MDedge Rheumatology

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

SEATTLE — Tissue resident memory (TRM) T cells are a hot topic lately in the treatment of psoriasis. These cells reside in the skin and other tissues and promote the inflammatory response, likely contributing to psoriasis symptoms. In fact, flare-ups often recur at the same site, a phenomenon that might be driven by these resident memory cells, according to Liv Eidsmo, MD, PhD.

This has led to their use as biomarkers in clinical trials for new therapies, but TRM T cells have a complex biology that is far from fully understood, Dr. Eidsmo said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “With time, we’re understanding that the regulation of the functionality is more complicated than we thought, so following these cells as a positive outcome of a clinical trial is a little bit premature,” said Dr. Eidsmo, who is a consultant dermatologist at the University of Copenhagen, Copenhagen, Denmark.

Treatment strategies focus on inhibition of interleukin (IL)-23, which is an activator of TRM T cells and probably keeps them alive, according to Dr. Eidsmo. “The hope is that these cells can be silenced by IL-23 inhibition, which is a great idea, and it probably works. It’s just a matter of what is the readout of long-term remission, because the big challenge in the clinical world is when do we stop these expensive biological treatments? When can we feel secure that patients are in deep remission?” she asked.

TRM cells are also far from the only immune cells involved in psoriasis. Others include keratinocytes, Langerhans cells, and fibroblasts. Dr. Eidsmo referenced a recent spatial analysis that used single-cell and spatial RNA sequencing to identify the localization of specific cell populations and inflammatory pathways within psoriasis lesions and epidermal compartments as well as also suggested crosstalk links between cell types. Epigenetic changes in stem cells may also maintain a lower threshold for tissue inflammation.

Dr. Eidsmo advised caution in eliminating TRM T cells, which play a key role in protecting against melanoma and other cancers, especially later in life. “We don’t want to get rid of them. We want to have the right balance.”

She noted a study in her own lab that mapped TRM T cells in healthy epidermis and found that they could be renewed from both circulating precursors and cells within the epidermis. “So getting rid of the mature TRM T cells will most likely just lead to a new generation of the same subset.”

Other data show that there are a wide range of subsets of TRM T cells, and she recommended focusing on the functionality of TRM T cells rather than sheer numbers. “This is something we’re working on now: Can we change the functionality [of TRM T cells], rather than eradicate them and hope for the best in the next generation? Can we change the functionality of the T cells we already have in the skin?”

There is also epigenetic data in TRM T cells, keratinocytes, stem cells, and other cells thus suggesting complexity and plasticity in the system that remains poorly understood. 

Taken together, the research is at too early of a stage to be clinically useful, said Dr. Eidsmo. “We need to go back to the drawing board and just realize what we need to measure, and with the new techniques coming out, maybe spatial [measurement] at a high resolution, we can find biomarkers that better dictate the future of this. Be a little bit wary when you read the outcomes from the clinical trials that are ongoing, because right now, it’s a bit of a race between different biologics. These cells are used as a readout of efficacy of the treatments, and we’re not quite there yet.”

During the Q&A session after the presentation, one audience member asked about the heterogeneity of cells found within the skin of patients with psoriasis and pointed out that many proinflammatory cells likely play a role in tumor control. Dr. Eidsmo responded that her group’s analysis of a large database of patients with metastatic melanoma found that a factor that is important to the development of TRM T cells was strongly correlated to survival in patients with metastatic melanoma receiving immune checkpoint blockade. “So we really don’t want to eradicate them,” she said.

Also during the Q&A, Iain McInnes, MD, PhD, commented about the need to understand the previous events that drove the creation of memory T cells. “For me, the question is about the hierarchy, the primacy of what really drives the memory. In the infectious world, we’re trained to think [that memory responses] are T cell driven memory, but I wonder whether you have an idea of whether the T cell is responding to other memories, particularly in the stroma. Because certainly in the arthropathies, we have really good evidence now of epigenetic change in the synovial stroma and subsets,” said Dr. McInnes, who is director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Glasgow, Scotland.

Dr. Eidsmo responded that she believes responses are different among different individuals. “We know too little about how these two systems interact with one another. I think the TRM T cells are very good at amplifying the stroma to recruit cells in. I think we need to think of two-step therapies. You need to normalize this [stromal] environment. How you can do that, I don’t know.”

Dr. McInnes agreed. “As a myeloid doctor, I strongly believe that perpetuators are innate and the adaptive is following on. But how do we test that? That’s really hard,” he said. 

Dr. Eidsmo did not list any disclosures. Dr. McInnes has financial relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer, Compugen, Cabaletta, Causeway, Dextera, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, Versus Arthritis, MRC, and UCB. 

SEATTLE — Tissue resident memory (TRM) T cells are a hot topic lately in the treatment of psoriasis. These cells reside in the skin and other tissues and promote the inflammatory response, likely contributing to psoriasis symptoms. In fact, flare-ups often recur at the same site, a phenomenon that might be driven by these resident memory cells, according to Liv Eidsmo, MD, PhD.

This has led to their use as biomarkers in clinical trials for new therapies, but TRM T cells have a complex biology that is far from fully understood, Dr. Eidsmo said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “With time, we’re understanding that the regulation of the functionality is more complicated than we thought, so following these cells as a positive outcome of a clinical trial is a little bit premature,” said Dr. Eidsmo, who is a consultant dermatologist at the University of Copenhagen, Copenhagen, Denmark.

