr. Mease has received research grants, consulting fees, and/or speaker fees from 15 pharmaceutical companies, including Sun Pharmaceutical Industries.

SOURCE: Mease PJ et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):77-9. Abstract LB0002, doi: 10.1136/annrheumdis-2019-eular.8669

What's new with potential treatment options such as tildrakizumab? Given the roles obesity and metabolic disease play in psoriatic arthritis, how does weight loss affect treatment response? Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania in Philadelphia, talks about the latest developments in psoriatic arthritis research.

What's new with potential treatment options such as tildrakizumab? Given the roles obesity and metabolic disease play in psoriatic arthritis, how does weight loss affect treatment response? Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania in Philadelphia, talks about the latest developments in psoriatic arthritis research.

What's new with potential treatment options such as tildrakizumab? Given the roles obesity and metabolic disease play in psoriatic arthritis, how does weight loss affect treatment response? Alexis Ogdie, MD, director of the psoriatic arthritis clinic at the University of Pennsylvania in Philadelphia, talks about the latest developments in psoriatic arthritis research.

MADRID – A considerable number of patients with psoriatic arthritis starting their first biologic treatment report unacceptable pain throughout the first year of treatment, even when their inflammation is controlled, according to Swedish researchers.

Mitchel L. Zoler/MDedge News

“Despite this often efficient therapy, 40% of patients still had unacceptable pain after 1 year, and pain with features indicative of a noninflammatory mechanism accounted for more than 60% of this pain load,” senior study author Tor Olofsson, MD, a rheumatologist and doctoral student at Lund (Sweden) University, said in an interview in advance of his presentation at the European Congress of Rheumatology.

“Within rheumatology, today we are generally very good at treating inflammation in many of the arthritides, but we have a lot of patients with persistent pain despite being well treated for their inflammation,” Dr. Olofsson said. “In psoriatic arthritis patients, this remaining pain seems to be even more frequent than in rheumatoid arthritis with the capturing instruments we use here.”

Dr. Olofsson and his colleagues studied prospectively collected records from 352 psoriatic arthritis patients (48% women) participating in the South Swedish Arthritis Group register who started a first anti–tumor necrosis factor (anti-TNF) therapy during 2004-2010. Participants had a mean age of 47 years and a mean disease duration of 10 years. At the start of anti-TNF therapy, 63% of patients were taking methotrexate, and 68% were taking any conventional disease-modifying antirheumatic drug (DMARD).

Based on the Patient Acceptable Symptom State, unacceptable pain was defined as greater than 40 mm on a 0-100 mm Visual Analog Scale (VAS). Inflammation control was captured through C-reactive protein level less than 10 mg/L in combination with one or no swollen joints. Assessments were performed at baseline, 1.5, 3, 6, and 12 months after the start of the first anti-TNF agent. Analyses were also conducted in relation to European League Against Rheumatism (EULAR)–defined treatment response after 3 months (good, moderate, or no response).

At the start of anti-TNF therapy, 85% of patients reported unacceptable pain, which declined to 43% after 3 months and then remained stable, reaching 39% at 12 months. The fraction of patients who had unacceptable pain despite inflammation control was largely unchanged over the study period (24% at treatment start, 27% at 3 months, and 26% at 12 months). Unacceptable pain at 3 months was strongly related to EULAR 3-month response (24% of good responders vs. 79% of nonresponders; P less than .001). This relationship was less pronounced among patients with unacceptable pain despite inflammation control (19% of good responders vs. 37% of nonresponders; P = .016). Among EULAR good responders, unacceptable pain despite inflammation control constituted 81% of all unacceptable pain at 3 months.

Dr. Olofsson said he was surprised by the high levels of pain despite inflammation control reported by these patients. A similar study he and others conducted in rheumatoid arthritis patients a year ago, soon to be published, found that only 12% had unacceptable pain despite inflammation control 1 year after start of a first anti-TNF agent, “so captured by the same instruments, it looks like this problem might be even bigger among patients with psoriatic arthritis.”

There is a possibility that psoriatic arthritis patients may have ongoing pain from low-grade inflammation, he said, but another hypothesis is that many psoriatic arthritis patients develop a more generalized pain condition in line with fibromyalgia. It could be that, if inflammation isn’t treated quickly enough in the beginning of the disease, it could sensitize the central pain system, he said, and it may not be reversible after it has developed.

Alternative treatment strategies are often needed in affected patients, Dr. Olofsson added. This could include regular painkillers or medicines used for more generalized, noninflammatory pain states, such as amitriptyline or duloxetine, as well as nonpharmacologic treatment options.

“The bottom line here is that, if patients are treated aggressively early enough, we might be able to prevent development of this sensitization process,” Dr. Olofsson said. “If we can also do predictive studies to describe which patients have a higher risk of developing this, then maybe we can be even more focused in the initial management before they become centrally sensitized.”

Dr. Olofsson had no financial conflicts to disclose. Two of his coauthors reported relationships with AbbVie, Eli Lilly, Celgene, Novartis, UCB, and Sandoz.

Mitchel L. Zoler contributed to this report.

SOURCE: Roseman C et al. Ann Rheum Dis. 2019 Jun;78(Suppl 2):129-30. Abstract OP0112, doi: 10.1136/annrheumdis-2019-eular.1839.

MADRID – A considerable number of patients with psoriatic arthritis starting their first biologic treatment report unacceptable pain throughout the first year of treatment, even when their inflammation is controlled, according to Swedish researchers.

Mitchel L. Zoler/MDedge News

“Despite this often efficient therapy, 40% of patients still had unacceptable pain after 1 year, and pain with features indicative of a noninflammatory mechanism accounted for more than 60% of this pain load,” senior study author Tor Olofsson, MD, a rheumatologist and doctoral student at Lund (Sweden) University, said in an interview in advance of his presentation at the European Congress of Rheumatology.

“Within rheumatology, today we are generally very good at treating inflammation in many of the arthritides, but we have a lot of patients with persistent pain despite being well treated for their inflammation,” Dr. Olofsson said. “In psoriatic arthritis patients, this remaining pain seems to be even more frequent than in rheumatoid arthritis with the capturing instruments we use here.”

Dr. Olofsson and his colleagues studied prospectively collected records from 352 psoriatic arthritis patients (48% women) participating in the South Swedish Arthritis Group register who started a first anti–tumor necrosis factor (anti-TNF) therapy during 2004-2010. Participants had a mean age of 47 years and a mean disease duration of 10 years. At the start of anti-TNF therapy, 63% of patients were taking methotrexate, and 68% were taking any conventional disease-modifying antirheumatic drug (DMARD).

