Key clinical point: Patients with active psoriatic arthritis (PsA) who initiated secukinumab treatment had stable improvements in synovitis and sustained clinical improvements in enthesitis up to week 52.

Major finding: At week 12, secukinumab vs placebo led to significant improvements in power Doppler ultrasound (PDUS)-assessed synovitis (Global EULAR-OMERACT Synovitis Score: −9 vs −6; one-sided P = .004) and PDUS-assessed enthesitis (Spondyloarthritis Research Consortium of Canada enthesitis index score: −2.2 vs −1.6; one-sided P = .03), with the improvements being sustained up to week 52.

Study details: This 52-week, phase 3 ULTIMATE study included 166 patients with active PsA, who were naive to biologics and intolerant to conventional synthetic disease-modifying anti-rheumatic drugs and were randomly assigned to receive secukinumab or placebo.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. Three authors declared being employees or stockholders of Novartis. Several authors declared ties with various sources, including Novartis. Three authors declared no conflicts of interest.

Source: D’Agostino MA et al. Effects of secukinumab on synovitis and enthesitis in patients with psoriatic arthritis: 52-week clinical and ultrasound results from the randomised, double-blind ULTIMATE trial with open label extension. Semin Arthritis Rheum. 2023;63:152259 (Aug 19). doi: 10.1016/j.semarthrit.2023.152259

Key clinical point: Patients with active psoriatic arthritis (PsA) who initiated secukinumab treatment had stable improvements in synovitis and sustained clinical improvements in enthesitis up to week 52.

Major finding: At week 12, secukinumab vs placebo led to significant improvements in power Doppler ultrasound (PDUS)-assessed synovitis (Global EULAR-OMERACT Synovitis Score: −9 vs −6; one-sided P = .004) and PDUS-assessed enthesitis (Spondyloarthritis Research Consortium of Canada enthesitis index score: −2.2 vs −1.6; one-sided P = .03), with the improvements being sustained up to week 52.

Study details: This 52-week, phase 3 ULTIMATE study included 166 patients with active PsA, who were naive to biologics and intolerant to conventional synthetic disease-modifying anti-rheumatic drugs and were randomly assigned to receive secukinumab or placebo.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. Three authors declared being employees or stockholders of Novartis. Several authors declared ties with various sources, including Novartis. Three authors declared no conflicts of interest.

Source: D’Agostino MA et al. Effects of secukinumab on synovitis and enthesitis in patients with psoriatic arthritis: 52-week clinical and ultrasound results from the randomised, double-blind ULTIMATE trial with open label extension. Semin Arthritis Rheum. 2023;63:152259 (Aug 19). doi: 10.1016/j.semarthrit.2023.152259

Key clinical point: Patients with active psoriatic arthritis (PsA) who initiated secukinumab treatment had stable improvements in synovitis and sustained clinical improvements in enthesitis up to week 52.

Major finding: At week 12, secukinumab vs placebo led to significant improvements in power Doppler ultrasound (PDUS)-assessed synovitis (Global EULAR-OMERACT Synovitis Score: −9 vs −6; one-sided P = .004) and PDUS-assessed enthesitis (Spondyloarthritis Research Consortium of Canada enthesitis index score: −2.2 vs −1.6; one-sided P = .03), with the improvements being sustained up to week 52.

Study details: This 52-week, phase 3 ULTIMATE study included 166 patients with active PsA, who were naive to biologics and intolerant to conventional synthetic disease-modifying anti-rheumatic drugs and were randomly assigned to receive secukinumab or placebo.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. Three authors declared being employees or stockholders of Novartis. Several authors declared ties with various sources, including Novartis. Three authors declared no conflicts of interest.

Source: D’Agostino MA et al. Effects of secukinumab on synovitis and enthesitis in patients with psoriatic arthritis: 52-week clinical and ultrasound results from the randomised, double-blind ULTIMATE trial with open label extension. Semin Arthritis Rheum. 2023;63:152259 (Aug 19). doi: 10.1016/j.semarthrit.2023.152259

Key clinical point: Secukinumab demonstrated sustained efficacy, high retention rates, and a consistent safety profile in patients with active psoriatic arthritis (PsA) who were followed for ≥ 2 years.

Major finding: The treatment retention rate with secukinumab was 78.2% in PsA. The mean swollen joint counts (enrolment vs 2 years: 4.5 vs 3.6) and tender joint counts (enrolment vs 2 years: 12.8 vs 9.2) remained stable over 2 years of treatment. Serious adverse events occurred in 13.6% of patients, but no deaths related to treatment-emergent adverse events were reported.

Study details: Findings are from an interim analysis of the ongoing SERENA study including patients with active PsA (n = 81) or radiographic axial spondyloarthritis (n = 108) who had received secukinumab for ≥16 weeks prior to enrolment.

Disclosures: This study was supported by Novartis Pharma AG. Two authors declared being employees of Novartis Pharmaceuticals U.K. Ltd. Three authors declared ties with various sources, including Novartis.

Source: Gaffney K et al. Real-world evidence for secukinumab in UK patients with psoriatic arthritis or radiographic axial spondyloarthritis: Interim 2-year analysis from SERENA. Rheumatol Adv Pract. 2023;7(3):rkad055 (Aug 21). doi: 10.1093/rap/rkad055

Key clinical point: Secukinumab demonstrated sustained efficacy, high retention rates, and a consistent safety profile in patients with active psoriatic arthritis (PsA) who were followed for ≥ 2 years.

Major finding: The treatment retention rate with secukinumab was 78.2% in PsA. The mean swollen joint counts (enrolment vs 2 years: 4.5 vs 3.6) and tender joint counts (enrolment vs 2 years: 12.8 vs 9.2) remained stable over 2 years of treatment. Serious adverse events occurred in 13.6% of patients, but no deaths related to treatment-emergent adverse events were reported.

Study details: Findings are from an interim analysis of the ongoing SERENA study including patients with active PsA (n = 81) or radiographic axial spondyloarthritis (n = 108) who had received secukinumab for ≥16 weeks prior to enrolment.

Disclosures: This study was supported by Novartis Pharma AG. Two authors declared being employees of Novartis Pharmaceuticals U.K. Ltd. Three authors declared ties with various sources, including Novartis.

Source: Gaffney K et al. Real-world evidence for secukinumab in UK patients with psoriatic arthritis or radiographic axial spondyloarthritis: Interim 2-year analysis from SERENA. Rheumatol Adv Pract. 2023;7(3):rkad055 (Aug 21). doi: 10.1093/rap/rkad055

Key clinical point: Secukinumab demonstrated sustained efficacy, high retention rates, and a consistent safety profile in patients with active psoriatic arthritis (PsA) who were followed for ≥ 2 years.

Major finding: The treatment retention rate with secukinumab was 78.2% in PsA. The mean swollen joint counts (enrolment vs 2 years: 4.5 vs 3.6) and tender joint counts (enrolment vs 2 years: 12.8 vs 9.2) remained stable over 2 years of treatment. Serious adverse events occurred in 13.6% of patients, but no deaths related to treatment-emergent adverse events were reported.

Study details: Findings are from an interim analysis of the ongoing SERENA study including patients with active PsA (n = 81) or radiographic axial spondyloarthritis (n = 108) who had received secukinumab for ≥16 weeks prior to enrolment.

Disclosures: This study was supported by Novartis Pharma AG. Two authors declared being employees of Novartis Pharmaceuticals U.K. Ltd. Three authors declared ties with various sources, including Novartis.

