Commentary: Predicting PsA Progression, Managing Comorbidities, and Evaluating New Therapies, December 2024

Recently published clinical research in psoriatic arthritis (PsA) has continued to focus on the transition from psoriasis to PsA, comorbidities, and effects of treatments. Garcia-Salinas and colleagues reported results of a large study that investigated 1419 patients with joint pain who were carefully clinically evaluated with imaging (ultrasonography and MRI) and laboratory tests. They found that among patients with arthralgia, 8.4% were at risk of developing PsA (ie, had a personal or family history of psoriasis), with 29% of these patients progressing to PsA within 1 year. Significant predictors of progression included a family history of psoriasis, synovitis detected by power Doppler ultrasound, enthesopathy on ultrasonography, and a low tender joint count. Thus, more than one quarter of patients with psoriasis and joint pain developed PsA in 1 year. Patients with psoriasis and joint pain, especially those with findings on imaging, should be referred to rheumatologists and carefully followed up for early diagnosis of PsA and therefore better outcomes.

Chronic kidney disease (CKD) is a known comorbidity in psoriatic disease but is less well characterised. In a prospective observational cohort study that included 1336 patients with PsA, Kharouf and colleagues reported that 123 (9.2%) had CKD. They demonstrated that diabetes, kidney stones, joint damage, high uric acid levels, and daily use of nonsteroidal anti-inflammatory drugs were associated with development of CKD, whereas methotrexate use had a renoprotective effect. Thus, patients with severe PsA and comorbidities such as diabetes are at higher risk for CKD. Better management of PsA using disease-modifying antirheumatic drugs may reduce the risk. Replication of these findings, especially in terms of the renoprotective effect of methotrexate, is required.

Patients with PsA who do not respond to treatment with tumour necrosis factor (TNF) inhibitors are generally less likely to respond to subsequent therapy. Evaluating newer modes of action in this treatment-resistant PsA population is important. COSMOS was a phase 3b trial that included 285 patients with PsA who had inadequate response or intolerance to TNF inhibitors and were randomly assigned to receive 100 mg guselkumab (a monoclonal antibody targeting interleukin-23; n = 189) or placebo (n = 96). In a post hoc analysis, Gossec and colleagues showed that at week 24, a greater proportion of patients receiving guselkumab vs placebo achieved minimal disease activity (MDA) (14.8% vs 3.1%). Most of the patients who achieved MDA at week 24 maintained the response at week 48. Thus, guselkumab treatment led to sustained MDA over 1 year in patients with PsA who had inadequate response or intolerance to TNF inhibitors.

Achieving MDA was also evaluated in another novel drug for PsA. Deucravacitinib is an oral TYK2 inhibitor that is approved for the treatment of psoriasis and is currently being evaluated in phase 3 PsA trials. In a post hoc analysis of a phase 2 trial that included 203 adults with PsA who did not respond to or were intolerant to one or more prior therapies and were randomly assigned to receive 6 mg or 12 mg deucravacitinib or placebo, Kavanaugh and colleagues found that after 16 weeks, a significantly higher proportion of patients treated with deucravacitinib vs placebo achieved MDA (6 mg: 22.9% vs 7.6%; P = .01 and 12 mg: 23.9% vs 7.6%; P = .007). Achieving MDA reflects a state of low disease activity or remission; therefore, these results are very encouraging. Results from phase 3 trials and a formal comparison with other drugs will inform rheumatologists about the place of deucravacitinib in the management of PsA.

Recently published clinical research in psoriatic arthritis (PsA) has continued to focus on the transition from psoriasis to PsA, comorbidities, and effects of treatments. Garcia-Salinas and colleagues reported results of a large study that investigated 1419 patients with joint pain who were carefully clinically evaluated with imaging (ultrasonography and MRI) and laboratory tests. They found that among patients with arthralgia, 8.4% were at risk of developing PsA (ie, had a personal or family history of psoriasis), with 29% of these patients progressing to PsA within 1 year. Significant predictors of progression included a family history of psoriasis, synovitis detected by power Doppler ultrasound, enthesopathy on ultrasonography, and a low tender joint count. Thus, more than one quarter of patients with psoriasis and joint pain developed PsA in 1 year. Patients with psoriasis and joint pain, especially those with findings on imaging, should be referred to rheumatologists and carefully followed up for early diagnosis of PsA and therefore better outcomes.

Chronic kidney disease (CKD) is a known comorbidity in psoriatic disease but is less well characterised. In a prospective observational cohort study that included 1336 patients with PsA, Kharouf and colleagues reported that 123 (9.2%) had CKD. They demonstrated that diabetes, kidney stones, joint damage, high uric acid levels, and daily use of nonsteroidal anti-inflammatory drugs were associated with development of CKD, whereas methotrexate use had a renoprotective effect. Thus, patients with severe PsA and comorbidities such as diabetes are at higher risk for CKD. Better management of PsA using disease-modifying antirheumatic drugs may reduce the risk. Replication of these findings, especially in terms of the renoprotective effect of methotrexate, is required.

