MDedge Rheumatology

Key clinical point: Risankizumab led to considerable improvements in skin- and joint-associated clinical outcomes in patients with psoriatic arthritis (PsA) who were followed-up for >28 weeks.

Major finding: Of the 31 patients with clinical disease activity index for PsA > 4 at baseline, 11 patients achieved remission at a follow-up visit between 28 and 40 weeks (P < .004). Risankizumab also led to a significant reduction in the mean psoriasis area severity index score between weeks 28 and 40 vs baseline (0.3 vs 8.4; P < .001).

Study details: Findings are from a prospective, multicenter real-world study including 40 patients with PsA who were treated with 150 mg risankizumab at week 0 and week 4 and every 12 weeks subsequently.

Disclosures: This study did not receive any funding. Five authors declared receiving consulting fees or honoraria from or having other ties with various sources. The other authors declared no conflicts of interest.

Source: Graceffa D, Zangrilli A, Caldarola G, et al. Effectiveness of risankizumab for the treatment of psoriatic arthritis: A multicenter, real-world study. Int J Dermatol. 2024 (Apr 7). doi: 10.1111/ijd.17156 Source

Key clinical point: Risankizumab led to considerable improvements in skin- and joint-associated clinical outcomes in patients with psoriatic arthritis (PsA) who were followed-up for >28 weeks.

Major finding: Of the 31 patients with clinical disease activity index for PsA > 4 at baseline, 11 patients achieved remission at a follow-up visit between 28 and 40 weeks (P < .004). Risankizumab also led to a significant reduction in the mean psoriasis area severity index score between weeks 28 and 40 vs baseline (0.3 vs 8.4; P < .001).

Study details: Findings are from a prospective, multicenter real-world study including 40 patients with PsA who were treated with 150 mg risankizumab at week 0 and week 4 and every 12 weeks subsequently.

Disclosures: This study did not receive any funding. Five authors declared receiving consulting fees or honoraria from or having other ties with various sources. The other authors declared no conflicts of interest.

Source: Graceffa D, Zangrilli A, Caldarola G, et al. Effectiveness of risankizumab for the treatment of psoriatic arthritis: A multicenter, real-world study. Int J Dermatol. 2024 (Apr 7). doi: 10.1111/ijd.17156 Source

Key clinical point: Risankizumab led to considerable improvements in skin- and joint-associated clinical outcomes in patients with psoriatic arthritis (PsA) who were followed-up for >28 weeks.

Major finding: Of the 31 patients with clinical disease activity index for PsA > 4 at baseline, 11 patients achieved remission at a follow-up visit between 28 and 40 weeks (P < .004). Risankizumab also led to a significant reduction in the mean psoriasis area severity index score between weeks 28 and 40 vs baseline (0.3 vs 8.4; P < .001).

Study details: Findings are from a prospective, multicenter real-world study including 40 patients with PsA who were treated with 150 mg risankizumab at week 0 and week 4 and every 12 weeks subsequently.

Disclosures: This study did not receive any funding. Five authors declared receiving consulting fees or honoraria from or having other ties with various sources. The other authors declared no conflicts of interest.

Source: Graceffa D, Zangrilli A, Caldarola G, et al. Effectiveness of risankizumab for the treatment of psoriatic arthritis: A multicenter, real-world study. Int J Dermatol. 2024 (Apr 7). doi: 10.1111/ijd.17156 Source

Key clinical point: A quarter of patients with early psoriatic arthritis who were naive to disease-modifying antirheumatic drugs (DMARD) reported bone erosions, with a decreased prevalence being observed in patients with shorter duration of PsA symptoms (<8 months).

Major finding: Overall, 4655 hand and feet joints were assessed in 122 patients, of whom 24.6% patients had bone erosions at baseline, with higher Disease Activity features observed in patients who did vs did not have bone erosions (P < .05). Prevalence of erosion was less in patients who had a <8 months vs >24 months of PsA symptoms (17.5% vs 24.3%).

Study details: This study included 122 newly diagnosed, DMARD-naive patients with early PsA from the Leeds Spondyloarthropathy Register for Research and Observation cohort who were assessed for bone erosions using conventional radiography or ultrasound.

Disclosures: This study was supported by the UK National Institute for Health Research Leeds Biomedical Research Centre. Sayam R. Dubash received support from Leeds Cares charity. The other authors declared no conflicts of interest.

Source: Hen O, Di Matteo A, Dubash SR, et al. High prevalence of radiographic erosions in early, untreated PsA: Results from the SpARRO cohort. RMD Open. 2024;10:e003841 (Apr 5). doi: 10.1136/rmdopen-2023-003841 Source

Key clinical point: A quarter of patients with early psoriatic arthritis who were naive to disease-modifying antirheumatic drugs (DMARD) reported bone erosions, with a decreased prevalence being observed in patients with shorter duration of PsA symptoms (<8 months).

Major finding: Overall, 4655 hand and feet joints were assessed in 122 patients, of whom 24.6% patients had bone erosions at baseline, with higher Disease Activity features observed in patients who did vs did not have bone erosions (P < .05). Prevalence of erosion was less in patients who had a <8 months vs >24 months of PsA symptoms (17.5% vs 24.3%).

Study details: This study included 122 newly diagnosed, DMARD-naive patients with early PsA from the Leeds Spondyloarthropathy Register for Research and Observation cohort who were assessed for bone erosions using conventional radiography or ultrasound.

Disclosures: This study was supported by the UK National Institute for Health Research Leeds Biomedical Research Centre. Sayam R. Dubash received support from Leeds Cares charity. The other authors declared no conflicts of interest.

Source: Hen O, Di Matteo A, Dubash SR, et al. High prevalence of radiographic erosions in early, untreated PsA: Results from the SpARRO cohort. RMD Open. 2024;10:e003841 (Apr 5). doi: 10.1136/rmdopen-2023-003841 Source

Key clinical point: A quarter of patients with early psoriatic arthritis who were naive to disease-modifying antirheumatic drugs (DMARD) reported bone erosions, with a decreased prevalence being observed in patients with shorter duration of PsA symptoms (<8 months).

Major finding: Overall, 4655 hand and feet joints were assessed in 122 patients, of whom 24.6% patients had bone erosions at baseline, with higher Disease Activity features observed in patients who did vs did not have bone erosions (P < .05). Prevalence of erosion was less in patients who had a <8 months vs >24 months of PsA symptoms (17.5% vs 24.3%).

Study details: This study included 122 newly diagnosed, DMARD-naive patients with early PsA from the Leeds Spondyloarthropathy Register for Research and Observation cohort who were assessed for bone erosions using conventional radiography or ultrasound.

Disclosures: This study was supported by the UK National Institute for Health Research Leeds Biomedical Research Centre. Sayam R. Dubash received support from Leeds Cares charity. The other authors declared no conflicts of interest.