Source: Gaffney K et al. Real-world evidence for secukinumab in UK patients with psoriatic arthritis or radiographic axial spondyloarthritis: Interim 2-year analysis from SERENA. Rheumatol Adv Pract. 2023;7(3):rkad055 (Aug 21). doi: 10.1093/rap/rkad055

Key clinical point: In a real-world population of patients with treatment-resistant, long-standing active psoriatic arthritis (PsA), nearly 80% persisted with guselkumab treatment for 6 months and showed improvements in peripheral joint and skin symptoms of PsA.

Major finding: Overall, 78.9% of patients who initiated guselkumab had persistent use at the 6-month follow-up. The mean scores for clinical Disease Activity in PsA (mean change [Δ] −5.4), overall joint+skin activity (Δ −19.0), patient-reported pain (Δ −9.1), and percentage of skin with psoriasis (Δ −5.1%) improved significantly in patients receiving guselkumab for 6 months (all P < .001).

Study details: This study evaluated 114 patients with active PsA from the CorEvitas PsA/Spondyloarthritis Registry who initiated guselkumab.

Disclosures: This study was sponsored by CorEvitas, LLC, and the analysis was funded by Janssen Scientific Affairs, LLC. Six authors declared employment with CorEvitas, LLC, or Janssen Scientific Affairs, LLC, or owned stock or stock options in Johnson & Johnson or others. Several authors declared ties with various sources, including Janssen and CorEvitas.

Source: Mease PJ et al. Six-month persistence and multi-domain effectiveness of guselkumab in adults with psoriatic arthritis: Real-world data from the CorEvitas psoriatic arthritis/spondyloarthritis registry. Rheumatol Ther. 2023 (Aug 19). doi: 10.1007/s40744-023-00582-w

Key clinical point: In a real-world population of patients with treatment-resistant, long-standing active psoriatic arthritis (PsA), nearly 80% persisted with guselkumab treatment for 6 months and showed improvements in peripheral joint and skin symptoms of PsA.

Major finding: Overall, 78.9% of patients who initiated guselkumab had persistent use at the 6-month follow-up. The mean scores for clinical Disease Activity in PsA (mean change [Δ] −5.4), overall joint+skin activity (Δ −19.0), patient-reported pain (Δ −9.1), and percentage of skin with psoriasis (Δ −5.1%) improved significantly in patients receiving guselkumab for 6 months (all P < .001).

Study details: This study evaluated 114 patients with active PsA from the CorEvitas PsA/Spondyloarthritis Registry who initiated guselkumab.

Disclosures: This study was sponsored by CorEvitas, LLC, and the analysis was funded by Janssen Scientific Affairs, LLC. Six authors declared employment with CorEvitas, LLC, or Janssen Scientific Affairs, LLC, or owned stock or stock options in Johnson & Johnson or others. Several authors declared ties with various sources, including Janssen and CorEvitas.

Source: Mease PJ et al. Six-month persistence and multi-domain effectiveness of guselkumab in adults with psoriatic arthritis: Real-world data from the CorEvitas psoriatic arthritis/spondyloarthritis registry. Rheumatol Ther. 2023 (Aug 19). doi: 10.1007/s40744-023-00582-w

Key clinical point: In a real-world population of patients with treatment-resistant, long-standing active psoriatic arthritis (PsA), nearly 80% persisted with guselkumab treatment for 6 months and showed improvements in peripheral joint and skin symptoms of PsA.

Major finding: Overall, 78.9% of patients who initiated guselkumab had persistent use at the 6-month follow-up. The mean scores for clinical Disease Activity in PsA (mean change [Δ] −5.4), overall joint+skin activity (Δ −19.0), patient-reported pain (Δ −9.1), and percentage of skin with psoriasis (Δ −5.1%) improved significantly in patients receiving guselkumab for 6 months (all P < .001).

Study details: This study evaluated 114 patients with active PsA from the CorEvitas PsA/Spondyloarthritis Registry who initiated guselkumab.

Disclosures: This study was sponsored by CorEvitas, LLC, and the analysis was funded by Janssen Scientific Affairs, LLC. Six authors declared employment with CorEvitas, LLC, or Janssen Scientific Affairs, LLC, or owned stock or stock options in Johnson & Johnson or others. Several authors declared ties with various sources, including Janssen and CorEvitas.

Source: Mease PJ et al. Six-month persistence and multi-domain effectiveness of guselkumab in adults with psoriatic arthritis: Real-world data from the CorEvitas psoriatic arthritis/spondyloarthritis registry. Rheumatol Ther. 2023 (Aug 19). doi: 10.1007/s40744-023-00582-w

Key clinical point: Ixekizumab was more effective than placebo in improving axial symptoms, such as back pain and morning stiffness, in patients with active psoriatic arthritis (PsA) presenting with axial manifestations.

Major finding: At weeks 16 and 24, ixekizumab vs placebo led to greater improvements in axial manifestations, such as back pain and morning stiffness (P < .001), as indicated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, with a significantly higher proportion of patients achieving a 50% improvement in BASDAI scores (P < .001). All improvements with ixekizumab were sustained through week 52.

Study details: This post hoc analysis of pooled data from two phase 3 studies included biologic-naive and tumor necrosis factor inhibitor-experienced patients with active PsA and axial manifestations (n = 313) who were randomly assigned to receive either ixekizumab or placebo.

Disclosures: The studies described in this post hoc analysis were sponsored by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly and Company. Several authors declared having ties with various sources, including Eli Lilly and Company.

Source: Deodhar A et al. The effect of ixekizumab on axial manifestations in patients with psoriatic arthritis from two phase III clinical trials: SPIRIT-P1 and SPIRIT-P2. Ther Adv Musculoskelet Dis. 2023 (Aug 24). doi: 10.1177/1759720X231189005

Key clinical point: Ixekizumab was more effective than placebo in improving axial symptoms, such as back pain and morning stiffness, in patients with active psoriatic arthritis (PsA) presenting with axial manifestations.

Major finding: At weeks 16 and 24, ixekizumab vs placebo led to greater improvements in axial manifestations, such as back pain and morning stiffness (P < .001), as indicated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, with a significantly higher proportion of patients achieving a 50% improvement in BASDAI scores (P < .001). All improvements with ixekizumab were sustained through week 52.

Study details: This post hoc analysis of pooled data from two phase 3 studies included biologic-naive and tumor necrosis factor inhibitor-experienced patients with active PsA and axial manifestations (n = 313) who were randomly assigned to receive either ixekizumab or placebo.

Disclosures: The studies described in this post hoc analysis were sponsored by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly and Company. Several authors declared having ties with various sources, including Eli Lilly and Company.

Source: Deodhar A et al. The effect of ixekizumab on axial manifestations in patients with psoriatic arthritis from two phase III clinical trials: SPIRIT-P1 and SPIRIT-P2. Ther Adv Musculoskelet Dis. 2023 (Aug 24). doi: 10.1177/1759720X231189005

Key clinical point: Ixekizumab was more effective than placebo in improving axial symptoms, such as back pain and morning stiffness, in patients with active psoriatic arthritis (PsA) presenting with axial manifestations.

Major finding: At weeks 16 and 24, ixekizumab vs placebo led to greater improvements in axial manifestations, such as back pain and morning stiffness (P < .001), as indicated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, with a significantly higher proportion of patients achieving a 50% improvement in BASDAI scores (P < .001). All improvements with ixekizumab were sustained through week 52.

Study details: This post hoc analysis of pooled data from two phase 3 studies included biologic-naive and tumor necrosis factor inhibitor-experienced patients with active PsA and axial manifestations (n = 313) who were randomly assigned to receive either ixekizumab or placebo.

Disclosures: The studies described in this post hoc analysis were sponsored by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly and Company. Several authors declared having ties with various sources, including Eli Lilly and Company.