Treatment strategies focus on inhibition of interleukin (IL)-23, which is an activator of TRM T cells and probably keeps them alive, according to Dr. Eidsmo. “The hope is that these cells can be silenced by IL-23 inhibition, which is a great idea, and it probably works. It’s just a matter of what is the readout of long-term remission, because the big challenge in the clinical world is when do we stop these expensive biological treatments? When can we feel secure that patients are in deep remission?” she asked.

TRM cells are also far from the only immune cells involved in psoriasis. Others include keratinocytes, Langerhans cells, and fibroblasts. Dr. Eidsmo referenced a recent spatial analysis that used single-cell and spatial RNA sequencing to identify the localization of specific cell populations and inflammatory pathways within psoriasis lesions and epidermal compartments as well as also suggested crosstalk links between cell types. Epigenetic changes in stem cells may also maintain a lower threshold for tissue inflammation.

Dr. Eidsmo advised caution in eliminating TRM T cells, which play a key role in protecting against melanoma and other cancers, especially later in life. “We don’t want to get rid of them. We want to have the right balance.”

She noted a study in her own lab that mapped TRM T cells in healthy epidermis and found that they could be renewed from both circulating precursors and cells within the epidermis. “So getting rid of the mature TRM T cells will most likely just lead to a new generation of the same subset.”

Other data show that there are a wide range of subsets of TRM T cells, and she recommended focusing on the functionality of TRM T cells rather than sheer numbers. “This is something we’re working on now: Can we change the functionality [of TRM T cells], rather than eradicate them and hope for the best in the next generation? Can we change the functionality of the T cells we already have in the skin?”

There is also epigenetic data in TRM T cells, keratinocytes, stem cells, and other cells thus suggesting complexity and plasticity in the system that remains poorly understood. 

Taken together, the research is at too early of a stage to be clinically useful, said Dr. Eidsmo. “We need to go back to the drawing board and just realize what we need to measure, and with the new techniques coming out, maybe spatial [measurement] at a high resolution, we can find biomarkers that better dictate the future of this. Be a little bit wary when you read the outcomes from the clinical trials that are ongoing, because right now, it’s a bit of a race between different biologics. These cells are used as a readout of efficacy of the treatments, and we’re not quite there yet.”

During the Q&A session after the presentation, one audience member asked about the heterogeneity of cells found within the skin of patients with psoriasis and pointed out that many proinflammatory cells likely play a role in tumor control. Dr. Eidsmo responded that her group’s analysis of a large database of patients with metastatic melanoma found that a factor that is important to the development of TRM T cells was strongly correlated to survival in patients with metastatic melanoma receiving immune checkpoint blockade. “So we really don’t want to eradicate them,” she said.

Also during the Q&A, Iain McInnes, MD, PhD, commented about the need to understand the previous events that drove the creation of memory T cells. “For me, the question is about the hierarchy, the primacy of what really drives the memory. In the infectious world, we’re trained to think [that memory responses] are T cell driven memory, but I wonder whether you have an idea of whether the T cell is responding to other memories, particularly in the stroma. Because certainly in the arthropathies, we have really good evidence now of epigenetic change in the synovial stroma and subsets,” said Dr. McInnes, who is director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Glasgow, Scotland.

Dr. Eidsmo responded that she believes responses are different among different individuals. “We know too little about how these two systems interact with one another. I think the TRM T cells are very good at amplifying the stroma to recruit cells in. I think we need to think of two-step therapies. You need to normalize this [stromal] environment. How you can do that, I don’t know.”

Dr. McInnes agreed. “As a myeloid doctor, I strongly believe that perpetuators are innate and the adaptive is following on. But how do we test that? That’s really hard,” he said. 

Dr. Eidsmo did not list any disclosures. Dr. McInnes has financial relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer, Compugen, Cabaletta, Causeway, Dextera, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, Versus Arthritis, MRC, and UCB. 

SEATTLE — Tissue resident memory (TRM) T cells are a hot topic lately in the treatment of psoriasis. These cells reside in the skin and other tissues and promote the inflammatory response, likely contributing to psoriasis symptoms. In fact, flare-ups often recur at the same site, a phenomenon that might be driven by these resident memory cells, according to Liv Eidsmo, MD, PhD.

This has led to their use as biomarkers in clinical trials for new therapies, but TRM T cells have a complex biology that is far from fully understood, Dr. Eidsmo said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “With time, we’re understanding that the regulation of the functionality is more complicated than we thought, so following these cells as a positive outcome of a clinical trial is a little bit premature,” said Dr. Eidsmo, who is a consultant dermatologist at the University of Copenhagen, Copenhagen, Denmark.

Treatment strategies focus on inhibition of interleukin (IL)-23, which is an activator of TRM T cells and probably keeps them alive, according to Dr. Eidsmo. “The hope is that these cells can be silenced by IL-23 inhibition, which is a great idea, and it probably works. It’s just a matter of what is the readout of long-term remission, because the big challenge in the clinical world is when do we stop these expensive biological treatments? When can we feel secure that patients are in deep remission?” she asked.

