Psoriatic Arthritis ICYMI

With the growing number of treatment options for psoriatic arthritis (PsA), therapeutic decision-making has shifted to an increasingly tailored and patient-centered approach. A number of factors contribute to the treatment decision-making process, including age, insurance restrictions, route of administration, side effect profile, comorbidities, and extra-articular manifestations of the disease. In this article, we discuss an extra-articular comorbidity, uveitis, which is frequently seen in patients with PsA. We discuss clinical characteristics of uveitis associated with PsA and describe how the presence of uveitis influences our treatment approach to PsA, based on existing data.

Uveitis refers broadly to inflammation of the uvea, the vascularized and pigmented layer of the eye composed of the iris, the ciliary body, and the choroid. While infection is a common cause of uveitis, many cases are noninfectious and are often associated with an underlying autoimmune or systemic inflammatory disorder. Uveitis is frequently reported in diseases in the spondyloarthritis (SpA) family, including axial spondyloarthritis (AxSpA) and reactive arthritis, as well as PsA. Exact estimates of the prevalence of uveitis in PsA vary widely from 7%-25%, depending on the particular cohort studied.^1,2 In all forms of SpA, the anterior chamber of the uvea is the most likely to be affected.³ However, compared to patients with AxSpA, patients with PsA appear to have a higher rate of posterior involvement. In addition, patients with PsA appear to have higher frequencies of insidious, bilateral uveitis, as compared to the acute, unilateral, anterior uveitis that is most characteristic of AxSpA.⁴ Women with PsA may be more likely than men to experience uveitis, although this has not been a consistent finding.⁵ 

Patients with PsA who are human leukocyte antigen B27 (HLA-B27) positive may be at risk for more severe and refractory anterior uveitis compared to those who do not express the allele.⁵ Those who are HLA-B27 positive are also known to have higher rates of axial involvement. It has therefore been postulated that 2 phenotypes of uveitis may exist in PsA: patients who are HLA-B27 positive who have axial disease and severe, unilateral anterior uveitis reminiscent of other forms of SpA, and patients who are HLA-B27 negative, often women, with peripheral-predominant arthritis who are prone to the classic anterior uveitis but may also develop atypical bilateral, insidious, and/or posterior involvement.⁴ Specific characteristics of PsA may also provide information about the risk for developing uveitis. For example, dactylitis has been linked to a higher risk of developing uveitis in some, but not all, cohorts of patients with PsA, and the risk of uveitis in PsA has been found in many studies to correlate with longer duration of disease.^6-8

The presence of uveitis signals a disruption in the blood-retina barrier and the subsequent entrance of inflammatory cells into the eye. An entire explanation of pathogenesis is beyond the scope of this article; however, it is worth noting that many of the inflammatory mediators of active uveitis mirror those of PsA. For instance, both the mesenchymal cells in enthesitis and the cells of the ciliary body express receptors for interleukin (IL)-23, suggesting a potential role of the signaling pathways involving this cytokine in both diseases.⁹ Another study found increased serum levels of IL-17, a known mediator of PsA disease, in patients with active uveitis.¹⁰ Despite these common pathogenesis links, there are limited data on the utility of certain existing PsA treatments on uveitis manifestations.

Our approach is always to manage uveitis associated with PsA in collaboration with a specialized and experienced ophthalmologist. Uncontrolled uveitis can be vision threatening and contribute to long-term morbidity associated with PsA, so timely recognition, evaluation, and appropriate treatment are important. Ocular glucocorticoid (GC) drops may be used as first-line therapy, particularly for anterior uveitis, to quickly quell inflammation. Escalation to systemic GCs for more severe or posteriorly localized disease may be considered carefully, given the known risk of worsening skin psoriasis (PsO) with GC withdrawal after a course of therapy. Use of GC-sparing therapy should be determined on a case-by-case basis. While generalized, noninfectious uveitis often resolves with GC treatment, the risk of uveitis recurrence in patients with PsA and the challenges of systemic GCs with PsO lead us to frequently consider GC-sparing therapy that addresses ocular, musculoskeletal, and cutaneous manifestations. Tumor necrosis factor inhibitors (TNF-I) are our typical first-line considerations for GC-sparing therapy in patients with PsA with inflammatory joint symptoms and uveitis, although nonbiologic therapy can be considered first-line therapy in select populations.

Data establishing the efficacy of TNF-I come largely from randomized controlled trials (RCTs) of adalimumab (ADA) compared to placebo in noninfectious uveitis.¹¹ While these trials focused on idiopathic posterior or pan-uveitis, these data have been extrapolated to SpA-associated anterior uveitis, and large registry analyses have supported use of TNF-I in this population.¹² When selecting a particular TNF-I in a patient with current or past uveitis, we frequently start with ADA, based on supportive, albeit uncontrolled, data suggesting a reduction in the risk of recurrence with this agent in patients with SpA and uveitis.¹² For patients who are unable to tolerate subcutaneous injections, who fail ADA, or who we suspect will require higher, titratable dosing, we favor infliximab infusions. Other data suggest that golimumab and certolizumab are also reasonable alternatives.^13,14 We do not generally use etanercept, as the limited data that are available suggest that it is less effective at reducing risk of uveitis recurrence.¹² Methotrexate or leflunomide may be an appropriate first line choice for patients with peripheral-predominant PsA and uveitis, but it is important to note that these agents are not effective for axial disease.

Despite the mechanistic data implicating the role of IL-17 in uveitis associated with PsA, the IL-17A inhibitor, secukinumab, failed to show a reduction in uveitis recurrence, compared to placebo, in pooled analysis of RCTs of noninfectious uveitis.¹⁵ However, a phase 2 trial of intravenous secukinumab in noninfectious uveitis showed promise, possibly because this dosing regimen can achieve higher effective concentrations.¹⁶ It is not our current practice to use secukinumab or ixekizumab as a first-line therapy in patients with PsA and concurrent uveitis, owing to a lack of data supporting efficacy. A novel IL-17A/F inhibitor, bimekizumab (BKZ), has recently been used in several successful phase 3 trials in patients with both TNF-naïve and TNF-nonresponder SpA, including AxSpA and PsA.¹⁷ Interestingly, data from the phase 2 and 3 trials of BKZ found low incidence rates of uveitis in patients with SpA treated with BKZ compared to placebo, suggesting that BKZ might be more effective in uveitis than other IL-17 inhibitors, but these data need to be confirmed.

Successful use of Janus kinase (JAK) inhibitors in noninfectious uveitis, including cases associated with inflammatory arthritis, has been described in case reports as well as in current phase 2 trials.¹⁸ The dual IL-12/IL-23 inhibitor, ustekinumab, also showed initial promise in a small, nonrandomized, uncontrolled phase 1/2 study of the treatment of posterior uveitis, as well as success in few case reports of PsA-associated uveitis.¹⁹ However, a post-hoc analysis of extra-intestinal manifestations, including uveitis and iritis, in patients with inflammatory bowel disease treated with ustekinumab found no benefit in preventing or treating ocular disease compared to placebo.²⁰ Given the paucity of available data, JAK inhibitors and the IL-12/IL-23 inhibitor, ustekinumab, are not part of our typical treatment algorithm for patients with PsA-associated uveitis.

In conclusion, uveitis is a frequent extra-articular comorbidity of PsA, and it may present differently than the typical acute onset, unilateral anterior uveitis seen in SpA. While uveitis may share many different immunologic threads with PsA, the most convincing data support the use of TNF-I as a GC-sparing agent in this setting, particularly ADA, infliximab, golimumab, or certolizumab. Our approach is generally to start with these agents or methotrexate when directed therapy is needed for uveitis in PsA. Further investigation into the use of the IL-17A/F inhibitor BKZ and JAK inhibitors, as well as tyrosine kinase 2 inhibitors, in PsA associated uveitis may yield additional options for our patients.²¹

With the growing number of treatment options for psoriatic arthritis (PsA), therapeutic decision-making has shifted to an increasingly tailored and patient-centered approach. A number of factors contribute to the treatment decision-making process, including age, insurance restrictions, route of administration, side effect profile, comorbidities, and extra-articular manifestations of the disease. In this article, we discuss an extra-articular comorbidity, uveitis, which is frequently seen in patients with PsA. We discuss clinical characteristics of uveitis associated with PsA and describe how the presence of uveitis influences our treatment approach to PsA, based on existing data.

Uveitis refers broadly to inflammation of the uvea, the vascularized and pigmented layer of the eye composed of the iris, the ciliary body, and the choroid. While infection is a common cause of uveitis, many cases are noninfectious and are often associated with an underlying autoimmune or systemic inflammatory disorder. Uveitis is frequently reported in diseases in the spondyloarthritis (SpA) family, including axial spondyloarthritis (AxSpA) and reactive arthritis, as well as PsA. Exact estimates of the prevalence of uveitis in PsA vary widely from 7%-25%, depending on the particular cohort studied.^1,2 In all forms of SpA, the anterior chamber of the uvea is the most likely to be affected.³ However, compared to patients with AxSpA, patients with PsA appear to have a higher rate of posterior involvement. In addition, patients with PsA appear to have higher frequencies of insidious, bilateral uveitis, as compared to the acute, unilateral, anterior uveitis that is most characteristic of AxSpA.⁴ Women with PsA may be more likely than men to experience uveitis, although this has not been a consistent finding.⁵ 

Patients with PsA who are human leukocyte antigen B27 (HLA-B27) positive may be at risk for more severe and refractory anterior uveitis compared to those who do not express the allele.⁵ Those who are HLA-B27 positive are also known to have higher rates of axial involvement. It has therefore been postulated that 2 phenotypes of uveitis may exist in PsA: patients who are HLA-B27 positive who have axial disease and severe, unilateral anterior uveitis reminiscent of other forms of SpA, and patients who are HLA-B27 negative, often women, with peripheral-predominant arthritis who are prone to the classic anterior uveitis but may also develop atypical bilateral, insidious, and/or posterior involvement.⁴ Specific characteristics of PsA may also provide information about the risk for developing uveitis. For example, dactylitis has been linked to a higher risk of developing uveitis in some, but not all, cohorts of patients with PsA, and the risk of uveitis in PsA has been found in many studies to correlate with longer duration of disease.^6-8

The presence of uveitis signals a disruption in the blood-retina barrier and the subsequent entrance of inflammatory cells into the eye. An entire explanation of pathogenesis is beyond the scope of this article; however, it is worth noting that many of the inflammatory mediators of active uveitis mirror those of PsA. For instance, both the mesenchymal cells in enthesitis and the cells of the ciliary body express receptors for interleukin (IL)-23, suggesting a potential role of the signaling pathways involving this cytokine in both diseases.⁹ Another study found increased serum levels of IL-17, a known mediator of PsA disease, in patients with active uveitis.¹⁰ Despite these common pathogenesis links, there are limited data on the utility of certain existing PsA treatments on uveitis manifestations.