Source: Hen O, Di Matteo A, Dubash SR, et al. High prevalence of radiographic erosions in early, untreated PsA: Results from the SpARRO cohort. RMD Open. 2024;10:e003841 (Apr 5). doi: 10.1136/rmdopen-2023-003841 Source

Key clinical point: Deucravacitinib improved patient-reported outcomes (PRO) for physical and social functioning, mental health, fatigue, and pain in patients with active psoriatic arthritis (PsA).

Major finding: At week 16, 6 mg deucravacitinib vs placebo led to significant changes in functional ability as assessed by the Health Assessment Questionnaire-Disability Index (−0.26; 95% CI −0.42 to −0.10) and the 36-Item Short-Form Health Survey physical component summary (3.3; 95% CI 0.9 to 5.7), with similar outcomes for 12 mg deucravacitinib. Improvements were also noted in mental health and quality of life at week 16 with deucravacitinib vs placebo.

Study details: Findings are from a phase 2, double-blind trial that included 203 patients with active PsA who were randomly assigned (1:1:1) to receive 6 mg deucravacitinib daily (n = 70), 12 mg deucravacitinib daily (n = 67), or placebo (n = 66) for 16 weeks.

Disclosures: This study was sponsored by Bristol Myers Squibb. The authors declared no conflicts of interest.

Source: Strand V, Gossec L, Coates LC, et al. Improvements in patient-reported outcomes after treatment with deucravacitinib in patients with psoriatic arthritis: Results from a randomized phase 2 trial. Arthritis Care Res (Hoboken). 2024 (Mar 26). doi: 10.1002/acr.25333  Source

Key clinical point: Deucravacitinib improved patient-reported outcomes (PRO) for physical and social functioning, mental health, fatigue, and pain in patients with active psoriatic arthritis (PsA).

Major finding: At week 16, 6 mg deucravacitinib vs placebo led to significant changes in functional ability as assessed by the Health Assessment Questionnaire-Disability Index (−0.26; 95% CI −0.42 to −0.10) and the 36-Item Short-Form Health Survey physical component summary (3.3; 95% CI 0.9 to 5.7), with similar outcomes for 12 mg deucravacitinib. Improvements were also noted in mental health and quality of life at week 16 with deucravacitinib vs placebo.

Study details: Findings are from a phase 2, double-blind trial that included 203 patients with active PsA who were randomly assigned (1:1:1) to receive 6 mg deucravacitinib daily (n = 70), 12 mg deucravacitinib daily (n = 67), or placebo (n = 66) for 16 weeks.

Disclosures: This study was sponsored by Bristol Myers Squibb. The authors declared no conflicts of interest.

Source: Strand V, Gossec L, Coates LC, et al. Improvements in patient-reported outcomes after treatment with deucravacitinib in patients with psoriatic arthritis: Results from a randomized phase 2 trial. Arthritis Care Res (Hoboken). 2024 (Mar 26). doi: 10.1002/acr.25333  Source

Key clinical point: Deucravacitinib improved patient-reported outcomes (PRO) for physical and social functioning, mental health, fatigue, and pain in patients with active psoriatic arthritis (PsA).

Major finding: At week 16, 6 mg deucravacitinib vs placebo led to significant changes in functional ability as assessed by the Health Assessment Questionnaire-Disability Index (−0.26; 95% CI −0.42 to −0.10) and the 36-Item Short-Form Health Survey physical component summary (3.3; 95% CI 0.9 to 5.7), with similar outcomes for 12 mg deucravacitinib. Improvements were also noted in mental health and quality of life at week 16 with deucravacitinib vs placebo.

Study details: Findings are from a phase 2, double-blind trial that included 203 patients with active PsA who were randomly assigned (1:1:1) to receive 6 mg deucravacitinib daily (n = 70), 12 mg deucravacitinib daily (n = 67), or placebo (n = 66) for 16 weeks.

Disclosures: This study was sponsored by Bristol Myers Squibb. The authors declared no conflicts of interest.

Source: Strand V, Gossec L, Coates LC, et al. Improvements in patient-reported outcomes after treatment with deucravacitinib in patients with psoriatic arthritis: Results from a randomized phase 2 trial. Arthritis Care Res (Hoboken). 2024 (Mar 26). doi: 10.1002/acr.25333  Source

Key clinical point: Among biologic-naive, guselkumab-treated patients with psoriatic arthritis (PsA), enthesitis resolution (ER) was associated with dactylitis resolution (DR), and those achieving ER or DR showed improvements in patient-reported outcomes.

Major finding: At weeks 24, 52, and 100, guselkumab-treated patients who achieved DR were more likely to achieve ER, and vice versa (all P < .05). At week 24, a higher proportion of patients who did vs did not achieve ER reported minimal pain (30%-45% vs 11%-21%; all P < .001), with similar pain outcomes in patients who did vs did not achieve DR.

Study details: This post hoc analysis included 739 biologic-naive patients with PsA who were randomly assigned to receive guselkumab (100 mg every 4 or 8 weeks) or placebo with crossover to guselkumab (100 mg every 4 weeks) at week 24, of whom 68.6% and 44.9% of patients had enthesitis and dactylitis, respectively.

Disclosures: This study was supported by Janssen Research & Development, LLC. Six authors declared being employees of Janssen and owning Johnson and Johnson stock or stock options. The other authors declared receiving consulting fees from or having other ties with various sources, including Janssen.

Source: Rahman P, McInnes IB, Deodhar A, et al. Association between enthesitis/dactylitis resolution and patient-reported outcomes in guselkumab-treated patients with psoriatic arthritis. Clin Rheumatol. 2024;43:1591-1604 (Mar 12). doi: 10.1007/s10067-024-06921-8  Source

Key clinical point: Among biologic-naive, guselkumab-treated patients with psoriatic arthritis (PsA), enthesitis resolution (ER) was associated with dactylitis resolution (DR), and those achieving ER or DR showed improvements in patient-reported outcomes.

Major finding: At weeks 24, 52, and 100, guselkumab-treated patients who achieved DR were more likely to achieve ER, and vice versa (all P < .05). At week 24, a higher proportion of patients who did vs did not achieve ER reported minimal pain (30%-45% vs 11%-21%; all P < .001), with similar pain outcomes in patients who did vs did not achieve DR.

Study details: This post hoc analysis included 739 biologic-naive patients with PsA who were randomly assigned to receive guselkumab (100 mg every 4 or 8 weeks) or placebo with crossover to guselkumab (100 mg every 4 weeks) at week 24, of whom 68.6% and 44.9% of patients had enthesitis and dactylitis, respectively.

Disclosures: This study was supported by Janssen Research & Development, LLC. Six authors declared being employees of Janssen and owning Johnson and Johnson stock or stock options. The other authors declared receiving consulting fees from or having other ties with various sources, including Janssen.