Based on the Patient Acceptable Symptom State, unacceptable pain was defined as greater than 40 mm on a 0-100 mm Visual Analog Scale (VAS). Inflammation control was captured through C-reactive protein level less than 10 mg/L in combination with one or no swollen joints. Assessments were performed at baseline, 1.5, 3, 6, and 12 months after the start of the first anti-TNF agent. Analyses were also conducted in relation to European League Against Rheumatism (EULAR)–defined treatment response after 3 months (good, moderate, or no response).

At the start of anti-TNF therapy, 85% of patients reported unacceptable pain, which declined to 43% after 3 months and then remained stable, reaching 39% at 12 months. The fraction of patients who had unacceptable pain despite inflammation control was largely unchanged over the study period (24% at treatment start, 27% at 3 months, and 26% at 12 months). Unacceptable pain at 3 months was strongly related to EULAR 3-month response (24% of good responders vs. 79% of nonresponders; P less than .001). This relationship was less pronounced among patients with unacceptable pain despite inflammation control (19% of good responders vs. 37% of nonresponders; P = .016). Among EULAR good responders, unacceptable pain despite inflammation control constituted 81% of all unacceptable pain at 3 months.

Dr. Olofsson said he was surprised by the high levels of pain despite inflammation control reported by these patients. A similar study he and others conducted in rheumatoid arthritis patients a year ago, soon to be published, found that only 12% had unacceptable pain despite inflammation control 1 year after start of a first anti-TNF agent, “so captured by the same instruments, it looks like this problem might be even bigger among patients with psoriatic arthritis.”

There is a possibility that psoriatic arthritis patients may have ongoing pain from low-grade inflammation, he said, but another hypothesis is that many psoriatic arthritis patients develop a more generalized pain condition in line with fibromyalgia. It could be that, if inflammation isn’t treated quickly enough in the beginning of the disease, it could sensitize the central pain system, he said, and it may not be reversible after it has developed.

Alternative treatment strategies are often needed in affected patients, Dr. Olofsson added. This could include regular painkillers or medicines used for more generalized, noninflammatory pain states, such as amitriptyline or duloxetine, as well as nonpharmacologic treatment options.

“The bottom line here is that, if patients are treated aggressively early enough, we might be able to prevent development of this sensitization process,” Dr. Olofsson said. “If we can also do predictive studies to describe which patients have a higher risk of developing this, then maybe we can be even more focused in the initial management before they become centrally sensitized.”

Dr. Olofsson had no financial conflicts to disclose. Two of his coauthors reported relationships with AbbVie, Eli Lilly, Celgene, Novartis, UCB, and Sandoz.

Mitchel L. Zoler contributed to this report.

SOURCE: Roseman C et al. Ann Rheum Dis. 2019 Jun;78(Suppl 2):129-30. Abstract OP0112, doi: 10.1136/annrheumdis-2019-eular.1839.

MADRID – A considerable number of patients with psoriatic arthritis starting their first biologic treatment report unacceptable pain throughout the first year of treatment, even when their inflammation is controlled, according to Swedish researchers.

Mitchel L. Zoler/MDedge News

“Despite this often efficient therapy, 40% of patients still had unacceptable pain after 1 year, and pain with features indicative of a noninflammatory mechanism accounted for more than 60% of this pain load,” senior study author Tor Olofsson, MD, a rheumatologist and doctoral student at Lund (Sweden) University, said in an interview in advance of his presentation at the European Congress of Rheumatology.

“Within rheumatology, today we are generally very good at treating inflammation in many of the arthritides, but we have a lot of patients with persistent pain despite being well treated for their inflammation,” Dr. Olofsson said. “In psoriatic arthritis patients, this remaining pain seems to be even more frequent than in rheumatoid arthritis with the capturing instruments we use here.”

Dr. Olofsson and his colleagues studied prospectively collected records from 352 psoriatic arthritis patients (48% women) participating in the South Swedish Arthritis Group register who started a first anti–tumor necrosis factor (anti-TNF) therapy during 2004-2010. Participants had a mean age of 47 years and a mean disease duration of 10 years. At the start of anti-TNF therapy, 63% of patients were taking methotrexate, and 68% were taking any conventional disease-modifying antirheumatic drug (DMARD).

Based on the Patient Acceptable Symptom State, unacceptable pain was defined as greater than 40 mm on a 0-100 mm Visual Analog Scale (VAS). Inflammation control was captured through C-reactive protein level less than 10 mg/L in combination with one or no swollen joints. Assessments were performed at baseline, 1.5, 3, 6, and 12 months after the start of the first anti-TNF agent. Analyses were also conducted in relation to European League Against Rheumatism (EULAR)–defined treatment response after 3 months (good, moderate, or no response).

At the start of anti-TNF therapy, 85% of patients reported unacceptable pain, which declined to 43% after 3 months and then remained stable, reaching 39% at 12 months. The fraction of patients who had unacceptable pain despite inflammation control was largely unchanged over the study period (24% at treatment start, 27% at 3 months, and 26% at 12 months). Unacceptable pain at 3 months was strongly related to EULAR 3-month response (24% of good responders vs. 79% of nonresponders; P less than .001). This relationship was less pronounced among patients with unacceptable pain despite inflammation control (19% of good responders vs. 37% of nonresponders; P = .016). Among EULAR good responders, unacceptable pain despite inflammation control constituted 81% of all unacceptable pain at 3 months.

Dr. Olofsson said he was surprised by the high levels of pain despite inflammation control reported by these patients. A similar study he and others conducted in rheumatoid arthritis patients a year ago, soon to be published, found that only 12% had unacceptable pain despite inflammation control 1 year after start of a first anti-TNF agent, “so captured by the same instruments, it looks like this problem might be even bigger among patients with psoriatic arthritis.”

There is a possibility that psoriatic arthritis patients may have ongoing pain from low-grade inflammation, he said, but another hypothesis is that many psoriatic arthritis patients develop a more generalized pain condition in line with fibromyalgia. It could be that, if inflammation isn’t treated quickly enough in the beginning of the disease, it could sensitize the central pain system, he said, and it may not be reversible after it has developed.