Our approach is always to manage uveitis associated with PsA in collaboration with a specialized and experienced ophthalmologist. Uncontrolled uveitis can be vision threatening and contribute to long-term morbidity associated with PsA, so timely recognition, evaluation, and appropriate treatment are important. Ocular glucocorticoid (GC) drops may be used as first-line therapy, particularly for anterior uveitis, to quickly quell inflammation. Escalation to systemic GCs for more severe or posteriorly localized disease may be considered carefully, given the known risk of worsening skin psoriasis (PsO) with GC withdrawal after a course of therapy. Use of GC-sparing therapy should be determined on a case-by-case basis. While generalized, noninfectious uveitis often resolves with GC treatment, the risk of uveitis recurrence in patients with PsA and the challenges of systemic GCs with PsO lead us to frequently consider GC-sparing therapy that addresses ocular, musculoskeletal, and cutaneous manifestations. Tumor necrosis factor inhibitors (TNF-I) are our typical first-line considerations for GC-sparing therapy in patients with PsA with inflammatory joint symptoms and uveitis, although nonbiologic therapy can be considered first-line therapy in select populations.

Data establishing the efficacy of TNF-I come largely from randomized controlled trials (RCTs) of adalimumab (ADA) compared to placebo in noninfectious uveitis.¹¹ While these trials focused on idiopathic posterior or pan-uveitis, these data have been extrapolated to SpA-associated anterior uveitis, and large registry analyses have supported use of TNF-I in this population.¹² When selecting a particular TNF-I in a patient with current or past uveitis, we frequently start with ADA, based on supportive, albeit uncontrolled, data suggesting a reduction in the risk of recurrence with this agent in patients with SpA and uveitis.¹² For patients who are unable to tolerate subcutaneous injections, who fail ADA, or who we suspect will require higher, titratable dosing, we favor infliximab infusions. Other data suggest that golimumab and certolizumab are also reasonable alternatives.^13,14 We do not generally use etanercept, as the limited data that are available suggest that it is less effective at reducing risk of uveitis recurrence.¹² Methotrexate or leflunomide may be an appropriate first line choice for patients with peripheral-predominant PsA and uveitis, but it is important to note that these agents are not effective for axial disease.

Despite the mechanistic data implicating the role of IL-17 in uveitis associated with PsA, the IL-17A inhibitor, secukinumab, failed to show a reduction in uveitis recurrence, compared to placebo, in pooled analysis of RCTs of noninfectious uveitis.¹⁵ However, a phase 2 trial of intravenous secukinumab in noninfectious uveitis showed promise, possibly because this dosing regimen can achieve higher effective concentrations.¹⁶ It is not our current practice to use secukinumab or ixekizumab as a first-line therapy in patients with PsA and concurrent uveitis, owing to a lack of data supporting efficacy. A novel IL-17A/F inhibitor, bimekizumab (BKZ), has recently been used in several successful phase 3 trials in patients with both TNF-naïve and TNF-nonresponder SpA, including AxSpA and PsA.¹⁷ Interestingly, data from the phase 2 and 3 trials of BKZ found low incidence rates of uveitis in patients with SpA treated with BKZ compared to placebo, suggesting that BKZ might be more effective in uveitis than other IL-17 inhibitors, but these data need to be confirmed.

Successful use of Janus kinase (JAK) inhibitors in noninfectious uveitis, including cases associated with inflammatory arthritis, has been described in case reports as well as in current phase 2 trials.¹⁸ The dual IL-12/IL-23 inhibitor, ustekinumab, also showed initial promise in a small, nonrandomized, uncontrolled phase 1/2 study of the treatment of posterior uveitis, as well as success in few case reports of PsA-associated uveitis.¹⁹ However, a post-hoc analysis of extra-intestinal manifestations, including uveitis and iritis, in patients with inflammatory bowel disease treated with ustekinumab found no benefit in preventing or treating ocular disease compared to placebo.²⁰ Given the paucity of available data, JAK inhibitors and the IL-12/IL-23 inhibitor, ustekinumab, are not part of our typical treatment algorithm for patients with PsA-associated uveitis.

In conclusion, uveitis is a frequent extra-articular comorbidity of PsA, and it may present differently than the typical acute onset, unilateral anterior uveitis seen in SpA. While uveitis may share many different immunologic threads with PsA, the most convincing data support the use of TNF-I as a GC-sparing agent in this setting, particularly ADA, infliximab, golimumab, or certolizumab. Our approach is generally to start with these agents or methotrexate when directed therapy is needed for uveitis in PsA. Further investigation into the use of the IL-17A/F inhibitor BKZ and JAK inhibitors, as well as tyrosine kinase 2 inhibitors, in PsA associated uveitis may yield additional options for our patients.²¹

With the growing number of treatment options for psoriatic arthritis (PsA), therapeutic decision-making has shifted to an increasingly tailored and patient-centered approach. A number of factors contribute to the treatment decision-making process, including age, insurance restrictions, route of administration, side effect profile, comorbidities, and extra-articular manifestations of the disease. In this article, we discuss an extra-articular comorbidity, uveitis, which is frequently seen in patients with PsA. We discuss clinical characteristics of uveitis associated with PsA and describe how the presence of uveitis influences our treatment approach to PsA, based on existing data.

Uveitis refers broadly to inflammation of the uvea, the vascularized and pigmented layer of the eye composed of the iris, the ciliary body, and the choroid. While infection is a common cause of uveitis, many cases are noninfectious and are often associated with an underlying autoimmune or systemic inflammatory disorder. Uveitis is frequently reported in diseases in the spondyloarthritis (SpA) family, including axial spondyloarthritis (AxSpA) and reactive arthritis, as well as PsA. Exact estimates of the prevalence of uveitis in PsA vary widely from 7%-25%, depending on the particular cohort studied.^1,2 In all forms of SpA, the anterior chamber of the uvea is the most likely to be affected.³ However, compared to patients with AxSpA, patients with PsA appear to have a higher rate of posterior involvement. In addition, patients with PsA appear to have higher frequencies of insidious, bilateral uveitis, as compared to the acute, unilateral, anterior uveitis that is most characteristic of AxSpA.⁴ Women with PsA may be more likely than men to experience uveitis, although this has not been a consistent finding.⁵ 

Patients with PsA who are human leukocyte antigen B27 (HLA-B27) positive may be at risk for more severe and refractory anterior uveitis compared to those who do not express the allele.⁵ Those who are HLA-B27 positive are also known to have higher rates of axial involvement. It has therefore been postulated that 2 phenotypes of uveitis may exist in PsA: patients who are HLA-B27 positive who have axial disease and severe, unilateral anterior uveitis reminiscent of other forms of SpA, and patients who are HLA-B27 negative, often women, with peripheral-predominant arthritis who are prone to the classic anterior uveitis but may also develop atypical bilateral, insidious, and/or posterior involvement.⁴ Specific characteristics of PsA may also provide information about the risk for developing uveitis. For example, dactylitis has been linked to a higher risk of developing uveitis in some, but not all, cohorts of patients with PsA, and the risk of uveitis in PsA has been found in many studies to correlate with longer duration of disease.^6-8

The presence of uveitis signals a disruption in the blood-retina barrier and the subsequent entrance of inflammatory cells into the eye. An entire explanation of pathogenesis is beyond the scope of this article; however, it is worth noting that many of the inflammatory mediators of active uveitis mirror those of PsA. For instance, both the mesenchymal cells in enthesitis and the cells of the ciliary body express receptors for interleukin (IL)-23, suggesting a potential role of the signaling pathways involving this cytokine in both diseases.⁹ Another study found increased serum levels of IL-17, a known mediator of PsA disease, in patients with active uveitis.¹⁰ Despite these common pathogenesis links, there are limited data on the utility of certain existing PsA treatments on uveitis manifestations.

Our approach is always to manage uveitis associated with PsA in collaboration with a specialized and experienced ophthalmologist. Uncontrolled uveitis can be vision threatening and contribute to long-term morbidity associated with PsA, so timely recognition, evaluation, and appropriate treatment are important. Ocular glucocorticoid (GC) drops may be used as first-line therapy, particularly for anterior uveitis, to quickly quell inflammation. Escalation to systemic GCs for more severe or posteriorly localized disease may be considered carefully, given the known risk of worsening skin psoriasis (PsO) with GC withdrawal after a course of therapy. Use of GC-sparing therapy should be determined on a case-by-case basis. While generalized, noninfectious uveitis often resolves with GC treatment, the risk of uveitis recurrence in patients with PsA and the challenges of systemic GCs with PsO lead us to frequently consider GC-sparing therapy that addresses ocular, musculoskeletal, and cutaneous manifestations. Tumor necrosis factor inhibitors (TNF-I) are our typical first-line considerations for GC-sparing therapy in patients with PsA with inflammatory joint symptoms and uveitis, although nonbiologic therapy can be considered first-line therapy in select populations.

Data establishing the efficacy of TNF-I come largely from randomized controlled trials (RCTs) of adalimumab (ADA) compared to placebo in noninfectious uveitis.¹¹ While these trials focused on idiopathic posterior or pan-uveitis, these data have been extrapolated to SpA-associated anterior uveitis, and large registry analyses have supported use of TNF-I in this population.¹² When selecting a particular TNF-I in a patient with current or past uveitis, we frequently start with ADA, based on supportive, albeit uncontrolled, data suggesting a reduction in the risk of recurrence with this agent in patients with SpA and uveitis.¹² For patients who are unable to tolerate subcutaneous injections, who fail ADA, or who we suspect will require higher, titratable dosing, we favor infliximab infusions. Other data suggest that golimumab and certolizumab are also reasonable alternatives.^13,14 We do not generally use etanercept, as the limited data that are available suggest that it is less effective at reducing risk of uveitis recurrence.¹² Methotrexate or leflunomide may be an appropriate first line choice for patients with peripheral-predominant PsA and uveitis, but it is important to note that these agents are not effective for axial disease.

Despite the mechanistic data implicating the role of IL-17 in uveitis associated with PsA, the IL-17A inhibitor, secukinumab, failed to show a reduction in uveitis recurrence, compared to placebo, in pooled analysis of RCTs of noninfectious uveitis.¹⁵ However, a phase 2 trial of intravenous secukinumab in noninfectious uveitis showed promise, possibly because this dosing regimen can achieve higher effective concentrations.¹⁶ It is not our current practice to use secukinumab or ixekizumab as a first-line therapy in patients with PsA and concurrent uveitis, owing to a lack of data supporting efficacy. A novel IL-17A/F inhibitor, bimekizumab (BKZ), has recently been used in several successful phase 3 trials in patients with both TNF-naïve and TNF-nonresponder SpA, including AxSpA and PsA.¹⁷ Interestingly, data from the phase 2 and 3 trials of BKZ found low incidence rates of uveitis in patients with SpA treated with BKZ compared to placebo, suggesting that BKZ might be more effective in uveitis than other IL-17 inhibitors, but these data need to be confirmed.

