Vinod Chandran, MBBS, MD, DM, PhD

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.

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.

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.

To address this gap in knowledge, Möller and colleagues compared the effectiveness of the first bDMARD in patients with PsA with low vs high joint counts (LJC and HJC, respectively). Using the Swiss Clinical Quality Management registry for rheumatic diseases, they obtained data on 387 patients with PsA who had either LJC (n = 197) or HJC (n = 190) and received bDMARD. As expected, patients with HJC had a higher burden of disease. Despite the higher burden, patients in both groups showed similar treatment efficacy in terms of drug retention. Consistent with previous reports, female sex was associated with lower treatment persistence, whereas concomitant treatment with conventional synthetic DMARD (csDMARD) was associated with longer bDMARD persistence. Thus, baseline joint counts may not be a good criterion for choosing who should be treated with bDMARD. The presence of active disease and lack of response to prior csDMARD is sufficient.

Persistence with therapy is an important indicator of drug effectiveness in the real world. A recent report from the CorEvitas registry by Mease and colleagues demonstrated that nearly 80% of patients with PsA persisted with guselkumab (an interleukin [IL]–23 inhibitor) treatment for 6 months and showed improvements in peripheral joint and skin symptoms. This study evaluated 114 patients with active PsA,  > 90% of whom were previously treated with b- and tsDMARD. The mean scores for clinical Disease Activity Index in PsA, overall joint and skin activity, patient-reported pain, and body surface area with psoriasis improved significantly.

Choosing the next therapy after lack of success with treatment with a tumour necrosis factor (TNF) inhibitor and an IL-17A inhibitor is difficult. One question is whether one should try another IL-17A inhibitor or move to another class of therapy. Hansen and colleagues tried to address this question by analyses of data from the Danish Rheumatology Registry. Patients with PsA who underwent prior treatment with one or more TNF inhibitor and switched to either first-line (n = 534) or second-line (n = 102) IL-17A inhibitors (ixekizumab or secukinumab) were included. Similar persistence with therapy was observed between first-line and second-line IL-17A inhibitor switchers and between second-line secukinumab and second-line ixekizumab switchers. Withdrawal reasons were similar for both first-line and second-line switchers when considering adverse events; however, withdrawal due to lack of successful therapy was higher for the first-line vs second-line switchers (34% vs 18%). An important piece of information missing in the report was whether the lack of successful treatment with first-line therapy with an IL-17A inhibitor was primary (no response at all) or secondary (initial response and later failure). One presumes that patients with primary failures are less likely to respond to another IL-17A inhibitor compared with patients with secondary failures. Nevertheless, this large population-based study suggests that the failure of first-line IL-17A inhibitor therapy should not deter treatment with second-line IL-17A inhibitors.

Finally, Schett and colleagues looked at serum cytokine changes after treatment with guselkumab in patients with PsA with inadequate response to TNF inhibitor (TNFI-IR). Using clinical data and biosamples from patients enrolled in the COSMOS study, which included patients with active PsA and TNFI-IR who were randomly assigned to receive either guselkumab (n = 189) or placebo (n = 96), they showed that the serum levels of IL-17A, IL-17F, IL-22, and serum amyloid A were reduced significantly by week 4 and were sustained through week 48 in the guselkumab group vs the placebo group. Patients who achieved a clinical response to guselkumab at week 24 showed higher baseline IL-22 and interferon-γ levels as well as a significant reduction in IL-6 levels at week 4 compared with nonresponders. These markers are candidates for predictors for response to guselkumab in this population.

To address this gap in knowledge, Möller and colleagues compared the effectiveness of the first bDMARD in patients with PsA with low vs high joint counts (LJC and HJC, respectively). Using the Swiss Clinical Quality Management registry for rheumatic diseases, they obtained data on 387 patients with PsA who had either LJC (n = 197) or HJC (n = 190) and received bDMARD. As expected, patients with HJC had a higher burden of disease. Despite the higher burden, patients in both groups showed similar treatment efficacy in terms of drug retention. Consistent with previous reports, female sex was associated with lower treatment persistence, whereas concomitant treatment with conventional synthetic DMARD (csDMARD) was associated with longer bDMARD persistence. Thus, baseline joint counts may not be a good criterion for choosing who should be treated with bDMARD. The presence of active disease and lack of response to prior csDMARD is sufficient.

Persistence with therapy is an important indicator of drug effectiveness in the real world. A recent report from the CorEvitas registry by Mease and colleagues demonstrated that nearly 80% of patients with PsA persisted with guselkumab (an interleukin [IL]–23 inhibitor) treatment for 6 months and showed improvements in peripheral joint and skin symptoms. This study evaluated 114 patients with active PsA,  > 90% of whom were previously treated with b- and tsDMARD. The mean scores for clinical Disease Activity Index in PsA, overall joint and skin activity, patient-reported pain, and body surface area with psoriasis improved significantly.