TRM cells are also far from the only immune cells involved in psoriasis. Others include keratinocytes, Langerhans cells, and fibroblasts. Dr. Eidsmo referenced a recent spatial analysis that used single-cell and spatial RNA sequencing to identify the localization of specific cell populations and inflammatory pathways within psoriasis lesions and epidermal compartments as well as also suggested crosstalk links between cell types. Epigenetic changes in stem cells may also maintain a lower threshold for tissue inflammation.

Dr. Eidsmo advised caution in eliminating TRM T cells, which play a key role in protecting against melanoma and other cancers, especially later in life. “We don’t want to get rid of them. We want to have the right balance.”

She noted a study in her own lab that mapped TRM T cells in healthy epidermis and found that they could be renewed from both circulating precursors and cells within the epidermis. “So getting rid of the mature TRM T cells will most likely just lead to a new generation of the same subset.”

Other data show that there are a wide range of subsets of TRM T cells, and she recommended focusing on the functionality of TRM T cells rather than sheer numbers. “This is something we’re working on now: Can we change the functionality [of TRM T cells], rather than eradicate them and hope for the best in the next generation? Can we change the functionality of the T cells we already have in the skin?”

There is also epigenetic data in TRM T cells, keratinocytes, stem cells, and other cells thus suggesting complexity and plasticity in the system that remains poorly understood. 

Taken together, the research is at too early of a stage to be clinically useful, said Dr. Eidsmo. “We need to go back to the drawing board and just realize what we need to measure, and with the new techniques coming out, maybe spatial [measurement] at a high resolution, we can find biomarkers that better dictate the future of this. Be a little bit wary when you read the outcomes from the clinical trials that are ongoing, because right now, it’s a bit of a race between different biologics. These cells are used as a readout of efficacy of the treatments, and we’re not quite there yet.”

During the Q&A session after the presentation, one audience member asked about the heterogeneity of cells found within the skin of patients with psoriasis and pointed out that many proinflammatory cells likely play a role in tumor control. Dr. Eidsmo responded that her group’s analysis of a large database of patients with metastatic melanoma found that a factor that is important to the development of TRM T cells was strongly correlated to survival in patients with metastatic melanoma receiving immune checkpoint blockade. “So we really don’t want to eradicate them,” she said.

Also during the Q&A, Iain McInnes, MD, PhD, commented about the need to understand the previous events that drove the creation of memory T cells. “For me, the question is about the hierarchy, the primacy of what really drives the memory. In the infectious world, we’re trained to think [that memory responses] are T cell driven memory, but I wonder whether you have an idea of whether the T cell is responding to other memories, particularly in the stroma. Because certainly in the arthropathies, we have really good evidence now of epigenetic change in the synovial stroma and subsets,” said Dr. McInnes, who is director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Glasgow, Scotland.

Dr. Eidsmo responded that she believes responses are different among different individuals. “We know too little about how these two systems interact with one another. I think the TRM T cells are very good at amplifying the stroma to recruit cells in. I think we need to think of two-step therapies. You need to normalize this [stromal] environment. How you can do that, I don’t know.”

Dr. McInnes agreed. “As a myeloid doctor, I strongly believe that perpetuators are innate and the adaptive is following on. But how do we test that? That’s really hard,” he said. 

Dr. Eidsmo did not list any disclosures. Dr. McInnes has financial relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer, Compugen, Cabaletta, Causeway, Dextera, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, Versus Arthritis, MRC, and UCB. 

Key clinical point: Levels of certain proteins found in the blood plasma affected the risk for development of psoriatic arthritis (PsA) and could serve as potential therapeutic targets for the condition.

Major finding: Apolipoprotein F increased the risk for PsA by 60% (odds ratio [OR] 1.69; P_FDR < .001), whereas interleukin-10 reduced the risk for PsA by 40% (OR 0.60; P_FDR = .034). Other proteins associated with an increased risk for PsA included tumor necrosis factor, V-type proton ATPase subunit G 2, receptor-type tyrosine protein phosphatase F, and septin-8.

Study details: This two-sample Mendelian randomization analysis included the data of 3537 patients with PsA and 262,844 control individuals without PsA from the FinnGen study and the data of 1837 unique plasma proteins from a genome-wide association study within the UK Biobank Pharma Proteomics Project.

Disclosures: This study was supported by the Natural Science Foundation of Guangxi Province and the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Zhao H, Zhou Y, Wang Z, Zhang X, Chen L, Hong Z. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 15:1417564 (July 3). Doi: 10.3389/fimmu.2024.1417564 Source

Key clinical point: Levels of certain proteins found in the blood plasma affected the risk for development of psoriatic arthritis (PsA) and could serve as potential therapeutic targets for the condition.

Major finding: Apolipoprotein F increased the risk for PsA by 60% (odds ratio [OR] 1.69; P_FDR < .001), whereas interleukin-10 reduced the risk for PsA by 40% (OR 0.60; P_FDR = .034). Other proteins associated with an increased risk for PsA included tumor necrosis factor, V-type proton ATPase subunit G 2, receptor-type tyrosine protein phosphatase F, and septin-8.

Study details: This two-sample Mendelian randomization analysis included the data of 3537 patients with PsA and 262,844 control individuals without PsA from the FinnGen study and the data of 1837 unique plasma proteins from a genome-wide association study within the UK Biobank Pharma Proteomics Project.