Successful use of Janus kinase (JAK) inhibitors in noninfectious uveitis, including cases associated with inflammatory arthritis, has been described in case reports as well as in current phase 2 trials.¹⁸ The dual IL-12/IL-23 inhibitor, ustekinumab, also showed initial promise in a small, nonrandomized, uncontrolled phase 1/2 study of the treatment of posterior uveitis, as well as success in few case reports of PsA-associated uveitis.¹⁹ However, a post-hoc analysis of extra-intestinal manifestations, including uveitis and iritis, in patients with inflammatory bowel disease treated with ustekinumab found no benefit in preventing or treating ocular disease compared to placebo.²⁰ Given the paucity of available data, JAK inhibitors and the IL-12/IL-23 inhibitor, ustekinumab, are not part of our typical treatment algorithm for patients with PsA-associated uveitis.

In conclusion, uveitis is a frequent extra-articular comorbidity of PsA, and it may present differently than the typical acute onset, unilateral anterior uveitis seen in SpA. While uveitis may share many different immunologic threads with PsA, the most convincing data support the use of TNF-I as a GC-sparing agent in this setting, particularly ADA, infliximab, golimumab, or certolizumab. Our approach is generally to start with these agents or methotrexate when directed therapy is needed for uveitis in PsA. Further investigation into the use of the IL-17A/F inhibitor BKZ and JAK inhibitors, as well as tyrosine kinase 2 inhibitors, in PsA associated uveitis may yield additional options for our patients.²¹

TOPLINE:

Patients with early psoriatic arthritis (PsA) were significantly more likely to have multiple comorbidities and cardiovascular risk factors than controls.

METHODOLOGY:

• The study population included 67 adults with early PsA and 61 healthy matched controls with mean ages of 47.9 years and 45 years, respectively.
• Early PsA was defined as symptom duration of less than 2 years; patients with conditions including active infection, malignancy, or other rheumatic or systemic disease were excluded.
• The researchers examined the prevalence of comorbidities and cardiovascular risk factors in treatment-naive, newly diagnosed patients with PsA at baseline and after 1 year.

TAKEAWAY:

• Adults with early PsA were significantly more likely to have two or more comorbidities and multiple cardiovascular risk factors at baseline, compared with healthy controls (odds ratios, 1.9 and 2.1, respectively).
• Dyslipidemia was the most prevalent comorbidity among patients with PsA and was more prevalent than in controls (64.2% vs. 39.3%; OR, 1.7).
• Obesity was more common in patients with PsA, compared with controls (40.3% vs. 18.3%, respectively), and more patients with PsA had cardiovascular disease at baseline than did controls (20.9% vs. 6.6%; OR, 3.2).
• Disease activity scores improved after 1 year, but the proportion of patients with comorbidities and CV risk factors remained stable.

IN PRACTICE:

The results support the early assessment of patients with PsA for comorbidities to inform treatment and suggest that comorbidities and CV risk factors are more than a consequence of long-term PsA and chronic systemic inflammation.

SOURCE:

The study was conducted by Alla Ishchenko, MD, and colleagues in the division of rheumatology at University Hospitals Leuven, Belgium. The study was published online in Arthritis Care & Research.

LIMITATIONS:

The study was exploratory in nature, with a short follow-up period and a relatively small sample size.

DISCLOSURES:

Dr. Ishchenko disclosed support from PARTNER, an international fellowship program to study disease mechanisms in psoriatic arthritis, as well as grants from Lilly and from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with early psoriatic arthritis (PsA) were significantly more likely to have multiple comorbidities and cardiovascular risk factors than controls.

METHODOLOGY:

• The study population included 67 adults with early PsA and 61 healthy matched controls with mean ages of 47.9 years and 45 years, respectively.
• Early PsA was defined as symptom duration of less than 2 years; patients with conditions including active infection, malignancy, or other rheumatic or systemic disease were excluded.
• The researchers examined the prevalence of comorbidities and cardiovascular risk factors in treatment-naive, newly diagnosed patients with PsA at baseline and after 1 year.

TAKEAWAY:

• Adults with early PsA were significantly more likely to have two or more comorbidities and multiple cardiovascular risk factors at baseline, compared with healthy controls (odds ratios, 1.9 and 2.1, respectively).
• Dyslipidemia was the most prevalent comorbidity among patients with PsA and was more prevalent than in controls (64.2% vs. 39.3%; OR, 1.7).
• Obesity was more common in patients with PsA, compared with controls (40.3% vs. 18.3%, respectively), and more patients with PsA had cardiovascular disease at baseline than did controls (20.9% vs. 6.6%; OR, 3.2).
• Disease activity scores improved after 1 year, but the proportion of patients with comorbidities and CV risk factors remained stable.

IN PRACTICE:

The results support the early assessment of patients with PsA for comorbidities to inform treatment and suggest that comorbidities and CV risk factors are more than a consequence of long-term PsA and chronic systemic inflammation.

SOURCE:

The study was conducted by Alla Ishchenko, MD, and colleagues in the division of rheumatology at University Hospitals Leuven, Belgium. The study was published online in Arthritis Care & Research.

LIMITATIONS:

The study was exploratory in nature, with a short follow-up period and a relatively small sample size.

DISCLOSURES:

Dr. Ishchenko disclosed support from PARTNER, an international fellowship program to study disease mechanisms in psoriatic arthritis, as well as grants from Lilly and from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with early psoriatic arthritis (PsA) were significantly more likely to have multiple comorbidities and cardiovascular risk factors than controls.

METHODOLOGY:

• The study population included 67 adults with early PsA and 61 healthy matched controls with mean ages of 47.9 years and 45 years, respectively.
• Early PsA was defined as symptom duration of less than 2 years; patients with conditions including active infection, malignancy, or other rheumatic or systemic disease were excluded.
• The researchers examined the prevalence of comorbidities and cardiovascular risk factors in treatment-naive, newly diagnosed patients with PsA at baseline and after 1 year.

TAKEAWAY:

• Adults with early PsA were significantly more likely to have two or more comorbidities and multiple cardiovascular risk factors at baseline, compared with healthy controls (odds ratios, 1.9 and 2.1, respectively).
• Dyslipidemia was the most prevalent comorbidity among patients with PsA and was more prevalent than in controls (64.2% vs. 39.3%; OR, 1.7).
• Obesity was more common in patients with PsA, compared with controls (40.3% vs. 18.3%, respectively), and more patients with PsA had cardiovascular disease at baseline than did controls (20.9% vs. 6.6%; OR, 3.2).
• Disease activity scores improved after 1 year, but the proportion of patients with comorbidities and CV risk factors remained stable.

IN PRACTICE:

The results support the early assessment of patients with PsA for comorbidities to inform treatment and suggest that comorbidities and CV risk factors are more than a consequence of long-term PsA and chronic systemic inflammation.

SOURCE:

The study was conducted by Alla Ishchenko, MD, and colleagues in the division of rheumatology at University Hospitals Leuven, Belgium. The study was published online in Arthritis Care & Research.

LIMITATIONS:

The study was exploratory in nature, with a short follow-up period and a relatively small sample size.

DISCLOSURES:

Dr. Ishchenko disclosed support from PARTNER, an international fellowship program to study disease mechanisms in psoriatic arthritis, as well as grants from Lilly and from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

A version of this article first appeared on Medscape.com.

In a new study, researchers report that they have found epigenetic methylation markers on 15 genes that appear to foreshadow psoriatic arthritis (PsA), a development that could bring scientists closer to developing a DNA test to predict which patients with psoriasis will develop the condition.

KTSDESIGN/SCIENCE PHOTO LIBRARY/Getty Images

While no predictive test is in sight yet, the findings published in Arthritis & Rheumatology mark an important step, study lead author Omar F. Cruz-Correa, PhD, of the Psoriatic Arthritis Research Program in the University Health Network, Toronto, said in an interview. “In the future, markers like these could be measured by dermatologists and even general practitioners to help identify new psoriasis patients at a high risk of developing PsA,” he said. “Then both the health care team and the patients themselves could be more aware of their increased risk and the pressing need of closer monitoring for musculoskeletal symptoms. Once the first symptoms appear, treatment can be initiated early on, helping to prevent permanent joint damage.”

An estimated 30% of patients with psoriasis will develop PsA, too, putting them at higher risk of disability and death. According to Dr. Cruz-Correa, “one of the more pressing matters in PsA is the lack of means of predicting which psoriasis patients will develop PsA.”

DNA methylation, the topic of the new study, has already been linked to psoriasis and PsA. It’s “relatively easy to measure and helps regulate gene expression in response to environmental effects,” Dr. Cruz-Correa said. “DNA methylation is also appealing because it serves as an intermediary between environment and genetic factors as it’s transmitted between generations of cells and influenced by external factors.”

For the new study, researchers examined the DNA of 117 patients with psoriasis – 58 who went on to develop PsA (“converters”) and another 59 who were matched to converters but did not develop PsA (“nonconverters”). The patients were in a larger group of 700 patients with psoriasis who had the disease for a mean of about 17 years at the time of blood sampling.

Samples from converters were taken an average of 5.16 years (± 12.77 years) before PsA set in.

The researchers report that they found “36 highly relevant methylation markers … across 15 genes and several intergenic regions. A classification model relying on these markers identified converters and nonconverters with an area under the ROC curve of 0.9644.”

Statistically, this number is high and means that “the DNA methylation markers are really good at identifying psoriasis patients who will develop PsA and those that will not,” at least in this specific patient group, Dr. Cruz-Correa said.

At this point, the number of markers is a bit too high to develop a feasible DNA test to predict PsA, he said. “However, the results from our study have also pointed us toward some interesting metabolic pathways that may warrant further study.”
 

What’s next?

The first step forward “is the validation of these predictive DNA methylation markers in a wider population of patients with varied clinical and demographic characteristics. This would help assess the potential for generalization of such a test,” Dr. Cruz-Correa said. “A second step is to assess the potential impact of these methylation markers on disease activity and treatment response, which are clinical outcomes of great importance to patients.”

Meanwhile, he said, “there are ongoing efforts to shed light into how DNA methylation integrates with other epigenetic mechanisms like micro-RNAs to regulate gene expression in concert with one another. An integrative look into these mechanisms may be able to give insight into the pathogenesis of psoriatic disease in a way that has not been possible before.”

In an interview, Johann E. Gudjonsson, MD, PhD, professor of skin molecular immunology at the University of Michigan, Ann Arbor, said the study “is interesting and important as it indicates that there are changes in the blood that occur before the development of psoriatic arthritis. However, it does not provide much in terms of novel insights into the mechanisms involved and is still a long way away from being useful as a clinical predictor or biomarker.”