Source: Rahman P, McInnes IB, Deodhar A, et al. Association between enthesitis/dactylitis resolution and patient-reported outcomes in guselkumab-treated patients with psoriatic arthritis. Clin Rheumatol. 2024;43:1591-1604 (Mar 12). doi: 10.1007/s10067-024-06921-8  Source

Key clinical point: Among biologic-naive, guselkumab-treated patients with psoriatic arthritis (PsA), enthesitis resolution (ER) was associated with dactylitis resolution (DR), and those achieving ER or DR showed improvements in patient-reported outcomes.

Major finding: At weeks 24, 52, and 100, guselkumab-treated patients who achieved DR were more likely to achieve ER, and vice versa (all P < .05). At week 24, a higher proportion of patients who did vs did not achieve ER reported minimal pain (30%-45% vs 11%-21%; all P < .001), with similar pain outcomes in patients who did vs did not achieve DR.

Study details: This post hoc analysis included 739 biologic-naive patients with PsA who were randomly assigned to receive guselkumab (100 mg every 4 or 8 weeks) or placebo with crossover to guselkumab (100 mg every 4 weeks) at week 24, of whom 68.6% and 44.9% of patients had enthesitis and dactylitis, respectively.

Disclosures: This study was supported by Janssen Research & Development, LLC. Six authors declared being employees of Janssen and owning Johnson and Johnson stock or stock options. The other authors declared receiving consulting fees from or having other ties with various sources, including Janssen.

Source: Rahman P, McInnes IB, Deodhar A, et al. Association between enthesitis/dactylitis resolution and patient-reported outcomes in guselkumab-treated patients with psoriatic arthritis. Clin Rheumatol. 2024;43:1591-1604 (Mar 12). doi: 10.1007/s10067-024-06921-8  Source

Key clinical point: Guselkumab treatment led to durable improvements in key Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (PsA)-recognized domains through 2 years and showed a consistent safety profile in biologic or Janus kinase inhibitor-naive patients with active PsA.

Major finding: At week 100, more than 50% of patients receiving guselkumab (100 mg every 4 or 8 weeks) achieved  achieved a low PsA Disease Activity Index, had enthesitis resolution, dactylitis resolution, and 100% improvement in Psoriasis Area and Severity Index. No new safety signals were observed.

Study details: This post hoc analysis included 442 biologic or Janus kinase inhibitor-naive patients with active PsA and previous inadequate response or intolerance to standard nonbiologics who received 100 mg guselkumab every 4 or 8 weeks through week 100.

Disclosures: This study was supported by Janssen Research & Development (R&D), LLC. Three authors declared being employees of Janssen R&D and owning Johnson and Johnson stocks or stock options. Several authors declared receiving honoraria from or having other ties with various sources, including Janssen.

Source: Coates LC, Gossec L, Zimmermann M, et al. Guselkumab provides durable improvement across psoriatic arthritis disease domains: Post hoc analysis of a phase 3, randomised, double-blind, placebo-controlled study. RMD Open. 2024;10:e003977 (Mar 26). doi: 10.1136/rmdopen-2023-003977 Source

Key clinical point: Guselkumab treatment led to durable improvements in key Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (PsA)-recognized domains through 2 years and showed a consistent safety profile in biologic or Janus kinase inhibitor-naive patients with active PsA.

Major finding: At week 100, more than 50% of patients receiving guselkumab (100 mg every 4 or 8 weeks) achieved  achieved a low PsA Disease Activity Index, had enthesitis resolution, dactylitis resolution, and 100% improvement in Psoriasis Area and Severity Index. No new safety signals were observed.

Study details: This post hoc analysis included 442 biologic or Janus kinase inhibitor-naive patients with active PsA and previous inadequate response or intolerance to standard nonbiologics who received 100 mg guselkumab every 4 or 8 weeks through week 100.

Disclosures: This study was supported by Janssen Research & Development (R&D), LLC. Three authors declared being employees of Janssen R&D and owning Johnson and Johnson stocks or stock options. Several authors declared receiving honoraria from or having other ties with various sources, including Janssen.

Source: Coates LC, Gossec L, Zimmermann M, et al. Guselkumab provides durable improvement across psoriatic arthritis disease domains: Post hoc analysis of a phase 3, randomised, double-blind, placebo-controlled study. RMD Open. 2024;10:e003977 (Mar 26). doi: 10.1136/rmdopen-2023-003977 Source

Key clinical point: Guselkumab treatment led to durable improvements in key Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (PsA)-recognized domains through 2 years and showed a consistent safety profile in biologic or Janus kinase inhibitor-naive patients with active PsA.

Major finding: At week 100, more than 50% of patients receiving guselkumab (100 mg every 4 or 8 weeks) achieved  achieved a low PsA Disease Activity Index, had enthesitis resolution, dactylitis resolution, and 100% improvement in Psoriasis Area and Severity Index. No new safety signals were observed.

Study details: This post hoc analysis included 442 biologic or Janus kinase inhibitor-naive patients with active PsA and previous inadequate response or intolerance to standard nonbiologics who received 100 mg guselkumab every 4 or 8 weeks through week 100.

Disclosures: This study was supported by Janssen Research & Development (R&D), LLC. Three authors declared being employees of Janssen R&D and owning Johnson and Johnson stocks or stock options. Several authors declared receiving honoraria from or having other ties with various sources, including Janssen.

Source: Coates LC, Gossec L, Zimmermann M, et al. Guselkumab provides durable improvement across psoriatic arthritis disease domains: Post hoc analysis of a phase 3, randomised, double-blind, placebo-controlled study. RMD Open. 2024;10:e003977 (Mar 26). doi: 10.1136/rmdopen-2023-003977 Source

Key clinical point: Risankizumab showed long-term efficacy and tolerability in patients having active psoriatic arthritis (PsA) with previous inadequate response or intolerance to one or more conventional synthetic disease-modifying antirheumatic drugs (csDMARD-IR).

Major finding: At week 100, more than half the patients who received risankizumab continuously (64.3%) or switched from placebo to risankizumab (62.1%) achieved ≥20% improvement in the American College of Rheumatology criteria (ACR20), with Minimal Disease Activity being reported by nearly 35% of patients in both cohorts. Risankizumab showed a consistent safety profile with no new concerns.

Study details: This long-term efficacy and safety analysis of the KEEPsAKE 1 trial included 828 csDMARD-IR patients with active PsA who received risankizumab or placebo followed by risankizumab till week 100.

Disclosures: This study was funded by AbbVie. Seven authors declared being employees of or holding stocks or stock options in AbbVie. Several authors declared serving as consultants or speakers for or having other ties with various sources, including AbbVie.