Alternative treatment strategies are often needed in affected patients, Dr. Olofsson added. This could include regular painkillers or medicines used for more generalized, noninflammatory pain states, such as amitriptyline or duloxetine, as well as nonpharmacologic treatment options.

“The bottom line here is that, if patients are treated aggressively early enough, we might be able to prevent development of this sensitization process,” Dr. Olofsson said. “If we can also do predictive studies to describe which patients have a higher risk of developing this, then maybe we can be even more focused in the initial management before they become centrally sensitized.”

Dr. Olofsson had no financial conflicts to disclose. Two of his coauthors reported relationships with AbbVie, Eli Lilly, Celgene, Novartis, UCB, and Sandoz.

Mitchel L. Zoler contributed to this report.

SOURCE: Roseman C et al. Ann Rheum Dis. 2019 Jun;78(Suppl 2):129-30. Abstract OP0112, doi: 10.1136/annrheumdis-2019-eular.1839.

MADRID – The draft revision of the European League Against Rheumatism’s recommendations for managing psoriatic arthritis sticks with the group’s already-existing conviction that psoriatic arthritis treatment best starts with an NSAID, and if that fails follow with a conventional synthetic antirheumatic drug such as methotrexate, a position in stark contrast with the 2018 recommendation from the American College of Rheumatology to first treat with a tumor necrosis factor (TNF) inhibitor.

Mitchel L. Zoler/MDedge News

For patients with psoriatic arthritis (PsA) manifesting with polyarthritis, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) “should be first,” and should “start rapidly” if brief, initial treatment with an NSAID proves inadequate, Laure Gossec, MD, PhD, said while presenting a draft version of an update to the PsA management recommendations from EULAR at the European Congress of Rheumatology.

The EULAR recommendations-revision panel had about the same advice for managing PsA patients with oligoarthritis, monoarthritis, or peripheral arthritis. For oligo- and monoarthritis, “consider a csDMARD after failing NSAIDS, but also consider the patient’s prognostic factors,” like structural damage, and dactylitis. For PsA patients with peripheral arthritis, “it still makes sense to keep csDMARDs as the first line treatment,” said Dr. Gossec, professor of rheumatology at Pitie-Salpétriere Hospital and Sorbonne University, Paris. Once published, the revision will replace existing EULAR recommendations from 2015 (Ann Rheum Dis. 2016 Mar;75[3]:499-510).

The list of csDMARDs she cited included not just methotrexate, still the top csDMARD, but also sulfasalazine and leflunomide as alternatives, she noted, with methotrexate also the preferred csDMARD for patients with skin involvement. When a PsA patient fails at least one csDMARD, then switching to a biologic DMARD is recommended. For a patient with skin involvement, a drug that targets interleukin-17 or IL-12 and -23 is preferred. If skin involvement is not a major issue, then treatment with a TNF inhibitor is equally valid, she said.

The 2018 PsA management guideline from the American College of Rheumatology (ACR) proposed a strikingly different sequence, endorsing initial treatment with a TNF inhibitor first over all other options, including methotrexate and other “oral small molecules” (the ACR term for csDMARD), and also including NSAIDs (Arthritis Rheumatol. 2019 Jan;71[1]:5-32).

This schism between EULAR and the ACR could be seen as predictable, given the different constraints the two societies have set for themselves.

Mitchel L. Zoler/MDedge News

“EULAR recommendations take into account drug costs; the ACR guideline is supposed to be agnostic to costs,” explained Philip J. Mease, MD, a rheumatologist at Swedish Medical Center in Seattle and a member of the ACR panel that wrote the 2018 PsA guideline.

In fact it was a study Dr. Mease recently led and reported results from that provided the most recent and perhaps best assessment of a TNF inhibitor, compared with methotrexate, as initial treatment for PsA, with findings that suggest that, although the advice from the two societies may sharply differ, the viewpoints of both groups are evidence based.

The SEAM-PsA (Study of Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) trial randomized 851 PsA patients receiving their first treatment to methotrexate only, the TNF inhibitor etanercept (Enbrel) only, or both drugs. The study’s two coprimary outcomes, the ACR 20 and minimal disease activity responses after 24 weeks, showed that etanercept monotherapy produced these responses in 61% and 36% of patients, respectively, while methotrexate monotherapy produced response rates of 51% and 23%, respectively. Both these differences between etanercept monotherapy and methotrexate monotherapy were statistically significant. Combining methotrexate with etanercept did not produce a significant improvement over etanercept alone.

Interpreting the meaning of this finding for clinical practice “depends on the lens you look through,” Dr. Mease said in an interview. “A lot of patients respond to methotrexate, which is good when treatment resources are challenged. But when there is no resource challenge, the data support going straight to a TNF inhibitor.”

Dr. Gossec confirmed the importance of the SEAM-PsA findings in the writing panel’s decision during discussion of the draft, replying to a question about consideration of the study’s findings. “We carefully looked at the SEAM-PsA trial results, which provide some of the only data we have on methotrexate” for PsA. “We felt that the results were in favor of methotrexate’s efficacy, and therefore did not go against our proposal to keep a graduated approach starting with a csDMARD.”

Patients who fail to receive adequate relief from a csDMARD could then try a biologic DMARD – a TNF inhibitor, IL-17 inhibitor, or IL-12/23 inhibitor, Dr. Gossec said. When skin involvement is minimal, any of these options are possible, she said. If skin involvement is significant, the panel recommended preferentially using an IL-17 or IL-12/23 inhibitor based on head-to-head trials in patients with psoriasis, she said.

When a biologic DMARD is not appropriate or fails, another option is to then try a targeted synthetic DMARD, such as a Janus kinase inhibitor. When none of these options are appropriate, or they all fail, another option for patients with mild oligo- or monoarthritis or in patients with limited skin involvement is apremilast (Otezla), a phosphodiesterase-4 inhibitor. The draft recommendations also advise clinicians to be sure to distinguish fibromyalgia pain from enthesitis involvement, and they introduce the possibility of, with “great caution,” tapering down DMARD treatment in PsA patients who show sustained remission.

Dr. Gossec and Dr. Mease have both been consultants to and received honoraria from several companies. SEAM-PsA was sponsored by Amgen, the company that markets Enbrel.

[email protected]

MADRID – The draft revision of the European League Against Rheumatism’s recommendations for managing psoriatic arthritis sticks with the group’s already-existing conviction that psoriatic arthritis treatment best starts with an NSAID, and if that fails follow with a conventional synthetic antirheumatic drug such as methotrexate, a position in stark contrast with the 2018 recommendation from the American College of Rheumatology to first treat with a tumor necrosis factor (TNF) inhibitor.