The National Psoriasis Foundation, Krembil Foundation, and Canadian Institutes of Health Research provided support for the study. Dr. Cruz-Correa reports support from the National Psoriasis Foundation and the Arthritis Society. Dr. Gudjonsson has no relevant financial relationships.
 

In a new study, researchers report that they have found epigenetic methylation markers on 15 genes that appear to foreshadow psoriatic arthritis (PsA), a development that could bring scientists closer to developing a DNA test to predict which patients with psoriasis will develop the condition.

KTSDESIGN/SCIENCE PHOTO LIBRARY/Getty Images

While no predictive test is in sight yet, the findings published in Arthritis & Rheumatology mark an important step, study lead author Omar F. Cruz-Correa, PhD, of the Psoriatic Arthritis Research Program in the University Health Network, Toronto, said in an interview. “In the future, markers like these could be measured by dermatologists and even general practitioners to help identify new psoriasis patients at a high risk of developing PsA,” he said. “Then both the health care team and the patients themselves could be more aware of their increased risk and the pressing need of closer monitoring for musculoskeletal symptoms. Once the first symptoms appear, treatment can be initiated early on, helping to prevent permanent joint damage.”

An estimated 30% of patients with psoriasis will develop PsA, too, putting them at higher risk of disability and death. According to Dr. Cruz-Correa, “one of the more pressing matters in PsA is the lack of means of predicting which psoriasis patients will develop PsA.”

DNA methylation, the topic of the new study, has already been linked to psoriasis and PsA. It’s “relatively easy to measure and helps regulate gene expression in response to environmental effects,” Dr. Cruz-Correa said. “DNA methylation is also appealing because it serves as an intermediary between environment and genetic factors as it’s transmitted between generations of cells and influenced by external factors.”

For the new study, researchers examined the DNA of 117 patients with psoriasis – 58 who went on to develop PsA (“converters”) and another 59 who were matched to converters but did not develop PsA (“nonconverters”). The patients were in a larger group of 700 patients with psoriasis who had the disease for a mean of about 17 years at the time of blood sampling.

Samples from converters were taken an average of 5.16 years (± 12.77 years) before PsA set in.

The researchers report that they found “36 highly relevant methylation markers … across 15 genes and several intergenic regions. A classification model relying on these markers identified converters and nonconverters with an area under the ROC curve of 0.9644.”

Statistically, this number is high and means that “the DNA methylation markers are really good at identifying psoriasis patients who will develop PsA and those that will not,” at least in this specific patient group, Dr. Cruz-Correa said.

At this point, the number of markers is a bit too high to develop a feasible DNA test to predict PsA, he said. “However, the results from our study have also pointed us toward some interesting metabolic pathways that may warrant further study.”
 

What’s next?

The first step forward “is the validation of these predictive DNA methylation markers in a wider population of patients with varied clinical and demographic characteristics. This would help assess the potential for generalization of such a test,” Dr. Cruz-Correa said. “A second step is to assess the potential impact of these methylation markers on disease activity and treatment response, which are clinical outcomes of great importance to patients.”

Meanwhile, he said, “there are ongoing efforts to shed light into how DNA methylation integrates with other epigenetic mechanisms like micro-RNAs to regulate gene expression in concert with one another. An integrative look into these mechanisms may be able to give insight into the pathogenesis of psoriatic disease in a way that has not been possible before.”

In an interview, Johann E. Gudjonsson, MD, PhD, professor of skin molecular immunology at the University of Michigan, Ann Arbor, said the study “is interesting and important as it indicates that there are changes in the blood that occur before the development of psoriatic arthritis. However, it does not provide much in terms of novel insights into the mechanisms involved and is still a long way away from being useful as a clinical predictor or biomarker.”

The National Psoriasis Foundation, Krembil Foundation, and Canadian Institutes of Health Research provided support for the study. Dr. Cruz-Correa reports support from the National Psoriasis Foundation and the Arthritis Society. Dr. Gudjonsson has no relevant financial relationships.
 

In a new study, researchers report that they have found epigenetic methylation markers on 15 genes that appear to foreshadow psoriatic arthritis (PsA), a development that could bring scientists closer to developing a DNA test to predict which patients with psoriasis will develop the condition.

KTSDESIGN/SCIENCE PHOTO LIBRARY/Getty Images

While no predictive test is in sight yet, the findings published in Arthritis & Rheumatology mark an important step, study lead author Omar F. Cruz-Correa, PhD, of the Psoriatic Arthritis Research Program in the University Health Network, Toronto, said in an interview. “In the future, markers like these could be measured by dermatologists and even general practitioners to help identify new psoriasis patients at a high risk of developing PsA,” he said. “Then both the health care team and the patients themselves could be more aware of their increased risk and the pressing need of closer monitoring for musculoskeletal symptoms. Once the first symptoms appear, treatment can be initiated early on, helping to prevent permanent joint damage.”

An estimated 30% of patients with psoriasis will develop PsA, too, putting them at higher risk of disability and death. According to Dr. Cruz-Correa, “one of the more pressing matters in PsA is the lack of means of predicting which psoriasis patients will develop PsA.”

DNA methylation, the topic of the new study, has already been linked to psoriasis and PsA. It’s “relatively easy to measure and helps regulate gene expression in response to environmental effects,” Dr. Cruz-Correa said. “DNA methylation is also appealing because it serves as an intermediary between environment and genetic factors as it’s transmitted between generations of cells and influenced by external factors.”

For the new study, researchers examined the DNA of 117 patients with psoriasis – 58 who went on to develop PsA (“converters”) and another 59 who were matched to converters but did not develop PsA (“nonconverters”). The patients were in a larger group of 700 patients with psoriasis who had the disease for a mean of about 17 years at the time of blood sampling.

Samples from converters were taken an average of 5.16 years (± 12.77 years) before PsA set in.

The researchers report that they found “36 highly relevant methylation markers … across 15 genes and several intergenic regions. A classification model relying on these markers identified converters and nonconverters with an area under the ROC curve of 0.9644.”

Statistically, this number is high and means that “the DNA methylation markers are really good at identifying psoriasis patients who will develop PsA and those that will not,” at least in this specific patient group, Dr. Cruz-Correa said.

At this point, the number of markers is a bit too high to develop a feasible DNA test to predict PsA, he said. “However, the results from our study have also pointed us toward some interesting metabolic pathways that may warrant further study.”
 

What’s next?

The first step forward “is the validation of these predictive DNA methylation markers in a wider population of patients with varied clinical and demographic characteristics. This would help assess the potential for generalization of such a test,” Dr. Cruz-Correa said. “A second step is to assess the potential impact of these methylation markers on disease activity and treatment response, which are clinical outcomes of great importance to patients.”

Meanwhile, he said, “there are ongoing efforts to shed light into how DNA methylation integrates with other epigenetic mechanisms like micro-RNAs to regulate gene expression in concert with one another. An integrative look into these mechanisms may be able to give insight into the pathogenesis of psoriatic disease in a way that has not been possible before.”

In an interview, Johann E. Gudjonsson, MD, PhD, professor of skin molecular immunology at the University of Michigan, Ann Arbor, said the study “is interesting and important as it indicates that there are changes in the blood that occur before the development of psoriatic arthritis. However, it does not provide much in terms of novel insights into the mechanisms involved and is still a long way away from being useful as a clinical predictor or biomarker.”

The National Psoriasis Foundation, Krembil Foundation, and Canadian Institutes of Health Research provided support for the study. Dr. Cruz-Correa reports support from the National Psoriasis Foundation and the Arthritis Society. Dr. Gudjonsson has no relevant financial relationships.
 

Although there are several treatment options for PsA, there have been few head-to-head studies conducted to determine comparative efficacy. Ustekinumab, a biologic agent targeting IL-p40, and therefore both IL-12 and IL-23, has proven efficacy in PsA, but the impression is that this drug is less effective than are TNF inhibitors for the treatment of the peripheral arthritis domain. However, in a prospective, observational study, Gossec and colleagues report that the improvements in patient-reported outcomes were generally comparable between ustekinumab and TNF inhibitor treatments. This study evaluated 437 patients with PsA from the PsABio study who initiated first- to third-line ustekinumab (n = 219) or TNF inhibitors (n = 218) and continued the initial treatment for 3 years. At 3 years, ustekinumab and TNF inhibitors were associated with comparable improvements in the EuroQol-5 dimensions health state visual analog scale scores, Psoriatic Arthritis Impact of Disease 12-item scores, and work productivity, although the improvements were generally greater in the TNF inhibitor–treated group. A randomized trial comparing ustekinumab to TNF inhibitors in PsA is warranted to confirm these findings and inform treatment decisions.

Targeted therapies, such as biologics, are proven to be more efficacious than are conventional therapies; however, only about 60% of patients initiating targeted therapies demonstrate treatment response. Identifying the predictors of treatment response is an active area of research. Linde and colleagues looked at data from 13,369 biologic-naive patients registered with a PsA diagnosis from 13 European registries who initiated a first TNF inhibitor treatment. The study demonstrated that sex, disease duration, C-reactive protein level, age at treatment initiation, and fatigue predicted the achievement of the Disease Activity in Psoriatic Arthritis in 28 joints remission at 6 months.

Could biomarkers help predict response beyond clinical predictors? An interesting study indicates that beta–defensin 2 (BD-2) may serve as a predictive biomarker for clinical response to secukinumab in PsA. BD-2 is an antimicrobial peptide and an important protein in innate immune response. Cardner and colleagues analyzed protein expression data in serum samples from the phase 3 FUTURE 1-5 trials that included 1989 patients with PsA who received secukinumab or placebo. Baseline BD-2 levels were associated with early as well as sustained PsA treatment response to secukinumab, independent of psoriasis severity. BD-2 levels did not predict response to adalimumab in PsA nor was it associated with treatment response to secukinumab in RA. The addition of BD-2 to the clinical prediction model significantly improved the prediction of the 16-week American College of Rheumatology 20 response. Thus, BD-2 seems to be a secukinumab treatment response biomarker and requires further evaluation.

Although there are several treatment options for PsA, there have been few head-to-head studies conducted to determine comparative efficacy. Ustekinumab, a biologic agent targeting IL-p40, and therefore both IL-12 and IL-23, has proven efficacy in PsA, but the impression is that this drug is less effective than are TNF inhibitors for the treatment of the peripheral arthritis domain. However, in a prospective, observational study, Gossec and colleagues report that the improvements in patient-reported outcomes were generally comparable between ustekinumab and TNF inhibitor treatments. This study evaluated 437 patients with PsA from the PsABio study who initiated first- to third-line ustekinumab (n = 219) or TNF inhibitors (n = 218) and continued the initial treatment for 3 years. At 3 years, ustekinumab and TNF inhibitors were associated with comparable improvements in the EuroQol-5 dimensions health state visual analog scale scores, Psoriatic Arthritis Impact of Disease 12-item scores, and work productivity, although the improvements were generally greater in the TNF inhibitor–treated group. A randomized trial comparing ustekinumab to TNF inhibitors in PsA is warranted to confirm these findings and inform treatment decisions.

