Vinod Chandran, MBBS, MD, DM, PhD

Although PsA affects men and women equally, the impact of the disease is often worse in women. In a large study from the Netherlands, in which 855 patients were carefully evaluated and follow up, Mulder MLM et al show that both subjective and objective measures of disease activity is more severe in women than men. The PsA Disease Activity Score, a validated composite measure of PsA disease activity, was also higher in women than men. The impact of disease on quality of life and function was significantly more in women and they were less often meeting treatment target. Further research into the impact of sex and gender in PsA is warranted and sex/gender-specific measures for managing PsA is required.

Janus kinase inhibitors (JAKi) are important new molecules increasingly being used in the management of inflammatory diseases. Tofacitinib is already available for the treatment of PsA. McInnes IB et al published results on the efficacy of upadacitinib, a more selective JAK1i already approved for treatment of RA, in treating PsA. In this phase 3 trial involving 1,704 patients with PsA who had an inadequate response to at least 1 nonbiologic disease-modifying antirheumatic drugs, the proportion of patients achieving at least 20% improvement in American College of Rheumatology (ACR20) response was significantly higher with upadacitinib 15 mg (70.6%) and 30 mg (78.5%) than with placebo (36.2%; P less than .001). Upadacitinib 15mg was found to have comparable efficacy as adalimumab (ACR20 65.0%), a well-established anti-TNF agent. However, adverse events were more frequent with upadacitinib.

Adverse events when on treatment with JAKi have recently come into sharp focus. Reassuringly, results from the OPAL Balance study, a 36-month, long-term extension phase 3 study involving 686 adult patients with active PsA on treatment with tofacitinib confirmed the long-term safety and efficacy of tofacitinib in patients with PsA. Nash P et al reported 1 instance of mortality occurred in tofacitinib group during the risk period (incidence, 0.1 patients with events [95% confidence interval, 0.0-0.3] per 100 person-years). The incidences of adverse events for herpes zoster, serious infections, opportunistic infections, adjudicated malignancies, and major adverse cardiovascular events were consistent with previous reports. However, given the reports of higher adverse events with tofacitinib compared to anti-TNF drugs in high-risk rheumatoid arthritis patients, more data is required to fully understand the risk profile of JAKi in patients with immune-mediated inflammatory diseases, including PsA.

With several drugs currently available to treat PsA and the paucity of head-to-head trials between them, choosing the most efficacious drug for treating patients with PsA has become challenging. To address this issue a network meta-analysis of 26 phase 3, randomized controlled trials that evaluated 13 targeted therapies among adults with active PsA was conducted. In a study sponsored by Janssen, Mease PJ et al report that guselkumab 100 mg every 8 weeks and every 4 weeks were comparable to anti IL-17A and subcutaneous anti-TNF agents for achieving ACR20 response. Guselkumab showed better Psoriasis Area Severity Index 90 and 75 responses than most of the other agents. The results indicate that guselkumab is as effective as other established agents in treating PsA, but formal head-to-head clinical trials will provide better evidence of relative efficacy and safety.

Although PsA affects men and women equally, the impact of the disease is often worse in women. In a large study from the Netherlands, in which 855 patients were carefully evaluated and follow up, Mulder MLM et al show that both subjective and objective measures of disease activity is more severe in women than men. The PsA Disease Activity Score, a validated composite measure of PsA disease activity, was also higher in women than men. The impact of disease on quality of life and function was significantly more in women and they were less often meeting treatment target. Further research into the impact of sex and gender in PsA is warranted and sex/gender-specific measures for managing PsA is required.

Janus kinase inhibitors (JAKi) are important new molecules increasingly being used in the management of inflammatory diseases. Tofacitinib is already available for the treatment of PsA. McInnes IB et al published results on the efficacy of upadacitinib, a more selective JAK1i already approved for treatment of RA, in treating PsA. In this phase 3 trial involving 1,704 patients with PsA who had an inadequate response to at least 1 nonbiologic disease-modifying antirheumatic drugs, the proportion of patients achieving at least 20% improvement in American College of Rheumatology (ACR20) response was significantly higher with upadacitinib 15 mg (70.6%) and 30 mg (78.5%) than with placebo (36.2%; P less than .001). Upadacitinib 15mg was found to have comparable efficacy as adalimumab (ACR20 65.0%), a well-established anti-TNF agent. However, adverse events were more frequent with upadacitinib.