Mitchel L. Zoler/MDedge News

For patients with psoriatic arthritis (PsA) manifesting with polyarthritis, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) “should be first,” and should “start rapidly” if brief, initial treatment with an NSAID proves inadequate, Laure Gossec, MD, PhD, said while presenting a draft version of an update to the PsA management recommendations from EULAR at the European Congress of Rheumatology.

The EULAR recommendations-revision panel had about the same advice for managing PsA patients with oligoarthritis, monoarthritis, or peripheral arthritis. For oligo- and monoarthritis, “consider a csDMARD after failing NSAIDS, but also consider the patient’s prognostic factors,” like structural damage, and dactylitis. For PsA patients with peripheral arthritis, “it still makes sense to keep csDMARDs as the first line treatment,” said Dr. Gossec, professor of rheumatology at Pitie-Salpétriere Hospital and Sorbonne University, Paris. Once published, the revision will replace existing EULAR recommendations from 2015 (Ann Rheum Dis. 2016 Mar;75[3]:499-510).

The list of csDMARDs she cited included not just methotrexate, still the top csDMARD, but also sulfasalazine and leflunomide as alternatives, she noted, with methotrexate also the preferred csDMARD for patients with skin involvement. When a PsA patient fails at least one csDMARD, then switching to a biologic DMARD is recommended. For a patient with skin involvement, a drug that targets interleukin-17 or IL-12 and -23 is preferred. If skin involvement is not a major issue, then treatment with a TNF inhibitor is equally valid, she said.

The 2018 PsA management guideline from the American College of Rheumatology (ACR) proposed a strikingly different sequence, endorsing initial treatment with a TNF inhibitor first over all other options, including methotrexate and other “oral small molecules” (the ACR term for csDMARD), and also including NSAIDs (Arthritis Rheumatol. 2019 Jan;71[1]:5-32).

This schism between EULAR and the ACR could be seen as predictable, given the different constraints the two societies have set for themselves.

Mitchel L. Zoler/MDedge News

“EULAR recommendations take into account drug costs; the ACR guideline is supposed to be agnostic to costs,” explained Philip J. Mease, MD, a rheumatologist at Swedish Medical Center in Seattle and a member of the ACR panel that wrote the 2018 PsA guideline.

In fact it was a study Dr. Mease recently led and reported results from that provided the most recent and perhaps best assessment of a TNF inhibitor, compared with methotrexate, as initial treatment for PsA, with findings that suggest that, although the advice from the two societies may sharply differ, the viewpoints of both groups are evidence based.

The SEAM-PsA (Study of Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) trial randomized 851 PsA patients receiving their first treatment to methotrexate only, the TNF inhibitor etanercept (Enbrel) only, or both drugs. The study’s two coprimary outcomes, the ACR 20 and minimal disease activity responses after 24 weeks, showed that etanercept monotherapy produced these responses in 61% and 36% of patients, respectively, while methotrexate monotherapy produced response rates of 51% and 23%, respectively. Both these differences between etanercept monotherapy and methotrexate monotherapy were statistically significant. Combining methotrexate with etanercept did not produce a significant improvement over etanercept alone.

Interpreting the meaning of this finding for clinical practice “depends on the lens you look through,” Dr. Mease said in an interview. “A lot of patients respond to methotrexate, which is good when treatment resources are challenged. But when there is no resource challenge, the data support going straight to a TNF inhibitor.”

Dr. Gossec confirmed the importance of the SEAM-PsA findings in the writing panel’s decision during discussion of the draft, replying to a question about consideration of the study’s findings. “We carefully looked at the SEAM-PsA trial results, which provide some of the only data we have on methotrexate” for PsA. “We felt that the results were in favor of methotrexate’s efficacy, and therefore did not go against our proposal to keep a graduated approach starting with a csDMARD.”

Patients who fail to receive adequate relief from a csDMARD could then try a biologic DMARD – a TNF inhibitor, IL-17 inhibitor, or IL-12/23 inhibitor, Dr. Gossec said. When skin involvement is minimal, any of these options are possible, she said. If skin involvement is significant, the panel recommended preferentially using an IL-17 or IL-12/23 inhibitor based on head-to-head trials in patients with psoriasis, she said.

When a biologic DMARD is not appropriate or fails, another option is to then try a targeted synthetic DMARD, such as a Janus kinase inhibitor. When none of these options are appropriate, or they all fail, another option for patients with mild oligo- or monoarthritis or in patients with limited skin involvement is apremilast (Otezla), a phosphodiesterase-4 inhibitor. The draft recommendations also advise clinicians to be sure to distinguish fibromyalgia pain from enthesitis involvement, and they introduce the possibility of, with “great caution,” tapering down DMARD treatment in PsA patients who show sustained remission.

Dr. Gossec and Dr. Mease have both been consultants to and received honoraria from several companies. SEAM-PsA was sponsored by Amgen, the company that markets Enbrel.

[email protected]

MADRID – The draft revision of the European League Against Rheumatism’s recommendations for managing psoriatic arthritis sticks with the group’s already-existing conviction that psoriatic arthritis treatment best starts with an NSAID, and if that fails follow with a conventional synthetic antirheumatic drug such as methotrexate, a position in stark contrast with the 2018 recommendation from the American College of Rheumatology to first treat with a tumor necrosis factor (TNF) inhibitor.

Mitchel L. Zoler/MDedge News

For patients with psoriatic arthritis (PsA) manifesting with polyarthritis, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) “should be first,” and should “start rapidly” if brief, initial treatment with an NSAID proves inadequate, Laure Gossec, MD, PhD, said while presenting a draft version of an update to the PsA management recommendations from EULAR at the European Congress of Rheumatology.

The EULAR recommendations-revision panel had about the same advice for managing PsA patients with oligoarthritis, monoarthritis, or peripheral arthritis. For oligo- and monoarthritis, “consider a csDMARD after failing NSAIDS, but also consider the patient’s prognostic factors,” like structural damage, and dactylitis. For PsA patients with peripheral arthritis, “it still makes sense to keep csDMARDs as the first line treatment,” said Dr. Gossec, professor of rheumatology at Pitie-Salpétriere Hospital and Sorbonne University, Paris. Once published, the revision will replace existing EULAR recommendations from 2015 (Ann Rheum Dis. 2016 Mar;75[3]:499-510).