Source: Deodhar A et al. The effect of ixekizumab on axial manifestations in patients with psoriatic arthritis from two phase III clinical trials: SPIRIT-P1 and SPIRIT-P2. Ther Adv Musculoskelet Dis. 2023 (Aug 24). doi: 10.1177/1759720X231189005

Key clinical point: The risk for psoriatic arthritis (PsA) was not higher among patients with psoriasis treated with acitretin vs disease-modifying antirheumatic drugs (DMARD), irrespective of the use of non-steroidal anti-inflammatory drugs (NSAID).

Major finding: The 5-year cumulative incidence rate for PsA was lower in the acitretin vs DMARD cohort (7.52% vs 9.93%; P = .005), with the incidence rates of PsA being markedly lower in the subgroup of patients receiving NSAID in the acitretin vs DMARD cohort (14.31% vs 23.83%; P = .008). Acitretin therapy showed no association with PsA development (hazard ratio 0.84; 95% CI 0.66-1.07).

Study details: Findings are from a retrospective cohort study including patients with psoriasis and without PsA who received either acitretin (n = 1948) or DMARD (n = 1948) for ≥ 30 days within a year.

Disclosures: This study was supported in part by the Taichung Veterans General Hospital. The authors declared no conflicts of interest.

Source: Lin TL et al. Psoriatic arthritis risk in psoriasis patients prescribed acitretin versus disease-modifying antirheumatic drugs: A nationwide cohort study. Rheumatology (Oxford). 2023 (Sep 1). doi: 10.1093/rheumatology/kead446

Key clinical point: The risk for psoriatic arthritis (PsA) was not higher among patients with psoriasis treated with acitretin vs disease-modifying antirheumatic drugs (DMARD), irrespective of the use of non-steroidal anti-inflammatory drugs (NSAID).

Major finding: The 5-year cumulative incidence rate for PsA was lower in the acitretin vs DMARD cohort (7.52% vs 9.93%; P = .005), with the incidence rates of PsA being markedly lower in the subgroup of patients receiving NSAID in the acitretin vs DMARD cohort (14.31% vs 23.83%; P = .008). Acitretin therapy showed no association with PsA development (hazard ratio 0.84; 95% CI 0.66-1.07).

Study details: Findings are from a retrospective cohort study including patients with psoriasis and without PsA who received either acitretin (n = 1948) or DMARD (n = 1948) for ≥ 30 days within a year.

Disclosures: This study was supported in part by the Taichung Veterans General Hospital. The authors declared no conflicts of interest.

Source: Lin TL et al. Psoriatic arthritis risk in psoriasis patients prescribed acitretin versus disease-modifying antirheumatic drugs: A nationwide cohort study. Rheumatology (Oxford). 2023 (Sep 1). doi: 10.1093/rheumatology/kead446

Key clinical point: The risk for psoriatic arthritis (PsA) was not higher among patients with psoriasis treated with acitretin vs disease-modifying antirheumatic drugs (DMARD), irrespective of the use of non-steroidal anti-inflammatory drugs (NSAID).

Major finding: The 5-year cumulative incidence rate for PsA was lower in the acitretin vs DMARD cohort (7.52% vs 9.93%; P = .005), with the incidence rates of PsA being markedly lower in the subgroup of patients receiving NSAID in the acitretin vs DMARD cohort (14.31% vs 23.83%; P = .008). Acitretin therapy showed no association with PsA development (hazard ratio 0.84; 95% CI 0.66-1.07).

Study details: Findings are from a retrospective cohort study including patients with psoriasis and without PsA who received either acitretin (n = 1948) or DMARD (n = 1948) for ≥ 30 days within a year.

Disclosures: This study was supported in part by the Taichung Veterans General Hospital. The authors declared no conflicts of interest.

Source: Lin TL et al. Psoriatic arthritis risk in psoriasis patients prescribed acitretin versus disease-modifying antirheumatic drugs: A nationwide cohort study. Rheumatology (Oxford). 2023 (Sep 1). doi: 10.1093/rheumatology/kead446

Key clinical point: Patients with psoriatic arthritis (PsA) showed similar adherence to secukinumab and ixekizumab as first-line or second-line interleukin (IL)-17A inhibitors, which indicates that the failure of a first-line IL-17A inhibitor therapy should not deter treatment with a second-line IL-17A inhibitors.

Major finding: Similar adherence to treatment 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 (14% for both); however, withdrawal due to failure of therapy was higher for the first-line vs second-line switchers (34% vs 18%).

Study details: Findings are from a population-based cohort study including patients with PsA who underwent prior treatment with ≥ 1 tumor necrosis factor inhibitor and switched to either first-line (n = 534) or second-line (n = 102) IL-17A inhibitors (ixekizumab or secukinumab).

Disclosures: This study was funded by the Oak Foundation. Five authors declared having ties with various sources, and three authors declared no conflicts of interest.

Source: Hansen RL et al. Adherence to therapy of ixekizumab and secukinumab in psoriatic arthritis patients using first- or second-line IL-17A inhibitor treatment: A Danish population-based cohort study. Rheumatology (Oxford). 2023 (Aug 30). doi: 10.1093/rheumatology/kead434

Key clinical point: Patients with psoriatic arthritis (PsA) showed similar adherence to secukinumab and ixekizumab as first-line or second-line interleukin (IL)-17A inhibitors, which indicates that the failure of a first-line IL-17A inhibitor therapy should not deter treatment with a second-line IL-17A inhibitors.

Major finding: Similar adherence to treatment 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 (14% for both); however, withdrawal due to failure of therapy was higher for the first-line vs second-line switchers (34% vs 18%).

Study details: Findings are from a population-based cohort study including patients with PsA who underwent prior treatment with ≥ 1 tumor necrosis factor inhibitor and switched to either first-line (n = 534) or second-line (n = 102) IL-17A inhibitors (ixekizumab or secukinumab).

Disclosures: This study was funded by the Oak Foundation. Five authors declared having ties with various sources, and three authors declared no conflicts of interest.

Source: Hansen RL et al. Adherence to therapy of ixekizumab and secukinumab in psoriatic arthritis patients using first- or second-line IL-17A inhibitor treatment: A Danish population-based cohort study. Rheumatology (Oxford). 2023 (Aug 30). doi: 10.1093/rheumatology/kead434

Key clinical point: Patients with psoriatic arthritis (PsA) showed similar adherence to secukinumab and ixekizumab as first-line or second-line interleukin (IL)-17A inhibitors, which indicates that the failure of a first-line IL-17A inhibitor therapy should not deter treatment with a second-line IL-17A inhibitors.

Major finding: Similar adherence to treatment 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 (14% for both); however, withdrawal due to failure of therapy was higher for the first-line vs second-line switchers (34% vs 18%).

Study details: Findings are from a population-based cohort study including patients with PsA who underwent prior treatment with ≥ 1 tumor necrosis factor inhibitor and switched to either first-line (n = 534) or second-line (n = 102) IL-17A inhibitors (ixekizumab or secukinumab).

Disclosures: This study was funded by the Oak Foundation. Five authors declared having ties with various sources, and three authors declared no conflicts of interest.

Source: Hansen RL et al. Adherence to therapy of ixekizumab and secukinumab in psoriatic arthritis patients using first- or second-line IL-17A inhibitor treatment: A Danish population-based cohort study. Rheumatology (Oxford). 2023 (Aug 30). doi: 10.1093/rheumatology/kead434

Key clinical point: Biological disease-modifying antirheumatic drugs (bDMARD) showed comparable efficacy in patients with psoriatic arthritis (PsA) with either low joint count (LJC) or high joint count (HJC), which highlights the feasibility of treatment escalation to bDMARD in symptomatic patients with LJC as well as in those with HJC.