Source: Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 100-week results from the phase 3 KEEPsAKE 1 randomized clinical trial. Rheumatol Ther. 2024 (Mar 18). doi: 10.1007/s40744-024-00654-5 Source

Key clinical point: Risankizumab showed long-term efficacy and tolerability in patients having active psoriatic arthritis (PsA) with previous inadequate response or intolerance to one or more conventional synthetic disease-modifying antirheumatic drugs (csDMARD-IR).

Major finding: At week 100, more than half the patients who received risankizumab continuously (64.3%) or switched from placebo to risankizumab (62.1%) achieved ≥20% improvement in the American College of Rheumatology criteria (ACR20), with Minimal Disease Activity being reported by nearly 35% of patients in both cohorts. Risankizumab showed a consistent safety profile with no new concerns.

Study details: This long-term efficacy and safety analysis of the KEEPsAKE 1 trial included 828 csDMARD-IR patients with active PsA who received risankizumab or placebo followed by risankizumab till week 100.

Disclosures: This study was funded by AbbVie. Seven authors declared being employees of or holding stocks or stock options in AbbVie. Several authors declared serving as consultants or speakers for or having other ties with various sources, including AbbVie.

Source: Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 100-week results from the phase 3 KEEPsAKE 1 randomized clinical trial. Rheumatol Ther. 2024 (Mar 18). doi: 10.1007/s40744-024-00654-5 Source

Key clinical point: Risankizumab showed long-term efficacy and tolerability in patients having active psoriatic arthritis (PsA) with previous inadequate response or intolerance to one or more conventional synthetic disease-modifying antirheumatic drugs (csDMARD-IR).

Major finding: At week 100, more than half the patients who received risankizumab continuously (64.3%) or switched from placebo to risankizumab (62.1%) achieved ≥20% improvement in the American College of Rheumatology criteria (ACR20), with Minimal Disease Activity being reported by nearly 35% of patients in both cohorts. Risankizumab showed a consistent safety profile with no new concerns.

Study details: This long-term efficacy and safety analysis of the KEEPsAKE 1 trial included 828 csDMARD-IR patients with active PsA who received risankizumab or placebo followed by risankizumab till week 100.

Disclosures: This study was funded by AbbVie. Seven authors declared being employees of or holding stocks or stock options in AbbVie. Several authors declared serving as consultants or speakers for or having other ties with various sources, including AbbVie.

Source: Kristensen LE, Keiserman M, Papp K, et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 100-week results from the phase 3 KEEPsAKE 1 randomized clinical trial. Rheumatol Ther. 2024 (Mar 18). doi: 10.1007/s40744-024-00654-5 Source

Key clinical point: The overall risk for serious infections was low in patients with psoriatic arthritis (PsA) who were new users of targeted therapies, with etanercept and ustekinumab being safer treatment options than adalimumab.

Major finding: The incidence of serious infections in new users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93).

Study details: This cohort study included 12,071 patients with PsA (age ≥ 18 years) from the French National Health Insurance Database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib).

Disclosures: This study did not receive any specific funding. Two authors declared receiving meeting support, consulting fees, etc., from or having other ties with various sources. The other authors declared no conflicts of interest.

Source: Bastard L, Claudepierre P, Penso L, et al. Risk of serious infection associated with different classes of targeted therapies used in psoriatic arthritis: A nationwide cohort study from the French Health Insurance Database (SNDS). RMD Open. 2024;10:e003865 (Mar 14). doi: 10.1136/rmdopen-2023-003865 Source

Key clinical point: The overall risk for serious infections was low in patients with psoriatic arthritis (PsA) who were new users of targeted therapies, with etanercept and ustekinumab being safer treatment options than adalimumab.

Major finding: The incidence of serious infections in new users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93).

Study details: This cohort study included 12,071 patients with PsA (age ≥ 18 years) from the French National Health Insurance Database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib).

Disclosures: This study did not receive any specific funding. Two authors declared receiving meeting support, consulting fees, etc., from or having other ties with various sources. The other authors declared no conflicts of interest.

Source: Bastard L, Claudepierre P, Penso L, et al. Risk of serious infection associated with different classes of targeted therapies used in psoriatic arthritis: A nationwide cohort study from the French Health Insurance Database (SNDS). RMD Open. 2024;10:e003865 (Mar 14). doi: 10.1136/rmdopen-2023-003865 Source

Key clinical point: The overall risk for serious infections was low in patients with psoriatic arthritis (PsA) who were new users of targeted therapies, with etanercept and ustekinumab being safer treatment options than adalimumab.

Major finding: The incidence of serious infections in new users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93).

Study details: This cohort study included 12,071 patients with PsA (age ≥ 18 years) from the French National Health Insurance Database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib).

Disclosures: This study did not receive any specific funding. Two authors declared receiving meeting support, consulting fees, etc., from or having other ties with various sources. The other authors declared no conflicts of interest.

Source: Bastard L, Claudepierre P, Penso L, et al. Risk of serious infection associated with different classes of targeted therapies used in psoriatic arthritis: A nationwide cohort study from the French Health Insurance Database (SNDS). RMD Open. 2024;10:e003865 (Mar 14). doi: 10.1136/rmdopen-2023-003865 Source

Key clinical point: Bimekizumab showed better long-term efficacy than guselkumab in patients with psoriatic arthritis (PsA) who were naive to biologic disease-modifying antirheumatic drugs (bDMARD) or had previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: In bDMARD-naive patients, bimekizumab (160 mg every 4 weeks [Q4W]) was associated with a greater likelihood of achievement of ≥70% improvement in the American College of Rheumatology response (odds ratio [OR] > 2.0; P ≤ .001) and minimal disease activity outcome (OR > 1.5; P ≤ .005) at week 52 compared with guselkumab (100 mg Q4W or every 8 weeks). Similar outcomes were observed in the TNFi-IR subgroup.

Study details: This matching-adjusted indirect comparison study included bDMARD-naive and TNFi-IR patients with PsA who received bimekizumab (431 and 267 patients, respectively) and guselkumab (495 and 189 patients, respectively).

Disclosures: This study was sponsored by UCB Pharma. Four authors declared being employees and stockholders of UCB Pharma. The other authors declared receiving consulting fees or honoraria from or having other ties with various sources, including UCB Pharma.

Source: Warren RB, McInnes IB, Nash P, et al. Comparative effectiveness of bimekizumab and guselkumab in patients with psoriatic arthritis at 52 weeks assessed using a matching-adjusted indirect comparison. Rheumatol Ther. 2024 (Mar 15). doi: 10.1007/s40744-024-00659-0 Source

Key clinical point: Bimekizumab showed better long-term efficacy than guselkumab in patients with psoriatic arthritis (PsA) who were naive to biologic disease-modifying antirheumatic drugs (bDMARD) or had previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: In bDMARD-naive patients, bimekizumab (160 mg every 4 weeks [Q4W]) was associated with a greater likelihood of achievement of ≥70% improvement in the American College of Rheumatology response (odds ratio [OR] > 2.0; P ≤ .001) and minimal disease activity outcome (OR > 1.5; P ≤ .005) at week 52 compared with guselkumab (100 mg Q4W or every 8 weeks). Similar outcomes were observed in the TNFi-IR subgroup.

