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Commentary: Difficult-to-Treat PsA and Medication Options, July 2024
A hot topic of PsA research is whether treating psoriasis patients with biologics reduces the risk of developing PsA. Floris and colleagues analyzed data from 1023 patients with psoriasis aged 18 years or older, of whom 29.6% received biologics at least once and 21.0% had PsA. They observed that patients treated at least once vs never treated with biologics had a significantly lower risk for PsA. The "protective" effect of biologics against PsA persisted irrespective of the class of biologic used. However, the study has many built-in biases; it was not a prospective study of psoriasis patients without PsA, but rather a retrospective analysis of data collected at enrollment. Nevertheless, effective psoriasis therapies may indeed reduce the risk for PsA; prospective interventional studies are required and are currently underway.
Development of radiographic damage indicates severe PsA and affects quality of life and physical function. Identifying patients at risk for joint damage may help treatment stratification. Using data from a real-world cohort of 476 patients with early PsA, of whom 14% demonstrated progressive radiographic damage, Koc and colleagues found that female sex was a protective factor whereas old age and initial radiographic damage were risk factors for radiographic progression. These results are consistent with previous studies. Male sex, older age, and presence of radiographic damage at first visit should prompt more aggressive management to prevent further joint damage.
Regarding newer treatments, Gossec and colleagues demonstrated that bimekizumab, a monoclonal antibody targeting both interleukin (IL)-17A and IL-17F, improved disease effects in a rapid and sustained manner in patients with PsA who had not used biologic disease-modifying antirheumatic drugs or had prior inadequate response to tumor necrosis factor inhibitors. Bimekizumab is a welcome addition to the drugs available to manage PsA. Its comparative efficacy against other targeted therapies, especially other IL-17 inhibitors, is yet to be determined.
Finally, a study from the Greek multicenter PsA registry by Vassilakis and colleagues showed that, of 467 patients with PsA, 16.5% had D2T PsA. Compared with non–D2T patients, those with D2T disease were more likely to have extensive psoriasis at diagnosis, higher body mass index, and a history of inflammatory bowel disease (IBD). Treatment-resistant disease is increasingly prevalent in PsA. Certain diseases and comorbidities, such as IBD and obesity, are associated with D2T PsA. A uniform definition of D2T PsA and prospective studies to identify risk factors, as well as new strategies to manage D2T PsA, are required.
A hot topic of PsA research is whether treating psoriasis patients with biologics reduces the risk of developing PsA. Floris and colleagues analyzed data from 1023 patients with psoriasis aged 18 years or older, of whom 29.6% received biologics at least once and 21.0% had PsA. They observed that patients treated at least once vs never treated with biologics had a significantly lower risk for PsA. The "protective" effect of biologics against PsA persisted irrespective of the class of biologic used. However, the study has many built-in biases; it was not a prospective study of psoriasis patients without PsA, but rather a retrospective analysis of data collected at enrollment. Nevertheless, effective psoriasis therapies may indeed reduce the risk for PsA; prospective interventional studies are required and are currently underway.
Development of radiographic damage indicates severe PsA and affects quality of life and physical function. Identifying patients at risk for joint damage may help treatment stratification. Using data from a real-world cohort of 476 patients with early PsA, of whom 14% demonstrated progressive radiographic damage, Koc and colleagues found that female sex was a protective factor whereas old age and initial radiographic damage were risk factors for radiographic progression. These results are consistent with previous studies. Male sex, older age, and presence of radiographic damage at first visit should prompt more aggressive management to prevent further joint damage.
Regarding newer treatments, Gossec and colleagues demonstrated that bimekizumab, a monoclonal antibody targeting both interleukin (IL)-17A and IL-17F, improved disease effects in a rapid and sustained manner in patients with PsA who had not used biologic disease-modifying antirheumatic drugs or had prior inadequate response to tumor necrosis factor inhibitors. Bimekizumab is a welcome addition to the drugs available to manage PsA. Its comparative efficacy against other targeted therapies, especially other IL-17 inhibitors, is yet to be determined.
Finally, a study from the Greek multicenter PsA registry by Vassilakis and colleagues showed that, of 467 patients with PsA, 16.5% had D2T PsA. Compared with non–D2T patients, those with D2T disease were more likely to have extensive psoriasis at diagnosis, higher body mass index, and a history of inflammatory bowel disease (IBD). Treatment-resistant disease is increasingly prevalent in PsA. Certain diseases and comorbidities, such as IBD and obesity, are associated with D2T PsA. A uniform definition of D2T PsA and prospective studies to identify risk factors, as well as new strategies to manage D2T PsA, are required.
A hot topic of PsA research is whether treating psoriasis patients with biologics reduces the risk of developing PsA. Floris and colleagues analyzed data from 1023 patients with psoriasis aged 18 years or older, of whom 29.6% received biologics at least once and 21.0% had PsA. They observed that patients treated at least once vs never treated with biologics had a significantly lower risk for PsA. The "protective" effect of biologics against PsA persisted irrespective of the class of biologic used. However, the study has many built-in biases; it was not a prospective study of psoriasis patients without PsA, but rather a retrospective analysis of data collected at enrollment. Nevertheless, effective psoriasis therapies may indeed reduce the risk for PsA; prospective interventional studies are required and are currently underway.
Development of radiographic damage indicates severe PsA and affects quality of life and physical function. Identifying patients at risk for joint damage may help treatment stratification. Using data from a real-world cohort of 476 patients with early PsA, of whom 14% demonstrated progressive radiographic damage, Koc and colleagues found that female sex was a protective factor whereas old age and initial radiographic damage were risk factors for radiographic progression. These results are consistent with previous studies. Male sex, older age, and presence of radiographic damage at first visit should prompt more aggressive management to prevent further joint damage.
Regarding newer treatments, Gossec and colleagues demonstrated that bimekizumab, a monoclonal antibody targeting both interleukin (IL)-17A and IL-17F, improved disease effects in a rapid and sustained manner in patients with PsA who had not used biologic disease-modifying antirheumatic drugs or had prior inadequate response to tumor necrosis factor inhibitors. Bimekizumab is a welcome addition to the drugs available to manage PsA. Its comparative efficacy against other targeted therapies, especially other IL-17 inhibitors, is yet to be determined.
Finally, a study from the Greek multicenter PsA registry by Vassilakis and colleagues showed that, of 467 patients with PsA, 16.5% had D2T PsA. Compared with non–D2T patients, those with D2T disease were more likely to have extensive psoriasis at diagnosis, higher body mass index, and a history of inflammatory bowel disease (IBD). Treatment-resistant disease is increasingly prevalent in PsA. Certain diseases and comorbidities, such as IBD and obesity, are associated with D2T PsA. A uniform definition of D2T PsA and prospective studies to identify risk factors, as well as new strategies to manage D2T PsA, are required.
Commentary: Difficult-to-Treat PsA and Medication Options, July 2024
A hot topic of PsA research is whether treating psoriasis patients with biologics reduces the risk of developing PsA. Floris and colleagues analyzed data from 1023 patients with psoriasis aged 18 years or older, of whom 29.6% received biologics at least once and 21.0% had PsA. They observed that patients treated at least once vs never treated with biologics had a significantly lower risk for PsA. The "protective" effect of biologics against PsA persisted irrespective of the class of biologic used. However, the study has many built-in biases; it was not a prospective study of psoriasis patients without PsA, but rather a retrospective analysis of data collected at enrollment. Nevertheless, effective psoriasis therapies may indeed reduce the risk for PsA; prospective interventional studies are required and are currently underway.
Development of radiographic damage indicates severe PsA and affects quality of life and physical function. Identifying patients at risk for joint damage may help treatment stratification. Using data from a real-world cohort of 476 patients with early PsA, of whom 14% demonstrated progressive radiographic damage, Koc and colleagues found that female sex was a protective factor whereas old age and initial radiographic damage were risk factors for radiographic progression. These results are consistent with previous studies. Male sex, older age, and presence of radiographic damage at first visit should prompt more aggressive management to prevent further joint damage.
Regarding newer treatments, Gossec and colleagues demonstrated that bimekizumab, a monoclonal antibody targeting both interleukin (IL)-17A and IL-17F, improved disease effects in a rapid and sustained manner in patients with PsA who had not used biologic disease-modifying antirheumatic drugs or had prior inadequate response to tumor necrosis factor inhibitors. Bimekizumab is a welcome addition to the drugs available to manage PsA. Its comparative efficacy against other targeted therapies, especially other IL-17 inhibitors, is yet to be determined.
Finally, a study from the Greek multicenter PsA registry by Vassilakis and colleagues showed that, of 467 patients with PsA, 16.5% had D2T PsA. Compared with non–D2T patients, those with D2T disease were more likely to have extensive psoriasis at diagnosis, higher body mass index, and a history of inflammatory bowel disease (IBD). Treatment-resistant disease is increasingly prevalent in PsA. Certain diseases and comorbidities, such as IBD and obesity, are associated with D2T PsA. A uniform definition of D2T PsA and prospective studies to identify risk factors, as well as new strategies to manage D2T PsA, are required.