Major finding: Patients with LJC (<3 tender or swollen joints) vs HJC (≥3 tender or swollen joints) showed similar treatment efficacy in terms of bDMARD retention (adjusted hazard ratio [aHR] 1.09; P = .63). Treatment discontinuation was unaffected by swollen or tender joint count status (aHR 1.12; P = .47).

Study details: Findings are from an observational cohort study that included 387 patients with PsA who had either LJC (n = 197) or HJC (n = 190) and received bDMARD.

Disclosures: This study was supported by Celgene International Sarl, Boudry, Switzerland. Five authors declared ties with various sources, whereas the other authors declared no conflicts of interest.

Source: Möller B et al for the Swiss Clinical Quality Management (SCQM) physicians, researchers and patients. Biological disease-modifying anti-rheumatic drugs are equally effective in psoriatic arthritis patients with low and high joint counts. Rheumatology (Oxford). 2023 (Sep 7). doi: 10.1093/rheumatology/kead455

Key clinical point: Biological disease-modifying antirheumatic drugs (bDMARD) showed comparable efficacy in patients with psoriatic arthritis (PsA) with either low joint count (LJC) or high joint count (HJC), which highlights the feasibility of treatment escalation to bDMARD in symptomatic patients with LJC as well as in those with HJC.

Major finding: Patients with LJC (<3 tender or swollen joints) vs HJC (≥3 tender or swollen joints) showed similar treatment efficacy in terms of bDMARD retention (adjusted hazard ratio [aHR] 1.09; P = .63). Treatment discontinuation was unaffected by swollen or tender joint count status (aHR 1.12; P = .47).

Study details: Findings are from an observational cohort study that included 387 patients with PsA who had either LJC (n = 197) or HJC (n = 190) and received bDMARD.

Disclosures: This study was supported by Celgene International Sarl, Boudry, Switzerland. Five authors declared ties with various sources, whereas the other authors declared no conflicts of interest.

Source: Möller B et al for the Swiss Clinical Quality Management (SCQM) physicians, researchers and patients. Biological disease-modifying anti-rheumatic drugs are equally effective in psoriatic arthritis patients with low and high joint counts. Rheumatology (Oxford). 2023 (Sep 7). doi: 10.1093/rheumatology/kead455

Key clinical point: Biological disease-modifying antirheumatic drugs (bDMARD) showed comparable efficacy in patients with psoriatic arthritis (PsA) with either low joint count (LJC) or high joint count (HJC), which highlights the feasibility of treatment escalation to bDMARD in symptomatic patients with LJC as well as in those with HJC.

Major finding: Patients with LJC (<3 tender or swollen joints) vs HJC (≥3 tender or swollen joints) showed similar treatment efficacy in terms of bDMARD retention (adjusted hazard ratio [aHR] 1.09; P = .63). Treatment discontinuation was unaffected by swollen or tender joint count status (aHR 1.12; P = .47).

Study details: Findings are from an observational cohort study that included 387 patients with PsA who had either LJC (n = 197) or HJC (n = 190) and received bDMARD.

Disclosures: This study was supported by Celgene International Sarl, Boudry, Switzerland. Five authors declared ties with various sources, whereas the other authors declared no conflicts of interest.

Source: Möller B et al for the Swiss Clinical Quality Management (SCQM) physicians, researchers and patients. Biological disease-modifying anti-rheumatic drugs are equally effective in psoriatic arthritis patients with low and high joint counts. Rheumatology (Oxford). 2023 (Sep 7). doi: 10.1093/rheumatology/kead455

Key clinical point: Guselkumab led to early reduction of inflammatory cytokines, which was sustained through 48 weeks, with subsequent improvements in clinical response in patients with active psoriatic arthritis (PsA) and an inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: Serum levels of interleukin (IL)-17A, IL-17F, IL-22, and serum amyloid A reduced significantly by week 4 and were sustained through week 48 in the guselkumab (P < .05) vs placebo group when compared with control individuals without PsA. Patients who achieved a clinical response to guselkumab at week 24 showed significant reduction in IL-6 levels at week 4 compared with non-responders (P < .05).

Study details: Findings are from the phase 3b COSMOS study including patients with active PsA and TNFi-IR who were randomly assigned to receive either guselkumab (n = 189) or placebo (n = 96) and compared with matched control individuals.

Disclosures: This study was sponsored by Janssen Research & Development (R&D), LLC, USA. Seven authors declared being employees of Janssen R&D, LLC, or others or owning stocks or stock options in Johnson & Johnson. Several authors declared ties with various sources, including Janssen.

Source: Schett G et al. Effect of guselkumab on serum biomarkers in patients with active psoriatic arthritis and inadequate response to tumor necrosis factor inhibitors: Results from the COSMOS phase 3b study. Arthritis Res Ther. 2023;25:150 (Aug 16, corrected Sep 15). doi: 10.1186/s13075-023-03125-4

Key clinical point: Guselkumab led to early reduction of inflammatory cytokines, which was sustained through 48 weeks, with subsequent improvements in clinical response in patients with active psoriatic arthritis (PsA) and an inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: Serum levels of interleukin (IL)-17A, IL-17F, IL-22, and serum amyloid A reduced significantly by week 4 and were sustained through week 48 in the guselkumab (P < .05) vs placebo group when compared with control individuals without PsA. Patients who achieved a clinical response to guselkumab at week 24 showed significant reduction in IL-6 levels at week 4 compared with non-responders (P < .05).

Study details: Findings are from the phase 3b COSMOS study including patients with active PsA and TNFi-IR who were randomly assigned to receive either guselkumab (n = 189) or placebo (n = 96) and compared with matched control individuals.

Disclosures: This study was sponsored by Janssen Research & Development (R&D), LLC, USA. Seven authors declared being employees of Janssen R&D, LLC, or others or owning stocks or stock options in Johnson & Johnson. Several authors declared ties with various sources, including Janssen.

Source: Schett G et al. Effect of guselkumab on serum biomarkers in patients with active psoriatic arthritis and inadequate response to tumor necrosis factor inhibitors: Results from the COSMOS phase 3b study. Arthritis Res Ther. 2023;25:150 (Aug 16, corrected Sep 15). doi: 10.1186/s13075-023-03125-4

Key clinical point: Guselkumab led to early reduction of inflammatory cytokines, which was sustained through 48 weeks, with subsequent improvements in clinical response in patients with active psoriatic arthritis (PsA) and an inadequate response to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: Serum levels of interleukin (IL)-17A, IL-17F, IL-22, and serum amyloid A reduced significantly by week 4 and were sustained through week 48 in the guselkumab (P < .05) vs placebo group when compared with control individuals without PsA. Patients who achieved a clinical response to guselkumab at week 24 showed significant reduction in IL-6 levels at week 4 compared with non-responders (P < .05).

Study details: Findings are from the phase 3b COSMOS study including patients with active PsA and TNFi-IR who were randomly assigned to receive either guselkumab (n = 189) or placebo (n = 96) and compared with matched control individuals.

Disclosures: This study was sponsored by Janssen Research & Development (R&D), LLC, USA. Seven authors declared being employees of Janssen R&D, LLC, or others or owning stocks or stock options in Johnson & Johnson. Several authors declared ties with various sources, including Janssen.

Source: Schett G et al. Effect of guselkumab on serum biomarkers in patients with active psoriatic arthritis and inadequate response to tumor necrosis factor inhibitors: Results from the COSMOS phase 3b study. Arthritis Res Ther. 2023;25:150 (Aug 16, corrected Sep 15). doi: 10.1186/s13075-023-03125-4

TOPLINE:

The drug mirabegron, used to treat overactive bladder disease, when added to standard treatment did not improve either left ventricular mass index or diastolic function over 12 months among patients with pre–heart failure (pre-HF) structural heart disease who were at risk of developing or worsening HF.