Study details: This matching-adjusted indirect comparison study included bDMARD-naive and TNFi-IR patients with PsA who received bimekizumab (431 and 267 patients, respectively) and guselkumab (495 and 189 patients, respectively).

Disclosures: This study was sponsored by UCB Pharma. Four authors declared being employees and stockholders of UCB Pharma. The other authors declared receiving consulting fees or honoraria from or having other ties with various sources, including UCB Pharma.

Source: Warren RB, McInnes IB, Nash P, et al. Comparative effectiveness of bimekizumab and guselkumab in patients with psoriatic arthritis at 52 weeks assessed using a matching-adjusted indirect comparison. Rheumatol Ther. 2024 (Mar 15). doi: 10.1007/s40744-024-00659-0 Source

Key clinical point: Bimekizumab showed better long-term efficacy than guselkumab in patients with psoriatic arthritis (PsA) who were naive to biologic disease-modifying antirheumatic drugs (bDMARD) or had previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR).

Major finding: In bDMARD-naive patients, bimekizumab (160 mg every 4 weeks [Q4W]) was associated with a greater likelihood of achievement of ≥70% improvement in the American College of Rheumatology response (odds ratio [OR] > 2.0; P ≤ .001) and minimal disease activity outcome (OR > 1.5; P ≤ .005) at week 52 compared with guselkumab (100 mg Q4W or every 8 weeks). Similar outcomes were observed in the TNFi-IR subgroup.

Study details: This matching-adjusted indirect comparison study included bDMARD-naive and TNFi-IR patients with PsA who received bimekizumab (431 and 267 patients, respectively) and guselkumab (495 and 189 patients, respectively).

Disclosures: This study was sponsored by UCB Pharma. Four authors declared being employees and stockholders of UCB Pharma. The other authors declared receiving consulting fees or honoraria from or having other ties with various sources, including UCB Pharma.

Source: Warren RB, McInnes IB, Nash P, et al. Comparative effectiveness of bimekizumab and guselkumab in patients with psoriatic arthritis at 52 weeks assessed using a matching-adjusted indirect comparison. Rheumatol Ther. 2024 (Mar 15). doi: 10.1007/s40744-024-00659-0 Source

Physician practice ownership by corporations, including health insurers, private equity firms, and large pharmacy chains, reached 30.1% as of January for the first time surpassing ownership by hospitals and health systems (28.4%), according to a new report.

As a result, about three in five physician practices are now owned by nonphysicians.

In early 2020, corporations owned just about 17% of US medical practices, while hospitals and health systems owned about 25%, according to the report released Thursday by nonprofit Physician Advocacy Institute (PAI). But corporate ownership of medical groups surged during the pandemic.

These trends raise questions about how best to protect patients and physicians in a changing employment landscape, said Kelly Kenney, PAI’s chief executive officer, in a statement.

“Corporate entities are assuming control of physician practices and changing the face of medicine in the United States with little to no scrutiny from regulators,” Ms. Kenney said.

The research, conducted by consulting group Avalere for PAI, used the IQVIA OneKey database that contains physician and practice location information on hospital and health system ownership.

By 2022-2023, there was a 7.3% increase in the percentage of practices owned by hospitals and 5.9% increase in the percentage of physicians employed by these organizations, PAI said. In the same time frame, there was an 11% increase in the percentage of practices owned by corporations and a 3.0% increase in the percentage of physicians employed by these entities.

“Physicians have an ethical responsibility to their patients’ health,” Ms. Kenney said. “Corporate entities have a fiduciary responsibility to their shareholders and are motivated to put profits first…these interests can conflict with providing the best medical care to patients.”
 

Federal Scrutiny Increases

However, both federal and state regulators are paying more attention to what happens to patients and physicians when corporations acquire practices.

“Given recent trends, we are concerned that some transactions may generate profits for those firms at the expense of patients’ health, workers’ safety, quality of care, and affordable healthcare for patients and taxpayers,” said the Federal Trade Commission (FTC) and the Justice (DOJ) and Health and Human Services (HHS) departments.

This statement appears in those agencies’ joint request for information (RFI) announced in March. An RFI is a tool that federal agencies can use to gauge the level of both support and opposition they would face if they were to try to change policies. Public comments are due May 6.

Corporations and advocacy groups often submit detailed comments outlining reasons why the federal government should or should not act on an issue. But individuals also can make their case in this forum.

The FTC, DOJ, and HHS are looking broadly at consolidation in healthcare, but they also spell out potential concerns related to acquisition of physician practices.

For example, they asked clinicians and support staff to provide feedback about whether acquisitions lead to changes in:

• Take-home pay
• Staffing levels
• Workplace safety
• Compensation model (eg, from fixed salary to volume based)
• Policies regarding patient referrals
• Mix of patients
• The volume of patients
• The way providers practice medicine (eg, incentives, prescribing decisions, forced protocols, restrictions on time spent with patients, or mandatory coding practices)
• Administrative or managerial organization (eg, transition to a management services organization).

A version of this article appeared on Medscape.com.

Physician practice ownership by corporations, including health insurers, private equity firms, and large pharmacy chains, reached 30.1% as of January for the first time surpassing ownership by hospitals and health systems (28.4%), according to a new report.

As a result, about three in five physician practices are now owned by nonphysicians.

In early 2020, corporations owned just about 17% of US medical practices, while hospitals and health systems owned about 25%, according to the report released Thursday by nonprofit Physician Advocacy Institute (PAI). But corporate ownership of medical groups surged during the pandemic.

These trends raise questions about how best to protect patients and physicians in a changing employment landscape, said Kelly Kenney, PAI’s chief executive officer, in a statement.

“Corporate entities are assuming control of physician practices and changing the face of medicine in the United States with little to no scrutiny from regulators,” Ms. Kenney said.

The research, conducted by consulting group Avalere for PAI, used the IQVIA OneKey database that contains physician and practice location information on hospital and health system ownership.

By 2022-2023, there was a 7.3% increase in the percentage of practices owned by hospitals and 5.9% increase in the percentage of physicians employed by these organizations, PAI said. In the same time frame, there was an 11% increase in the percentage of practices owned by corporations and a 3.0% increase in the percentage of physicians employed by these entities.

“Physicians have an ethical responsibility to their patients’ health,” Ms. Kenney said. “Corporate entities have a fiduciary responsibility to their shareholders and are motivated to put profits first…these interests can conflict with providing the best medical care to patients.”
 

Federal Scrutiny Increases

However, both federal and state regulators are paying more attention to what happens to patients and physicians when corporations acquire practices.