Targeted therapies, such as biologics, are proven to be more efficacious than are conventional therapies; however, only about 60% of patients initiating targeted therapies demonstrate treatment response. Identifying the predictors of treatment response is an active area of research. Linde and colleagues looked at data from 13,369 biologic-naive patients registered with a PsA diagnosis from 13 European registries who initiated a first TNF inhibitor treatment. The study demonstrated that sex, disease duration, C-reactive protein level, age at treatment initiation, and fatigue predicted the achievement of the Disease Activity in Psoriatic Arthritis in 28 joints remission at 6 months.

Could biomarkers help predict response beyond clinical predictors? An interesting study indicates that beta–defensin 2 (BD-2) may serve as a predictive biomarker for clinical response to secukinumab in PsA. BD-2 is an antimicrobial peptide and an important protein in innate immune response. Cardner and colleagues analyzed protein expression data in serum samples from the phase 3 FUTURE 1-5 trials that included 1989 patients with PsA who received secukinumab or placebo. Baseline BD-2 levels were associated with early as well as sustained PsA treatment response to secukinumab, independent of psoriasis severity. BD-2 levels did not predict response to adalimumab in PsA nor was it associated with treatment response to secukinumab in RA. The addition of BD-2 to the clinical prediction model significantly improved the prediction of the 16-week American College of Rheumatology 20 response. Thus, BD-2 seems to be a secukinumab treatment response biomarker and requires further evaluation.

Although there are several treatment options for PsA, there have been few head-to-head studies conducted to determine comparative efficacy. Ustekinumab, a biologic agent targeting IL-p40, and therefore both IL-12 and IL-23, has proven efficacy in PsA, but the impression is that this drug is less effective than are TNF inhibitors for the treatment of the peripheral arthritis domain. However, in a prospective, observational study, Gossec and colleagues report that the improvements in patient-reported outcomes were generally comparable between ustekinumab and TNF inhibitor treatments. This study evaluated 437 patients with PsA from the PsABio study who initiated first- to third-line ustekinumab (n = 219) or TNF inhibitors (n = 218) and continued the initial treatment for 3 years. At 3 years, ustekinumab and TNF inhibitors were associated with comparable improvements in the EuroQol-5 dimensions health state visual analog scale scores, Psoriatic Arthritis Impact of Disease 12-item scores, and work productivity, although the improvements were generally greater in the TNF inhibitor–treated group. A randomized trial comparing ustekinumab to TNF inhibitors in PsA is warranted to confirm these findings and inform treatment decisions.

Targeted therapies, such as biologics, are proven to be more efficacious than are conventional therapies; however, only about 60% of patients initiating targeted therapies demonstrate treatment response. Identifying the predictors of treatment response is an active area of research. Linde and colleagues looked at data from 13,369 biologic-naive patients registered with a PsA diagnosis from 13 European registries who initiated a first TNF inhibitor treatment. The study demonstrated that sex, disease duration, C-reactive protein level, age at treatment initiation, and fatigue predicted the achievement of the Disease Activity in Psoriatic Arthritis in 28 joints remission at 6 months.

Could biomarkers help predict response beyond clinical predictors? An interesting study indicates that beta–defensin 2 (BD-2) may serve as a predictive biomarker for clinical response to secukinumab in PsA. BD-2 is an antimicrobial peptide and an important protein in innate immune response. Cardner and colleagues analyzed protein expression data in serum samples from the phase 3 FUTURE 1-5 trials that included 1989 patients with PsA who received secukinumab or placebo. Baseline BD-2 levels were associated with early as well as sustained PsA treatment response to secukinumab, independent of psoriasis severity. BD-2 levels did not predict response to adalimumab in PsA nor was it associated with treatment response to secukinumab in RA. The addition of BD-2 to the clinical prediction model significantly improved the prediction of the 16-week American College of Rheumatology 20 response. Thus, BD-2 seems to be a secukinumab treatment response biomarker and requires further evaluation.

Janus kinase inhibitors (JAKi) are a novel class of oral, targeted small-molecule inhibitors that are increasingly used to treat several different autoimmune conditions. In terms of rheumatologic indications, the FDA first approved tofacitinib (TOF) for use in moderate to severe rheumatoid arthritis (RA) unresponsive to methotrexate therapy. Eleven years later, the indications for JAKi use have expanded to include ulcerative colitis, ankylosing spondylitis, and psoriatic arthritis (PsA), among other diseases. As with any new therapeutic mechanism, there are questions as to how JAKi should be incorporated into the treatment paradigm of PsA. In this article, we briefly review the efficacy and safety data of these agents and discuss our approach to their use in PsA.

Two JAKi are currently FDA approved for the treatment of PsA: tofacitinib (TOF) and upadacitinib (UPA). Other JAKi, such as filgotinib and peficitinib, are only approved outside the United States and will not be discussed here. 

TOF was originally studied in skin psoriasis (PsO) before 2 pivotal studies demonstrated efficacy in PsA. TOF or adalimumab (ADA) were compared with placebo in patients who had failed conventional synthetic disease-modifying antirheumatic drugs (DMARD).¹ ACR20 response was superior with TOF 5 mg twice daily (BID) (50%) and 10 mg BID (61%) vs placebo (33%), and it was comparable to ADA (52%), which was used in this study as an active comparator. The overall rate of adverse events was similar with both doses of TOF when compared with ADA; however, patients taking TOF had numerically more cases of cancer, serious infection, and herpes zoster. 

Another study evaluated TOF compared with placebo in patients with PsA who had an inadequate response to tumor necrosis factor inhibitor (TNFi) therapy.² The study showed an ACR20 response of 50% in patients taking TOF 5 mg BID and 47% in patients taking 10 mg BID, compared with 24% in those taking placebo. Patients who received the 10 mg TOF dose continuously had higher rates of adverse events compared to TOF 5 mg, placebo, and patients who crossed over from placebo to TOF at either dose. In the TOF groups, there were cases of serious infection and herpes zoster, as well as 2 patients with major adverse cardiovascular events (MACE). Following review of these data, the FDA approved only the 5 mg BID dose, and later an 11-mg daily extended-release formulation that was pharmacokinetically similar.

The efficacy for UPA in PsA was shown in 2 pivotal phase 3 trials. SELECT-PsA1 compared UPA at 2 doses, 15 mg and 30 mg daily, vs placebo and vs ADA in patients with biologic DMARD (bDMARD)-naïve PsA.³ This trial demonstrated superiority of UPA in the ACR20 response at both doses (71% and 79%, respectively) compared with placebo (36%). The 15-mg dose of UPA was comparable to ADA (65%), while the 30-mg dose achieved superiority compared to ADA. Secondary outcomes including skin activity, patient-reported symptoms, and inhibition of radiographic progression were also superior in UPA compared with placebo and similar or greater with UPA compared with ADA, depending on the specific outcome.⁴ SELECT-PsA2 compared UPA 15 mg, 30 mg, and placebo in patients with prior incomplete response or intolerance to a bDMARD.⁵ At week 12 of the study, patients taking UPA 15 mg and 30 mg had an ACR20 response of 57% and 64%, respectively, compared with placebo (24%). At week 24, minimal disease activity was achieved by 25% of patients taking UPA 15 mg and 29% of patients taking UPA 30 mg, which was superior to placebo (3%). 

Both studies found a significant increase in infections, including serious infections, at the 30-mg UPA dose compared with the placebo and adalimumab groups. Cytopenia and elevated creatine kinase (CK) level also occurred more frequently in the UPA 30-mg group. Rates of cancer were low overall and comparable between the patients treated with UPA and ADA. Given the higher incidence of adverse events with the 30-mg dose and the relatively similar efficacy, the sponsor elected to submit only the lower dose to the FDA for approval.

In the last few years, concerns for safety with JAKi use grew after the publication of data from the ORAL SURVEILLANCE trial, an FDA-mandated, post-approval safety study of TOF in RA. In this trial, patients with active RA over 50 years of age and with at least 1 additional cardiovascular risk factor were randomized to TOF at 1 of 2 doses, 5 mg or 10 mg BID, or a TNFi.⁶ This trial was designed as a noninferiority study, and TOF did not meet the noninferiority threshold compared to TNFi, with hazard ratios of 1.33 and 1.48 for MACE and malignancy, respectively. The results of this trial prompted the FDA to add a black box warning to the label for all JAKi, pointing out the risk of malignancy and MACE, as well as infection, mortality, and thrombosis. 

In the ORAL SURVEILLANCE trial, the increased risk of MACE and malignancy was primarily seen in the study patients with high risk for a cardiovascular event. To address the question of whether a similar risk profile exists when using JAKi to treat PsA, or whether this is a disease-specific process related to RA, a post hoc analysis of 3 PsA trials and 7 PsO trials of patients treated with TOF was conducted.⁷ The analysis found that patients with a history of atherosclerotic cardiovascular disease (ASCVD) or metabolic syndrome, or patients at high risk for ASCVD (score > 20%) had increased incidence rates of MACE compared with those with low risk scores for ASCVD. Interestingly, as in RA, increased incidence rates of malignancy were seen in patients with preexisting or at high risk for ASCVD.

While the FDA recommends JAKi use in patients who have failed or are inappropriate for treatment with a TNFi, we would consider the use of JAKi for first-line therapy in PsA on an individual basis. One advantage of JAKi is their efficacy across multiple PsA domains, including peripheral arthritis, axial disease, enthesitis, dactylitis, and skin disease (although the approved dose of TOF was not statistically effective for PsO in the pivotal trials). Based on this efficacy, we believe that patients with overlapping, multifaceted disease may benefit the most from these medications. Patient risk factors and comorbidities are a prominent consideration in our use of JAKi to ensure safety, as the risk for MACE and malignancy is informed partly by baseline cardiovascular status. In younger patients without cardiovascular risk factors, JAKi may be a strong candidate for first-line therapy, particularly in patients averse to subcutaneous or intravenous therapy. We do counsel all patients on the increased risk of infection, and we do recommend inactivated herpes zoster vaccination in previously unvaccinated patients planning to start JAKi therapy. 

On the horizon are the development of novel, oral agents targeting tyrosine kinase 2 (TYK2), which is a member of the JAK family of signaling proteins. In fact, the TYK2 inhibitor deucravacitinib was approved by the FDA in 2022 for the treatment of PsO. TYK2 inhibitors appear to have the advantage of a more selective mechanism of action, with fewer off-target effects. There were fewer adverse events in the deucravacitinib trials, which led to its prompt PsO authorization, and the FDA approval for the drug did not include the same black box warning that appears in the label for other JAKi.⁸ A phase 2 study showed early promise for the efficacy and safety of deucravacitinib in PsA.⁹ Further investigation will be needed to better understand the role of deucravacitinib and other TYK2 inhibitors being developed for the treatment of PsA. In the meantime, JAKi continue to be a prominent consideration for first-line PsA therapy in a carefully selected patient population. 