METHODOLOGY:

• Interventions for patients with asymptomatic pre-HF may be important in reducing the incidence of clinically overt HF, including HF with preserved ejection fraction (HFpEF).
• Mirabegron activates the cardiac beta-3 adrenergic receptor, which may offer an alternative activation of the cyclic guanosine monophosphate protein/kinase G (cGMP/PKG) pathway for patients at risk of or with mild HF and protect against worsening left ventricular hypertrophy (LVH) and/or diastolic dysfunction, but few clinical trials have evaluated the effect of mirabegron on cardiovascular outcomes.
• The phase 2b Beta3_LVH trial included 296 patients, some with and some without HF symptoms (mean age, 63 years), at 10 centers in Europe and the United Kingdom. All had an increased LV mass index (LVMI) (≥ 115 g/m² for men and ≥ 95 g/m² for women) or end-diastolic wall thickness of ≥ 13 mm in at least one wall segment.
• Patients, many of whom had risk factors, including hypertension, and were receiving cardiovascular therapies, were randomly assigned to receive mirabegron 50 mg/day or placebo and underwent various tests, including cardiac MRI, Doppler echocardiography, and urine and blood sampling for fasting glucose, insulin, hemoglobin A1c, serum lipids, and other measures.
• The two primary endpoints were change in left ventricular mass index (LVMI), expressed in grams per meters squared, and change in diastolic function, assessed as the ratio of peak early transmitral ventricular filling velocity to early diastolic tissue Doppler velocity (E/e´).

TAKEAWAY:

• Neither primary outcome reached statistical significance at 12 months; adjusted differences between groups included a 1.3g/m² increase in LVMI (95% confidence interval, −0.15 to 2.74; P = .08) and a −0.15 decrease in E/e´ (95% CI, −0.69 to 0.4; P = .60).
• There was no statistically significant effect of mirabegron, in comparison with placebo, on lipids, glycemic control, or insulin sensitivity.
• The effect of mirabegron remained neutral in exploratory subgroup analyses, including age (≤ 65 years or > 65 years at baseline), sex (men or women), body mass index (≤ 30 kg/m² or > 30 at baseline), presence of type 2 diabetes, atrial fibrillation, beta-blocker use, and geographic region.
• There were no deaths. There was a total of 428 adverse events (AEs), but there were no statistically significant between-group differences in the occurrence of these AEs.

IN PRACTICE:

While this study showed that mirabegron had a neutral effect on LV mass and diastolic function for patients with pre-HF or mild HF, the researchers suggest that longer-term effects of beta-3 adrenergic stimulation on myocardial remodeling and function “need to be tested in patients with established HFpEF, including with recent, more potent agonists.”

SOURCE:

The study was conducted by Jean-Luc Balligand, MD, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, and colleagues. It was published online in JAMA Cardiology.

LIMITATIONS:

Inclusion of patients with mild HF and use of a single standard mirabegron dosage (50 mg/day) may have prevented detection of a treatment effect. More advanced techniques than measurements of E/e´, such as cardiac strain, may have been better for assessing early changes in diastolic function. Although missing data and dropouts were relatively infrequent and were compensated for in the study, these remain limitations.

DISCLOSURES:

The study was funded by European Commission Horizon 2020 Framework Programme. Dr. Balligand reported receiving grants from the European Commission during the conduct of the study, grants from Novartis and Daiichi Sankyo outside the submitted work, and consulting fees from Amgen, Novartis, and Daiichi Sankyo outside the submitted work; he also reported being a minor shareholder of Spinovit and serving as a board member for the Wallonia Health and Biotech Cluster, Biowin, and the AstraZeneca Foundation.

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

TOPLINE:

The drug mirabegron, used to treat overactive bladder disease, when added to standard treatment did not improve either left ventricular mass index or diastolic function over 12 months among patients with pre–heart failure (pre-HF) structural heart disease who were at risk of developing or worsening HF.

METHODOLOGY:

• Interventions for patients with asymptomatic pre-HF may be important in reducing the incidence of clinically overt HF, including HF with preserved ejection fraction (HFpEF).
• Mirabegron activates the cardiac beta-3 adrenergic receptor, which may offer an alternative activation of the cyclic guanosine monophosphate protein/kinase G (cGMP/PKG) pathway for patients at risk of or with mild HF and protect against worsening left ventricular hypertrophy (LVH) and/or diastolic dysfunction, but few clinical trials have evaluated the effect of mirabegron on cardiovascular outcomes.
• The phase 2b Beta3_LVH trial included 296 patients, some with and some without HF symptoms (mean age, 63 years), at 10 centers in Europe and the United Kingdom. All had an increased LV mass index (LVMI) (≥ 115 g/m² for men and ≥ 95 g/m² for women) or end-diastolic wall thickness of ≥ 13 mm in at least one wall segment.
• Patients, many of whom had risk factors, including hypertension, and were receiving cardiovascular therapies, were randomly assigned to receive mirabegron 50 mg/day or placebo and underwent various tests, including cardiac MRI, Doppler echocardiography, and urine and blood sampling for fasting glucose, insulin, hemoglobin A1c, serum lipids, and other measures.
• The two primary endpoints were change in left ventricular mass index (LVMI), expressed in grams per meters squared, and change in diastolic function, assessed as the ratio of peak early transmitral ventricular filling velocity to early diastolic tissue Doppler velocity (E/e´).

TAKEAWAY:

• Neither primary outcome reached statistical significance at 12 months; adjusted differences between groups included a 1.3g/m² increase in LVMI (95% confidence interval, −0.15 to 2.74; P = .08) and a −0.15 decrease in E/e´ (95% CI, −0.69 to 0.4; P = .60).
• There was no statistically significant effect of mirabegron, in comparison with placebo, on lipids, glycemic control, or insulin sensitivity.
• The effect of mirabegron remained neutral in exploratory subgroup analyses, including age (≤ 65 years or > 65 years at baseline), sex (men or women), body mass index (≤ 30 kg/m² or > 30 at baseline), presence of type 2 diabetes, atrial fibrillation, beta-blocker use, and geographic region.
• There were no deaths. There was a total of 428 adverse events (AEs), but there were no statistically significant between-group differences in the occurrence of these AEs.

IN PRACTICE:

While this study showed that mirabegron had a neutral effect on LV mass and diastolic function for patients with pre-HF or mild HF, the researchers suggest that longer-term effects of beta-3 adrenergic stimulation on myocardial remodeling and function “need to be tested in patients with established HFpEF, including with recent, more potent agonists.”

SOURCE:

The study was conducted by Jean-Luc Balligand, MD, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, and colleagues. It was published online in JAMA Cardiology.

LIMITATIONS:

Inclusion of patients with mild HF and use of a single standard mirabegron dosage (50 mg/day) may have prevented detection of a treatment effect. More advanced techniques than measurements of E/e´, such as cardiac strain, may have been better for assessing early changes in diastolic function. Although missing data and dropouts were relatively infrequent and were compensated for in the study, these remain limitations.

DISCLOSURES:

The study was funded by European Commission Horizon 2020 Framework Programme. Dr. Balligand reported receiving grants from the European Commission during the conduct of the study, grants from Novartis and Daiichi Sankyo outside the submitted work, and consulting fees from Amgen, Novartis, and Daiichi Sankyo outside the submitted work; he also reported being a minor shareholder of Spinovit and serving as a board member for the Wallonia Health and Biotech Cluster, Biowin, and the AstraZeneca Foundation.

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

TOPLINE:

The drug mirabegron, used to treat overactive bladder disease, when added to standard treatment did not improve either left ventricular mass index or diastolic function over 12 months among patients with pre–heart failure (pre-HF) structural heart disease who were at risk of developing or worsening HF.