“Given recent trends, we are concerned that some transactions may generate profits for those firms at the expense of patients’ health, workers’ safety, quality of care, and affordable healthcare for patients and taxpayers,” said the Federal Trade Commission (FTC) and the Justice (DOJ) and Health and Human Services (HHS) departments.

This statement appears in those agencies’ joint request for information (RFI) announced in March. An RFI is a tool that federal agencies can use to gauge the level of both support and opposition they would face if they were to try to change policies. Public comments are due May 6.

Corporations and advocacy groups often submit detailed comments outlining reasons why the federal government should or should not act on an issue. But individuals also can make their case in this forum.

The FTC, DOJ, and HHS are looking broadly at consolidation in healthcare, but they also spell out potential concerns related to acquisition of physician practices.

For example, they asked clinicians and support staff to provide feedback about whether acquisitions lead to changes in:

• Take-home pay
• Staffing levels
• Workplace safety
• Compensation model (eg, from fixed salary to volume based)
• Policies regarding patient referrals
• Mix of patients
• The volume of patients
• The way providers practice medicine (eg, incentives, prescribing decisions, forced protocols, restrictions on time spent with patients, or mandatory coding practices)
• Administrative or managerial organization (eg, transition to a management services organization).

A version of this article appeared on Medscape.com.

Physician practice ownership by corporations, including health insurers, private equity firms, and large pharmacy chains, reached 30.1% as of January for the first time surpassing ownership by hospitals and health systems (28.4%), according to a new report.

As a result, about three in five physician practices are now owned by nonphysicians.

In early 2020, corporations owned just about 17% of US medical practices, while hospitals and health systems owned about 25%, according to the report released Thursday by nonprofit Physician Advocacy Institute (PAI). But corporate ownership of medical groups surged during the pandemic.

These trends raise questions about how best to protect patients and physicians in a changing employment landscape, said Kelly Kenney, PAI’s chief executive officer, in a statement.

“Corporate entities are assuming control of physician practices and changing the face of medicine in the United States with little to no scrutiny from regulators,” Ms. Kenney said.

The research, conducted by consulting group Avalere for PAI, used the IQVIA OneKey database that contains physician and practice location information on hospital and health system ownership.

By 2022-2023, there was a 7.3% increase in the percentage of practices owned by hospitals and 5.9% increase in the percentage of physicians employed by these organizations, PAI said. In the same time frame, there was an 11% increase in the percentage of practices owned by corporations and a 3.0% increase in the percentage of physicians employed by these entities.

“Physicians have an ethical responsibility to their patients’ health,” Ms. Kenney said. “Corporate entities have a fiduciary responsibility to their shareholders and are motivated to put profits first…these interests can conflict with providing the best medical care to patients.”
 

Federal Scrutiny Increases

However, both federal and state regulators are paying more attention to what happens to patients and physicians when corporations acquire practices.

“Given recent trends, we are concerned that some transactions may generate profits for those firms at the expense of patients’ health, workers’ safety, quality of care, and affordable healthcare for patients and taxpayers,” said the Federal Trade Commission (FTC) and the Justice (DOJ) and Health and Human Services (HHS) departments.

This statement appears in those agencies’ joint request for information (RFI) announced in March. An RFI is a tool that federal agencies can use to gauge the level of both support and opposition they would face if they were to try to change policies. Public comments are due May 6.

Corporations and advocacy groups often submit detailed comments outlining reasons why the federal government should or should not act on an issue. But individuals also can make their case in this forum.

The FTC, DOJ, and HHS are looking broadly at consolidation in healthcare, but they also spell out potential concerns related to acquisition of physician practices.

For example, they asked clinicians and support staff to provide feedback about whether acquisitions lead to changes in:

• Take-home pay
• Staffing levels
• Workplace safety
• Compensation model (eg, from fixed salary to volume based)
• Policies regarding patient referrals
• Mix of patients
• The volume of patients
• The way providers practice medicine (eg, incentives, prescribing decisions, forced protocols, restrictions on time spent with patients, or mandatory coding practices)
• Administrative or managerial organization (eg, transition to a management services organization).

A version of this article appeared on Medscape.com.

If your gut is telling you that your disease-modifying antirheumatic drugs (DMARDs) aren’t working as well as they should, listen to it.

That’s the advice of Rebecca B. Blank, MD, PhD, a rheumatologist at NYU Langone Health in New York City, who studies methods for modulating the gut microbiome to enhance DMARD efficacy for patients with rheumatoid arthritis (RA).

“The baseline gut microbiome can predict patient responsiveness to methotrexate,” said Dr. Blank at the 2024 Rheumatoid Arthritis Research Summit, presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.

Dr. Blank and colleagues are investigating how the intestinal microbiome may influence drug metabolism and the therapeutic potential of short-chain fatty acids for improving the efficacy of methotrexate in patients with RA.
 

Mucosal Barrier Disruption

There are myriad factors contributing to the development and progression of RA, including dysbiosis, or disruption, of the mucosal barrier, Dr. Blank explained.

“Dysbiosis can be detected in at-risk individuals before clinical signs of rheumatoid arthritis even occur,” she said.

Dr. Blank cited a 2021 study of the gut-joint axis in RA,which indicated that subclinical inflammation in the oral, gut, and/or lung mucosa may lead to inflammatory arthritis.

“When there’s a break in the mucosal barrier, either bacteria or their bacterial products can translocate into the lamina propria and then lead to an inflammatory T-cell response, and in addition, bacteria or their products can induce auto-antibody formation, which can then lead to joint inflammation,” she said.

Dr. Blank and colleagues, as well as other research groups, showed that gut bacterial colonization by Prevotella copri can induce an inflammatory response in gut lamina propria, and that people with RA have increased abundance of P copri relative to people without RA.
 

DMARD Resistance

To see whether microbial dysbiosis might play a role in DMARD-resistant RA, Dr. Blank and her team looked at patients with new-onset RA who were scheduled for treatment with methotrexate as their first-line medication. They classified responders as those patients with a change in Disease Activity Score in 28 joints (DAS28) of at least 1.8 points.

They then conducted 16S rRNA sequencing and shotgun sequencing on patient fecal samples taken at baseline to determine whether baseline microbiome differences might contribute to responses to methotrexate.

“And so indeed, we were able to find a human gut microbial signature that predicted methotrexate responsiveness in these baseline microbiome samples,” Dr. Blank said.

They identified 462 differences in gene orthologs (ie, genes preserved during evolution and speciation) that differed between responders and nonresponders, narrowed the list down to the top 38, and then developed a predictive model for response to methotrexate with an area under the receiver operating characteristic curve of 0.84.

The investigators then cultured fecal baseline samples with methotrexate to see how levels of the drug would be affected over time and found that samples from nonresponders metabolized methotrexate at a faster rate than samples from patients who had clinical responses to the drug.