Janus kinase inhibitors (JAKi) are a novel class of oral, targeted small-molecule inhibitors that are increasingly used to treat several different autoimmune conditions. In terms of rheumatologic indications, the FDA first approved tofacitinib (TOF) for use in moderate to severe rheumatoid arthritis (RA) unresponsive to methotrexate therapy. Eleven years later, the indications for JAKi use have expanded to include ulcerative colitis, ankylosing spondylitis, and psoriatic arthritis (PsA), among other diseases. As with any new therapeutic mechanism, there are questions as to how JAKi should be incorporated into the treatment paradigm of PsA. In this article, we briefly review the efficacy and safety data of these agents and discuss our approach to their use in PsA.

Two JAKi are currently FDA approved for the treatment of PsA: tofacitinib (TOF) and upadacitinib (UPA). Other JAKi, such as filgotinib and peficitinib, are only approved outside the United States and will not be discussed here. 

TOF was originally studied in skin psoriasis (PsO) before 2 pivotal studies demonstrated efficacy in PsA. TOF or adalimumab (ADA) were compared with placebo in patients who had failed conventional synthetic disease-modifying antirheumatic drugs (DMARD).¹ ACR20 response was superior with TOF 5 mg twice daily (BID) (50%) and 10 mg BID (61%) vs placebo (33%), and it was comparable to ADA (52%), which was used in this study as an active comparator. The overall rate of adverse events was similar with both doses of TOF when compared with ADA; however, patients taking TOF had numerically more cases of cancer, serious infection, and herpes zoster. 

Another study evaluated TOF compared with placebo in patients with PsA who had an inadequate response to tumor necrosis factor inhibitor (TNFi) therapy.² The study showed an ACR20 response of 50% in patients taking TOF 5 mg BID and 47% in patients taking 10 mg BID, compared with 24% in those taking placebo. Patients who received the 10 mg TOF dose continuously had higher rates of adverse events compared to TOF 5 mg, placebo, and patients who crossed over from placebo to TOF at either dose. In the TOF groups, there were cases of serious infection and herpes zoster, as well as 2 patients with major adverse cardiovascular events (MACE). Following review of these data, the FDA approved only the 5 mg BID dose, and later an 11-mg daily extended-release formulation that was pharmacokinetically similar.

The efficacy for UPA in PsA was shown in 2 pivotal phase 3 trials. SELECT-PsA1 compared UPA at 2 doses, 15 mg and 30 mg daily, vs placebo and vs ADA in patients with biologic DMARD (bDMARD)-naïve PsA.³ This trial demonstrated superiority of UPA in the ACR20 response at both doses (71% and 79%, respectively) compared with placebo (36%). The 15-mg dose of UPA was comparable to ADA (65%), while the 30-mg dose achieved superiority compared to ADA. Secondary outcomes including skin activity, patient-reported symptoms, and inhibition of radiographic progression were also superior in UPA compared with placebo and similar or greater with UPA compared with ADA, depending on the specific outcome.⁴ SELECT-PsA2 compared UPA 15 mg, 30 mg, and placebo in patients with prior incomplete response or intolerance to a bDMARD.⁵ At week 12 of the study, patients taking UPA 15 mg and 30 mg had an ACR20 response of 57% and 64%, respectively, compared with placebo (24%). At week 24, minimal disease activity was achieved by 25% of patients taking UPA 15 mg and 29% of patients taking UPA 30 mg, which was superior to placebo (3%). 

Both studies found a significant increase in infections, including serious infections, at the 30-mg UPA dose compared with the placebo and adalimumab groups. Cytopenia and elevated creatine kinase (CK) level also occurred more frequently in the UPA 30-mg group. Rates of cancer were low overall and comparable between the patients treated with UPA and ADA. Given the higher incidence of adverse events with the 30-mg dose and the relatively similar efficacy, the sponsor elected to submit only the lower dose to the FDA for approval.

In the last few years, concerns for safety with JAKi use grew after the publication of data from the ORAL SURVEILLANCE trial, an FDA-mandated, post-approval safety study of TOF in RA. In this trial, patients with active RA over 50 years of age and with at least 1 additional cardiovascular risk factor were randomized to TOF at 1 of 2 doses, 5 mg or 10 mg BID, or a TNFi.⁶ This trial was designed as a noninferiority study, and TOF did not meet the noninferiority threshold compared to TNFi, with hazard ratios of 1.33 and 1.48 for MACE and malignancy, respectively. The results of this trial prompted the FDA to add a black box warning to the label for all JAKi, pointing out the risk of malignancy and MACE, as well as infection, mortality, and thrombosis. 

In the ORAL SURVEILLANCE trial, the increased risk of MACE and malignancy was primarily seen in the study patients with high risk for a cardiovascular event. To address the question of whether a similar risk profile exists when using JAKi to treat PsA, or whether this is a disease-specific process related to RA, a post hoc analysis of 3 PsA trials and 7 PsO trials of patients treated with TOF was conducted.⁷ The analysis found that patients with a history of atherosclerotic cardiovascular disease (ASCVD) or metabolic syndrome, or patients at high risk for ASCVD (score > 20%) had increased incidence rates of MACE compared with those with low risk scores for ASCVD. Interestingly, as in RA, increased incidence rates of malignancy were seen in patients with preexisting or at high risk for ASCVD.

While the FDA recommends JAKi use in patients who have failed or are inappropriate for treatment with a TNFi, we would consider the use of JAKi for first-line therapy in PsA on an individual basis. One advantage of JAKi is their efficacy across multiple PsA domains, including peripheral arthritis, axial disease, enthesitis, dactylitis, and skin disease (although the approved dose of TOF was not statistically effective for PsO in the pivotal trials). Based on this efficacy, we believe that patients with overlapping, multifaceted disease may benefit the most from these medications. Patient risk factors and comorbidities are a prominent consideration in our use of JAKi to ensure safety, as the risk for MACE and malignancy is informed partly by baseline cardiovascular status. In younger patients without cardiovascular risk factors, JAKi may be a strong candidate for first-line therapy, particularly in patients averse to subcutaneous or intravenous therapy. We do counsel all patients on the increased risk of infection, and we do recommend inactivated herpes zoster vaccination in previously unvaccinated patients planning to start JAKi therapy. 

On the horizon are the development of novel, oral agents targeting tyrosine kinase 2 (TYK2), which is a member of the JAK family of signaling proteins. In fact, the TYK2 inhibitor deucravacitinib was approved by the FDA in 2022 for the treatment of PsO. TYK2 inhibitors appear to have the advantage of a more selective mechanism of action, with fewer off-target effects. There were fewer adverse events in the deucravacitinib trials, which led to its prompt PsO authorization, and the FDA approval for the drug did not include the same black box warning that appears in the label for other JAKi.⁸ A phase 2 study showed early promise for the efficacy and safety of deucravacitinib in PsA.⁹ Further investigation will be needed to better understand the role of deucravacitinib and other TYK2 inhibitors being developed for the treatment of PsA. In the meantime, JAKi continue to be a prominent consideration for first-line PsA therapy in a carefully selected patient population. 

Janus kinase inhibitors (JAKi) are a novel class of oral, targeted small-molecule inhibitors that are increasingly used to treat several different autoimmune conditions. In terms of rheumatologic indications, the FDA first approved tofacitinib (TOF) for use in moderate to severe rheumatoid arthritis (RA) unresponsive to methotrexate therapy. Eleven years later, the indications for JAKi use have expanded to include ulcerative colitis, ankylosing spondylitis, and psoriatic arthritis (PsA), among other diseases. As with any new therapeutic mechanism, there are questions as to how JAKi should be incorporated into the treatment paradigm of PsA. In this article, we briefly review the efficacy and safety data of these agents and discuss our approach to their use in PsA.

Two JAKi are currently FDA approved for the treatment of PsA: tofacitinib (TOF) and upadacitinib (UPA). Other JAKi, such as filgotinib and peficitinib, are only approved outside the United States and will not be discussed here. 

TOF was originally studied in skin psoriasis (PsO) before 2 pivotal studies demonstrated efficacy in PsA. TOF or adalimumab (ADA) were compared with placebo in patients who had failed conventional synthetic disease-modifying antirheumatic drugs (DMARD).¹ ACR20 response was superior with TOF 5 mg twice daily (BID) (50%) and 10 mg BID (61%) vs placebo (33%), and it was comparable to ADA (52%), which was used in this study as an active comparator. The overall rate of adverse events was similar with both doses of TOF when compared with ADA; however, patients taking TOF had numerically more cases of cancer, serious infection, and herpes zoster. 

Another study evaluated TOF compared with placebo in patients with PsA who had an inadequate response to tumor necrosis factor inhibitor (TNFi) therapy.² The study showed an ACR20 response of 50% in patients taking TOF 5 mg BID and 47% in patients taking 10 mg BID, compared with 24% in those taking placebo. Patients who received the 10 mg TOF dose continuously had higher rates of adverse events compared to TOF 5 mg, placebo, and patients who crossed over from placebo to TOF at either dose. In the TOF groups, there were cases of serious infection and herpes zoster, as well as 2 patients with major adverse cardiovascular events (MACE). Following review of these data, the FDA approved only the 5 mg BID dose, and later an 11-mg daily extended-release formulation that was pharmacokinetically similar.

The efficacy for UPA in PsA was shown in 2 pivotal phase 3 trials. SELECT-PsA1 compared UPA at 2 doses, 15 mg and 30 mg daily, vs placebo and vs ADA in patients with biologic DMARD (bDMARD)-naïve PsA.³ This trial demonstrated superiority of UPA in the ACR20 response at both doses (71% and 79%, respectively) compared with placebo (36%). The 15-mg dose of UPA was comparable to ADA (65%), while the 30-mg dose achieved superiority compared to ADA. Secondary outcomes including skin activity, patient-reported symptoms, and inhibition of radiographic progression were also superior in UPA compared with placebo and similar or greater with UPA compared with ADA, depending on the specific outcome.⁴ SELECT-PsA2 compared UPA 15 mg, 30 mg, and placebo in patients with prior incomplete response or intolerance to a bDMARD.⁵ At week 12 of the study, patients taking UPA 15 mg and 30 mg had an ACR20 response of 57% and 64%, respectively, compared with placebo (24%). At week 24, minimal disease activity was achieved by 25% of patients taking UPA 15 mg and 29% of patients taking UPA 30 mg, which was superior to placebo (3%). 