Choosing the next therapy after lack of success with treatment with a tumour necrosis factor (TNF) inhibitor and an IL-17A inhibitor is difficult. One question is whether one should try another IL-17A inhibitor or move to another class of therapy. Hansen and colleagues tried to address this question by analyses of data from the Danish Rheumatology Registry. Patients with PsA who underwent prior treatment with one or more TNF inhibitor and switched to either first-line (n = 534) or second-line (n = 102) IL-17A inhibitors (ixekizumab or secukinumab) were included. Similar persistence with therapy was observed between first-line and second-line IL-17A inhibitor switchers and between second-line secukinumab and second-line ixekizumab switchers. Withdrawal reasons were similar for both first-line and second-line switchers when considering adverse events; however, withdrawal due to lack of successful therapy was higher for the first-line vs second-line switchers (34% vs 18%). An important piece of information missing in the report was whether the lack of successful treatment with first-line therapy with an IL-17A inhibitor was primary (no response at all) or secondary (initial response and later failure). One presumes that patients with primary failures are less likely to respond to another IL-17A inhibitor compared with patients with secondary failures. Nevertheless, this large population-based study suggests that the failure of first-line IL-17A inhibitor therapy should not deter treatment with second-line IL-17A inhibitors.

Finally, Schett and colleagues looked at serum cytokine changes after treatment with guselkumab in patients with PsA with inadequate response to TNF inhibitor (TNFI-IR). Using clinical data and biosamples from patients enrolled in the COSMOS study, which included patients with active PsA and TNFI-IR who were randomly assigned to receive either guselkumab (n = 189) or placebo (n = 96), they showed that the serum levels of IL-17A, IL-17F, IL-22, and serum amyloid A were reduced significantly by week 4 and were sustained through week 48 in the guselkumab group vs the placebo group. Patients who achieved a clinical response to guselkumab at week 24 showed higher baseline IL-22 and interferon-γ levels as well as a significant reduction in IL-6 levels at week 4 compared with nonresponders. These markers are candidates for predictors for response to guselkumab in this population.

To address this gap in knowledge, Möller and colleagues compared the effectiveness of the first bDMARD in patients with PsA with low vs high joint counts (LJC and HJC, respectively). Using the Swiss Clinical Quality Management registry for rheumatic diseases, they obtained data on 387 patients with PsA who had either LJC (n = 197) or HJC (n = 190) and received bDMARD. As expected, patients with HJC had a higher burden of disease. Despite the higher burden, patients in both groups showed similar treatment efficacy in terms of drug retention. Consistent with previous reports, female sex was associated with lower treatment persistence, whereas concomitant treatment with conventional synthetic DMARD (csDMARD) was associated with longer bDMARD persistence. Thus, baseline joint counts may not be a good criterion for choosing who should be treated with bDMARD. The presence of active disease and lack of response to prior csDMARD is sufficient.

Persistence with therapy is an important indicator of drug effectiveness in the real world. A recent report from the CorEvitas registry by Mease and colleagues demonstrated that nearly 80% of patients with PsA persisted with guselkumab (an interleukin [IL]–23 inhibitor) treatment for 6 months and showed improvements in peripheral joint and skin symptoms. This study evaluated 114 patients with active PsA,  > 90% of whom were previously treated with b- and tsDMARD. The mean scores for clinical Disease Activity Index in PsA, overall joint and skin activity, patient-reported pain, and body surface area with psoriasis improved significantly.

Choosing the next therapy after lack of success with treatment with a tumour necrosis factor (TNF) inhibitor and an IL-17A inhibitor is difficult. One question is whether one should try another IL-17A inhibitor or move to another class of therapy. Hansen and colleagues tried to address this question by analyses of data from the Danish Rheumatology Registry. Patients with PsA who underwent prior treatment with one or more TNF inhibitor and switched to either first-line (n = 534) or second-line (n = 102) IL-17A inhibitors (ixekizumab or secukinumab) were included. Similar persistence with therapy was observed between first-line and second-line IL-17A inhibitor switchers and between second-line secukinumab and second-line ixekizumab switchers. Withdrawal reasons were similar for both first-line and second-line switchers when considering adverse events; however, withdrawal due to lack of successful therapy was higher for the first-line vs second-line switchers (34% vs 18%). An important piece of information missing in the report was whether the lack of successful treatment with first-line therapy with an IL-17A inhibitor was primary (no response at all) or secondary (initial response and later failure). One presumes that patients with primary failures are less likely to respond to another IL-17A inhibitor compared with patients with secondary failures. Nevertheless, this large population-based study suggests that the failure of first-line IL-17A inhibitor therapy should not deter treatment with second-line IL-17A inhibitors.