The list of csDMARDs she cited included not just methotrexate, still the top csDMARD, but also sulfasalazine and leflunomide as alternatives, she noted, with methotrexate also the preferred csDMARD for patients with skin involvement. When a PsA patient fails at least one csDMARD, then switching to a biologic DMARD is recommended. For a patient with skin involvement, a drug that targets interleukin-17 or IL-12 and -23 is preferred. If skin involvement is not a major issue, then treatment with a TNF inhibitor is equally valid, she said.

The 2018 PsA management guideline from the American College of Rheumatology (ACR) proposed a strikingly different sequence, endorsing initial treatment with a TNF inhibitor first over all other options, including methotrexate and other “oral small molecules” (the ACR term for csDMARD), and also including NSAIDs (Arthritis Rheumatol. 2019 Jan;71[1]:5-32).

This schism between EULAR and the ACR could be seen as predictable, given the different constraints the two societies have set for themselves.

Mitchel L. Zoler/MDedge News

“EULAR recommendations take into account drug costs; the ACR guideline is supposed to be agnostic to costs,” explained Philip J. Mease, MD, a rheumatologist at Swedish Medical Center in Seattle and a member of the ACR panel that wrote the 2018 PsA guideline.

In fact it was a study Dr. Mease recently led and reported results from that provided the most recent and perhaps best assessment of a TNF inhibitor, compared with methotrexate, as initial treatment for PsA, with findings that suggest that, although the advice from the two societies may sharply differ, the viewpoints of both groups are evidence based.

The SEAM-PsA (Study of Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) trial randomized 851 PsA patients receiving their first treatment to methotrexate only, the TNF inhibitor etanercept (Enbrel) only, or both drugs. The study’s two coprimary outcomes, the ACR 20 and minimal disease activity responses after 24 weeks, showed that etanercept monotherapy produced these responses in 61% and 36% of patients, respectively, while methotrexate monotherapy produced response rates of 51% and 23%, respectively. Both these differences between etanercept monotherapy and methotrexate monotherapy were statistically significant. Combining methotrexate with etanercept did not produce a significant improvement over etanercept alone.

Interpreting the meaning of this finding for clinical practice “depends on the lens you look through,” Dr. Mease said in an interview. “A lot of patients respond to methotrexate, which is good when treatment resources are challenged. But when there is no resource challenge, the data support going straight to a TNF inhibitor.”

Dr. Gossec confirmed the importance of the SEAM-PsA findings in the writing panel’s decision during discussion of the draft, replying to a question about consideration of the study’s findings. “We carefully looked at the SEAM-PsA trial results, which provide some of the only data we have on methotrexate” for PsA. “We felt that the results were in favor of methotrexate’s efficacy, and therefore did not go against our proposal to keep a graduated approach starting with a csDMARD.”

Patients who fail to receive adequate relief from a csDMARD could then try a biologic DMARD – a TNF inhibitor, IL-17 inhibitor, or IL-12/23 inhibitor, Dr. Gossec said. When skin involvement is minimal, any of these options are possible, she said. If skin involvement is significant, the panel recommended preferentially using an IL-17 or IL-12/23 inhibitor based on head-to-head trials in patients with psoriasis, she said.

When a biologic DMARD is not appropriate or fails, another option is to then try a targeted synthetic DMARD, such as a Janus kinase inhibitor. When none of these options are appropriate, or they all fail, another option for patients with mild oligo- or monoarthritis or in patients with limited skin involvement is apremilast (Otezla), a phosphodiesterase-4 inhibitor. The draft recommendations also advise clinicians to be sure to distinguish fibromyalgia pain from enthesitis involvement, and they introduce the possibility of, with “great caution,” tapering down DMARD treatment in PsA patients who show sustained remission.

Dr. Gossec and Dr. Mease have both been consultants to and received honoraria from several companies. SEAM-PsA was sponsored by Amgen, the company that markets Enbrel.

[email protected]

Treating Psoriatic Arthritis to Target: Defining Psoriatic Arthritis Disease Activity Score (PASDAS) That Reflects State Of Minimal Disease Activity (MDA).

Perruccio AV, Got M, Li S, Ye Y, Gladman DD, Chandran V. J Rheumatol. 2019 Jun 15.

PsA Disease Activity Score (PASDAS) is a composite disease activity measure (range 0-10) for psoriatic arthritis. The study aimed to validate a cutoff value of PASDAS that defines minimal disease activity state, as well as validate previously defined PASDAS cutoffs for low and high disease activity.

Evaluating current definitions of low disease activity in psoriatic arthritis using ultrasound.

Bosch P, Husic R, Ficjan A, et al. Rheumatology (Oxford). 2019 Jun 14.

The aim of the study was to evaluate low disease activity (LDA) cut-offs in psoriatic arthritis (PsA) using ultrasound. Eighty-three PsA patients underwent clinical and ultrasound examinations at two visits. Pain and pain-related items are the main reason why PsA patients without signs of ultrasound inflammation are classified with higher disease activity.

A Threshold of Meaning for Work Disability Improvement in Psoriatic Arthritis Measured by the Work Productivity and Activity Impairment Questionnaire.

Tillett W, Lin CY, Zbrozek A, Sprabery AT, Birt J.  Rheumatol Ther. 2019 Jun 1.

The Work Productivity and Activity Impairment Specific Health Problem Questionnaire (WPAI:SHP) is used to assess the impact of an intervention on work productivity in patients with psoriatic arthritis (PsA). Unfortunately, studies reporting changes or improvements in domains of WPAI:SHP by patients with PsA have a limited threshold of meaning due to the absence of published minimal clinically important differences (MCIDs). The objective of the study was to determine the MCIDs for improvement in WPAI:SHP in patients with active PsA.

Measuring Psoriatic Arthritis Symptoms, A Core Domain in Psoriasis Clinical Trials.

Perez-Chada LM, Gottlieb AB, Cohen J, et al. J Am Acad Dermatol. 2019 Jun 1.

The International Dermatology Outcome Measures (IDEOM) established a set of core domains to be measured in all psoriasis trials. This set indicates that symptoms of psoriatic arthritis (PsA) should be measured in all psoriasis studies. The objective of the study was to identify the approach to PsA screening, and the most appropriate outcome measure for capturing PsA symptoms. The overwhelming majority of expert stakeholders agreed that all psoriasis trial subjects should be screened for PsA with subsequent measurement of PsA symptoms with use of the PsAID9 (with the RAPID3 as an acceptable alternative measure).