A hot topic of PsA research is whether treating psoriasis patients with biologics reduces the risk of developing PsA. Floris and colleagues analyzed data from 1023 patients with psoriasis aged 18 years or older, of whom 29.6% received biologics at least once and 21.0% had PsA. They observed that patients treated at least once vs never treated with biologics had a significantly lower risk for PsA. The "protective" effect of biologics against PsA persisted irrespective of the class of biologic used. However, the study has many built-in biases; it was not a prospective study of psoriasis patients without PsA, but rather a retrospective analysis of data collected at enrollment. Nevertheless, effective psoriasis therapies may indeed reduce the risk for PsA; prospective interventional studies are required and are currently underway.
Development of radiographic damage indicates severe PsA and affects quality of life and physical function. Identifying patients at risk for joint damage may help treatment stratification. Using data from a real-world cohort of 476 patients with early PsA, of whom 14% demonstrated progressive radiographic damage, Koc and colleagues found that female sex was a protective factor whereas old age and initial radiographic damage were risk factors for radiographic progression. These results are consistent with previous studies. Male sex, older age, and presence of radiographic damage at first visit should prompt more aggressive management to prevent further joint damage.
Regarding newer treatments, Gossec and colleagues demonstrated that bimekizumab, a monoclonal antibody targeting both interleukin (IL)-17A and IL-17F, improved disease effects in a rapid and sustained manner in patients with PsA who had not used biologic disease-modifying antirheumatic drugs or had prior inadequate response to tumor necrosis factor inhibitors. Bimekizumab is a welcome addition to the drugs available to manage PsA. Its comparative efficacy against other targeted therapies, especially other IL-17 inhibitors, is yet to be determined.
Finally, a study from the Greek multicenter PsA registry by Vassilakis and colleagues showed that, of 467 patients with PsA, 16.5% had D2T PsA. Compared with non–D2T patients, those with D2T disease were more likely to have extensive psoriasis at diagnosis, higher body mass index, and a history of inflammatory bowel disease (IBD). Treatment-resistant disease is increasingly prevalent in PsA. Certain diseases and comorbidities, such as IBD and obesity, are associated with D2T PsA. A uniform definition of D2T PsA and prospective studies to identify risk factors, as well as new strategies to manage D2T PsA, are required.
A hot topic of PsA research is whether treating psoriasis patients with biologics reduces the risk of developing PsA. Floris and colleagues analyzed data from 1023 patients with psoriasis aged 18 years or older, of whom 29.6% received biologics at least once and 21.0% had PsA. They observed that patients treated at least once vs never treated with biologics had a significantly lower risk for PsA. The "protective" effect of biologics against PsA persisted irrespective of the class of biologic used. However, the study has many built-in biases; it was not a prospective study of psoriasis patients without PsA, but rather a retrospective analysis of data collected at enrollment. Nevertheless, effective psoriasis therapies may indeed reduce the risk for PsA; prospective interventional studies are required and are currently underway.
Development of radiographic damage indicates severe PsA and affects quality of life and physical function. Identifying patients at risk for joint damage may help treatment stratification. Using data from a real-world cohort of 476 patients with early PsA, of whom 14% demonstrated progressive radiographic damage, Koc and colleagues found that female sex was a protective factor whereas old age and initial radiographic damage were risk factors for radiographic progression. These results are consistent with previous studies. Male sex, older age, and presence of radiographic damage at first visit should prompt more aggressive management to prevent further joint damage.
Regarding newer treatments, Gossec and colleagues demonstrated that bimekizumab, a monoclonal antibody targeting both interleukin (IL)-17A and IL-17F, improved disease effects in a rapid and sustained manner in patients with PsA who had not used biologic disease-modifying antirheumatic drugs or had prior inadequate response to tumor necrosis factor inhibitors. Bimekizumab is a welcome addition to the drugs available to manage PsA. Its comparative efficacy against other targeted therapies, especially other IL-17 inhibitors, is yet to be determined.
Finally, a study from the Greek multicenter PsA registry by Vassilakis and colleagues showed that, of 467 patients with PsA, 16.5% had D2T PsA. Compared with non–D2T patients, those with D2T disease were more likely to have extensive psoriasis at diagnosis, higher body mass index, and a history of inflammatory bowel disease (IBD). Treatment-resistant disease is increasingly prevalent in PsA. Certain diseases and comorbidities, such as IBD and obesity, are associated with D2T PsA. A uniform definition of D2T PsA and prospective studies to identify risk factors, as well as new strategies to manage D2T PsA, are required.
Commentary: Transition from Psoriasis to PsA and New Drug Analyses, June 2024
In regard to treatment, bimekizumab is a new monoclonal antibody that dually targets interleukin (IL)-17A and IL-17F and is highly efficacious for the treatment of psoriasis. In a meta-analysis of four placebo-controlled randomized clinical trials that included 1323 patients with PsA (age 18 years or older), of whom 853 received bimekizumab, Su and colleagues demonstrated that bimekizumab led to a significantly higher response rate for minimal disease activity (risk ratio [RR] 4.188; P < .001) and a 70% or greater improvement in the American College of Rheumatology (ACR) criteria (RR 7.932; P < .0001) when compared with placebo. Bimekizumab was superior to placebo in achieving ACR20/50/70 response at a dose of 160 mg. The risk for treatment-emergent adverse events was modestly higher with bimekizumab vs placebo (RR 1.423; P = .023), whereas the risk for serious cancers, upper respiratory tract infection, injection site reactions, and pharyngitis was similar for both. Thus, bimekizumab is an efficacious agent for the treatment of PsA. Future head-to-head studies will help clinicians determine the role of this drug in the management of PsA.
Not all patients respond equally well to targeted therapies, and the so-called challenging-to-treat patients are being increasingly described. Kivitz and colleagues recently described the efficacy of secukinumab, a monoclonal antibody targeting IL-17A, in these challenging-to-treat patients from the United States. In a post hoc subgroup analysis of four phase 3 studies that included 279 patients, they demonstrated that patients receiving 300 mg secukinumab and 150 mg with a loading dose had a higher rate of achieving the ACR20 response (59.7% and 43.4%, respectively) vs 15.6% for placebo (both P < .0001). The Psoriasis Area and Severity Index 90 response was 47.1% and 22.2%, respectively, vs 5.3% (both P < .05). Thus, secukinumab is efficacious in more challenging-to-treat patients. However, such patients need to be better characterized so that effective treatment strategies to achieve a state of low disease activity may be implemented.
In regard to treatment, bimekizumab is a new monoclonal antibody that dually targets interleukin (IL)-17A and IL-17F and is highly efficacious for the treatment of psoriasis. In a meta-analysis of four placebo-controlled randomized clinical trials that included 1323 patients with PsA (age 18 years or older), of whom 853 received bimekizumab, Su and colleagues demonstrated that bimekizumab led to a significantly higher response rate for minimal disease activity (risk ratio [RR] 4.188; P < .001) and a 70% or greater improvement in the American College of Rheumatology (ACR) criteria (RR 7.932; P < .0001) when compared with placebo. Bimekizumab was superior to placebo in achieving ACR20/50/70 response at a dose of 160 mg. The risk for treatment-emergent adverse events was modestly higher with bimekizumab vs placebo (RR 1.423; P = .023), whereas the risk for serious cancers, upper respiratory tract infection, injection site reactions, and pharyngitis was similar for both. Thus, bimekizumab is an efficacious agent for the treatment of PsA. Future head-to-head studies will help clinicians determine the role of this drug in the management of PsA.
Not all patients respond equally well to targeted therapies, and the so-called challenging-to-treat patients are being increasingly described. Kivitz and colleagues recently described the efficacy of secukinumab, a monoclonal antibody targeting IL-17A, in these challenging-to-treat patients from the United States. In a post hoc subgroup analysis of four phase 3 studies that included 279 patients, they demonstrated that patients receiving 300 mg secukinumab and 150 mg with a loading dose had a higher rate of achieving the ACR20 response (59.7% and 43.4%, respectively) vs 15.6% for placebo (both P < .0001). The Psoriasis Area and Severity Index 90 response was 47.1% and 22.2%, respectively, vs 5.3% (both P < .05). Thus, secukinumab is efficacious in more challenging-to-treat patients. However, such patients need to be better characterized so that effective treatment strategies to achieve a state of low disease activity may be implemented.