Disclosures: This study was supported by the Natural Science Foundation of Guangxi Province and the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Zhao H, Zhou Y, Wang Z, Zhang X, Chen L, Hong Z. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 15:1417564 (July 3). Doi: 10.3389/fimmu.2024.1417564 Source

Key clinical point: Levels of certain proteins found in the blood plasma affected the risk for development of psoriatic arthritis (PsA) and could serve as potential therapeutic targets for the condition.

Major finding: Apolipoprotein F increased the risk for PsA by 60% (odds ratio [OR] 1.69; P_FDR < .001), whereas interleukin-10 reduced the risk for PsA by 40% (OR 0.60; P_FDR = .034). Other proteins associated with an increased risk for PsA included tumor necrosis factor, V-type proton ATPase subunit G 2, receptor-type tyrosine protein phosphatase F, and septin-8.

Study details: This two-sample Mendelian randomization analysis included the data of 3537 patients with PsA and 262,844 control individuals without PsA from the FinnGen study and the data of 1837 unique plasma proteins from a genome-wide association study within the UK Biobank Pharma Proteomics Project.

Disclosures: This study was supported by the Natural Science Foundation of Guangxi Province and the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Zhao H, Zhou Y, Wang Z, Zhang X, Chen L, Hong Z. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 15:1417564 (July 3). Doi: 10.3389/fimmu.2024.1417564 Source

Key clinical point: The presence of type 2 diabetes (T2D) and smoking history increased the risk for psoriatic arthritis (PsA) in patients with psoriasis; however, T2D seemed to have a greater impact than smoking history in increasing incidence rate of PsA.

Major finding: The risk for PsA was significantly higher in patients with psoriasis who did vs did not have T2D (hazard ratio [HR] 1.11; 95% CI 1.03-1.20) and in those with vs without smoking history (HR 1.11; 95% CI 1.06-1.17). However, the risk was not significant in patients with psoriasis and T2D with vs without smoking history (HR 1.05; 95% CI 0.92-1.20).

Study details: This retrospective cohort study included patients with psoriasis with or without T2D (n = 42,315 each), those with or without smoking history (n = 74,046 each), and those with T2D with or without smoking history (n = 13,065 each).

Disclosures: This study was funded by the Chung Shan Medical University Hospital research project. The authors declared no conflicts of interest.

Source: Huo A-P, Liao P-L, Leong P-Y, Wei JC-C. From psoriasis to psoriatic arthritis: Epidemiological insights from a retrospective cohort study of 74,046 patients. Front Med. 2024;11:1419722 (June 26). Doi: 10.3389/fmed.2024.1419722 Source

Key clinical point: The presence of type 2 diabetes (T2D) and smoking history increased the risk for psoriatic arthritis (PsA) in patients with psoriasis; however, T2D seemed to have a greater impact than smoking history in increasing incidence rate of PsA.

Major finding: The risk for PsA was significantly higher in patients with psoriasis who did vs did not have T2D (hazard ratio [HR] 1.11; 95% CI 1.03-1.20) and in those with vs without smoking history (HR 1.11; 95% CI 1.06-1.17). However, the risk was not significant in patients with psoriasis and T2D with vs without smoking history (HR 1.05; 95% CI 0.92-1.20).

Study details: This retrospective cohort study included patients with psoriasis with or without T2D (n = 42,315 each), those with or without smoking history (n = 74,046 each), and those with T2D with or without smoking history (n = 13,065 each).

Disclosures: This study was funded by the Chung Shan Medical University Hospital research project. The authors declared no conflicts of interest.

Source: Huo A-P, Liao P-L, Leong P-Y, Wei JC-C. From psoriasis to psoriatic arthritis: Epidemiological insights from a retrospective cohort study of 74,046 patients. Front Med. 2024;11:1419722 (June 26). Doi: 10.3389/fmed.2024.1419722 Source

Key clinical point: The presence of type 2 diabetes (T2D) and smoking history increased the risk for psoriatic arthritis (PsA) in patients with psoriasis; however, T2D seemed to have a greater impact than smoking history in increasing incidence rate of PsA.

Major finding: The risk for PsA was significantly higher in patients with psoriasis who did vs did not have T2D (hazard ratio [HR] 1.11; 95% CI 1.03-1.20) and in those with vs without smoking history (HR 1.11; 95% CI 1.06-1.17). However, the risk was not significant in patients with psoriasis and T2D with vs without smoking history (HR 1.05; 95% CI 0.92-1.20).

Study details: This retrospective cohort study included patients with psoriasis with or without T2D (n = 42,315 each), those with or without smoking history (n = 74,046 each), and those with T2D with or without smoking history (n = 13,065 each).

Disclosures: This study was funded by the Chung Shan Medical University Hospital research project. The authors declared no conflicts of interest.

Source: Huo A-P, Liao P-L, Leong P-Y, Wei JC-C. From psoriasis to psoriatic arthritis: Epidemiological insights from a retrospective cohort study of 74,046 patients. Front Med. 2024;11:1419722 (June 26). Doi: 10.3389/fmed.2024.1419722 Source

Key clinical point: In individuals with vs without psoriatic arthritis (PsA), periodontitis was highly prevalent and negatively affected oral Health-Related Quality of Life (HRQOL).