Adverse events when on treatment with JAKi have recently come into sharp focus. Reassuringly, results from the OPAL Balance study, a 36-month, long-term extension phase 3 study involving 686 adult patients with active PsA on treatment with tofacitinib confirmed the long-term safety and efficacy of tofacitinib in patients with PsA. Nash P et al reported 1 instance of mortality occurred in tofacitinib group during the risk period (incidence, 0.1 patients with events [95% confidence interval, 0.0-0.3] per 100 person-years). The incidences of adverse events for herpes zoster, serious infections, opportunistic infections, adjudicated malignancies, and major adverse cardiovascular events were consistent with previous reports. However, given the reports of higher adverse events with tofacitinib compared to anti-TNF drugs in high-risk rheumatoid arthritis patients, more data is required to fully understand the risk profile of JAKi in patients with immune-mediated inflammatory diseases, including PsA.

With several drugs currently available to treat PsA and the paucity of head-to-head trials between them, choosing the most efficacious drug for treating patients with PsA has become challenging. To address this issue a network meta-analysis of 26 phase 3, randomized controlled trials that evaluated 13 targeted therapies among adults with active PsA was conducted. In a study sponsored by Janssen, Mease PJ et al report that guselkumab 100 mg every 8 weeks and every 4 weeks were comparable to anti IL-17A and subcutaneous anti-TNF agents for achieving ACR20 response. Guselkumab showed better Psoriasis Area Severity Index 90 and 75 responses than most of the other agents. The results indicate that guselkumab is as effective as other established agents in treating PsA, but formal head-to-head clinical trials will provide better evidence of relative efficacy and safety.

Although PsA affects men and women equally, the impact of the disease is often worse in women. In a large study from the Netherlands, in which 855 patients were carefully evaluated and follow up, Mulder MLM et al show that both subjective and objective measures of disease activity is more severe in women than men. The PsA Disease Activity Score, a validated composite measure of PsA disease activity, was also higher in women than men. The impact of disease on quality of life and function was significantly more in women and they were less often meeting treatment target. Further research into the impact of sex and gender in PsA is warranted and sex/gender-specific measures for managing PsA is required.

Janus kinase inhibitors (JAKi) are important new molecules increasingly being used in the management of inflammatory diseases. Tofacitinib is already available for the treatment of PsA. McInnes IB et al published results on the efficacy of upadacitinib, a more selective JAK1i already approved for treatment of RA, in treating PsA. In this phase 3 trial involving 1,704 patients with PsA who had an inadequate response to at least 1 nonbiologic disease-modifying antirheumatic drugs, the proportion of patients achieving at least 20% improvement in American College of Rheumatology (ACR20) response was significantly higher with upadacitinib 15 mg (70.6%) and 30 mg (78.5%) than with placebo (36.2%; P less than .001). Upadacitinib 15mg was found to have comparable efficacy as adalimumab (ACR20 65.0%), a well-established anti-TNF agent. However, adverse events were more frequent with upadacitinib.

Adverse events when on treatment with JAKi have recently come into sharp focus. Reassuringly, results from the OPAL Balance study, a 36-month, long-term extension phase 3 study involving 686 adult patients with active PsA on treatment with tofacitinib confirmed the long-term safety and efficacy of tofacitinib in patients with PsA. Nash P et al reported 1 instance of mortality occurred in tofacitinib group during the risk period (incidence, 0.1 patients with events [95% confidence interval, 0.0-0.3] per 100 person-years). The incidences of adverse events for herpes zoster, serious infections, opportunistic infections, adjudicated malignancies, and major adverse cardiovascular events were consistent with previous reports. However, given the reports of higher adverse events with tofacitinib compared to anti-TNF drugs in high-risk rheumatoid arthritis patients, more data is required to fully understand the risk profile of JAKi in patients with immune-mediated inflammatory diseases, including PsA.