In regard to treatment, bimekizumab is a new monoclonal antibody that dually targets interleukin (IL)-17A and IL-17F and is highly efficacious for the treatment of psoriasis. In a meta-analysis of four placebo-controlled randomized clinical trials that included 1323 patients with PsA (age 18 years or older), of whom 853 received bimekizumab, Su and colleagues demonstrated that bimekizumab led to a significantly higher response rate for minimal disease activity (risk ratio [RR] 4.188; P < .001) and a 70% or greater improvement in the American College of Rheumatology (ACR) criteria (RR 7.932; P < .0001) when compared with placebo. Bimekizumab was superior to placebo in achieving ACR20/50/70 response at a dose of 160 mg. The risk for treatment-emergent adverse events was modestly higher with bimekizumab vs placebo (RR 1.423; P = .023), whereas the risk for serious cancers, upper respiratory tract infection, injection site reactions, and pharyngitis was similar for both. Thus, bimekizumab is an efficacious agent for the treatment of PsA. Future head-to-head studies will help clinicians determine the role of this drug in the management of PsA.
Not all patients respond equally well to targeted therapies, and the so-called challenging-to-treat patients are being increasingly described. Kivitz and colleagues recently described the efficacy of secukinumab, a monoclonal antibody targeting IL-17A, in these challenging-to-treat patients from the United States. In a post hoc subgroup analysis of four phase 3 studies that included 279 patients, they demonstrated that patients receiving 300 mg secukinumab and 150 mg with a loading dose had a higher rate of achieving the ACR20 response (59.7% and 43.4%, respectively) vs 15.6% for placebo (both P < .0001). The Psoriasis Area and Severity Index 90 response was 47.1% and 22.2%, respectively, vs 5.3% (both P < .05). Thus, secukinumab is efficacious in more challenging-to-treat patients. However, such patients need to be better characterized so that effective treatment strategies to achieve a state of low disease activity may be implemented.
Commentary: Comparisons Among PsA Therapies, May 2024
Bimekizumab is a novel biologic therapy that inhibits interleukin (IL)–17A and IL-17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. In the absence of a formal head-to-head study, matching-adjusted indirect comparison is a method to evaluate comparative effectiveness. Warren and colleagues ran a study that included biological DMARD-naive patients and patients with inadequate response to tumor necrosis factor inhibitors (TNFi-IR) with PsA who received bimekizumab (160 mg every 4 weeks; 431 and 267 patients, respectively) and guselkumab (100 mg every 4 weeks or every 8 weeks; 495 and 189 patients, respectively). They demonstrate that in biological DMARD-naive patients, bimekizumab was associated with a greater likelihood of achieving ≥70% improvement in American College of Rheumatology (ACR) response and minimal disease activity outcome at week 52 compared with guselkumab. Similar outcomes were observed in the TNFi-IR subgroup. Thus, bimekizumab may be more effective than guselkumab in PsA. Formal head-to-head studies comparing bimekizumab vs guselkumab are required.
With the availability of multiple targeted therapies for PsA, choosing the most effective and safe drug for a patient is difficult, especially in the absence of many head-to-head clinical trials. To help address this problem, Lin and Ren conducted a network meta-analysis of head-to-head active comparison studies in PsA. They included 17 studies in their analysis and demonstrated that Janus kinase inhibitors had the highest probability of achieving ACR 20/50/70 response. Treatment with IL-17A inhibitors was more likely than TNFi therapy to lead to resolution of enthesitis and dactylitis and achieving combined ACR 50 and Psoriasis Area Severity Index 100 response. Patients receiving phosphodiesterase 4 inhibitors were least likely to have adverse events. They conclude that when both efficacy and safety are considered, IL-17A inhibitors may be the better agent for initial therapy for PsA. IL-17A inhibitors are indeed safe and efficacious in PsA; more direct head-to-head comparisons as well as strategy trials are required to determine choice of first and subsequent therapy in PsA.
Infections are the most important adverse effects of targeted therapies. The risk for infection in PsA in real-world settings is not well known. In a cohort study that included 12,071 patients with PsA from the French national health insurance database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib), Bastard and colleagues demonstrated that the incidence of serious infections in users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93). Thus, the overall risk for serious infections is low, with etanercept and ustekinumab being safer treatment options than adalimumab.
Bimekizumab is a novel biologic therapy that inhibits interleukin (IL)–17A and IL-17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. In the absence of a formal head-to-head study, matching-adjusted indirect comparison is a method to evaluate comparative effectiveness. Warren and colleagues ran a study that included biological DMARD-naive patients and patients with inadequate response to tumor necrosis factor inhibitors (TNFi-IR) with PsA who received bimekizumab (160 mg every 4 weeks; 431 and 267 patients, respectively) and guselkumab (100 mg every 4 weeks or every 8 weeks; 495 and 189 patients, respectively). They demonstrate that in biological DMARD-naive patients, bimekizumab was associated with a greater likelihood of achieving ≥70% improvement in American College of Rheumatology (ACR) response and minimal disease activity outcome at week 52 compared with guselkumab. Similar outcomes were observed in the TNFi-IR subgroup. Thus, bimekizumab may be more effective than guselkumab in PsA. Formal head-to-head studies comparing bimekizumab vs guselkumab are required.
With the availability of multiple targeted therapies for PsA, choosing the most effective and safe drug for a patient is difficult, especially in the absence of many head-to-head clinical trials. To help address this problem, Lin and Ren conducted a network meta-analysis of head-to-head active comparison studies in PsA. They included 17 studies in their analysis and demonstrated that Janus kinase inhibitors had the highest probability of achieving ACR 20/50/70 response. Treatment with IL-17A inhibitors was more likely than TNFi therapy to lead to resolution of enthesitis and dactylitis and achieving combined ACR 50 and Psoriasis Area Severity Index 100 response. Patients receiving phosphodiesterase 4 inhibitors were least likely to have adverse events. They conclude that when both efficacy and safety are considered, IL-17A inhibitors may be the better agent for initial therapy for PsA. IL-17A inhibitors are indeed safe and efficacious in PsA; more direct head-to-head comparisons as well as strategy trials are required to determine choice of first and subsequent therapy in PsA.
Infections are the most important adverse effects of targeted therapies. The risk for infection in PsA in real-world settings is not well known. In a cohort study that included 12,071 patients with PsA from the French national health insurance database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib), Bastard and colleagues demonstrated that the incidence of serious infections in users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93). Thus, the overall risk for serious infections is low, with etanercept and ustekinumab being safer treatment options than adalimumab.
Bimekizumab is a novel biologic therapy that inhibits interleukin (IL)–17A and IL-17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. In the absence of a formal head-to-head study, matching-adjusted indirect comparison is a method to evaluate comparative effectiveness. Warren and colleagues ran a study that included biological DMARD-naive patients and patients with inadequate response to tumor necrosis factor inhibitors (TNFi-IR) with PsA who received bimekizumab (160 mg every 4 weeks; 431 and 267 patients, respectively) and guselkumab (100 mg every 4 weeks or every 8 weeks; 495 and 189 patients, respectively). They demonstrate that in biological DMARD-naive patients, bimekizumab was associated with a greater likelihood of achieving ≥70% improvement in American College of Rheumatology (ACR) response and minimal disease activity outcome at week 52 compared with guselkumab. Similar outcomes were observed in the TNFi-IR subgroup. Thus, bimekizumab may be more effective than guselkumab in PsA. Formal head-to-head studies comparing bimekizumab vs guselkumab are required.
With the availability of multiple targeted therapies for PsA, choosing the most effective and safe drug for a patient is difficult, especially in the absence of many head-to-head clinical trials. To help address this problem, Lin and Ren conducted a network meta-analysis of head-to-head active comparison studies in PsA. They included 17 studies in their analysis and demonstrated that Janus kinase inhibitors had the highest probability of achieving ACR 20/50/70 response. Treatment with IL-17A inhibitors was more likely than TNFi therapy to lead to resolution of enthesitis and dactylitis and achieving combined ACR 50 and Psoriasis Area Severity Index 100 response. Patients receiving phosphodiesterase 4 inhibitors were least likely to have adverse events. They conclude that when both efficacy and safety are considered, IL-17A inhibitors may be the better agent for initial therapy for PsA. IL-17A inhibitors are indeed safe and efficacious in PsA; more direct head-to-head comparisons as well as strategy trials are required to determine choice of first and subsequent therapy in PsA.
Infections are the most important adverse effects of targeted therapies. The risk for infection in PsA in real-world settings is not well known. In a cohort study that included 12,071 patients with PsA from the French national health insurance database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib), Bastard and colleagues demonstrated that the incidence of serious infections in users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93). Thus, the overall risk for serious infections is low, with etanercept and ustekinumab being safer treatment options than adalimumab.
Commentary: Gut Dysbiosis, DMARD, Joint Involvement, and MACE in PsA, April 2024
After PsA onset, early diagnosis and management leads to better long-term outcomes. These prior observations were confirmed in a study by Snoeck Henkemans and colleagues that included 708 newly diagnosed patients with PsA naive to disease-modifying antirheumatic drugs (DMARD) who were followed up for 3 years or more. Patients with a short (<12 weeks) vs long delay (>1 year) in PsA diagnosis after symptom onset were more likely to achieve minimum disease activity (OR 2.55; 95% CI 1.37-4.76). Thus, longer delay in diagnosing PsA is associated with worse clinical outcomes.