Their work was further supported by colleagues at the University of California San Francisco, who found evidence in mouse models to suggest that microbial metabolism plays a role in methotrexate levels in plasma.
 

Modulating the Gut

“Our next question was: Can we modulate the gut microbiome to improve methotrexate efficacy?” Dr. Blank said.

They considered probiotics and prebiotics as possible means for modulating gut microbiota, but evidence of efficacy for these agents has been decidedly mixed, she noted.

Instead, the investigators focused on short-chain fatty acids, gut microbial fermentation byproducts of indigestible carbohydrates, which have been demonstrated to help improve gut mucosal barrier integrity and promote a more tolerant immune response.

One such short-chain fatty acid, butyrate, is produced through microbial fermentation of dietary fiber in the colon; it is available in various foods and in supplement form.

Butyrate has been shown to ameliorate inflammatory arthritis in a collagen-induced arthritis model, and in this model, methotrexate efficacy was increased with the addition of butyrate or butyrate-producing bacterial species.

Dr. Blank and colleagues compared patients with new-onset RA treated with methotrexate alone or methotrexate plus butyrate for 4 months and looked at up to 2 months of methotrexate plus butyrate treatment in patients who had suboptimal response to methotrexate alone.

In preliminary analyses, they found that at baseline, fecal butyrate was significantly elevated in methotrexate responders compared with in nonresponders. In addition, in the new-onset RA cohort, they saw that the 4-month responsiveness rate was 52.6% for those treated with methotrexate compared with 64.7% for those treated with methotrexate plus butyrate.

“Although this difference was not statistically significant, it’s exciting to think we may have an impact. What’s more, we were really excited to find that oral butyrate can lead to increased microbial diversity,” she said.
 

What Are You Measuring?

In the Q & A following the presentation, Clifton O. Bingham III, MD, director of the Johns Hopkins Arthritis Center in Baltimore, Maryland, commented that “the definitions of response and nonresponse are quite variable, depending on the studies that you use, and I think this is potentially a real problem for this entire line of investigation.”

Johns Hopkins Medicine, Johns Hopkins Division of Rheumatology

He noted that the DAS28, as used by Dr. Blank and colleagues, was developed in 1993, and that American College of Rheumatology response criteria, employed by other investigators who also presented during the session, were developed in 1990.

“It was a very different world when those criteria and those response indices were developed for patients with a very different disease from what we know as RA today,” he said.

He added that “I see a tremendous need for the rheumatology community to reevaluate what we define as responders and nonresponders, so that in all of these studies that are being done around the world, there is one definition that we understand [for] someone who is doing better, responding, or not responding.”

Dr. Blank’s work is supported by NYU, the Arthritis Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. She reported having no conflicts of interest to disclose. Dr. Bingham had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

If your gut is telling you that your disease-modifying antirheumatic drugs (DMARDs) aren’t working as well as they should, listen to it.

That’s the advice of Rebecca B. Blank, MD, PhD, a rheumatologist at NYU Langone Health in New York City, who studies methods for modulating the gut microbiome to enhance DMARD efficacy for patients with rheumatoid arthritis (RA).

“The baseline gut microbiome can predict patient responsiveness to methotrexate,” said Dr. Blank at the 2024 Rheumatoid Arthritis Research Summit, presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.

Dr. Blank and colleagues are investigating how the intestinal microbiome may influence drug metabolism and the therapeutic potential of short-chain fatty acids for improving the efficacy of methotrexate in patients with RA.
 

Mucosal Barrier Disruption

There are myriad factors contributing to the development and progression of RA, including dysbiosis, or disruption, of the mucosal barrier, Dr. Blank explained.

“Dysbiosis can be detected in at-risk individuals before clinical signs of rheumatoid arthritis even occur,” she said.

Dr. Blank cited a 2021 study of the gut-joint axis in RA,which indicated that subclinical inflammation in the oral, gut, and/or lung mucosa may lead to inflammatory arthritis.

“When there’s a break in the mucosal barrier, either bacteria or their bacterial products can translocate into the lamina propria and then lead to an inflammatory T-cell response, and in addition, bacteria or their products can induce auto-antibody formation, which can then lead to joint inflammation,” she said.

Dr. Blank and colleagues, as well as other research groups, showed that gut bacterial colonization by Prevotella copri can induce an inflammatory response in gut lamina propria, and that people with RA have increased abundance of P copri relative to people without RA.
 

DMARD Resistance

To see whether microbial dysbiosis might play a role in DMARD-resistant RA, Dr. Blank and her team looked at patients with new-onset RA who were scheduled for treatment with methotrexate as their first-line medication. They classified responders as those patients with a change in Disease Activity Score in 28 joints (DAS28) of at least 1.8 points.

They then conducted 16S rRNA sequencing and shotgun sequencing on patient fecal samples taken at baseline to determine whether baseline microbiome differences might contribute to responses to methotrexate.

“And so indeed, we were able to find a human gut microbial signature that predicted methotrexate responsiveness in these baseline microbiome samples,” Dr. Blank said.

They identified 462 differences in gene orthologs (ie, genes preserved during evolution and speciation) that differed between responders and nonresponders, narrowed the list down to the top 38, and then developed a predictive model for response to methotrexate with an area under the receiver operating characteristic curve of 0.84.

The investigators then cultured fecal baseline samples with methotrexate to see how levels of the drug would be affected over time and found that samples from nonresponders metabolized methotrexate at a faster rate than samples from patients who had clinical responses to the drug.

Their work was further supported by colleagues at the University of California San Francisco, who found evidence in mouse models to suggest that microbial metabolism plays a role in methotrexate levels in plasma.
 

Modulating the Gut

“Our next question was: Can we modulate the gut microbiome to improve methotrexate efficacy?” Dr. Blank said.

They considered probiotics and prebiotics as possible means for modulating gut microbiota, but evidence of efficacy for these agents has been decidedly mixed, she noted.

Instead, the investigators focused on short-chain fatty acids, gut microbial fermentation byproducts of indigestible carbohydrates, which have been demonstrated to help improve gut mucosal barrier integrity and promote a more tolerant immune response.

One such short-chain fatty acid, butyrate, is produced through microbial fermentation of dietary fiber in the colon; it is available in various foods and in supplement form.

Butyrate has been shown to ameliorate inflammatory arthritis in a collagen-induced arthritis model, and in this model, methotrexate efficacy was increased with the addition of butyrate or butyrate-producing bacterial species.

Dr. Blank and colleagues compared patients with new-onset RA treated with methotrexate alone or methotrexate plus butyrate for 4 months and looked at up to 2 months of methotrexate plus butyrate treatment in patients who had suboptimal response to methotrexate alone.

In preliminary analyses, they found that at baseline, fecal butyrate was significantly elevated in methotrexate responders compared with in nonresponders. In addition, in the new-onset RA cohort, they saw that the 4-month responsiveness rate was 52.6% for those treated with methotrexate compared with 64.7% for those treated with methotrexate plus butyrate.