Finally, Schett and colleagues looked at serum cytokine changes after treatment with guselkumab in patients with PsA with inadequate response to TNF inhibitor (TNFI-IR). Using clinical data and biosamples from patients enrolled in the COSMOS study, which included patients with active PsA and TNFI-IR who were randomly assigned to receive either guselkumab (n = 189) or placebo (n = 96), they showed that the serum levels of IL-17A, IL-17F, IL-22, and serum amyloid A were reduced significantly by week 4 and were sustained through week 48 in the guselkumab group vs the placebo group. Patients who achieved a clinical response to guselkumab at week 24 showed higher baseline IL-22 and interferon-γ levels as well as a significant reduction in IL-6 levels at week 4 compared with nonresponders. These markers are candidates for predictors for response to guselkumab in this population.

Although the usual age at onset of PsA is in the fourth or fifth decade of life, children may develop juvenile-onset PsA (JPsA). Less attention has been paid to this form of juvenile idiopathic arthritis (JIA), and the impact of JPsA vis-à-vis other forms of JIA is not well known. In addition, only about half of the patients with JPsA have cutaneous psoriasis. The impact of psoriasis on children with JPsA is not known. In order to evaluate differences in disease outcomes in patients with JPsA, Low and colleagues evaluated 1653 children and young people with JIA who were recruited to the Childhood Arthritis Prospective Study, of whom 111 had JPsA at diagnosis. They demonstrated that there were no significant differences in patient-reported outcomes between children with JPsA and other JIA categories. However, children with JPsA and psoriasis at JPsA diagnosis had more depressive symptoms compared with those without psoriasis. Moreover, children with JPsA vs other JIA categories had 2.35 times higher odds of having persistently poor well-being scores despite improvements in joint counts and physician global scores. Thus, children with JPsA have poorer well-being scores and a higher prevalence of depression, which requires multidisciplinary care.

Apart from immunomodulatory therapies, weight loss leads to improvement in disease activity in patients with obesity and PsA. However, the mechanisms by which weight loss improves PsA is currently not known, but is likely to be due to changes in adipokines and inflammation-related cytokines. In a recent study¹that included patients with PsA and obesity, it was demonstrated that weight loss through a Very Low Energy Diet (VLED) resulted in significant improvements in PsA disease activity. Landgren and colleagues now aimed to determine the effects of VLED on cytokines and adipokines. They obtained blood samples from patients with PsA and obesity (n = 41) and matched control individuals without rheumatic disease or psoriasis (n = 39) who were on VLED. At month 6, along with significant weight loss, serum levels of interleukin-23 and leptin decreased significantly, while those of total adiponectin and high-molecular-weight adiponectin increased significantly in patients with PsA and control individuals. The change in body mass index correlated positively with a reduction in serum interleukin-23 (r_S = 0.671, P < .001) and improvement in PsA disease activity (P = .003). This study highlights the anti-inflammatory effect of weight loss in patients with PsA. Weight loss can complement immunomodulatory therapy in PsA patients with obesity.

Additional Reference

1. Klingberg E, Bilberg A, Björkman S, et al. Weight loss improves disease activity in patients with psoriatic arthritis and obesity: an interventional study. Arthritis Res Ther. 2019;21:17. doi: 10.1186/s13075-019-1810-5

Although the usual age at onset of PsA is in the fourth or fifth decade of life, children may develop juvenile-onset PsA (JPsA). Less attention has been paid to this form of juvenile idiopathic arthritis (JIA), and the impact of JPsA vis-à-vis other forms of JIA is not well known. In addition, only about half of the patients with JPsA have cutaneous psoriasis. The impact of psoriasis on children with JPsA is not known. In order to evaluate differences in disease outcomes in patients with JPsA, Low and colleagues evaluated 1653 children and young people with JIA who were recruited to the Childhood Arthritis Prospective Study, of whom 111 had JPsA at diagnosis. They demonstrated that there were no significant differences in patient-reported outcomes between children with JPsA and other JIA categories. However, children with JPsA and psoriasis at JPsA diagnosis had more depressive symptoms compared with those without psoriasis. Moreover, children with JPsA vs other JIA categories had 2.35 times higher odds of having persistently poor well-being scores despite improvements in joint counts and physician global scores. Thus, children with JPsA have poorer well-being scores and a higher prevalence of depression, which requires multidisciplinary care.