Bimekizumab is a novel biologic therapy that inhibits interleukins (IL)-17A and -17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. However, the effectiveness in PsA vis-à-vis other IL-17A inhibitors is not known. In the absence of a formal head-to-head study, matching-adjusted indirect comparisons is a method to evaluate comparative effectiveness. Such a study by Mease and colleagues included the data of patients with PsA who were biological DMARD–naive or who had an inadequate response to tumor necrosis factor inhibitors (TNFi-IR), and who received bimekizumab from the BE OPTIMAL (n = 236) and BE COMPLETE (n = 146) trials and secukinumab from the FUTURE 2 trial (n = 200). They demonstrated that, in the biological DMARD–naive subgroup, the probability of achieving at least 70% improvement in American College of Rheumatology (ACR) response was two times higher with bimekizumab (160 mg every 4 weeks) vs secukinumab (150 mg or 300 mg every 4 weeks) at week 52. In the TNFi-IR subgroup, bimekizumab had a greater likelihood of response compared with 150 mg secukinumab for ACR20, ACR70, and minimal disease activity outcomes and a greater likelihood of response compared with 300 mg secukinumab for ACR50 and minimal disease activity. Thus, bimekizumab is at least as effective as secukinumab in PsA. Formal head-to-head studies comparing bimekizumab with other IL-17A inhibitors are required.
Distal interphalangeal (DIP) joint involvement is an important manifestation of PsA and is closely related to nail dystrophy in the adjacent nail. Ixekizumab is another biologic that targets IL-17A. In a post hoc analysis of the SPIRIT-H2H study, McGonagle and colleagues confirmed that over 96% of patients with PsA and simultaneous DIP joint involvement reported adjacent nail psoriasis. When compared with adalimumab, ixekizumab led to greater improvements in DIP involvement and adjacent nail psoriasis as early as week 12 (38.8% vs 28.4%; P < .0001), with improvements sustained up to week 52 (64.9% vs 57.5%; P = .0055). This probably reflects a greater effectiveness of IL-17A inhibition in treating skin and nail psoriasis compared with TNFi.
Finally, in a population-based retrospective cohort study that included 13,905 patients with PsA (n = 1672) or rheumatoid arthritis (n = 12,233) who did not have any previous history of major adverse cardiovascular events (MACE), Meng and colleagues showed that the incidence rates of MACE were similar in patients with PsA and rheumatoid arthritis. Thus, cardiovascular risk management should be similarly aggressive in patients with PsA and rheumatoid arthritis.
After PsA onset, early diagnosis and management leads to better long-term outcomes. These prior observations were confirmed in a study by Snoeck Henkemans and colleagues that included 708 newly diagnosed patients with PsA naive to disease-modifying antirheumatic drugs (DMARD) who were followed up for 3 years or more. Patients with a short (<12 weeks) vs long delay (>1 year) in PsA diagnosis after symptom onset were more likely to achieve minimum disease activity (OR 2.55; 95% CI 1.37-4.76). Thus, longer delay in diagnosing PsA is associated with worse clinical outcomes.
Bimekizumab is a novel biologic therapy that inhibits interleukins (IL)-17A and -17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. However, the effectiveness in PsA vis-à-vis other IL-17A inhibitors is not known. In the absence of a formal head-to-head study, matching-adjusted indirect comparisons is a method to evaluate comparative effectiveness. Such a study by Mease and colleagues included the data of patients with PsA who were biological DMARD–naive or who had an inadequate response to tumor necrosis factor inhibitors (TNFi-IR), and who received bimekizumab from the BE OPTIMAL (n = 236) and BE COMPLETE (n = 146) trials and secukinumab from the FUTURE 2 trial (n = 200). They demonstrated that, in the biological DMARD–naive subgroup, the probability of achieving at least 70% improvement in American College of Rheumatology (ACR) response was two times higher with bimekizumab (160 mg every 4 weeks) vs secukinumab (150 mg or 300 mg every 4 weeks) at week 52. In the TNFi-IR subgroup, bimekizumab had a greater likelihood of response compared with 150 mg secukinumab for ACR20, ACR70, and minimal disease activity outcomes and a greater likelihood of response compared with 300 mg secukinumab for ACR50 and minimal disease activity. Thus, bimekizumab is at least as effective as secukinumab in PsA. Formal head-to-head studies comparing bimekizumab with other IL-17A inhibitors are required.
Distal interphalangeal (DIP) joint involvement is an important manifestation of PsA and is closely related to nail dystrophy in the adjacent nail. Ixekizumab is another biologic that targets IL-17A. In a post hoc analysis of the SPIRIT-H2H study, McGonagle and colleagues confirmed that over 96% of patients with PsA and simultaneous DIP joint involvement reported adjacent nail psoriasis. When compared with adalimumab, ixekizumab led to greater improvements in DIP involvement and adjacent nail psoriasis as early as week 12 (38.8% vs 28.4%; P < .0001), with improvements sustained up to week 52 (64.9% vs 57.5%; P = .0055). This probably reflects a greater effectiveness of IL-17A inhibition in treating skin and nail psoriasis compared with TNFi.
Finally, in a population-based retrospective cohort study that included 13,905 patients with PsA (n = 1672) or rheumatoid arthritis (n = 12,233) who did not have any previous history of major adverse cardiovascular events (MACE), Meng and colleagues showed that the incidence rates of MACE were similar in patients with PsA and rheumatoid arthritis. Thus, cardiovascular risk management should be similarly aggressive in patients with PsA and rheumatoid arthritis.
After PsA onset, early diagnosis and management leads to better long-term outcomes. These prior observations were confirmed in a study by Snoeck Henkemans and colleagues that included 708 newly diagnosed patients with PsA naive to disease-modifying antirheumatic drugs (DMARD) who were followed up for 3 years or more. Patients with a short (<12 weeks) vs long delay (>1 year) in PsA diagnosis after symptom onset were more likely to achieve minimum disease activity (OR 2.55; 95% CI 1.37-4.76). Thus, longer delay in diagnosing PsA is associated with worse clinical outcomes.
Bimekizumab is a novel biologic therapy that inhibits interleukins (IL)-17A and -17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. However, the effectiveness in PsA vis-à-vis other IL-17A inhibitors is not known. In the absence of a formal head-to-head study, matching-adjusted indirect comparisons is a method to evaluate comparative effectiveness. Such a study by Mease and colleagues included the data of patients with PsA who were biological DMARD–naive or who had an inadequate response to tumor necrosis factor inhibitors (TNFi-IR), and who received bimekizumab from the BE OPTIMAL (n = 236) and BE COMPLETE (n = 146) trials and secukinumab from the FUTURE 2 trial (n = 200). They demonstrated that, in the biological DMARD–naive subgroup, the probability of achieving at least 70% improvement in American College of Rheumatology (ACR) response was two times higher with bimekizumab (160 mg every 4 weeks) vs secukinumab (150 mg or 300 mg every 4 weeks) at week 52. In the TNFi-IR subgroup, bimekizumab had a greater likelihood of response compared with 150 mg secukinumab for ACR20, ACR70, and minimal disease activity outcomes and a greater likelihood of response compared with 300 mg secukinumab for ACR50 and minimal disease activity. Thus, bimekizumab is at least as effective as secukinumab in PsA. Formal head-to-head studies comparing bimekizumab with other IL-17A inhibitors are required.
Distal interphalangeal (DIP) joint involvement is an important manifestation of PsA and is closely related to nail dystrophy in the adjacent nail. Ixekizumab is another biologic that targets IL-17A. In a post hoc analysis of the SPIRIT-H2H study, McGonagle and colleagues confirmed that over 96% of patients with PsA and simultaneous DIP joint involvement reported adjacent nail psoriasis. When compared with adalimumab, ixekizumab led to greater improvements in DIP involvement and adjacent nail psoriasis as early as week 12 (38.8% vs 28.4%; P < .0001), with improvements sustained up to week 52 (64.9% vs 57.5%; P = .0055). This probably reflects a greater effectiveness of IL-17A inhibition in treating skin and nail psoriasis compared with TNFi.
Finally, in a population-based retrospective cohort study that included 13,905 patients with PsA (n = 1672) or rheumatoid arthritis (n = 12,233) who did not have any previous history of major adverse cardiovascular events (MACE), Meng and colleagues showed that the incidence rates of MACE were similar in patients with PsA and rheumatoid arthritis. Thus, cardiovascular risk management should be similarly aggressive in patients with PsA and rheumatoid arthritis.