Major finding: Individuals with vs without PsA were 2.67 times more likely to develop periodontitis (prevalence 57.0% vs 33.1%; odds ratio 2.67; P < .001), which was significantly associated with worsened oral HRQOL (odds ratio 1.92; P < .001). The mean Oral Impacts on Daily Performance scores, indicative of oral HRQOL, were also higher in individuals with vs without PsA (P < .001).

Study details: This case-control study included 86 individuals with PsA, 210 individuals with psoriasis, and 359 control individuals without psoriasis, all age 35-65 years and having ≥ 14 teeth.

Disclosures: This study was supported by the National Council for Scientific and Technological Development - CNPq, Brazil. The authors declared no conflicts of interest.

Source: Costa AA, Cota LOM, Esteves Lima RP, et al. The association between periodontitis and the impact of oral health on the quality of life of individuals with psoriasis and psoriatic arthritis. PLoS One. 2024;19(6):e0301158 (June 25). Doi: 10.1371/journal.pone.0301158 Source

Key clinical point: In individuals with vs without psoriatic arthritis (PsA), periodontitis was highly prevalent and negatively affected oral Health-Related Quality of Life (HRQOL).

Major finding: Individuals with vs without PsA were 2.67 times more likely to develop periodontitis (prevalence 57.0% vs 33.1%; odds ratio 2.67; P < .001), which was significantly associated with worsened oral HRQOL (odds ratio 1.92; P < .001). The mean Oral Impacts on Daily Performance scores, indicative of oral HRQOL, were also higher in individuals with vs without PsA (P < .001).

Study details: This case-control study included 86 individuals with PsA, 210 individuals with psoriasis, and 359 control individuals without psoriasis, all age 35-65 years and having ≥ 14 teeth.

Disclosures: This study was supported by the National Council for Scientific and Technological Development - CNPq, Brazil. The authors declared no conflicts of interest.

Source: Costa AA, Cota LOM, Esteves Lima RP, et al. The association between periodontitis and the impact of oral health on the quality of life of individuals with psoriasis and psoriatic arthritis. PLoS One. 2024;19(6):e0301158 (June 25). Doi: 10.1371/journal.pone.0301158 Source

Key clinical point: In individuals with vs without psoriatic arthritis (PsA), periodontitis was highly prevalent and negatively affected oral Health-Related Quality of Life (HRQOL).

Major finding: Individuals with vs without PsA were 2.67 times more likely to develop periodontitis (prevalence 57.0% vs 33.1%; odds ratio 2.67; P < .001), which was significantly associated with worsened oral HRQOL (odds ratio 1.92; P < .001). The mean Oral Impacts on Daily Performance scores, indicative of oral HRQOL, were also higher in individuals with vs without PsA (P < .001).

Study details: This case-control study included 86 individuals with PsA, 210 individuals with psoriasis, and 359 control individuals without psoriasis, all age 35-65 years and having ≥ 14 teeth.

Disclosures: This study was supported by the National Council for Scientific and Technological Development - CNPq, Brazil. The authors declared no conflicts of interest.

Source: Costa AA, Cota LOM, Esteves Lima RP, et al. The association between periodontitis and the impact of oral health on the quality of life of individuals with psoriasis and psoriatic arthritis. PLoS One. 2024;19(6):e0301158 (June 25). Doi: 10.1371/journal.pone.0301158 Source

Key clinical point: Around 25% patients with psoriatic arthritis (PsA) had a sedentary lifestyle (< 90 min of physical activity per week), with lack of physical activity associated with pain, worsened clinical activity, functionality, and disease impact.

Major finding: Overall, 25.9% of patients had a sedentary lifestyle. Patients with a sedentary vs non-sedentary lifestyle had more enthesitis, fatigue, higher disease activity, greater disease impact, and lower functionality (all P < .05). Sedentary lifestyle was also associated with increased risk for pain (odds ratio 1.5; P < .001).

Study details: This cross-sectional study included 232 patients with PsA aged 18-69 years with no radiographic damage or respiratory or cardiac diseases that limit physical activity.

Disclosures: This study did not receive any financial support. The authors declared no conflicts of interest. During the review, the reviewer declared a shared affiliation, with no collaboration, of the lead author to the handling editor.

Source: Toledano E, Chacón CC, Compán O, et al. Analysis of physical activity in psoriatic arthritis: Relationship with clinical and analytical parameters and comorbidity—description of the sedentary patient. Front Med. 2024;11:1385842 (June 23). Doi: 10.3389/fmed.2024.1385842 Source

Key clinical point: Around 25% patients with psoriatic arthritis (PsA) had a sedentary lifestyle (< 90 min of physical activity per week), with lack of physical activity associated with pain, worsened clinical activity, functionality, and disease impact.

Major finding: Overall, 25.9% of patients had a sedentary lifestyle. Patients with a sedentary vs non-sedentary lifestyle had more enthesitis, fatigue, higher disease activity, greater disease impact, and lower functionality (all P < .05). Sedentary lifestyle was also associated with increased risk for pain (odds ratio 1.5; P < .001).

Study details: This cross-sectional study included 232 patients with PsA aged 18-69 years with no radiographic damage or respiratory or cardiac diseases that limit physical activity.

Disclosures: This study did not receive any financial support. The authors declared no conflicts of interest. During the review, the reviewer declared a shared affiliation, with no collaboration, of the lead author to the handling editor.