With several drugs currently available to treat PsA and the paucity of head-to-head trials between them, choosing the most efficacious drug for treating patients with PsA has become challenging. To address this issue a network meta-analysis of 26 phase 3, randomized controlled trials that evaluated 13 targeted therapies among adults with active PsA was conducted. In a study sponsored by Janssen, Mease PJ et al report that guselkumab 100 mg every 8 weeks and every 4 weeks were comparable to anti IL-17A and subcutaneous anti-TNF agents for achieving ACR20 response. Guselkumab showed better Psoriasis Area Severity Index 90 and 75 responses than most of the other agents. The results indicate that guselkumab is as effective as other established agents in treating PsA, but formal head-to-head clinical trials will provide better evidence of relative efficacy and safety.

Psoriatic arthritis may be associated with excess mortality risk but the current evidence to support excess mortality in psoriatic arthritis is inconclusive. Nevertheless, identifying risk factors for mortality in patients with psoriatic arthritis is important so that modifiable factors could be addressed. Vela et al investigated whether the cumulative pain experienced by psoriatic arthritis patients was associated with increased mortality. Using data from the Danish nationwide registry of biological therapies (DANBIO), the authors showed that although there was a significant association between pain intensity and mortality (odds ratio 1.06 (95%CI 1.02 to 1.10) per 5 VAS unit increase), no association was found when the analyses was adjusted for confounders including age, CRP, joint counts, HAQ score, treatment, and comorbidities. As expected, recent glucocorticoid use, chronic obstructive pulmonary disease, diabetes mellitus, cancer and cardiovascular disease were associated with excess mortality. The results indicate that mortality in psoriatic arthritis is primarily driven by associated comorbidities; holistic management of psoriatic disease should include management of associated comorbidities.

Comorbidities have a major impact on patients with psoriatic arthritis and influence a patient’s quality of life and function as well as treatment response. Neuropsychiatric comorbidities have been less studied in psoriatic arthritis. An intriguing study by Garcia et al indicate that cognitive impairment may be associated with psoriatic arthritis. In a small cross-sectional study, they demonstrated that patients with psoriatic arthritis score worse on the Montreal Cognitive Assessment (MoCA) tool compared to controls, with executive skills, naming, language, and abstraction being most affected. Further research is required to explore whether other comorbidities such as cerebrovascular disease, depression or sleep disturbances explain the cognitive impairment. Depression and anxiety are also associated with reduced likelihood of achieving remission or low disease activity state in psoriatic arthritis. In a study of 743 patients, Wong et al demonstrated that patients with depression or anxiety are less likely to achieve a state of sustained minimal disease activity. These studies once again highlight the management of comorbidities to achieve improved outcomes in patients with psoriatic arthritis.

New data also indicate efficacy of targeted therapy in psoriatic arthritis. In two phase 3 trials funded by LEO pharma, Mease et al report that brodalumab, an interleukin 17 receptor inhibitor that is already available for the treatment for psoriasis, is efficacious in the treatment of psoriatic arthritis. Although the trial was terminated early, pooled data from the two trials showed that higher proportions of patients on 140 mg and 210 mg of brodalumab achieved American College of Rheumatology (ACR)20 response at week 16 compared to placebo group (45.8% and 47.9%, respectively vs. 20.9%; P less than .0001).

There are limited data on treatment withdrawal in patients with psoriatic arthritis. Coates et al investigated whether continued treatment with ixekizumab, an interleukin 17A inhibitor was superior to withdrawing ixekizumab in maintaining minimal disease activity state in patents with psoriatic arthritis. They showed that more patients relapsed rapidly after ixekizumab was withdrawn compared to those continuing ixekizumab treatment. Importantly, >95% of patients who relapsed with treatment withdrawal re-achieved MDA on retreatment with ixekizumab within a median duration of 4.1 weeks. Thus, ixekizumab treatment is best maintained after a patient achieves a state of minimal disease activity. If the treatment needs to be interrupted (e.g., infection, surgery), most patients will re-achieve the state of minimal disease activity on retreatment.