Commentary: PsA Comorbidities and Treatment Safety and Effectiveness, March 2024
An important comorbidity of PsA is vascular inflammation leading to accelerated atherosclerosis, and higher risk for cardiovascular and cerebrovascular disease. Previously, vascular imaging modalities have demonstrated vascular inflammation in PsA. In a cross-sectional study that included 75 patients with active PsA and 40 control individuals without PsA, Kleinrensink and colleagues demonstrated that vascular inflammation of the whole aorta was significantly increased in patients with PsA vs control individuals. Of note, the association remained significant after adjusting for gender, age, body mass index, mean arterial pressure, and aortic calcification, but it was not associated with disease-related parameters. Further studies to determine the contributions of PsA per se and its comorbidities to vascular inflammation are required. Nevertheless, the management of PsA should include close monitoring and aggressive treatment of risk factors for atherosclerotic vascular disease.
Psychotic disorders are known to be associated with psoriasis, but their association with PsA is less well known. Using French health administrative data, Brenaut and colleagues showed that the prevalence of psychotic disorders was higher in individuals with psoriasis but surprisingly lower in individuals with PsA, compared with the general population. Moreover, a co-diagnosis of psoriasis/PsA and psychotic disorders was associated with an increased mortality rate and at a lower age.
Clinical trials have demonstrated that Janus kinase (JAK) inhibitors have a remarkable efficacy in the treatment of the musculoskeletal manifestations of PsA. Observational studies are important to evaluate effectiveness in real-world settings. In a study that included 123 patients with PsA from the CorEvitas PsA/Spondyloarthritis Registry who were treated with tofacitinib, Mease and colleagues observed that a quarter of patients achieved a state of low disease activity, based on the Clinical Disease Activity Index for PsA at 6 ± 3 months of follow-up. A substantial proportion of patients also reported the resolution of dactylitis (29.4%) and enthesitis (42.9%). Although these results are remarkable compared with what was seen with older therapies, one must note that only a quarter of patients achieved remission; more effective regimens for improving outcomes in PsA are required.
The safety of newer therapies is always of concern. It is reassuring that a meta-analysis of six randomized controlled trials that included 5038 patients with PsA who received either risankizumab (an anti-interleukin-23 antibody) or placebo by Su and colleagues demonstrated that the incidences of serious adverse events and serious treatment-emergent adverse events were similar between the risankizumab and placebo groups. Given the excellent safety profile of some of the newer therapies for PsA, trials with combinations of newer targeted therapies in treatment-resistant PsA should be conducted.
An important comorbidity of PsA is vascular inflammation leading to accelerated atherosclerosis, and higher risk for cardiovascular and cerebrovascular disease. Previously, vascular imaging modalities have demonstrated vascular inflammation in PsA. In a cross-sectional study that included 75 patients with active PsA and 40 control individuals without PsA, Kleinrensink and colleagues demonstrated that vascular inflammation of the whole aorta was significantly increased in patients with PsA vs control individuals. Of note, the association remained significant after adjusting for gender, age, body mass index, mean arterial pressure, and aortic calcification, but it was not associated with disease-related parameters. Further studies to determine the contributions of PsA per se and its comorbidities to vascular inflammation are required. Nevertheless, the management of PsA should include close monitoring and aggressive treatment of risk factors for atherosclerotic vascular disease.
Psychotic disorders are known to be associated with psoriasis, but their association with PsA is less well known. Using French health administrative data, Brenaut and colleagues showed that the prevalence of psychotic disorders was higher in individuals with psoriasis but surprisingly lower in individuals with PsA, compared with the general population. Moreover, a co-diagnosis of psoriasis/PsA and psychotic disorders was associated with an increased mortality rate and at a lower age.
Clinical trials have demonstrated that Janus kinase (JAK) inhibitors have a remarkable efficacy in the treatment of the musculoskeletal manifestations of PsA. Observational studies are important to evaluate effectiveness in real-world settings. In a study that included 123 patients with PsA from the CorEvitas PsA/Spondyloarthritis Registry who were treated with tofacitinib, Mease and colleagues observed that a quarter of patients achieved a state of low disease activity, based on the Clinical Disease Activity Index for PsA at 6 ± 3 months of follow-up. A substantial proportion of patients also reported the resolution of dactylitis (29.4%) and enthesitis (42.9%). Although these results are remarkable compared with what was seen with older therapies, one must note that only a quarter of patients achieved remission; more effective regimens for improving outcomes in PsA are required.
The safety of newer therapies is always of concern. It is reassuring that a meta-analysis of six randomized controlled trials that included 5038 patients with PsA who received either risankizumab (an anti-interleukin-23 antibody) or placebo by Su and colleagues demonstrated that the incidences of serious adverse events and serious treatment-emergent adverse events were similar between the risankizumab and placebo groups. Given the excellent safety profile of some of the newer therapies for PsA, trials with combinations of newer targeted therapies in treatment-resistant PsA should be conducted.
An important comorbidity of PsA is vascular inflammation leading to accelerated atherosclerosis, and higher risk for cardiovascular and cerebrovascular disease. Previously, vascular imaging modalities have demonstrated vascular inflammation in PsA. In a cross-sectional study that included 75 patients with active PsA and 40 control individuals without PsA, Kleinrensink and colleagues demonstrated that vascular inflammation of the whole aorta was significantly increased in patients with PsA vs control individuals. Of note, the association remained significant after adjusting for gender, age, body mass index, mean arterial pressure, and aortic calcification, but it was not associated with disease-related parameters. Further studies to determine the contributions of PsA per se and its comorbidities to vascular inflammation are required. Nevertheless, the management of PsA should include close monitoring and aggressive treatment of risk factors for atherosclerotic vascular disease.
Psychotic disorders are known to be associated with psoriasis, but their association with PsA is less well known. Using French health administrative data, Brenaut and colleagues showed that the prevalence of psychotic disorders was higher in individuals with psoriasis but surprisingly lower in individuals with PsA, compared with the general population. Moreover, a co-diagnosis of psoriasis/PsA and psychotic disorders was associated with an increased mortality rate and at a lower age.
Clinical trials have demonstrated that Janus kinase (JAK) inhibitors have a remarkable efficacy in the treatment of the musculoskeletal manifestations of PsA. Observational studies are important to evaluate effectiveness in real-world settings. In a study that included 123 patients with PsA from the CorEvitas PsA/Spondyloarthritis Registry who were treated with tofacitinib, Mease and colleagues observed that a quarter of patients achieved a state of low disease activity, based on the Clinical Disease Activity Index for PsA at 6 ± 3 months of follow-up. A substantial proportion of patients also reported the resolution of dactylitis (29.4%) and enthesitis (42.9%). Although these results are remarkable compared with what was seen with older therapies, one must note that only a quarter of patients achieved remission; more effective regimens for improving outcomes in PsA are required.
The safety of newer therapies is always of concern. It is reassuring that a meta-analysis of six randomized controlled trials that included 5038 patients with PsA who received either risankizumab (an anti-interleukin-23 antibody) or placebo by Su and colleagues demonstrated that the incidences of serious adverse events and serious treatment-emergent adverse events were similar between the risankizumab and placebo groups. Given the excellent safety profile of some of the newer therapies for PsA, trials with combinations of newer targeted therapies in treatment-resistant PsA should be conducted.
Commentary: PsA in Women, February 2024
Another study investigated the persistence of targeted therapies for PsA in women compared with men. In a nationwide cohort study using administrative information from French health insurance, the study looked at 14,778 patients (57% women) with PsA who were new users of targeted therapies. The study showed that women had 20%-40% lower treatment persistence rates than men for tumour necrosis factor (TNF) inhibitors (adjusted hazard ratio [aHR] 1.4; 99% CI 1.3-1.5) and interleukin (IL)-17 inhibitors (aHR 1.2; 99% CI 1.1-1.3). However, the treatment persistence between both sexes was comparable for IL-12/23 inhibitor (aHR 1.1; 99% CI 0.9-1.3), IL-23 inhibitor (aHR 1.1; 99% CI 0.7-1.5), and Janus kinase (JAK) inhibitor (aHR 1.2; 99% CI 0.9-1.6) therapies. The paradigm that women have lower treatment persistence is based on studies done primarily in patients treated with TNF inhibitors. This study and a few other recent studies challenge this paradigm by indicating that other targeted therapies, especially JAK inhibitors, may not have lower persistence in women. Sex should be taken into consideration while choosing and counseling women about PsA therapies.
There are few studies on exercise and its impact on PsA. Functional training (FT) and resistance training (RT) may improve functional capacity and quality of life of patients with PsA. The safety of exercise is also not known, given that (micro)trauma is a risk factor for PsA. To evaluate this, Silva and colleagues conducted a 12-week, single-blind trial including 41 patients with PsA who were randomly assigned to undergo FT with elastic bands or RT with weight machines. They demonstrated that FT and RT led to similar improvements in functional capacity measured by the Bath Ankylosing Spondylitis Functional Index (P = .919), functional status measured by the Health Assessment Questionnaire for Spondyloarthritis (P = .932), disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (P = .700), and muscle strength. No adverse events occurred in either group. Thus, FT and RT improved functional capacity, functional status, disease activity, and muscle strength to a comparable extent in patients with PsA, with no adverse events. Both modalities may be recommended for PsA patients.