Source: Toledano E, Chacón CC, Compán O, et al. Analysis of physical activity in psoriatic arthritis: Relationship with clinical and analytical parameters and comorbidity—description of the sedentary patient. Front Med. 2024;11:1385842 (June 23). Doi: 10.3389/fmed.2024.1385842 Source

Key clinical point: Around 25% patients with psoriatic arthritis (PsA) had a sedentary lifestyle (< 90 min of physical activity per week), with lack of physical activity associated with pain, worsened clinical activity, functionality, and disease impact.

Major finding: Overall, 25.9% of patients had a sedentary lifestyle. Patients with a sedentary vs non-sedentary lifestyle had more enthesitis, fatigue, higher disease activity, greater disease impact, and lower functionality (all P < .05). Sedentary lifestyle was also associated with increased risk for pain (odds ratio 1.5; P < .001).

Study details: This cross-sectional study included 232 patients with PsA aged 18-69 years with no radiographic damage or respiratory or cardiac diseases that limit physical activity.

Disclosures: This study did not receive any financial support. The authors declared no conflicts of interest. During the review, the reviewer declared a shared affiliation, with no collaboration, of the lead author to the handling editor.

Source: Toledano E, Chacón CC, Compán O, et al. Analysis of physical activity in psoriatic arthritis: Relationship with clinical and analytical parameters and comorbidity—description of the sedentary patient. Front Med. 2024;11:1385842 (June 23). Doi: 10.3389/fmed.2024.1385842 Source

Key clinical point: A genetic variant of the IL-13 gene that was designed to mimic the therapeutic effects of interleukin-13 (IL-13) inhibition was associated with an increased risk for psoriatic arthritis (PsA).

Major finding: IL-13 inhibition, genetically mimicked using an IL-13 gene variant was associated with an increased risk for PsA (odds ratio 37.39; P = 1.64×10^-9).

Study details: This two-sample Mendelian randomization study analyzed the data of 563,946 individuals with exposure to IL-13 inhibition while the genetic outcomes were assessed in 3609 patients with PsA and 9192 control individuals without PsA.

Disclosures: This study was supported by the National Institute for Health Research Manchester Biomedical Research Centre, UK. Three authors declared receiving grants, consulting fees, speaker fees, honoraria, or travel support from various sources unrelated to this study. Other authors declared no conflicts of interest.

Source: Zhao SS, Hyrich K, Yiu Z, et al. Genetically proxied IL-13 inhibition is associated with risk of psoriatic disease: Mendelian randomization study. Arthritis Rheumatol. 2024 (July 8). Doi: 10.1002/art.42942 Source

Key clinical point: A genetic variant of the IL-13 gene that was designed to mimic the therapeutic effects of interleukin-13 (IL-13) inhibition was associated with an increased risk for psoriatic arthritis (PsA).

Major finding: IL-13 inhibition, genetically mimicked using an IL-13 gene variant was associated with an increased risk for PsA (odds ratio 37.39; P = 1.64×10^-9).

Study details: This two-sample Mendelian randomization study analyzed the data of 563,946 individuals with exposure to IL-13 inhibition while the genetic outcomes were assessed in 3609 patients with PsA and 9192 control individuals without PsA.

Disclosures: This study was supported by the National Institute for Health Research Manchester Biomedical Research Centre, UK. Three authors declared receiving grants, consulting fees, speaker fees, honoraria, or travel support from various sources unrelated to this study. Other authors declared no conflicts of interest.

Source: Zhao SS, Hyrich K, Yiu Z, et al. Genetically proxied IL-13 inhibition is associated with risk of psoriatic disease: Mendelian randomization study. Arthritis Rheumatol. 2024 (July 8). Doi: 10.1002/art.42942 Source

Key clinical point: A genetic variant of the IL-13 gene that was designed to mimic the therapeutic effects of interleukin-13 (IL-13) inhibition was associated with an increased risk for psoriatic arthritis (PsA).

Major finding: IL-13 inhibition, genetically mimicked using an IL-13 gene variant was associated with an increased risk for PsA (odds ratio 37.39; P = 1.64×10^-9).

Study details: This two-sample Mendelian randomization study analyzed the data of 563,946 individuals with exposure to IL-13 inhibition while the genetic outcomes were assessed in 3609 patients with PsA and 9192 control individuals without PsA.

Disclosures: This study was supported by the National Institute for Health Research Manchester Biomedical Research Centre, UK. Three authors declared receiving grants, consulting fees, speaker fees, honoraria, or travel support from various sources unrelated to this study. Other authors declared no conflicts of interest.

Source: Zhao SS, Hyrich K, Yiu Z, et al. Genetically proxied IL-13 inhibition is associated with risk of psoriatic disease: Mendelian randomization study. Arthritis Rheumatol. 2024 (July 8). Doi: 10.1002/art.42942 Source

Key clinical point: Multimorbidity was present in nearly 50% of patients with psoriatic arthritis (PsA) and significantly affected the physical aspects of their quality of life.

Major finding: Multimorbidity was observed in 50.2% patients, with cardiovascular diseases being the most prevalent comorbidity. Patients with vs without multimorbidity had worsened scores for various 36-Item Short Form Health Survey domains, including bodily pain (34.7 vs 47.5; P < .01), physical functioning (52.1 vs 63.1; P < .01), and ability to perform roles due to physical health problems (28.5 vs 42.8; P < .01).