Apart from immunomodulatory therapies, weight loss leads to improvement in disease activity in patients with obesity and PsA. However, the mechanisms by which weight loss improves PsA is currently not known, but is likely to be due to changes in adipokines and inflammation-related cytokines. In a recent study¹that included patients with PsA and obesity, it was demonstrated that weight loss through a Very Low Energy Diet (VLED) resulted in significant improvements in PsA disease activity. Landgren and colleagues now aimed to determine the effects of VLED on cytokines and adipokines. They obtained blood samples from patients with PsA and obesity (n = 41) and matched control individuals without rheumatic disease or psoriasis (n = 39) who were on VLED. At month 6, along with significant weight loss, serum levels of interleukin-23 and leptin decreased significantly, while those of total adiponectin and high-molecular-weight adiponectin increased significantly in patients with PsA and control individuals. The change in body mass index correlated positively with a reduction in serum interleukin-23 (r_S = 0.671, P < .001) and improvement in PsA disease activity (P = .003). This study highlights the anti-inflammatory effect of weight loss in patients with PsA. Weight loss can complement immunomodulatory therapy in PsA patients with obesity.

Additional Reference

1. Klingberg E, Bilberg A, Björkman S, et al. Weight loss improves disease activity in patients with psoriatic arthritis and obesity: an interventional study. Arthritis Res Ther. 2019;21:17. doi: 10.1186/s13075-019-1810-5

Although the usual age at onset of PsA is in the fourth or fifth decade of life, children may develop juvenile-onset PsA (JPsA). Less attention has been paid to this form of juvenile idiopathic arthritis (JIA), and the impact of JPsA vis-à-vis other forms of JIA is not well known. In addition, only about half of the patients with JPsA have cutaneous psoriasis. The impact of psoriasis on children with JPsA is not known. In order to evaluate differences in disease outcomes in patients with JPsA, Low and colleagues evaluated 1653 children and young people with JIA who were recruited to the Childhood Arthritis Prospective Study, of whom 111 had JPsA at diagnosis. They demonstrated that there were no significant differences in patient-reported outcomes between children with JPsA and other JIA categories. However, children with JPsA and psoriasis at JPsA diagnosis had more depressive symptoms compared with those without psoriasis. Moreover, children with JPsA vs other JIA categories had 2.35 times higher odds of having persistently poor well-being scores despite improvements in joint counts and physician global scores. Thus, children with JPsA have poorer well-being scores and a higher prevalence of depression, which requires multidisciplinary care.

Apart from immunomodulatory therapies, weight loss leads to improvement in disease activity in patients with obesity and PsA. However, the mechanisms by which weight loss improves PsA is currently not known, but is likely to be due to changes in adipokines and inflammation-related cytokines. In a recent study¹that included patients with PsA and obesity, it was demonstrated that weight loss through a Very Low Energy Diet (VLED) resulted in significant improvements in PsA disease activity. Landgren and colleagues now aimed to determine the effects of VLED on cytokines and adipokines. They obtained blood samples from patients with PsA and obesity (n = 41) and matched control individuals without rheumatic disease or psoriasis (n = 39) who were on VLED. At month 6, along with significant weight loss, serum levels of interleukin-23 and leptin decreased significantly, while those of total adiponectin and high-molecular-weight adiponectin increased significantly in patients with PsA and control individuals. The change in body mass index correlated positively with a reduction in serum interleukin-23 (r_S = 0.671, P < .001) and improvement in PsA disease activity (P = .003). This study highlights the anti-inflammatory effect of weight loss in patients with PsA. Weight loss can complement immunomodulatory therapy in PsA patients with obesity.

Additional Reference

1. Klingberg E, Bilberg A, Björkman S, et al. Weight loss improves disease activity in patients with psoriatic arthritis and obesity: an interventional study. Arthritis Res Ther. 2019;21:17. doi: 10.1186/s13075-019-1810-5

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

Despite using methotrexate (MTX) in the management of psoriasis and PsA for more than 50 years, there is paucity of data on its effectiveness in PsA. It is also largely assumed that MTX is more effective for rheumatoid arthritis (RA) than for PsA. To evaluate MTX effectiveness vis-à-vis RA, Lindström and colleagues conducted an observational study with disease-modifying antirheumatic drug (DMARD)–naive patients with newly diagnosed PsA (n = 3642) who initiated MTX and matched comparator patients with RA (n = 3642) from national Swedish registers. At 6 months, although both groups of patients had improvement in pain, global health, and remission, the rates were higher in RA compared with PsA. Overall, 71% of patients with PsA and 76% of patients with RA were still taking MTX 2 years after initiating MTX. The time to starting another DMARD was shorter in RA compared with PsA. Thus, in early PsA, MTX treatment seems to provide significant benefits. However, the improvements are less impressive than they are for RA.