Finally, a cross-sectional study that included 503 patients with PsA, of whom 160 patients underwent treatment escalation, evaluated whether the patient-reported outcome (PsA Impact of Disease questionnaire [PsAID-12]) affected treatment decisions by the treating rheumatologist. Coyle and colleagues demonstrated that although PsAID-12 scores were higher in patients who did vs did not have a treatment escalation, physicians relied more on their assessment of disease activity rather than the PsAID-12 scores when making treatment-related decisions. Of note, physicians also reported that PsAID-12 scores influenced treatment reduction decisions.
Another study investigated the persistence of targeted therapies for PsA in women compared with men. In a nationwide cohort study using administrative information from French health insurance, the study looked at 14,778 patients (57% women) with PsA who were new users of targeted therapies. The study showed that women had 20%-40% lower treatment persistence rates than men for tumour necrosis factor (TNF) inhibitors (adjusted hazard ratio [aHR] 1.4; 99% CI 1.3-1.5) and interleukin (IL)-17 inhibitors (aHR 1.2; 99% CI 1.1-1.3). However, the treatment persistence between both sexes was comparable for IL-12/23 inhibitor (aHR 1.1; 99% CI 0.9-1.3), IL-23 inhibitor (aHR 1.1; 99% CI 0.7-1.5), and Janus kinase (JAK) inhibitor (aHR 1.2; 99% CI 0.9-1.6) therapies. The paradigm that women have lower treatment persistence is based on studies done primarily in patients treated with TNF inhibitors. This study and a few other recent studies challenge this paradigm by indicating that other targeted therapies, especially JAK inhibitors, may not have lower persistence in women. Sex should be taken into consideration while choosing and counseling women about PsA therapies.
There are few studies on exercise and its impact on PsA. Functional training (FT) and resistance training (RT) may improve functional capacity and quality of life of patients with PsA. The safety of exercise is also not known, given that (micro)trauma is a risk factor for PsA. To evaluate this, Silva and colleagues conducted a 12-week, single-blind trial including 41 patients with PsA who were randomly assigned to undergo FT with elastic bands or RT with weight machines. They demonstrated that FT and RT led to similar improvements in functional capacity measured by the Bath Ankylosing Spondylitis Functional Index (P = .919), functional status measured by the Health Assessment Questionnaire for Spondyloarthritis (P = .932), disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (P = .700), and muscle strength. No adverse events occurred in either group. Thus, FT and RT improved functional capacity, functional status, disease activity, and muscle strength to a comparable extent in patients with PsA, with no adverse events. Both modalities may be recommended for PsA patients.
Finally, a cross-sectional study that included 503 patients with PsA, of whom 160 patients underwent treatment escalation, evaluated whether the patient-reported outcome (PsA Impact of Disease questionnaire [PsAID-12]) affected treatment decisions by the treating rheumatologist. Coyle and colleagues demonstrated that although PsAID-12 scores were higher in patients who did vs did not have a treatment escalation, physicians relied more on their assessment of disease activity rather than the PsAID-12 scores when making treatment-related decisions. Of note, physicians also reported that PsAID-12 scores influenced treatment reduction decisions.
Another study investigated the persistence of targeted therapies for PsA in women compared with men. In a nationwide cohort study using administrative information from French health insurance, the study looked at 14,778 patients (57% women) with PsA who were new users of targeted therapies. The study showed that women had 20%-40% lower treatment persistence rates than men for tumour necrosis factor (TNF) inhibitors (adjusted hazard ratio [aHR] 1.4; 99% CI 1.3-1.5) and interleukin (IL)-17 inhibitors (aHR 1.2; 99% CI 1.1-1.3). However, the treatment persistence between both sexes was comparable for IL-12/23 inhibitor (aHR 1.1; 99% CI 0.9-1.3), IL-23 inhibitor (aHR 1.1; 99% CI 0.7-1.5), and Janus kinase (JAK) inhibitor (aHR 1.2; 99% CI 0.9-1.6) therapies. The paradigm that women have lower treatment persistence is based on studies done primarily in patients treated with TNF inhibitors. This study and a few other recent studies challenge this paradigm by indicating that other targeted therapies, especially JAK inhibitors, may not have lower persistence in women. Sex should be taken into consideration while choosing and counseling women about PsA therapies.
There are few studies on exercise and its impact on PsA. Functional training (FT) and resistance training (RT) may improve functional capacity and quality of life of patients with PsA. The safety of exercise is also not known, given that (micro)trauma is a risk factor for PsA. To evaluate this, Silva and colleagues conducted a 12-week, single-blind trial including 41 patients with PsA who were randomly assigned to undergo FT with elastic bands or RT with weight machines. They demonstrated that FT and RT led to similar improvements in functional capacity measured by the Bath Ankylosing Spondylitis Functional Index (P = .919), functional status measured by the Health Assessment Questionnaire for Spondyloarthritis (P = .932), disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (P = .700), and muscle strength. No adverse events occurred in either group. Thus, FT and RT improved functional capacity, functional status, disease activity, and muscle strength to a comparable extent in patients with PsA, with no adverse events. Both modalities may be recommended for PsA patients.
Finally, a cross-sectional study that included 503 patients with PsA, of whom 160 patients underwent treatment escalation, evaluated whether the patient-reported outcome (PsA Impact of Disease questionnaire [PsAID-12]) affected treatment decisions by the treating rheumatologist. Coyle and colleagues demonstrated that although PsAID-12 scores were higher in patients who did vs did not have a treatment escalation, physicians relied more on their assessment of disease activity rather than the PsAID-12 scores when making treatment-related decisions. Of note, physicians also reported that PsAID-12 scores influenced treatment reduction decisions.
Commentary: Variations in DMARD Effectiveness and Enthesitis Treatment in PsA, January 2024
Treatment of enthesitis can be challenging. Head-to-head clinical trials using clinical enthesitis indices have indicated that TNF inhibitors and IL-17 inhibitors have similar efficacy in treating enthesitis. However, clinically determined enthesitis may not be true inflammatory enthesitis. Ultrasonography-confirmed enthesitis probably reflects true enthesitis. Therefore, Elliot and colleagues conducted an observational study that compared the change in MAdrid Sonographic Enthesitis Index (MASEI) at 16 weeks of treatment with either TNF inhibitors or secukinumab. They observed that the mean reduction in MASEI that assesses both active and chronic entheseal disease was not significantly different with TNF inhibitors vs secukinumab treatment. However, TNF inhibitors were significantly more effective than secukinumab when only active entheseal lesions were considered. Thus, TNF inhibitors may be more effective for active enthesitis; randomized trials using ultrasonographic enthesitis indices comparing the two treatments are required.
Serum drug levels have previously been shown to be associated with response to bDMARD therapy, but use of drug-level measurement is not routine in rheumatology practice. Moreover, trough levels are emphasized and may not often be feasible to obtain. Curry and colleagues investigated the relationship between serum non-trough drug levels (SDL) and treatment response at 3 months in patients with PsA who initiated treatment with adalimumab (n = 104) or etanercept (n = 97). They demonstrated that patients with higher etanercept SDL or higher adalimumab SDL were significantly more likely to be responders. A non-trough etanercept SDL of 2.0 µg/mL and adalimumab SDL of 3.6 µg/mL could differentiate between responders and nonresponders with ~50% specificity and > 60% sensitivity. However, the area under the receiver operating characteristic curves were only about 65%; thus, the ability of SDL to discriminate between responders and nonresponders is low.
Treatment of enthesitis can be challenging. Head-to-head clinical trials using clinical enthesitis indices have indicated that TNF inhibitors and IL-17 inhibitors have similar efficacy in treating enthesitis. However, clinically determined enthesitis may not be true inflammatory enthesitis. Ultrasonography-confirmed enthesitis probably reflects true enthesitis. Therefore, Elliot and colleagues conducted an observational study that compared the change in MAdrid Sonographic Enthesitis Index (MASEI) at 16 weeks of treatment with either TNF inhibitors or secukinumab. They observed that the mean reduction in MASEI that assesses both active and chronic entheseal disease was not significantly different with TNF inhibitors vs secukinumab treatment. However, TNF inhibitors were significantly more effective than secukinumab when only active entheseal lesions were considered. Thus, TNF inhibitors may be more effective for active enthesitis; randomized trials using ultrasonographic enthesitis indices comparing the two treatments are required.