The Genetics of Psoriasis and Psoriatic Arthritis.

O'Rielly DD, Jani M, Rahman P, Elder JT. J Rheumatol Suppl. 2019 Jun;95:46-50.

Psoriatic arthritis (PsA) is an inflammatory arthritis that manifests in 20-30% of patients diagnosed with psoriasis. Epidemiologic studies suggest a substantial genetic contribution to PsA. There is a strong need for genome-wide association studies on patients with PsA, including PsA-weighted or specific variants. Genomics and serological factors may also predict treatment response in tumor necrosis factor inhibitors (TNFi) in PsA, and genetics may play a role in treatment response to TNFi. Collaborations through the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) are essential to increase study population size, which will enhance the ability to detect the genetic variants that create a predisposition to psoriatic disease and to predict response to biological therapy.

Treating Psoriatic Arthritis to Target: Defining Psoriatic Arthritis Disease Activity Score (PASDAS) That Reflects State Of Minimal Disease Activity (MDA).

Perruccio AV, Got M, Li S, Ye Y, Gladman DD, Chandran V. J Rheumatol. 2019 Jun 15.

PsA Disease Activity Score (PASDAS) is a composite disease activity measure (range 0-10) for psoriatic arthritis. The study aimed to validate a cutoff value of PASDAS that defines minimal disease activity state, as well as validate previously defined PASDAS cutoffs for low and high disease activity.

Evaluating current definitions of low disease activity in psoriatic arthritis using ultrasound.

Bosch P, Husic R, Ficjan A, et al. Rheumatology (Oxford). 2019 Jun 14.

The aim of the study was to evaluate low disease activity (LDA) cut-offs in psoriatic arthritis (PsA) using ultrasound. Eighty-three PsA patients underwent clinical and ultrasound examinations at two visits. Pain and pain-related items are the main reason why PsA patients without signs of ultrasound inflammation are classified with higher disease activity.

A Threshold of Meaning for Work Disability Improvement in Psoriatic Arthritis Measured by the Work Productivity and Activity Impairment Questionnaire.

Tillett W, Lin CY, Zbrozek A, Sprabery AT, Birt J.  Rheumatol Ther. 2019 Jun 1.

The Work Productivity and Activity Impairment Specific Health Problem Questionnaire (WPAI:SHP) is used to assess the impact of an intervention on work productivity in patients with psoriatic arthritis (PsA). Unfortunately, studies reporting changes or improvements in domains of WPAI:SHP by patients with PsA have a limited threshold of meaning due to the absence of published minimal clinically important differences (MCIDs). The objective of the study was to determine the MCIDs for improvement in WPAI:SHP in patients with active PsA.

Measuring Psoriatic Arthritis Symptoms, A Core Domain in Psoriasis Clinical Trials.

Perez-Chada LM, Gottlieb AB, Cohen J, et al. J Am Acad Dermatol. 2019 Jun 1.

The International Dermatology Outcome Measures (IDEOM) established a set of core domains to be measured in all psoriasis trials. This set indicates that symptoms of psoriatic arthritis (PsA) should be measured in all psoriasis studies. The objective of the study was to identify the approach to PsA screening, and the most appropriate outcome measure for capturing PsA symptoms. The overwhelming majority of expert stakeholders agreed that all psoriasis trial subjects should be screened for PsA with subsequent measurement of PsA symptoms with use of the PsAID9 (with the RAPID3 as an acceptable alternative measure).

The Genetics of Psoriasis and Psoriatic Arthritis.

O'Rielly DD, Jani M, Rahman P, Elder JT. J Rheumatol Suppl. 2019 Jun;95:46-50.

Psoriatic arthritis (PsA) is an inflammatory arthritis that manifests in 20-30% of patients diagnosed with psoriasis. Epidemiologic studies suggest a substantial genetic contribution to PsA. There is a strong need for genome-wide association studies on patients with PsA, including PsA-weighted or specific variants. Genomics and serological factors may also predict treatment response in tumor necrosis factor inhibitors (TNFi) in PsA, and genetics may play a role in treatment response to TNFi. Collaborations through the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) are essential to increase study population size, which will enhance the ability to detect the genetic variants that create a predisposition to psoriatic disease and to predict response to biological therapy.

Treating Psoriatic Arthritis to Target: Defining Psoriatic Arthritis Disease Activity Score (PASDAS) That Reflects State Of Minimal Disease Activity (MDA).

Perruccio AV, Got M, Li S, Ye Y, Gladman DD, Chandran V. J Rheumatol. 2019 Jun 15.

PsA Disease Activity Score (PASDAS) is a composite disease activity measure (range 0-10) for psoriatic arthritis. The study aimed to validate a cutoff value of PASDAS that defines minimal disease activity state, as well as validate previously defined PASDAS cutoffs for low and high disease activity.

Evaluating current definitions of low disease activity in psoriatic arthritis using ultrasound.

Bosch P, Husic R, Ficjan A, et al. Rheumatology (Oxford). 2019 Jun 14.

The aim of the study was to evaluate low disease activity (LDA) cut-offs in psoriatic arthritis (PsA) using ultrasound. Eighty-three PsA patients underwent clinical and ultrasound examinations at two visits. Pain and pain-related items are the main reason why PsA patients without signs of ultrasound inflammation are classified with higher disease activity.

A Threshold of Meaning for Work Disability Improvement in Psoriatic Arthritis Measured by the Work Productivity and Activity Impairment Questionnaire.

Tillett W, Lin CY, Zbrozek A, Sprabery AT, Birt J.  Rheumatol Ther. 2019 Jun 1.

The Work Productivity and Activity Impairment Specific Health Problem Questionnaire (WPAI:SHP) is used to assess the impact of an intervention on work productivity in patients with psoriatic arthritis (PsA). Unfortunately, studies reporting changes or improvements in domains of WPAI:SHP by patients with PsA have a limited threshold of meaning due to the absence of published minimal clinically important differences (MCIDs). The objective of the study was to determine the MCIDs for improvement in WPAI:SHP in patients with active PsA.

Measuring Psoriatic Arthritis Symptoms, A Core Domain in Psoriasis Clinical Trials.

Perez-Chada LM, Gottlieb AB, Cohen J, et al. J Am Acad Dermatol. 2019 Jun 1.