METHODOLOGY:

• Interventions for patients with asymptomatic pre-HF may be important in reducing the incidence of clinically overt HF, including HF with preserved ejection fraction (HFpEF).
• Mirabegron activates the cardiac beta-3 adrenergic receptor, which may offer an alternative activation of the cyclic guanosine monophosphate protein/kinase G (cGMP/PKG) pathway for patients at risk of or with mild HF and protect against worsening left ventricular hypertrophy (LVH) and/or diastolic dysfunction, but few clinical trials have evaluated the effect of mirabegron on cardiovascular outcomes.
• The phase 2b Beta3_LVH trial included 296 patients, some with and some without HF symptoms (mean age, 63 years), at 10 centers in Europe and the United Kingdom. All had an increased LV mass index (LVMI) (≥ 115 g/m² for men and ≥ 95 g/m² for women) or end-diastolic wall thickness of ≥ 13 mm in at least one wall segment.
• Patients, many of whom had risk factors, including hypertension, and were receiving cardiovascular therapies, were randomly assigned to receive mirabegron 50 mg/day or placebo and underwent various tests, including cardiac MRI, Doppler echocardiography, and urine and blood sampling for fasting glucose, insulin, hemoglobin A1c, serum lipids, and other measures.
• The two primary endpoints were change in left ventricular mass index (LVMI), expressed in grams per meters squared, and change in diastolic function, assessed as the ratio of peak early transmitral ventricular filling velocity to early diastolic tissue Doppler velocity (E/e´).

TAKEAWAY:

• Neither primary outcome reached statistical significance at 12 months; adjusted differences between groups included a 1.3g/m² increase in LVMI (95% confidence interval, −0.15 to 2.74; P = .08) and a −0.15 decrease in E/e´ (95% CI, −0.69 to 0.4; P = .60).
• There was no statistically significant effect of mirabegron, in comparison with placebo, on lipids, glycemic control, or insulin sensitivity.
• The effect of mirabegron remained neutral in exploratory subgroup analyses, including age (≤ 65 years or > 65 years at baseline), sex (men or women), body mass index (≤ 30 kg/m² or > 30 at baseline), presence of type 2 diabetes, atrial fibrillation, beta-blocker use, and geographic region.
• There were no deaths. There was a total of 428 adverse events (AEs), but there were no statistically significant between-group differences in the occurrence of these AEs.

IN PRACTICE:

While this study showed that mirabegron had a neutral effect on LV mass and diastolic function for patients with pre-HF or mild HF, the researchers suggest that longer-term effects of beta-3 adrenergic stimulation on myocardial remodeling and function “need to be tested in patients with established HFpEF, including with recent, more potent agonists.”

SOURCE:

The study was conducted by Jean-Luc Balligand, MD, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, and colleagues. It was published online in JAMA Cardiology.

LIMITATIONS:

Inclusion of patients with mild HF and use of a single standard mirabegron dosage (50 mg/day) may have prevented detection of a treatment effect. More advanced techniques than measurements of E/e´, such as cardiac strain, may have been better for assessing early changes in diastolic function. Although missing data and dropouts were relatively infrequent and were compensated for in the study, these remain limitations.

DISCLOSURES:

The study was funded by European Commission Horizon 2020 Framework Programme. Dr. Balligand reported receiving grants from the European Commission during the conduct of the study, grants from Novartis and Daiichi Sankyo outside the submitted work, and consulting fees from Amgen, Novartis, and Daiichi Sankyo outside the submitted work; he also reported being a minor shareholder of Spinovit and serving as a board member for the Wallonia Health and Biotech Cluster, Biowin, and the AstraZeneca Foundation.

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

Successful catheter ablation in a recent study may have helped alleviate anxiety or depression in patients with atrial fibrillation (AFib) who had initially tested high for such psychological distress.

The finding, said the researchers, may point to an overlooked potential benefit of ablation that can be discussed with patients considering whether to have the procedure.

Importantly, the 100 adults with symptomatic paroxysmal or persistent AFib in the randomized trial weren’t blinded to treatment assignment, which was either ablation or continued medical therapy.

That leaves open the possibility that psychological distress improved in the ablation group not from any unique effect of ablation itself but because patients expected to benefit from the procedure.

The investigators acknowledged that their trial, called REMEDIAL, can’t rule out a placebo effect as part of the observed benefit. Indeed, studies suggest that there is a substantial placebo component of AFib ablation – which, notably, is usually done to make patients feel better.

But the current findings are more consistent with the conventional view that patients feel better primarily because ablation reduces the AFib causing their symptoms, the group said.

Psychological stress in the study started to fall early after the procedure and continued to decline consistently over the next 6 months (P = .006) and 12 months (P = .005), not a typical pattern for placebo, they wrote.

Moreover, the mental health benefits “correlated very strongly” with less recurrent AFib, reduced AFib burden, and withdrawal of beta-blockers and antiarrhythmic agents, outcomes that might be expected from ablation, said Jonathan M. Kalman, MBBS, PhD.

“Of course, I cannot say there is no placebo effect from having had the procedure, and maybe that something to consider,” but it’s probably not the main driver of benefit, he said in an interview. The relationship between successful AFib ablation “and improvements in physical and now mental health is overwhelming.”

Dr. Kalman, who is affiliated with Royal Melbourne Hospital, is senior author on the study, published in JAMA.

The findings add to “strong, reproducible evidence that ablation is the best way to tackle rhythm control in [AFib] populations” regardless of age, mental health status, or AFib burden, said Auroa Badin, MD, who wasn’t involved in REMEDIAL but has studied the psychological effects of arrhythmia ablation.

For example, there is “very good evidence” from CABANA and other trials that AFib ablation “considerably improves quality of life,” Dr. Badin, of OhioHealth Heart & Vascular Physicians, Columbus, said in an interview. The current study “just emphasizes that there’s also a psychological effect.”

Some of that response could be a placebo or even a nocebo effect. Most of the patients assigned to the medical arm had already been on medications that failed at rhythm control. And their management in the trial, he said, “even if you optimize it, was still drug therapy.”

Patients in the control group, therefore, could have been “disappointed” at the prospect of continued ineffective therapy in a way that influenced their outcomes. “That is another confounding factor,” Dr. Badin said.

But if the psychological results of ablation in the trial were predominantly a placebo effect, early differences in psychological test scores would not have persisted for long, certainly not for a year, he observed. Moreover, the ablation group had better test scores at 12 months than at 6 months, “indicating a likelihood of improvement over time.”

Differences between the groups would probably have been less pronounced if the control group had received a sham procedure, Dr. Badin proposed. That would potentially differentiate ablation’s clinical and placebo contributions to the outcomes.

Still, he said, any observed placebo effect in a sham-controlled trial would probably have been limited. “I think it still would have been a positive trial. It may not show the same difference, but I don’t think you would have a neutral trial just by doing a sham.”

REMEDIAL has “good data,” and its conclusions about ablation’s potential psychological benefits are “reasonable” and worth bringing up when discussing the procedure with patients, Dr. Badin said.

Indeed, psychological distress is “important and often overlooked” in patients with AFib, Dr. Kalman observed. “The dominant indication for atrial fibrillation ablation is symptomatic impact on quality of life. We should think about that broadly, about not just the physical symptoms but the impact on their mental health.”

The trial was conducted at two centers in Australia. It enrolled patients, one-third of whom were women, who were on medical management for AFib. Patients receiving treatment for severe depression were excluded. The included patients were randomly assigned to undergo catheter ablation or to continue on closely managed rhythm-control medication, with cardioversion as indicated.