Serum drug levels have previously been shown to be associated with response to bDMARD therapy, but use of drug-level measurement is not routine in rheumatology practice. Moreover, trough levels are emphasized and may not often be feasible to obtain. Curry and colleagues investigated the relationship between serum non-trough drug levels (SDL) and treatment response at 3 months in patients with PsA who initiated treatment with adalimumab (n = 104) or etanercept (n = 97). They demonstrated that patients with higher etanercept SDL or higher adalimumab SDL were significantly more likely to be responders. A non-trough etanercept SDL of 2.0 µg/mL and adalimumab SDL of 3.6 µg/mL could differentiate between responders and nonresponders with ~50% specificity and > 60% sensitivity. However, the area under the receiver operating characteristic curves were only about 65%; thus, the ability of SDL to discriminate between responders and nonresponders is low.
Treatment of enthesitis can be challenging. Head-to-head clinical trials using clinical enthesitis indices have indicated that TNF inhibitors and IL-17 inhibitors have similar efficacy in treating enthesitis. However, clinically determined enthesitis may not be true inflammatory enthesitis. Ultrasonography-confirmed enthesitis probably reflects true enthesitis. Therefore, Elliot and colleagues conducted an observational study that compared the change in MAdrid Sonographic Enthesitis Index (MASEI) at 16 weeks of treatment with either TNF inhibitors or secukinumab. They observed that the mean reduction in MASEI that assesses both active and chronic entheseal disease was not significantly different with TNF inhibitors vs secukinumab treatment. However, TNF inhibitors were significantly more effective than secukinumab when only active entheseal lesions were considered. Thus, TNF inhibitors may be more effective for active enthesitis; randomized trials using ultrasonographic enthesitis indices comparing the two treatments are required.
Serum drug levels have previously been shown to be associated with response to bDMARD therapy, but use of drug-level measurement is not routine in rheumatology practice. Moreover, trough levels are emphasized and may not often be feasible to obtain. Curry and colleagues investigated the relationship between serum non-trough drug levels (SDL) and treatment response at 3 months in patients with PsA who initiated treatment with adalimumab (n = 104) or etanercept (n = 97). They demonstrated that patients with higher etanercept SDL or higher adalimumab SDL were significantly more likely to be responders. A non-trough etanercept SDL of 2.0 µg/mL and adalimumab SDL of 3.6 µg/mL could differentiate between responders and nonresponders with ~50% specificity and > 60% sensitivity. However, the area under the receiver operating characteristic curves were only about 65%; thus, the ability of SDL to discriminate between responders and nonresponders is low.
Commentary: Examining DMARD Use in PsA, December 2023
Limiting radiographic progression is an important long-term goal of treatment of PsA. In a post hoc analysis that included 449 biologic-naive patients with PsA from the DISCOVER-2 trial who received 100 mg guselkumab every 4 or 8 weeks, Mease and colleagues demonstrated that a greater improvement in the Disease Activity Index for PsA (DAPSA) scores as early as week 8 and the achievement of DAPSA low disease activity at week 8 were associated with a significantly lower progression of radiographic joint damage (total PsA-modified van der Heijde-Sharp score) through week 100. Thus, patients who respond well early have better long-term outcomes.
The safety of targeted therapies is always of concern and is inadequately addressed by individual clinical trials. Meta-analyses may provide further insights. In a network meta-analysis of 94 randomized controlled trials that included a total of 54,369 patients with PsA or psoriasis who were treated with 14 biologics, five small molecules, or placebo, Chiu and colleagues found that for patients with psoriasis, infliximab, deucravacitinib, and bimekizumab had the highest risks for infection. In patients with PsA, bimekizumab, apremilast, and 30 mg upadacitinib led to a significantly higher risk for infection compared with placebo, and 30 mg upadacitinib also increasing the risk for serious infection compared with placebo. The risk for infection in patients with PsA did not increase with most bDMARD and targeted synthetic DMARD (tsDMARD), except bimekizumab, apremilast, and 30 mg upadacitinib.
There is increasing recognition of the difficulty in managing patients with refractory PsA. One approach to such difficult-to-treat disease is dual targeted therapy (DTT). However, the safety of these combinations is of major concern. There is currently an ongoing clinical trial comparing a combination of guselkumab and golimumab vs guselkumab alone for treatment-resistant PsA. In the meantime, Valero-Martinez and colleagues have reported results from an observational, retrospective, cross-sectional study that included patients with refractory PsA (n = 14) or spondyloarthritis (n = 22) who simultaneously received two bDMARD or tsDMARD with different therapeutic targets. The most commonly used combinations were a tumor necrosis factor (TNF) inhibitor plus an interleukin (IL)-12/23 pathway inhibitor, followed by a TNF inhibitor plus an IL-17 inhibitor. They found that at a median exposure of 14.86 months, the DTT retention rate in patients with PsA was 42.8%, with 40.0% and 53.3% of patients achieving remission or low activity and major clinical improvements, respectively. Treatment discontinuation due to adverse events was reported in one patient with PsA and multiple comorbidities. Thus, DTT led to satisfactory clinical improvements and no serious adverse events in patients with refractory PsA. The results of larger observational and randomized trials are awaited.
Limiting radiographic progression is an important long-term goal of treatment of PsA. In a post hoc analysis that included 449 biologic-naive patients with PsA from the DISCOVER-2 trial who received 100 mg guselkumab every 4 or 8 weeks, Mease and colleagues demonstrated that a greater improvement in the Disease Activity Index for PsA (DAPSA) scores as early as week 8 and the achievement of DAPSA low disease activity at week 8 were associated with a significantly lower progression of radiographic joint damage (total PsA-modified van der Heijde-Sharp score) through week 100. Thus, patients who respond well early have better long-term outcomes.
The safety of targeted therapies is always of concern and is inadequately addressed by individual clinical trials. Meta-analyses may provide further insights. In a network meta-analysis of 94 randomized controlled trials that included a total of 54,369 patients with PsA or psoriasis who were treated with 14 biologics, five small molecules, or placebo, Chiu and colleagues found that for patients with psoriasis, infliximab, deucravacitinib, and bimekizumab had the highest risks for infection. In patients with PsA, bimekizumab, apremilast, and 30 mg upadacitinib led to a significantly higher risk for infection compared with placebo, and 30 mg upadacitinib also increasing the risk for serious infection compared with placebo. The risk for infection in patients with PsA did not increase with most bDMARD and targeted synthetic DMARD (tsDMARD), except bimekizumab, apremilast, and 30 mg upadacitinib.
There is increasing recognition of the difficulty in managing patients with refractory PsA. One approach to such difficult-to-treat disease is dual targeted therapy (DTT). However, the safety of these combinations is of major concern. There is currently an ongoing clinical trial comparing a combination of guselkumab and golimumab vs guselkumab alone for treatment-resistant PsA. In the meantime, Valero-Martinez and colleagues have reported results from an observational, retrospective, cross-sectional study that included patients with refractory PsA (n = 14) or spondyloarthritis (n = 22) who simultaneously received two bDMARD or tsDMARD with different therapeutic targets. The most commonly used combinations were a tumor necrosis factor (TNF) inhibitor plus an interleukin (IL)-12/23 pathway inhibitor, followed by a TNF inhibitor plus an IL-17 inhibitor. They found that at a median exposure of 14.86 months, the DTT retention rate in patients with PsA was 42.8%, with 40.0% and 53.3% of patients achieving remission or low activity and major clinical improvements, respectively. Treatment discontinuation due to adverse events was reported in one patient with PsA and multiple comorbidities. Thus, DTT led to satisfactory clinical improvements and no serious adverse events in patients with refractory PsA. The results of larger observational and randomized trials are awaited.
Limiting radiographic progression is an important long-term goal of treatment of PsA. In a post hoc analysis that included 449 biologic-naive patients with PsA from the DISCOVER-2 trial who received 100 mg guselkumab every 4 or 8 weeks, Mease and colleagues demonstrated that a greater improvement in the Disease Activity Index for PsA (DAPSA) scores as early as week 8 and the achievement of DAPSA low disease activity at week 8 were associated with a significantly lower progression of radiographic joint damage (total PsA-modified van der Heijde-Sharp score) through week 100. Thus, patients who respond well early have better long-term outcomes.
The safety of targeted therapies is always of concern and is inadequately addressed by individual clinical trials. Meta-analyses may provide further insights. In a network meta-analysis of 94 randomized controlled trials that included a total of 54,369 patients with PsA or psoriasis who were treated with 14 biologics, five small molecules, or placebo, Chiu and colleagues found that for patients with psoriasis, infliximab, deucravacitinib, and bimekizumab had the highest risks for infection. In patients with PsA, bimekizumab, apremilast, and 30 mg upadacitinib led to a significantly higher risk for infection compared with placebo, and 30 mg upadacitinib also increasing the risk for serious infection compared with placebo. The risk for infection in patients with PsA did not increase with most bDMARD and targeted synthetic DMARD (tsDMARD), except bimekizumab, apremilast, and 30 mg upadacitinib.