Study details: This cross-sectional observational study included 267 patients with PsA, age > 18 years.

Disclosures: This study was supported by a grant from the National Centre for Research and Development, Warsaw, Poland. The authors declared no conflicts of interest.

Source: Biedroń G, Wilk M, Nowakowski J, et al. Impact of comorbidities on patient-reported outcomes in psoriatic arthritis: A single centre cohort study. Rheumatol Int. Published online 2024;44:1435-1443. Doi: 10.1007/s00296-024-05632-2 Source

Key clinical point: Multimorbidity was present in nearly 50% of patients with psoriatic arthritis (PsA) and significantly affected the physical aspects of their quality of life.

Major finding: Multimorbidity was observed in 50.2% patients, with cardiovascular diseases being the most prevalent comorbidity. Patients with vs without multimorbidity had worsened scores for various 36-Item Short Form Health Survey domains, including bodily pain (34.7 vs 47.5; P < .01), physical functioning (52.1 vs 63.1; P < .01), and ability to perform roles due to physical health problems (28.5 vs 42.8; P < .01).

Study details: This cross-sectional observational study included 267 patients with PsA, age > 18 years.

Disclosures: This study was supported by a grant from the National Centre for Research and Development, Warsaw, Poland. The authors declared no conflicts of interest.

Source: Biedroń G, Wilk M, Nowakowski J, et al. Impact of comorbidities on patient-reported outcomes in psoriatic arthritis: A single centre cohort study. Rheumatol Int. Published online 2024;44:1435-1443. Doi: 10.1007/s00296-024-05632-2 Source

Key clinical point: Multimorbidity was present in nearly 50% of patients with psoriatic arthritis (PsA) and significantly affected the physical aspects of their quality of life.

Major finding: Multimorbidity was observed in 50.2% patients, with cardiovascular diseases being the most prevalent comorbidity. Patients with vs without multimorbidity had worsened scores for various 36-Item Short Form Health Survey domains, including bodily pain (34.7 vs 47.5; P < .01), physical functioning (52.1 vs 63.1; P < .01), and ability to perform roles due to physical health problems (28.5 vs 42.8; P < .01).

Study details: This cross-sectional observational study included 267 patients with PsA, age > 18 years.

Disclosures: This study was supported by a grant from the National Centre for Research and Development, Warsaw, Poland. The authors declared no conflicts of interest.

Source: Biedroń G, Wilk M, Nowakowski J, et al. Impact of comorbidities on patient-reported outcomes in psoriatic arthritis: A single centre cohort study. Rheumatol Int. Published online 2024;44:1435-1443. Doi: 10.1007/s00296-024-05632-2 Source

Key clinical point: The onset rate of psoriatic arthritis (PsA) in patients with psoriasis was lower with biologics than with methotrexate, with topical therapy being associated with the lowest rate.

Major finding: Treatment with biologics vs methotrexate significantly reduced the risk of developing PsA (adjusted hazard ratio [aHR] 0.46; 95% CI 0.35-0.62); however, biologics were associated with an increased risk of developing PsA when compared to topical therapy (aHR 2.16; 95% CI 1.44-3.24). Prior exposure to at least two biologics (odds ratio [OR] 6.09; P < .001) or methotrexate (OR 1.88; P = .026) was tied to increased PsA risk.

Study details: This retrospective cohort study included 58,671 patients with psoriasis treated with biologics, methotrexate, phototherapy, or topical therapy; patients who received phototherapy or topical therapy did not undergo any prior systemic treatment.

Disclosures: This study was supported by an educational grant from Janssen Pharmaceuticals. Alen Zabotti declared being an editorial board member of Rheumatology and Therapy. The other authors declared no conflicts of interest.

Source: Watad A, Zabotti A, Patt YS, et al. From psoriasis to psoriatic arthritis: Decoding the impact of treatment modalities on the prevention of psoriatic arthritis. Rheumatol Ther. 2024;11:963-976 (June 7). Doi: 10.1007/s40744-024-00680-3 Source

Key clinical point: The onset rate of psoriatic arthritis (PsA) in patients with psoriasis was lower with biologics than with methotrexate, with topical therapy being associated with the lowest rate.

Major finding: Treatment with biologics vs methotrexate significantly reduced the risk of developing PsA (adjusted hazard ratio [aHR] 0.46; 95% CI 0.35-0.62); however, biologics were associated with an increased risk of developing PsA when compared to topical therapy (aHR 2.16; 95% CI 1.44-3.24). Prior exposure to at least two biologics (odds ratio [OR] 6.09; P < .001) or methotrexate (OR 1.88; P = .026) was tied to increased PsA risk.

Study details: This retrospective cohort study included 58,671 patients with psoriasis treated with biologics, methotrexate, phototherapy, or topical therapy; patients who received phototherapy or topical therapy did not undergo any prior systemic treatment.

Disclosures: This study was supported by an educational grant from Janssen Pharmaceuticals. Alen Zabotti declared being an editorial board member of Rheumatology and Therapy. The other authors declared no conflicts of interest.