Both studies found a significant increase in infections, including serious infections, at the 30-mg UPA dose compared with the placebo and adalimumab groups. Cytopenia and elevated creatine kinase (CK) level also occurred more frequently in the UPA 30-mg group. Rates of cancer were low overall and comparable between the patients treated with UPA and ADA. Given the higher incidence of adverse events with the 30-mg dose and the relatively similar efficacy, the sponsor elected to submit only the lower dose to the FDA for approval.

In the last few years, concerns for safety with JAKi use grew after the publication of data from the ORAL SURVEILLANCE trial, an FDA-mandated, post-approval safety study of TOF in RA. In this trial, patients with active RA over 50 years of age and with at least 1 additional cardiovascular risk factor were randomized to TOF at 1 of 2 doses, 5 mg or 10 mg BID, or a TNFi.⁶ This trial was designed as a noninferiority study, and TOF did not meet the noninferiority threshold compared to TNFi, with hazard ratios of 1.33 and 1.48 for MACE and malignancy, respectively. The results of this trial prompted the FDA to add a black box warning to the label for all JAKi, pointing out the risk of malignancy and MACE, as well as infection, mortality, and thrombosis. 

In the ORAL SURVEILLANCE trial, the increased risk of MACE and malignancy was primarily seen in the study patients with high risk for a cardiovascular event. To address the question of whether a similar risk profile exists when using JAKi to treat PsA, or whether this is a disease-specific process related to RA, a post hoc analysis of 3 PsA trials and 7 PsO trials of patients treated with TOF was conducted.⁷ The analysis found that patients with a history of atherosclerotic cardiovascular disease (ASCVD) or metabolic syndrome, or patients at high risk for ASCVD (score > 20%) had increased incidence rates of MACE compared with those with low risk scores for ASCVD. Interestingly, as in RA, increased incidence rates of malignancy were seen in patients with preexisting or at high risk for ASCVD.

While the FDA recommends JAKi use in patients who have failed or are inappropriate for treatment with a TNFi, we would consider the use of JAKi for first-line therapy in PsA on an individual basis. One advantage of JAKi is their efficacy across multiple PsA domains, including peripheral arthritis, axial disease, enthesitis, dactylitis, and skin disease (although the approved dose of TOF was not statistically effective for PsO in the pivotal trials). Based on this efficacy, we believe that patients with overlapping, multifaceted disease may benefit the most from these medications. Patient risk factors and comorbidities are a prominent consideration in our use of JAKi to ensure safety, as the risk for MACE and malignancy is informed partly by baseline cardiovascular status. In younger patients without cardiovascular risk factors, JAKi may be a strong candidate for first-line therapy, particularly in patients averse to subcutaneous or intravenous therapy. We do counsel all patients on the increased risk of infection, and we do recommend inactivated herpes zoster vaccination in previously unvaccinated patients planning to start JAKi therapy. 

On the horizon are the development of novel, oral agents targeting tyrosine kinase 2 (TYK2), which is a member of the JAK family of signaling proteins. In fact, the TYK2 inhibitor deucravacitinib was approved by the FDA in 2022 for the treatment of PsO. TYK2 inhibitors appear to have the advantage of a more selective mechanism of action, with fewer off-target effects. There were fewer adverse events in the deucravacitinib trials, which led to its prompt PsO authorization, and the FDA approval for the drug did not include the same black box warning that appears in the label for other JAKi.⁸ A phase 2 study showed early promise for the efficacy and safety of deucravacitinib in PsA.⁹ Further investigation will be needed to better understand the role of deucravacitinib and other TYK2 inhibitors being developed for the treatment of PsA. In the meantime, JAKi continue to be a prominent consideration for first-line PsA therapy in a carefully selected patient population. 

Key clinical point: Serum neutrophil gelatinase-associated lipocalin (NGAL) showed no value as a biomarker either for disease activity or for monitoring in relation to anti-inflammatory treatment in patients with peripheral psoriatic arthritis (PsA).

Major finding: Overall, the mean serum NGAL reduced by 11% after 12 months of treatment with any disease-modifying antirheumatic drug (DMARD), with no clear trend of a clinically significant increase or decrease after 12 months of treatment with conventional-synthetic DMARDs, tumor necrosis factor-alpha inhibitors, or interleukin-17 inhibitors. The changes in NGAL levels showed no correlation with changes in PsA outcomes (Spearman correlation coefficients close to 0.0).

Study details: This exploratory prospective cohort study included 117 patients with peripheral PsA who initiated conventional synthetic or biologic DMARDs, 20 patients with psoriasis without arthritis who did not receive systemic treatment, and 20 control individuals.

Disclosures: This study was supported by the Danish Rheumatism Association and others. Five authors reported ties with various sources. The other authors declared no conflict of interests.

Source: Stisen ZR et al. Treatment-related changes in serum neutrophil gelatinase-associated lipocalin (NGAL) in psoriatic arthritis: Results from the PIPA cohort study. Scand J Rheumatol. 2023;1-8 (Jun 20). Doi: 10.1080/03009742.2023.2216046.

Key clinical point: Serum neutrophil gelatinase-associated lipocalin (NGAL) showed no value as a biomarker either for disease activity or for monitoring in relation to anti-inflammatory treatment in patients with peripheral psoriatic arthritis (PsA).

Major finding: Overall, the mean serum NGAL reduced by 11% after 12 months of treatment with any disease-modifying antirheumatic drug (DMARD), with no clear trend of a clinically significant increase or decrease after 12 months of treatment with conventional-synthetic DMARDs, tumor necrosis factor-alpha inhibitors, or interleukin-17 inhibitors. The changes in NGAL levels showed no correlation with changes in PsA outcomes (Spearman correlation coefficients close to 0.0).

Study details: This exploratory prospective cohort study included 117 patients with peripheral PsA who initiated conventional synthetic or biologic DMARDs, 20 patients with psoriasis without arthritis who did not receive systemic treatment, and 20 control individuals.

Disclosures: This study was supported by the Danish Rheumatism Association and others. Five authors reported ties with various sources. The other authors declared no conflict of interests.

Source: Stisen ZR et al. Treatment-related changes in serum neutrophil gelatinase-associated lipocalin (NGAL) in psoriatic arthritis: Results from the PIPA cohort study. Scand J Rheumatol. 2023;1-8 (Jun 20). Doi: 10.1080/03009742.2023.2216046.

Key clinical point: Serum neutrophil gelatinase-associated lipocalin (NGAL) showed no value as a biomarker either for disease activity or for monitoring in relation to anti-inflammatory treatment in patients with peripheral psoriatic arthritis (PsA).

Major finding: Overall, the mean serum NGAL reduced by 11% after 12 months of treatment with any disease-modifying antirheumatic drug (DMARD), with no clear trend of a clinically significant increase or decrease after 12 months of treatment with conventional-synthetic DMARDs, tumor necrosis factor-alpha inhibitors, or interleukin-17 inhibitors. The changes in NGAL levels showed no correlation with changes in PsA outcomes (Spearman correlation coefficients close to 0.0).

Study details: This exploratory prospective cohort study included 117 patients with peripheral PsA who initiated conventional synthetic or biologic DMARDs, 20 patients with psoriasis without arthritis who did not receive systemic treatment, and 20 control individuals.

Disclosures: This study was supported by the Danish Rheumatism Association and others. Five authors reported ties with various sources. The other authors declared no conflict of interests.

Source: Stisen ZR et al. Treatment-related changes in serum neutrophil gelatinase-associated lipocalin (NGAL) in psoriatic arthritis: Results from the PIPA cohort study. Scand J Rheumatol. 2023;1-8 (Jun 20). Doi: 10.1080/03009742.2023.2216046.

Key clinical point: The combination of serum interleukin-6 (IL-6), platelet to lymphocyte ratio (PLR), and nail psoriasis can help screen and predict early stage of psoriatic arthritis (PsA).

Major finding: The proportion of patients with elevated serum IL-6 levels was significantly higher in the PsA vs. plaque psoriasis group (P < .0167), with the elevations in PLR levels and systemic immune-inflammation index being significantly higher among patients with PsA and early PsA vs. plaque psoriasis (P < .05 for all). The combination of nail psoriasis (P = .002), IL-6 (P < .001), and PLR (P < .001) as a predictor for early PsA diagnosis showed an area under curve of 0.84 (95% CI, 0.77-0.90).

Study details: Findings are from a case-control study including 109 patients with plaque psoriasis without joint involvement, 47 patients with PsA, and 41 patients with rheumatoid arthritis.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Liu X et al. The combination of IL-6, PLR and nail psoriasis: Screen for the early diagnosis of psoriatic arthritis. Clin Cosmet Investig Dermatol. 2023;16:1703-1713 (Jun 28). Doi: 10.2147/CCID.S413853.

Key clinical point: The combination of serum interleukin-6 (IL-6), platelet to lymphocyte ratio (PLR), and nail psoriasis can help screen and predict early stage of psoriatic arthritis (PsA).

Major finding: The proportion of patients with elevated serum IL-6 levels was significantly higher in the PsA vs. plaque psoriasis group (P < .0167), with the elevations in PLR levels and systemic immune-inflammation index being significantly higher among patients with PsA and early PsA vs. plaque psoriasis (P < .05 for all). The combination of nail psoriasis (P = .002), IL-6 (P < .001), and PLR (P < .001) as a predictor for early PsA diagnosis showed an area under curve of 0.84 (95% CI, 0.77-0.90).

Study details: Findings are from a case-control study including 109 patients with plaque psoriasis without joint involvement, 47 patients with PsA, and 41 patients with rheumatoid arthritis.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Liu X et al. The combination of IL-6, PLR and nail psoriasis: Screen for the early diagnosis of psoriatic arthritis. Clin Cosmet Investig Dermatol. 2023;16:1703-1713 (Jun 28). Doi: 10.2147/CCID.S413853.

Key clinical point: The combination of serum interleukin-6 (IL-6), platelet to lymphocyte ratio (PLR), and nail psoriasis can help screen and predict early stage of psoriatic arthritis (PsA).

Major finding: The proportion of patients with elevated serum IL-6 levels was significantly higher in the PsA vs. plaque psoriasis group (P < .0167), with the elevations in PLR levels and systemic immune-inflammation index being significantly higher among patients with PsA and early PsA vs. plaque psoriasis (P < .05 for all). The combination of nail psoriasis (P = .002), IL-6 (P < .001), and PLR (P < .001) as a predictor for early PsA diagnosis showed an area under curve of 0.84 (95% CI, 0.77-0.90).

Study details: Findings are from a case-control study including 109 patients with plaque psoriasis without joint involvement, 47 patients with PsA, and 41 patients with rheumatoid arthritis.

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Liu X et al. The combination of IL-6, PLR and nail psoriasis: Screen for the early diagnosis of psoriatic arthritis. Clin Cosmet Investig Dermatol. 2023;16:1703-1713 (Jun 28). Doi: 10.2147/CCID.S413853.