Finally, research continues to demonstrate delayed diagnosis of psoriatic arthritis. Karmacharya et al showed that only 45% of patients receive a diagnosis of psoriatic arthritis by 2 years after symptom onset. This study from the population-based Rochester Epidemiology Project indicates that earlier age of onset of symptoms, the presence of higher body mass index and enthesitis are associated with diagnostic delay. Further education of health care providers and patients with psoriasis about psoriatic arthritis may help reduce diagnostic delay; delayed diagnosis leads to poorer long-term outcomes.

Psoriatic arthritis may be associated with excess mortality risk but the current evidence to support excess mortality in psoriatic arthritis is inconclusive. Nevertheless, identifying risk factors for mortality in patients with psoriatic arthritis is important so that modifiable factors could be addressed. Vela et al investigated whether the cumulative pain experienced by psoriatic arthritis patients was associated with increased mortality. Using data from the Danish nationwide registry of biological therapies (DANBIO), the authors showed that although there was a significant association between pain intensity and mortality (odds ratio 1.06 (95%CI 1.02 to 1.10) per 5 VAS unit increase), no association was found when the analyses was adjusted for confounders including age, CRP, joint counts, HAQ score, treatment, and comorbidities. As expected, recent glucocorticoid use, chronic obstructive pulmonary disease, diabetes mellitus, cancer and cardiovascular disease were associated with excess mortality. The results indicate that mortality in psoriatic arthritis is primarily driven by associated comorbidities; holistic management of psoriatic disease should include management of associated comorbidities.

Comorbidities have a major impact on patients with psoriatic arthritis and influence a patient’s quality of life and function as well as treatment response. Neuropsychiatric comorbidities have been less studied in psoriatic arthritis. An intriguing study by Garcia et al indicate that cognitive impairment may be associated with psoriatic arthritis. In a small cross-sectional study, they demonstrated that patients with psoriatic arthritis score worse on the Montreal Cognitive Assessment (MoCA) tool compared to controls, with executive skills, naming, language, and abstraction being most affected. Further research is required to explore whether other comorbidities such as cerebrovascular disease, depression or sleep disturbances explain the cognitive impairment. Depression and anxiety are also associated with reduced likelihood of achieving remission or low disease activity state in psoriatic arthritis. In a study of 743 patients, Wong et al demonstrated that patients with depression or anxiety are less likely to achieve a state of sustained minimal disease activity. These studies once again highlight the management of comorbidities to achieve improved outcomes in patients with psoriatic arthritis.

New data also indicate efficacy of targeted therapy in psoriatic arthritis. In two phase 3 trials funded by LEO pharma, Mease et al report that brodalumab, an interleukin 17 receptor inhibitor that is already available for the treatment for psoriasis, is efficacious in the treatment of psoriatic arthritis. Although the trial was terminated early, pooled data from the two trials showed that higher proportions of patients on 140 mg and 210 mg of brodalumab achieved American College of Rheumatology (ACR)20 response at week 16 compared to placebo group (45.8% and 47.9%, respectively vs. 20.9%; P less than .0001).

There are limited data on treatment withdrawal in patients with psoriatic arthritis. Coates et al investigated whether continued treatment with ixekizumab, an interleukin 17A inhibitor was superior to withdrawing ixekizumab in maintaining minimal disease activity state in patents with psoriatic arthritis. They showed that more patients relapsed rapidly after ixekizumab was withdrawn compared to those continuing ixekizumab treatment. Importantly, >95% of patients who relapsed with treatment withdrawal re-achieved MDA on retreatment with ixekizumab within a median duration of 4.1 weeks. Thus, ixekizumab treatment is best maintained after a patient achieves a state of minimal disease activity. If the treatment needs to be interrupted (e.g., infection, surgery), most patients will re-achieve the state of minimal disease activity on retreatment.