“Although this difference was not statistically significant, it’s exciting to think we may have an impact. What’s more, we were really excited to find that oral butyrate can lead to increased microbial diversity,” she said.
 

What Are You Measuring?

In the Q & A following the presentation, Clifton O. Bingham III, MD, director of the Johns Hopkins Arthritis Center in Baltimore, Maryland, commented that “the definitions of response and nonresponse are quite variable, depending on the studies that you use, and I think this is potentially a real problem for this entire line of investigation.”

Johns Hopkins Medicine, Johns Hopkins Division of Rheumatology

He noted that the DAS28, as used by Dr. Blank and colleagues, was developed in 1993, and that American College of Rheumatology response criteria, employed by other investigators who also presented during the session, were developed in 1990.

“It was a very different world when those criteria and those response indices were developed for patients with a very different disease from what we know as RA today,” he said.

He added that “I see a tremendous need for the rheumatology community to reevaluate what we define as responders and nonresponders, so that in all of these studies that are being done around the world, there is one definition that we understand [for] someone who is doing better, responding, or not responding.”

Dr. Blank’s work is supported by NYU, the Arthritis Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. She reported having no conflicts of interest to disclose. Dr. Bingham had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

If your gut is telling you that your disease-modifying antirheumatic drugs (DMARDs) aren’t working as well as they should, listen to it.

That’s the advice of Rebecca B. Blank, MD, PhD, a rheumatologist at NYU Langone Health in New York City, who studies methods for modulating the gut microbiome to enhance DMARD efficacy for patients with rheumatoid arthritis (RA).

“The baseline gut microbiome can predict patient responsiveness to methotrexate,” said Dr. Blank at the 2024 Rheumatoid Arthritis Research Summit, presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.

Dr. Blank and colleagues are investigating how the intestinal microbiome may influence drug metabolism and the therapeutic potential of short-chain fatty acids for improving the efficacy of methotrexate in patients with RA.
 

Mucosal Barrier Disruption

There are myriad factors contributing to the development and progression of RA, including dysbiosis, or disruption, of the mucosal barrier, Dr. Blank explained.

“Dysbiosis can be detected in at-risk individuals before clinical signs of rheumatoid arthritis even occur,” she said.

Dr. Blank cited a 2021 study of the gut-joint axis in RA,which indicated that subclinical inflammation in the oral, gut, and/or lung mucosa may lead to inflammatory arthritis.

“When there’s a break in the mucosal barrier, either bacteria or their bacterial products can translocate into the lamina propria and then lead to an inflammatory T-cell response, and in addition, bacteria or their products can induce auto-antibody formation, which can then lead to joint inflammation,” she said.

Dr. Blank and colleagues, as well as other research groups, showed that gut bacterial colonization by Prevotella copri can induce an inflammatory response in gut lamina propria, and that people with RA have increased abundance of P copri relative to people without RA.
 

DMARD Resistance

To see whether microbial dysbiosis might play a role in DMARD-resistant RA, Dr. Blank and her team looked at patients with new-onset RA who were scheduled for treatment with methotrexate as their first-line medication. They classified responders as those patients with a change in Disease Activity Score in 28 joints (DAS28) of at least 1.8 points.

They then conducted 16S rRNA sequencing and shotgun sequencing on patient fecal samples taken at baseline to determine whether baseline microbiome differences might contribute to responses to methotrexate.

“And so indeed, we were able to find a human gut microbial signature that predicted methotrexate responsiveness in these baseline microbiome samples,” Dr. Blank said.

They identified 462 differences in gene orthologs (ie, genes preserved during evolution and speciation) that differed between responders and nonresponders, narrowed the list down to the top 38, and then developed a predictive model for response to methotrexate with an area under the receiver operating characteristic curve of 0.84.

The investigators then cultured fecal baseline samples with methotrexate to see how levels of the drug would be affected over time and found that samples from nonresponders metabolized methotrexate at a faster rate than samples from patients who had clinical responses to the drug.

Their work was further supported by colleagues at the University of California San Francisco, who found evidence in mouse models to suggest that microbial metabolism plays a role in methotrexate levels in plasma.
 

Modulating the Gut

“Our next question was: Can we modulate the gut microbiome to improve methotrexate efficacy?” Dr. Blank said.

They considered probiotics and prebiotics as possible means for modulating gut microbiota, but evidence of efficacy for these agents has been decidedly mixed, she noted.

Instead, the investigators focused on short-chain fatty acids, gut microbial fermentation byproducts of indigestible carbohydrates, which have been demonstrated to help improve gut mucosal barrier integrity and promote a more tolerant immune response.

One such short-chain fatty acid, butyrate, is produced through microbial fermentation of dietary fiber in the colon; it is available in various foods and in supplement form.

Butyrate has been shown to ameliorate inflammatory arthritis in a collagen-induced arthritis model, and in this model, methotrexate efficacy was increased with the addition of butyrate or butyrate-producing bacterial species.

Dr. Blank and colleagues compared patients with new-onset RA treated with methotrexate alone or methotrexate plus butyrate for 4 months and looked at up to 2 months of methotrexate plus butyrate treatment in patients who had suboptimal response to methotrexate alone.

In preliminary analyses, they found that at baseline, fecal butyrate was significantly elevated in methotrexate responders compared with in nonresponders. In addition, in the new-onset RA cohort, they saw that the 4-month responsiveness rate was 52.6% for those treated with methotrexate compared with 64.7% for those treated with methotrexate plus butyrate.

“Although this difference was not statistically significant, it’s exciting to think we may have an impact. What’s more, we were really excited to find that oral butyrate can lead to increased microbial diversity,” she said.
 

What Are You Measuring?

In the Q & A following the presentation, Clifton O. Bingham III, MD, director of the Johns Hopkins Arthritis Center in Baltimore, Maryland, commented that “the definitions of response and nonresponse are quite variable, depending on the studies that you use, and I think this is potentially a real problem for this entire line of investigation.”

Johns Hopkins Medicine, Johns Hopkins Division of Rheumatology

He noted that the DAS28, as used by Dr. Blank and colleagues, was developed in 1993, and that American College of Rheumatology response criteria, employed by other investigators who also presented during the session, were developed in 1990.

“It was a very different world when those criteria and those response indices were developed for patients with a very different disease from what we know as RA today,” he said.

He added that “I see a tremendous need for the rheumatology community to reevaluate what we define as responders and nonresponders, so that in all of these studies that are being done around the world, there is one definition that we understand [for] someone who is doing better, responding, or not responding.”

Dr. Blank’s work is supported by NYU, the Arthritis Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. She reported having no conflicts of interest to disclose. Dr. Bingham had no relevant conflicts of interest to disclose.

A version of this article appeared on Medscape.com.