Key clinical point: The presentation of disease domains is heterogenous in psoriatic arthritis (PsA) making assessment of all domains important for optimal disease management.

Major finding: Peripheral arthritis (86%) and skin disease (82%) were the most common, whereas dactylitis (23%) and axial disease (20%) were the least common disease domains identified in the overall PsA population and across treatment groups. The triad of peripheral arthritis, nail psoriasis, and skin disease was the most common domain combination (13.7%) not only in the overall PsA population but also when stratified by those who initiated tumor necrosis factor inhibitors (TNFis; 14.4%) or interleukin-17 inhibitors (IL-17is; 12.6%). At 6 months, the minimal disease activity improved across PsA domains.

Study details: This real-world analysis included 1,005 patients with PsA from the CorEvitas PsA/Spondyloarthritis Registry who initiated either TNFis or IL-17is at baseline.

Disclosures: This study was sponsored by Amgen Inc. Three authors declared being employees of and owning stocks or options in Amgen. Two authors declared being employees of CorEvitas, LLC. PJ Mease and A Ogdie declared ties with various sources, including Amgen.

Source: Mease PJ et al. Real-world evidence assessing psoriatic arthritis by disease domain: An evaluation of the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. ACR Open Rheumatol. 2023 (Jun 25). Doi: 10.1002/acr2.11556.

Key clinical point: The presentation of disease domains is heterogenous in psoriatic arthritis (PsA) making assessment of all domains important for optimal disease management.

Major finding: Peripheral arthritis (86%) and skin disease (82%) were the most common, whereas dactylitis (23%) and axial disease (20%) were the least common disease domains identified in the overall PsA population and across treatment groups. The triad of peripheral arthritis, nail psoriasis, and skin disease was the most common domain combination (13.7%) not only in the overall PsA population but also when stratified by those who initiated tumor necrosis factor inhibitors (TNFis; 14.4%) or interleukin-17 inhibitors (IL-17is; 12.6%). At 6 months, the minimal disease activity improved across PsA domains.

Study details: This real-world analysis included 1,005 patients with PsA from the CorEvitas PsA/Spondyloarthritis Registry who initiated either TNFis or IL-17is at baseline.

Disclosures: This study was sponsored by Amgen Inc. Three authors declared being employees of and owning stocks or options in Amgen. Two authors declared being employees of CorEvitas, LLC. PJ Mease and A Ogdie declared ties with various sources, including Amgen.

Source: Mease PJ et al. Real-world evidence assessing psoriatic arthritis by disease domain: An evaluation of the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. ACR Open Rheumatol. 2023 (Jun 25). Doi: 10.1002/acr2.11556.

Key clinical point: The presentation of disease domains is heterogenous in psoriatic arthritis (PsA) making assessment of all domains important for optimal disease management.

Major finding: Peripheral arthritis (86%) and skin disease (82%) were the most common, whereas dactylitis (23%) and axial disease (20%) were the least common disease domains identified in the overall PsA population and across treatment groups. The triad of peripheral arthritis, nail psoriasis, and skin disease was the most common domain combination (13.7%) not only in the overall PsA population but also when stratified by those who initiated tumor necrosis factor inhibitors (TNFis; 14.4%) or interleukin-17 inhibitors (IL-17is; 12.6%). At 6 months, the minimal disease activity improved across PsA domains.

Study details: This real-world analysis included 1,005 patients with PsA from the CorEvitas PsA/Spondyloarthritis Registry who initiated either TNFis or IL-17is at baseline.

Disclosures: This study was sponsored by Amgen Inc. Three authors declared being employees of and owning stocks or options in Amgen. Two authors declared being employees of CorEvitas, LLC. PJ Mease and A Ogdie declared ties with various sources, including Amgen.

Source: Mease PJ et al. Real-world evidence assessing psoriatic arthritis by disease domain: An evaluation of the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. ACR Open Rheumatol. 2023 (Jun 25). Doi: 10.1002/acr2.11556.

Key clinical point: Patients with moderate-high psoriatic arthritis (PsA) disease activity without traditional cardiovascular risk factors had an increased prevalence of subclinical myocardial dysfunction, lower adiponectin levels, and higher serum interleukin-17A (IL-17A) levels.

Major finding: Patients with moderate and high PsA disease activity had lower global longitudinal strain (GLS), tricuspid annular plane systolic excursion, left ventricular ejection fraction, and adiponectin levels and higher IL-17A levels compared with patients with low PsA disease activity and control individuals (all P < .05). GLS was significantly associated with serum IL-17A (P = .001) and adiponectin (P = .032) levels.

Study details: This study included 55 patients with PsA and 25 control individuals without cardiovascular disease.

Disclosures: This study did not disclose the funding source. The authors declared no conflict of interests.

Source: Pletikosic I et al. Association of inflammatory biomarkers and disease activity with subclinical myocardial dysfunction in psoriatic arthritis. Sci Rep. 2023;13(1):10371 (Jun 26). Doi: 10.1038/s41598-023-37412-6.

Key clinical point: Patients with moderate-high psoriatic arthritis (PsA) disease activity without traditional cardiovascular risk factors had an increased prevalence of subclinical myocardial dysfunction, lower adiponectin levels, and higher serum interleukin-17A (IL-17A) levels.

Major finding: Patients with moderate and high PsA disease activity had lower global longitudinal strain (GLS), tricuspid annular plane systolic excursion, left ventricular ejection fraction, and adiponectin levels and higher IL-17A levels compared with patients with low PsA disease activity and control individuals (all P < .05). GLS was significantly associated with serum IL-17A (P = .001) and adiponectin (P = .032) levels.

Study details: This study included 55 patients with PsA and 25 control individuals without cardiovascular disease.

Disclosures: This study did not disclose the funding source. The authors declared no conflict of interests.

Source: Pletikosic I et al. Association of inflammatory biomarkers and disease activity with subclinical myocardial dysfunction in psoriatic arthritis. Sci Rep. 2023;13(1):10371 (Jun 26). Doi: 10.1038/s41598-023-37412-6.

Key clinical point: Patients with moderate-high psoriatic arthritis (PsA) disease activity without traditional cardiovascular risk factors had an increased prevalence of subclinical myocardial dysfunction, lower adiponectin levels, and higher serum interleukin-17A (IL-17A) levels.

Major finding: Patients with moderate and high PsA disease activity had lower global longitudinal strain (GLS), tricuspid annular plane systolic excursion, left ventricular ejection fraction, and adiponectin levels and higher IL-17A levels compared with patients with low PsA disease activity and control individuals (all P < .05). GLS was significantly associated with serum IL-17A (P = .001) and adiponectin (P = .032) levels.

Study details: This study included 55 patients with PsA and 25 control individuals without cardiovascular disease.

Disclosures: This study did not disclose the funding source. The authors declared no conflict of interests.

Source: Pletikosic I et al. Association of inflammatory biomarkers and disease activity with subclinical myocardial dysfunction in psoriatic arthritis. Sci Rep. 2023;13(1):10371 (Jun 26). Doi: 10.1038/s41598-023-37412-6.

Key clinical point: A 12-month anti-tumor necrosis factor-alpha (anti-TNF-α) regimen improved nailfold capillaroscopic abnormalities in patients with psoriatic arthritis (PsA), highlighting the usefulness of nailfold videocapillaroscopy in the evaluation of disease severity and in monitoring the efficacy of biologic treatment.

Major finding: After 12 months of initiating anti-TNF-α therapy, the proportion of patients with PsA showing structural integrity increased from 29.4% to 67.6% and those of patients with low capillaroscopic density and avascular areas decreased from 30.3% to 15.2% and 39.4% to 24.2%, respectively. The use of anti-TNF-α therapy was positively associated with a decrease in angiogenesis (P = .0003) and in the number of giant capillaries (P = .007) and elongated capillaries (P = .0003).

Study details: Findings are from a retrospective observational study including patients with PsA (n=34) and those with rheumatoid arthritis (n=34) who received anti-TNF-α therapy and control individuals (n=24).

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Anghel D et al. Nailfold videocapillaroscopy in patients with rheumatoid arthritis and psoriatic arthropathy on ANTI-TNF-ALPHA therapy. Diagnostics (Basel). 2023;13(12):2079 (Jun 15). Doi: 10.3390/diagnostics13122079.

Key clinical point: A 12-month anti-tumor necrosis factor-alpha (anti-TNF-α) regimen improved nailfold capillaroscopic abnormalities in patients with psoriatic arthritis (PsA), highlighting the usefulness of nailfold videocapillaroscopy in the evaluation of disease severity and in monitoring the efficacy of biologic treatment.

Major finding: After 12 months of initiating anti-TNF-α therapy, the proportion of patients with PsA showing structural integrity increased from 29.4% to 67.6% and those of patients with low capillaroscopic density and avascular areas decreased from 30.3% to 15.2% and 39.4% to 24.2%, respectively. The use of anti-TNF-α therapy was positively associated with a decrease in angiogenesis (P = .0003) and in the number of giant capillaries (P = .007) and elongated capillaries (P = .0003).

Study details: Findings are from a retrospective observational study including patients with PsA (n=34) and those with rheumatoid arthritis (n=34) who received anti-TNF-α therapy and control individuals (n=24).

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Anghel D et al. Nailfold videocapillaroscopy in patients with rheumatoid arthritis and psoriatic arthropathy on ANTI-TNF-ALPHA therapy. Diagnostics (Basel). 2023;13(12):2079 (Jun 15). Doi: 10.3390/diagnostics13122079.

Key clinical point: A 12-month anti-tumor necrosis factor-alpha (anti-TNF-α) regimen improved nailfold capillaroscopic abnormalities in patients with psoriatic arthritis (PsA), highlighting the usefulness of nailfold videocapillaroscopy in the evaluation of disease severity and in monitoring the efficacy of biologic treatment.

Major finding: After 12 months of initiating anti-TNF-α therapy, the proportion of patients with PsA showing structural integrity increased from 29.4% to 67.6% and those of patients with low capillaroscopic density and avascular areas decreased from 30.3% to 15.2% and 39.4% to 24.2%, respectively. The use of anti-TNF-α therapy was positively associated with a decrease in angiogenesis (P = .0003) and in the number of giant capillaries (P = .007) and elongated capillaries (P = .0003).

Study details: Findings are from a retrospective observational study including patients with PsA (n=34) and those with rheumatoid arthritis (n=34) who received anti-TNF-α therapy and control individuals (n=24).

Disclosures: This study did not receive any funding. The authors declared no conflict of interests.

Source: Anghel D et al. Nailfold videocapillaroscopy in patients with rheumatoid arthritis and psoriatic arthropathy on ANTI-TNF-ALPHA therapy. Diagnostics (Basel). 2023;13(12):2079 (Jun 15). Doi: 10.3390/diagnostics13122079.