The International Dermatology Outcome Measures (IDEOM) established a set of core domains to be measured in all psoriasis trials. This set indicates that symptoms of psoriatic arthritis (PsA) should be measured in all psoriasis studies. The objective of the study was to identify the approach to PsA screening, and the most appropriate outcome measure for capturing PsA symptoms. The overwhelming majority of expert stakeholders agreed that all psoriasis trial subjects should be screened for PsA with subsequent measurement of PsA symptoms with use of the PsAID9 (with the RAPID3 as an acceptable alternative measure).

The Genetics of Psoriasis and Psoriatic Arthritis.

O'Rielly DD, Jani M, Rahman P, Elder JT. J Rheumatol Suppl. 2019 Jun;95:46-50.

Psoriatic arthritis (PsA) is an inflammatory arthritis that manifests in 20-30% of patients diagnosed with psoriasis. Epidemiologic studies suggest a substantial genetic contribution to PsA. There is a strong need for genome-wide association studies on patients with PsA, including PsA-weighted or specific variants. Genomics and serological factors may also predict treatment response in tumor necrosis factor inhibitors (TNFi) in PsA, and genetics may play a role in treatment response to TNFi. Collaborations through the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) are essential to increase study population size, which will enhance the ability to detect the genetic variants that create a predisposition to psoriatic disease and to predict response to biological therapy.

MADRID – Several novel risk associations with psoriasis progression were found to differ by sex, and collectively appeared to implicate infections and the “stress response” as a trigger of psoriatic arthritis.

Mitchel L. Zoler/MDedge News

The findings come from a risk factor analysis of a U.S. claims database of more than 200,000 adults with psoriasis including more than 4,000 patients who progressed to psoriatic arthritis during nearly 6 years of follow-up.

The new analysis confirmed several previously described risk associations linked with progression to psoriatic arthritis (PsA) that have roughly equal impact on both women and men: fatigue, obesity, and depression, Alexis Ogdie, MD, said at the European Congress of Rheumatology. The new findings also showed several novel, sex-specific associations. In women, these associations included salmonella infection, sepsis, and uveitis; in men, they included gangrene, encephalitis, and hidradenitis suppurativa.

The links with various infections were generally rare; they showed strong nominal associations in multivariate analyses but with wide confidence limits. The findings suggest that events that induce major stress responses, such as infections, often preceded the progression of psoriasis to a diagnosis of PsA, said Dr. Ogdie, director of the psoriatic arthritis clinic at the University of Pennsylvania in Philadelphia. Other, noninfectious clinical features that significantly linked with PsA development but at a lower magnitude included anemia and diabetes in women, and irritable bowel syndrome and venous thromboembolism in men.

Dr. Ogdie cautioned that the findings were preliminary and need confirmation in different data sets, as well as in additional subgroup analyses of the data used in the current analysis, taken from the electronic medical records of 215,386 U.S. residents diagnosed with psoriasis in the Optum medical-claims database for 2006-2017.

The analysis focused on patients who received a second diagnostic code in their EMR for psoriasis during the 12 months after the index psoriasis entry. The identified group averaged 50 years old; 55% of the psoriasis patients were women, and 86% were white.


During the year after their first diagnostic-code entry for psoriasis, 4.6% of the patients received a biological drug and 4.2% received an oral drug for their psoriasis. During 5.6 years of follow-up, 4,288 patients (2%) developed PsA, a rate of 3.5 cases/1,000 patient-years. Dr. Ogdie noted that prior studies have documented the challenge of diagnosing PsA in patients with psoriasis, so this may be a conservative estimate of the progression rate.

The researchers assessed possible linkage with PsA progression for more than 250 different entries in the EMR, but the analysis was limited by the absence of measures of rheumatoid susceptibility, such as immunologic markers, which were not included in the EMR. In multivariate analysis of the full cohort, fatigue at baseline was linked with a 77% higher rate of progression to PsA, obesity was linked with a 48% higher rate, and depression with a 29% higher rate of progression when compared with psoriasis patients without each of these factors. All three differences were statistically significant. Dr. Ogdie cited an article she recently coauthored that detailed the background to this approach in studying the etiology of PsA (Nat Rev Rheumatol. 2019 March;15:153-66).

This is the first study to report sex-linked differences in clinical measures that link with progression to PsA, Dr. Ogdie noted. In women, salmonella infection linked with a 9-fold higher rate of PsA development compared with women with psoriasis without salmonella infection, women with uveitis had a 2.9-fold higher rate of PsA development, and those with sepsis had a 2.4-fold increased rate of PsA. Among men, those with gangrene, encephalitis, or hidradenitis suppurativa each had a greater than 4-fold higher rate of developing PsA, and men with osteomyelitis had a 2.7-fold increase.

All these between-group differences were statistically significant. But because each of these was a relatively rare event, the confidence intervals around these point estimates were wide. For example, in women with salmonella infection from a statistical standpoint the possible range of increased risk could be anywhere from 1.3 to 66. The analysis identified among women and men several additional sex-specific risk associations that were statistically significant but with smaller point estimates.

[email protected]

SOURCE: Ogdie A et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):131-2. Abstract OP0115. doi: 10.1136/annrheumdis-2019-eular.4390.

MADRID – Several novel risk associations with psoriasis progression were found to differ by sex, and collectively appeared to implicate infections and the “stress response” as a trigger of psoriatic arthritis.

Mitchel L. Zoler/MDedge News

The findings come from a risk factor analysis of a U.S. claims database of more than 200,000 adults with psoriasis including more than 4,000 patients who progressed to psoriatic arthritis during nearly 6 years of follow-up.

The new analysis confirmed several previously described risk associations linked with progression to psoriatic arthritis (PsA) that have roughly equal impact on both women and men: fatigue, obesity, and depression, Alexis Ogdie, MD, said at the European Congress of Rheumatology. The new findings also showed several novel, sex-specific associations. In women, these associations included salmonella infection, sepsis, and uveitis; in men, they included gangrene, encephalitis, and hidradenitis suppurativa.

The links with various infections were generally rare; they showed strong nominal associations in multivariate analyses but with wide confidence limits. The findings suggest that events that induce major stress responses, such as infections, often preceded the progression of psoriasis to a diagnosis of PsA, said Dr. Ogdie, director of the psoriatic arthritis clinic at the University of Pennsylvania in Philadelphia. Other, noninfectious clinical features that significantly linked with PsA development but at a lower magnitude included anemia and diabetes in women, and irritable bowel syndrome and venous thromboembolism in men.