Psychological distress was measured at baseline and throughout follow-up by a battery of self-administered, validated questionnaires. Baseline test scores for the two groups were similar.

Recurrence and burden of AFib were tracked primarily by daily KardiaMobile (AliveCor) ECG monitoring. A few patients were followed using already implanted cardiac rhythm devices or by 24-hour Holter monitor every 3 months, Dr. Kalman said.

Composite scores on the Hospital Anxiety and Depression Scale (HADS) at 12 months, the primary endpoint, were 7.6 and 11.8 (P = .005) for the ablation and medical groups, respectively. They were 8.2 and 11.9 (P = .006), respectively, at 6 months.

The prevalence of severe psychological distress, defined as a HADS score greater than 15, was lower in the ablation group at 6 months (14.2% vs. 34%; P = .02) and 12 months (10.2% vs. 31.9%; P = .01).

Scores on the Beck Depression Inventory–II questionnaire were also consistently and significantly better for the ablation group at 6 and at 12 months (P = .01 for both).

Monitoring picked up AFib in 47% of the ablation group and 96% of the control group (P < .001) over 12 months. Their median AFib burdens were 0% (interquartile range, 0%-3.2%) and 15.5% (IQR, 1%-46%), respectively (P < .001).

Antiarrhythmic drug use fell from a baseline of 90% to 53% 3 months after ablation and 30% at 12 months (P = .003). Use of these drugs in the control group was 89% at baseline and remained essentially the same, 85%, at 12 months.

AFib symptom severity scores were significantly lower after ablation, compared with medical management at 3, 6, and 12 months.

The observed effect of ablation on psychological stress “clearly speaks in favor of effective rhythm control, and moreover catheter ablation” and is a “novel argument” in support of catheter ablation for AFib, Julia Lurz, MD, Heart Center Leipzig (Germany) at University Leipzig, and Karl-Heinz Ladwig, MD, PhD, Technical University Munich (Germany), wrote in an editorial accompanying publication of REMEDIAL.

But the findings also “raise the question of why rhythm control was so ineffective in the medical treatment group,” they wrote.

They agreed that the randomization process itself may have had its own psychological effects. “Potential disappointment” in the medical group and “high expectations” among patients who received ablation “could have fueled the success of catheter ablation” with respect to mental health endpoints.

Dr. Kalman reported receiving grants from the National Health and Medical Research Council of Australia, Medtronic, Mooney, and Biosense Webster. Dr. Badin, Dr. Lurz, and Dr. Ladwig reported no conflicts of interest.

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

Successful catheter ablation in a recent study may have helped alleviate anxiety or depression in patients with atrial fibrillation (AFib) who had initially tested high for such psychological distress.

The finding, said the researchers, may point to an overlooked potential benefit of ablation that can be discussed with patients considering whether to have the procedure.

Importantly, the 100 adults with symptomatic paroxysmal or persistent AFib in the randomized trial weren’t blinded to treatment assignment, which was either ablation or continued medical therapy.

That leaves open the possibility that psychological distress improved in the ablation group not from any unique effect of ablation itself but because patients expected to benefit from the procedure.

The investigators acknowledged that their trial, called REMEDIAL, can’t rule out a placebo effect as part of the observed benefit. Indeed, studies suggest that there is a substantial placebo component of AFib ablation – which, notably, is usually done to make patients feel better.

But the current findings are more consistent with the conventional view that patients feel better primarily because ablation reduces the AFib causing their symptoms, the group said.

Psychological stress in the study started to fall early after the procedure and continued to decline consistently over the next 6 months (P = .006) and 12 months (P = .005), not a typical pattern for placebo, they wrote.

Moreover, the mental health benefits “correlated very strongly” with less recurrent AFib, reduced AFib burden, and withdrawal of beta-blockers and antiarrhythmic agents, outcomes that might be expected from ablation, said Jonathan M. Kalman, MBBS, PhD.

“Of course, I cannot say there is no placebo effect from having had the procedure, and maybe that something to consider,” but it’s probably not the main driver of benefit, he said in an interview. The relationship between successful AFib ablation “and improvements in physical and now mental health is overwhelming.”

Dr. Kalman, who is affiliated with Royal Melbourne Hospital, is senior author on the study, published in JAMA.

The findings add to “strong, reproducible evidence that ablation is the best way to tackle rhythm control in [AFib] populations” regardless of age, mental health status, or AFib burden, said Auroa Badin, MD, who wasn’t involved in REMEDIAL but has studied the psychological effects of arrhythmia ablation.

For example, there is “very good evidence” from CABANA and other trials that AFib ablation “considerably improves quality of life,” Dr. Badin, of OhioHealth Heart & Vascular Physicians, Columbus, said in an interview. The current study “just emphasizes that there’s also a psychological effect.”

Some of that response could be a placebo or even a nocebo effect. Most of the patients assigned to the medical arm had already been on medications that failed at rhythm control. And their management in the trial, he said, “even if you optimize it, was still drug therapy.”

Patients in the control group, therefore, could have been “disappointed” at the prospect of continued ineffective therapy in a way that influenced their outcomes. “That is another confounding factor,” Dr. Badin said.

But if the psychological results of ablation in the trial were predominantly a placebo effect, early differences in psychological test scores would not have persisted for long, certainly not for a year, he observed. Moreover, the ablation group had better test scores at 12 months than at 6 months, “indicating a likelihood of improvement over time.”

Differences between the groups would probably have been less pronounced if the control group had received a sham procedure, Dr. Badin proposed. That would potentially differentiate ablation’s clinical and placebo contributions to the outcomes.

Still, he said, any observed placebo effect in a sham-controlled trial would probably have been limited. “I think it still would have been a positive trial. It may not show the same difference, but I don’t think you would have a neutral trial just by doing a sham.”

REMEDIAL has “good data,” and its conclusions about ablation’s potential psychological benefits are “reasonable” and worth bringing up when discussing the procedure with patients, Dr. Badin said.

Indeed, psychological distress is “important and often overlooked” in patients with AFib, Dr. Kalman observed. “The dominant indication for atrial fibrillation ablation is symptomatic impact on quality of life. We should think about that broadly, about not just the physical symptoms but the impact on their mental health.”

The trial was conducted at two centers in Australia. It enrolled patients, one-third of whom were women, who were on medical management for AFib. Patients receiving treatment for severe depression were excluded. The included patients were randomly assigned to undergo catheter ablation or to continue on closely managed rhythm-control medication, with cardioversion as indicated.

Psychological distress was measured at baseline and throughout follow-up by a battery of self-administered, validated questionnaires. Baseline test scores for the two groups were similar.

Recurrence and burden of AFib were tracked primarily by daily KardiaMobile (AliveCor) ECG monitoring. A few patients were followed using already implanted cardiac rhythm devices or by 24-hour Holter monitor every 3 months, Dr. Kalman said.

Composite scores on the Hospital Anxiety and Depression Scale (HADS) at 12 months, the primary endpoint, were 7.6 and 11.8 (P = .005) for the ablation and medical groups, respectively. They were 8.2 and 11.9 (P = .006), respectively, at 6 months.

The prevalence of severe psychological distress, defined as a HADS score greater than 15, was lower in the ablation group at 6 months (14.2% vs. 34%; P = .02) and 12 months (10.2% vs. 31.9%; P = .01).

Scores on the Beck Depression Inventory–II questionnaire were also consistently and significantly better for the ablation group at 6 and at 12 months (P = .01 for both).

Monitoring picked up AFib in 47% of the ablation group and 96% of the control group (P < .001) over 12 months. Their median AFib burdens were 0% (interquartile range, 0%-3.2%) and 15.5% (IQR, 1%-46%), respectively (P < .001).