Biologic agents are generally safe and effective in the treatment of PsA. However, there are limited data on the safety and effectiveness in older and younger populations with PsA. Gossec and colleagues conducted a post hoc analysis of the PsABio trial that included patients with PsA who received ustekinumab, an interleukin 12/23 inhibitor, and were subgrouped into those < 60 years (n = 336) and ≥ 60 years (n = 103). At 6 months, a numerically higher proportion of patients < 60 years achieved clinical Disease Activity Index for Psoriatic Arthritis low disease activity compared with those ≥ 60 years. The proportions of patients reporting at least one (32.7% vs 40.9%) or serious (5.3% vs 9.6%) adverse events were numerically higher in the older population. However, treatment persistence was numerically higher in the older subgroup. These differences were not clinically meaningful; thus, ustekinumab may be safely used in older populations.

There are also limited data on the effectiveness of biologics in patients with juvenile PsA (jPsA). To address this, Correll and colleagues evaluated the safety and effectiveness of etanercept, an anti–tumor necrosis factor agent, in patients with jPsA using data from the Childhood Arthritis and Rheumatology Research Alliance Registry. In 226 patients, the overall incidence of adverse events of special interest and serious adverse events were low and included three cases of uveitis (incidence rate [IR]/100 person-years 0.55; 95% CI 0.18-1.69), one of neuropathy (IR/100 person-years 0.18; 95% CI 0.03-1.29), and one of cancer (IR/100 person-years 0.13; 95% CI 0.02-0.90). The ACR provisional criteria for inactive disease were achieved by 51.9% and 43.8% of patients at 6 and 12 months. Thus, etanercept is safe and effective in jPsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.

The relationship between enthesitis and synovitis is of considerable interest to both clinicians and researchers. This relationship is best evaluated using imaging, particularly ultrasonography, and could provide pathophysiologic insights. Balulu and colleagues recruited 158 patients with PsA who underwent sonographic assessment of 52 joints, 40 tendons, and 14 entheses as well as clinical evaluation. Overall, total sonographic enthesitis scores were significantly associated with total sonographic synovitis and sonographic tenosynovitis scores and also with older age, male sex, swollen joint count, C-reactive protein, physical occupation, and patient-reported outcomes. The association between enthesitis and synovitis was also demonstrated at the elbows, knees, and ankles. This study demonstrates that psoriatic enthesitis and synovitis are closely related and thus may share pathophysiologic mechanisms. Longitudinal studies in very early PsA using ultrasound might provide clues to confirm the hypothesis that psoriatic synovitis is secondary to enthesitis.

Another important domain that is increasingly studied is axial PsA. Currently, the evidence for treatment of axial PsA is extrapolated from that for axial spondyloarthritis (SpA), in the belief that the two diseases are pathophysiologically similar. However, there is increasing evidence for differences between axial PsA and axial SpA that might influence the choice of treatment. In a recent study, de Hooge and colleagues demonstrated that patients with axial PsA have lower severity of damage to the spine compared with those with axial SpA. Using data from 312 patients with PsA and 213 patients with SpA who underwent radiographic imaging assessment in the Belgian Epidemiological Psoriatic Arthritis Study (BEPAS) and the Ghent and Belgian Inflammatory Arthritis and Spondylitis (Be-GIANT) study, respectively, they show that the proportion of patients with PsA vs SpA having spinal damage was comparable. Patients with SpA and spinal damage had higher modified Stoke Ankylosing Spondylitis Spine Scores, indicating more severe damage. These results are consistent with other published studies and indicate that patients with PsA have less severe spinal disease compared with other patients with axial SpA. Randomized controlled trials (RCTs) specifically investigating the treatment of axial PsA are currently underway. Nevertheless, post hoc analyses of data from PsA RCTs indicate that most drugs efficacious for PsA overall also provide benefit in axial disease.

In a recent report, Baraliakos and colleagues analyzed data from the SELECT-PsA 1 and SELECT-PsA 2 trials that evaluated the efficacy of upadacitinib in PsA. They show that, compared with placebo, 15 mg upadacitinib led to a greater improvement in axial symptoms. The improvement in overall Bath Ankylosing Spondylitis Disease Activity Index score at week 24 was significantly higher with 15 mg upadacitinib compared with placebo in both trials. However, these results are not definitive because there is yet no consensus on the definition of and outcome measures for axial PsA.