Dr. Ogdie cautioned that the findings were preliminary and need confirmation in different data sets, as well as in additional subgroup analyses of the data used in the current analysis, taken from the electronic medical records of 215,386 U.S. residents diagnosed with psoriasis in the Optum medical-claims database for 2006-2017.

The analysis focused on patients who received a second diagnostic code in their EMR for psoriasis during the 12 months after the index psoriasis entry. The identified group averaged 50 years old; 55% of the psoriasis patients were women, and 86% were white.


During the year after their first diagnostic-code entry for psoriasis, 4.6% of the patients received a biological drug and 4.2% received an oral drug for their psoriasis. During 5.6 years of follow-up, 4,288 patients (2%) developed PsA, a rate of 3.5 cases/1,000 patient-years. Dr. Ogdie noted that prior studies have documented the challenge of diagnosing PsA in patients with psoriasis, so this may be a conservative estimate of the progression rate.

The researchers assessed possible linkage with PsA progression for more than 250 different entries in the EMR, but the analysis was limited by the absence of measures of rheumatoid susceptibility, such as immunologic markers, which were not included in the EMR. In multivariate analysis of the full cohort, fatigue at baseline was linked with a 77% higher rate of progression to PsA, obesity was linked with a 48% higher rate, and depression with a 29% higher rate of progression when compared with psoriasis patients without each of these factors. All three differences were statistically significant. Dr. Ogdie cited an article she recently coauthored that detailed the background to this approach in studying the etiology of PsA (Nat Rev Rheumatol. 2019 March;15:153-66).

This is the first study to report sex-linked differences in clinical measures that link with progression to PsA, Dr. Ogdie noted. In women, salmonella infection linked with a 9-fold higher rate of PsA development compared with women with psoriasis without salmonella infection, women with uveitis had a 2.9-fold higher rate of PsA development, and those with sepsis had a 2.4-fold increased rate of PsA. Among men, those with gangrene, encephalitis, or hidradenitis suppurativa each had a greater than 4-fold higher rate of developing PsA, and men with osteomyelitis had a 2.7-fold increase.

All these between-group differences were statistically significant. But because each of these was a relatively rare event, the confidence intervals around these point estimates were wide. For example, in women with salmonella infection from a statistical standpoint the possible range of increased risk could be anywhere from 1.3 to 66. The analysis identified among women and men several additional sex-specific risk associations that were statistically significant but with smaller point estimates.

[email protected]

SOURCE: Ogdie A et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):131-2. Abstract OP0115. doi: 10.1136/annrheumdis-2019-eular.4390.

MADRID – Several novel risk associations with psoriasis progression were found to differ by sex, and collectively appeared to implicate infections and the “stress response” as a trigger of psoriatic arthritis.

Mitchel L. Zoler/MDedge News

The findings come from a risk factor analysis of a U.S. claims database of more than 200,000 adults with psoriasis including more than 4,000 patients who progressed to psoriatic arthritis during nearly 6 years of follow-up.

The new analysis confirmed several previously described risk associations linked with progression to psoriatic arthritis (PsA) that have roughly equal impact on both women and men: fatigue, obesity, and depression, Alexis Ogdie, MD, said at the European Congress of Rheumatology. The new findings also showed several novel, sex-specific associations. In women, these associations included salmonella infection, sepsis, and uveitis; in men, they included gangrene, encephalitis, and hidradenitis suppurativa.

The links with various infections were generally rare; they showed strong nominal associations in multivariate analyses but with wide confidence limits. The findings suggest that events that induce major stress responses, such as infections, often preceded the progression of psoriasis to a diagnosis of PsA, said Dr. Ogdie, director of the psoriatic arthritis clinic at the University of Pennsylvania in Philadelphia. Other, noninfectious clinical features that significantly linked with PsA development but at a lower magnitude included anemia and diabetes in women, and irritable bowel syndrome and venous thromboembolism in men.

Dr. Ogdie cautioned that the findings were preliminary and need confirmation in different data sets, as well as in additional subgroup analyses of the data used in the current analysis, taken from the electronic medical records of 215,386 U.S. residents diagnosed with psoriasis in the Optum medical-claims database for 2006-2017.

The analysis focused on patients who received a second diagnostic code in their EMR for psoriasis during the 12 months after the index psoriasis entry. The identified group averaged 50 years old; 55% of the psoriasis patients were women, and 86% were white.


During the year after their first diagnostic-code entry for psoriasis, 4.6% of the patients received a biological drug and 4.2% received an oral drug for their psoriasis. During 5.6 years of follow-up, 4,288 patients (2%) developed PsA, a rate of 3.5 cases/1,000 patient-years. Dr. Ogdie noted that prior studies have documented the challenge of diagnosing PsA in patients with psoriasis, so this may be a conservative estimate of the progression rate.

The researchers assessed possible linkage with PsA progression for more than 250 different entries in the EMR, but the analysis was limited by the absence of measures of rheumatoid susceptibility, such as immunologic markers, which were not included in the EMR. In multivariate analysis of the full cohort, fatigue at baseline was linked with a 77% higher rate of progression to PsA, obesity was linked with a 48% higher rate, and depression with a 29% higher rate of progression when compared with psoriasis patients without each of these factors. All three differences were statistically significant. Dr. Ogdie cited an article she recently coauthored that detailed the background to this approach in studying the etiology of PsA (Nat Rev Rheumatol. 2019 March;15:153-66).

This is the first study to report sex-linked differences in clinical measures that link with progression to PsA, Dr. Ogdie noted. In women, salmonella infection linked with a 9-fold higher rate of PsA development compared with women with psoriasis without salmonella infection, women with uveitis had a 2.9-fold higher rate of PsA development, and those with sepsis had a 2.4-fold increased rate of PsA. Among men, those with gangrene, encephalitis, or hidradenitis suppurativa each had a greater than 4-fold higher rate of developing PsA, and men with osteomyelitis had a 2.7-fold increase.

All these between-group differences were statistically significant. But because each of these was a relatively rare event, the confidence intervals around these point estimates were wide. For example, in women with salmonella infection from a statistical standpoint the possible range of increased risk could be anywhere from 1.3 to 66. The analysis identified among women and men several additional sex-specific risk associations that were statistically significant but with smaller point estimates.

[email protected]

SOURCE: Ogdie A et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):131-2. Abstract OP0115. doi: 10.1136/annrheumdis-2019-eular.4390.