Patients with PsA who do not respond to treatment with tumour necrosis factor (TNF) inhibitors are generally less likely to respond to subsequent therapy. Evaluating newer modes of action in this treatment-resistant PsA population is important. COSMOS was a phase 3b trial that included 285 patients with PsA who had inadequate response or intolerance to TNF inhibitors and were randomly assigned to receive 100 mg guselkumab (a monoclonal antibody targeting interleukin-23; n = 189) or placebo (n = 96). In a post hoc analysis, Gossec and colleagues showed that at week 24, a greater proportion of patients receiving guselkumab vs placebo achieved minimal disease activity (MDA) (14.8% vs 3.1%). Most of the patients who achieved MDA at week 24 maintained the response at week 48. Thus, guselkumab treatment led to sustained MDA over 1 year in patients with PsA who had inadequate response or intolerance to TNF inhibitors.

Achieving MDA was also evaluated in another novel drug for PsA. Deucravacitinib is an oral TYK2 inhibitor that is approved for the treatment of psoriasis and is currently being evaluated in phase 3 PsA trials. In a post hoc analysis of a phase 2 trial that included 203 adults with PsA who did not respond to or were intolerant to one or more prior therapies and were randomly assigned to receive 6 mg or 12 mg deucravacitinib or placebo, Kavanaugh and colleagues found that after 16 weeks, a significantly higher proportion of patients treated with deucravacitinib vs placebo achieved MDA (6 mg: 22.9% vs 7.6%; P = .01 and 12 mg: 23.9% vs 7.6%; P = .007). Achieving MDA reflects a state of low disease activity or remission; therefore, these results are very encouraging. Results from phase 3 trials and a formal comparison with other drugs will inform rheumatologists about the place of deucravacitinib in the management of PsA.

Recently published clinical research in psoriatic arthritis (PsA) has continued to focus on the transition from psoriasis to PsA, comorbidities, and effects of treatments. Garcia-Salinas and colleagues reported results of a large study that investigated 1419 patients with joint pain who were carefully clinically evaluated with imaging (ultrasonography and MRI) and laboratory tests. They found that among patients with arthralgia, 8.4% were at risk of developing PsA (ie, had a personal or family history of psoriasis), with 29% of these patients progressing to PsA within 1 year. Significant predictors of progression included a family history of psoriasis, synovitis detected by power Doppler ultrasound, enthesopathy on ultrasonography, and a low tender joint count. Thus, more than one quarter of patients with psoriasis and joint pain developed PsA in 1 year. Patients with psoriasis and joint pain, especially those with findings on imaging, should be referred to rheumatologists and carefully followed up for early diagnosis of PsA and therefore better outcomes.

Chronic kidney disease (CKD) is a known comorbidity in psoriatic disease but is less well characterised. In a prospective observational cohort study that included 1336 patients with PsA, Kharouf and colleagues reported that 123 (9.2%) had CKD. They demonstrated that diabetes, kidney stones, joint damage, high uric acid levels, and daily use of nonsteroidal anti-inflammatory drugs were associated with development of CKD, whereas methotrexate use had a renoprotective effect. Thus, patients with severe PsA and comorbidities such as diabetes are at higher risk for CKD. Better management of PsA using disease-modifying antirheumatic drugs may reduce the risk. Replication of these findings, especially in terms of the renoprotective effect of methotrexate, is required.

Patients with PsA who do not respond to treatment with tumour necrosis factor (TNF) inhibitors are generally less likely to respond to subsequent therapy. Evaluating newer modes of action in this treatment-resistant PsA population is important. COSMOS was a phase 3b trial that included 285 patients with PsA who had inadequate response or intolerance to TNF inhibitors and were randomly assigned to receive 100 mg guselkumab (a monoclonal antibody targeting interleukin-23; n = 189) or placebo (n = 96). In a post hoc analysis, Gossec and colleagues showed that at week 24, a greater proportion of patients receiving guselkumab vs placebo achieved minimal disease activity (MDA) (14.8% vs 3.1%). Most of the patients who achieved MDA at week 24 maintained the response at week 48. Thus, guselkumab treatment led to sustained MDA over 1 year in patients with PsA who had inadequate response or intolerance to TNF inhibitors.

Achieving MDA was also evaluated in another novel drug for PsA. Deucravacitinib is an oral TYK2 inhibitor that is approved for the treatment of psoriasis and is currently being evaluated in phase 3 PsA trials. In a post hoc analysis of a phase 2 trial that included 203 adults with PsA who did not respond to or were intolerant to one or more prior therapies and were randomly assigned to receive 6 mg or 12 mg deucravacitinib or placebo, Kavanaugh and colleagues found that after 16 weeks, a significantly higher proportion of patients treated with deucravacitinib vs placebo achieved MDA (6 mg: 22.9% vs 7.6%; P = .01 and 12 mg: 23.9% vs 7.6%; P = .007). Achieving MDA reflects a state of low disease activity or remission; therefore, these results are very encouraging. Results from phase 3 trials and a formal comparison with other drugs will inform rheumatologists about the place of deucravacitinib in the management of PsA.