There is increasing recognition of the difficulty in managing patients with refractory PsA. One approach to such difficult-to-treat disease is dual targeted therapy (DTT). However, the safety of these combinations is of major concern. There is currently an ongoing clinical trial comparing a combination of guselkumab and golimumab vs guselkumab alone for treatment-resistant PsA. In the meantime, Valero-Martinez and colleagues have reported results from an observational, retrospective, cross-sectional study that included patients with refractory PsA (n = 14) or spondyloarthritis (n = 22) who simultaneously received two bDMARD or tsDMARD with different therapeutic targets. The most commonly used combinations were a tumor necrosis factor (TNF) inhibitor plus an interleukin (IL)-12/23 pathway inhibitor, followed by a TNF inhibitor plus an IL-17 inhibitor. They found that at a median exposure of 14.86 months, the DTT retention rate in patients with PsA was 42.8%, with 40.0% and 53.3% of patients achieving remission or low activity and major clinical improvements, respectively. Treatment discontinuation due to adverse events was reported in one patient with PsA and multiple comorbidities. Thus, DTT led to satisfactory clinical improvements and no serious adverse events in patients with refractory PsA. The results of larger observational and randomized trials are awaited.
Commentary: Diagnostic Delay and Optimal Treatments for PsA, November 2023
There is steady advance in the treatment of PsA. Bimekizumab is a novel monoclonal antibody that, by binding to similar sites on interleukin (IL)-17A and IL-17F, inhibits these cytokines. Ritchlin and colleagues recently reported the 52-week results from the phase 3 BE OPTIMAL study including 852 biological disease-modifying antirheumatic drug (bDMARD)-naive patients with active PsA who were randomly assigned to receive bimekizumab, adalimumab, or placebo. At week 16, 43.9% of patients receiving bimekizumab achieved ≥ 50% improvement in the American College of Rheumatology scores (ACR50), with the response being maintained up to week 52 (54.5%). Among patients who switched from placebo to bimekizumab at week 16, a similar proportion (53.0%) achieved ACR50 at week 52. No new safety signals were observed. Thus, bimekizumab led to sustained improvements in clinical response up to week 52 and probably will soon be available to patients with PsA.
The optimal management of axial PsA continues to be investigated. One major question is whether IL-23 inhibitors, which are not efficacious in axial spondyloarthritis, have efficacy in axial PsA. A post hoc analysis of the DISCOVER-2 study included 246 biologic-naive patients with active PsA and sacroiliitis who were randomly assigned to guselkumab every 4 weeks (Q4W; n = 82), guselkumab every 8 weeks (Q8W; n = 68), or placebo with crossover to guselkumab Q4W at week 24 (n = 96), Mease and colleagues report that at week 24, guselkumab Q4W and Q8W vs placebo showed significantly greater scores in the total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as well as Ankylosing Spondylitis Disease Activity Score (ASDAS), with further improvements noted at week 100. Thus, in patients with active PsA and imaging-confirmed sacroiliitis, 100 mg guselkumab Q4W and Q8W yielded clinically meaningful and sustained improvements in axial symptoms through 2 years.
Finally, attention is currently being paid to patients with refractory or difficult-to-treat (D2T) PsA. These patients are generally characterized as having active disease despite treatment with two or more targeted DMARD (tDMARD). Philippoteaux and colleagues have reported results from their retrospective cohort study that included 150 patients with PsA who initiated treatment with tDMARD and were followed for at least 2 years, of whom 49 patients had D2T PsA. They found that peripheral structural damage, axial involvement, and the discontinuation of bDMARD due to poor skin psoriasis control were more prevalent in patients with D2T PsA compared with in non-D2T PsA. Thus, patients with D2T PsA are more likely to have more structural damage. Early diagnosis and treatment to reduce structural damage might reduce the prevalence of D2T PsA.
There is steady advance in the treatment of PsA. Bimekizumab is a novel monoclonal antibody that, by binding to similar sites on interleukin (IL)-17A and IL-17F, inhibits these cytokines. Ritchlin and colleagues recently reported the 52-week results from the phase 3 BE OPTIMAL study including 852 biological disease-modifying antirheumatic drug (bDMARD)-naive patients with active PsA who were randomly assigned to receive bimekizumab, adalimumab, or placebo. At week 16, 43.9% of patients receiving bimekizumab achieved ≥ 50% improvement in the American College of Rheumatology scores (ACR50), with the response being maintained up to week 52 (54.5%). Among patients who switched from placebo to bimekizumab at week 16, a similar proportion (53.0%) achieved ACR50 at week 52. No new safety signals were observed. Thus, bimekizumab led to sustained improvements in clinical response up to week 52 and probably will soon be available to patients with PsA.
The optimal management of axial PsA continues to be investigated. One major question is whether IL-23 inhibitors, which are not efficacious in axial spondyloarthritis, have efficacy in axial PsA. A post hoc analysis of the DISCOVER-2 study included 246 biologic-naive patients with active PsA and sacroiliitis who were randomly assigned to guselkumab every 4 weeks (Q4W; n = 82), guselkumab every 8 weeks (Q8W; n = 68), or placebo with crossover to guselkumab Q4W at week 24 (n = 96), Mease and colleagues report that at week 24, guselkumab Q4W and Q8W vs placebo showed significantly greater scores in the total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as well as Ankylosing Spondylitis Disease Activity Score (ASDAS), with further improvements noted at week 100. Thus, in patients with active PsA and imaging-confirmed sacroiliitis, 100 mg guselkumab Q4W and Q8W yielded clinically meaningful and sustained improvements in axial symptoms through 2 years.
Finally, attention is currently being paid to patients with refractory or difficult-to-treat (D2T) PsA. These patients are generally characterized as having active disease despite treatment with two or more targeted DMARD (tDMARD). Philippoteaux and colleagues have reported results from their retrospective cohort study that included 150 patients with PsA who initiated treatment with tDMARD and were followed for at least 2 years, of whom 49 patients had D2T PsA. They found that peripheral structural damage, axial involvement, and the discontinuation of bDMARD due to poor skin psoriasis control were more prevalent in patients with D2T PsA compared with in non-D2T PsA. Thus, patients with D2T PsA are more likely to have more structural damage. Early diagnosis and treatment to reduce structural damage might reduce the prevalence of D2T PsA.
There is steady advance in the treatment of PsA. Bimekizumab is a novel monoclonal antibody that, by binding to similar sites on interleukin (IL)-17A and IL-17F, inhibits these cytokines. Ritchlin and colleagues recently reported the 52-week results from the phase 3 BE OPTIMAL study including 852 biological disease-modifying antirheumatic drug (bDMARD)-naive patients with active PsA who were randomly assigned to receive bimekizumab, adalimumab, or placebo. At week 16, 43.9% of patients receiving bimekizumab achieved ≥ 50% improvement in the American College of Rheumatology scores (ACR50), with the response being maintained up to week 52 (54.5%). Among patients who switched from placebo to bimekizumab at week 16, a similar proportion (53.0%) achieved ACR50 at week 52. No new safety signals were observed. Thus, bimekizumab led to sustained improvements in clinical response up to week 52 and probably will soon be available to patients with PsA.
The optimal management of axial PsA continues to be investigated. One major question is whether IL-23 inhibitors, which are not efficacious in axial spondyloarthritis, have efficacy in axial PsA. A post hoc analysis of the DISCOVER-2 study included 246 biologic-naive patients with active PsA and sacroiliitis who were randomly assigned to guselkumab every 4 weeks (Q4W; n = 82), guselkumab every 8 weeks (Q8W; n = 68), or placebo with crossover to guselkumab Q4W at week 24 (n = 96), Mease and colleagues report that at week 24, guselkumab Q4W and Q8W vs placebo showed significantly greater scores in the total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as well as Ankylosing Spondylitis Disease Activity Score (ASDAS), with further improvements noted at week 100. Thus, in patients with active PsA and imaging-confirmed sacroiliitis, 100 mg guselkumab Q4W and Q8W yielded clinically meaningful and sustained improvements in axial symptoms through 2 years.
Finally, attention is currently being paid to patients with refractory or difficult-to-treat (D2T) PsA. These patients are generally characterized as having active disease despite treatment with two or more targeted DMARD (tDMARD). Philippoteaux and colleagues have reported results from their retrospective cohort study that included 150 patients with PsA who initiated treatment with tDMARD and were followed for at least 2 years, of whom 49 patients had D2T PsA. They found that peripheral structural damage, axial involvement, and the discontinuation of bDMARD due to poor skin psoriasis control were more prevalent in patients with D2T PsA compared with in non-D2T PsA. Thus, patients with D2T PsA are more likely to have more structural damage. Early diagnosis and treatment to reduce structural damage might reduce the prevalence of D2T PsA.