Source: Watad A, Zabotti A, Patt YS, et al. From psoriasis to psoriatic arthritis: Decoding the impact of treatment modalities on the prevention of psoriatic arthritis. Rheumatol Ther. 2024;11:963-976 (June 7). Doi: 10.1007/s40744-024-00680-3 Source

Key clinical point: The onset rate of psoriatic arthritis (PsA) in patients with psoriasis was lower with biologics than with methotrexate, with topical therapy being associated with the lowest rate.

Major finding: Treatment with biologics vs methotrexate significantly reduced the risk of developing PsA (adjusted hazard ratio [aHR] 0.46; 95% CI 0.35-0.62); however, biologics were associated with an increased risk of developing PsA when compared to topical therapy (aHR 2.16; 95% CI 1.44-3.24). Prior exposure to at least two biologics (odds ratio [OR] 6.09; P < .001) or methotrexate (OR 1.88; P = .026) was tied to increased PsA risk.

Study details: This retrospective cohort study included 58,671 patients with psoriasis treated with biologics, methotrexate, phototherapy, or topical therapy; patients who received phototherapy or topical therapy did not undergo any prior systemic treatment.

Disclosures: This study was supported by an educational grant from Janssen Pharmaceuticals. Alen Zabotti declared being an editorial board member of Rheumatology and Therapy. The other authors declared no conflicts of interest.

Source: Watad A, Zabotti A, Patt YS, et al. From psoriasis to psoriatic arthritis: Decoding the impact of treatment modalities on the prevention of psoriatic arthritis. Rheumatol Ther. 2024;11:963-976 (June 7). Doi: 10.1007/s40744-024-00680-3 Source

Key clinical point: Patients with psoriatic arthritis (PsA) who did vs did not have Achilles tendon (AT) pain reported severe functional impairment and disability.

Major finding: Patients with PsA with vs without AT pain had significantly greater AT-related morning stiffness (90.9% vs 9.1%; P < .001), impaired AT function (median heel raise repetition rate 0.72 vs 1.24; P = .005), worse Psoriatic Arthritis Impact of Disease questionnaire score (mean 5.52 vs 3.38; P = .018), and pain on passive dorsiflexion (36.4% vs 0%; P = .011) and resisted plantarflexion (45.5% vs 0%; P = .003).

Study details: This cross-sectional, observational study included 22 patients with PsA with (n = 11) and without (n = 11) self-reported AT pain and 11 healthy individuals without PsA or AT pain.

Disclosures: This study was funded by a Glasgow (UK) Caledonian University-funded PhD studentship. The authors declared no conflicts of interest.

Source: Patience A, Steultjens M, Siebert S, Hendry G. Significant functional impairment and disability in individuals with psoriatic arthritis and Achilles tendon pain: A cross-sectional observational study. Rheumatol Int. 2024;44:1469-1479 (June 8). Doi: 10.1007/s00296-024-05629-x Source

Key clinical point: Patients with psoriatic arthritis (PsA) who did vs did not have Achilles tendon (AT) pain reported severe functional impairment and disability.

Major finding: Patients with PsA with vs without AT pain had significantly greater AT-related morning stiffness (90.9% vs 9.1%; P < .001), impaired AT function (median heel raise repetition rate 0.72 vs 1.24; P = .005), worse Psoriatic Arthritis Impact of Disease questionnaire score (mean 5.52 vs 3.38; P = .018), and pain on passive dorsiflexion (36.4% vs 0%; P = .011) and resisted plantarflexion (45.5% vs 0%; P = .003).

Study details: This cross-sectional, observational study included 22 patients with PsA with (n = 11) and without (n = 11) self-reported AT pain and 11 healthy individuals without PsA or AT pain.

Disclosures: This study was funded by a Glasgow (UK) Caledonian University-funded PhD studentship. The authors declared no conflicts of interest.

Source: Patience A, Steultjens M, Siebert S, Hendry G. Significant functional impairment and disability in individuals with psoriatic arthritis and Achilles tendon pain: A cross-sectional observational study. Rheumatol Int. 2024;44:1469-1479 (June 8). Doi: 10.1007/s00296-024-05629-x Source

Key clinical point: Patients with psoriatic arthritis (PsA) who did vs did not have Achilles tendon (AT) pain reported severe functional impairment and disability.

Major finding: Patients with PsA with vs without AT pain had significantly greater AT-related morning stiffness (90.9% vs 9.1%; P < .001), impaired AT function (median heel raise repetition rate 0.72 vs 1.24; P = .005), worse Psoriatic Arthritis Impact of Disease questionnaire score (mean 5.52 vs 3.38; P = .018), and pain on passive dorsiflexion (36.4% vs 0%; P = .011) and resisted plantarflexion (45.5% vs 0%; P = .003).

Study details: This cross-sectional, observational study included 22 patients with PsA with (n = 11) and without (n = 11) self-reported AT pain and 11 healthy individuals without PsA or AT pain.

Disclosures: This study was funded by a Glasgow (UK) Caledonian University-funded PhD studentship. The authors declared no conflicts of interest.

Source: Patience A, Steultjens M, Siebert S, Hendry G. Significant functional impairment and disability in individuals with psoriatic arthritis and Achilles tendon pain: A cross-sectional observational study. Rheumatol Int. 2024;44:1469-1479 (June 8). Doi: 10.1007/s00296-024-05629-x Source