Antiarrhythmic drug use fell from a baseline of 90% to 53% 3 months after ablation and 30% at 12 months (P = .003). Use of these drugs in the control group was 89% at baseline and remained essentially the same, 85%, at 12 months.

AFib symptom severity scores were significantly lower after ablation, compared with medical management at 3, 6, and 12 months.

The observed effect of ablation on psychological stress “clearly speaks in favor of effective rhythm control, and moreover catheter ablation” and is a “novel argument” in support of catheter ablation for AFib, Julia Lurz, MD, Heart Center Leipzig (Germany) at University Leipzig, and Karl-Heinz Ladwig, MD, PhD, Technical University Munich (Germany), wrote in an editorial accompanying publication of REMEDIAL.

But the findings also “raise the question of why rhythm control was so ineffective in the medical treatment group,” they wrote.

They agreed that the randomization process itself may have had its own psychological effects. “Potential disappointment” in the medical group and “high expectations” among patients who received ablation “could have fueled the success of catheter ablation” with respect to mental health endpoints.

Dr. Kalman reported receiving grants from the National Health and Medical Research Council of Australia, Medtronic, Mooney, and Biosense Webster. Dr. Badin, Dr. Lurz, and Dr. Ladwig reported no conflicts of interest.

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

Successful catheter ablation in a recent study may have helped alleviate anxiety or depression in patients with atrial fibrillation (AFib) who had initially tested high for such psychological distress.

The finding, said the researchers, may point to an overlooked potential benefit of ablation that can be discussed with patients considering whether to have the procedure.

Importantly, the 100 adults with symptomatic paroxysmal or persistent AFib in the randomized trial weren’t blinded to treatment assignment, which was either ablation or continued medical therapy.

That leaves open the possibility that psychological distress improved in the ablation group not from any unique effect of ablation itself but because patients expected to benefit from the procedure.

The investigators acknowledged that their trial, called REMEDIAL, can’t rule out a placebo effect as part of the observed benefit. Indeed, studies suggest that there is a substantial placebo component of AFib ablation – which, notably, is usually done to make patients feel better.

But the current findings are more consistent with the conventional view that patients feel better primarily because ablation reduces the AFib causing their symptoms, the group said.

Psychological stress in the study started to fall early after the procedure and continued to decline consistently over the next 6 months (P = .006) and 12 months (P = .005), not a typical pattern for placebo, they wrote.

Moreover, the mental health benefits “correlated very strongly” with less recurrent AFib, reduced AFib burden, and withdrawal of beta-blockers and antiarrhythmic agents, outcomes that might be expected from ablation, said Jonathan M. Kalman, MBBS, PhD.

“Of course, I cannot say there is no placebo effect from having had the procedure, and maybe that something to consider,” but it’s probably not the main driver of benefit, he said in an interview. The relationship between successful AFib ablation “and improvements in physical and now mental health is overwhelming.”

Dr. Kalman, who is affiliated with Royal Melbourne Hospital, is senior author on the study, published in JAMA.

The findings add to “strong, reproducible evidence that ablation is the best way to tackle rhythm control in [AFib] populations” regardless of age, mental health status, or AFib burden, said Auroa Badin, MD, who wasn’t involved in REMEDIAL but has studied the psychological effects of arrhythmia ablation.

For example, there is “very good evidence” from CABANA and other trials that AFib ablation “considerably improves quality of life,” Dr. Badin, of OhioHealth Heart & Vascular Physicians, Columbus, said in an interview. The current study “just emphasizes that there’s also a psychological effect.”

Some of that response could be a placebo or even a nocebo effect. Most of the patients assigned to the medical arm had already been on medications that failed at rhythm control. And their management in the trial, he said, “even if you optimize it, was still drug therapy.”

Patients in the control group, therefore, could have been “disappointed” at the prospect of continued ineffective therapy in a way that influenced their outcomes. “That is another confounding factor,” Dr. Badin said.

But if the psychological results of ablation in the trial were predominantly a placebo effect, early differences in psychological test scores would not have persisted for long, certainly not for a year, he observed. Moreover, the ablation group had better test scores at 12 months than at 6 months, “indicating a likelihood of improvement over time.”

Differences between the groups would probably have been less pronounced if the control group had received a sham procedure, Dr. Badin proposed. That would potentially differentiate ablation’s clinical and placebo contributions to the outcomes.

Still, he said, any observed placebo effect in a sham-controlled trial would probably have been limited. “I think it still would have been a positive trial. It may not show the same difference, but I don’t think you would have a neutral trial just by doing a sham.”

REMEDIAL has “good data,” and its conclusions about ablation’s potential psychological benefits are “reasonable” and worth bringing up when discussing the procedure with patients, Dr. Badin said.

Indeed, psychological distress is “important and often overlooked” in patients with AFib, Dr. Kalman observed. “The dominant indication for atrial fibrillation ablation is symptomatic impact on quality of life. We should think about that broadly, about not just the physical symptoms but the impact on their mental health.”

The trial was conducted at two centers in Australia. It enrolled patients, one-third of whom were women, who were on medical management for AFib. Patients receiving treatment for severe depression were excluded. The included patients were randomly assigned to undergo catheter ablation or to continue on closely managed rhythm-control medication, with cardioversion as indicated.

Psychological distress was measured at baseline and throughout follow-up by a battery of self-administered, validated questionnaires. Baseline test scores for the two groups were similar.

Recurrence and burden of AFib were tracked primarily by daily KardiaMobile (AliveCor) ECG monitoring. A few patients were followed using already implanted cardiac rhythm devices or by 24-hour Holter monitor every 3 months, Dr. Kalman said.

Composite scores on the Hospital Anxiety and Depression Scale (HADS) at 12 months, the primary endpoint, were 7.6 and 11.8 (P = .005) for the ablation and medical groups, respectively. They were 8.2 and 11.9 (P = .006), respectively, at 6 months.

The prevalence of severe psychological distress, defined as a HADS score greater than 15, was lower in the ablation group at 6 months (14.2% vs. 34%; P = .02) and 12 months (10.2% vs. 31.9%; P = .01).

Scores on the Beck Depression Inventory–II questionnaire were also consistently and significantly better for the ablation group at 6 and at 12 months (P = .01 for both).

Monitoring picked up AFib in 47% of the ablation group and 96% of the control group (P < .001) over 12 months. Their median AFib burdens were 0% (interquartile range, 0%-3.2%) and 15.5% (IQR, 1%-46%), respectively (P < .001).

Antiarrhythmic drug use fell from a baseline of 90% to 53% 3 months after ablation and 30% at 12 months (P = .003). Use of these drugs in the control group was 89% at baseline and remained essentially the same, 85%, at 12 months.

AFib symptom severity scores were significantly lower after ablation, compared with medical management at 3, 6, and 12 months.

The observed effect of ablation on psychological stress “clearly speaks in favor of effective rhythm control, and moreover catheter ablation” and is a “novel argument” in support of catheter ablation for AFib, Julia Lurz, MD, Heart Center Leipzig (Germany) at University Leipzig, and Karl-Heinz Ladwig, MD, PhD, Technical University Munich (Germany), wrote in an editorial accompanying publication of REMEDIAL.

But the findings also “raise the question of why rhythm control was so ineffective in the medical treatment group,” they wrote.

They agreed that the randomization process itself may have had its own psychological effects. “Potential disappointment” in the medical group and “high expectations” among patients who received ablation “could have fueled the success of catheter ablation” with respect to mental health endpoints.

Dr. Kalman reported receiving grants from the National Health and Medical Research Council of Australia, Medtronic, Mooney, and Biosense Webster. Dr. Badin, Dr. Lurz, and Dr. Ladwig reported no conflicts of interest.

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