Finally, research continues to demonstrate delayed diagnosis of psoriatic arthritis. Karmacharya et al showed that only 45% of patients receive a diagnosis of psoriatic arthritis by 2 years after symptom onset. This study from the population-based Rochester Epidemiology Project indicates that earlier age of onset of symptoms, the presence of higher body mass index and enthesitis are associated with diagnostic delay. Further education of health care providers and patients with psoriasis about psoriatic arthritis may help reduce diagnostic delay; delayed diagnosis leads to poorer long-term outcomes.

Psoriatic arthritis may be associated with excess mortality risk but the current evidence to support excess mortality in psoriatic arthritis is inconclusive. Nevertheless, identifying risk factors for mortality in patients with psoriatic arthritis is important so that modifiable factors could be addressed. Vela et al investigated whether the cumulative pain experienced by psoriatic arthritis patients was associated with increased mortality. Using data from the Danish nationwide registry of biological therapies (DANBIO), the authors showed that although there was a significant association between pain intensity and mortality (odds ratio 1.06 (95%CI 1.02 to 1.10) per 5 VAS unit increase), no association was found when the analyses was adjusted for confounders including age, CRP, joint counts, HAQ score, treatment, and comorbidities. As expected, recent glucocorticoid use, chronic obstructive pulmonary disease, diabetes mellitus, cancer and cardiovascular disease were associated with excess mortality. The results indicate that mortality in psoriatic arthritis is primarily driven by associated comorbidities; holistic management of psoriatic disease should include management of associated comorbidities.

Comorbidities have a major impact on patients with psoriatic arthritis and influence a patient’s quality of life and function as well as treatment response. Neuropsychiatric comorbidities have been less studied in psoriatic arthritis. An intriguing study by Garcia et al indicate that cognitive impairment may be associated with psoriatic arthritis. In a small cross-sectional study, they demonstrated that patients with psoriatic arthritis score worse on the Montreal Cognitive Assessment (MoCA) tool compared to controls, with executive skills, naming, language, and abstraction being most affected. Further research is required to explore whether other comorbidities such as cerebrovascular disease, depression or sleep disturbances explain the cognitive impairment. Depression and anxiety are also associated with reduced likelihood of achieving remission or low disease activity state in psoriatic arthritis. In a study of 743 patients, Wong et al demonstrated that patients with depression or anxiety are less likely to achieve a state of sustained minimal disease activity. These studies once again highlight the management of comorbidities to achieve improved outcomes in patients with psoriatic arthritis.

New data also indicate efficacy of targeted therapy in psoriatic arthritis. In two phase 3 trials funded by LEO pharma, Mease et al report that brodalumab, an interleukin 17 receptor inhibitor that is already available for the treatment for psoriasis, is efficacious in the treatment of psoriatic arthritis. Although the trial was terminated early, pooled data from the two trials showed that higher proportions of patients on 140 mg and 210 mg of brodalumab achieved American College of Rheumatology (ACR)20 response at week 16 compared to placebo group (45.8% and 47.9%, respectively vs. 20.9%; P less than .0001).

There are limited data on treatment withdrawal in patients with psoriatic arthritis. Coates et al investigated whether continued treatment with ixekizumab, an interleukin 17A inhibitor was superior to withdrawing ixekizumab in maintaining minimal disease activity state in patents with psoriatic arthritis. They showed that more patients relapsed rapidly after ixekizumab was withdrawn compared to those continuing ixekizumab treatment. Importantly, >95% of patients who relapsed with treatment withdrawal re-achieved MDA on retreatment with ixekizumab within a median duration of 4.1 weeks. Thus, ixekizumab treatment is best maintained after a patient achieves a state of minimal disease activity. If the treatment needs to be interrupted (e.g., infection, surgery), most patients will re-achieve the state of minimal disease activity on retreatment.

Finally, research continues to demonstrate delayed diagnosis of psoriatic arthritis. Karmacharya et al showed that only 45% of patients receive a diagnosis of psoriatic arthritis by 2 years after symptom onset. This study from the population-based Rochester Epidemiology Project indicates that earlier age of onset of symptoms, the presence of higher body mass index and enthesitis are associated with diagnostic delay. Further education of health care providers and patients with psoriasis about psoriatic arthritis may help reduce diagnostic delay; delayed diagnosis leads to poorer long-term outcomes.